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Factors influencing the efficacy of rTMS in the treatment of auditory hallucinations
Abstracts / Brain Stimulation 8 (2015) 310e325
16 Effects of Age on Motor Learning and Prefrontal-motorcortical Excitability Susy Lam MSc Candidate a,b, Carolyn Gunraj MHSc b, Michael Vesia PhD b, Gaayathiri Jegatheeswaran PhD Candidate a,b, Jeanette Hui b, Robert Chen MA, MB, BChir b a Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada b Toronto Western Research Institute, Toronto, Ontario, Canada Background: The dorsolateral prefrontal cortex (DLPFC) is a critical substrate for motor learning. Given its strong roles in motor learning, it is important to understand the involvement of the DLPFC in goal-directed, sequence specific learning, and also how age changes the connections of this area to the primary motor cortex (M1). Specific Aims: (1) Examine DLPFC-M1 connectivity in healthy subjects and how it changes with age; (2) Determine whether sequence motor learning affects neurophysiology differently than non-sequence learning; (3) Study clinical and neurophysiologic effects of motor learning in PD. Methods: Twenty right-handed healthy subjects, ranging from 2080 years old, will be recruited. Subjects participated in two sessions; one visit consisting of a repeating pattern (sequence) and one with no pattern (random). A minimum of three days between visits will minimize carry-over effects. During each visit, clinical, baseline behavioural, and electrophysiological measures were initially obtained. Participants then trained with their dominant right-hand on a Serial Visual Isometric Pinch Task (SVIPT). After training, clinical assessments, behavioural, and electrophysiological measures were repeated. Results: Preliminary results in 5 healthy subjects indicate a decreased short intracortical inhibition and increased DLPFCconditioned M1 MEP during and immediately after training for certain settings. Data pertaining to remainder of subjects remain to be completely collected and analysed to correlate effects of age. Conclusions: The initial results of this study suggest that motor training modulates the short intracortical and DLPFC dual site cortical excitability of the primary motor cortex. This work will be the first to examine the causal interactions between DLPFC and M1 after motor learning, aiming to critically understand the corticocortical connections involved in motor learning and learn of any age-related effects that change these circuits. These results can bridge to rehabilitative strategies using motor learning patients with movement disorders.
19 Factors influencing the efficacy of rTMS in the treatment of auditory hallucinations Clément Nathou a,b,c, Grégory Simon d,e,f, Sonia Dollfus a,b,c, Olivier Etard b,g a CHU de Caen, Department of psychiatry, Centre Esquirol, Caen, France b Unicaen, UFR of Medecine, Caen,France c Unicaen, UMR 6301, Caen, Centre Cyceron, France d University of Paris Descartes, Sorbonne Paris City, LaPsyDÉ, Paris, France e Unicaen, LaPsyDÉ, Caen, France f CNRS, UMR 8240 LaPsyDÉ, Paris, France g CHU de Caen Laboratory of Neurological Functional Exploratory, Caen, France Background: Repetitive transcranial magnetic stimulation (rTMS) shows a high inter-subjects variability in the efficacy of the treatment of resistant auditory verbal hallucinations (AVH) in schizophrenia, but causal factors of this variability are not known. Focal anatomical alterations of the left temporal cortex that is targeted in
313
the rTMS treatment are well demonstrated, and could be one cause of this variability, but they are not taken into account in the treatment procedure. Objective: This study proposes to specifically study the links between anatomical characteristics underlying the temporal cortex target and the efficacy of the rTMS treatment used to alleviate AVH in patients with schizophrenia. Methods: In each of the fifteen recruited schizophrenic patients (DSM IV), we measured scalp to cortex distances (SCDs), gray matter densities (GMDs) in two regions of interest: the motor cortex where the resting motor threshold (rMT) was measured and the superior temporal sulcus where the treatment was delivered. We studied the correlations between these measures and the clinical efficacy assessed with the Auditory Hallucinations Rating Scale (AHRS) before and after rTMS. Results: We found correlations between the clinical efficacy of the treatment and on one hand the temporal target SCD (p ¼ 0.0396) and on the other hand the GMD (p ¼ 0.0331). No correlations between rMT and GMD or SCD in the motor cortex region were observed. Conclusion: These results support the idea that the treatment efficacy could be related to the depth of the temporal target. The closer the temporal target to scalp was, the greater efficacy of the treatment was. Furthermore, rMT may not be a so relevant tool to assay a temporal rTMS treatment.
23 Dopamine Inhibits Excitatory Synaptic Transmission in the Premotor Nuclei via Activating D1 Receptor in Adult Male Zebra Finches Shaoyi Liu , Songhua Wang , Wei Meng , Dongfeng Li School of Life Science, South China Normal University, Guangzhou 510631, China Dopamine (DA) can precisely modify neural circuits, and affect behaviors. Songbirds provide an excellent model for studying the role of DA in modifying circuits that underlie behavior. We examined the effects of DA on synaptic inputs to the robust nucleus of the arcopallium (RA) in adult male zebra finches using the whole cell voltage-clamp recording in vitro. DA was found to significantly decrease the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs), but the amplitude and the kinetic properties (rise and decay time) of the sEPSCs/mEPSCs were not altered by DA. The effects of DA were attenuated by the Dl receptor (D1R) antagonist SCH23390 but not D2 receptor (D2R) antagonist sulpiride, and mimicked by the D1R agonist SKF38393 but not D2R agonist quinpirole, which implies that DA significantly inhibited excitatory synaptic transmission via activating D1R. We also found the degree of inhibition did not increase even in a high extracellular concentration of potassium, which would activate presynaptic voltagedependent Ca2+ channels, implying the inhibition effect of DA was independent of cadium-sensitive calcium channels.
24 Deep Brain Stimulation versus lesionotomy F. Ysmail Dahlouk , L. Guenane , B.I. Merrouche , B. Abdennebi Departement of neurosurgery - Salim Zemirli Introduction: Parkinson’s disease (PD) remains a major cause of neurological disability affecting millions of patients worldwide. While pharmacotherapy remains the primary treatment of PD symptoms, surgical therapies have enjoyed a resurgence in the successful treatment of patients with advanced PD and complications of drug therapy. In carefully selected patients, deep brain stimulation (DBS) is now consideredone of the most important
16 Effects of Age on Motor Learning and Prefrontal-motorcortical Excitability Susy Lam MSc Candidate a,b, Carolyn Gunraj MHSc b, Michael Vesia PhD b, Gaayathiri Jegatheeswaran PhD Candidate a,b, Jeanette Hui b, Robert Chen MA, MB, BChir b a Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada b Toronto Western Research Institute, Toronto, Ontario, Canada Background: The dorsolateral prefrontal cortex (DLPFC) is a critical substrate for motor learning. Given its strong roles in motor learning, it is important to understand the involvement of the DLPFC in goal-directed, sequence specific learning, and also how age changes the connections of this area to the primary motor cortex (M1). Specific Aims: (1) Examine DLPFC-M1 connectivity in healthy subjects and how it changes with age; (2) Determine whether sequence motor learning affects neurophysiology differently than non-sequence learning; (3) Study clinical and neurophysiologic effects of motor learning in PD. Methods: Twenty right-handed healthy subjects, ranging from 2080 years old, will be recruited. Subjects participated in two sessions; one visit consisting of a repeating pattern (sequence) and one with no pattern (random). A minimum of three days between visits will minimize carry-over effects. During each visit, clinical, baseline behavioural, and electrophysiological measures were initially obtained. Participants then trained with their dominant right-hand on a Serial Visual Isometric Pinch Task (SVIPT). After training, clinical assessments, behavioural, and electrophysiological measures were repeated. Results: Preliminary results in 5 healthy subjects indicate a decreased short intracortical inhibition and increased DLPFCconditioned M1 MEP during and immediately after training for certain settings. Data pertaining to remainder of subjects remain to be completely collected and analysed to correlate effects of age. Conclusions: The initial results of this study suggest that motor training modulates the short intracortical and DLPFC dual site cortical excitability of the primary motor cortex. This work will be the first to examine the causal interactions between DLPFC and M1 after motor learning, aiming to critically understand the corticocortical connections involved in motor learning and learn of any age-related effects that change these circuits. These results can bridge to rehabilitative strategies using motor learning patients with movement disorders.
19 Factors influencing the efficacy of rTMS in the treatment of auditory hallucinations Clément Nathou a,b,c, Grégory Simon d,e,f, Sonia Dollfus a,b,c, Olivier Etard b,g a CHU de Caen, Department of psychiatry, Centre Esquirol, Caen, France b Unicaen, UFR of Medecine, Caen,France c Unicaen, UMR 6301, Caen, Centre Cyceron, France d University of Paris Descartes, Sorbonne Paris City, LaPsyDÉ, Paris, France e Unicaen, LaPsyDÉ, Caen, France f CNRS, UMR 8240 LaPsyDÉ, Paris, France g CHU de Caen Laboratory of Neurological Functional Exploratory, Caen, France Background: Repetitive transcranial magnetic stimulation (rTMS) shows a high inter-subjects variability in the efficacy of the treatment of resistant auditory verbal hallucinations (AVH) in schizophrenia, but causal factors of this variability are not known. Focal anatomical alterations of the left temporal cortex that is targeted in
313
the rTMS treatment are well demonstrated, and could be one cause of this variability, but they are not taken into account in the treatment procedure. Objective: This study proposes to specifically study the links between anatomical characteristics underlying the temporal cortex target and the efficacy of the rTMS treatment used to alleviate AVH in patients with schizophrenia. Methods: In each of the fifteen recruited schizophrenic patients (DSM IV), we measured scalp to cortex distances (SCDs), gray matter densities (GMDs) in two regions of interest: the motor cortex where the resting motor threshold (rMT) was measured and the superior temporal sulcus where the treatment was delivered. We studied the correlations between these measures and the clinical efficacy assessed with the Auditory Hallucinations Rating Scale (AHRS) before and after rTMS. Results: We found correlations between the clinical efficacy of the treatment and on one hand the temporal target SCD (p ¼ 0.0396) and on the other hand the GMD (p ¼ 0.0331). No correlations between rMT and GMD or SCD in the motor cortex region were observed. Conclusion: These results support the idea that the treatment efficacy could be related to the depth of the temporal target. The closer the temporal target to scalp was, the greater efficacy of the treatment was. Furthermore, rMT may not be a so relevant tool to assay a temporal rTMS treatment.
23 Dopamine Inhibits Excitatory Synaptic Transmission in the Premotor Nuclei via Activating D1 Receptor in Adult Male Zebra Finches Shaoyi Liu , Songhua Wang , Wei Meng , Dongfeng Li School of Life Science, South China Normal University, Guangzhou 510631, China Dopamine (DA) can precisely modify neural circuits, and affect behaviors. Songbirds provide an excellent model for studying the role of DA in modifying circuits that underlie behavior. We examined the effects of DA on synaptic inputs to the robust nucleus of the arcopallium (RA) in adult male zebra finches using the whole cell voltage-clamp recording in vitro. DA was found to significantly decrease the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs), but the amplitude and the kinetic properties (rise and decay time) of the sEPSCs/mEPSCs were not altered by DA. The effects of DA were attenuated by the Dl receptor (D1R) antagonist SCH23390 but not D2 receptor (D2R) antagonist sulpiride, and mimicked by the D1R agonist SKF38393 but not D2R agonist quinpirole, which implies that DA significantly inhibited excitatory synaptic transmission via activating D1R. We also found the degree of inhibition did not increase even in a high extracellular concentration of potassium, which would activate presynaptic voltagedependent Ca2+ channels, implying the inhibition effect of DA was independent of cadium-sensitive calcium channels.
24 Deep Brain Stimulation versus lesionotomy F. Ysmail Dahlouk , L. Guenane , B.I. Merrouche , B. Abdennebi Departement of neurosurgery - Salim Zemirli Introduction: Parkinson’s disease (PD) remains a major cause of neurological disability affecting millions of patients worldwide. While pharmacotherapy remains the primary treatment of PD symptoms, surgical therapies have enjoyed a resurgence in the successful treatment of patients with advanced PD and complications of drug therapy. In carefully selected patients, deep brain stimulation (DBS) is now consideredone of the most important