Interregional coupling of distant brain regions can be measured by electroencephalographic (EEG) coherence reflecting the spatial-temporal correlation between two oscillatory signals. It has been suggested that this coherence in activity is a signature of functional integration of multimodal neuronal networks. Repetitive transcranial magnetic stimulation (rTMS) is a well-established technique for non-invasive cortical stimulation. Its modulating effects outlast the train of stimulation and affect behavior. In the present study, we tested the hypothesis that cortico-cortical coherence between distant brain areas can be selectively enhanced by synchronous bifocal rTMS. Cortico-cortical coherence was assessed in 16 healthy human subjects before and after three trains of synchronous high-frequency (10 Hz) rTMS to the left primary motor cortex and the visual cortex at the occipital pole simultaneously. Stimulation of the left M1 alone served as the control condition. Coherence and spectral power were measured between these areas on the stimulated and the homologue contralateral side. Synchronous bifocal rTMS induced an increase of interregional coupling in the alpha and lower beta band on the stimulated side without effects on spectral power. These data indicate that synchronous bifocal rTMS is a feasible technique for selective modulation of interregional EEG coherence. Furthermore, they raise the hypothesis that interventional enhancement of long-range coherence may effectively modulate interregional integration with behavioral consequences.
Present pathophysiological concepts of neuropathic tremor assume mistimed and defective afferent input resulting in deregulation of cerebello-thalamo-cortical motor networks. Here, we provide direct evidence of central tremor processing in a 76-year-old female who underwent bilateral deep brain stimulation of the ventral intermedial nucleus of the thalamus (Vim-DBS) because of neuropathic tremor associated with IgM paraproteinemia. Electrophysiological recordings of EEG and EMG were performed in three perioperative sessions: (1) preoperatively, (2) intraoperatively, and (3) 4 days after surgery in both rest and postural tremor conditions. Tremor-related synchronization (coherence) between motor cortex (M1) and muscles (M. extensor digitorum, M. flexor digitorum) was assessed, and additional intraoperative local field potential (LFP) recordings from Vim allowed comprehensive coherence mapping in thalamo-cortico-muscular networks. Directionality of information flow was determined by directed transfer function (DTF) and phase analyses. Stimulation effects on tremor and corticomuscular coherence were assessed and the patient was followed for 12 months on clinical outcome measures (Tremor Rating Scale, CADET-Score). Vim-DBS reduced tremor (59%) and improved motor functionality in daily activities (31%, CADET-A) after 12 months. Intraoperative recordings demonstrated significant coherence in the tremor frequency (4 Hz) between M1 and contralateral muscle, Vim and ipsilateral M1, Vim and contralateral muscle, but not between Vim and contralateral M1. Information flow was directed from M1 to Vim and bidirectional between M1 and muscle and between Vim and muscle, respectively. Corticomuscular coherence at tremor frequency was completely suppressed by Vim-DBS. Our case study demonstrates central oscillators underlying neuropathic tremor and implies a strong pathophysiological rationale for Vim-DBS.
In developmental biology, zebrafish are widely used to study the impact of mutations. The fast pace of development allows for a definitive morphological evaluation of the phenotype usually 5 days post fertilization (dpf). At that age, a functional analysis is already feasible using electroretinographic (ERG) methods. Corneal Ganzfeld ERGs were recorded with a glass microelectrode in anaesthetized, dark-adapted larvae aged 5 dpf, using a platinum wire beneath a moist paper towel as reference. ERG protocols included flash, flicker, and ON/OFF stimuli, both under scotopic and photopic conditions. Repetitive, isoluminant stimuli were used to assess the dynamic effect of pharmacological agents on the ERG. Single flash, flicker, and ON/OFF responses had adequately matured at this point to be informative. Typical signs of the cone dominance were the small scotopic a-wave and the large OFF responses. The analysis of consecutive single traces was possible because of the lack of EKG, breathing, and blink artefacts. After application of APB, which selectively blocks the ON channel via the mGluR6 receptor, the successive loss of the b-wave could be observed, which was quite different from the deterioration of the ERG after a circulatory arrest. The above techniques allowed to reliably obtain Ganzfeld ERGs in larvae aged 5 dpf. This underlines the important role of the zebrafish as a model for the functional analysis of mutations disrupting the visual system.
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