Comparative risk of seizure with use of first- and second-generation antipsychotics in patients with schizophrenia and mood disorders.

OBJECTIVE: To compare the risk of antipsychotic-related seizure (ARS) by identifying seizures first diagnosed within 12 months after starting new antipsychotics, using a 12-year total population health claims database from Taiwan. METHODS: Seizure events were identified through emergency department visits or hospitalization with a diagnosis of convulsion (ICD-9-CM: 780.3) or epilepsy (ICD-9-CM: 345). Subjects had an ICD-9-CM diagnosis of schizophrenia, bipolar disorders, or major depressive disorders. Incidence rates of ARS were calculated by person-years of exposure. The ARS risk, adjusted for patient characteristics and medical conditions, of individual antipsychotics versus risperidone was examined by high-dimensional propensity score stratification analyses, followed by sensitivity analyses. RESULTS: The overall 1-year incidence rate of ARS was 9.6 (95% CI, 8.8-10.4) per 1,000 person-years (550 ARS events among 288,397 new antipsychotic users). First-generation antipsychotics were marginally associated with a higher ARS risk than second-generation antipsychotics (adjusted hazard ratio [aHR] = 1.34; 95% CI, 0.99-1.81; P = .061). Most antipsychotics, first- or second-generation, had comparable ARS risks versus risperidone. Notably, clozapine (aHR = 3.06; 95% CI, 1.40-6.71), thioridazine (aHR = 2.90; 95% CI, 1.65-5.10), chlorprothixene (aHR = 2.60; 95% CI, 1.04-6.49), and haloperidol (aHR = 2.34; 95% CI, 1.48-3.71) had higher ARS risks than risperidone, whereas aripiprazole (aHR = 0.41; 95% CI, 0.17-1.00; P = .050) had a marginally lower ARS risk. Sensitivity analyses largely confirmed such findings. CONCLUSIONS: Higher vigilance for ARS is warranted during use of clozapine, chlorprothixene, thioridazine, and haloperidol. The possible lower ARS risk associated with aripiprazole can be clinically significant but needs to be confirmed by larger-scale systematic studies. The comparative ARS risks of antipsychotics supplement empirical knowledge for making judicious choices in prescribing antipsychotics.

Movement related potentials and oscillatory activities in the human internal globus pallidus during voluntary movements.

OBJECTIVE: To study internal globus pallidus (GPi) activities and the interactions among the bilateral GPi and motor cortical areas during voluntary movements. METHODS: Five patients with cervical dystonia who underwent bilateral GPi deep brain stimulation (DBS) were studied. Local field potentials from the GPi DBS electrodes and EEG were recorded while the patients performed externally triggered and self-initiated right wrist movements. RESULTS: Movement related potentials were recorded at the GPi bilaterally before the onset of self-initiated but not externally triggered movements. In all movements studied, frequency analysis revealed a ≈ 10-24 Hz beta event related desynchronisation at bilateral GPi and with EEG recorded over the mid-frontal (Cz-Fz) and the bilateral sensorimotor cortical regions (C3/C4-Cz). A ≈ 64-68 Hz, gamma event related synchronisation was found with EEG recorded over the mid-frontal (Cz-Fz), the sensorimotor cortices (C3-Cz) and the GPi contralateral to movements. Both beta event related desynchronisation and gamma event related synchronisation occurred before the onset of self-initiated movements and at the onset of externally triggered movements. There was a resting ≈ 5-18 Hz coherence between the bilateral GPi, which attenuated for ≈ 1 s during movements. Gamma coherences were observed between EEG recorded over the mid-frontal (Cz-Fz), contralateral sensorimotor cortices (C3-Cz) and the GPi from 0 to 0.5 s after movement onset for externally triggered movements and from 0.5 s before to 0.5 s after movement onset for self-initiated movements. CONCLUSIONS: The beta and gamma frequency bands in the GPi are modulated by the preparation of self-initiated movements and the execution of self-initiated and externally triggered movements. The 5-18 Hz coherence at the bilateral GPi may be related to dystonia and its attenuation may facilitate voluntary movements.

Transcranial magnetic stimulation in different current directions activates separate cortical circuits.

Transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) produces a series of corticospinal descending waves, with a direct (D) wave followed by several indirect (I) waves. TMS inducing posterior-anterior (PA) current in the brain predominantly recruits the early I1-wave, whereas anterior-posterior (AP) directed current preferentially recruits the late I3-wave. However, it is not known whether I-waves elicited by different current directions are mediated by the same neuronal populations. We studied the neuronal mechanisms mediating I-waves by examining the influence of short-latency afferent inhibition (SAI) on various I-waves. SAI was tested with electrical median nerve stimulation at the wrist followed by TMS to the contralateral M1 at different current directions. Surface electromyograms and single motor units were recorded from the first dorsal interosseous muscle. SAI was weaker for the AP compared with that for the PA current direction. With increasing median nerve stimulation intensities, SAI increased for the PA direction but showed a U-shaped relationship for the AP direction. SAI produced more inhibition of late I-waves generated by PA than those generated by AP current direction. We conclude that late I-waves generated by PA and AP current directions are mediated by different neuronal mechanisms.

Somatosensory evoked potentials recorded from the human pedunculopontine nucleus region.

The pedunculopontine nucleus region (PPNR) is an integral component of the midbrain locomotor region and has widespread connections with the cortex, thalamus, brain stem, cerebellum, spinal cord, and especially, the basal ganglia. No previous study examined the somatosensory connection of the PPNR in human. We recorded somatosensory evoked potentials (SEP) from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in the PPNR in 8 patients (6 with Parkinson's disease, 2 with progressive supranuclear palsy). Monopolar recordings from the PPNR contacts showed triphasic or biphasic potentials. The latency of the largest negative peak was between 16.8 and 18.7 milliseconds. Bipolar derivation revealed phase reversal with median nerve stimulation contralateral to the DBS electrode in 6 patients. There was no difference in SEP amplitude and latency between on and off medication states. We also studied the high frequency oscillations (HFOs) by filtering the signal between 500 and 2,500 Hz. The HFOs could be identified only from contralateral stimulation and had intraburst frequencies of 1061 ± 121 Hz, onset latencies of 13.8 ± 1.2 milliseconds, and burst durations of 7.3 ± 1.1 milliseconds. Among the 10 recordings with HFOs, only 1 had possible phase reversal in the bipolar derivation. Our results suggest that there are direct somatosensory inputs to the PPNR. The slow components and HFOs of the SEP have different origins.

Two phases of interhemispheric inhibition between motor related cortical areas and the primary motor cortex in human.

Interhemispheric inhibition (IHI) refers to the neurophysiological mechanism in which one hemisphere of the brain inhibits the opposite hemisphere. IHI can be studied by transcranial magnetic stimulation using a conditioning-test paradigm. We investigated IHI from 5 motor related cortical areas in the right hemisphere to the left primary motor cortex (M1). These areas are hand and face representations of M1, dorsal premotor cortex, somatosensory cortex, and dorsolateral prefrontal cortex. Test stimulus was delivered to the left M1 and conditioning stimulus (CS) was delivered to one of 5 motor related cortical areas in the right hemisphere. The time course of IHI, effects of different CS intensities and current directions on IHI were tested. Maximum IHI was found at interstimulus intervals of approximately 10 ms (short latency IHI, SIHI) and approximately 50 ms (long latency IHI, LIHI) for the motor related areas tested. LIHI could be elicited over a wide range of CS intensities, whereas SIHI required higher CS intensities. We conclude that there are 2 distinct phases of IHI from motor related cortical areas to the opposite M1 through the corpus callosum, and they are mediated by different neuronal populations.