Reduction in left frontal alpha oscillations by transcranial alternating current stimulation in major depressive disorder is context-dependent in a randomized-clinical trial

Background: Left frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for non-invasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind placebo controlled clinical trial. Methods: In this current study, we aimed to replicate such successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD. Electrical brain activity was recorded during rest and while viewing emotionally-salient images before and after stimulation to investigate if the modulation of alpha oscillation by tACS exhibited specificity with regards to valence. Results: In agreement with the previous study of tACS in MDD, we found that a single session of bifrontal IAF-tACS reduced left frontal alpha power during the resting state when compared to placebo. Furthermore, the reduction of left frontal alpha oscillation by tACS was specific for stimuli with positive valence. In contrast, these effects on left frontal alpha power were not found in healthy control participants. Conclusion: Together these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD. National Clinical Trial: NCT03449979, Single Session of tACS in a Depressive Episode (SSDE) https://www.clinicaltrials.gov/ct2/show/NCT03449979 .

Transcranial alternating current stimulation entrains alpha oscillations by preferential phase synchronization of fast-spiking cortical neurons to stimulation waveform

Computational modeling and human studies suggest that transcranial alternating current stimulation (tACS) modulates alpha oscillations by entrainment. Yet, a direct examination of how tACS interacts with neuronal spiking activity that gives rise to the alpha oscillation in the thalamo-cortical system has been lacking. Here, we demonstrate how tACS entrains endogenous alpha oscillations in head-fixed awake ferrets. We first show that endogenous alpha oscillations in the posterior parietal cortex drive the primary visual cortex and the higher-order visual thalamus. Spike-field coherence is largest for the alpha frequency band, and presumed fast-spiking inhibitory interneurons exhibit strongest coupling to this oscillation. We then apply alpha-tACS that results in a field strength comparable to what is commonly used in humans (<0.5 mV/mm). Both in these ferret experiments and in a computational model of the thalamo-cortical system, tACS entrains alpha oscillations by following the theoretically predicted Arnold tongue. Intriguingly, the fast-spiking inhibitory interneurons exhibit a stronger entrainment response to tACS in both the ferret experiments and the computational model, likely due to their stronger endogenous coupling to the alpha oscillation. Our findings demonstrate the in vivo mechanism of action for the modulation of the alpha oscillation by tACS.

Attenuated alpha oscillations as an index of cortical hyperexcitability: Evidence from migraine patients

Anomalous phantom visual perceptions coupled to an aversion to some visual patterns has been associated with aberrant cortical hyperexcitability in migraine patients. Previous literature has found fluctuations of alpha oscillation (8-14 Hz) over the visual cortex to be associated with the gating of the visual stream. In the current study, we examined whether alpha activity was differentially modulated in migraineurs in anticipation of an upcoming stimulus as well as post-stimulus periods. We used EEG to examine the brain activity in a group of 28 migraineurs (17 with aura/11 without) and 29 non-migraineurs and compared the modulations of alpha power in the pre/post-stimulus period relative to onset of stripped gratings of 3 spatial frequencies 0.5, 3, and 13 cycles per degree (cpd). Overall, we found that that migraineurs had significantly less alpha power prior to the onset of the stimulus relative to controls. Moreover, relative to the control group, migraineurs had significantly greater post-stimulus alpha suppression (i.e event-related desynchronization) induced by the 3 cpd grating at the 2nd half of the experiment, the stimulus most often reported to induce visual disturbances. These findings taken together provide strong support of the presence of elevated cortical excitability in the visual cortex of migraine sufferers. We speculate that cortical hyperexcitation could be the consequence of impaired perceptual learning driven by the dysfunction of GABAergic inhibitory mechanism.

Visual Thalamocortical Mechanisms of Waking State Dependent Activity and Alpha Oscillations

SummaryThe brain exhibits distinct patterns of recurrent activity closely related to the behavioral state of the animal. The neural mechanisms that underlie state-dependent activity in the awake animal are incompletely understood. Here, we demonstrate that two types of state-dependent activity - rapid arousal/movement related signals and a 3-5 Hz alpha-like rhythm - in the primary visual cortex (V1) of mice strongly correlate with activity in the visual thalamus. Inactivation of V1 does not interrupt arousal/movement related signals in most visual thalamic neurons, but it abolishes the 3-5 Hz oscillation. Silencing of the visual thalamus similarly eradicates the alpha-like rhythm and perturbs arousal/movement-related activation in V1. Finally, we observed that whisker movement or locomotion is not required for rapid increases in cortical activation. Our results indicate that thalamocortical interactions together with cell-intrinsic properties of thalamocortical cells play a crucial role in shaping state-dependent activity in V1 of the awake animal.HighlightsWhisker movements correlate with rapid synaptic activation in V1 and visual thalamusSilencing of V1 does not abolish movement related activation in most dLGN or LP cellsSilencing of visual thalamus strongly reduces movement related activation in V1Thalamocortical interactions generate state-dependent alpha frequency oscillationVisual thalamic cells exhibit LTS firing during alpha oscillation in the awake mouse

Psychological and Electrophysiological Correlates of Word Learning Success

Background. A rich vocabulary supports human achievements in socio-economic activities, education, and communication. It is therefore important to clarify the nature of language acquisition as a complex multidimensional process. However, both the psychological and neurophysiological mechanisms underpinning language learning, as well as the links between them, are still poorly understood. Objective. This study aims to explore the psychological and neurophysiological correlates of successful word acquisition in a person’s native language. Design. Thirty adults read sentences with novel nouns, following which the participants’ electroencephalograms were recorded during a word-reading task. Event-related potentials in response to novel words and alpha oscillation parameters (amplitude, variability, and long-range temporal correlation dynamics) were analyzed. Learning outcomes were assessed at the lexical and semantic levels. Psychological variables measured using Amthauer’s test (verbal abilities), BIS/BAS scales (motivation), and the MSTAT-1 (ambiguity tolerance) and alpha oscillation parameters were factored. Results. Better recognition of novel words was related to two factors which had high factor loadings for all measured alpha oscillation parameters, indicating the role of attention networks and respective neural activity for enabling information processing. More successful learners had lower P200 amplitude, which also suggests higher attention-system involvement. Another factor predicted better acquisition of word meanings for less ambiguity-tolerant students, while the factor which pooled logical conceptual thinking ability and persistence in goal-reaching, positively correlated with acquisition of both word forms and meanings. Conclusion. The psychological factors predominantly correlated with word-learning success in semantic tasks, while neurophysiological variables were linked to performance in the recognition task.