Effect of cognitive-behavioral therapy on brain activity related to stimulus-response conflict processing in Gilles de la Tourette Syndrome Lori Baltazar1,4 , Geneviève Thibault1,3, Kieron, O’Connor1,2,3, Emmanuel Stip1,2, Marc E. Lavoie1,2 Centre de Recherche Fernand Seguin et Hôpital Louis-H Lafontaine1 Département de psychiatrie2 et psychologie3 Université de Montréal Collège Jean de Brébeuf4 Introduction Stimulus-response compatibility task Gilles de la Tourette syndrome (TS) is characterized by involuntary movements or sounds also known as tics. Cognitive-behavioural therapy (CBT) can successfully improve tic symptoms in adult patients diagnosed with TS. Past research using Event-Related Potentials (ERPs) underlined important discrepancies between TS and control groups. However, no ERP comparisons were made pre-post treatment, especially CBT. Our CBT program specifically targets motor execution and inhibition in TS. Consequently, we focused on the impact of CBT on motor functioning with the Lateralized Readiness Potentials (LRPs). TS patients will have more difficulty processing incompatible (conflicting) stimuli. CBT will improve tic symptoms which in turn will help normalize brain activity related to motor activations associated with conflicting response processing. A clinical group comprised of 14 non medicated TS patients was matched with 16 control participants for gender, age, education, laterality and intelligence. In addition, there is no differences in visual acuity and color perception. The clinical group was: - Diagnosed with the DSM-IV-TR criteria. - Significantly more anxious and depressive than the control before CBT. They also have more obsessive-compulsive symptoms (Table 2). After therapy, the Tourette group improve significantly on their tics, anxiety and depression symptoms (Table 2). EEG signals were: - Acquired through an analog amplifier (SAI Inc). - Recorded from 26 tin electrodes - Continuously sampled at 250 Hz - High-low pass filter settings at 0.01 and 30 Hz. Treatment undergone consisted of 12 sessions of CBT therapy. CBT is preceded and followed by electrophysiological as well as clinical evaluations for TS patients. Pre Category 1 : Left Black Category 4 : Right Blue Post Right hand Control Incorrect activation Correct Onset 20% criteria Category 2 : Left Blue Category 3 : Right Black Left hand Fig 2a. The LRP onset to the incompatible tend to normalize after successful CBT session (Figure 2a and 2b). Category 5 : Left Red Category 6 : Right Red No response Hypotheses Fig 1. * Blue, black and red arrows are presented on a computer screen. Each stimulus is shown for 350 ms. Arrows requiring a response (cat 1-4) each appear 50 times and those where a response must be inhibited ( 5 and 6) 25 times. Black arrows require an incompatible response, blue a compatible response and red no response (inhibition) see figure 1 Methodology BDI and BAI scores used as covariates Fig 2b. Table 1. Demographic variables Tourette (n=14) Control (n=16) Mean σ p Age (years) 40 12 43 13 ns Schooling (years) 14 5 2 Non-verbal intelligence (percentiles) 84 11 75 27 Laterality (right%) 100 --- Gender (M/F ratio) 6/8 5/11 Visual Acuity (Snellen) 1.38 0.25 1.32 0.33 Colour perception (Ishihara) 0.28 0.50 Only the improvement in the TSGS score is correlated to the improvement of the incompatible onset (table 4 and figure 3). Signal extraction ERPs were averaged time-locked from stimulus (-100 to 1900 ms) from raw EEG using two electrodes (C1 and C2). LRPs used in our study were derived from the following equation: LRP = [Mean(C2-C1)left hand] + [Mean(C2-C1)right hand] / 2 LRP onset latency differences (for cat. 1 - 4) between the control and the clinical groups (pre therapy) were analyzed using MANOVA tables (table 3a). The same analysis was carried out when comparing the TS group before and after therapy (table 3b). The results of the Beck Depression and the Beck Anxiety Inventories were used as covariates. The onset latency or motor activation was the amount of time needed for the LRP to reach 20% of its peak amplitude. Table 4. Correlations between LRP and symptoms Improvements Incompatible LRP onset Compatible LRP onset TSGS 0.534* -1.02 Padova -0.062 -0.093 BDI 0.419 -0.234 BAI 0.47 -0.212 Statistical analysis * R values in bold are statistically significant. Table 2. Clinical variables before and after therapy Tourette Before CBT Control T-test Group effect After CBT pre-post effect   Mean σ p Beck Depression (BDI) 9 8 3 4 0.02 2 0.01 Beck Anxiety (BAI) 13 5 6 0.04 Padua (obsessive-compulsive symptoms) 31 18 16 11 25 15 ns Tourette's Syndrome Global Scale (TSGS) 21 - 10 0.00 Results Table 3a. TS Before therapy VS Control group Before therapy After therapy MANCOVA results with the group effects   df F p Group 1,26 4.928 0.035 Compatibility 1.250 0.274 Compatibilty X Group 4.522 0.043 Fig 3. Material and data acquisition Conclusion CBT improves significantly symptoms of depression and anxiety as well as tics. CBT improves and normalizes cerebral motor activation associated with incompatible responses. The improvement of the incompatible onset in the clinical group (post therapy) is negatively correlated to their improvement in tic symptoms and behavioural problems (TSGS scores) Table 3b. TS Before therapy VS TS after therapy MANCOVA results with the effect of therapy   df F p Time – pre-post 1,10 0.090 0.926 Compatibility 0.102 0.757 Compatibility X Time 5.213 0.046 Evaluations and therapy Sponsored by: