predictionProductionTMS SilcoxMickeyPayne

Running head: PREDICTION, INFERIOR FRONTAL CORTEX, AND TMS 1
Disruption to left inferior frontal cortex modulates semantic prediction effects in reading
and subsequent memory: Evidence from simultaneous TMS-EEG
Jack W Silcox1, Brian Mickey2,3, Brennan R. Payne1,3
1
Department of Psychology, University of Utah, Salt Lake City, Utah
2
Department of Psychiatry, Huntsman Mental Health Institute, University of Utah, Salt Lake City,
Utah
3
Neuroscience Program, University of Utah, Salt Lake City, Utah
Financial Disclosures/Conflict of Interest: The research was supported by a research grant from
the Office of the Vice President for Research at the University of Utah. The authors have no
competing interests to disclose.
All correspondence should be addressed to:

Jack W Silcox, 380 South 1530 East, Suite 906 BEHS, Salt Lake City, UT 84112.
Email: jack.silcox@utah.edu
Author Contributions:
Jack W Silcox = Conceptualization; Methodology; Formal Analysis; Investigation; Data Curation;
Writing – Original Draft; Visualization; Software
Brian Mickey = Conceptualization; Resources; Writing – Review & Editing; Funding Acquisition
Brennan R. Payne = Conceptualization; Methodology; Resources; Writing – Review & Editing;
Supervision; Project Administration; Funding Acquisition
PREDICTION, INFERIOR FRONTAL CORTEX, AND TMS 2
Abstract
Readers use prior context to predict features of upcoming words. When predictions are accurate,
this increases the efficiency of comprehension. However, little is known about the fate of
predictable and unpredictable words in memory or the neural systems governing these processes.
Several theories suggest that the speech production system, including the left inferior frontal cortex
(LIFC), is recruited for prediction but evidence that LIFC plays a causal role is lacking. We first
examined the effects of predictability on memory and then tested the role of posterior LIFC using
transcranial magnetic stimulation (TMS). In Experiment 1, participants read category cues,
followed by a predictable, unpredictable, or incongruent target word for later recall. We observed
a predictability benefit to memory, with predictable words remembered better than unpredictable
words. In Experiment 2, participants performed the same task with electroencephalography (EEG)
while undergoing event-related TMS over posterior LIFC using a protocol known to disrupt speech
production, or over the right hemisphere homologue as an active control site. Under control
stimulation, predictable words were better recalled than unpredictable words, replicating
Experiment 1. This predictability benefit to memory was eliminated under LIFC stimulation.
Moreover, while an a priori ROI-based analysis did not yield evidence for a reduction in the N400
predictability effect, mass-univariate analyses did suggest that the N400 predictability effect was
reduced in spatial and temporal extent under LIFC stimulation. Collectively, these results provide
causal evidence that the LIFC is recruited for prediction during silent reading, consistent with
prediction-through-production accounts.
Impact statement
It has been proposed that the left-hemisphere dominant speech production network in the brain is
recruited during silent reading comprehension to make predictions about possible upcoming
words, but causal evidence is lacking. In the current study, we found evidence that disrupting a
hub of the production network (the left inferior frontal cortex) via repetitive TMS during active
prediction impaired subsequent predictive benefits to both real-time word processing and memory
in silent reading.
Introduction
The human brain is widely considered “a fundamentally proactive device” (p. 184, Van
Berkum, 2010), that “continuously generates predictions that anticipate the relevant future” (p.
1235, Bar, 2009; see also Bar, 2007; Mesulam, 2008). In language comprehension, it has been
argued that readers/listeners use prior context in an anticipatory manner, leading to the pre-
conscious prediction of semantic, syntactic or perceptual features of likely upcoming words. This
pre-activation, when accurate, facilitates processing when the predicted word is encountered
(Federmeier, 2007). Although the idea that prediction occurs during comprehension has become
ubiquitous, with debates moving from whether or not prediction occurs to determining how this
prediction takes place, there is still substantial debate on the mechanisms by which linguistic
prediction is implemented (see Kuperberg & Jaeger, 2016; Kutas et al., 2011, 2014; Van Petten &
Luka, 2012; Federmeier, 2007; Friederici, 2011; Pickering & Garrod, 2013; Ferreira & Lowder,
2016; Luke & Christianson, 2016; Lau et al., 2013; Dell & Chang, 2014; Huettig, Audring, &
Jackendoff, 2022). One leading idea is that such prediction is implemented by recruiting the speech
production system during comprehension (Federmeier, 2007; Dell & Chang, 2014; Pickering &
Garrod, 2007, 2013; Mani & Huettig, 2012). The goal of the present study is to assess this theory
using transcranial magnetic stimulation (TMS) to directly modulate a key neural node of the
language production system during an online reading comprehension and subsequent memory
task. Before describing the current study in detail, we first review relevant background information
on production theories of prediction, TMS, and implications for memory.
The Production Affects Reception in the Left (hemisphere) Only (PARLO) model
(Federmeier, 2007; see also, Federmeier, 2022) hypothesizes that the left-hemisphere dominant
production system is recruited for prediction during comprehension. Consistent with this theory,
hemispheric asymmetries in the sensitivity of the N400 event-related potential (ERP) component
to predictive processes have been consistently reported (Federmeier, 2022). The N400 is a centro-
posteriorly distributed negative deflection that peaks around 400 milliseconds after the onset of
meaningful stimuli and is an index of semantic memory access for meaningful stimuli (Kutas &
Federmeier, 2011). While using the visual half-field paradigm to bias processing towards the right
or left hemisphere, Federmeier and Kutas (1999b) found prediction-related facilitation of the N400
only when words were biased to the left hemisphere, consistent with the recruitment of the left-
hemisphere dominant production system to generate specific predictions. Older adults, as a group,
are less likely to show such prediction-related ERP effects (e.g., Federmeier et al., 2002, 2010;
Federmeier & Kutas, 2019; Payne & Federmeier, 2018; Wlotko et al., 2012). This may be because
older adults rely less on the left-hemisphere dominant language production system, as evidenced
by decreased left-hemisphere asymmetry in brain activation during verbal tasks (Cabeza, 2002;
Berlingeri et al., 2013; Eyler et al., 2011; Johansson et al., 2020), and reduced fluency in explicit
production (Burke & Shafto, 2004; Tremblay et al., 2019). At the same time, a number of studies
have found that older adults with intact language production skills—for example, higher verbal
fluency—are more likely to elicit young-like prediction-related ERP effects (for a review see
Payne & Silcox, 2019), which has been taken to reflect a putative link between the left-hemisphere
dominant speech production system and prediction. Similarly, work with patients with intact
temporal cortices but lesions in the left inferior frontal cortex (LIFC)—a hub of the speech
production network—failed to elicit early ERP syntactic prediction effects that are typically seen
to subject-verb agreement violations, which has been argued as evidence for a lack of top-down
predictions coming from LIFC (Jakuszeit et al., 2013; see also Opitz & Kotz, 2012). Further
evidence for links between production and comprehension come from functional neuroimaging
studies showing overlap in activation in the LIFC during separate production and comprehension
tasks performed by the same participants (Silbert et al., 2014; Giglio et al., 2021; Menenti et al.,
2011). Moreover, a recent study by Bonhage and colleagues (2015) measured simultaneous eye
movements and fMRI during a reading task in which the final (predictable) word position varied
on the screen based on predicted syntactic category. They found evidence for increased activation
in LIFC when participants showed language-driven anticipatory eye movements, suggesting a link
between LIFC and predictive processing (see also Fiebach & Schubotz, 2006). Collectively, these
findings suggest that LIFC represents a strong candidate for linking implicit prediction during
comprehension with explicit verbal production.
Finally, recent studies have attempted to more directly engage the language production
system during comprehension by having participants perform a secondary production task while
reading (Lelonkiewicz et a., 2021; Martin et al., 2018). For example, Lelonkiewicz and colleagues
(2021) had individuals read either highly predictable or less predictable sentences while measuring
response times to recognizing, naming, or using a sentence-final word to identify a picture. They
found that response times were generally faster for words read in a more predictable sentence
context but that this effect was even greater when the sentences were read aloud compared to when
they were read silently. In contrast, Martin and colleagues (2018) found that when the production
system was engaged by a secondary production task that was unrelated to the reading task,
prediction-related N400 effects were attenuated. Collectively, these studies suggest a strong
relationship between the engagement of production and predictive effects during reading—when
the production system is engaged in a task that overlaps with comprehension, prediction effects
are augmented but when the production system is made unavailable during comprehension, by
engaging in an unrelated production task, prediction effects are attenuated. At the same time, these
studies are not informative about the neural locus of such prediction-through-production effects.
While the benefits of predictive processes for word processing are well understood, less is
known about the fate of predictable words in long-term memory. Some work finds that when
context-based prediction during comprehension is possible, words and sentences are better
remembered (e.g., Gordon-Salant & Fitzgibbons, 1997; Kutas, 1993; McCoy et al., 2005). For
example, Silcox and Payne (2021) found that sentences that provided contextual constraints that
supported prediction were generally remembered better than sentences that did not. Moreover, the
negative effects of background noise on memory were attenuated for sentence contexts that
allowed for predictive processes. Rommers and colleagues (2020) found that the production effect
(i.e., superior memory for words read aloud versus read silent) was smaller for sentences that were
predictable compared to sentences that were not, consistent with the idea that the production
system is used for making predictions during reading. Additionally, they found that participants
had a harder time remembering whether a sentence was read aloud or not if the sentence was
predictable, consistent with the idea that the production system is brought online for prediction
during silent reading, leading to poorer source discriminability as to whether a sentence was read
aloud or silently.
While there is evidence which suggests that the production system may be recruited in
generating predictions during comprehension, prior work implicating a specific neural generator
(such as LIFC) has either been correlational in nature or relied on indirect manipulations of the
involvement of the speech production system. In the current study we directly test the neural
underpinnings of prediction during comprehension and its effects on subsequent memory using
transcranial magnetic stimulation (TMS). TMS is a safe and non-invasive way of directly
modulating brain activity (Eldaief et al., 2013; Fregni & Pascual-Leone, 2007; Murphy et al., 2016;
Noda et al., 2015). Short, controlled bursts of TMS can create temporary “virtual lesions” that
induce transient changes in language (Nuñez et al., 2020; Klaus & Hartwigsen, 2019; Hartwigsen
et al., 2015) and memory (Ferrari et al., 2018; Wang et al., 2018; Gatti et al., 2021). Importantly,
TMS has been used successfully to disrupt cortical activity and impair speech production (e.g.,
Pascual-Leone et al., 1991; Epstein et al., 1999; Hauck et al., 2015; Freigang et al., 2020; Krieg et
al., 2014; Rösler et al., 2014). So-called “speech mapping protocols” combine a production task
(e.g., object naming) with (typically) a 5-pulse train, 5-Hz repetitive TMS stimulation, with
stimulation time-locked to the onset of the visual object. Stimulation is continued as the coil is
systematically moved around pre-selected cortical targets to map out speech-eloquent cortical
areas in the brain (Krieg et al., 2017). During an object naming task, this type of protocol has been
shown to consistently elicit temporary speech disruptions (e.g., speech arrest, paraphasias, etc.) in
both patients and healthy controls (Hauck et al., 2015; Krieg et al., 2017). This stimulation protocol
when applied over posterior LIFC specifically elicits consistent speech disruptions (Hernandez-
Pavon et al., 2014; Picht et al., 2013; Nettekoven et al., 2021; Sakreida et al., 2018). For example,
Rogic and colleagues (2014) found that all of the participants in their study showed some speech
disruption when using the above described TMS protocols over the LIFC. Tarapore and colleagues
(2013) reported that the most consistent speech positive site in left perisylvian mapping was the
posterior IFC, which was also the same region that showed the highest overlap in these patients
when they later underwent pre-surgical direct cortical stimulation speech mapping (see also, Picht
et al., 2013). Thus, TMS speech mapping findings consistently implicate LIFC as a major hub in
the language production system that is sensitive to TMS stimulation.

For the present work, we first examined the effects of predictability on subsequent memory
(Experiment 1) and then tested the role of LIFC on online predictive processing and subsequent
memory by disrupting its function during silent reading (Experiment 2). In both experiments, we
used a silent reading category decision task that has been used successfully in the past to study
predictive processes (Federmeier et al., 2010; Ryskin et al., 2020). Although the
electrophysiological responses in this task have been previously characterized, to the best of our
knowledge, no one has examined the fate of predictable or unpredictable words in long-term
memory in this task. Therefore, the purpose of Experiment 1 was to establish the type of pattern
that may be expected when adding a delayed cued recall task to the category decision task. Thus,
in Experiment 1, the primary outcome of interest was memory performance so that we can assess
whether there were any benefits of prediction to subsequent memory.
In Experiment 2, we simultaneously recorded electroencephalography (EEG) and
administered repetitive TMS over posterior LIFC using a stimulation protocol known to impair
speech production, while participants performed the same category decision and subsequent
memory task that was used in Experiment 1. Importantly, stimulation was applied just prior to the
target word, when predictive mechanisms should be most strongly engaged (see below for more
details). Like in Experiment 1, we were primarily interested in performance on the memory test.
If the LIFC-mediated language production system is implicated in prediction-related memory
benefits, then we predicted that whatever prediction-related benefit was observed in Experiment 1
should be reduced or eliminated in Experiment 2 when repetitive TMS was applied over posterior
LIFC but not right IFC. In addition to prediction-related effects on memory, we examined how
TMS over the LIFC influences the N400 predictability effect. If LIFC is recruited for predictive
processing, then stimulation over LIFC during prediction should lead to a reduction in the
subsequent N400 predictability effect at the target word.
EXPERIMENT 1
Materials & Methods
Participants
Informed consent was obtained for thirty-one adults (16 female, mean age = 21.4, range =
18-35) from the University of Utah community who participated in the experiment for course
credit. For all participants, English was their first and primary language. For this sample, 9.7%
were Latinx, 74.2% were Caucasian, 3.2% were of Chinese descent, 3.2% reported being
multiracial, and 9.7% declined to report their ethnicity. Thirteen of the participants self-reported
having some history of mental health issues, including depression, anxiety, ADHD or bipolar.
Materials
Experimental stimuli included 120 category cues (e.g., “A type of condiment”, “A common
color”, “A type of bird”), each with three different types of target words: a highly predictable target
(i.e., high typicality), a low predictability target (i.e., low typicality), and an incongruent target.
For example, if the category cue was A type of flower, then a high predictability target word would
be rose, a low predictability target word would be poppy, and an incongruent target word would
be opera. Target words were controlled for word length and frequency. Category cues were taken
from those used by Federmeier and colleagues (2010; see also Ryskin et al., 2020), and from
norming studies done by McEnvoy and Nelson (1982), Hunt and Hodge (1971), and Van
Overschelde and colleagues (2004). Categories for this study were modified such that the defining
word of the category was in the final word position. A complete list of the categories and
corresponding target words can be found in the Supplemental Materials found at
https://osf.io/yrngx/. To ensure that each stimulus was used in each of the conditions, stimuli were
counterbalanced across three separate lists.
Procedures
Participants were seated approximately 55 cm from a monitor. Participants were instructed
that they would be seeing categories followed by a target word, and that their task was to decide
whether the target word belonged to the preceding category. They were not instructed that there
would be a delayed memory test after the entire category decision task was completed. All
responses for the category decision task were made on a Cedrus RB-840 response pad. Each of the
120 trials followed the same pattern. A trial would begin after a self-paced break. After the
participant pressed a button on the response to end the self-paced break, a white fixation cross
appeared in the middle of a black screen for 3,000 msec. The category cue would then be presented
one word at a time in the center of the screen in white text. Each word of the cue was presented
for 500 msec before being replaced on screen by the subsequent cue word. Between the category
cue and the target word a fixation cross was displayed. The target word would then remain on
screen until the participant responded with their decision about whether the target word was part
of the preceding category cue. On average, this category decision task took approximately 15
minutes. An example of a single trial can be seen in Figure 2. Immediately upon completing this
category decision task, participants completed a cued word recall task. Participants were given a
list of sixty category cues that they had seen previously and were asked to recall the corresponding
target word that they had seen.
Data Analyses
Similar analytical approaches were used for both category judgement accuracy and delayed
cued recall accuracy. Item-level responses were used as the response. First, generalized linear
mixed effects models assuming a binomial distribution with a logit link function were fit using
either judgement accuracy or recall accuracy as the response variable and target word predictability
as the predictor. Random intercepts for subjects and items were used (adding random slopes did
not allow for convergence; Barr et al., 2013; Bates et al., 2015). These mixed models were fit using
the glmer() function from the lme4 package in R. Second, omnibus likelihood ratio tests were run
using the mixed() function from the afex package in R to assess the significance of the fixed “target
word type” factor. Lastly, to parse condition differences, pairwise odds ratios were calculated and
assessed using the emmeans() function and pairwise comparisons between conditions were
estimated with the pairs() function from the emmeans package in R.
Data and Code Availability Statement
All data and code related to this study can be found at: https://osf.io/yrngx/.
Results
The left panel of Figure 1A show the estimated marginal means of the category judgement
accuracies. For the analysis of category judgement accuracy, we found that there was a significant
effect of target word type (χ2(2) = 75.82, p < 0.001). Decision accuracy was not significantly
different between highly predictable and incongruent words (Odds ratio (high vs incongruent) =
0.55, SE = 0.24, z = -1.38, p = 0.35). However, low predictability words were significantly less
likely to be judged accurately than both highly predictable (Odds ratio (high vs low) = 11.85, SE
= 4.30, z = 6.82, p < 0.001) and incongruent words (Odds ratio (incongruent vs low) = 21.45, SE
= 8.65, z = 7.60, p < 0.001).

Figure 1 Behavioral results from both experiments. A. Category judgement accuracy. Left portion of plot contains the
results from Experiment 1. Right portion of the plot contains results from Experiment 2. B. Recall accuracy results
for both experiments. Left portion of the plot contains results from Experiment 1. Right portion of the plot contains
results from Experiment 2. HP = Highly predictable target words; LP = Low predictability target words; IN =
Incongruent target words. Error bars represent standard error.

The left panel of Figure 1B show the estimated marginal means of accuracy from the
delayed cued recall test. For the recall accuracy analysis, we found that there was a significant
effect of target word type (χ2(2) = 255.15, p < 0.001). Incongruent words were much less likely to
be recalled than both low predictability words (Odds ratio (low vs incongruent) = 49.89, SE =
12.55, z = 15.54, p < 0.001) and high predictability words (Odds ratio (high vs incongruent) =
93.91, SE = 25.07, z = 17.02, p < 0.001). Importantly, within congruent words, the more expected,
highly predictable words were recalled significantly better than less predictable words (Odds ratio
(high vs. low) = 1.88, SE = 0.42, z = 2.85, p < 0.05).
Discussion
In summary, in Experiment 1, we found that participants had near-ceiling performance
overall in accuracy judgement, and a small but significant decrease in judgement accuracy when
judging whether a less predictable target word is part of a category. This pattern is expected and
consistent with prior work (Federmeier et al., 2010) that shows that for less typical words (i.e., the
less predictable words), whose fit to the category cue was more marginal by design, accuracy was
poorer, but still quite high (over 90%). For the delayed cued recall measures, we found that
participants were able to generally recall in-category words (i.e., highly predictable and less
predictable target words) much better than out-of-category words (i.e., incongruent target words).
This is in line with a long line of work showing that cue-target pairs that share semantic or
categorical associations tend to be remembered better than items that are wholly unrelated (e.g.,
Epstein et al., 1975; Koriat & Bjork, 2005; Castel, McCabe, & Roediger, 2007).
Importantly though, we found evidence for a predictability benefit within congruent
conditions such that higher predictability words were remembered better than lower predictability
words. Better cued recall performance for predictable versus unpredictable words replicates what
has been seen previously (e.g., Silcox & Payne, 2021; Kutas, 1993; McCoy et al., 2005; Miller &
Selfridge, 1950; Riggs et al., 1993). Silcox and Payne (2021) argued that this type of predictability
effect in memory suggests that “predictive processes [may] help to alleviate some of the burden of
processing, allowing for more resources to be available for memory encoding and maintenance”
(pg. 310).
Therefore, having established that there is a predictability effect seen in the memory
outcome for this paradigm, in Experiment 2, we sought to investigate the role that LIFC may play
in modulating this effect. Additionally, we examined the role that this system may play in the N400
predictability effect previously reported by Federmeier and colleagues (2007; 2010). To do this,
in Experiment 2, we utilized an online, event-related TMS protocol.
EXPERIMENT 2
Materials & Methods
Participants
Informed consent was obtained for thirty-seven community-dwelling adults (17 female,
mean age = 22.8, range = 18-35) who participated in the experiment for $15/hour. All were right-
handed individuals (handedness was assessed using the Edinburgh Handedness Inventory;
Oldfield, 1971) with no prior history of neurological issues and no exposure to a language other
than English before the age of 3. All female participants took pregnancy tests upon arrival at the
lab, per the University of Utah’s IRB requirements for TMS studies. All female participants were
negative on their pregnancy tests. All participants were native English speakers. One participant
exited the study before data collection began because of a temporary malfunction with the
neuronavigation system. Two participants were turned away after obtaining consent because it was
learned that they were taking medications that are known to lower seizure threshold. Two
participants requested to terminate their participation early because they reported discomfort with
the TMS protocol. One participant’s session was terminated after a few TMS pulses because the
participant reported feeling faint and nauseous. This left a total sample size of 31 (16 female, mean
age = 22.7, range = 18-35). Of the final sample, 6.5% were Latinx, 3.2% were African American,
77.5% were Caucasian, 3.2% were Pacific Islander, and 9.7% declined to respond to the question
about ethnicity. Eight of the participants self-reported having some history of mental health issues,
including depression or anxiety.
Materials and Design
The same stimuli were used for Experiment 2 for both the category decision task and the
delayed cued recall task. The three target-word conditions were then crossed with two levels of
TMS stimulation (left IFC vs right IFC), with counterbalanced stimulation order, creating twelve
stimulus presentation lists (3 target word x 2 stimulation site x 2 stimulation order). Thus, the final
design was a within-subjects, repeated-measures design crossing stimulation site (2: LIFC vs.
RIFC) with target word type (3: high predictability, low predictability, incongruent). Stimulation
site was blocked, while target word type was counterbalanced across items within each stimulation
block.
Procedure
Participants were seated in a specialized TMS chair and then co-registered to an MNI
template brain (ICBM152) using BrainSight software (Rogue Research) to assist in real-time
stereotactic localization of stimulation targets (Mazziotta et al., 2001; Lancaster et al., 2007). Next,
TMS stimulation intensity was determined by acquiring the resting motor evoked potential (MEP)
threshold for each subject (Rossini et al., 2015). We used a Rogue cTMS stimulator to deliver
biphasic pulses with a 15.87-uH (regular inductance) figure-8 coil. This was done by using single
pulse TMS over the left primary motor hand area cortex with the coil oriented at an angle of 45
degrees and finding the lowest stimulation intensity that elicited a MEP in the relaxed abductor
pollicis brevis muscle in the right hand of approximately 50 µV from peak to peak, 50% of the
time. To locate a participant’s specific primary motor hand area cortex, we used the MNI co-
ordinates on the template brain (x = -36, y = -19, z = 48) as the starting point and methodically
searched the area using a stimulation intensity that was higher than average until we found a spot
that consistently elicited a MEP. We then lowered the stimulation intensity until we reached the
50% threshold. Participants were then offered a break, after which they were equipped with EEG
and reregistered to the neuronavigation system.
For the category decision task, trial-level procedures were identical to Experiment 1, with
a few exceptions. Repetitive TMS stimulation (described below) was applied to the scalp directly
over the mean MNI coordinates for the posterior left (x = -48, y = 13, z = 17) and posterior right
IFC (x = 49, y = 12, z = 17). For stimulation over the left and right IFC, we used a stimulation
intensity that was 100% of the MEP threshold but lowered the stimulation intensity for comfort if
the participant requested. Participants were told that stimulation intensity could be lowered at any
time to ensure that they felt no pain. Sixteen participants requested that we lower stimulation
intensity. For those that requested this, the average stimulation level was at 91.3% of resting MEP
threshold (SD = 6.0%).
Figure 2 depicts a single trial. Online, event-related stimulation was performed over the
left and right posterior IFC, time-locked to the last word in the category cue (i.e., the defining word
of the category). The TMS protocol was based on clinical speech mapping research (e.g., Krieg et
al., 2017), where stimulation over LIFC consistently leads to speech arrest and transient
paraphasias during object naming in speech mapping tasks, strongly suggesting that this
stimulation protocol inhibits speech production, as reviewed above. Specifically, we used a burst
of 5 pulses at 5 Hz with the coil oriented at a 45-degree angle to the sagittal plane, time-locked to
the category-defining pre-target word. This type of stimulation over posterior LIFC, in particular,
has shown to consistently inhibit speech production during speech mapping (Sakrieda et al., 2018).
It is important to emphasize that stimulation was not induced at the presentation of the target word
but rather prior to the target word, at the presentation of the defining word of the category cue,
when readers are putatively recruiting the language production system to generate predictions for
likely upcoming words. Figure 2 also shows the estimated e-fields for the RIFC and LIFC
stimulations generated with SimNIBS software, version 3.2.6 (Thielscher et al., 2015).
Figure 2. Diagrams depicting the structure of a single trial for each experiment (on the left), as well as the results of
e-field simulations for the two experimental TMS targets (on the right) for Experiment 2. Note that for Experiment 2,
TMS stimulation occurs at the defining word of the category cue (depicted by the brain and magnet icon). In
Experiment 1, judgement responses occurred at the target where, whereas in Experiment 2, judgement responses
occurred at the “Yes or No?” prompt. Judgement responses are represented by the gavel icon. Times displayed below
each screen show the SOAs.
Between the category cue and the target word, there was a 2,000 msec interval to
accommodate event-related repetitive TMS. Also, because we were recording EEG, decision
responses were delayed until a “Yes or No?” prompt appeared on screen 2,000 msec after the offset
of the target word to avoid decision-related contamination of event-related brain potentials to the
target word. The 120 trials were split into 60-trial blocks, with each block consisting of one of the
two stimulation conditions, with order counterbalanced across participants. Between each block,
participants took a fifteen-minute break. After the break, the TMS coil was moved to the second
stimulation site. From the beginning of the category decision task in the first block to its conclusion
in the second block, on average, it took approximately 1 hour and 5 minutes for a participant to
complete. Once the category decision task was complete and all EEG and TMS equipment had
been removed from the participant, the incidental cued recall test was administered, which was
identical to the test used in Experiment 1. The average amount of time that a participant was in the
lab was approximately 3.5 hours.
EEG Recording and Processing
EEG data were recorded from 64 evenly spaced silver-silver chloride actiCap slim active
electrodes distributed by Brain Products (Brain Vision, LLC, Morrisville, NC, United States of
America), following the standard international 10-10 localization system for 64 electrodes.
Electrode impedances were kept below 15 kOhms. Electrodes were referenced online to the Cz
electrode and re-referenced offline to the average of the TP9 and TP10 electrodes, which are close
to the left and right mastoids, respectively. Continuous EEG was amplified through a BrainAmp
DC amplifier and was recorded with a lower cutoff at DC (0Hz) and an online low pass filter of
1000 Hz at a sampling rate of 500 Hz using BrainVision Recorder software. EEG data were
downsampled offline to 250 Hz. Prior to analysis, data were bandpass filtered at 0.1 to 30 Hz.
The continuous EEG data were then epoched 100 msec before to 920 msec after the onset
of the target word. The epoched EEG was baseline corrected using the mean amplitude from -100
msec to 0 msec. Epoched EEG data were examined for artifacts, including eyeblinks, eye
movements, flatlines, and signal drifts. We excluded from analysis any trials that had been flagged
as containing any of these artifacts. Any subjects that had more than 40% of their trials flagged as
containing artifacts were completely removed from any EEG analysis. Three subjects had greater
than or equal to 40% of their trials containing artifacts. With these subjects removed, the average
number of trials containing artifacts was 9.5% (SD=7.6%; range across participants <1-30.8%).
There were no reliable differences in artifact rates between conditions. It is important to note that
TMS stimulation (which occurred during the word just prior to the target word) had completely
resolved well before the target word was presented, so there was no direct stimulation induced
artifacts related to TMS in the ERPs. This can be seen in the Supplementary Materials found at:
https://osf.io/yrngx/. Details on the selection of time windows and electrodes for statistical
analyses are discussed in Data Analyses, below.
Data Analyses
In Experiment 2, there were two main sets of analyses. First, we conducted similar as in
Experiment 1 on the behavioral data. Second, we ran a set of analyses on the ERP data. For each
statistical model, we followed the general pattern seen in the models for Experiment 1. That is, we
fit a (generalized) linear mixed effects model and then conducted likelihood ratio tests for each
fixed factor. We then followed those tests up with pairwise post-hoc tests on the estimated odds
ratios or the contrast between estimated marginal means. However, it is important to note that
because of the change in experimental design (i.e., adding TMS stimulation) our models for
Experiment 2 would now have two main effects and an interaction, instead of just one main effect
like we did in Experiment 1. In addition to a priori ERP analyses, we conducted an additional
exploratory mass-univariate analysis on the ERP data, which is detailed below. Adjustments were
made for all multiple comparisons using the false discovery rate (FDR) procedure.
For both category judgement accuracy and delayed cued recall accuracy, single-trial level
responses were used as the response variables. For both models we fit generalized linear mixed
effects models assuming a binomial distribution with a logit link function with either judgement
accuracy or recall accuracy as the response variable and target word type (high predictability, low
predictability or incongruent), stimulation type (LIFC vs RIFC), and their interaction as the fixed-
effect predictors. Random intercepts for subject and item were used (Baayen et al., 2008).
However, the addition of a random intercept for item in the model for the recall data did not allow
for convergence. Therefore, we did not include this in our random effects structure for the recall
data (Barr et al., 2013). We then ran likelihood ratio tests on the fixed effects and followed these
up with pairwise odds ratio tests to parse any significant omnibus effects.
For the ERP-related analyses, three participants had greater than 40% of their trials
containing artifacts and were excluded from ERP analyses (but were not removed from the
behavioral analyses). This left 28 participants to be used. Our first analysis was done on the N400
ERP component. This analysis was conducted using an a priori spatio-temporal region of interest
(ROI) encompassing six centro-parietal electrode sites (CP1, CP2, CPz, P1, P2, and Pz), where
N400 effects are typically the largest and a 300-500 msec time window, which is standard for
visual-N400 responses (see Kutas & Federmeier, 2011). Measurements of mean amplitude were
made at the single-trial level. For analysis, we used single-trial N400 mean amplitude as the
response variable and, like the above-described behavioral analyses, we used target word type,
TMS stimulation site and their interaction as predictors in our N400 mean amplitude model.
However, we added a random intercept for electrode in addition to a random intercept for subject
and item. We ran likelihood ratio tests for each fixed effect and followed these up with pairwise
contrasts on the estimated marginal means to help decompose any significant effects.
Because this is among the first studies to examine effects of repetitive TMS on prediction-
related ERPs, and therefore the effects are largely unknown, we also conducted a supplementary
exploratory analysis to more broadly examine the effects of TMS on the prediction-related ERP
responses. Specifically, we conducted a mass-univariate analysis of the predictability effect (low
predictability minus high predictability) over all channels and timepoints. Difference waves were
constructed via pointwise subtraction of the subject-level ERP waveforms for the high and low
predictability conditions separately for the RIFC and LIFC stimulation conditions across
electrodes. We then used these difference waves to construct raster plots by calculating t-statistics
at each time point for representative electrodes (i.e., except for the temporal channels, to improve
visualization of raster plots) and plotting these separately for the RIFC stimulation and LIFC
stimulation conditions (Groppe, Urbach, & Kutas, 2011a,b). An FDR correction on the p-values
associated with each t-statistic was applied accounting for both the number of electrodes and
timepoints included in the analysis. After applying FDR correction, we can then visualize the
temporal and spatial extent of statistically reliable predictability effects under LIFC and RIFC
stimulation across electrodes and timepoints, allowing for a broader examination of predictability
effects than ROI-based analyses (for an example see Silcox & Payne, 2021). Only t-statistics with
FDR-adjusted p-values less than .05 were included in these visualizations.
Results
Category Decision Behavior Results
The right panel of Figure 1A show the results of accuracy on the category judgement
portion of the task from Experiment 2. We found that there was no significant interaction effect
(χ2(2) = 0.62, p = 0.73) and no significant main effect of TMS stimulation site (χ2(1) = 0.55, p =
0.46) on judgement accuracy. However, there was a significant main effect of target word type
(χ2(2) = 47.22, p < 0.001). The effect of target word type on judgement accuracy followed a pattern
similar to that seen in Experiment 1, with highly predictable words having a similar accuracy rate
as incongruent words (Odds ratio (high vs incongruent) = 0.68, SE = 0.39, z = -0.68, p = 0.78),
highly predictable words being judged more accurately than low predictability words (Odds ratio
(high vs low) = 18.01, SE = 8.63, z = 6.03, p < 0.001), and incongruent words also being more
likely to be judged accurately than low predictability target words (Odds ratio (incongruent vs low)
= 26.67, SE = 13.82, z = 6.34, p < 0.001). Thus, there was no apparent effect of TMS on participants
ability to judge whether a target word was part of a cued category, resulting in a replication of the
pattern observed under no brain stimulation in Experiment 1.
Memory Results
The right panel of Figure 1B show the results of the delayed cued recall test. We found a
significant main effect of target word type on recall accuracy (χ2(2) = 757.28, p < 0.001) but no
main effect of TMS stimulation site (χ2(1) = 0.49, p = 0.49). However, we did find a significant
interaction between TMS stimulation site and target word type (χ2(2) = 7.84, p = 0.02), suggesting
that TMS modulated the effects of target word type on memory. For RIFC stimulation, we found
that both high (Odds ratio (high vs incongruent) = 71.78, SE = 21.12, z = 12.54, p < 0.001) and
low predictability words (Odds ratio (low vs incongruent) = 33. 89, SE = 9.62, z = 12.41, p < 0.001)
were recalled better than incongruent words. Importantly, we found that for the RIFC stimulation
condition, highly predictable words were recalled better than low predictability words (Odds ratio
(high vs low) = 2.12, SE = 0.42, z = 3.81, p = 0.002). Thus, in the RIFC stimulation condition we
replicated the predictability benefit to memory that we observed in Experiment 1. For the LIFC
stimulation condition, we found that both high (Odds ratio (high vs incongruent) = 36.15, SE =
9.89, z = 13.12, p < 0.001) and low predictability words (Odds ratio (low vs incongruent) = 34.87,
SE = 9.44, z = 13.12, p < 0.001) were recalled better than incongruent words. However, in the
LIFC condition we did not see that highly predictable words were recalled better than low
predictability words (Odds ratio (high vs low) = 1.04, SE = 0.19, z = 0.20, p ≈ 1.00). Therefore,
we saw that the predictability benefit seen in the absence of stimulation and during control (RIFC)
stimulation, was not present under the experimental (LIFC) stimulation condition. In comparing
recall of target word types between the RIFC and LIFC conditions, we found that there was no
difference in recall for incongruent (Odds ratio (LIFC incongruent vs RIFC incongruent) = 0.89,
SE = 0.30, z = -0.35, p = 0.99) or for low predictability words (Odds ratio (LIFC low vs RIFC low)
= 0.86, SE = 0.16, z = -0.82, p = 0.96). However, we did find a significant reduction in recall
accuracy for high predictability words from RIFC stimulation to LIFC stimulation (Odds ratio
(LIFC high vs RIFC high = 1.76, SE = 0.35, z = 2.89, p = 0.04). To assess whether there were any
significant effects of the order of stimulation (i.e., LIFC first vs RIFC first) on recall accuracy, a
separate model was created which included stimulation order as a covariate. This model showed
that there was no significant effect of stimulation order on the original model.1
Electrophysiology Results
Figure 3A contains the ERPs from the average of the six posterior electrodes used in our
N400 mean amplitude analysis (i.e., CP1, CP2, CPz, P1, P2, and Pz). Additionally, the scalp
topography maps for the predictability effect (ERP response to low predictability targets minus
the response to high predictability words) are also presented in Figure 3B. For our a priori ROI-
based analysis on the single-trial N400 mean amplitudes, we found that the interaction between
target word type and TMS stimulation site was not statistically significant (χ2(2) = 2.33, p = 0.31).
There was no significant main effect of TMS stimulation site (χ2(1) = 2.93, p = 0.09). We found
evidence of a main effect of target word type on N400 mean amplitude (χ2(2) = 123.84, p < 0.001).
The N400 response to highly predictable words was smaller than the responses to both low
predictability words (z = 4.01, p < 0.001) and incongruent words (z = 11.52, p < 0.001). The N400
response was larger to incongruent words than it was to low predictability words (z = 7.54, p <
0.001). This set of patterns replicates what has been seen previously with similar stimuli
(Federmeier et al., 2010). To assess whether there were any significant effects of the order of
stimulation (i.e., LIFC first vs RIFC first) on N400 mean amplitude, a separate model was created
which included stimulation order as a covariate. This model showed that there was no significant
effect of stimulation order on the original model.2
1
This model found that there was a significant main effect of target word type on recall accuracy (χ2(2) = 757.61, p
< 0.001) but no significant main effect of TMS stimulation site (χ2(1) = 0.48, p = 0.49). However, there was a
significant interaction between TMS stimulation and target word type (χ2(2) = 7.82, p = 0.02). Note that these
statistics are almost identical to the model reported in the main text that did not include stimulation order as a
covariate. We also saw that stimulation order had no significant impact on recall accuracy (χ2(1) = 2.30, p = 0.13).
2
Like the original model, we found no significant interaction between TMS stimulation site and target word
type(χ2(2) = 2.33, p = 0.31), a significant main effect of target word type (χ2(2) = 123.93, p < 0.001) and no
Figure 3 This figure displays the ERP results from Experiment 2. A. The ERP waveforms from all six experimental
conditions. The top ERP waveforms are under RIFC TMS stimulation. The bottom ERP waveforms are under LIFC
TMS stimulation. These ERPs are the average across the six electrodes used in the N400 mean amplitude analyses
(i.e., CP1, CP2, CPz, P1, P2, and Pz). B. Scalp topography plots for the predictability effect (low predictability minus
high predictability) during the 300-500 msec time window. C. Raster plots of the predictability effect (i.e., the
difference between the low and high predictability conditions). Only t-values that survived false discovery rate
significant main effect of TMS stimulation site (χ2(1) = 2.93, p = 0.09). Note that the statistics are quite similar
between this model and the original model. We also found no significant stimulation order effect (χ2(1) = 3.42, p =
0.06).
correction are displayed. HP = High Predictability; LP = Low Predictability; IN = Incongruent; RIFC = right inferior
frontal cortex; LIFC = left inferior frontal cortex.
In addition to our ROI-based analysis, we conducted an exploratory mass-univariate
analysis (Groppe, Urbach, & Kutas, 2011a,b) of the target predictability effect (low minus high
predictability) under LIFC and RIFC stimulation. The results of the mass univariate analysis are
summarized in Figure 3C using FDR-corrected raster plots, plotting the predictability difference
separately for the LIFC and RIFC stimulation. Under RIFC stimulation, we observe a clear
negativity between 300-500 msecs largely over central posterior electrodes, consistent with a
robust N400 predictability effect. However, under LIFC stimulation, that negativity, while still
present, is reduced in both spatial and temporal extent, suggesting a weaker N400 predictability
response under LIFC stimulation (see also Figure 3B).
We also ran a planned analysis to investigate how the late frontal positivity ERP
component—which has been seen in other studies using these same types of stimuli (Federmeier
et al., 2010; Ryskin et al., 2020)—was modulated by TMS stimulation to LIFC. We, however, did
not find any evidence for the typical late frontal positivity in either condition in this study. These
results can be found in these supplemental materials here: https://osf.io/yrngx/. Similarly, there
was no evidence for the presence of the late frontal positivity in the mass univariate analyses
which, if present, would have been observed as a sustained difference over anterior channels
following the N400 (see Figure 3C).
Discussion
In Experiment 2, under RIFC stimulation, we saw a similar pattern in recall that we saw in
Experiment 1. That is, in-category words were remembered better than incongruent target words
and for in-category words, we saw that high predictability words were recalled significantly better
than low predictability words. Thus, under RIFC stimulation conditions, we replicated the
predictability benefit to memory that was seen in Experiment 1. However, under LIFC stimulation,
while in-category words were recalled better than incongruent words, we found that the
predictability benefit effect seen to in-category words was completely eliminated. It is important
to keep in mind that stimulation occurred during the defining word of the category (when
prediction in this paradigm would arguably be able to begin) rather than at the target word. Thus,
the application of TMS protocol over LIFC known to disrupt speech production (Sakrieda et al.,
2018), prior to the processing and encoding of the target word, appeared to completely eliminate
the beneficial effects that prediction afforded in allowing individuals to better encode and/or recall
high predictability words. This finding provides strong evidence of the involvement of LIFC in
making top-down predictions during reading. Because the LIFC is unarguably a part of the
language production system, and we used a TMS protocol known to impair production, this finding
is consistent with the claim that the LIFC-mediated production system is recruited for generating
predictions during silent reading, consistent with a number of prediction-through-production
models (Federmeier, 2007; Dell & Chang, 2014; Pickering & Garrod, 2007, 2013; Mani & Huettig,
2012).
While the memory results offer strong evidence in support of the prediction is production
hypothesis, the N400 results are less clear. We did find a typical N400 pattern in the a priori mean
amplitude analysis, with the N400 response being largest to incongruent target words, smallest to
high predictability target words, and there being an intermediate response to low predictability
target words. However, our mean amplitude analysis did not find that this measure was statistically
sensitive to our TMS stimulation protocols. Moreover, we found no evidence that N400
congruency effects (i.e., in versus out of category) were modulated by TMS, suggesting that
disruption of the LIFC-mediated speech production network does not impact the canonical N400
congruency effect. However, our mass univariate analysis, which allows for a broader examination
of predictability effects across all time-points and electrodes, did reveal evidence that the N400
predictability effect was reduced in its spatial and temporal extent selectively for LIFC stimulation,
consistent with our prediction that disrupting speech-eloquent LIFC via TMS attenuates predictive
processing, leading to a reduced N400 facilitation for more predictable target words. This, taken
together with the memory results, again supports the hypothesis that prediction during
comprehension may be at least partially driven by LIFC. Importantly however, N400 effects of
both congruency and predictability were still clearly present under LIFC stimulation. This is not
necessarily surprising. Although the N400 has been found to be at least partially sensitive to
predictive processes (e.g., Federmeier & Kutas, 1999a), it is far more sensitive to contextual fit
than prediction (for a recent review of the N400 see Federmeier, 2022). We return to this point in
the general discussion.
One possible explanation for the discrepant results between the ROI-based and mass-
univariate-based results centers on the distribution of the N400 effect. Our conservative ROI-based
approach relied on selecting a small number of central and posterior electrodes and a small time
window in which the canonical N400 effect is largest. While visual N400 effect timing is
remarkably stable (Federmeier & Laszlo, 2009; Payne & Federmeier, 2017), the spatial
distribution of N400 effects is known to differ across studies as a function of different experimental
conditions (see Kutas & Federmeier, 2011 for a review). Moreover, the effects of TMS on N400
timing and scalp distribution are not well characterized, with this study being one of only a few
studies to examine such effects (see also Dave et al., 2020; Kroczek et a., 2019). In the mass-
univariate analysis, we observed the predictability effect under RIFC stimulation appeared largest
over central and posterior electrodes, consistent with our conservative ROI, but the spatial extent
was much larger than the six a priori electrodes, extending through all posterior and occipital
electrodes, as well as showing some significant effects across frontal electrodes as well. Similarly,
the temporal extent of the effect onset prior to 300 ms and extended well beyond 500 ms,
suggesting that the N400 predictability effect under RIFC stimulation was broader than what was
covered by our a priori ROI. As seen in Figure 3c, under LIFC stimulation, the predictability effect,
while still present, was largely diminished across the broad array of electrodes, and effects outside
of the a priori 300-500 ms window that were present under RIFC stimulation were largely
eliminated. These differences in spatial and temporal extent are likely driving the difference across
the two analysis approaches.
We also found similar patterns in online category judgement task accuracy as those seen
in Experiment 1. That is, that high predictability and incongruent target words were correctly
identified as being part of a category significantly better than low predictability words.
Importantly, this pattern held for both TMS stimulation conditions. This suggests that the TMS
stimulation at the category cue did not affect participants’ ability to perceive and judge target
words. In fact, our model showed that participants did even better in Experiment 2 than Experiment
1 at correctly identifying low predictability words as part of a category. Thus, the effects we found
on memory performance and the N400 predictability effect were likely not driven by an
elimination of the ability to comprehend or accurately categorize target words.
We note that, across Experiments 1 and 2, there did appear to be a general reduction in
recall accuracy. While this could suggest that TMS over both RIFC and LIFC globally impaired
verbal memory compared to no stimulation, we are cautious in drawing such conclusions across
the two samples due to the protocol differences added in order to accommodate adding TMS and
EEG to Experiment 2. For example, we increased the length of each trial and instituted mandatory
breaks between stimulation blocks. This led to a longer period of time between the start of the
category decision task and the start of the cued recall test in Experiment 2 compared to Experiment
1. Likewise, there were more protocols added before the beginning of the category decision task
(e.g., finding the MEP threshold, EEG capping, registering the participant to the neuro-navigation
system, etc.) all of which could have increased fatigue levels before beginning the category
decision task. Therefore, we restrict our interpretation to the within-subject effects of interests (i.e.,
the predictability effects) within each experiment.
GENERAL DISCUSSION
In two experiments, we investigated whether prediction benefits memory (Experiment 1)
and what role the LIFC plays in providing those benefits (Experiment 2). Our findings were clear.
In our first experiment, we established that there is a predictability benefit to long-term memory,
with better cued recall for higher predictability words compared to lower predictability words. In
the second experiment, we introduced a novel modification of an event-related TMS protocol
originally used to disrupt speech production (Krieg et al., 2017), which allowed us to disrupt LIFC
activity while participants read the same category-target pairs that were presented in Experiment
1. Critically, our event-related rTMS was applied prior to the target word, during presentation of
the meaning bearing word in the category context (e.g., A type of insect), when predictive
processing would be engaged, if it were engaged.
Thus, by using a protocol that is known to disrupt speech production when applied over
posterior LIFC (Hernandez-Pavon et al., 2014; Picht et al., 2013; Nettekoven et al., 2021; Sakreida
et al., 2018; Rogic et al., 2014; Tarapore et al., 2013), during a period of time when prediction
should be taking place, we could directly test if the LIFC-mediated language production system is
providing prediction-related benefits to memory by observing whether prediction-related benefits
observed in Experiment 1 were reduced when this system was disrupted. Indeed, we found that
the predictability benefit observed in the first experiment was completely eliminated under LIFC
(but not RIFC) stimulation. Importantly, online judgement accuracy was not affected by TMS
stimulation, suggesting that LIFC stimulation did not interfere with eventual comprehension or
categorization performance. In other words, our stimulation protocols did not disrupt the ability to
recognize and categorize the target word and integrate the target and context to make the
appropriate judgements during the online task. However, it did selectively impair any
predictability benefits to memory encoding. Below we discuss these findings in more detail, as
well as the electrophysiological findings from Experiment 2, and discuss the implications of these
findings for theories and models that implicate the production system in prediction.
In Experiment 2, we additionally measured the ERP response to target words. In both
stimulation conditions, we replicated past work showing graded brain N400 amplitudes as a
function of semantic fit between the category and target (e.g., Federmeier et al., 2010; Rysin et al.,
2020). Specifically, we found that the N400 response was largest to completely incongruent target
words, smallest to highly predictable targets and intermediate to low predictability but
categorically-congruent words. This adds to the ever-growing literature supporting the theory that
the N400 represents processes associated with accessing semantic memory (for a recent review
see Federmeier, 2022). Importantly however, while this general pattern was observed across both
RIFC and LIFC stimulation, we did observe some evidence that the N400 predictability effect (i.e.,
difference between high- and low- predictability target words) selectively differed in spatial and
temporal extent as a function of stimulation. Although our a priori mean amplitude analysis did
not reveal a statistically significant interaction, our mass univariate analyses did reveal evidence
consistent with a reduced predictability effect under LIFC stimulation compared to RIFC
stimulation (see Figure 3c). That is, under the control RIFC stimulation, we observed a robust
predictability effect in the expected N400 time window (300-500 ms) across a large array of central
and posterior electrodes, as well as significant predictability effects starting earlier (before 300
msec) and persisting later (600-700 msec) than the canonical N400 time windows. However, under
LIFC stimulation, the predictability effect appeared to be substantially reduced in both spatial and
temporal extent, with only a small number of posterior electrodes showing any statistically
significant time-points between 300-700 msec.
Much of the work on the N400 over the past several decades has found that, while the N400
is at least partially sensitive to predictive processes (e.g., Federmeier & Kutas, 1999a; Van Petten
et al., 1999), its amplitude is also strongly sensitive to contextual fit (see Federmeier, 2022; Kutas
& Federmeier, 2011), even in the absence of prediction (e.g., Federmeier & Kutas, 1999b, 2019;
Federmeier et al., 2002, 2010; Payne & Federmeier, 2018; Wlotko et al., 2012). Thus, it is not
surprising that our TMS protocol did not completely eliminate the N400 predictability effect, but
instead appeared to weakly modulate the magnitude of the benefit. It is important to keep in mind
that prediction is most likely not necessary for comprehension to occur (Huettig & Mani, 2016).
Indeed, we saw that performance on the online category decision task was the same in both
stimulation conditions, suggesting that our disruption to prediction, which was easily seen in the
memory data, did not impair individuals’ ability to categorize target words.
Importantly, our collective pattern of findings would be difficult to reconcile with a purely
bottom-up account, for example as driven by associative priming (Rhodes & Donaldson, 2008) or
difficulty in integration/unification (Zhu et al., 2019). Under this account, stimulation of LIFC
during the context would weaken or impair the representation of the context, leading to reduced
effects at the target word in the absence of any appeal to a predictive mechanism. First, LIFC
stimulation did not have any influence on the magnitude of the congruity ERP effect (incongruent
versus unpredictable but congruent). Under a bottom-up account, the out-of-category target by
definition shares fewer semantic features with the target and would be more difficult to integrate
with the prior context. However, LIFC stimulation did not appear to influence processing of the
incongruent target word. More strikingly, our primary memory results—a reduced predictability
benefit selectively under LIFC stimulation—appears to be driven by reduced memory for the
predictable word, whereas LIFC stimulation did not appear to have any effect on memory for
unpredictable or incongruent words (in fact, memory was numerically but not significantly better
for unpredictable words under LIFC stimulation). Finally, we observed that performance on the
online category decision task was the same in both stimulation conditions, suggesting that our
disruption to LIFC did not impair individuals’ ability to categorize target words, which would be
expected under a purely bottom-up account. Instead, our findings are more compatible with the
idea that LIFC-mediated predictive processing selectively facilitates some stages of processing for
predictable words (i.e., semantic access, memory encoding and/or retrieval), but does not appear
necessary for all aspects of comprehension (Huettig & Mani, 2016), such as processing a word as
incongruent with its prior context.
It is also important to interpret our findings within a growing set of literatures suggesting
that the LIFC clearly plays multiple roles in both language-specific and domain-general functions
(Fedorenko & Blank, 2020; Novick et al., 2005, 2010; Matchin, 2018; Friederici, 2020;
Grodzinsky & Santi, 2008; Hagoort, 2013; Matchin & Hickok, 2020; Tremblay & Dick, 2016;
Zaccarella et al., 2017). Moreover, while LIFC clearly plays a role as a hub of the speech
production system, the neural architecture supporting speech production is complex, widespread,
and context-dependent (Hickok et al., 2022; Bulut, 2022; Coutinho et al., 2021). Indeed, whereas
the anterior portion of LIFC (pars triangularis or Brodmann’s Area 45) is often associated with
semantic processing (Schell et al., 2017; Friederici, 2011, 2012; Hagoort, 2013), the posterior
portion of LIFC (pars opercularis or Brodmann’s Area 44) is involved in syntactic processing
(Hagoort, 2013; Ullman, 2016; Friederici, 2011, 2012) and domain-general cognitive control
processes (Novick et al., 2010; Fedorenko & Blank, 2020), in addition to being strongly linked to
multiple features of high-level speech production, including phonological retrieval (Matchin,
2018), lexical selection (Conner et al., 2019), and syllabic sequencing (Rong et al., 2018; Hickok
et al., 2022). Although, it is important to note that these mappings between anatomical sub-
divisions of LIFC and functional role do not always maintain at the individual level, as there is
substantial individual variability in the language network (Fedorenko, 2021), a topic we return to
below.
Although the functions of LIFC are multiply determined, we review below why we believe
our findings are still most compatible with a prediction-through-production interpretation of LIFC
stimulation. In our study, we specifically targeted posterior IFC not only because it was the
strongest candidate site for disrupting speech production based on the existing TMS literature but
also to avoid directly disrupting semantic processing. This approach appears to have been
successful, as categorical semantic processing was still clearly evident under LIFC stimulation
(see above discussion). Additionally, we designed our stimuli, simple sentence fragments with
identical syntactic structure (e.g., “A type of X”), to reduce any difficulty with syntactic parsing
that may be induced under LIFC stimulation (Udden et al., 2017). Because the locus of the
semantic predictability effect in our items was driven by a single category-defining word (and thus,
arguably, a message-level syntactic representation is not even necessary to elicit these effects) it
would be difficult to attribute our current findings to a selective disruption in syntactic parsing—
particularly the sort of non-adjacent dependency processing that has been recently proposed as
being disrupted due to TMS of LIFC (Udden et al., 2017).
Finally, we consider our pattern of findings under a domain-general cognitive control or
multiple demand account, whereby LIFC stimulation impairs domain-general (non-linguistic)
cognitive resources. First, under this account, we would expect the effects of stimulation to be
strongest in the most cognitively challenging conditions (e.g., Thompson-Schill et al., 1997). We
thus chose a task and stimuli that has very little demand on cognitive control and working memory
resources (Federmeier et al., 2010). Moreover, as discussed above, our TMS effects had no
influence on categorization performance for any condition, much less the unpredictable condition,
which showed relatively poorer categorization performance (despite high overall performance
levels, above 90%). Instead, the effects of LIFC TMS, as reflected in the memory task, appeared
to be more selective to the least-challenging high predictability condition. These findings are
difficult to account for under a domain-general cognitive demand account.
Overall then, while we relied on a stimulation protocol that reliably disrupts speech
production (Krieg et al., 2017), we do not argue that our stimulation selectively or only disrupted
production. It is entirely possible that our stimulation protocol over LIFC disrupted other linguistic
and non-linguistic processes in addition to (or in concert with) modulating one or more core
processes underlying successful speech production. However, given the simplicity of the stimuli
used and the task being performed, we believe that the most parsimonious explanation of the results
from this study is that the selective effects of LIFC TMS stimulation on prediction were likely due
to disrupting production-mediated predictive processing, as predicted under multiple models
(Federmeier, 2007; Dell & Chang, 2014; Pickering & Garrod, 2007, 2013; Mani & Huettig, 2012).
While we argue that evidence from our study is consistent with the involvement of the
production system in generating predictions during comprehension, it is difficult to make strong
claims underlying what stages of production or prediction are jointly disrupted by LIFC
stimulation. Indeed, Huettig (2015) argued that at least four different mechanisms are minimally
required for prediction to occur during comprehension, including: (1) recruitment of the production
system, (2) simple associative priming that occurs due to the structure of the lexicon, (3) the
buildup of higher-order meaning, and (4) pre-activation via event simulation. Based on these
proposals for multiple mechanisms, we cannot conclude from the present study that all kinds of
pre-activation or anticipatory phenomena in comprehension engage the production system nor that
we have found the neural locus of language prediction during comprehension. Indeed, Lesage and
colleagues (2012) found that repetitive TMS over the right cerebellum disrupted anticipatory eye
movements in a visual world paradigm. Likewise, Dave and colleagues (2020) found that theta
band TMS stimulation over the cerebellum specifically modulated episodic memory outcomes
while stimulation in the beta band range over the same region selectively modulated semantic
prediction, as measured by the N400 response. Taking this together with our study suggests that
there is no one location in the brain in which prediction occurs during comprehension. Therefore,
much work is needed to tease apart multiple different types of predictive mechanisms and how
these mechanisms are implemented in the brain. Additionally, the current study stimuli and
experimental task make it difficult to know which specific production processes are recruited for
prediction in general. For example, Pickering and Garrod (2007) proposed that the production
system is used to predict multiple features including phonological, syntactic, and semantic
features. Although our study was not designed specifically to differentiate between these potential
mechanisms, our target words were always nouns. Thus, it is unlikely that syntactic predictions
would be beneficial in our paradigm. Likewise, our category cues were non-constraining contexts,
so it is plausible that the prediction mechanism used could have co-activated multiple candidate
words—or at least features associated with multiple candidate words. Future work could use online
neuromodulatory techniques inspired by clinical speech mapping, such as the event-related TMS
protocol introduced here, to help differentiate which production processes are required for
predictive processes, and which are shared between prediction and production systems.
In the present study, our TMS targeting was selected using MNI coordinates for posterior
L/RIFC on a template MNI brain that was registered to each participant for stereotactic neuro-
navigation (Mazziota et al., 2001; Lancaster et al., 2007). Therefore, a successful registration relies
on reliable mapping between individual anatomy and the group-based template. Indeed, while
individualized anatomical mapping is the gold standard, recent evidence suggests that template-
based MNI localization can be used as an accurate and effective alternative to individualized
anatomical localization for TMS studies (Fleischmann et al., 2020). Perhaps more importantly,
given that the functional organization of LIFC can vary substantially from individual to individual
as discussed above (Mahowald & Fedorenko, 2016; Fedorenko et al., 2012), a need for
individualized functional localizers is critical for future research, arguably more so than
individualized anatomical targeting. Indeed, we believe that our findings provide a useful proof-
of-concept for considering speech mapping TMS stimulation as an individualized functional
localizer in future research. Building on our current findings, we are currently conducting work in
which we use a speech mapping protocol to identify individualized LIFC speech positive targets.
We believe this functional targeting may allow for even stronger modulatory effects in future work.
Nevertheless, without individualized imaging or a functional localizer, we still observed robust
theory-congruent effects of TMS on brain and behavioral outcomes.

In conclusion, we add to the growing evidence that prediction during comprehension can
benefit memory performance. Importantly, we found that the posterior LIFC, which is strongly
implicated in speech production, plays a major role in providing this prediction-related memory
benefit and may modulate real-time semantic-access during word processing, as reflected in the
N400 predictability effect. More broadly, this study demonstrates the pivotal role that combined
event-related TMS and ERPs play in delineating the neural mechanisms underlying complex
higher-order processes of human language comprehension.

References
Baayen, R. H., Davidson, D. J., & Bates, D. M. (2008). Mixed-effects modeling with crossed
random effects for subjects and items. Journal of Memory and Language, 59(4), 390-412.
http://dx.doi.org/10.1016/j.jml.2007.12.005
Bar, M. (2007). The proactive brain: Using analogies and associations to generate
predictions. Trends in Cognitive Sciences, 11(7), 280-289.
http://dx.doi.org/10.1016/j.tics.2007.05.005
Bar, M. (2009). Predictions: a universal principle in the operation of the human
brain. Philosophical Transactions of the Royal Society B: Biological Sciences, 364(1521),
1181-1182. http://dx.doi.org/10.1098/rstb.2008.0321
Barr, D. J., Levy, R., Scheepers, C., & Tily, H. J. (2013). Random effects structure for confirmatory
hypothesis testing: Keep it maximal. Journal of Memory and Language, 68(3), 255-278.
http://dx.doi.org/10.1016/j.jml.2012.11.001
Bates, D., Kliegl, R., Vasishth, S., & Baayen, H. (2015). Parsimonious mixed models. arXiv
preprint arXiv:1506.04967.
Berlingeri, M., Danelli, L., Bottini, G., Sberna, M., & Paulesu, E. (2013). Reassessing the
HAROLD model: Is the hemispheric asymmetry reduction in older adults a special case of
compensatory-related utilisation of neural circuits? Experimental Brain Research, 224(3),
393-410. http://dx.doi.org/10.1007/s00221-012-3319-x
Bonhage, C. E., Mueller, J. L., Friederici, A. D., & Fiebach, C. J. (2015). Combined eye tracking
and fMRI reveals neural basis of linguistic predictions during sentence
comprehension. Cortex, 68, 33-47. http://dx.doi.org/10.1016/j.cortex.2015.04.011
Bulut, T. (2022). Meta-analytic connectivity modeling of the left and right inferior frontal
gyri. Cortex, 155, 107-131 http://dx.doi.org/10.1016/j.cortex.2022.07.003
Burke, D. M., & Shafto, M. A. (2004). Aging and language production. Current Directions in
Psychological Science, 13(1), 21-24. http://dx.doi.org/10.1111/j.0963-
7214.2004.01301006.x
Cabeza, R. (2002). Hemispheric asymmetry reduction in older adults: The HAROLD
model. Psychology and Aging, 17(1), 85. http://dx.doi.org/10.1037/0882-7974.17.1.85
Castel, A.D., McCabe, H.L., & Roediger, H.L. (2007). Illusions of competence and overestimation
of associative memory for identical items: Evidence from judgements of learning.
Psychonomic Bulletin & Review. 14(1), 107-111. http://dx.doi.org/10.3758/BF03194036
Conner, C. R., Kadipasaoglu, C. M., Shouval, H. Z., Hickok, G., & Tandon, N. (2019). Network
dynamics of Broca’s area during word selection. PLoS One, 14(12), e0225756.
http://dx.doi.org/10.1371/journal.pone.0225756
Corina, D. P., Loudermilk, B. C., Detwiler, L., Martin, R. F., Brinkley, J. F., & Ojemann, G.
(2010). Analysis of naming errors during cortical stimulation mapping: implications for
models of language representation. Brain and Language, 115(2), 101-112.
http://dx.doi.org/10.1016/j.bandl.2010.04.001
Coutinho, L., Caramelli, P., & Teive, H. A. G. (2021). Aphasia localization: Was Pierre Marie
right? Brain, 144(12), 3547-3549. http://dx.doi.org/10.1093/brain/awab400
Dave, S., VanHaerents, S., & Voss, J. L. (2020). Cerebellar theta and beta noninvasive stimulation
rhythms differentially influence episodic memory versus semantic prediction. Journal of
Neuroscience, 40(38), 7300-7310.
Dell, G. S., & Chang, F. (2014). The P-chain: Relating sentence production and its disorders to
comprehension and acquisition. Philosophical Transactions of the Royal Society B:
Biological Sciences, 369(1634), 20120394. http://dx.doi.org/10.1523/JNEUROSCI.0595-
20.2020
DeLong, K. A., Troyer, M., & Kutas, M. (2014). Pre‐processing in sentence comprehension:
Sensitivity to likely upcoming meaning and structure. Language and Linguistics
Compass, 8(12), 631-645. http://dx.doi.org/10.1111/lnc3.12093
Eldaief, M. C., Press, D. Z., & Pascual-Leone, A. (2013). Transcranial magnetic stimulation in
neurology: A review of established and prospective applications. Neurology: Clinical
Practice, 3(6), 519-526. http://dx.doi.org/10.1212/01.CPJ.0000436213.11132.8e
Epstein, C. M., Meador, K. J., Loring, D. W., Wright, R. J., Weissman, J. D., Sheppard, S., ... &
Davey, K. R. (1999). Localization and characterization of speech arrest during transcranial
magnetic stimulation. Clinical Neurophysiology, 110(6), 1073-1079.
http://dx.doi.org/10.1016/S1388-2457(99)00047-4
Epstein, C. M., Meador, K. J., Loring, D. W., Wright, R. J., Weissman, J. D., Sheppard, S., ... &
Davey, K. R. (1999). Localization and characterization of speech arrest during transcranial

magnetic stimulation. Clinical Neurophysiology, 110(6), 1073-1079.
http://dx.doi.org/10.1016/S1388-2457(99)00047-4
Eyler, L. T., Sherzai, A., Kaup, A. R., & Jeste, D. V. (2011). A review of functional brain imaging
correlates of successful cognitive aging. Biological Psychiatry, 70(2), 115-122.
http://dx.doi.org/10.1016/j.biopsych.2010.12.032
Federmeier, K. D. (2007). Thinking ahead: The role and roots of prediction in language
comprehension. Psychophysiology, 44(4), 491-505. http://dx.doi.org/10.1111/j.1469-
8986.2007.00531.x
Federmeier, K. D. (2022). Connecting and considering: Electrophysiology provides insights into
comprehension. Psychophysiology, e13940-e13940. http://dx.doi.org/10.1111/psyp.13940
Federmeier, K. D., & Kutas, M. (1999a). A rose by any other name: Long-term memory structure
and sentence processing. Journal of Memory and Language, 41(4), 469-495.
http://dx.doi.org/10.1006/jmla.1999.2660
Federmeier, K. D., & Kutas, M. (1999b). Right words and left words: Electrophysiological
evidence for hemispheric differences in meaning processing. Cognitive Brain
Research, 8(3), 373-392. http://dx.doi.org/10.1016/S0926-6410(99)00036-1
Federmeier, K. D., & Kutas, M. (2019). What's “left”? Hemispheric sensitivity to predictability
and congruity during sentence reading by older adults. Neuropsychologia, 133, 107173.
http://dx.doi.org/10.1016/j.neuropsychologia.2019.107173
Federmeier, K. D., Kutas, M., & Schul, R. (2010). Age-related and individual differences in the
use of prediction during language comprehension. Brain and Language, 115(3), 149-161.
Federmeier, K. D., & Laszlo, S. (2009). Time for meaning: Electrophysiology provides insights
into the dynamics of representation and processing in semantic memory. Psychology of
Learning and Motivation, 51, 1-44.
Federmeier, K. D., McLennan, D. B., De Ochoa, E., & Kutas, M. (2002). The impact of semantic
memory organization and sentence context information on spoken language processing by
younger and older adults: An ERP study. Psychophysiology, 39(2), 133-146.
http://dx.doi.org/10.1111/1469-8986.3920133
Fedorenko, E. (2021). The early origins and the growing popularity of the individual-subject
analytic approach in human neuroscience. Current Opinion in Behavioral Sciences, 40,
105-112. http://dx.doi.org/10.1016/j.cobeha.2021.02.023
Fedorenko, E., & Blank, I. A. (2020). Broca’s area is not a natural kind. Trends in Cognitive
Sciences, 24(4), 270-284. http://dx.doi.org/10.1016/j.tics.2020.01.001
Ferrari, C., Cattaneo, Z., Oldrati, V., Casiraghi, L., Castelli, F., D’Angelo, E., & Vecchi, T. (2018).
TMS over the cerebellum interferes with short-term memory of visual sequences. Scientific
Reports, 8(1), 1-8. http://dx.doi.org/10.1038/s41598-018-25151-y
Ferreira, F., & Lowder, M. W. (2016). Prediction, information structure, and good-enough
language processing. In Psychology of Learning and Motivation (Vol. 65, pp. 217-247).
Academic Press. http://dx.doi.org/10.1016/bs.plm.2016.04.002

Fiebach, C. J., & Schubotz, R. I. (2006). Dynamic anticipatory processing of hierarchical
sequential events: a common role for Broca's area and ventral premotor cortex across
domains? Cortex, 42(4), 499-502. http://dx.doi.org/10.1016/S0010-9452(08)70386-1
Fleischmann, R., Köhn, A., Tränkner, S., Brandt, S. A., & Schmidt, S. (2020). Individualized
template MRI is a valid and reliable alternative to individual mri for spatial tracking in
navigated TMS studies in healthy subjects. Frontiers in Human Neuroscience, 14, 174.
http://dx.doi.org/10.3389/fnhum.2020.00174
Fregni, F., & Pascual-Leone, A. (2007). Technology insight: noninvasive brain stimulation in
neurology—perspectives on the therapeutic potential of rTMS and tDCS. Nature clinical
practice Neurology, 3(7), 383-393. http://dx.doi.org/10.1038/ncpneuro0530
Freigang, S., Fresnoza, S., Ali, K. M., Zaar, K., Jehna, M., Reishofer, G., ... & von Campe, G.
(2020). Impact of priming on effectiveness of TMS in detecting language-eloquent brain
areas in tumor patients. Journal of Neurological Surgery Part A: Central European
Neurosurgery, 81(02), 111-129. http://dx.doi.org/10.1055/s-0039-1698382
Friederici, A. D. (2011). The brain basis of language processing: from structure to
function. Physiological Reviews, 91(4), 1357-1392.
http://dx.doi.org/10.1152/physrev.00006.2011
Friederici, A. D. (2012). The cortical language circuit: from auditory perception to sentence
comprehension. Trends in Cognitive Sciences, 16(5), 262-268.
Friederici, A. D. (2020). Hierarchy processing in human neurobiology: How specific is
it? Philosophical Transactions of the Royal Society B, 375(1789), 20180391.
http://dx.doi.org/10.1098/rstb.2018.0391
Gatti, D., Vecchi, T., & Mazzoni, G. (2021). Cerebellum and semantic memory: A TMS study
using the DRM paradigm. Cortex, 135, 78-91.
http://dx.doi.org/10.1016/j.cortex.2020.11.017
Giglio, L., Ostarek, M., Weber, K., & Hagoort, P. (2021). Commonalities and asymmetries in the
neurobiological infrastructure for language production and comprehension. Cerebral
Cortex. Advance online publication. doi:10.1093/cercor/bhab287.
http://dx.doi.org/10.1093/cercor/bhab287
Gordon-Salant, S., & Fitzgibbons, P. J. (1997). Selected cognitive factors and speech recognition
performance among young and elderly listeners. Journal of Speech, Language, and Hearing
Research, 40(2), 423-431. http://dx.doi.org/10.1044/jslhr.4002.423
Grodzinsky, Y., & Santi, A. (2008). The battle for Broca’s region. Trends in cognitive
sciences, 12(12), 474-480.
Groppe, D. M., Urbach, T. P., & Kutas, M. (2011a). Mass univariate analysis of event‐related brain
potentials/fields I: A critical tutorial review. Psychophysiology, 48(12), 1711-1725.
http://dx.doi.org/10.1111/j.1469-8986.2011.01273.x
Groppe, D. M., Urbach, T. P., & Kutas, M. (2011b). Mass univariate analysis of event‐related
brain potentials/fields II: Simulation studies. Psychophysiology, 48(12), 1726-1737.
http://dx.doi.org/10.1111/j.1469-8986.2011.01272.x
Hagoort, P. (2013). MUC (memory, unification, control) and beyond. Frontiers in Psychology, 4,
416. http://dx.doi.org/10.3389/fpsyg.2013.00416
Hartwigsen, G., Golombek, T., & Obleser, J. (2015). Repetitive transcranial magnetic stimulation
over left angular gyrus modulates the predictability gain in degraded speech
comprehension. Cortex, 68, 100-110. http://dx.doi.org/10.1016/j.cortex.2014.08.027
Hauck, T., Tanigawa, N., Probst, M., Wohlschlaeger, A., Ille, S., Sollmann, N., ... & Krieg, S. M.
(2015). Stimulation frequency determines the distribution of language positive cortical
regions during navigated transcranial magnetic brain stimulation. BMC
Neuroscience, 16(1), 1-14. http://dx.doi.org/10.1186/s12868-015-0143-9
Hernandez-Pavon, J. C., Mäkelä, N., Lehtinen, H., Lioumis, P., & Mäkelä, J. P. (2014). Effects of
navigated TMS on object and action naming. Frontiers in Human Neuroscience, 8, 660.
http://dx.doi.org/10.3389/fnhum.2014.00660
Hickok, G., & Poeppel, D. (2004). Dorsal and ventral streams: a framework for understanding
aspects of the functional anatomy of language. Cognition, 92(1-2), 67-99.
http://dx.doi.org/10.1016/j.cognition.2003.10.011
Hickok, G., & Poeppel, D. (2007). The cortical organization of speech processing. Nature Reviews
Neuroscience, 8(5), 393-402. http://dx.doi.org/10.1038/nrn2113
Hickok, G., Venezia, J., & Teghipco, A. (2022). Beyond broca: neural architecture and evolution
of a dual motor speech coordination system. Brain.
http://dx.doi.org/10.1093/brain/awac454
Huettig, F. (2015). Four central questions about prediction in language processing. Brain
Research, 1626, 118-135. http://dx.doi.org/10.1016/j.brainres.2015.02.014
Huettig, F., & Mani, N. (2016). Is prediction necessary to understand language? Probably
not. Language, Cognition and Neuroscience, 31(1), 19-31.
http://dx.doi.org/10.1080/23273798.2015.1072223
Huettig, F., Audring, J., & Jackendoff, R. (2022). A parallel architecture perspective on pre-
activation and prediction in language processing. Cognition.
http://dx.doi.org/10.1016/j.cognition.2022.105050
Hunt, K. P., & Hodge, M. H. (1971). Category-item frequency and category-name meaningfulness
(m'): Taxonomic norms for 84 categories. Psychonomic Monograph Supplements.
Ishkhanyan, B., Michel Lange, V., Boye, K., Mogensen, J., Karabanov, A., Hartwigsen, G., &
Siebner, H. R. (2020). Anterior and posterior left inferior frontal gyrus contribute to the
implementation of grammatical determiners during language production. Frontiers in
psychology, 11, 685. http://dx.doi.org/10.3389/fpsyg.2020.00685
Jakuszeit, M., Kotz, S. A., & Hasting, A. S. (2013). Generating predictions: Lesion evidence on
the role of left inferior frontal cortex in rapid syntactic analysis. Cortex, 49(10), 2861-2874.
Johansson, J., Salami, A., Lundquist, A., Wåhlin, A., Andersson, M., & Nyberg, L. (2020).
Longitudinal evidence that reduced hemispheric encoding/retrieval asymmetry predicts
episodic-memory impairment in aging. Neuropsychologia, 137, 107329.
http://dx.doi.org/10.1016/j.neuropsychologia.2019.107329
Klaus, J., & Hartwigsen, G. (2019). Dissociating semantic and phonological contributions of the
left inferior frontal gyrus to language production. Human Brain Mapping, 40(11), 3279-
3287. http://dx.doi.org/10.1002/hbm.24597
Koriat, A., & Bjork, R.A. (2005). Illusions of competence in monitoring one’s knowledge during
study. Journal of Experimental Psychology: Learning, Memory, and Cognition, 31(2),
187-194. http://dx.doi.org/10.1037/0278-7393.31.2.187
Krieg, S. M., Lioumis, P., Mäkelä, J. P., Wilenius, J., Karhu, J., Hannula, H., ... & Picht, T. (2017).
Protocol for motor and language mapping by navigated TMS in patients and healthy
volunteers; workshop report. Acta Neurochirurgica, 159(7), 1187-1195.
http://dx.doi.org/10.1007/s00701-017-3187-z
Krieg, S. M., Tarapore, P. E., Picht, T., Tanigawa, N., Houde, J., Sollmann, N., ... & Nagarajan,
S. (2014). Optimal timing of pulse onset for language mapping with navigated repetitive
transcranial magnetic stimulation. Neuroimage, 100, 219-236.
http://dx.doi.org/10.1016/j.neuroimage.2014.06.016
Kroczek, L. O., Gunter, T. C., Rysop, A. U., Friederici, A. D., & Hartwigsen, G. (2019).
Contributions of left frontal and temporal cortex to sentence comprehension: Evidence from
simultaneous TMS-EEG. Cortex, 115, 86-98.
Kuperberg, G. R., & Jaeger, T. F. (2016). What do we mean by prediction in language
comprehension? Language, Cognition and Neuroscience, 31(1), 32-59.
http://dx.doi.org/10.1080/23273798.2015.1102299
Kutas, M. (1993). In the company of other words: Electrophysiological evidence for single-word
and sentence context effects. Language and Cognitive Processes, 8(4), 533-572.
http://dx.doi.org/10.1080/01690969308407587
Kutas, M., & Federmeier, K. D. (2011). Thirty years and counting: finding meaning in the N400
component of the event-related brain potential (ERP). Annual Review of Psychology, 62,
621-647. http://dx.doi.org/10.1146/annurev.psych.093008.131123
Kutas, M., DeLong, K. A., & Smith, N. J. (2011). A Look around at What Lies Ahead: Prediction
and Predictability in Language Processing. Predictions in the Brain: Using Our Past to
Generate a Future, 190. http://dx.doi.org/10.1093/acprof:oso/9780195395518.003.0065
Kutas, M., Federmeier, K. D., & Urbach, T. P. (2014). The "negatives" and "positives" of
prediction in language. In M. S. Gazzaniga & G. R. Mangun (Eds.), The Cognitive
Neurosciences (pp. 649–656). MIT Press.
http://dx.doi.org/10.7551/mitpress/9504.003.0071
Lancaster, J. L., Tordesillas‐Gutiérrez, D., Martinez, M., Salinas, F., Evans, A., Zilles, K., ... &
Fox, P. T. (2007). Bias between MNI and Talairach coordinates analyzed using the ICBM‐
152 brain template. Human Brain Mapping, 28(11), 1194-1205.
http://dx.doi.org/10.1002/hbm.20345
Lau, E. F., Holcomb, P. J., & Kuperberg, G. R. (2013). Dissociating N400 effects of prediction
from association in single-word contexts. Journal of Cognitive Neuroscience, 25(3), 484-
502. http://dx.doi.org/10.1162/jocn_a_00328
Lelonkiewicz, J. R., Rabagliati, H., & Pickering, M. J. (2021). The role of language production in
making predictions during comprehension. Quarterly Journal of Experimental
Psychology, 74(12), 2193-2209. http://dx.doi.org/10.1177/17470218211028438
Lesage, E., Morgan, B. E., Olson, A. C., Meyer, A. S., & Miall, R. C. (2012). Cerebellar rTMS
disrupts predictive language processing. Current Biology, 22(18), R794-R795.
http://dx.doi.org/10.1016/j.cub.2012.07.006
Luke, S. G., & Christianson, K. (2016). Limits on lexical prediction during reading. Cognitive
Psychology, 88, 22-60. http://dx.doi.org/10.1016/j.cogpsych.2016.06.002
Martin, C. D., Branzi, F. M., & Bar, M. (2018). Prediction is Production: The missing link between
language production and comprehension. Scientific Reports, 8(1), 1-9.
http://dx.doi.org/10.1038/s41598-018-19499-4
Matchin, W. G. (2018). A neuronal retuning hypothesis of sentence-specificity in Broca’s
area. Psychonomic Bulletin & Review, 25(5), 1682-1694.
http://dx.doi.org/10.3758/s13423-017-1377-6
Matchin, W., & Hickok, G. (2020). The cortical organization of syntax. Cerebral Cortex, 30(3),
1481-1498. http://dx.doi.org/10.1093/cercor/bhz180
Mazziotta, J., Toga, A., Evans, A., Fox, P., Lancaster, J., Zilles, K., ... & Mazoyer, B. (2001). A
probabilistic atlas and reference system for the human brain: International Consortium for
Brain Mapping (ICBM). Philosophical Transactions of the Royal Society of London. Series
B: Biological Sciences, 356(1412), 1293-1322. http://dx.doi.org/10.1098/rstb.2001.0915

McCoy, S. L., Tun, P. A., Cox, L. C., Colangelo, M., Stewart, R. A., & Wingfield, A. (2005).
Hearing loss and perceptual effort: Downstream effects on older adults’ memory for
speech. The Quarterly Journal of Experimental Psychology Section A, 58(1), 22-33.
http://dx.doi.org/10.1080/02724980443000151
McEvoy, C. L., & Nelson, D. L. (1982). Category name and instance norms for 106 categories of
various sizes. The American Journal of Psychology, 581-634.
http://dx.doi.org/10.2307/1422189
Menenti, L., Gierhan, S. M., Segaert, K., & Hagoort, P. (2011). Shared language: overlap and
segregation of the neuronal infrastructure for speaking and listening revealed by functional
MRI. Psychological Science, 22(9), 1173-1182.
http://dx.doi.org/10.1177/0956797611418347
Mesulam, M. (2008). Representation, inference, and transcendent encoding in neurocognitive
networks of the human brain. Annals of Neurology, 64(4), 367-378.
http://dx.doi.org/10.1002/ana.21534
Miller, G. A., & Selfridge, J. A. (1950). Verbal context and the recall of meaningful material. The
American Journal of Psychology, 63(2), 176-185. http://dx.doi.org/10.2307/1418920
Murphy, S. C., Palmer, L. M., Nyffeler, T., Müri, R. M., & Larkum, M. E. (2016). Transcranial
magnetic stimulation (TMS) inhibits cortical dendrites. Elife, 5, e13598.
http://dx.doi.org/10.7554/eLife.13598
Nettekoven, C., Pieczewski, J., Neuschmelting, V., Jonas, K., Goldbrunner, R., Grefkes, C., &
Weiss Lucas, C. (2021). Improving the efficacy and reliability of rTMS language mapping
by increasing the stimulation frequency. Human Brain Mapping, 42(16), 5309-5321.
http://dx.doi.org/10.1002/hbm.25619
Noda, Y., Silverstein, W. K., Barr, M. S., Vila-Rodriguez, F., Downar, J., Rajji, T. K., ... &
Blumberger, D. M. (2015). Neurobiological mechanisms of repetitive transcranial magnetic
stimulation of the dorsolateral prefrontal cortex in depression: A systematic
review. Psychological Medicine, 45(16), 3411-3432.
http://dx.doi.org/10.1017/S0033291715001609
Novick, J. M., Trueswell, J. C., & Thompson-Schill, S. L. (2005). Cognitive control and parsing:
Reexamining the role of Broca’s area in sentence comprehension. Cognitive, Affective, &
Behavioral Neuroscience, 5(3), 263-281. http://dx.doi.org/10.3758/CABN.5.3.263
Novick, J. M., Trueswell, J. C., & Thompson‐Schill, S. L. (2010). Broca’s area and language
processing: Evidence for the cognitive control connection. Language and Linguistics
Compass, 4(10), 906-924. http://dx.doi.org/10.1111/j.1749-818X.2010.00244.x
Nuñez, A. I. R., Yue, Q., Pasalar, S., & Martin, R. C. (2020). The role of left vs. right superior
temporal gyrus in speech perception: An fMRI-guided TMS study. Brain and
Language, 209, 104838. https://doi.org/10.1016/j.bandl.2020.104838
Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh
inventory. Neuropsychologia, 9(1), 97-113. http://dx.doi.org/10.1016/0028-
3932(71)90067-4
Opitz, B., & Kotz, S. A. (2012). Ventral premotor cortex lesions disrupt learning of sequential
grammatical structures. Cortex, 48(6), 664-673.
Pascual‐Leone, A., Gates, J. R., & Dhuna, A. (1991). Induction of speech arrest and counting
errors with rapid‐rate transcranial magnetic stimulation. Neurology, 41(5), 697-702.
http://dx.doi.org/10.1212/WNL.41.5.697
Payne, B. R., & Silcox, J. W. (2019). Aging, context processing, and comprehension.
In Psychology of Learning and Motivation (Vol. 71, pp. 215-264). Academic Press.
http://dx.doi.org/10.1016/bs.plm.2019.07.001
Payne, B. R., & Federmeier, K. D. (2017). Pace yourself: Intraindividual variability in context use
revealed by self-paced event-related brain potentials. Journal of Cognitive
Neuroscience, 29(5), 837-854. http://dx.doi.org/10.1162/jocn_a_01090
Payne, B.R., & Federmeier, K.D. (2018). Contextual constraints on lexico-semantic processing in
aging: Evidence from single-word event-related brain potentials. Brain Research, 1687,
117-128. http://dx.doi.org/10.1016/j.brainres.2018.02.021
Picht, T., Krieg, S. M., Sollmann, N., Rösler, J., Niraula, B., Neuvonen, T., ... & Ringel, F. (2013).
A comparison of language mapping by preoperative navigated transcranial magnetic
stimulation and direct cortical stimulation during awake surgery. Neurosurgery, 72(5), 808-
819. doi: 10.1227/NEU.0b013e3182889e01
Pickering, M. J., & Garrod, S. (2007). Do people use language production to make predictions
during comprehension?. Trends in Cognitive Sciences, 11(3), 105-110.
Pickering, M. J., & Garrod, S. (2013). An integrated theory of language production and
comprehension. Behavioral and Brain Sciences, 36(4), 329-347.
http://dx.doi.org/10.1017/S0140525X12001495
Poeppel, D., Emmorey, K., Hickok, G., & Pylkkänen, L. (2012). Towards a new neurobiology of
language. Journal of Neuroscience, 32(41), 14125-14131.
http://dx.doi.org/10.1523/JNEUROSCI.3244-12.2012
Rhodes, S. M., & Donaldson, D. I. (2008). Association and not semantic relationships elicit the
N400 effect: Electrophysiological evidence from an explicit language comprehension
task. Psychophysiology, 45(1), 50-59. http://dx.doi.org/10.1111/j.1469-8986.2007.00598.x
Riggs, K. M., Wingfield, A., & Tun, P. A. (1993). Passage difficulty, speech rate, and age
differences in memory for spoken text: Speech recall and the complexity
hypothesis. Experimental Aging Research, 19(2), 111-128.
http://dx.doi.org/10.1080/03610739308253926
RogiĆ, M., DeletiS, V., & Fernández-Conejero, I. (2014). Inducing transient language disruptions
by mapping of Broca's area with modified patterned repetitive transcranial magnetic
stimulation protocol. Journal of Neurosurgery, 120(5), 1033-1041.
https://doi.org/10.3171/2013.11.JNS13952
Rommers, J., Dell, G. S., & Benjamin, A. S. (2020). Word predictability blurs the lines between
production and comprehension: Evidence from the production effect in
memory. Cognition, 198, 104206. http://dx.doi.org/10.1016/j.cognition.2020.104206
Rong, F., Isenberg, A. L., Sun, E., & Hickok, G. (2018). The neuroanatomy of speech sequencing
at the syllable level. PloS One, 13(10), e0196381.
http://dx.doi.org/10.1371/journal.pone.0196381
Rösler, J., Niraula, B., Strack, V., Zdunczyk, A., Schilt, S., Savolainen, P., ... & Picht, T. (2014).
Language mapping in healthy volunteers and brain tumor patients with a novel navigated
TMS system: Evidence of tumor-induced plasticity. Clinical Neurophysiology, 125(3), 526-
536. https://doi.org/10.1016/j.clinph.2013.08.015
Rossini, P. M., Burke, D., Chen, R., Cohen, L. G., Daskalakis, Z., Di Iorio, R., ... & Ziemann, U.
(2015). Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and
peripheral nerves: Basic principles and procedures for routine clinical and research
application. An updated report from an IFCN Committee. Clinical Neurophysiology, 126(6),
1071-1107. http://dx.doi.org/10.1016/j.clinph.2015.02.001
Ryskin, R., Ng, S., Mimnaugh, K., Brown-Schmidt, S., & Federmeier, K. D. (2020). Talker-
specific predictions during language processing. Language, Cognition and
Neuroscience, 35(6), 797-812. http://dx.doi.org/10.1080/23273798.2019.1630654
Sakreida, K., Lange, I., Willmes, K., Heim, S., Binkofski, F., Clusmann, H., & Neuloh, G. (2018).
High-resolution language mapping of Broca’s region with transcranial magnetic
stimulation. Brain Structure and Function, 223(3), 1297-1312.
http://dx.doi.org/10.1007/s00429-017-1550-8
Schell, M., Zaccarella, E., & Friederici, A. D. (2017). Differential cortical contribution of syntax
and semantics: An fMRI study on two-word phrasal processing. Cortex, 96, 105-120.
Silbert, L. J., Honey, C. J., Simony, E., Poeppel, D., & Hasson, U. (2014). Coupled neural systems
underlie the production and comprehension of naturalistic narrative speech. Proceedings of
the National Academy of Sciences, 111(43), E4687-E4696.
http://dx.doi.org/10.1073/pnas.1323812111
Silcox, J. W., & Payne, B. R. (2021). The costs (and benefits) of effortful listening on context
processing: A simultaneous electrophysiology, pupillometry, and behavioral
study. Cortex, 142, 296-316. http://dx.doi.org/10.1016/j.cortex.2021.06.007
Tarapore, P. E., Findlay, A. M., Honma, S. M., Mizuiri, D., Houde, J. F., Berger, M. S., &
Nagarajan, S. S. (2013). Language mapping with navigated repetitive TMS: Proof of
technique and validation. Neuroimage, 82, 260-272.
http://dx.doi.org/10.1016/j.neuroimage.2013.05.018
Thielscher, A., Antunes, A., & Saturnino, G. B. (2015, August). Field modeling for transcranial
magnetic stimulation: a useful tool to understand the physiological effects of TMS? In 2015
37th Annual International Conference of the IEEE Engineering in Medicine and Biology
Society (EMBC) (pp. 222-225). IEEE. http://dx.doi.org/10.1109/EMBC.2015.7318340
Thompson-Schill, S. L., D’Esposito, M., Aguirre, G. K., & Farah, M. J. (1997). Role of left inferior
prefrontal cortex in retrieval of semantic knowledge: a reevaluation. Proceedings of the
National Academy of Sciences, 94(26), 14792-14797.
http://dx.doi.org/10.1073/pnas.94.26.14792
Thornhill, D. E., & Van Petten, C. (2012). Lexical versus conceptual anticipation during sentence
processing: Frontal positivity and N400 ERP components. International Journal of
Psychophysiology, 83(3), 382-392. http://dx.doi.org/10.1016/j.ijpsycho.2011.12.007
Tremblay, P., & Dick, A. S. (2016). Broca and Wernicke are dead, or moving past the classic
model of language neurobiology. Brain and Language, 162, 60-71.
Tremblay, P., Poulin, J., Martel-Sauvageau, V., & Denis, C. (2019). Age-related deficits in speech
production: From phonological planning to motor implementation. Experimental
Gerontology, 126, 110695. http://dx.doi.org/10.1016/j.exger.2019.110695
Uddén, J., Ingvar, M., Hagoort, P., & Petersson, K. M. (2017). Broca’s region: A causal role in
implicit processing of grammars with crossed non-adjacent dependencies. Cognition, 164,
188-198. http://dx.doi.org/10.1016/j.cognition.2017.03.010
Ullman, M. T. (2016). The declarative/procedural model: A neurobiological model of language
learning, knowledge, and use. In Neurobiology of Language (pp. 953-968). Academic
Press. https://doi.org/10.1016/B978-0-12-407794-2.00076-6
Van Berkum, J. J. (2010). The brain is a prediction machine that cares about good and bad-any
implications for neuropragmatics? Italian Journal of Linguistics, 22, 181-208.
https://hdl.handle.net/11858/00-001M-0000-0012-C6B0-9
Van Overschelde, J. P., Rawson, K. A., & Dunlosky, J. (2004). Category norms: An updated and
expanded version of the norms. Journal of Memory and Language, 50(3), 289-335.
https://doi.org/10.1016/j.jml.2003.10.003
Van Petten, C., & Luka, B. J. (2012). Prediction during language comprehension: Benefits, costs,
and ERP components. International Journal of Psychophysiology, 83(2), 176-190.
https://doi.org/10.1016/j.ijpsycho.2011.09.015
Van Petten, C., Coulson, S., Rubin, S., Plante, E., & Parks, M. (1999). Time course of word
identification and semantic integration in spoken language. Journal of Experimental
Psychology: Learning, Memory, and Cognition, 25(2), 394. https://doi.org/10.1037/0278-
7393.25.2.394
Wang, W. C., Wing, E. A., Murphy, D. L., Luber, B. M., Lisanby, S. H., Cabeza, R., & Davis, S.
W. (2018). Excitatory TMS modulates memory representations. Cognitive
Neuroscience, 9(3-4), 151-166. http://dx.doi.org/10.1080/17588928.2018.1512482
Wlotko, E. W., Federmeier, K. D., & Kutas, M. (2012). To predict or not to predict: Age-related
differences in the use of sentential context. Psychology and Aging, 27(4), 975.
http://dx.doi.org/10.1037/a0029206
Zaccarella, E., Schell, M., & Friederici, A. D. (2017). Reviewing the functional basis of the
syntactic Merge mechanism for language: A coordinate-based activation likelihood
estimation meta-analysis. Neuroscience & Biobehavioral Reviews, 80, 646-656.
http://dx.doi.org/10.1016/j.neubiorev.2017.06.011
Zhu, Z., Bastiaansen, M., Hakun, J. G., Petersson, K. M., Wang, S., & Hagoort, P. (2019).
Semantic unification modulates N400 and BOLD signal change in the brain: A
simultaneous EEG-fMRI study. Journal of Neurolinguistics, 52, 100855.
http://dx.doi.org/10.1016/j.jneuroling.2019.100855

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Running head: PREDICTION, INFERIOR FRONTAL CORTEX, AND TMS 1

and subsequent memory: Evidence from simultaneous TMS-EEG

Jack W Silcox1, Brian Mickey2,3, Brennan R. Payne1,3

All correspondence should be addressed to:

on production theories of prediction, TMS, and implications for memory.

comprehension with explicit verbal production.

the language production system that is sensitive to TMS stimulation.

whether there were any benefits of prediction to subsequent memory.

In Experiment 2, we simultaneously recorded electroencephalography (EEG) and

If the LIFC-mediated language production system is implicated in prediction-related memory

subsequent N400 predictability effect at the target word.

Materials & Methods

corresponding target words can be found in the Supplemental Materials found at

counterbalanced across three separate lists.

Participants were seated approximately 55 cm from a monitor. Participants were instructed

target word that they had seen.

estimated with the pairs() function from the emmeans package in R.

Data and Code Availability Statement

= 8.65, z = 7.60, p < 0.001).

Incongruent target words. Error bars represent standard error.

(high vs. low) = 1.88, SE = 0.42, z = 2.85, p < 0.05).

In summary, in Experiment 1, we found that participants had near-ceiling performance

Importantly though, we found evidence for a predictability benefit within congruent

in Experiment 2, we utilized an online, event-related TMS protocol.

Materials & Methods

including depression or anxiety.

Materials and Design

and reregistered to the neuronavigation system.

threshold (SD = 6.0%).

each screen show the SOAs.

lab was approximately 3.5 hours.

EEG Recording and Processing

analyses are discussed in Data Analyses, below.

like we did in Experiment 1. In addition to a priori ERP analyses, we conducted an additional

responses. Specifically, we conducted a mass-univariate analysis of the predictability effect (low

FDR-adjusted p-values less than .05 were included in these visualizations.

Category Decision Behavior Results

pattern observed under no brain stimulation in Experiment 1.

effect of stimulation order on the original model.2

frontal cortex; LIFC = left inferior frontal cortex.

In addition to our ROI-based analysis, we conducted an exploratory mass-univariate

response under LIFC stimulation (see also Figure 3B).

following the N400 (see Figure 3C).

predictions during silent reading, consistent with a number of prediction-through-production

the general discussion.

the two analysis approaches.

elimination of the ability to comprehend or accurately categorize target words.

the predictability effects) within each experiment.

In two experiments, we investigated whether prediction benefits memory (Experiment 1)

the second experiment, we introduced a novel modification of an event-related TMS protocol

processing would be engaged, if it were engaged.

providing prediction-related benefits to memory by observing whether prediction-related benefits

In Experiment 2, we additionally measured the ERP response to target words. In both

significant time-points between 300-700 msec.

incongruent with its prior context.

multiple features of high-level speech production, including phonological retrieval (Matchin,

being disrupted due to TMS of LIFC (Udden et al., 2017).

Finally, we consider our pattern of findings under a domain-general cognitive control or

multiple demand account, whereby LIFC stimulation impairs domain-general (non-linguistic)

difficult to account for under a domain-general cognitive demand account.

to disrupting production-mediated predictive processing, as predicted under multiple models

production system in generating predictions during comprehension, it is difficult to make strong