Tuned to Tremor: Increased Sensitivity of Cortico-Basal Ganglia Neurons to Tremor Frequency in the MPTP Nonhuman Primate Model of Parkinson's Disease.

Rest tremor is one of the most prominent clinical features of Parkinson's disease (PD). Here, we hypothesized that cortico-basal ganglia neurons tend to fire in a pattern that matches PD tremor frequency, suggesting a resonance phenomenon. We recorded spiking activity in the primary motor cortex (M1) and globus pallidus external segment of 2 female nonhuman primates, before and after parkinsonian state induction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The arm of nonhuman primates was passively rotated at seven different frequencies surrounding and overlapping PD tremor frequency. We found entrainment of the spiking activity to arm rotation and a significant sharpening of the tuning curves in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine state, with a peak response at frequencies that matched the frequency of PD tremor. These results reveal increased sensitivity of the cortico-basal ganglia network to tremor frequency and could indicate that this network acts not only as a tremor switch but is involved in setting its frequency.SIGNIFICANCE STATEMENT Tremor is a prominent clinical feature of Parkinson's disease; however, its underlying pathophysiology is still poorly understood. Using electrophysiological recordings of single cortico-basal ganglia neurons before and after the induction of a parkinsonian state, and in response to passive arm rotation, this study reports increased sensitivity to tremor frequency in Parkinson's disease. We found sharpening of the population tuning to the midrange of the tested frequencies (1-13.3 Hz) in the healthy state that further increased in the parkinsonian state. These results hint at the increased frequency-tuned sensitivity of cortico-basal ganglia neurons and suggest that they tend to resonate with the tremor.

Validation of behavioral measures of social cognition in individuals diagnosed with schizophrenia.

Schizophrenia, a complex neuropsychiatric disorder, manifests severe impairments in social cognition, notably in Theory of Mind (ToM), empathy, and emotion recognition, which significantly influence social competence and overall functioning. These aspects are crucial for prognosis in individuals diagnosed with schizophrenia (SZ). This study validates a comics strip paradigm for ToM and empathy assessment, the Montreal Affective Voices (MAV) for measuring emotion recognition, and a Go-NoGo task for inhibition control estimation in individuals diagnosed with SZ, comparing their performance with healthy controls. SZ participants exhibited diminished abilities in the comics strip task, especially in ToM and empathy conditions, alongside challenges in identifying emotions from vocal cues in MAV. They responded slower and tended to be less accurate in the Go-NoGo task. The validated behavioral battery addresses the limitations of previous measures and emerges as a promising tool for future investigations into the neural systems underlying social cognition in schizophrenia. Such insights can lead to the development of long-needed treatment for negative symptoms and social dysfunctions in schizophrenia.