In vitro neuronal network activity in NMDA receptor encephalitis.

BACKGROUND: Anti-NMDA-encephalitis is caused by antibodies against the N-methyl-D-aspartate receptor (NMDAR) and characterized by a severe encephalopathy with psychosis, epileptic seizures and autonomic disturbances. It predominantly occurs in young women and is associated in 59% with an ovarian teratoma. RESULTS: We describe effects of cerebrospinal fluid (CSF) from an anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patient on in vitro neuronal network activity (ivNNA). In vitro NNA of dissociated primary rat cortical populations was recorded by the microelectrode array (MEA) system.The 23-year old patient was severely affected but showed an excellent recovery following multimodal immunomodulatory therapy and removal of an ovarian teratoma. Patient CSF (pCSF) taken during the initial weeks after disease onset suppressed global spike- and burst rates of ivNNA in contrast to pCSF sampled after clinical recovery and decrease of NMDAR antibody titers. The synchrony of pCSF-affected ivNNA remained unaltered during the course of the disease. CONCLUSION: Patient CSF directly suppresses global activity of neuronal networks recorded by the MEA system. In contrast, pCSF did not regulate the synchrony of ivNNA suggesting that NMDAR antibodies selectively regulate distinct parameters of ivNNA while sparing their functional connectivity. Thus, assessing ivNNA could represent a new technique to evaluate functional consequences of autoimmune encephalitis-related CSF changes.

Increased sensory feedback in Tourette syndrome.

Tourette syndrome (TS) is a neuro-psychiatric disorder being characterized by motor and phonic tics typically preceded by sensory urges. Given the latter the role of the sensory system and sensorimotor interaction in TS has recently gained increased attention. 12 TS patients and 12 matched control subjects performed two tasks, requiring simple finger movements: a Go/NoGo task and a self paced movement task. Neurophysiological data was recorded using magnetoencephalography (MEG). Event related responses around movement onset, i.e. motor field (MF) occurring directly prior to the movement and movement evoked field (MEF) immediately after movement onset were analyzed using dipole modeling. MF peak amplitudes did not differ between groups in either task. In contrast, in both tasks MEF peak amplitudes were increased in TS patients. Moreover, larger MEF amplitudes during self paced movements were inversely correlated with motor tic frequency and severity. Enlarged MEF amplitudes as a marker of early sensory feedback of one's own movements probably represent enlarged sensory input from the periphery resulting from altered subcortical gating. We conclude that TS patients exhibit altered sensory-motor processing involved in voluntary movement control, which might also be successful in tic control.

The effect of 10 Hz transcranial alternating current stimulation (tACS) on corticomuscular coherence.

Synchronous oscillatory activity at alpha (8-12 Hz), beta (13-30 Hz), and gamma (30-90 Hz) frequencies is assumed to play a key role for motor control. Corticomuscular coherence (CMC) represents an established measure of the pyramidal system's integrity. Transcranial alternating current stimulation (tACS) offers the possibility to modulate ongoing oscillatory activity. Behaviorally, 20 Hz tACS in healthy subjects has been shown to result in movement slowing. However, the neurophysiological changes underlying these effects are not entirely understood yet. The present study aimed at ascertaining the effects of tACS at 10 and 20 Hz in healthy subjects on CMC and local power of the primary sensorimotor cortex. Neuromagnetic activity was recorded during isometric contraction before and at two time points (2-10 min and 30-38 min) after tACS of the left primary motor cortex (M1), using a 306 channel whole head magnetoencephalography (MEG) system. Additionally, electromyography (EMG) of the right extensor digitorum communis (EDC) muscle was measured. TACS was applied at 10 and 20 Hz, respectively, for 10 min at 1 mA. Sham stimulation served as control condition. The data suggest that 10 Hz tACS significantly reduced low gamma band CMC during isometric contraction. This implies that tACS does not necessarily cause effects at stimulation frequency. Rather, the findings suggest cross-frequency interplay between alpha and low gamma band activity modulating functional interaction between motor cortex and muscle.

Cortico-muscular coupling and motor performance are modulated by 20 Hz transcranial alternating current stimulation (tACS) in Parkinson's disease.

Parkinson's disease (PD) is associated with pathologically altered oscillatory activity. While synchronized oscillations between 13 and 30 Hz are increased within a cortico-subcortical network, cortico-muscular coupling (CMC) is decreased. The present study aims at investigating the effect of non-invasive transcranial alternating current stimulation (tACS) of the primary motor cortex (M1) on motor symptoms and motor-cortical oscillations in PD. In 10 PD patients and 10 healthy control subjects, static isometric contraction, dynamic fast finger tapping, and diadochokinesia of the more severely affected hand were investigated prior to and shortly after tACS of the contralateral M1 at 10 Hz vs. 20 Hz vs. sham. During isometric contraction, neuromagnetic activity was recorded using magnetoencephalography. 20 Hz tACS attenuated beta band CMC during isometric contraction and amplitude variability during finger tapping in PD patients but not in healthy control subjects. 10 Hz tACS yielded no significant after-effects. The present data suggest that PD is associated with pathophysiological alterations which abet a higher responsiveness toward frequency-specific tACS - possibly due to pathologically altered motor-cortical oscillatory synchronization at frequencies between 13 and 30 Hz.