The impact of GABAergic drugs on TMS-induced brain oscillations in human motor cortex

Brain responses to transcranial magnetic stimulation (TMS) as measured with electroencephalography (EEG) have so far been assessed either by TMS-evoked EEG potentials (TEPs), mostly reflecting phase-locked neuronal activity, or time-frequency-representations (TFRs), reflecting oscillatory power arising from a mixture of both evoked (i.e., phase-locked) and induced (i.e., non-phase-locked) responses. Single-pulse TMS of the human primary motor cortex induces a specific pattern of oscillatory changes, characterized by an early (30–200 ms after TMS) synchronization in the α- and β-bands over the stimulated sensorimotor cortex and adjacent lateral frontal cortex, followed by a late (200–400 ms) α- and β-desynchronization over the stimulated and contralateral sensorimotor cortex. As GABAergic inhibition plays an important role in shaping oscillatory brain activity, we sought here to understand if GABAergic inhibition contributes to these TMS-induced oscillations. We tested single oral doses of alprazolam, diazepam, zolpidem (positive modulators of the GABAA receptor), and baclofen (specific GABAB receptor agonist). Diazepam and zolpidem enhanced, and alprazolam tended to enhance while baclofen decreased the early α-synchronization. Alprazolam and baclofen enhanced the early β-synchronization. Baclofen enhanced the late α-desynchronization, and alprazolam, diazepam and baclofen enhanced the late β-desynchronization. The observed GABAergic drug effects on TMS-induced α- and β-band oscillations were not explained by drug-induced changes on corticospinal excitability, muscle response size, or resting-state EEG power. Our results provide first insights into the pharmacological profile of TMS-induced oscillatory responses of motor cortex

Reduced Affective Biasing of Instrumental Action With tDCS Over the Prefrontal Cortex

AbstractBackgroundInstrumental action is well known to be vulnerable to affective value. Excessive transfer of affective value to instrumental action is thought to contribute to psychiatric disorders. The brain region most commonly implicated in overriding such affective biasing of instrumental action is the prefrontal cortex.ObjectiveThe aim of the present study was to reduce affective biasing of instrumental action using transcranial direct current stimulation (tDCS) in young healthy human volunteers.MethodsIn a double-blind, randomized between-group design, 120 participants received anodal, cathodal and sham tDCS while at the same time (online) performing a task that assessed affective biasing of instrumental action. We placed tDCS electrodes over the anterior part of the prefrontal cortex based on evidence from brain stimulation work demonstrating the role of this brain region in controlling affective biasing of instrumental action.ResultsWe showed that prefrontal tDCS reduced affective biasing of instrumental action. Specifically, prefrontal tDCS reduced the degree to which aversive (versus appetitive) cues potentiated instrumental avoidance and suppressed instrumental approach. Contrary to our hypothesis, this effect was seen for cathodal tDCS rather than anodal tDCS.ConclusionThe results demonstrate the potential utility of prefrontal tDCS as a tool for reducing affective biasing of instrumental behavior, thus opening avenues for interventional research on psychiatric disorders that implicate excessive transfer of affective value

Associative Stimulation of the Supraorbital Nerve Fails to Induce Timing-Specific Plasticity in the Human Blink Reflex

BACKGROUND: Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS(LTP)) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS(LTD)) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006). METHODOLOGY/PRINCIPAL FINDINGS: We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD). Controls also received (iv) HFS(LTD) alone and (v) a non-intervention protocol. In BEB patients, HFS(LTP) followed by HFS(LTD) was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment. CONCLUSION/SIGNIFICANCE: Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex

Low-frequency alternating current stimulation rhythmically suppresses gamma-band oscillations and impairs perceptual performance

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On the relationship between cortical excitability and visual oscillatory responses - A concurrent tDCS-MEG study

Neuronal oscillations in the alpha band (8–12 Hz) in visual cortex are considered to instantiate ‘attentional gating’ via the inhibition of activity in regions representing task-irrelevant parts of space. In contrast, visual gamma-band activity (40–100 Hz) is regarded as representing a bottom-up drive from incoming visual information, with increased synchronisation producing a stronger feedforward impulse for relevant information. However, little is known about the direct relationship between excitability of the visual cortex and these oscillatory mechanisms. In this study we used transcranial direct current stimulation (tDCS) in an Oz–Cz montage in order to stimulate visual cortex, concurrently recording whole-brain oscillatory activity using magnetoencephalography (MEG) whilst participants performed a visual task known to produce strong modulations of alpha- and gamma-band activity. We found that visual stimuli produced expected modulations of alpha and gamma – presenting a moving annulus stimulus led to a strong gamma increase and alpha decrease – and that this pattern was observable both during active (anodal and cathodal) tDCS and sham tDCS. However, tDCS did not seem to produce systematic alterations of these oscillatory responses. The present study thus demonstrates that concurrent tDCS/MEG of the visual system is a feasible tool for investigating visual neuronal oscillations, and we discuss potential reasons for the apparent inability of tDCS to effectively change the amplitude of visual stimulus induced oscillatory responses in the current study

Low-frequency alternating current stimulation rhythmically suppresses gamma-band oscillations and impairs perceptual performance

Low frequency oscillations such as alpha (8–12 Hz) are hypothesized to rhythmically gate sensory processing, reflected by 40–100 Hz gamma band activity, via the mechanism of pulsed inhibition. We applied transcranial alternating current stimulation (TACS) at individual alpha frequency (IAF) and flanking frequencies (IAF-4 Hz, IAF+4 Hz) to the occipital cortex of healthy human volunteers during concurrent magnetoencephalography (MEG), while participants performed a visual detection task inducing strong gamma-band responses. Occipital (but not retinal) TACS phasically suppressed stimulus-induced gamma oscillations in the visual cortex and impaired target detection, with stronger phase-to-amplitude coupling predicting behavioral impairments. Retinal control TACS ruled out retino-thalamo-cortical entrainment resulting from (subthreshold) retinal stimulation. All TACS frequencies tested were effective, suggesting that visual gamma-band responses can be modulated by a range of low frequency oscillations. We propose that TACS-induced membrane potential modulations mimic the rhythmic change in cortical excitability by which spontaneous low frequency oscillations may eventually exert their impact when gating sensory processing via pulsed inhibition