Impairment of Auditory-Motor Timing and Compensatory Reorganization after Ventral Premotor Cortex Stimulation

Integrating auditory and motor information often requires precise timing as in speech and music. In humans, the position of the ventral premotor cortex (PMv) in the dorsal auditory stream renders this area a node for auditory-motor integration. Yet, it remains unknown whether the PMv is critical for auditory-motor timing and which activity increases help to preserve task performance following its disruption. 16 healthy volunteers participated in two sessions with fMRI measured at baseline and following rTMS (rTMS) of either the left PMv or a control region. Subjects synchronized left or right finger tapping to sub-second beat rates of auditory rhythms in the experimental task, and produced self-paced tapping during spectrally matched auditory stimuli in the control task. Left PMv rTMS impaired auditory-motor synchronization accuracy in the first sub-block following stimulation (p<0.01, Bonferroni corrected), but spared motor timing and attention to task. Task-related activity increased in the homologue right PMv, but did not predict the behavioral effect of rTMS. In contrast, anterior midline cerebellum revealed most pronounced activity increase in less impaired subjects. The present findings suggest a critical role of the left PMv in feed-forward computations enabling accurate auditory-motor timing, which can be compensated by activity modulations in the cerebellum, but not in the homologue region contralateral to stimulation

Clinical Complications Due to Combined Therapy of Narcoleptics

Proceedings of the 9th International Multidisciplinary Conference «Stress and Behavior» Saint-Petersburg, Russia, 16–19 May 2005.Agranulocytosis is a well known life-threatening side effect connected to clozapine treatment. Other dopamine blockers, typical and atypical, have been reported to induce neutropenia and agranulocytosis during treatment in adults and children. Three reports have described a decrease in white blood cells during treatment by neuroleptics other then clozapine, following clozapine-induced agranulocytosis. We report a 44-year-old woman with a previous course of clozapine treatment who developed neutropenia on combined treatment with clozapine and sulpiride, which was then followed by neutropenia on amisulpride treatment and pancytopenia on chlorpromazine treatment. Following treatment by a combination ECT and haloperidol, her condition improved without any signs of blood dyscrasia. The etiology of clozapine-induced agranulocytosis remains unknown. Leading hypothesis include an immune mechanism that is possibly complement- or drug- dependent and a toxic effect. We consider cross-sensitization of the immune system, triggered by the combination of clozapine and sulpiride and then expanded to include amisulpride and chlorpromazine, as a possible explanation of the event. The previous clozapine treatment might have been an additional risk factor. Clinicians should consider this possible complication in everyday practice when prescribing combined therapy