CHAPTER V

Noncognitive Treatments
of Memory Impairments

1. TRANSCRANIAL DIRECT CURRENT STIMULATION

During the past 10 years, transcranial direct current stimulation (tDCS) has
been applied in neurological rehabilitation, especially in motor but also in
cognitive rehabilitation. The mechanism underlying tDCS is a change in
neuronal membrane potentials that is dependent on the direction of the cur-
rent flow (anodal vs cathodal). Anodal stimulation increases the excitability
of the neurons below the electrode and cathodal stimulation decreases the
excitability. Therefore, depending on the current flow, it is possible to facil-
itate or to inhibit neuronal processes. Although the cortical areas that are
influenced by tDCS are considerably large and it is impossible to restrict
the stimulation to highly specialized areas, some impact on more motor
(than, e.g., more sensory or more cognitive) areas can still be realized.
One other important limit of tDCS is that the current only reaches cortical
surface areas (at least with an effective intensity). Subcortical nuclei or cor-
tical structures not adjacent to the skull cannot be stimulated directly by
tDCS. This is of major importance for tDCS as a tool for memory rehabil-
itation, because recollection is based on hippocampal and thalamic processes.
Due to the localization of these two structures they cannot be reached by
tDCS. On the other hand, structures like the prefrontal cortex, an area
highly associated with encoding and retrieval processes, are open to tDCS
stimulation.
Manenti, Cotelli, Robertson, and Miniussi (2012) reviewed tDCS stud-
ies on episodic memory performance in healthy subjects and also in patients
with brain diseases. They concluded that stimulation of the left dorsolateral
prefrontal cortex seems to induce a positive effect on verbal learning and
retrieval in healthy controls. A more recent review (Passow, Thurm, &
Li, 2017) argues that there is strong evidence for a positive effect of left pre-
frontal stimulation on verbal memory in older and younger healthy subjects.
The effect of temporal lobe stimulation is still unclear, as only a few studies
focused on this question. On the other hand, Meier and Sauter (2018) did

Cognitive Rehabilitation of Memory © 2019 Elsevier Inc.

https://doi.org/10.1016/B978-0-12-816981-0.00005-9 All rights reserved. 179
180 Cognitive Rehabilitation of Memory

not find any effect of tDCS to frontal and parietal brain regions for perfor-
mance in recognition memory and conclude that memory benefits of tDCS
are not easily replicated.
Manenti et al. (2012) reviewed three patient studies using tDCS. The
three studies concerned the treatment of Alzheimer’s disease patients using
anodal tDCS and all showed positive effects. One of the studies used
repeated sessions of anodal tDCS applied bilaterally over the temporal cor-
tex. Performance in a visual recognition test was used as the outcome var-
iable. Stimulation with tDCS increased memory performance in this group
and the effect was still observed at a follow-up session, 4 weeks after the end
of the stimulation. This result is interesting, but because of visual recognition
being a rather experimental outcome variable, the transfer to free recall and
everyday memory performance remains unclear. Moreover, the study did
not include a control group.
Bystad et al. (2016) conducted an RCT with tDCS applied over the left
temporal cortex in six 30-min sessions distributed over 10 days. Twenty-five
Alzheimer’s disease patients were included in the study: 12 received active
stimulation and 13 were given sham stimulation. Bystad et al. (2016) used
the California Verbal Learning Test (CVLT) as the outcome variable. They
found no significant change in the CVLT comparing the two groups, but the
increase in delayed recall approached significance (p ¼ 0.052). Compared to
the study reviewed by Manenti et al. (2012), Bystad et al. (2016) used fewer
tDCS sessions and included a very small sample of patients. This and focusing
on free recall instead of recognition may explain the differences between the
studies. Still, it seems to be fair to argue that evidence for using tDCS in Alz-
heimer’s patient to improve their memory performance is missing. How-
ever, there are several trials running on this topic, which will help to
clarify the prospect of tDCS in this patients group.
Two studies used tDCS to treat patients with memory impairments
resulting from a stroke. Yun, Chun, and Kim (2015) randomized 45 stroke
patients to three groups: one receiving anodal stimulation of the left anterior
temporal lobe, one receiving stimulation of the right anterior temporal lobe,
and one group receiving sham stimulation. Stimulation was delivered five
times a week for 30 min, for 3 weeks. The study was double-blinded, but
no information is available about concealment. Also, the definition of a pri-
mary outcome variable is somewhat vague, as the defined test (a verbal learn-
ing test) allowed for different evaluations (learning sum, delayed recall,
recognition, etc.). Inclusion criteria were experiencing a stroke within
the last 6 months, no lesion concerning the temporal lobes, and a score lower
 Noncognitive Treatments of Memory Impairments 181

than 27 in the Mini Mental State Examination (MMSE). The exclusion of

patients with lesions in the temporal lobe is straightforward because the
intervention concerned tDCS of this brain region. On the other hand, such
an exclusion criterion implies that patients with hippocampal lesions or
lesions in adjacent regions belonging to the limbic system would not be trea-
ted. The 15 days of tDCS stimulation led to a significant increase in delayed
recall for the verbal learning test, but not group differences in absolute
scores. Other tests, such as the MMSE and tests for attention and working
memory were not differentially changed by the stimulation. Thus, the
impact of the 15 sessions of tDCS was restricted to one neuropsychological
outcome variable, did not lead to different performance levels between the
groups (but to a higher intragroup increase of performance), and there was
no follow-up; two aspects that weaken the significance of this study.
The second study on the impact of tDCS on stroke patients was an
experimental study, which only looked for short-term after-effects of stim-
ulation (Kazuta et al., 2017). They also used stimulation of the temporal lobe
and found that stimulation increased the learning ability of the stroke
patients.
As yet, there have not been any studies combining tDCS and functional
memory training or studies on the combination of tDCS and teaching the
patients different strategies for encoding and retrieval. Moreover, the patient
studies did not rely on left prefrontal stimulation. The current research indi-
cates that stimulating this region shows the most convincing effect in healthy
subjects. Because of the important role of the prefrontal cortex in encoding
and retrieval (analyzed in Chapter II), one would expect a major impact of its
stimulation not only in healthy subjects but also in patients with acquired
brain damage who do not suffer from a lesion in the Papez circuit. Unfor-
tunately, we have no data on this question.
In summary, it seems fair to state that tDCS might have an impact on
memory rehabilitation, but this still must be shown in “real world” rehabil-
itation studies.

2. NEUROFEEDBACK
Neurofeedback has been used as a treatment of developmental disorders
such as attention deficit hyperactivity disorder (ADHD), but there are only
a few studies focusing on the prospect of this method in patients with mem-
ory deficits due to acquired brain damage. Recently, Renton, Tibbles, and
Topolovec-Vranic (2017) reviewed the application of neurofeedback in
182 Cognitive Rehabilitation of Memory

stroke patients with memory impairments. The systematic review identified

eight studies that could be included into the qualitative synthesis. Five of
these studies were case studies, three were group studies, two of the three
studies were nonrandomized and none of the group studies were blinded.
One of the two group studies that also assessed memory performance
showed improved memory performance and one study did not show an
improvement. Overall, publications scored poorly concerning both external
and internal validity categories, i.e., they showed a high risk of a confound-
ing and selection bias. Power was also insufficient for most of the publica-
tions (case studies). Therefore, at this point in time, the significance of
neurofeedback for memory rehabilitation is at best unclear.