Beta Power May Mediate the Effect of Gamma-TACS on Motor Performance

Transcranial alternating current stimulation (tACS) is becoming an important method in the field of motor rehabilitation because of its ability to non-invasively influence ongoing brain oscillations at arbitrary frequencies. However, substantial variations in its effect across individuals are reported, making tACS a currently unreliable treatment tool. One reason for this variability is the lack of knowledge about the exact way tACS entrains and interacts with ongoing brain oscillations. The present crossover stimulation study on 20 healthy subjects contributes to the understanding of cross-frequency effects of gamma (70 Hz) tACS over the contralateral motor cortex by providing empirical evidence which is consistent with a role of low- (12~-20 Hz) and high- (20-~30 Hz) beta power as a mediator of gamma-tACS on motor performance.Comment: 7 pages, 5 figures, in Proceedings of IEEE Engineering in Medicine and Biology Conference, July 2019 (IEEE license notice

Driving human motor cortical oscillations leads to behaviorally relevant changes in local GABAA inhibition: a tACS-TMS study

Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABAA inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAA decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAA inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention.SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAA inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAA inhibition induced by tACS and the magnitude of GABAA inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool

Dynamic Oscillatory Interactions Between Neural Attention and Sensorimotor Systems

The adaptive and flexible ability of the human brain to preference the processing of salient environmental features in the visual space is essential to normative cognitive function, and various neurologically afflicted patient groups report negative impacts on visual attention. While the brain-bases of human attentional processing have begun to be unraveled, very little is known regarding the interactions between attention systems and systems supporting sensory and motor processing. This is essential, as these interactions are dynamic; evolving rapidly in time and across a wide range of functionally defined rhythmic frequencies. Using magnetoencephalography (MEG) and a range of novel cognitive paradigms and analytical techniques, this work attempts to fill critical gaps in this knowledge. Specifically, we unravel the role of dynamic oscillatory interactions between attention and three sensorimotor systems. First, we establish the importance of sub-second occipital alpha (8 – 14 Hz) oscillatory responses in visual distractor suppression during selective attention (Chapter 1) and their essential role in fronto-parietal attention networks during visual orienting (Chapter 2). Next, we examine the divergent effects of directed attention on multi-frequency primary somatosensory neural oscillations in the theta (4 – 8 Hz), alpha, and beta (18 – 26 Hz) bands (Chapter 3). Finally, we extend these findings to the motor system (Chapter 4), and find that the frontal and parietal beta-frequency oscillations known to support motor planning and execution are modulated equivalently by differing subtypes of attentional interference, whereas frontal gamma (64 – 84 Hz) oscillations specifically index the superadditive effect of this interference. These findings provide new insight into the dynamic nature of attention-sensorimotor interactions in the human brain, and will be the foundation for groundbreaking new studies of attentional deficits in patients with common neurological disorders (e.g., Alzheimer’s disease, HIV-associated neurocognitive disorders, Parkinson’s disease). With an enhanced knowledge of the temporal and spectral definitions of these impairments, new therapeutic interventions utilizing frequency-targeted neural stimulation can be developed

Investigating the relationship between cholinergic system integrity and Parkinson’s disease symptoms using MRI and EEG

Cholinergic cells of the basal forebrain (cBF) and pedunculopontine nucleus (PPN) are implicated in Parkinson’s disease (PD), but current understanding of their role in PD symptomology is limited. Neuropathological and recent in vivo imaging research implies that cBF and PPN degeneration is associated with PD cognitive and mobility impairments. There remains a need to identify and validate widely accessible markers of cholinergic system degeneration to better understand its contribution to these symptoms. The aim of this thesis was to investigate how structural changes in the cBF and PPN relate to cortical activity and cognitive and mobility performance in people with PD, people with mild cognitive impairment (MCI), and healthy age-matched controls. T1 and diffusion-weighted images were used in combination with stereotactic maps of the cBF and PPN to extract volumetric and diffusivity metrics from these regions as in vivo surrogate markers of structural integrity. These structural measures were assessed for their relationship with resting-state EEG, and cognitive and functional mobility performance. People with PD showed reduced cBF volumes compared to healthy controls, and elevated PPN diffusivity compared to people with MCI. Subregional cBF volumes correlated with EEG changes in the theta-alpha range in people with PD and people with MCI. Volume loss in the cBF was also shown to mediate the relationship between executive function and Timed Up and Go dual-task performance in people with PD. PPN diffusivity metrics demonstrated correlations with cognitive performance and EEG changes in the alpha range in people with PD, and in the beta-gamma range in people with MCI. Cortical activity measured with EEG may hold physiological relevance for structural changes occurring in the cBF and PPN. Volumetric loss in the cBF may impair the attentional-executive control of mobility functions. Elevated PPN diffusivity may impair attentional performance during tasks that require sensorimotor integration

Serotonergic modulation of the ventral pallidum by 5HT1A, 5HT5A, 5HT7 AND 5HT2C receptors

Introduction: Serotonin's involvement in reward processing is controversial. The large number of serotonin receptor sub-types and their individual and unique contributions have been difficult to dissect out, yet understanding how specific serotonin receptor sub-types contribute to its effects on areas associated with reward processing is an essential step. Methods: The current study used multi-electrode arrays and acute slice preparations to examine the effects of serotonin on ventral pallidum (VP) neurons. Approach for statistical analysis: extracellular recordings were spike sorted using template matching and principal components analysis, Consecutive inter-spike intervals were then compared over periods of 1200 seconds for each treatment condition using a student’s t test. Results and conclusions: Our data suggests that excitatory responses to serotonin application are pre-synaptic in origin as blocking synaptic transmission with low-calcium aCSF abolished these responses. Our data also suggests that 5HT1a, 5HT5a and 5HT7 receptors contribute to this effect, potentially forming an oligomeric complex, as 5HT1a antagonists completely abolished excitatory responses to serotonin application, while 5HT5a and 5HT7 only reduced the magnitude of excitatory responses to serotonin. 5HT2c receptors were the only serotonin receptor sub-type tested that elicited inhibitory responses to serotonin application in the VP. These findings, combined with our previous data outlining the mechanisms underpinning dopamine's effects in the VP, provide key information, which will allow future research to fully examine the interplay between serotonin and dopamine in the VP. Investigation of dopamine and serotonins interaction may provide vital insights into our understanding of the VP's involvement in reward processing. It may also contribute to our understanding of how drugs of abuse, such as cocaine, may hijack these mechanisms in the VP resulting in sensitization to drugs of abuse