Experimental Neurology 197 (2006) 244 – 251

www.elsevier.com/locate/yexnr

Regular Article

Intra-operative STN DBS attenuates the prominent beta rhythm

in the STN in Parkinson’s disease
Brett Wingeier c, Tom Tcheng c, Mandy Miller Koop a, Bruce C. Hill a,
Gary Heit b, Helen M. Bronte-Stewart a,b,*
a
Department of Neurology and Neurosciences Institute, Stanford University, 300 Pasteur Dr., Rm. A343, Stanford, CA 94305-5327, USA
b
Department of Neurosurgery, Stanford University, Stanford, CA 94305-5327, USA
c
NeuroPace Inc., Mountain View, California, USA

Received 6 July 2005; revised 12 September 2005; accepted 16 September 2005

Available online 10 November 2005

Abstract

Power spectra from local field potentials (LFPs) recorded post-operatively from the deep brain stimulation (DBS) macroelectrode show
prominence of the beta rhythm (11 – 30 Hz) in untreated Parkinson’s disease (PD). Dopaminergic medication and movement attenuate this beta
band in PD. In this pilot study of six sides in four patients, we recorded LFPs from the DBS electrode in untreated PD patients in the operating
room. In all cases, there was a peak in the time-frequency spectrogram in the beta frequency range when the patients were at rest, which was
associated with attenuation in the same range with movement. The actual frequency range and the strength of the beta peak varied among cases. In
two patients, intra-operative constraints permitted recording of LFPs at rest, before and immediately after subthalamic nucleus (STN) DBS. In both
patients we documented that STN DBS caused a significant attenuation in power in the beta band at rest that persisted for 15 – 25 s after DBS had
been turned off ( P < 0.01). From one case, our data suggest that the beta rhythm attenuation was most prominent within the STN itself. This study
shows for the first time that STN DBS attenuates the power in the prominent beta band recorded in the STN of patients with PD. These pilot
findings raise the interesting possibility of using this biomarker for closed loop DBS or neuromodulation.
D 2005 Elsevier Inc. All rights reserved.

Keywords: Parkinson’s disease; Subthalamic nucleus; Deep brain stimulation; Beta rhythm; Neuronal oscillations

Introduction 1989; Alexander and Crutcher, 1990; DeLong, 1990; Wichmann

In Parkinson’s disease (PD) and in animal models of
parkinsonism, neurons of basal ganglia nuclei such as the
subthalamic nucleus (STN) and the globus pallidus interna (GPi)
fire at increased rates and with irregular, oscillatory and often
bursting temporal patterns (Bergman et al., 1990, 1994; DeLong,
1990; Filion and Tremblay, 1991; Kühn et al., 2005; Levy et al.,
2001; Lozano et al., 1996; Miller and DeLong, 1987; Vitek et al.,
1998; Wichmann et al., 1994). Traditional models of the
pathophysiology in PD have used firing rate changes in GPi
and STN and their resultant downstream target modulation to
account for signs such as bradykinesia and akinesia (Albin et al.,
* Corresponding author. Department of Neurology and Neurosciences
Institute, Stanford University, 300 Pasteur Dr., Rm. A343, Stanford, CA
94305-5327, USA. Fax: +1 650 725 7459.
E-mail address: hbs@stanford.edu (H.M. Bronte-Stewart).
0014-4886/$ - see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.expneurol.2005.09.016
and DeLong, 1996). Changes in firing rates in STN and GPi are
more likely to influence their projection targets if the post-
synaptic efficacy of neuronal activity is increased through the
synchronization of neuronal discharges within these nuclei. In
primate models of PD using the neurotoxin MPTP, synchronized
neuronal oscillations have been demonstrated in GPi, STN and
the external segment of the globus pallidus (GPe) (Nini et al.,
1995; Raz et al., 2000). Oscillatory firing patterns appear to be
synchronized through the basal ganglia circuits and are reflected
by increased power and abnormally synchronized firing patterns
in the beta band in the motor cortex (Goldberg et al., 2002; Raz et
al., 2001). Intra-operative single unit recordings in human
patients with PD have confirmed the presence of coupling and
synchronization of neuronal firing in the beta band in STN, GPi,
and GPe (Levy et al., 2002a; Levy et al., 2000).
With the advent of functional mapping procedures used for
deep brain stimulation (DBS) to treat patients with PD, it has
 B. Wingeier et al. / Experimental Neurology 197 (2006) 244 – 251
now become possible to record both single- and multi-unit
neuronal discharges from microelectrodes and to record local
field potentials (LFPs) from the permanently implanted
macroelectrode. The LFP is the result of synchronous activity
within a population of neurons, and the timing of neuronal
discharge has been correlated in the cortex to fluctuations in the
LFP (Creutzfeldt et al., 1966; Frost, 1968). There is evidence
that LFPs recorded in basal ganglia nuclei also reflect
synchronized aggregate neuronal activity (Goto and O’Don-
nell, 2001; Kühn et al., 2004; Tsubokawa and Sutin, 1972).
Several groups have now recorded LFPs from the DBS
macroelectrode in GPi and/or STN during the immediate post-
operative period prior to the implantation of the pulse
generator. These studies have demonstrated that in PD patients,
LFPs recorded from the STN and GPi show increased power
and increased coherence in the alpha and beta frequency bands
(Brown et al., 2001; Cassidy et al., 2002; Kühn et al., 2004;
Levy et al., 2002a; Priori et al., 2004). Coherence in the beta
band has also been found between STN and the cortex and
between the STN and contralateral EMG activity. Stimulation
at the sites in STN that had the greatest coherence with the
cortex led to the greatest improvement in parkinsonian
symptoms (Marsden et al., 2001; Williams et al., 2002).
Active movement and levodopa treatment both decrease the
beta band power and coherence found in basal ganglia nuclei
LFPs (Cassidy et al., 2002; Kühn et al., 2004; Levy et al.,
2001, 2002b; Priori et al., 2002). The inverse relation between
levodopa and the beta band signal has led to the hypothesis that
prominence of the beta band rhythm is a pathophysiological
biomarker of the parkinsonian state. Therefore, interventions to
reduce subcortical and cortical beta band prominence seem
promising therapeutic strategies, although no study has shown
that the prominence of beta frequencies is correlated with the
degree of bradykinesia in PD.
Brown et al. (2004) have shown that STN DBS at beta
frequencies (20 Hz) increases beta band power in the GPi in
patients with PD, whereas DBS at high frequencies decreases
beta band power. However, no study has yet shown whether
STN DBS, like levodopa, reduces the prominent beta
synchrony in the STN itself.
In this pilot study, we show that intra-operative LFP
recordings from the DBS macroelectrode confirm the promi-
nence of the beta band power in the STN in a series of patients
with PD, at rest, off medication. In one side each from two
patients, where the data were available, we show that the power
in the beta frequency band at rest is significantly attenuated
after STN DBS and that the attenuation was most prominent
within the STN itself.
Methods
Patient assessment
Intra-operative recordings were collected during STN DBS
implantation, from six sides in four patients with PD. All
patients signed a written informed consent for the study, which
was approved by the Stanford Institutional Review Board. The
245
pre-operative selection criteria and assessment of patients have
been previously described (Taylor Tavares et al., 2005).
One week prior to the STN DBS implant procedure, long-
acting medications were replaced with short-acting medications
for all patients. Short-acting medications were then withdrawn
12 h before the procedure. Intra-operative assessments were
made on unmedicated, awake patients.
Surgical technique
Patients meeting the surgical inclusion criteria underwent
functional stereotactic, microelectrode-guided implantation of
chronic stimulating electrodes in the STN. Details of the
surgical technique, including intra-operative ventriculography
and radiography, have been described previously (Romanelli et
al., 2004). The sensorimotor region of the STN was identified
with multipass microelectrode mapping. The dorsal border of
the STN for each microelectrode track was identified by an
increase in the background signal level with the characteristic
firing pattern as the microelectrode entered the STN. Using
intra-operative radiographs of each microelectrode track and
the DBS electrode position, we determined the locations of
both the dorsal border of STN and of each contact in intra-
cranial coordinates (dorsal – ventral, lateral –medial, anterior –
posterior) referenced to the anterior commissural – posterior
commissural (AC –PC) plane. We estimate that our measure-
ments of DBS lead position are accurate within 0.3 mm. This
figure is based on the expected error when radiographs of the
microelectrode and the DBS electrode are overlaid (0.2 mm),
the resolution of the radiograph film (0.1 mm), and the
expected error in determination of STN boundaries resulting
from error in microelectrode depth reading (0.2 mm) (Roma-
nelli et al., 2004). Assuming these to be normally-distributed
random errors, the expected cumulative standard error is the
square root of the sum of the squares of the individual errors;
thus, approximately 0.3 mm. In cases where the DBS electrode
was not implanted exactly along a microelectrode track, we
estimated the position of each contact with respect to the dorsal
or ventral border of the STN by using the location of either
along the microelectrode track that was closest to the DBS
electrode.
Intra-operative assessment
After microelectrode mapping and determination of the
anatomical site of the sensorimotor region, the DBS electrode
(model 3389, Medtronic, Inc., Minneapolis, Minnesota) was
placed in the center of this region, not necessarily coincident
with a previous microelectrode track. The base of the most
ventral contact of the DBS electrode was always placed at or
dorsal to the base of the STN, as determined from electro-
physiological recording. Therapeutic effectiveness of this
electrode placement was then verified by clinical assessment
of improvements in rigidity, and quantitative assessment of
upper extremity bradykinesia using an angular velocity sensor
(MOTUS Bioengineering Inc., Benicia, CA) attached to the
wrist (Miller Koop et al., in press), during intra-operative DBS.
246 B. Wingeier et al. / Experimental Neurology 197 (2006) 244 – 251
Intra-operative DBS was applied using a hand held pulse
generator (Medtronic, Inc. Minneapolis Minnesota, USA).
Standard intra-operative screening parameters were used;
namely, bipolar stimulation between contact 0 ( ) and contact
3 (+), with frequency 185 Hz, pulse width 90 micros, and
voltage 3 Volts. Note that these stimulation parameters are to be
distinguished from the standard electrical parameters used post-
operatively to optimize clinical efficacy and minimize adverse
effects, where a monopolar mode is usually employed (Obeso
et al., 2001). The distance between the centers of the most
ventral and dorsal contacts (0 and 3 respectively) using the
3389 DBS macroelectrode is 6.0 mm. Any adverse effects of
stimulation were also documented.
Intra-operative local field potential (LFP) recordings
After radiographic documentation of the anatomical location
of the DBS electrode, LFPs were recorded from the DBS
macroelectrode, with the patient awake and not under any
anesthesia. A custom built electronic switch was included to
allow the DBS lead to be used alternately for recording and
stimulation. During stimulation, an attenuated version of the
stimulation waveform was recorded in order to allow precise
identification of DBS ON and DBS OFF time points.
LFP signals were preamplified by Axon Instruments
BioAmp 100 amplifiers, band-pass filtered with 3 dB
attenuation at 1 Hz and 800 Hz, and amplified further. The
filtered signals were then digitized at 10 KHz (using an Axon
Digidata 1200B 12-bit analog-to-digital converter controlled
by Axoscope V8.1) or at 2.5 KHz (using a National
Instruments PCI-MIO-16XE-50 16-bit analog-to-digital con-
verter controlled by LabVIEW V6) and stored in electronic
format for offline analysis. Of the two patients labeled herein
S1 and S2, from whom pre- and post-DBS recordings were
collected, S1 was studied with the 10 KHz system and S2 was
studied with the 2.5 KHz system. In each case, four bipolar
channels were recorded from the DBS lead; specifically,
contact pairs 0 –1, 1 – 2, 2– 3, and 0 –3, where contact 0 is
most ventral and contact 3 is most dorsal. Surface EMG from
wrist flexor and extensor muscles, and wrist angular velocity
data (MOTUS Bioengineering Inc., Benicia CA), were col
lected in parallel with LFP signals in order to verify movement
state during later, offline analysis.
Three movement states were used during recording: resting
(forearm and hand contralateral to implant comfortably
supported), passive movement (hand manipulated through
flexion and extension at approximately one cycle per second),
and active movement (patient flexed and extended the hand at
approximately one cycle per second). Note that these tasks
were used throughout the DBS implantation to assess motor
function; tasks were not novel to the patient at the time of LFP
recording. During the resting and movement states other parts
of the patient’s body were still.
For each patient, in this pilot study, the sequence of
movement states and stimulations during recording was
necessarily dictated by intra-operative constraints. Thus, no
single protocol was used for all patients. Task sequences used
during recording were based on two templates. In the first
template, labeled RPA (resting, passive and active), the patient
was guided through approximately 20 s each of the resting,
passive, and active states. In the second template, labeled
PERISTIM, the patient remained in a single movement state for
approximately 60 s. Pre-stimulation LFPs were recorded for 20
s; stimulation was delivered for 20 s; and post-stimulation
LFPs were recorded for 20 s. The electrical parameters for all
stimulations were the same as those used to test for clinical
efficacy (see above). In each case, LFP data were recorded for
approximately 30 min, after the DBS lead was implanted.
During these thirty min, intraoperative constraints permitted
execution of the RPA sequence an average of twice per patient,
and execution of the PERISTIM sequence only in two patients
(including patient S1).
Data analysis: identification of beta band
All data were inspected visually, including EMG and
MOTUS data, to confirm that movement states were as
expected. Data with unexpected movement or other artifact
were excluded from analysis. Between 1 and 5 s of data were
excised from each task transition in the RPA sequence, again
based upon examination of EMG and MOTUS data, to ensure
analysis only of data during clearly-defined task states. DBS
ON and DBS OFF time points were determined from all
recordings. Periods of switching artifact, resulting from the
stimulation-to-recording transition, were identified and labeled
as such and excluded from spectral analysis. All offline signal
analysis was performed using MATLAB software (version 6.5,
The MathWorks, Inc., Natick, MA).
Power spectral density was calculated for each movement
state in the RPA data, using an averaged periodogram method
with Hanning windows of 1 s width and 0.5 s overlap (Bendat
and Piersol, 2000). In those patients for whom multiple
instances of a movement state were collected, stationarity over
the recording period was assumed and spectra were averaged
over these instances.
Power spectra in the resting state, and the ratio of active-
movement power to resting-state power, were examined for each
DBS recording channel in each implant in order to identify a
contiguous beta band in which power was peaked in the resting
state and attenuated by movement. Identification of this beta
band for each implant was based on the following criteria,
chosen empirically after preliminary inspection of the data. First,
a generalized power law relation, of the form power = 1/f a, was
fit to each channel’s resting-state power spectrum using linear
regression in the log – log domain. The beta band was then
defined as the widest contiguous range of frequencies within 10
to 40 Hz in which (1) at least two of three adjacent-pairs channels
(0– 1, 1– 2, 2 –3) showed power elevated over the smooth 1/f a
curve, and (2) at least two of three adjacent-pair channels
showed a decrease of power with active movement (ratio of
active-movement power to resting power less than 1). Note that
the same channels were not required to meet the criteria
continuously through the identified beta band; rather, a
frequency bin was considered part of the beta band if any two
 B. Wingeier et al. / Experimental Neurology 197 (2006) 244 – 251 247

or more channels met the criteria in that bin. The fourth channel
(0– 3) was not included in these criteria since it is redundant in
simple linear relation to the other channels.
Data analysis: examination for DBS effects
All data were further inspected in order to locate se
quences in which LFPs were recorded in the resting state
within 5 s after DBS OFF, and in which these post-
stimulation LFPs could be compared with a pre-stimulation
or distant post-stimulation resting-state. A time-frequency
spectrogram was generated for each such sequence, exclud-
ing periods of DBS ON and post-stimulation switching
artifact. Each spectrogram was produced using an averaged
periodogram method, with Hanning windows of 1 s length
and 0.5 s overlap, yielding temporal resolution of 0.5 s and
frequency resolution of 1 Hz. Frequencies of 3 Hz and
below were judged inseparable from low-frequency artifact
and are not shown in spectrograms. The variation over time
of total beta band power (using the beta band previously
identified for each implant) was determined by summing
total power over the beta frequencies yielding a beta-power
sum for each time point in the resulting spectrograms.
A single mean value was calculated for total beta band
power over each LFP epoch. Roughly 25 s of LFP data were
recorded in the resting state after DBS was switched off,
including a delay of about 4– 5 s when switching from the
stimulating to recording mode. After exclusion of switching
delay, this post-DBS period was divided in half, yielding an
early post-stimulation epoch (¨5– 15 s post-DBS OFF) and a
late post-stimulation epoch (¨15– 25 s post-DBS OFF), and a
single mean value was calculated for beta band power over
each of these epochs. Confidence intervals of 99% were
determined for each such value using the chi-square distribu-
tion method given by Bendat and Piersol (2000) in order to
facilitate assignment of significance to differences in beta
power between these epochs. Note that arrangement of these
epochs is clarified and shown fully in Results below.
Results
Local field potentials were recorded from the DBS
electrode (model 3389, Medtronic Int., Minneapolis, Minne-
sota, USA) during STN DBS implantation of six sides in
four subjects with advanced PD. Each LFP recording was
performed after the DBS electrode had been placed in the
final desired location and had been tested for efficacy using
intra-operative STN DBS (Romanelli et al., 2004). As
discussed in Methods, recording of data was governed by
intra-operative constraints, including the need to manually
switch between recording and stimulation. Of the 6 sides,
two (patient S1, R STN, and patient S2, R STN) yielded
recordings of resting state LFPs, free of artifact, beginning 5
or fewer seconds after the ‘‘DBS OFF’’ time point. We note
that these two recordings were acquired with different
acquisition systems and controlling software (see Methods),
as evidence that our results are not attributable to recording
or switching artifact.
Fig. 1 displays the power spectra (upper traces) from DBS
electrode contact pairs 0 –1, 1 –2, 2 – 3, and 0– 3, in the 2
patients S1 and S2. The lower traces of each panel represent the
ratio of spectral power during movement to spectral power at
rest. Traditional definitions of frequency bands in cortical
oscillatory activity recorded in electroencephalograms have
defined the beta band as those frequencies between 13 and 30
Hz. Instead of taking this range of frequencies a priori, in each
case we identified the widest contiguous frequency band
between 10 and 40 Hz where two of the three adjacent-pair
channels (0 –1, 1 – 2, and 2– 3) showed a spectral peak at rest
(elevation of upper traces above the best-fit smooth power law
curve, as described in Methods) coincident with attenuation
during active movement (depression of lower traces below the
horizontal line representing a ratio of one). Spectral peaks in
the resting state nearly spanned the beta range in both patients
(16 – 29 Hz in S1 and 17– 31 Hz in S2). Recordings from
different pairs of contacts revealed that in each case there was
variability in the dominance of the beta band at rest among

Fig. 1. Beta band, prominent in resting state and attenuated by active movement, is shown for two implants. Logarithmic power spectra of local field potentials,
averaged over artifact-free intervals of the resting state, are traced in the upper portion of each panel for S1 (R STN, panel A) and S2 (R STN, panel B). Sixty Hz line
noise artifact has been excised from spectra when present (S2). Ratios of similarly-determined power spectra in the active movement state, to power spectra in the
resting state, are traced in the lower portion of each panel. Power spectra and power ratios are shown for all bipolar DBS lead channels (contacts 0 – 1, 1 – 2, 2 – 3, and
0 – 3). Grey vertical bands represent the region of beta prominence in the resting state, and beta attenuation in the active movement state, identifiable for each implant
as described in Methods.
248 B. Wingeier et al. / Experimental Neurology 197 (2006) 244 – 251
contact pairs. For instance, in Fig. 1A (S1 right STN) the beta
peak is more prominent across contact pair 1 – 2 than across
contact pair 2 – 3, while in Fig. 1B (S2 right STN) the beta peak
is most prominent across contact pair 0 – 1, although the signal
from contact pair 2– 3 is also peaked above the best-fit power
law curve (fit not shown). Although we present in detail only
those patients and sides (S1 and S2) for whom resting-state
post-DBS data were available, we note that a contiguous beta
band was identifiable in each of the six sides studied. Across
the six sides, the beta bands identified included frequencies
from 14 to 35 Hz and the mean band width was 9.8 Hz (r = 5.0
Hz).
In the first case (S1, Fig. 1A), we recorded from the
STN DBS electrode immediately before and after intra-
operative DBS (the PERISTIM sequence), while the patient
was at rest. The recording, shown in Fig. 2, was made from
the right STN of subject S1 who was a 70-year-old woman
with an 8-year history of PD whose UPDRS motor
disability score off medication was 63 (advanced disease
severity). Figs. 2A, C, and E show power spectra in a
time –frequency plot, recorded over contact pairs 0 –1 (A),
1 –2 (C), and 2– 3 (E) immediately before and after 20 s of
intra-operative DBS. Visual inspection of Fig. 2C (between
contacts 1 – 2) suggests a prominence of frequencies below
10 Hz and in the beta band (13 –35 Hz) before DBS.
Inspection of Fig. 2A (contacts 0 – 1) suggests a lesser
degree of beta-band prominence, and still less activity in the
beta band was evident in the power spectrum recorded from
the most dorsal contact pair (2 – 3, Fig. 2E). Visual
inspection of Figs. 2A and C also shows a decrease in
activity in beta band frequencies after intra-operative DBS
and a later resumption of this activity. Figs. 2B, D, and F
quantify the relative strength of the beta frequency band
over time over the corresponding contacts. Over contacts 1 –
2 (Fig. 2D), there was a significant decrease of power in
beta frequencies for approximately 15 s after DBS was
switched off ( P < 0.01), after which it increased back to
pre-DBS levels. Over contacts 0 –1 (Fig. 2C), the baseline
power in the resting state was less than measured over
contacts 1 – 2. However, there was still significant attenua-
tion of beta frequencies after STN DBS. In contrast, there
was little activity in the beta frequency band recorded over
contacts 2 –3, and this activity did not change significantly
after intra-operative STN DBS (Fig. 2F). The location of the
center of contact 3 was measured to be 0.2 mm above the
roof of the STN, as determined by the depth at which STN
was entered in the nearest microelectrode track, which was
within 0.5 mm of the DBS electrode track. The distance
between the centers of the most ventral and dorsal contacts
using the 3389 DBS macroelectrode is 6.0 mm and the
spacing between the centers of each contact is 2 mm. Thus,
the recording over contact pair 1 –2 (Figs. 2C and D), which
showed higher power in beta frequencies, reflects synchro-
nized neural activity from the STN itself and the recording
from contact pair 2 –3, which showed lower power in beta
frequencies, reflects a lesser degree of synchronized activity
at the dorsal border and above STN. The recording over
contact pair 0– 1 reflects synchronized neural activity from a
more ventral region of the STN. Repeated trials (data not
shown) confirmed the result of Fig. 2 in each case, showing
significant (P < 0.01) attenuation of the beta frequencies
immediately after STN DBS.
In a second patient S2 (right STN, power spectra in Fig.
1B), LFPs were recorded for a prolonged period during
active and passive movement as well as at rest, before,
during, and after intra-operative DBS, Fig. 3. This patient
was a 53 year-old man with a 12-year duration of PD,
whose UPDRS motor disability score pre-operatively off
medication was 29. The recording is shown during the
resting state. These segments were those identified as resting
in the protocol and which showed no movement on the
angular velocity or EMG recordings. Fig. 3B demonstrates
the reduction in beta dominance over contact pair 0 –1 after
intra-operative DBS. In this case the center of contact 0 was
measured to be 1.5 mm above the ventral border of STN,
based on the location of the closest microelectrode track
(less than 0.5 mm from the site of the DBS electrode).
The baseline power in the beta range during the resting
state is shown at the left of Fig. 3B (‘‘Rest, pre-stim’’) and
then again at the far right (‘‘Rest, distant post-stim’’). In
between there are 2 intervals during which there were active
and passive movement and DBS, and active and passive
movement only (insets Fig. 3A). After 227 s of STN DBS,
the power in the beta band decreased significantly in both
the early and late post-stimulation epochs (P < 0.01, middle
grey bars, Fig. 3B) as compared to pre-stimulation (left) and
distant post-stimulation (far right). In addition, the power in
the beta band was significantly less (P < 0.01) in the early
post-stimulation epoch as compared to the late post-
stimulation epoch. As described in Methods, the early and
late post-stimulation epochs were each defined as 50% of
the period of time in which artifact free data were recorded
after DBS was turned off.
Although beta frequencies in basal ganglia nuclei are
known to decrease during active movement (Cassidy et al.,
2002; Kühn et al., 2004; Levy et al., 2002b; Priori et al.,
2002), Fig. 3B demonstrates that the decrease in beta that
persisted after movement and STN DBS (first interval) was
due to DBS and not to movement, as this decrease did not
occur after the second interval, during which there was
movement but no DBS.
In this patient, we also observed a significant reduction
in power in the beta band for 11 s after STN DBS in
contact pairs 1– 2 and 0 – 3, although EKG artifact and other
interference resulted in poor data for the second post-DBS
epoch in these contacts. Over contact pair 2 –3, there also
was a trend of a decrease in the power in beta frequencies
but an additional longer switching delay resulted in too
short an interval of post-DBS data for statistical processing.
Of interest, we observed that after 20 s of intra-operative
STN DBS the beta power was attenuated for 15 s or less after
DBS was turned off (Fig. 2D) but, after 227 s of STN DBS,
power in beta frequencies was significantly reduced for the
full period of time that data were recorded (about 25 s).
 B. Wingeier et al. / Experimental Neurology 197 (2006) 244 – 251
Fig. 2. Attenuation of beta band after STN-DBS, patient S1 Right STN. Time-frequency spectrograms (A, C, E) are shown for patient S1 (R STN), at rest, immediately before and after 20 s of intra-operative DBS (3 V,
90 micros pulse width, 185 Hz, contact 0 , contact 3+). Warmer colors indicate increased power. Timecourse (dots) and epochal averages (grey bars) of total beta band power are shown for the same recording (B, D,
F). Horizontal extent of grey bars indicates span of time over which power averages were calculated for (respectively) pre-DBS baseline, immediate post-DBS, and late post-DBS epochs. Vertical error bars (blue)
indicate 99% confidence interval of epochal averages. Beta band power in marked immediate post-DBS epochs (*, panels B and D) is significantly different ( P < 0.01) from pre-DBS baseline and late post-DBS
epochs. Note that contact pair 2 – 3 (panel F), believed to span the dorsal boundary of the STN, shows minimal beta power and no significant attenuation.

249
250 B. Wingeier et al. / Experimental Neurology 197 (2006) 244 – 251

Fig. 3. Attenuation of beta band after STN-DBS, patient S2 Right STN. Resting-state segments of an extended time – frequency spectrogram (A) are shown for
patient S2 (R STN). Warmer colors indicate increased power. As in Fig. 2, timecourse (dots) and epochal averages (grey bars) of total beta band power are shown for
the same recording (B). Horizontal extent of grey bars indicates span of time over which power averages were calculated for, from left to right: pre-DBS, immediate
post-DBS, late post-DBS, and distant post-DBS epochs. Vertical error bars (blue) indicate 99% confidence interval of epochal averages. Beta band power in each
marked post-DBS epoch (*) is significantly different ( P < 0.01) from the other marked post-DBS epoch and from both pre-DBS and distant post-DBS epochs.

Movement did not produce a prolonged attenuation of beta
power (Fig. 3B).
Discussion
In this pilot study we have shown that it is possible to record
LFPs from the implanted STN macroelectrode in the operating
room, in patients with PD who are undergoing STN DBS. In the
literature to date, most such recordings have been done 2 – 3 days
post-operatively from externalized leads. Our data confirm
previous findings that there is a prominence of power in the beta
frequency band in the STN region in patients with PD at rest, in
the un-medicated state (Brown et al., 2001; Cassidy et al., 2002;
Kühn et al., 2004; Levy et al., 2002a; Marsden et al., 2001; Priori
et al., 2004; Williams et al., 2002). We defined the band of
interest as that which showed an increase in power at rest and a
reduction in power with active movement, instead of pre-
determining the frequency band of interest.
In the two patients in whom we recorded LFPs both before
and immediately after intra-operative STN DBS at rest, we
documented that DBS significantly reduced the power in the
beta band. This effect persisted for about 15 s after the end of a
short period of STN DBS (20 s) and for at least 22 s after a
longer (227 s) period of DBS. This is the first report to
document that STN DBS reduces beta prominence in the STN
in humans with PD.
In one patient where data from all contact pairs were
available, it appeared that the prominence of beta and the degree
of attenuation after DBS appeared to be greater across contacts
which lay within the STN than across the pair in the dorsal aspect
and above the STN itself. The location of the contacts with
respect to the roof of the STN was calculated using intra-
operative ventriculography and radiography in concert with
MER. Activity in the beta band was less prominent in a more
ventral region of STN, although there was still a significant
attenuation from STN DBS. These findings support those from a
recent study of LFPs recorded from microelectrodes intra-
operatively, which found an increase in beta prominence as the
microelectrode passed from above the STN into the STN and a
trend for decreased beta prominence as the microelectrode
moved in a ventral direction (Kühn et al., 2005).
Dopaminergic medication reduces the prominence of beta
frequencies in basal ganglia nuclei and the cortex (Brown et al.,
2001; Levy et al., 2002b; Marsden et al., 2001; Williams et al.,
2002), suggesting that a decrease in beta prominence may be a
biomarker of a therapeutic effect for mobility in PD. Although
we cannot prove that the therapeutic mechanism of action of
DBS is solely that of reducing aberrant prominence of beta
activity in circuits through the STN, the fact that DBS mirrors the
effect of medication in reducing beta is supportive of a
hypothesis that reduction in beta synchrony is therapeutic in
PD. However, at this point the clinical standard for determina-
tion of an optimal location for the DBS electrode remains
observation of reduction in the signs of PD with intra-operative
DBS.
The results of this pilot study raise an interesting possibility
of closed loop DBS or neuromodulation, using the attenuation
of beta prominence as a neurophysiological biomarker. These
preliminary findings need to be confirmed with a larger study.
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