Striatal and Thalamic Auditory Response During Deep Brain Stimulation for Essential Tremor: Implications for Psychosis.

INTRODUCTION: The P50, a positive auditory-evoked potential occurring 50 msec after an auditory click, has been characterized extensively with electroencephalography (EEG) to detect aberrant auditory electrophysiology in disorders like schizophrenia (SZ) where 61-74% have an auditory gating deficit. The P50 response occurs in primary auditory cortex and several thalamocortical regions. In rodents, the gated P50 response has been identified in the reticular thalamic nucleus (RT)-a deep brain structure traversed during deep brain stimulation (DBS) targeting of the ventral intermediate nucleus (VIM) of the thalamus to treat essential tremor (ET) allowing for interspecies comparison. The goal was to utilize the unique opportunity provided by DBS surgery for ET to map the P50 response in multiple deep brain structures in order to determine the utility of intraoperative P50 detection for facilitating DBS targeting of auditory responsive subterritories. MATERIALS AND METHODS: We developed a method to assess P50 response intraoperatively with local field potentials (LFP) using microelectrode recording during routine clinical electrophysiologic mapping for awake DBS surgery in seven ET patients. Recording sites were mapped into a common stereotactic space. RESULTS: Forty significant P50 responses of 155 recordings mapped to the ventral thalamus, RT and CN head/body interface at similar rates of 22.7-26.7%. P50 response exhibited anatomic specificity based on distinct positions of centroids of positive and negative responses within brain regions and the fact that P50 response was not identified in the recordings from either the internal capsule or the dorsal thalamus. CONCLUSIONS: Detection of P50 response intraoperatively may guide DBS targeting RT and subterritories within CN head/body interface-DBS targets with the potential to treat psychosis and shown to modulate schizophrenia-like aberrancies in mouse models.

Does COMT val158met polymorphism influence P50 sensory gating, eye tracking or saccadic inhibition dysfunctions in schizophrenia?

Three electrophysiological endophenotypes are routinely studied in schizophrenia (SCZ): smooth pursuit eye movement (SPEM) dysfunction, deficits in P50 auditory-evoked potential inhibition, and saccadic inhibition deficits. The current study aimed to investigate the relationship between the COMT val158met polymorphism and these three endophenotypes. One hundred four SCZ patients (DSM-IV-R criteria) and 89 healthy controls were included in this study. P50 auditory-evoked potential inhibition, antisaccade paradigm and SPEM were analyzed. All individuals were genotyped for the COMT val158met. SCZ patients showed a higher rate of deficits measured by the SPEM, antisaccade and P50 inhibition paradigms without association with COMT val158met. However, in our control group, we have found an association between the Val polymorphism and the smoking status. More importantly, we have found a higher accuracy of saccades during the predictive pursuit task associated to the Met polymorphism in controls but not in SCZ patients who were receiving antidopaminergic medications. This result is in line with the hypothesis of the relationship between the Met polymorphism of the COMT gene, a higher level of dopamine in the prefrontal cortex and the role of the fronto-cerebellar loop in smooth predictive pursuit.

Pattern of P50 suppression deficit in patients with epilepsy and individuals with schizophrenia / Padrão do déficit de supressão do P50 em pacientes com epilepsia e em indivíduos com esquizofrenia

OBJECTIVE: To identify P50 suppression in patients with epilepsy, to investigate the effect of seizure control on P50 suppression, and to compare epilepsy patients with individuals with schizophrenia and healthy volunteers. METHOD: P50 evoked potential parameters and P50 suppression were studied crossectionally in patients with uncontrolled or controlled epilepsy, in individuals with schizophrenia and in healthy volunteers. RESULTS: Individuals with schizophrenia had significantly smaller conditioning stimulus (S1) amplitude, and patients with epilepsy had larger test stimulus (S2) amplitude. Mean S2/S1 ratio was 0.71±0.33 for patients with uncontrolled epilepsy; 0.68±0.36 for patients with controlled epilepsy; 0.96±0.47 for individuals with schizophrenia, and 0.42±0.24 for healthy volunteers. CONCLUSION: The sensory filter of patients with epilepsy is altered, and this alteration is not associated with seizure control. Also, it works differently from the sensory filter of individuals with schizophrenia.

OBJETIVO: Identificar se existe déficit de supressão do P50 em pacientes com epilepsia, verificar a influência do controle das crises nesse déficit, comparando com pacientes com esquizofrenia e com voluntários saudáveis. MÉTODO: Os parâmetros do potencial evocado P50 e sua supressão foram estudados, com um corte transversal, em pacientes com epilepsia controlada ou não, esquizofrenia e em voluntários saudáveis. RESULTADOS: Indivíduos com esquizofrenia apresentam uma amplitude de S1 significativamente menor que os demais, sendo que os pacientes com epilepsia apresentavam uma resposta S2 de maior amplitude. A média da razão S2/S1 foi de 0,71±0,33 nos pacientes com epilepsia não controlada; 0,68±0,36 naqueles com epilepsia controlada; 0,96±0,47 nos com esquizofrenia e 0,42±0,24 nos controles normais. CONCLUSÃO: O filtro sensitivo de pacientes com epilepsia é alterado, e essa alteração não está associada com o controle das crises. Além disso, ele funciona de forma diferente do filtro sensitivo dos indivíduos com esquizofrenia.