The Impact of a Cognitive–Behavioral Therapy on Event-Related Potentials in Patients with Tic Disorders or Body-Focused Repetitive Behaviors

Abstract

Context
Tic disorders (TD) are characterized by the presence of non-voluntary contractions of functionally related groups of skeletal muscles in one or multiple body parts. Patients with body-focused repetitive behaviors (BFRB) present frequent and repetitive behaviors, such as nail biting or hair pulling. TD and BFRB can be treated with a cognitive–behavioral therapy (CBT) that regulates the excessive amount of sensorimotor activation and muscular tension. Our CBT, which is called the cognitive–psychophysiological (CoPs) model, targets motor execution and inhibition, and it was reported to modify brain activity in TD. However, psychophysiological effects of therapy are still poorly understood in TD and BFRB patients. Our goals were to compare the event-related potentials (ERP) of TD and BFRB patients to control participants and to investigate the effects of the CoPs therapy on the P200, N200, and P300 components during a motor and a non-motor oddball task.

Method
Event-related potential components were compared in 26 TD patients, 27 BFRB patients, and 27 control participants. ERP were obtained from 63 EEG electrodes during two oddball tasks. In the non-motor task, participants had to count rare stimuli. In the motor task, participants had to respond with a left and right button press for rare and frequent stimuli, respectively. ERP measures were recorded before and after therapy in both patient groups.

Results
CoPs therapy improved symptoms similarly in both clinical groups. Before therapy, TD and BFRB patients had reduced P300 oddball effect during the non-motor task, in comparison with controls participants. An increase in the P300 oddball effect was observed posttherapy. This increase was distributed over the whole cortex in BFRB patients, but localized in the parietal area in TD patients.

Discussion
These results suggest a modification of neural processes following CoPs therapy in TD and BFRB patients. CoPs therapy seems to impact patients’ attentional processes and context updating capacities in working memory (i.e., P300 component). Our results are consistent with a possible role of the prefrontal cortex and corpus callosum in mediating interhemispheric interference in TD.

Full text

May 2016 | Volume 7 | Article 811
ORIGINAL RESEARCH
published: 10 May 2016
doi: 10.3389/fpsyt.2016.00081
Frontiers in Psychiatry | www.frontiersin.org
Edited by:
Kirsten R. Müller-Vahl,
Hannover Medical School, Hannover,
Germany
Reviewed by:
Katja Biermann-Ruben,
Institute of Clinical Neuroscience and
Medical Psychology, Germany
Joseph Mcguire,
UCLA, USA
*Correspondence:
Marc E. Lavoie
marc.lavoie@umontreal.ca
Specialty section:
This article was submitted to Child
and Adolescent Psychiatry,
a section of the journal
Frontiers in Psychiatry
Received: 26February2016
Accepted: 25April2016
Published: 10May2016
Citation:
Morand-BeaulieuS, O’ConnorKP,
RichardM, SauvéG, LeclercJB,
BlanchetPJ and LavoieME (2016)
The Impact of a Cognitive–Behavioral
Therapy on Event-Related Potentials
in Patients with Tic Disorders or
Body-Focused Repetitive Behaviors.
Front. Psychiatry 7:81.
doi: 10.3389/fpsyt.2016.00081
The Impact of a Cognitive–Behavioral
Therapy on Event-Related Potentials
in Patients with Tic Disorders or
Body-Focused Repetitive Behaviors
Simon Morand-Beaulieu1,2,3, Kieron P. O’Connor
2,4, Maxime Richard1,2,3,
Geneviève Sauvé1,2, Julie B. Leclerc
2,5, Pierre J. Blanchet
2,6 and Marc E. Lavoie1,2,4*
1 Laboratoire de psychophysiologie cognitive et sociale, Montreal, QC, Canada, 2 Centre de recherche de l’Institut
universitaire en santé mentale de Montréal, Montreal, QC, Canada, 3 Département de neurosciences, Faculté de médecine,
Université de Montréal, Montreal, QC, Canada, 4 Département de psychiatrie, Faculté de médecine, Université de Montréal,
Montreal, QC, Canada, 5 Département de psychologie, Faculté des sciences humaines, Université du Québec à Montréal,
Montreal, QC, Canada, 6 Département de stomatologie, Faculté de médecine dentaire, Université de Montréal, Montreal,
QC, Canada
Context: Tic disorders (TD) are characterized by the presence of non-voluntary con-
tractions of functionally related groups of skeletal muscles in one or multiple body parts.
Patients with body-focused repetitive behaviors (BFRB) present frequent and repetitive
behaviors, such as nail biting or hair pulling. TD and BFRB can be treated with a cogni-
tive–behavioral therapy (CBT) that regulates the excessive amount of sensorimotor acti-
vation and muscular tension. Our CBT, which is called the cognitive–psychophysiological
(CoPs) model, targets motor execution and inhibition, and it was reported to modify brain
activity in TD. However, psychophysiological effects of therapy are still poorly understood
in TD and BFRB patients. Our goals were to compare the event-related potentials (ERP)
of TD and BFRB patients to control participants and to investigate the effects of the CoPs
therapy on the P200, N200, and P300 components during a motor and a non-motor
oddball task.
Method: Event-related potential components were compared in 26 TD patients, 27
BFRB patients, and 27 control participants. ERP were obtained from 63 EEG electrodes
during two oddball tasks. In the non-motor task, participants had to count rare stimuli.
In the motor task, participants had to respond with a left and right button press for rare
and frequent stimuli, respectively. ERP measures were recorded before and after therapy
in both patient groups.
Results: CoPs therapy improved symptoms similarly in both clinical groups. Before
therapy, TD and BFRB patients had reduced P300 oddball effect during the non-motor
task, in comparison with controls participants. An increase in the P300 oddball effect
was observed posttherapy. This increase was distributed over the whole cortex in BFRB
patients, but localized in the parietal area in TD patients.

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Morand-Beaulieu et al.
Psychophysiological Therapy in TD and BFRB
Frontiers in Psychiatry | www.frontiersin.org May 2016 | Volume 7 | Article 81
INTRODUCTION
Tic disorders (TD) are characterized by repetitive non-voluntary
contractions of functionally related groups of skeletal muscles
in one or more parts of the body, including blinking, cheek
twitches, and head or knee jerks among others. Tics can also
be more complex and take the form of self-inicted repetitive
actions, such as teeth grinding, head slapping, or tense-release
hand gripping cycles. ey also appear as more purposive and
stereotyped movements of longer duration, such as facial gestures
and grooming-like movements. Furthermore, tics can be vocal,
and they range from simple sounds, such as sning, coughing,
or barking, to more complex vocalizations, such as echolalia or
coprolalia. e tics may wax and wane over the course of weeks,
months, and years. ey can appear in bouts many times a day
with onset longer than a year and arise prior to 18years old with
a peak in symptoms intensity around 12years old. Tourette syn-
drome, which is the best known TD, involves multiple motor tics
and at least one vocal tic. In comparison, persistent TD implies
either motor or phonic tics, but not both. Tourette syndrome and
persistent TD patients are oen pooled together as a sole group,
and the need for a distinction between both has been debated,
since phonic tics have an inherent motor component (1).
Recent brain imaging investigations have revealed impair-
ment in cortico-striato-thalamo-cortical (CSTC) pathways,
which assure the communication between the basal ganglia
andthe motor cortex (2–4). At the cortical level, the overactivity
of the supplementary motor area (SMA) was also observed in
TD. e SMA is an important structure related, in large part, to
the generation of tics and also to sensory urges (5, 6). Consistent
with these ndings, gray matter thinning was also found within
the SMA, and this was also correlated to the severity of tics (7)
and premonitory urges (8).
e large majority of patients with TD also face various
comorbidities (9), which include obsessive–compulsive disorder
(OCD) or at least some obsessive–compulsive symptoms (OCS),
attention-decit hyperactivity disorder (ADHD), depression,
and anxiety disorders. Another pathology oen associated with
TD is body-focused repetitive behaviors (BFRB), also known
as habit disorder. BFRB represent a clinical term that includes
various diagnoses, such as trichotillomania, skin picking, and
onychophagia. Despite the heterogeneity of symptoms comprised
of the BFRB category, their main symptoms are directed toward
the body, in reaction to feelings of discomfort, which is oen
present in TD. In the DSM-IV-TR, trichotillomania was catego-
rized as an impulse control disorder, not elsewhere classied,
and was associated with skin picking and onychophagia (10).
In the DSM-V, trichotillomania and skin picking are now clas-
sied within the obsessive–compulsive and related disorders
category, while onychophagia and dermatophagia are mentioned
as “other specied obsessive–compulsive and related disorders.”
Despite the fact that these disorders have been relocated to the
obsessive–compulsive category, impulse control and feeling of
sensory discomfort remain an important communality of their
prole. is incapacity to resist a specic impulse or urge is a
characteristic shared with TD patients. Both groups also show
heightened levels of sensorimotor activation (11–13). However,
even though BFRB resemble to TD in certain ways and these two
disorders sometimes co-occur with one another, it must be noted
that are dierent diagnoses.
ere is a clear benet in distinguishing between TD and
BFRB, for the reason that the relationship between these two
entities is sometimes clinically unclear, because the presence of
complex movements in BFRB can oen be confounded with com-
plex tics. We propose that a reasonable method of dierentiating
these two groups would be to compare directly their brain activity
during the performance of contrasting tasks with dierent levels
of motor demand. For instance, O’Connor etal. (14) reported that
TD and BFRB patients both failed to adequately adjust their hand
responses to automated or controlled movements. More precisely,
TD patients had the most severe impairment in synchronizing
motor-related brain activity with their actual response time, fol-
lowed by the BFRB and the control groups. ese ndings give
support to a dimensional model of classication with BFRB falling
between TD and controls along a continuum of motor arousal.
Recent brain imaging investigations on trichotillomania sug-
gest that BFRB could share common impaired neural networks
with TD, aecting mainly motor processing. For instance,
increased gray matter density in the le striatum, the le amygda-
lohippocampal formation, the cingulate gyrus, the SMA, and the
frontal cortex was found in trichotillomania (15). Furthermore,
BFRB patients with trichotillomania or skin picking as their main
habit have less fractional anisotropy in the anterior cingulate
and temporal areas, which indicate a lower ber density, axonal
diameter, and myelination in white matter tracts involved in
motor habits generation and suppression (16, 17). Additional
circuits seem aected in unmedicated TD, where engagement in
habit formation behavior correlated with greater connectivity of
motor structures in the right hemisphere and stronger structural
connectivity between the SMA and the putamen, which predicted
more severe tics (18). All in all, aberrant reinforcement signals
to the sensorimotor cortex and the striatum might be crucial for
habit formation and tic generation as well. ese areas are all
known to be involved in cognition and habit learning and could
Discussion: These results suggest a modication of neural processes following CoPs
therapy in TD and BFRB patients. CoPs therapy seems to impact patients’ attentional
processes and context updating capacities in working memory (i.e., P300 component).
Our results are consistent with a possible role of the prefrontal cortex and corpus callo-
sum in mediating interhemispheric interference in TD.
Keywords: Tourette syndrome, tic disorders, body-focused repetitive behaviors, habit disorder, cognitive–
behavioral therapy, cognitive–psychophysiological therapy, event-related potentials, electrophysiology

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Psychophysiological Therapy in TD and BFRB
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contribute to the development of pathological habits, but more
research are needed to incorporate other types of impulse control
disorders.
Another good reason to characterize TD and BFRB is mainly
related to their response to treatment. Currently, cognitive–
behavioral therapy (CBT) constitutes an eective line of treat-
ment for adults with both TD (19, 20) and BFRB (21–24), but
the cognitive–behavioral and physiological outcomes are not
well understood. e therapy proposed by our group is based
on the cognitive–psychophysiological (CoPs) model and aims at
regulating the high level of sensorimotor activation present in
these populations and preventing the build-up of tension that
leads to tic bursts or to the compulsive habit related to BFRB
(12, 25, 26). Its eectiveness in treating adults aected by either
disorder has been demonstrated many times (26–28). e posi-
tive eects of the CoPs therapy in TD patients are also reected at
the cerebral level. is was rst reported with a TD group, which
showed reduced electrocortical activity related to the inhibition
of automatic motor responses. It was shown that the motor-
related brain response during automatic inhibition, normalized
following successful CoPs therapy (29). ese results are also
consistent with fMRI recordings during a motor inhibition task,
which found a signicant decrease in putamen activation aer
cognitive–behavioral treatment in adult TD (30). More recently,
the CoPs therapy induced a reduction of the lateralized readiness
potentials, a brain electrical potential partly generated by the
SMA and the basal ganglia (13). us, these results are strongly
consistent with the cortical–striatal and basal ganglia impairment
hypothesis in TD. More importantly, these results showed that
psychological treatments have the potential to induce changes in
behavior and cognitive processes that are followed by modica-
tion of brain activity. e next question to explore is the cerebral
impact of therapy in the BFRB.
One eective way to follow various levels of cognitive and
electrocortical activity within milliseconds accuracy is the use
of event-related potentials (ERPs). us, we specically aimed at
the investigation of three ERP components, the P200, the N200,
and the P300 recorded at pre- and posttherapy. e P200 is a
component that indexes evaluation of stimulus salience and its
task-related adequacy (31, 32). e N200 indexes target detec-
tion and conict monitoring (33), whereas the P300 is related to
stimulus evaluation and context updating in working memory
(34). To the best of our knowledge, no study has, so far, investi-
gated the ERPs in BFRB patients, although several have studied
TD patients (35–42). us, our rst goal is to compare specic
ERP components in TD and BFRB patients before any treatment.
Our second aim is to focus on cerebral changes that accompany
behavioral and cognitive modication, aer CoPs therapy. We
expect an improvement in tics and habits symptoms in TD and
BFRB patients, respectively. e main hypothesis predicts that
TD and BFRB patients will show intact early evaluation of sali-
ence as reected by the P200 (31, 32), while showing larger target
detection and conict monitoring as indexed by a larger N200
(33), which is consistent with earlier clinical ndings with TD
reporting an intact P200 amplitude (42), and larger N200 ampli-
tude (39). Finally, we hypothesize a reduced P300 oddball eect
in our clinical groups, which was also consistently found in TD
patients with OCS (42), with OCD (43–46), and without comor-
bidity (39, 47). Such reduced P300 would indicate a decrease in
memory updating processes (34) in both disorders. We propose
to contrast ERPs across motor and non-motor oddball tasks,
which will ascribe the contribution of motor responses. Earlier
studies involving healthy participants with the counting and the
motor oddball task showed activation of the SMA, the cerebel-
lum, the thalamus, and the parietal cortex. However, activation
of the middle frontal gyrus central opercular cortex and parietal
operculum was specic to the motor oddball task, suggesting a
specic contribution of these regions in action execution (48).
Finally, we hypothesize an equivalent normalization of the P300
in both patient groups aer treatment.
MATERIALS AND METHODS
Participants
Patients with either TD or BFRB were recruited from the Centre
d’études sur les troubles obsessionnels-compulsifs et les tics from the
Centre de recherche de l’Institut universitaire en santé mentale de
Montréal to participate in this study. Patients with TD as their
main concern were assigned to the TD group. erefore, the TD
group was composed of 26 patients who met the DSM-IV-TR
criteria for either Tourette syndrome (307.23) or chronic TD
(307.22) (10). Patients with BFRB as their main concern were
assigned to the BFRB group. e latter group was composed of
27 patients with specic habit disorders, such as trichotillomania
(n=12), onychophagia (n=8), skin picking (n=5), and bruxism
(n=2). ese two patients’ groups were matched to a group of
27 healthy controls on the basis of age, intelligence (Raven), and
laterality.1 e project was approved by the ethics committee of
the Centre de recherche de l’Institut universitaire en santé mentale
de Montréal, and all participants granted their written informed
consent, in accordance with the Declaration of Helsinki. Seven
TD patients and four BFRB patients were under medication
during the study. ose medication were α2-adrenergic agonists
(n=1), β2-adrenergic agonists (n=1), antidepressants (n=7),
benzodiazepine (n=3), non-benzodiazepine (n=1) hypnotics,
neuroleptics (n=2), and lithium (n=1). However, to be included
in our study, their medication had to remain stable throughout
the entire process. Socio-demographic characteristics of our
participants can be found in Table1.
Exclusion criteria consisted of the presence of a psychiatric
diagnosis, such as schizophrenia, mood disorders, somatoform
disorders, dissociative disorders, and substance-related dis orders.
e presence of personality disorders was screened with the
personality diagnostic questionnaire-fourth edition (49–51), and
participants with personality disorders were excluded. Other
medical conditions, such as neurological diseases, were screened
by a neurologist (Pierre J. Blanchet) and were also a criterion for
exclusion.
1 Twenty of the 26 TS patients and 19 of the 27 controls included in this study
werealso included in one of our previous study, but with a dierent experimental
task (13).

TABLE 1 | Socio-demographic and clinical characteristics.
TD (n=26) BFRB (n=27) Controls (n=27)
Mean SD Mean SD Mean SD F p Group difference
Age 38 11.9 40 14.4 36 13.0 0.48 ns
Sex (% of males) 65% N/A 26% N/A 41% N/A 4.60*<0.05 TD>BFRB
Intelligence (percentiles) 88 13.8 80 17.2 84 17.1 1.49 ns
Laterality (R:L:A) 24:2:0 N/A 24:3:0 N/A 25:0:3 N/A 5.42ans
OCS (Padua) 32 32.1 35 25.8 17 15.6 4.14*<0.05 BFRB>controls
Depression (BDI) 11 10.2 14 7.8 3 3.8 15.70*** <0.001 TD and BFRB>controls
Anxiety (BAI) 8 5.9 11 6.6 5 4.6 7.19** <0.01 BFRB>controls
Impulsivity (BIS-10)b71 8.8 72 7.9 64 8.7 5.82** <0.01 TD and BFRB>controls
Laterality: R, right-handed; L, left-handed; A, ambidextrous. Intelligence: Raven’s matrices percentiles; OCS, obsessive–compulsive symptoms; BDI, Beck depression inventory; BAI,
Beck anxiety inventory; BIS-10, Barratt impulsiveness scale; ns, not statistically signicant.
*p<0.05.
**p<0.01.
***p<0.001.
aFisher’s exact test was used to analyze categorical data with cells containing an expected count below 5.
bOne TD patient and eight controls with missing data.
Every signicant result is in bold.
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Psychophysiological Therapy in TD and BFRB
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Procedures
Clinical Assessment
Patients underwent a battery of psychological tests to assess
symptoms. e Tourette Syndrome Global Scale [TSGS (52)]
and the Yale Global Tic Severity Scale [YGTSS (53)] were used
to assess tics symptoms in TD patients. We adapted the TSGS
and the YGTSS to assess the presence of habit disorders in the
BFRB group. In these adapted versions of both questionnaires,
the word “tic” was replaced by the word “habit.” ese question-
naires were adapted to quantify both tics and habits on the same
metric uniformly. is adaptation has been validated in a prior
research from our group (54).
We also used the Massachusetts General Hospital Hair Pulling
Scale [MGH-HPS (55)] to assess BFRB severity. e MGH-HPS
is a seven-point inventory measuring the severity of trichotillo-
mania symptoms. Again, an adaptation of this scale was pro-
posed to assess onychophagia, skin picking, and skin scratching.
erefore, the current data reported in the MGH-scale column
reected the severity score of the principal habit of each BFRB
patient. Good convergent validity was found between TSGS and
MGH scales, as prior research found correlations between TSGS
tic scores and the MGH-HPS (r=0.49, p<0.05), as well as the
MGH scales adapted for nail biting and skin picking (r=0.52,
p<0.05) (54).
Obsessive–compulsive symptoms were assessed with the Padua
inventory (56). e 10th version of the Barratt Impulsiveness
Scale (BIS-10) was administered to assess impulsivity in our
participants (57). e Beck anxiety inventory [BAI (58)] and the
Beck depression inventory [BDI (59)] were used to assess anxiety
and depression symptomatology, respectively. e occurrence of
anxiety disorders was assessed by a structured interview with the
anxiety disorders interview schedule (60). Severe psychological
stressors, time availability, and other psychological problems
were also screened.
Cognitive–Behavioral Therapy Based on the
Cognitive–Psychophysiological Model
e two clinical groups, which are composed of 26 patients with
TD and 27 patients with BFRB, underwent the same CBT, based
on the cognitive–psychophysiological (CoPs) model (12). is
treatment, while including some classic principles of symptom
awareness and habit reversal therapy, focuses on cognitive and
behavioral restructuration insituations presenting a high risk for
tic bouts. e therapy was delivered by two licensed psychologist
(supervised by Kieron P. O’Connor) on a weekly one-to-one basis.
e treatment program includes basic clinical steps, which are
cumulative and administered over 14 60-min sessions: awareness
training (psychoeducation, daily diary, video, situational prole),
muscle discrimination (gradation of tension, normalize contrac-
tions), muscular relaxation, reducing sensorimotor activation,
modifying background style of action, cognitive and behavioral
restructuring (development of alternative goal driven responses
using cognitive and behavioral strategies), generalization, and
preventing relapse.2 At the end of the 14th week, there is a home-
based practice period lasting 4weeks with weekly phone contact
with the therapist to ensure compliance and deal with trouble
shooting. erefore, there was a time lapse of 18weeks between
the beginning of the program and the posttreatment evaluation.
Conditions of treatment delivery, duration, homework, and treat-
ment monitoring were equivalent and supervised for integrity.
Oddball Paradigms
Two types of oddball paradigms were used in this study. During
both oddball tasks, 200 black letters (X and O on a white
background) were randomly presented during 100 ms on a
2 Contact the authors for more information about the CoPs program. Also, see
Lavoie etal. (25) or O’Connor etal. (26) for further details.

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computer screen (Viewsonic SVGA 17″ monitor), with a random
1700–2200ms inter-trial interval. e frequent stimulus (the let-
ter “O”) was presented 80% of the time (n=160), whereas the rare
stimulus (the letter “X”) was presented with a 20% probability
(n=40). e rst task is a counting oddball task, which presented
the same stimuli, but this time participants must only count the
number of rare stimuli. At the end of the experiment, the partici-
pants had to report the exact amount of rare stimuli (n=40). e
second task is a motor oddball task, where participants pressed the
keyboard le arrow key with their le index nger when frequent
stimuli were presented and pressed the right arrow key with their
right index nger, when the rare stimuli were presented. e
order of presentation of the counting and the motor tasks was
counterbalanced across participants.
Electrophysiological Recordings
e EEG was recorded during both oddball tasks, with a
digital amplier (Sensorium Inc., Charlotte, VT, USA). EEG
signal was recorded from 63 Ag/AgCl electrodes mounted in
a lycra cap (Electrode Arrays, El Paso, TX, USA)3 and placed
according to standard EEG guidelines (61). All electrodes were
referenced to the nose. e signal was sampled continuously
at 500 Hz and recorded with 0.01Hz high-pass lter and a
100-Hz low-pass lter (60Hz notch lter). Impedance was kept
below 5kΩ, using an electrolyte gel (JNetDirect Biosciences,
Herndon, VA, USA). Bipolar electro-oculogram (EOG) was
recorded to clear EEG from eye artifacts, such as blinks and
eye movements. Electrodes were placed at the outer canthus
of each eye (horizontal EOG) and below and above le eye
(vertical EOG). e stimuli were monitored by Presentation
(Neurobehavioral Systems, Albany, CA, USA),4 and the signal
was recorded with IWave (InstEP Systems, Montréal, QC,
USA) running on two PCs.
ERP Extraction from Raw EEG Signal
Ocular artifacts were corrected oine with the Gratton algorithm
(62). Raw signals were averaged oine and time-locked to the
stimulus onset, in a time window of 100ms prior to stimulus
onset until 900ms aer stimulus onset. Stimuli were categorized
across frequent and rare conditions. ERP data were ltered oine
with a 0.30-Hz high-pass lter and a 30-Hz low-pass lter. During
the averaging procedure, clippings due to ampliers saturation
and remaining epochs exceeding 100μV were removed. Finally,
participants had to have at least 20 valid trials in each condition
to be included in the analyses.
e amplitude of the P200 was calculated as the maximum
peak during the 150–300 ms interval, whereas the amplitude
of the N200 was calculated as the lowest peak during the same
interval. e amplitude of the P300 component was calculated as
the mean amplitude in the 300–550ms interval. irty electrodes
were used to analyze each of these components: AF1, AF2, AF3,
AF4, F1, F2, F3, F4, F5, F6 (frontal region), FC1, FC2, FC3, FC4,
C1, C2, C3, C4, C5, C6 (central region), CP1, CP2, CP5, CP6, P1,
P2, P3, P4, P5, and P6 (parietal region).
3 http://www.sandsresearch.com/electrode-caps.html
4 http://www.neurobs.com/
Statistical Analyses
Since the control group was only tested once, two separate sets
of analyses were performed. e rst set of analyses compared
the TD, BFRB, and control groups at the baseline, whereas the
second set of analyses compared the TD and BFRB groups at
baseline and aer CoPs therapy. erefore, we performed each
MANOVA twice, rst with the between-group factor group (TD/
BFRB/controls), and then the within-group factor therapy (pre/
post) was added. e between-group factor Group only contained
two levels in this second set of analyses (TD/BFRB). Independent
samples t-tests were performed to compare the two groups on
age, intelligence, depression, and anxiety scores. Paired samples
t-tests were also performed to compare TSGS, YGTSS, BDI, and
BAI scores before and aer the therapy.
To compare TD and BFRB patients with controls on N200,
P200, and P300 peak amplitude, repeated-measures MANOVAs
were performed with the between-group factor Group (TD/
BFRB/controls), and three within-group factors: condition (fre-
quent/rare), region (frontal/central/parietal), and hemisphere
(le/right). To assess the therapy eects, a within-group factor
therapy was added (pre/post) in the second set of analyses.
Signicant interactions in all components were further analyzed
with paired and independent samples t-tests. Further analyses
were performed on each clinical group (TD and BFRB) to
examine if the impact of CoPs therapy diered between groups.
Huynh–Feldt corrections for repeated-measures analyses were
performed when required. Tukey’s test was used to assess dier-
ences between groups before therapy.
RESULTS
Impact of CoPs Therapy on Clinical
Measures
e therapy induced a reduction in tics and habits symptoms in
TD and BFRB patients, respectively. In both groups, there were
reductions in TSGS [F(1,51) = 67.09, p< 0.001] and YGTSS
total scores [F(1,51) =89.13, p<0.001]. Reductions in TSGS
total score remained signicant when covarying for depres-
sion [F(1,51)= 26.39, p< 0.001] and anxiety [F(1,51)= 23.99,
p< 0.001]. With impulsivity as a covariant, there was a trend
toward a signicant reduction in TSGS score [F(1,50) = 3.23,
p=0.078]. Reductions in YGTSS total score remained signicant
when covarying for depression [F(1,51)=31.16, p<0.001], anxi-
ety [F(1,51)=17.07, p<0.001], and impulsivity [F(1,50)=5.15,
p<0.05].
ere were also reductions in YTGSS tics/habits impairment
[F(1,51) = 60.42, p< 0.001] and motor tics/habits subscales
[F(1,51) = 55.84, p< 0.001]. Moreover, there was a therapy
by group interaction on the YGTSS motor tics/habits subscale
[F(1,51)=5.84, p<0.05], which showed that motor tics/habits
severity decrease following CoPs therapy in both patient groups,
but improvements were more pronounced in the BFRB group.
Moreover, the therapy induced a signicant improvement
in YGTSS scores on the phonic tic subscale in TD patients
[F(1,25) = 19.30, p< 0.001], as well as reduced MGH scales
scores for BFRB patients [F(1,23)=25.90, p<0.001]. Following
therapy, anxiety and depressive symptoms were also diminished

TABLE 2 | CBT impact on clinical scales.
Pre Post
TD
(n=26)
BFRB
(n=27)
TD
(n=26)
BFRB
(n=27)
Mean SD Mean SD Mean SD Mean SD F p d Group difference
Depression (BDI) 11 10.2 14 7.8 6 6.5 7 6.0 26.69*** <0.001 0.73 TD and BFRB: pre>post
Anxiety (BAI) 8 5.9 11 6.6 6 6.5 8 4.7 6.29* <0.05 0.41 TD and BFRB: pre>post
OCS (Padua)a30 30.9 35 25.8 28 23.5 35 24.4 0.22 ns 0.04
Tic severity TSGS total score 18 9.8 17 9.7 9 8.6 7 7.0 67.09*** <0.001 1.06 TD and BFRB: pre>post
YGTSS Total 40 15.3 28 10.8 26 11.2 16 9.3 89.13*** <0.001 1.04 TD and BFRB: pre>post
Tics/habits impairment 20 10.5 14 5.9 10 5.0 7 5.2 60.42*** <0.001 1.11 TD and BFRB: pre>post
Motor tics/habits severity 13 4.3 13 3.5 11 4.6 8 4.4 55.84*** <0.001 0.86 TD and BFRB: pre>post
Phonic tics severityb7 5.6 N/A N/A 5 4.7 N/A N/A 19.30*** <0.001 0.53 TD: pre>post
MGH scalescN/A N/A 17 3.6 N/A N/A 10 5.6 25.90*** <0.001 1.49 BFRB: pre>post
Impulsivity (BIS-10)d71 8.8 72 7.9 69 9.0 71 7.4 2.76 ns 0.13
BDI, Beck depression inventory; BAI, Beck anxiety inventory; OCS, obsessive–compulsive symptoms; TSGS, Tourette’s syndrome global scale; YGTSS, Yale Global Tic Severity
Scale; MGH scales, Massachusetts General Hospital Hairpulling Scale and its adapted versions for other BFRB; ns, not statistically signicant; d, Cohen’s d were calculated with
both clinical groups pooled together, except for YGTSS phonic tics subscale (TD only) and MGH scales (BFRB only).
*p<0.05.
***p<0.001.
a11 TD patients and ve BFRB patients with missing data.
bOnly for TD patients.
cOnly for BFRB patients. Three patients with missing data.
dOne TD patient with missing data.
Every signicant result is in bold.
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in both patient groups, as shown by signicant reductions in
BAI [F(1,51)=6.29, p<0.05] and BDI scores [F(1,51)=26.69,
p< 0.001]. e CoPs therapy had no impact on impulsivity.
Clinical results are shown in Table2.
Counting Oddball Task
P200 Component
Before CoPs therapy, there were main eects of condition
[F(1,77)=170.52, p<0.001], region [F(2,76)=7.30, p<0.005],
and hemisphere [F(1,77)=15.80, p<0.001]. e rare–frequent
oddball eect was larger over the central region in all groups,
which lead to a condition by region interaction [F(2,76)=80.50,
p<0.001]. ere was no group main eect or interaction for that
component. No therapy eect reached statistical signicance. ERP
waveforms for the counting oddball task are shown in Figure1.
N200 Component
Before CoPs therapy, there was a region main eect [F(2,76)=12.71,
p< 0.001], as well as condition by region [F(2,76) = 13.86,
p<0.001] and region by hemisphere [F(2,76)=4.58, p<0.05]
interactions. ere was also a condition by region by hemisphere
by group interaction [F(3.89,149.63)= 23.65, p< 0.05], which
revealed that BFRB patients had a larger N200 amplitude than
controls over the right-central region during frequent stimuli
[F(2,77)=3.36, p<0.05, Tukey: p<0.05], thus reducing the N200
oddball eect. No signicant change due to therapy was noted.
P300 Component
Before CoPs therapy, there were main eects of condition
[F(1,77) = 97.94, p<0.001], region [F(1.30,100.32) = 51.46,
p<0.001], and hemisphere [F(1,77)=4.31, p< 0.05], as well
as condition by region [F(1.34,103.02)=45.58, p< 0.001] and
condition by hemisphere [F(1,77)=4.75, p<0.05] interactions.
Most importantly, there was a condition by group [F(2,77)=5.26,
p< 0.01] interaction, which revealed smaller P300 amplitude
during rare trials for both clinical groups, in comparison with the
control group (Figure2). is interaction remained signicant
even when covarying for medication [F(2,76)=4.65, p<0.05].
ere was also a condition by region by hemisphere by group
four-way interaction [F(3.34,128.65) = 3.20, p< 0.05], which
revealed that there were signicant between-group dierences
during rare trials over the le frontal [F(2,77)=3.25, p<0.05],
le [F(2,77)=3.56, p<0.05] and right-central [F(2,77)=3.34,
p<0.05], and right parietal [F(2,77) =3.35, p<0.05] regions.
ere were no such group dierences during frequent trials.
When clinical groups were pooled together, the TSGS global
score was negatively correlated with the P300 oddball eect in
the right-central (r=−0.28, p<0.05) and the le (r=−0.27,
p<0.05) and right (r=−0.28, p<0.05) parietal regions. In the
TD group, the P300 oddball eect was positively correlated with
the BIS-10 score in the le-central (r=0.43, p<0.05) and parietal
regions (r=0.48, p<0.05). ere was no such correlation in the
BFRB or the control group.
ere was a main eect of therapy [F(1,51)=5.20, p<0.05], and
a therapy by condition interaction [F(1,51)=10.63, p<0.005],
which revealed an increase in amplitude during rare trials fol-
lowing therapy (see Figure2). When covarying with medication,
the therapy main eect was no longer signicant, but the therapy
by condition interaction remained signicant [F(1,50) = 5.42,
p<0.05]. Also, when we analyzed groups separately, there was

FIGURE 1 | ERP waveforms during the counting oddball task. The initial positive deection that arises about 200ms after stimulus presentation corresponds
to the P200 component. The negative deection that follows is the N200, which is then followed by the P300, a positive deection that emerges 300ms after
stimulus presentation. The oddball effect is represented by the P300 amplitude to rare (dotted line)−frequent (solid line) stimuli. Before therapy, TD and BFRB
patients had reduced P300 amplitude than controls during rare trials. A signicant amplitude increase was induced by the CoPs therapy. This increase occurred in
all three regions in BFRB patients but was more localized in the parietal region in TD patients.
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Psychophysiological Therapy in TD and BFRB
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a therapy main eect [F(1,26)= 4.61, p< 0.05] and a therapy
by condition interaction [F(1,26)=8.17, p< 0.01] in the BFRB
group (which also revealed amplitude increase in rare trials). In
comparison, there was only a trend toward a therapy by condition
interaction in the TD group [F(1,25)=3,39, p=0.078], when ana-
lyzing the entire cortex. However, there was a localized therapy by
condition interaction in the le parietal region [F(1,25)=3.88,
p<0.05] in TD patients, revealing an amplitude increase during
rare trials and thus, a larger oddball eect in this region aer CoPs
therapy (Figure3).
Motor Oddball Task
Reaction Times
Before CoPs therapy, there was a main eect of condition
[F(1,77)=169.37, p<0.001], which indicated that all participants
responded faster to frequent than to rare stimuli. ere was also a
group main eect [F(2,77)=4.02, p<0.05] on median reaction
times, which revealed that BFRB patients reaction times were
delayed compared to the control group (Tukey: p<0.05). ere
was no signicant dierence between TD patients and controls
and no signicant eect of therapy perse on reaction times.
P200
Event-related potentials waveforms for the motor oddball task
are shown in Figure4. Before CoPs therapy, there were condi-
tion by region [F(2,76)=98.10, p<0.001], condition by hemi-
sphere [F(1,77)= 16.45, p<0.001], and region by hemisphere
[F(2,76)=10.87, p<0.001] interactions.
N200
Before CoPs therapy, there were condition by region
[F(2,76) = 10.44, p< 0.001] and condition by hemisphere

FIGURE 3 | P300 scalp topographies of activation changes induced by
CoPs therapy. P300 data before therapy were subtracted from P300 data
after CoPs therapy to illustrate the activation changes induced by CoPs
therapy in frequent and rare conditions. Red color represents an activation
increase following CoPs therapy, whereas blue color represents a decrease in
activation in microvolts. The SLORETA number indicates the timeframe of
each scalp. The timeframes were selected as the maximum peak during the
300–550ms interval following stimulus presentation, for the frequent and rare
condition. For both groups, scalp topographies show that most of the pre–
posttherapy difference in P300 activation occurred during rare condition. In
TD patients, the activation increase was localized in the parietal area,
especially the central and left hemisphere. In BFRB patients, the increase
was generalized to the whole cortex. Scalp topographies were obtained
through LORETA (63).
FIGURE 2 | The P300 oddball effect (therapy by condition). The P300
oddball effect represents the subtraction of frequent condition from the rare
condition across all scalp regions. With the counting oddball task, the oddball
effect was signicantly reduced in both clinical groups at pretherapy (black).
However, there were no signicant differences across groups during the
motor task (gray) and no effect of therapy reached signicance. At
posttherapy, a normalization of the oddball effect was induced during the
counting oddball task (black), especially in BFRB patients, where it almost
reaches the level of control participants. Note: error bars represent the SEM.
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Morand-Beaulieu et al.
Psychophysiological Therapy in TD and BFRB
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[F(1,77)=12.62, p<0.01] interactions, which revealed a larger
condition eect over the frontal le hemisphere.
P300
Before CoPs therapy, there were main effects of condition
[F(1,77) = 71.57, p< 0.001] and region [F(2,76) = 41.45,
p<0.001] followed by condition by region [F(2,76)=13.65,
p< 0.001] and condition by hemisphere [F(1,77) = 45.81,
p<0.001] interactions. There was no significant group dif-
ference or effect of therapy in all three components during the
motor oddball task (see Figure3).
DISCUSSION
e main goal was to compare brain function in TD and BFRB
patients during two oddball tasks and to record the eect of the
CoPs therapy on clinical measures and brain functioning. To
achieve this goal, we used ERP, a technique with high temporal
resolution, which is well suited to follow complex stages of the
processing stream. We expected that the CoPs therapy would
induce a signicant reduction in tic symptom severity in both
clinical groups, whereas an increase in P300 amplitude was
hypothesized to accompany that clinical improvement.
Our results showed that the P300 oddball eect was reduced
in both clinical groups. en, the CoPs therapy induced a
normalization of the P300 oddball eect. e clinical change
following therapy conrmed our hypothesis with a signicant
reduction in tics and habit disorders scale scores. Moreover, anxi-
ety and depression symptoms also improved following therapy.
ese results were observed only in the counting oddball where
no motor response was required.
Counting Oddball Task
Habit symptoms induced an increase in N200 amplitude over the
right-central region, during the counting oddball task. Indeed,
in BFRB patients, the N200 was larger for frequent stimuli, thus
reducing the oddball eect. In an oddball paradigm, the N200 is
traditionally representative of attention and detection processes
(64). At a functional level, this central N200 is generated by the
anterior cingulate cortex and is related to conict monitoring and
cognitive control (64, 65). e obser ved N200 asymmetry toward

FIGURE 4 | ERP waveforms during the motor oddball task. No signicant group differences were observed during the motor oddball task.
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Psychophysiological Therapy in TD and BFRB
Frontiers in Psychiatry | www.frontiersin.org May 2016 | Volume 7 | Article 81
the right hemisphere could be caused by the impaired function-
ing of the corpus callosum (66). e corpus callosum and the
prefrontal cortex have a role in mediating interhemispheric inter-
ference (67). Smaller corpus callosum could be due to accelerated
pruning, whereas axonal pruning is reduced in the frontal cortex
of TD patients (68). erefore, such reports are consistent with
our results of hemispheric discrepancy in the frontal and central
regions, and the BFRB group seems to share that characteristic
with the TD.
Since the N200 reects monitoring and control, an increase
in N200 amplitude could be considered as a function of the
amount of eort that the individual put into regulating the urge
to perform their habits and/or tics. However, the fact that the
therapy failed to aect the N200 oddball eect could mean that
despite better tics/habits awareness and modication of action
style, this is not reected by cerebral activity, at least in that ERP
temporal window.
Later in the processing stream, for both patient group there
was a signicant reduction of the P300 oddball eect, particularly
over the le anterior hemisphere (frontal and central) and the
right posterior hemisphere (central and parietal). Moreover, the
P300 oddball eect in the right-central region and bilaterally in
the parietal region was negatively correlated with TSGS score,
showing that the P300 oddball eect was reduced when tic/
habits symptoms were more severe. Such correlation was not
found with the YGTSS total score or one of its subscales. is
could be explained by the fact that the TSGS has a more detailed
behavioral subscale, including individual rating of learning prob-
lems, occupational problems, and motor restlessness (52). On the
other side, the YGTSS has a 0–50 impairment subscale in which
global impairment caused by TD is scored (53). erefore, this
dierence between those two scales could explain why we found
correlations between the P300 oddball eect with the TSGS, but
not with the YGTSS.
e P300, which indexes processes of stimulus evaluation and
categorization (69, 70), is generated by a network that includes
the prefrontal cortex, the temporoparietal junction, the inferior
parietal lobule, the supramarginal gyrus, and the cingulate gyrus
(70, 71). In a study on a specic subtype of BFRB (i.e., tricho-
tillomania) with MRI, it was reported that patients show higher

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levels of gray matter in the cingulate and parietal regions, in
comparison with healthy controls (15). Trichotillomania patients
also showed impairments in white matter tracts in the anterior
cingulate gyrus, as shown by reduced fractional anisotropy in that
region (16). In comparison, TD patients showed decrease gray
matter in the anterior cingulate gyrus and the sensorimotor areas
and reductions in white matter in the right cingulate gyrus (72).
e P300 reduction has been related to impairments in gray mat-
ter of these regions (73), whereas another study reported positive
correlations between P300 amplitude and white matter volumes
in the prefrontal cortex and the temporoparietal junction,
which were found in both healthy controls and patients at risk
for psychosis (74). erefore, P300 reduction could potentially
reect reduced white or gray matter of the prefrontal cortex and
sensorimotor regions of the brain that in turn aect tics/habit
symptoms.
Interestingly, the non-motor P300 oddball eect increased
in both clinical groups following therapy. While this enhance-
ment was found over the entire cortex in BFRB patients, it was
localized to the parietal cortex in TD patients. One component
of CoPs treatment model for tics and habits is awareness training,
in which patients learn to better integrate information from the
social, geographical, physical, and emotional context (12). Hence,
the larger P300 oddball eect, found aer therapy during a non-
motor task, may depict enhance cognitive resources mobilized
for working memory and contextual updating processes acquired
through persistent training, during the CoPs therapy and prac-
tice sessions. us, the treatment may promote normalization
of aberrant cortical pathways in adults with TD and BFRB. e
change in P300 oddball eect could also represent an adaptive
mechanism to update information in working memory despite
reduced gray and white matter in sensorimotor and prefrontal
areas (7, 8, 72,75). Our ndings are also consistent with recent
ndings in fMRI, which revealed that patients with greater tic
severity reduction had higher activity in the inferior frontal gyrus
(30). e authors argue that since the inferior frontal gyrus is
involved in task-switching and set-shiing, greater activity of this
region could be associated with less impairment in TD patients.
However, these results were obtained from a motor inhibition
priming task, which dier from our own non-motor oddball
task that mobilize cerebral structures, such as the cerebellum, the
thalamus, and the frontal and parietal cortex (48). Intriguingly,
our posttherapy increase was found only with the counting
oddball task, which could suggest that the non-motor P300
amplitude forms a good marker of tic/habits normalization that
accompanies change in cortical activation.
Motor Oddball Task
Consistently, our ERP results during the motor oddball task
conrmed that there were no signicant group dierence in all
components during the motor oddball task and these ERP com-
ponents, along with the reaction times, also were not aected by
the CoPs therapy. While all participants showed delayed reaction
times for rare than for frequent stimuli, which is expected with
this type of motor oddball task, both clinical groups’ reaction
times were not signicantly dierent from controls. is is
consistent with prior ndings with similar oddball paradigms in
TD patients (39). Intact reaction times in adults with TD have
also been found in Go/NoGo motor inhibition tasks (76, 77) and
during a stimulus–response compatibility paradigm (13, 78).
As seen in Figure2, the oddball eect is generally smaller in
the motor than the counting task, in all groups. e amplitude
of the P300 oddball eect during the motor task does not dier
between groups. Motor-related potentials have been reported
to overlap with the P300 and, thus, motor responses can have
an attenuating eect on P300 component (79, 80). is could
explain, in part, why that motor-related P300 was not signi-
cantly aected by tic/habit symptoms or by therapy in the motor
oddball task. is suggests that TD and BFRB patients do not
dier from healthy controls in the evaluation of stimuli salience
and its task-related adequacy (N200/P200) in the context of a
motor oddball task. Again, this is consistent with prior research
on adults with TD that also showed intact P200 in counting
oddball paradigm (42).
Limitations
e principal limitation of the current study is the fact that the
control group was only tested once. Ideally, controls could have
been tested a second time, with the same time interval between
electrophysiological recordings than our patient groups. However,
previous investigations showed good test–retest reliability of
the P300 amplitude over time (81, 82), suggesting that control
participants’ electrocortical activity would not dier signicantly
in a second recording. Another limitation is that there were more
males in the TD group and more females in the BFRB group, but
this is consistent with the inherent gender ratio of both disorders
(9, 83). Literature on this matter does not reveal signicant gen-
der dierence on P300 amplitude in oddball paradigms (84–86).
Also, some patients were under medication, and others had
sub-clinical comorbid disorders. Even though some of our
results could be explained by these factors, we chose to include
patients with comorbidities to have a better ecological validity,
since comorbidities are the norm rather than the exception in
TD (9, 87) and BFRB as well (88, 89). Finally, clinical scales were
administered by unblinded clinicians, which could have aected
the rating of symptom severity.
CONCLUSION
Our ndings constitute one of many building blocks that seek
integration of psychophysiological measures into evidence-based
treatment of TD and BFRB. Consistent with that approach, the
CoPs model considers the release of tension as a part of a general
regulation system, which postulates that the evaluation of tics
must focus further on situational triggers and on a particular
style of action characterized by sensorimotor functioning that
tends to increase muscular activation and tension. Our results
allowed to improve the cerebral and cognitive outcome follow-
ing the CoPs therapy, for these clinical groups. In conclusion,
we demonstrated that TD and BFRB patients have smaller P300
oddball eect, reecting impairments in attention and working
memory. We also found a modication of this neural process aer
therapy, which was generalized throughout all brain regions in

11
Morand-Beaulieu et al.
Psychophysiological Therapy in TD and BFRB
Frontiers in Psychiatry | www.frontiersin.org May 2016 | Volume 7 | Article 81
BFRB patients and more localized in the parietal motor area in
TD patients.
AUTHOR CONTRIBUTIONS
SMB has written this article in partial fulllment for his doctoral
thesis in neuroscience. KO is chief of the Tourette and OCD clinic,
and he was responsible for English text revision for the current
article. MR performed the analyses and wrote some sections of the
manuscript. GS has co-written this article with SMB, particularly
the pretherapy phase. JL was responsible, with KO, of the CoPs
treatment. She also made editorial revisions. PB was responsible
for the dierential diagnosis. He also made editorial revisions.
ML supervised all aspects of data acquisition and analysis with
the rst author. He also made editorial revisions.
ACKNOWLEDGMENTS
We wish to express our gratitude to Martine Germain for electro-
physiological recordings, to Maite Hernandez for psychological
testing, and to Karine Bergeron and Natalia Koszegi for clinical
coordination. We also want to thank all the participants for their
participation in our study.
FUNDING
is research was funded by an operating grant from the Canadian
Institutes of Health Research (CIHR #93556) and a team grant
from the Fonds de Recherche du Québec–Santé (FRQS #20573)
awarded to ML, KO, and PB. SMB and GS both received doctoral
scholarships from the FRQS for their work related to this article.
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Conict of Interest Statement: e authors declare that the research was con-
ducted in the absence of any commercial or nancial relationships that could be
construed as a potential conict of interest.
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