# Repetitive Transcranial Magnetic Stimulation of Dorsolateral Prefrontal Cortex Affects Performance of the Wisconsin Card Sorting Task during Provision of Feedback

Authors: Ji Hyun Ko; Oury Monchi; Alain Ptito; Michael Petrides; Antonio P. Strafella
Journal: International Journal of Biomedical Imaging
 (2008)

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## Abstract

Early functional neuroimaging studies of tasks evaluating executive processes, such as the Wisconsin card sorting task (WCST), only assessed trials in blocks that may contain a large amount of different cognitive processes. More recently, we showed using event-related fMRI that the dorsolateral prefrontal cortex (DL-PFC) significantly increased activity during feedback but not matching periods of the WCST, consistent with its proposed role in the monitoring of information in working memory. Repetitive transcranial magnetic stimulation (rTMS) is a method that allows to disrupt processing within a given cortical region and to affect task performance for which this region is significantly solicited. Here we applied rTMS to test the hypothesis that the DL-PFC stimulation influences monitoring of working memory without interfering with other executive functions. We applied rTMS to the right DL-PFC and the vertex (control site) in different time points of the WCST. When rTMS was applied to the DL-PFC specifically during the period when subjects were receiving feedback regarding their previous response, WCST performance deteriorated, while rTMS did not affect performance during matching either when maintaining set or during set-shifting. This selective impairment of the DL-PFC is consistent with its proposed role in monitoring of events in working memory.


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## Body

## 1. Introduction

There is considerable evidence that damage to the prefrontal cortex impairs performance on cognitive
set-shifting tasks [1–3].
In one such task, the Wisconsin card sorting task (WCST), the subject has to match, over successive trials, a
test card to one of four reference cards based on a matching rule that the
subject acquires on the basis of feedback provided after each matching
response. Patients with prefrontal lesions are often impaired in shifting the
principle of matching when the feedback provided indicates that a cognitive
shift in mental set is required. Functional neuroimaging studies support these
observations [4–6].
In a recent study, conducted with functional magnetic resonance imaging (fMRI),
we demonstrated differential activation of different parts of the prefrontal
cortex during the performance of the WCST. In particular, we were able to show
that the dorsolateral prefrontal cortex (DL-PFC) was engaged when feedback was
provided [4].
This selective engagement of the
mid-DL-PFC during the provision of feedback after each matching response by the
subject is consistent with the proposed role of this part of the prefrontal
cortex in the monitoring of events
in working memory [7–9].
Neuroimaging studies, however, suffer from the limitation that they provide
neuronal correlates of cognitive performance and cannot determine a causal
relation between observed brain activity and cognitive performance [10, 11].
Thus the specific functional relevance of the DL-PFC in monitoring the feedback
provided during the performance of set-shifting tasks remains to be
established.Here we have used repetitive
transcranial magnetic stimulation (rTMS) to
examine this issue. The application of rTMS to an area of cortex that, at a
particular point in time, is actively involved in the processing of task-relevant information should cause
performance to decline [12–14]. In other words, rTMS acts
as a “virtual lesion” producing a
temporary interruption of processing [15].
In the present study, we tested the hypothesis that rTMS of the human DL-PFC influences monitoring of the
information held in the working memory without interfering with other executive functions. To test this
specific hypothesis, we used a computerized
version of the WCST [4] in which different stages of task performance
can be isolated. We applied rTMS to the right DL-PFC and over a control site
(the vertex) in three different ways: at the beginning of the feedback period, at the beginning of the matching response
period, and independently of task timing. Our previous functional neuroimaging
study had indicated the involvement of the DL-PFC during the provision of
feedback, but not during the matching response. To further strengthen our
findings, we also added a control task (Figure 3(b)) that only required
matching to a twin card.


## 2. Materials and Methods

Ten healthy subjects (19–33 years)
participated in the study after having given written informed consent. All subjects were right-handed according to the
Edinburgh handedness inventory [16], they had no previous personal or family
history of neurological or psychiatric disorders and were not taking any
medication at the time of experiments. The experiments were approved by
the Research Ethics Committee of the Montreal Neurological Institute and
Hospital. Figure 2 displays an overview and timing of the experimental
setup.


### 2.1. Cognitive Task

Subjects were trained for 30 minutes on the WCST
before the rTMS sessions. Prior to the training sessions, the subjects were instructed to perform as well as
they could. During the WCST, four
reference cards and one matching
card were presented on a computer screen
(Figure3(a)). On each trial, the subjects had to match a test card to
one of the four reference cards according to one of three rules: shape, number,
or color. The currently appropriate rule for classification is found by trial
and error based on the 3-second positive or negative feedback that is provided
immediately after each matching decision. The rule for classification changed randomly after the subject answers
correctly on six consecutive trials. In the control task, the matching card was identical
to one of the reference cards so that the subject simply selected the
identical card and did not have to find an appropriate rule for classification
as in the WCST (Figure 3(b)). Subjects performed the card-sorting
tasks in six different rTMS sessions (2 ×  3 design). Five-minute breaks were
given in between sessions. Each session lasted six minutes.


### 2.2. Frameless Stereotaxy System

In order to target the DL-PFC and vertex (control site) in all our subjects
(Figure1), we used a procedure that takes advantage of the standardized
stereotaxic space of Talairach and Tournoux [17] and frameless stereotaxy [18, 19]. A high-resolution MRI of the subjects’ brain was
acquired and transformed into standardized stereotaxic space using the
algorithm of Collins et al. [20]. The coordinates selected for the right DL-PFC
(X = 45, Y = 33, Z = 25) were based
on a previous functional activation study that yielded increased activity
during the feedback period [4]. Of note, in this study, we stimulated the DL-PFC
located in the right hemisphere because this side appeared to be more
consistently and robustly activated [4]. The control stimulation site (i.e., vertex
region, X = 0, Y =
−35, Z = 80) was
also chosen based on its lack of activation during performance of the WCST in
these previous studies.TMS coil
was located over (a) the right DL-PFC (X = 45,  Y = 33,  Z = 25) or (b) the vertex (control) (X = 0,  Y = −35,  Z = 80). The positioning of the TMS coil over these
locations, marked on the native MRI, was performed with the aid of a frameless
stereotaxic system.
(a)(b)Figure 2
Timeline of the experimental setup. All
subjects were trained for approximately 30 minutes at the beginning of the
experiment. After registering the subjects’ anatomical land marks to their
structural MRIs, the subjects performed 6 minutes of the behavioral tasks while
rTMS was administered at DL-PFC or vertex (control) in three different timing
conditions. The orders of stimulation sites and timings were counterbalanced. The behavioral
tasks consisted of WCST and control task.Behavioral tasks. (a) WCST: the four
cards shown on the top in the computer screen are reference cards, and the card
on the bottom is the test card. The subjects could move a yellow bar which was
displayed under the reference cards by pressing the left button of a mouse with
their index finger. Pressing the right button with the middle finger confirmed
the selection of the card followed by negative or positive feedback. The
subjects had to find out the rule of classification (color, shape, and number)
by trial and error. (b) Control task: the
test card was identical to one of the reference cards. The rest was the same as
WCST.
(a)
WCST(b)
Control taskThe Talairach coordinates were converted into each subject’s native MRI
space using the reverse native-to-talairach transformation [18]. The positioning of the TMS coil over these
locations, marked on the native MRI (Figure 1), was performed with the aid of a
frameless stereotaxic system (Rogue Research, Montreal, Canada).


### 2.3. TMS Protocol

Repetitive TMS was carried out with the Magstim high-speed magnetic
stimulator (Magstim, UK) using a figure-eight coil. The
coil was held in a fixed position over the stimulation sites by a mechanical arm. It was positioned so that magnetically induced current under the coil
flowed in a posterior-anterior direction. Stimulus intensities, expressed as a
percentage of the maximum stimulator output, were set at 110% of the resting motor threshold
(RMT). RMT was defined as the lowest stimulus intensity able to elicit, in the
contralateral first dorsal interosseous (FDI) muscle, 5 motor evoked potentials
(MEPs) of at least 50 uV amplitude in a series of 10 stimuli delivered over the
right primary motor cortex at intervals longer than 5 seconds. MEPs were
recorded from the FDI muscle with Ag∖Cl surface electrodes fixed on the skin
with a belly-tendon montage. The EMG signal was filtered (10 Hz–1 kHz bandpass), digitized at 2 kHz, and displayed on a computer screen [19].Three rTMS blocks (6 minutes
each) were applied to the right DL-PFC and the vertex during the WCST and
control task (Figure2). Each block was separated by a 5-minute interval. In
each block, 5 pulse trains of 250-millisecond
duration were delivered at a stimulation frequency of 20 Hz with between-train
interval dependent on the subject’s performance
time (PT) (i.e., 4 to 6 second). For each block, rTMS was delivered
either (block-1) at the beginning of each feedback period (number of
trials: 72.05±0.75) (Figure 4), (block-2) at the beginning of each
matching period (number of trials: 74.15±1.19) (Figure 5), or (block-3) every 6 second regardless of the moment in the task (i.e., desynchronized
condition) (number trials: 75.53±2.14) (Figure 6). This last paradigm was
applied in order to investigate whether the rTMS effect was timing dependent
(i.e., block-1 and -2) or not (block-3). Block order was counterbalanced across
subjects and performed on the same day (Figure 2). The stimulation
parameters followed safety guidelines for rTMS [21].(a) rTMS at the beginning of feedback: while the subject performed the WCST or
control task, rTMS was applied over the right DL-PFC or vertex at the beginning
of receiving feedback. (b) DL-PFC
stimulation during the feedback phase of the WCST increased performance time
(PT) compared to the vertex stimulation (*P = .023; two-tailed). No stimulation effect was observed in the control
task.
(a)(b)(a) rTMS at the beginning of matching: while the subject performed the WCST or
control task, rTMS was applied over the right DL-PFC or vertex at the beginning
of matching. (b) DL-PFC
stimulation during the matching phase of WCST or control task had no effect on
PT compared to the vertex stimulation.
(a)(b)(a) Desynchronized rTMS: while the subject performed the WCST or
control task, rTMS was applied over the right DL-PFC or vertex at every 6
seconds which was desynchronized with the tasks. (b) Desynchronized DL-PFC
stimulation had no effect on PT compared to the vertex stimulation.
(a)(b)


### 2.4. Data Analysis

PT and error rate were calculated. Each
subject’s PT and error rate were averaged
within each condition (stimulation site, timing, and task). PT was measured
from the presentation of the test card to the subject's response, that
is, the selection of a reference card (Figures4, 5, and 6).Repeated-measures ANOVA was used to compare the effect of the two different
stimulation sites, the three timings of
stimulation, and the two different tasks on PT.The paired samplest-test (two-tailed) was used to compare the mean
PT and error rate in the WCST between the DL-PFC and vertex stimulations during
the three different rTMS timing conditions (rTMS during feedback, during
matching, and desynchronized). The mean PT for the control task was also
compared in the same manner. Data are presented as mean ± SE. All statistical analysis was performed using SPSS 13.0 for Windows (SPSS
Inc., USA).


## 2.1. Cognitive Task

Subjects were trained for 30 minutes on the WCST
before the rTMS sessions. Prior to the training sessions, the subjects were instructed to perform as well as
they could. During the WCST, four
reference cards and one matching
card were presented on a computer screen
(Figure3(a)). On each trial, the subjects had to match a test card to
one of the four reference cards according to one of three rules: shape, number,
or color. The currently appropriate rule for classification is found by trial
and error based on the 3-second positive or negative feedback that is provided
immediately after each matching decision. The rule for classification changed randomly after the subject answers
correctly on six consecutive trials. In the control task, the matching card was identical
to one of the reference cards so that the subject simply selected the
identical card and did not have to find an appropriate rule for classification
as in the WCST (Figure 3(b)). Subjects performed the card-sorting
tasks in six different rTMS sessions (2 ×  3 design). Five-minute breaks were
given in between sessions. Each session lasted six minutes.


## 2.2. Frameless Stereotaxy System

In order to target the DL-PFC and vertex (control site) in all our subjects
(Figure1), we used a procedure that takes advantage of the standardized
stereotaxic space of Talairach and Tournoux [17] and frameless stereotaxy [18, 19]. A high-resolution MRI of the subjects’ brain was
acquired and transformed into standardized stereotaxic space using the
algorithm of Collins et al. [20]. The coordinates selected for the right DL-PFC
(X = 45, Y = 33, Z = 25) were based
on a previous functional activation study that yielded increased activity
during the feedback period [4]. Of note, in this study, we stimulated the DL-PFC
located in the right hemisphere because this side appeared to be more
consistently and robustly activated [4]. The control stimulation site (i.e., vertex
region, X = 0, Y =
−35, Z = 80) was
also chosen based on its lack of activation during performance of the WCST in
these previous studies.TMS coil
was located over (a) the right DL-PFC (X = 45,  Y = 33,  Z = 25) or (b) the vertex (control) (X = 0,  Y = −35,  Z = 80). The positioning of the TMS coil over these
locations, marked on the native MRI, was performed with the aid of a frameless
stereotaxic system.
(a)(b)Figure 2
Timeline of the experimental setup. All
subjects were trained for approximately 30 minutes at the beginning of the
experiment. After registering the subjects’ anatomical land marks to their
structural MRIs, the subjects performed 6 minutes of the behavioral tasks while
rTMS was administered at DL-PFC or vertex (control) in three different timing
conditions. The orders of stimulation sites and timings were counterbalanced. The behavioral
tasks consisted of WCST and control task.Behavioral tasks. (a) WCST: the four
cards shown on the top in the computer screen are reference cards, and the card
on the bottom is the test card. The subjects could move a yellow bar which was
displayed under the reference cards by pressing the left button of a mouse with
their index finger. Pressing the right button with the middle finger confirmed
the selection of the card followed by negative or positive feedback. The
subjects had to find out the rule of classification (color, shape, and number)
by trial and error. (b) Control task: the
test card was identical to one of the reference cards. The rest was the same as
WCST.
(a)
WCST(b)
Control taskThe Talairach coordinates were converted into each subject’s native MRI
space using the reverse native-to-talairach transformation [18]. The positioning of the TMS coil over these
locations, marked on the native MRI (Figure 1), was performed with the aid of a
frameless stereotaxic system (Rogue Research, Montreal, Canada).


## 2.3. TMS Protocol

Repetitive TMS was carried out with the Magstim high-speed magnetic
stimulator (Magstim, UK) using a figure-eight coil. The
coil was held in a fixed position over the stimulation sites by a mechanical arm. It was positioned so that magnetically induced current under the coil
flowed in a posterior-anterior direction. Stimulus intensities, expressed as a
percentage of the maximum stimulator output, were set at 110% of the resting motor threshold
(RMT). RMT was defined as the lowest stimulus intensity able to elicit, in the
contralateral first dorsal interosseous (FDI) muscle, 5 motor evoked potentials
(MEPs) of at least 50 uV amplitude in a series of 10 stimuli delivered over the
right primary motor cortex at intervals longer than 5 seconds. MEPs were
recorded from the FDI muscle with Ag∖Cl surface electrodes fixed on the skin
with a belly-tendon montage. The EMG signal was filtered (10 Hz–1 kHz bandpass), digitized at 2 kHz, and displayed on a computer screen [19].Three rTMS blocks (6 minutes
each) were applied to the right DL-PFC and the vertex during the WCST and
control task (Figure2). Each block was separated by a 5-minute interval. In
each block, 5 pulse trains of 250-millisecond
duration were delivered at a stimulation frequency of 20 Hz with between-train
interval dependent on the subject’s performance
time (PT) (i.e., 4 to 6 second). For each block, rTMS was delivered
either (block-1) at the beginning of each feedback period (number of
trials: 72.05±0.75) (Figure 4), (block-2) at the beginning of each
matching period (number of trials: 74.15±1.19) (Figure 5), or (block-3) every 6 second regardless of the moment in the task (i.e., desynchronized
condition) (number trials: 75.53±2.14) (Figure 6). This last paradigm was
applied in order to investigate whether the rTMS effect was timing dependent
(i.e., block-1 and -2) or not (block-3). Block order was counterbalanced across
subjects and performed on the same day (Figure 2). The stimulation
parameters followed safety guidelines for rTMS [21].(a) rTMS at the beginning of feedback: while the subject performed the WCST or
control task, rTMS was applied over the right DL-PFC or vertex at the beginning
of receiving feedback. (b) DL-PFC
stimulation during the feedback phase of the WCST increased performance time
(PT) compared to the vertex stimulation (*P = .023; two-tailed). No stimulation effect was observed in the control
task.
(a)(b)(a) rTMS at the beginning of matching: while the subject performed the WCST or
control task, rTMS was applied over the right DL-PFC or vertex at the beginning
of matching. (b) DL-PFC
stimulation during the matching phase of WCST or control task had no effect on
PT compared to the vertex stimulation.
(a)(b)(a) Desynchronized rTMS: while the subject performed the WCST or
control task, rTMS was applied over the right DL-PFC or vertex at every 6
seconds which was desynchronized with the tasks. (b) Desynchronized DL-PFC
stimulation had no effect on PT compared to the vertex stimulation.
(a)(b)


## 2.4. Data Analysis

PT and error rate were calculated. Each
subject’s PT and error rate were averaged
within each condition (stimulation site, timing, and task). PT was measured
from the presentation of the test card to the subject's response, that
is, the selection of a reference card (Figures4, 5, and 6).Repeated-measures ANOVA was used to compare the effect of the two different
stimulation sites, the three timings of
stimulation, and the two different tasks on PT.The paired samplest-test (two-tailed) was used to compare the mean
PT and error rate in the WCST between the DL-PFC and vertex stimulations during
the three different rTMS timing conditions (rTMS during feedback, during
matching, and desynchronized). The mean PT for the control task was also
compared in the same manner. Data are presented as mean ± SE. All statistical analysis was performed using SPSS 13.0 for Windows (SPSS
Inc., USA).


## 3. Results

TMS intensity was58.4±2.8
%. There was no significant
difference between numbers of trials among different blocks. Repeated-measures
ANOVA on PT revealed a significant main effect of different tasks (WCST versus control; F(1,9) = 71.3; P < .001) confirming that the WCST was more demanding than the control task. There
was also a significant main effect of stimulation timing on PT (beginning of
feedback versus beginning of matching versus desynchronized; F(2,18) = 23.845; P < .001) indicating
that the timing of stimulation, overall, was an important factor influencing
task performance more than stimulation site (DL-PFC versus vertex; F(1,9) =
2.516; P = .147). A significant
interaction effect was observed between tasks and stimulation site (F(1,9) = 7.642; P = .022) indicating that stimulation site affected PT differently
depending on which task was used.To test the effect of different
stimulation sites within each task and stimulation timing condition, a pairedt-test
(two-tailed) was performed. When comparing DL-PFC versus vertex during the
WCST, PT increased significantly when rTMS was delivered at the beginning of
the feedback period (DL-PFC = 1840.04±87.18 ms, Vertex = 1682.46±61.23 ms; t(9) = 2.727; P = .023) (Figure 4). Further analysis revealed that the magnitude
of impairment did not correlate with intensity of TMS (r = −0.063; P = .863). No changes in PT were observed
when rTMS was given at the beginning of the matching period (DL-PFC = 1419.19±107.48 ms, Vertex = 1309.87±88.07 ms; t(9) = 1.382; P = .200) (Figure 5) nor when it was desynchronized with task
performance (DL-PFC = 1739.13±148.26 ms, Vertex = 1659.70±98.24 ms; t(9) = 0.944; P = .370) (Figure 6). When comparing DL-PFC versus vertex during the control task, rTMS did not induce significant changes
in PT either during the feedback (DL-PFC = 1491.66±65.47 ms, Vertex = 1459.48±59.60 ms; t(9) = 0.669; P = .521) (Figure 4), matching (DL-PFC =
1084.92±62.15 ms,
Vertex =1080.26±77.11 ms; t(9) = 0.074; P = .943) (Figure 5), or desynchronized (DL-PFC = 1517.38±147.72 ms, Vertex = 1490.91±90.36 ms; t(9) = 0.314; P = .760) conditions (Figure 6).The repeated-measures ANOVA on error rate did not show any significant main
effect of task conditions, stimulation timing, or the sites of stimulation, nor
significant interaction effects except when comparing DL-PFC and vertex at the
beginning of feedback which came close to significance. More specifically, the
results obtained when performing a pairedt-test
on the error rates between DL-PFC and vertex stimulation during the WCST were
at the beginning of the feedback (DL-PFC = 6.10±1.71, Vertex = 3.28±1.16; t(9) = 2.120; P = .063); at the beginning of matching (DL-PFC = 4.79±1.04, Vertex =4.86±1.27; t(9) = −0.057; P = .956); during the
desynchronized condition (DL-PFC = 5.21±0.83, Vertex = 3.56±0.51; t(9) = 1.941; P = .084).


## 4. Discussion

The present study demonstrated that when rTMS was
applied to the DL-PFC specifically during the period when the subject was
receiving feedback regarding his/her matching response, performance of the WCST
deteriorated. It appeared that the effect of rTMS was significantly timing
dependent. In fact, rTMS-induced interference of DL-PFC affected performance
specifically during the receiving of feedback (Figure4), but not during the matching
response (Figure 5) nor when the interference was desynchronized with specific
stages of the WCST (Figure 6).This observation of a selective rTMS-induced
impairment in task performance during specific timing of a task has already
been reported in the literature in relation to several of the tasks and
cortical areas stimulated. For instance, rTMS of the medial frontal cortex
affected task switching and at the time of response set switching when
delivered before or at time of response selection [10, 22]. Similarly, rTMS affected DL-PFC
depending on whether this area, at a particular point in time, is
actively involved in processing task relevant information [11, 23].The
selective rTMS-induced
impairment in WCST performance of DL-PFC during
the receiving of
feedback is in accordance with imaging, lesion,
and neurophysiological investigations. In a previous fMRI study, Monchi et al. [4] have shown that DL-PFC is engaged
when the subject is receiving feedback during the WCST. That is, the period
when monitoring of information held in working memory, as demonstrated by
lesion studies in monkeys, is critical [8, 24]. This specific involvement has
also been confirmed with neuronal recordings from DL-PFC in monkeys during a
WCST analog which have shown the activation of DL-PFC cells during monitoring
and useof feedback information. A large population of DL-PFC
cells were strongly engaged in assessing behavioral outcome/feedback [25].Interestingly, while rTMS induced
selective impairment in WCST performance, it did not affect error rate very
significantly.  This observation is
consistent with previous work by Wagner et al. [26] who, stimulating the DL-PFC,
observed no significant effect on error making during the WCST. There are two potential alternatives that could
explain these findings.The first explanation is that error
making may be influenced by a different prefrontal area. In fact, lesions of DL-PFC
in monkeys have shown impairment in monitoring of information but did not
compromise maintenance of information and set shifting per se [8, 9, 24], which presumably may influence
errors during set-shifting tasks. Set shifting from a previously relevant to a
new response mode engages a more ventral area of the PFC (i.e., ventrolateral
PFC) [4] and is impaired by lesioning of
this area [24, 27]. Another cortical area that may
also have a relevant role is the medial PFC which can influence error trials
during performance-monitoring processes [25].A second explanation, considering
the fact that rTMS-induced error trials have been reported less frequently in
relation to different tasks and cortical area stimulated [10, 22, 23, 28], it may also be that rTMS
parameters (e.g., intensity, frequency, and unilateral stimulation) used so far
in different studies have not been strong enough to induce a complete “virtual
lesion.” Against the latter hypothesis, however, stands the fact that the
magnitude of selective impairment in WCST performance observed in this study
did not correlate with intensity of TMS which at least excludes a possible
relationship between intensity and effect on performance.While our study provides some insights over
the debate regarding the role of DL-PFC during set-shifting tasks, overall it
emphasizes the importance of rTMS in delineating the functional relevance of
neuronal correlates of performance observed during neuroimaging studies [10, 11].
In other words, our results suggest that just because a cortical area (i.e.,
DL-PFC) is functionally activated during the course of an executive task [4],
it may not necessarily play the same critical and essential role during the
whole task, and that rTMS may be a useful tool to complement fMRI in order to
infer functionality of a cortical region of the human brain.To date, the neural mechanisms underlying executive
processes are still poorly understood, even less are the mechanisms by which
rTMS interferes with cortical information processing and induces such a “temporary
lesion.” It is believed that the rTMS-induced “noise” into neural processes may,
perhaps, be the consequence of a stimulation-induced synchronization of
neuronal firing disrupting active processing in the underlying cortex [15, 29]. A valid alternative, however, may
also be represented by a suppression in cortical excitability (lasting up to 1
second) observed following short trains of rTMS at 20 Hz [30] or induced abnormality in the
release of prefronto-striatal dopamine [19].The latter is suggested by the contribution of the striatum and role
played by dopamine during the performance
of tasks requiring executive processes. Indeed, studies of dopamine
depletion in nonhuman primates suggest a possible involvement of striatal
dopamine in set-shifting tasks [31, 32]
while other neuroimaging studies have proposed that changes in striatal
dopamine levels can modulate certain set-shifting processes [33]
and that level of cognitive impairment may be dependent on the level of
dopamine depletion [34].Whatever the rTMS mechanisms may be, the ultimate
outcome appears to be a transient interruption of the specific normal cortical
processing (i.e., provision of feedback) in a restricted area of the prefrontal
cortex (i.e., DL-PFC).



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*Source: 143238-2008-02-27.xml*