Binding Mechanisms in Visual Perception and Their Link With Neural Oscillations: A Review of Evidence From tACS

Neurophysiological studies in humans employing magneto- (MEG) and electro- (EEG) encephalography increasingly suggest that oscillatory rhythmic activity of the brain may be a core mechanism for binding sensory information across space, time, and object features to generate a unified perceptual representation. To distinguish whether oscillatory activity is causally related to binding processes or whether, on the contrary, it is a mere epiphenomenon, one possibility is to employ neuromodulatory techniques such as transcranial alternating current stimulation (tACS). tACS has seen a rising interest due to its ability to modulate brain oscillations in a frequency-dependent manner. In the present review, we critically summarize current tACS evidence for a causal role of oscillatory activity in spatial, temporal, and feature binding in the context of visual perception. For temporal binding, the emerging picture supports a causal link with the power and the frequency of occipital alpha rhythms (8–12 Hz); however, there is no consistent evidence on the causal role of the phase of occipital tACS. For feature binding, the only study available showed a modulation by occipital alpha tACS. The majority of studies that successfully modulated oscillatory activity and behavioral performance in spatial binding targeted parietal areas, with the main rhythms causally linked being the theta (~7 Hz) and beta (~18 Hz) frequency bands. On the other hand, spatio-temporal binding has been directly modulated by parieto-occipital gamma (~40–60 Hz) and alpha (10 Hz) tACS, suggesting a potential role of cross-frequency coupling when binding across space and time. Nonetheless, negative or partial results have also been observed, suggesting methodological limitations that should be addressed in future research. Overall, the emerging picture seems to support a causal role of brain oscillations in binding processes and, consequently, a certain degree of plasticity for shaping binding mechanisms in visual perception, which, if proved to have long lasting effects, can find applications in different clinical populations

Local and Distributed fMRI Changes Induced by 40 Hz Gamma tACS of the Bilateral Dorsolateral Prefrontal Cortex: A Pilot Study

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its spatial specificity, are still unclear. Here, we present a concurrent tACS-fMRI block design study to characterize the impact of 40 Hz tACS applied over the left and right dorsolateral prefrontal cortex (DLPFC) in healthy subjects. Results suggest an increase in blood oxygenation level-dependent (BOLD) activity in the targeted bilateral DLPFCs, as well as in surrounding brain areas affected by stimulation according to biophysical modeling, i.e., the premotor cortex and anterior cingulate cortex (ACC). However, off-target effects were also observed, primarily involving the visual cortices, with further effects on the supplementary motor areas (SMA), left subgenual cingulate, and right superior temporal gyrus. The specificity of 40 Hz tACS over bilateral DLPFC and the possibility for network-level effects should be considered in future studies, especially in the context of recently promoted gamma-induction therapeutic protocols for neurodegenerative disorders. © 2022 Lucia Mencarelli et al

Lasting EEG/MEG aftereffects on human brain oscillations after rhythmic transcranial brain stimulation: Level of control over oscillatory network activity

A number of rhythmic protocols have emerged for non-invasive brain stimulation (NIBS) in humans, including transcranial alternating current stimulation (tACS), oscillatory transcranial direct current stimulation (otDCS) and repetitive (also called rhythmic) transcranial magnetic stimulation (rTMS). With these techniques, it is possible to match the frequency of the externally applied electromagnetic fields to the intrinsic frequency of oscillatory neural population activity ("frequency-tuning"). Mounting evidence suggests that by this means tACS, otDCS, and rTMS can entrain brain oscillations and promote associated functions in a frequency-specific manner, in particular during (i.e. online to) stimulation. Here, we focus instead on the changes in oscillatory brain activity that persist after the end of stimulation. Understanding such aftereffects in healthy participants is an important step for developing these techniques into potentially useful clinical tools for the treatment of specific patient groups. Reviewing the electrophysiological evidence in healthy participants, we find aftereffects on brain oscillations to be a common outcome following tACS/otDCS and rTMS. However, we did not find a consistent, predictable pattern of aftereffects across studies, which is in contrast to the relative homogeneity of reported online effects. This indicates that aftereffects are partially dissociated from online, frequency-specific (entrainment) effects during tACS/otDCS and rTMS. We outline possible accounts and future directions for a better understanding of the link between online entrainment and offline aftereffects, which will be key for developing more targeted interventions into oscillatory brain activity

Targeting the neurophysiology of cognitive systems with transcranial alternating current stimulation

Cognitive impairment represents one of the most debilitating and most difficult symptom to treat of many psychiatric illnesses. Human neurophysiology studies have suggested specific pathologies of cortical network activity correlate with cognitive impairment. However, we lack (1) demonstration of causal relationships between specific network activity patterns and cognitive capabilities and (2) treatment modalities that directly target impaired network dynamics of cognition. Transcranial alternating current stimulation (tACS), a novel non-invasive brain stimulation approach, may provide a crucial tool to tackle these challenges. We here propose that tACS can be used to elucidate the causal role of cortical synchronization in cognition and, eventually, to enhance pathologically weakened synchrony that may underlie cognitive deficits. To accelerate such development of tACS as a treatment for cognitive deficits, we discuss studies on tACS and cognition (all performed in healthy participants) according to the Research Domain Criteria (RDoC) of the National Institute of Mental Health

Neurobiological After-Effects of Low Intensity Transcranial Electric Stimulation of the Human Nervous System: From Basic Mechanisms to Metaplasticity

Non-invasive low-intensity transcranial electrical stimulation (tES) of the brain is an evolving field that has brought remarkable attention in the past few decades for its ability to directly modulate specific brain functions. Neurobiological after-effects of tES seems to be related to changes in neuronal and synaptic excitability and plasticity, however mechanisms are still far from being elucidated. We aim to review recent results from in vitro and in vivo studies that highlight molecular and cellular mechanisms of transcranial direct (tDCS) and alternating (tACS) current stimulation. Changes in membrane potential and neural synchronization explain the ongoing and short-lasting effects of tES, while changes induced in existing proteins and new protein synthesis is required for long-lasting plastic changes (LTP/LTD). Glial cells, for decades supporting elements, are now considered constitutive part of the synapse and might contribute to the mechanisms of synaptic plasticity. This review brings into focus the neurobiological mechanisms and after-effects of tDCS and tACS from in vitro and in vivo studies, in both animals and humans, highlighting possible pathways for the development of targeted therapeutic applications

Deep Brain Stimulation (DBS) Applications

The issue is dedicated to applications of Deep Brain Stimulation and, in this issue, we would like to highlight the new developments that are taking place in the field. These include the application of new technology to existing indications, as well as ‘new’ indications. We would also like to highlight the most recent clinical evidence from international multicentre trials. The issue will include articles relating to movement disorders, pain, psychiatric indications, as well as emerging indications that are not yet accompanied by clinical evidence. We look forward to your expert contribution to this exciting issue

Targeting cognition in schizophrenia through transcranial direct current stimulation: a systematic review and perspective

Cognitive deficits are a fundamental feature of schizophrenia for which currently no effective treatments exist. This paper examines the possibility to use transcranial direct current stimulation (tDCS) to target cognitive deficits in schizophrenia as evidence from studies in healthy participants suggests that tDCS may improve cognitive functions and associated neural processes. We carried out a systematic review with the following search terms: ‘tDCS’, ‘electric brain stimulation’, ‘schizophrenia’, ‘cognitive’, ‘cognition’ until March 2019. 659 records were identified initially, 612 of which were excluded after abstract screening. The remaining 47 articles were assessed for eligibility based on our criteria and 26 studies were excluded. In addition, we compared several variables, such as online vs. offline-stimulation protocols, stimulation type and intensity on mediating positive vs. negative study outcomes. The majority of studies (n = 21) identified significant behavioural and neural effects on a range of cognitive functions (versus n = 11 with null results), including working memory, attention and social cognition. However, we could not identify tDCS parameters (electrode montage, stimulation protocol, type and intensity) that clearly mediated effects on cognitive deficits. There is preliminary evidence for the possibility that tDCS may improve cognitive deficits in schizophrenia. We discuss the rationale and strength of evidence for using tDCS for targeting cognitive deficits in schizophrenia as well as methodological issues and potential mechanisms of action

The Role of Alpha Oscillations among the Main Neuropsychiatric Disorders in the Adult and Developing Human Brain: Evidence from the Last 10 Years of Research

Alpha oscillations (7–13 Hz) are the dominant rhythm in both the resting and active brain. Accordingly, translational research has provided evidence for the involvement of aberrant alpha activ- ity in the onset of symptomatological features underlying syndromes such as autism, schizophrenia, major depression, and Attention Deficit and Hyperactivity Disorder (ADHD). However, findings on the matter are difficult to reconcile due to the variety of paradigms, analyses, and clinical phenotypes at play, not to mention recent technical and methodological advances in this domain. Herein, we seek to address this issue by reviewing the literature gathered on this topic over the last ten years. For each neuropsychiatric disorder, a dedicated section will be provided, containing a concise account of the current models proposing characteristic alterations of alpha rhythms as a core mechanism to trigger the associated symptomatology, as well as a summary of the most relevant studies and scientific con- tributions issued throughout the last decade. We conclude with some advice and recommendations that might improve future inquiries within this field

Mental Activity as the Bridge between Neural Biomarkers and Symptoms of Psychiatric Illness

The Research Domain Criteria (RDoC) initiative challenges researchers to build neurobehavioral models of psychiatric illness with the hope that such models identify better targets that will yield more effective treatment. However, a guide for building such models was not provided and symptom heterogeneity within Diagnostic Statistical Manual categories has hampered progress in identifying endophenotypes that underlie mental illness. We propose that the best chance to discover viable biomarkers and treatment targets for psychiatric illness is to investigate a triangle of relationships: severity of a specific psychiatric symptom that correlates to mental activity that correlates to a neural activity signature. We propose that this is the minimal model complexity required to advance the field of psychiatry. With an understanding of how neural activity relates to the experience of the patient, a genuine understanding for how treatment imparts its therapeutic effect is possible. After the discovery of this three-fold relationship, causal testing is required in which the neural activity pattern is directly enhanced or suppressed to provide causal, instead of just correlational, evidence for the biomarker. We suggest using non-invasive brain stimulation (NIBS) as these techniques provide tools to precisely manipulate spatial and temporal activity patterns. We detail how this approach enabled the discovery of two orthogonal electroencephalography (EEG) activity patterns associated with anhedonia and anxiosomatic symptoms in depression that can serve as future treatment targets. Altogether, we propose a systematic approach for building neurobehavioral models for dimensional psychiatry