Central oscillators in a patient with neuropathic tremor: evidence from intraoperative local field potential recordings.

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.

Theta burst stimulation in the treatment of incapacitating tinnitus accompanied by severe depression.

This case report describes the use of transcranial magnetic theta burst stimulation (TBS) in the treatment of incapacitating tinnitus accompanied by symptoms of severe depression. Tinnitus is known to be associated with hyperactivity and maladaptive cortical reorganization of the central auditory system. Combined with anxiety and depression, it can occasionally constitute a psychiatric emergency. Recently, it has been demonstrated that tinnitus can be temporarily suppressed by non-invasive transcranial magnetic stimulation. TBS is a newly developed technique for rapid and lasting modulation of cortical excitability. Herein, we present a case of a 54-year-old woman with incapacitating tinnitus that has significantly decreased after three cycles of 1-week treatment with continuous TBS to the temporo-parietal auditory association cortex. According to the Tinnitus Questionnaire, tinnitus intensity decreased from 84 points before to 59 points after treatment. Hamilton Rating Scale for Depression score dropped from 44 to 23 points. TBS showed to be efficient, well-tolerated, and practical in the management of distressing tinnitus accompanied by symptoms of severe depression.

Enhancement of long-range EEG coherence by synchronous bifocal transcranial magnetic stimulation.

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.

Visual short-term effects of Viagra: double-blind study in healthy young subjects.

PURPOSE: To investigate short-term visual effects of a single 100-mg dose of Viagra (sildenafil citrate) in healthy men. DESIGN: Randomized, double-blind, placebo-controlled clinical trial of drug effects on normal volunteers conducted by a single center. METHODS: Twenty men, aged 20 to 40 years, were treated with either a placebo or 100 mg sildenafil. Visual function tests included electroretinogram (ERG) recordings, on-/off- and 3.3 Hz-flicker-ERG recordings, anomaloscope matches, and measurements of cone contrast sensitivities and transient tritanopia. RESULTS: Most visual tests did not differ between the sildenafil and placebo groups. However, statistically significant increases in sensitivity during transient tritanopia were observed as well as significant prolongations in the implicit times of scotopic a-wave, photopic b-wave, and 3.3 Hz-flicker a-wave and b-wave ERG recordings. The magnitude of the differences correlated with peak sidenafil plasma concentration. Although rod amplitudes of the ERG recordings tended to be higher and cone amplitudes lower in the sildenafil group after drug ingestion, the differences were nonsignificant. There were no reports of visual side effects, and all electrophysiologic and psychophysical measurements returned to the normal range within 24 hours. CONCLUSIONS: A single oral dose of 100-mg sildenafil given to healthy young men led to small but statistically significant transient changes of outer and inner retinal function, as detected by ERG and psychophysical methods. Although the acute effects were fully reversible within 24 hours, it would be worthwhile to compare them with those induced by other PDE5 and PDE6 inhibitors.

Alpha coherence predicts accuracy during a visuomotor tracking task.

It has been shown that synchrony of neuronal oscillations plays a critical role in effective communication between functionally distinct brain areas involving motor-sensory integration. However, the patterns of cortico-cortical coupling and their relation to behavioural success are widely unknown. Here, we analysed changes in cortico-cortical coherence during an unimanual visuomotor task and their correlation with performance. A 28-channel-EEG was attained in 27 healthy subjects during the tracking of an irregularly fluctuating target on a screen by manipulating a force sensor with the right index finger and thumb. For oscillatory power in the alpha (8-12 Hz) and the lower beta-band (beta1, 13-20 Hz), we found a decrease in central and occipital areas during performance. Interregional coherence between contralateral frontal and central areas was enhanced in the alpha band. In beta1, we observed a marked increase of coherence in centroparietal regions of both hemispheres extending to occipital and frontal regions in beta2 (21-30 Hz). Most prominently, correlation analysis between alpha coherence and performance accuracy indicated that higher occipitocentral (i.e. visuomotor) coherence is associated with better visuomotor performance whereas high tracking error is associated with enhanced frontocentral coupling, suggesting additional activation of a frontoparietal control network. These results provide further evidence that coherent brain oscillations in alpha and beta bands significantly contribute to effective functional integration of visual and motor areas.

Ganzfeld ERG in zebrafish larvae.

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.