MEG sensor and source measures of visually induced gamma-band oscillations are highly reliable

High frequency brain oscillations are associated with numerous cognitive and behavioral processes. Non-invasive measurements using electro-/magnetoencephalography (EEG/MEG) have revealed that high frequency neural signals are heritable and manifest changes with age as well as in neuropsychiatric illnesses. Despite the extensive use of EEG/MEG-measured neural oscillations in basic and clinical research, studies demonstrating test–retest reliability of power and frequency measures of neural signals remain scarce. Here, we evaluated the test–retest reliability of visually induced gamma (30–100 Hz) oscillations derived from sensor and source signals acquired over two MEG sessions. The study required participants (N = 13) to detect the randomly occurring stimulus acceleration while viewing a moving concentric grating. Sensor and source MEG measures of gamma-band activity yielded comparably strong reliability (average intraclass correlation, ICC = 0.861). Peak stimulus-induced gamma frequency (53–72 Hz) yielded the highest measures of stability (ICCsensor = 0.940; ICCsource = 0.966) followed by spectral signal change (ICCsensor = 0.890; ICCsource = 0.893) and peak frequency bandwidth (ICCsensor = 0.856; ICCsource = 0.622). Furthermore, source-reconstruction significantly improved signal-to-noise for spectral amplitude of gamma activity compared to sensor estimates. Our assessments highlight that both sensor and source derived estimates of visually induced gamma-band oscillations from MEG signals are characterized by high test–retest reliability, with source derived oscillatory measures conferring an improvement in the stability of peak-frequency estimates. Importantly, our finding of high test–retest reliability supports the feasibility of pharma-MEG studies and longitudinal aging or clinical studies

Hearing through your eyes: neural basis of audiovisual cross-activation, revealed by transcranial alternating current stimulation

Some people experience auditory sensations when seeing visual flashes or movements. This prevalent synaesthesia-like ‘visual-evoked auditory response’ (vEAR) could result either from over-exuberant cross-activation between brain areas, and/or reduced inhibition of normally-occurring cross-activation. We have used transcranial alternating current stimulation (tACS) to test these theories. We applied tACS at 10Hz (alpha-band frequency) or 40Hz (gamma-band), bilaterally either to temporal or occipital sites, while measuring same/different discrimination of paired auditory (A) versus visual (V) 'Morse code' sequences. At debriefing, participants were classified as vEAR or non-vEAR depending on whether they reported 'hearing' the silent flashes. In non-vEAR participants, temporal 10Hz tACS caused impairment of A performance, which correlated with improved V; conversely under occipital tACS, poorer V performance correlated with improved A. This reciprocal pattern suggests that sensory cortices are normally mutually inhibitory, and that alpha-frequency tACS may bias the balance of competition between them. vEAR participants showed no tACS effects, consistent with reduced inhibition, or enhanced cooperation between modalities. In addition, temporal 40Hz tACS impaired V performance, specifically in individuals who showed a performance advantage for V (relative to A). Gamma-frequency tACS may therefore modulate the ability of these individuals to benefit from recoding flashes into the auditory modality, possibly by disrupting cross-activation of auditory areas by visual stimulation. Our results support both theories, suggesting that vEAR may depend on disinhibition of normally-occurring sensory cross-activation, which may be expressed more strongly in some individuals. Furthermore, endogenous alpha and gamma-frequency oscillations may function respectively to inhibit or promote this cross-activation

Gamma oscillations in human primary somatosensory cortex reflect pain perception

Pain is a highly subjective sensation of inherent behavioral importance and is therefore expected to receive enhanced processing in relevant brain regions. We show that painful stimuli induce high-frequency oscillations in the electrical activity of the human primary somatosensory cortex. Amplitudes of these pain-induced gamma oscillations were more closely related to the subjective perception of pain than to the objective stimulus attributes. They correlated with participants' ratings of pain and were stronger for laser stimuli that caused pain, compared with the same stimuli when no pain was perceived. These findings indicate that gamma oscillations may represent an important mechanism for processing behaviorally relevant sensory information

High-frequency neural oscillations and visual processing deficits in schizophrenia

Visual information is fundamental to how we understand our environment, make predictions, and interact with others. Recent research has underscored the importance of visuo-perceptual dysfunctions for cognitive deficits and pathophysiological processes in schizophrenia. In the current paper, we review evidence for the relevance of high frequency (beta/gamma) oscillations towards visuo-perceptual dysfunctions in schizophrenia. In the first part of the paper, we examine the relationship between beta/gamma band oscillations and visual processing during normal brain functioning. We then summarize EEG/MEG-studies which demonstrate reduced amplitude and synchrony of high-frequency activity during visual stimulation in schizophrenia. In the final part of the paper, we identify neurobiological correlates as well as offer perspectives for future research to stimulate further inquiry into the role of high-frequency oscillations in visual processing impairments in the disorder

Prefrontal gamma oscillations encode tonic pain in humans

Under physiological conditions, momentary pain serves vital protective functions. Ongoing pain in chronic pain states, on the other hand, is a pathological condition that causes widespread suffering and whose treatment remains unsatisfactory. The brain mechanisms of ongoing pain are largely unknown. In this study, we applied tonic painful heat stimuli of varying degree to healthy human subjects, obtained continuous pain ratings, and recorded electroencephalograms to relate ongoing pain to brain activity. Our results reveal that the subjective perception of tonic pain is selectively encoded by gamma oscillations in the medial prefrontal cortex. We further observed that the encoding of subjective pain intensity experienced by the participants differs fundamentally from that of objective stimulus intensity and from that of brief pain stimuli. These observations point to a role for gamma oscillations in the medial prefrontal cortex in ongoing, tonic pain and thereby extend current concepts of the brain mechanisms of pain to the clinically relevant state of ongoing pain. Furthermore, our approach might help to identify a brain marker of ongoing pain, which may prove useful for the diagnosis and therapy of chronic pain

EFFECTS OF NEUROMODULATION ON NEUROVASCULAR COUPLING

The communication between neurons within neural circuits relies on neurotransmitters (glutamate, γ-aminobutyric acid (GABA)) and neuromodulators (acetylcholine, dopamine, serotonin, etc.). However, despite sharing similar molecular elements, neurotransmitters and neuromodulators are distinct classes of molecules and mediate different aspects of neural activity and metabolism. Neurotransmitters on one hand are responsible for synaptic signal transmission (classical transmission) while neuromodulators exert their functions by mediating different postsynaptic events that result in changes to the balance between excitation and inhibition. Neuromodulation, while essential to nervous system function, has been significantly more difficult to study than neurotransmission. This is principally due to the fact that effects elicited by neuromodulators are usually of slow onset, long lasting, and are not simply excitation or inhibition. In contrast to the effects of neurotransmitters, neuromodulators enable neurons to be more flexible in their ability to encode different sorts of information (e.g. sensory information) on a variety of time scales. However, it is important to appreciate that one of the challenges in the study of neuromodulation is to understand the extent to which neuromodulators’ actions are coordinated at all levels of brain function. That is, from the cellular and metabolic level to network and cognitive control. Therefore, understanding the molecules that mediate brain networks interactions is essential to understanding the brain dynamic, and also helps to put the cellular and molecular processes in perspective. Functional magnetic resonance imaging (fMRI) is a technique that allows access to various cellular and metabolic aspects of network communication that are difficult to access when studying one neuron at the time. Its non-invasiveness nature allows the comparison of data and hypotheses of the primate brain to that of the human brain. Hence, understanding the effects of neuromodulation on local microcircuits is needed. Furthermore, given the massive projections of the neuromodulatory diffuse ascending systems, fMRI combined with pharmacological and neurophysiological methods may provide true insight into their organization and dynamics. However, little is known about how to interpret the effects of neuromodulation in fMRI and neurophysiological data, for instance, how to disentangle blood oxygenation level dependent (BOLD) signal changes relating to cognitive changes (presumably neuromodulatory influences) from stimulus-driven or perceptual effects. The purpose of this dissertation is to understand the causal relationship between neural activity and hemodynamic responses under the influence of neuromodulation. To this end we present the results of six studies. In the first study, we aimed to establish a mass-spectrometry-based technique to uncover the distribution of different metabolites, neurotransmitters and neuromodulators in the macaque brain. We simultaneously measured the concentrations of these biomolecules in brain and in blood. In a second study, we developed a multimodal approach consisting of fMRI (BOLD and cerebral blood flow or CBF), electrophysiological recording with a laminar probe and pharmacology to assess the effects of neuromodulation on neurovascular coupling. We developed a pharmacological injection delivery system using pressure-operated pumps to reliably apply drugs either systemically or intracortically in the NMR scanner. In our third study, we systemically injected lactate and pyruvate to explore whether the plasma concentration of either of these metabolites affects the BOLD responses. This is important given that both metabolites are in a metabolic equilibrium; if this equilibrium is disrupted, changes in the NAD and NADH concentrations would elicit changes in the CBF. In a fourth study, we explored the influence of dopaminergic (DAergic) neuromodulation in the BOLD, CBF and neurophysiological activity. Here we found that DAergic neuromodulation dissociated the BOLD responses from the underlying neural activity. Interestingly, the changes in the neural activity were tightly coupled to the effects seen in the CBF responses. In a subsequent study, we explored whether the effects of dopamine (DA) on the electrophysiological responses are cortical layer dependent and whether specific patterns of neural activity can be used to infer the effects of neuromodulation on the neural activity. This is important, given that different types of neural activity provide independent information about the amplitude and dynamics from BOLD responses, and studies have shown that these bands originate from different cortical layers. What this study revealed, is that local field potentials (LFPs) in the midrange frequencies can indeed provide indications about the sustained effects of neuromodulation on cortical sensory processing. Given the results from the previous study, in our sixth study, we aimed at understanding how different cortical layers may process incoming and outgoing information in the different LFP bands. These findings provide evidence that neuromodulation has profound effects on neurovascular coupling. By changing the excitation-inhibition balance of neural circuits, neuromodulators not only mediate the neural activity, but also adjust the metabolic demands. Therefore, understanding how the different types of neuromodulators affect the BOLD response is essential for an effective interpretation of fMRI-data, not only in tasks involving attentional and reward-related processes, but also for future diagnostic use of fMRI, since many psychiatric disorders are the result of alterations in neuromodulatory systems.Die Kommunikation zwischen den Neuronen innerhalb neuronalen Schaltkreise beruht auf Neurotransmitter (Glutamat, γ-Aminobuttersäure (GABA)) und Neuromodulatoren (Acetylcholin, Dopamin, Serotonin, etc.). Neurotransmitter und Neuromodulatoren sind jedoch unterschiedliche Klassen von Molekülen und verschiedenen Aspekte der neuronalen Aktivität und den Stoffwechsel vermitteln. Neurotransmitters sind einerseits verantwortlich für die synaptische Signalübertragung (klassische Übertragung), während ihre Funktionen ausüben, Neuromodulatoren durch verschiedene postsynaptischen Ereignisse zu vermitteln, die in Änderungen an der Balance zwischen Erregung und Hemmung führen. Neuromodulation , während wesentlich Funktion des Nervensystems hat sich als Neurotransmission wesentlich schwieriger gewesen, zu studieren. Dies ist hauptsächlich auf die Tatsache zurückzuführen, die durch Neuromodulatoren sind in der Regel von langsamen Beginn, langlebig, und sind nicht einfach Anregung oder Hemmung ausgelöst beeinflusst. Im Gegensatz zu den Wirkungen von Neurotransmittern, Neuromodulatoren ermöglichen Neuronen flexibler zu sein in ihrer Fähigkeit, verschiedene Arten von Informationen (beispielsweise sensorische Informationen) auf einer Vielzahl von Zeitskalen zu kodieren. Im Gegensatz zu den Wirkungen von Neurotransmittern, Neuromodulatoren ermöglichen Neuronen flexibler zu sein in ihrer Fähigkeit, verschiedene Arten von Informationen (beispielsweise sensorische Informationen) auf einer Vielzahl von Zeitskalen zu kodieren. Im Gegensatz zu den Wirkungen von Neurotransmittern, Neuromodulatoren ermöglichen Neuronen flexibler zu sein in ihrer Fähigkeit, verschiedene Arten von Informationen (beispielsweise sensorische Informationen) auf einer Vielzahl von Zeitskalen zu kodieren. Jedoch ist es wichtig, dass eine der Herausforderungen bei der Untersuchung von Neuromodulations zu schätzen ist, das Ausmaß, in dem Neuromodulatoren Aktionen koordiniert sind auf allen Ebenen der Gehirnfunktion zu verstehen. Das heißt, von der zellulären und metabolischen Ebene zu vernetzen und kognitive Kontrolle. Daher die Moleküle zu verstehen, die Gehirn Netzwerke Interaktionen vermitteln ist wesentlich für das Verständnis des Gehirns dynamisch, und hilft auch, die zellulären und molekularen Prozesse in Perspektive zu setzen. Funktionellen Kernspintomographie (fMRI) ist eine Technik, die Zugang zu verschiedenen zellulären und metabolischen Aspekte der Netzwerk-Kommunikation ermöglicht, die schwer zugänglich sind, wenn zu der Zeit eines Neurons zu studieren. Seine nicht-Invasivität Natur ermöglicht den Vergleich von Daten und Hypothesen des Primatengehirn zu der des menschlichen Gehirns. Somit wurde das Verständnis der Auswirkungen der Neuromodulation auf lokale Mikro benötigt. Darüber hinaus sind die massiven Projektionen der neuromodulatorischen diffuse Aufstiegsanlagen gegeben, kombiniert fMRI mit pharmakologischen und neurophysiologischen Methoden wahren Einblick in ihre Organisation und Dynamik liefern. Allerdings ist nur wenig darüber bekannt, wie die Auswirkungen der Neuromodulations in fMRI und neurophysiologische Daten zu interpretieren, zum Beispiel, wie Blutoxydation pegelabhängig (BOLD) Signaländerungen in Bezug auf kognitive Veränderungen (vermutlich neuromodulatorischen Einflüsse) von Stimulus-driven oder Wahrnehmungseffekte zu entwirren. Der Zweck dieser Arbeit ist es, die kausale Beziehung zwischen neuronaler Aktivität und hämodynamischen Reaktionen unter dem Einfluss der Neuromodulations zu verstehen. Zu diesem Zweck stellen wir die Ergebnisse von sechs Studien. In der ersten Studie wollten wir eine auf Massenspektrometrie basierende Technik einzurichten, um die Verteilung von verschiedenen Metaboliten, Neurotransmittern und Neuromodulatoren in Makakengehirn aufzudeckenWir maßen gleichzeitig die Konzentrationen dieser Biomoleküle im Gehirn und im Blut. In einer zweiten Studie entwickelten wir einen multimodalen Ansatz, bestehend aus fMRI (BOLD und zerebralen Blutflusses oder CBF), elektrophysiologische Aufzeichnung mit einer laminaren Sonde und Pharmakologie, die Auswirkungen der Neuromodulation auf neurovaskulären Kopplung zu beurteilen. Wir entwickelten eine pharmakologische Injektionsverabreichungssystem druckbetriebenen Pumpen mit zuverlässiger Medikamente gelten entweder systemisch oder intrakortikale im NMR-Scanner. In unserer dritten Studie injizierten wir systemisch Laktat und Pyruvat zu untersuchen, ob die Plasmakonzentration von entweder dieser Metaboliten die BOLD-Antworten beeinflusst. Dies ist wichtig, dass beide gegeben Metaboliten in einem Stoffwechselgleichgewicht sind; wenn dieses Gleichgewicht gestört ist, Veränderungen in den NAD und NADH-Konzentrationen würden Veränderungen in der CBF entlocken. In einer vierten Studie untersuchten wir den Einfluss von dopaminergen (DA-erge) -Neuromodulation im BOLD, CBF und neurophysiologische Aktivität. Hier fanden wir, dass DAerge -Neuromodulation die BOLD-Antworten von der zugrunde liegenden neuronalen Aktivität distanzierte. Interessanterweise waren verbunden, um die Veränderungen in der neuronalen Aktivität eng auf die in den CBF Reaktionen gesehen Wirkungen. In einer nachfolgenden Studie untersuchten wir, ob die Wirkungen von Dopamin (DA) auf die elektrophysiologischen Reaktionen sind Rindenschicht abhängig, und ob bestimmte Muster der neuronalen Aktivität verwendet werden kann, die Wirkungen von Neuromodulations auf die neurale Aktivität zu schließen. Dies ist wichtig, da verschiedene Arten von neuralen Aktivität liefern unabhängige Informationen über die Amplitude und die Dynamik von BOLD-Antworten, und Studien haben gezeigt, dass diese Bands aus verschiedenen kortikalen Schichten stammen. Was diese Studie ergab, dass lokale Feldpotentiale (LFP) in den mittleren Frequenzen in der Tat Hinweise über die nachhaltige Wirkung der Neuromodulation auf die kortikale sensorische Verarbeitung zur Verfügung stellen kann. In Anbetracht der Ergebnisse der früheren Studie, in unserer sechsten Studie wollten wir auf das Verständnis, wie die verschiedenen kortikalen Schichten verarbeiten kann ein- und ausgehenden Informationen in den verschiedenen LFP-Bands. Diese Ergebnisse belegen, dass -Neuromodulation profunde Auswirkungen auf die neurovaskulären Kopplung hat. Durch die Veränderung der Erregungs Hemmung Gleichgewicht neuronaler Schaltkreise vermitteln Neuromodulatoren nicht nur die neurale Aktivität, sondern auch die metabolischen Anforderungen anzupassen. Daher verstehen, wie die verschiedenen Arten von Neuromodulatoren beeinflussen die BOLD-Antwort für eine effektive Interpretation von fMRI-Daten notwendig ist, nicht nur in Aufgaben attentional und Belohnung bezogenen Prozessen mit, sondern auch für zukünftige diagnostische Verwendung von fMRI, da viele psychiatrische Störungen sind das Ergebnis von Veränderungen in neuromodulatorischen Systemen.La comunicación de las neuronas en los circuitos neuronales depende de los neurotransmisores (glutamato, acido γ-amino-butírico o GABA) y los neuromoduladores (acetilcolina, dopamina, serotonina, etc.). Sin embargo, tanto neurotransmisores como neuromoduladores son diferentes clases de moléculas y median diferentes aspectos de la actividad neuronal y del metabolismo, a pesar de compartir elementos moleculares muy similares. Los neurotransmisores, por una lado, son responsables de la transmisión sináptica de la información mientras que los neuromoduladores median diferentes eventos pos-sinápticos que resultan en cambios en el balance de la excitación e inhibición. La influencia de la neuromodulación es esencial para la función del sistema nerviosos, sin embargo es más difícil de estudiar que neurotransmisión. Esto se debe a que los efectos de los neuromoduladores suelen ser de un inicio lento, de larga duración, y no reflejan excitación o inhibición. En contraste a los efectos de los neurotransmisores, los neuromoduladores permiten que las neuronas sean más flexibles en su habilidad de codificar diferentes tipos de información (por ejemplo, información sensorial) en varias escalas temporales. Sin embargo, es importante darse cuenta que uno de objetivos primordiales en el estudio de neuromodulación es el de entender el grado en que la acción de los neuromoduladores está coordinada a todos los niveles de la función cerebral. Es decir, desde los aspectos celulares y metabólicos hasta los niveles de redes neuronales y control cognitivo. Por lo tanto, comprender los forma en la que diferentes moléculas median la interacción entre redes neuronal es esencial para el entendimiento de la dinámica cerebral, y también nos ayudara a comprender los procesos celulares y moleculares asociados a la percepción. La resonancia magnética funcional (fMRI, por sus siglas en inglés) es una técnica que permite acceder a varios aspectos celulares y metabólicos de la comunicación entre redes neuronales que suele ser de difícil acceso. Al mismo tiempo y debido que la fMRI es de naturaleza no invasiva, también permite comparar resultados e hipótesis entre humanos y primates. Por lo tanto, entender los efectos de la neuromodulación en la actividad de los circuitos neuronales es de alta relevancia. Dado que las proyecciones anatómicas de los sistemas de neuromoduladores, el uso de fMRI en combinación con farmacología y neurofisiología puede incrementar nuestro conocimiento sobre la estructura y dinámica de los sistemas de neuromoduladores. Sin embargo, poco se sabe sobre cómo interpretar los efectos de neuromodulation usando fMRI y neurofisiología, por ejemplo, como diferenciar los cambios en la señal BOLD que están relacionados a diferentes estados cognitivos (presumiblemente reflejando la influencia de neuromodulation). El propósito de esta disertación es la de comprender la relación causal que existe entre la actividad neural y la respuesta hemodinámica bajo la influencia de neuromodulación. Para tal fin presentamos los resultados de seis estudios que fueron producto de esta disertacion. En el primer estudio, desarrollamos una técnica basada en espectrometría de masa para detectar y medir la concentración de diferente metabolitos, neurotransmisores y neuromoduladores en el cerebro de primates. Dicha cuantificación se desarrollo simultáneamente tanto in sangre y cerebro. En un segundo estudio, utilizamos varias técnicas de fMRI (BOLD y flujo cerebral sanguíneo, CBF por sus siglas en ingles), registros electrofisiológicos con electrodos laminares y farmacología para acceder a los efectos de neuromodulation en el acople neurovascular. Para este fin, desarrollamos un sistema de inyecciones, basada en cambios de presión, para aplicar substancias sistémicamente o intracorticalmente dentro de un escáner de resonancia magnética. En nuestro tercer estudio, comparamos los efectos de lactato y piruvato para explorar como el desequilibrio metabólico de estas dos substancias afecta la respuesta BOLD. Esto es de gran importancia ya que ambas substancias metabólicas usualmente están en equilibrio. Sin embargo, cuando dicho equilibrio es interrumpido, los procesos metabólicos que acontecen en la mitocondria afectan las concentraciones de NAD y NADH causado cambios en el CBF. En un cuarto estudio, exploramos los efectos de las modulación dopaminergica (DAergic) en las señales BOLD, CBF y en la actividad neuronal. Encontramos que la modulación DAergic disocia las respuesta BOLD de la respuesta neuronal. Interesalmente, los cambios que observamos en la actividad de las neuronas estaba altamente acoplados a los efectos que observamos en la señal de CBF. En un estudio subsecuente, exploramos si los efectos de dopamina en la actividad neuronal es diferentes en las distintas capas de la corteza cerebral. Al mismo tiempo y ya que los neuromoduladores afectan la actividad de circuitos neuronales, exploramos si dichos efectos pueden usados como marcadores de la influencia de la neuromodulación . Esto es importante, ya que diferentes tipos de actividad neuronal brinda información sobre la amplitud y dinámica de la repuesta BOLD, y estudies han demostrado que estas bandas se originan de diferentes capas cortical. Este estudio revelo, que los potenciales de capo (LFPs, por sus siglas en ingles) en frecuencias intermedias puede ser indicativos sobre los efectos de neuromodulation en el procesamiento cortical. Dado los resultados en el estudio previo, en un sexto estudio, nos enfocamos a entender que tan diferentes las capas de la corteza procesan información entrante y saliente en diferentes frecuencias de los LFPs. Estos descubrimientos demuestran que los efectos de los neuromoduladores tiene una fuerte influencia en el acople neurovascular. Los neuromoduladores cambian el balance de excitación e inhibición de los circuitos neuronal, pero también median las demandas metabólicas. De esta manera, entender cómo interpretar los efectos de los neuromoduladores en la respuesta BOLD es esencial para una interpretación veraz y efectiva de los datos generados con fMRI. Estos resultados, no solo nos permiten comprender los procesos que están relacionados a la atención o de varios procesos cognitivos, sino que a su vez, nos permite comprender la señal de fMRI para su futuro uso en la medicina diagnostica, ya que muchas enfermedades psiquiátricas están asociadas a trastornos en el sistemas neuromoduladores

Effects of transcranial alternating current stimulation on repetitive finger movements in healthy humans

Transcranial alternating current stimulation (tACS) is a noninvasive neurophysiological technique that can entrain brain oscillations. Only few studies have investigated the effects of tACS on voluntary movements. We aimed to verify whether tACS, delivered over M1 at beta and gamma frequencies, has any effect on repetitive finger tapping as assessed by means of kinematic analysis. Eighteen healthy subjects were enrolled. Objective measurements of repetitive finger tapping were obtained by using a motion analysis system. M1 excitability was assessed by using single-pulse TMS and measuring the amplitude of motor-evoked potentials (MEPs). Movement kinematic measures and MEPs were collected during beta, gamma, and sham tACS and when the stimulation was off. Beta tACS led to an amplitude decrement (i.e., progressive reduction in amplitude) across the first ten movements of the motor sequence while gamma tACS had the opposite effect. The results did not reveal any significant effect of tACS on other movement parameters, nor any changes in MEPs. These findings demonstrate that tACS modulates finger tapping in a frequency-dependent manner with no concurrent changes in corticospinal excitability. The results suggest that cortical beta and gamma oscillations are involved in the motor control of repetitive finger movements

Phase Dependency of the Human Primary Motor Cortex and Cholinergic Inhibition Cancelation during Beta tACS

The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases. The effect of cholinergic short-latency afferent inhibition (SAI) was abolished by 20 Hz tACS, linking cortical beta activity to sensorimotor integration. However, this effect occurred regardless of the tACS phase. In contrast, 20 Hz tACS selectively modulated MEP size according to the phase of tACS during single pulse, GABAAergic short-interval intracortical inhibition (SICI) and glutamatergic intracortical facilitation (ICF). For SICI this phase effect was more marked during 20 Hz stimulation. Phase modulation of SICI also depended on whether or not spontaneous beta activity occurred at ~20 Hz, supporting an interaction effect between tACS and underlying circuit resonances. The present study provides in vivo evidence linking cortical beta activity to sensorimotor integration, and for beta oscillations in motor cortex being promoted by resonance in GABAAergic interneuronal circuits

Spontaneous and visually driven high‐frequency oscillations in the occipital cortex: Intracranial recording in epileptic patients

High‐frequency oscillations (HFOs) at ≥80 Hz of nonepileptic nature spontaneously emerge from human cerebral cortex. In 10 patients with extraoccipital lobe epilepsy, we compared the spectral‐spatial characteristics of HFOs spontaneously arising from the nonepileptic occipital cortex with those of HFOs driven by a visual task as well as epileptogenic HFOs arising from the extraoccipital seizure focus. We identified spontaneous HFOs at ≥80 Hz with a mean duration of 330 ms intermittently emerging from the occipital cortex during interictal slow‐wave sleep. The spectral frequency band of spontaneous occipital HFOs was similar to that of visually driven HFOs. Spontaneous occipital HFOs were spatially sparse and confined to smaller areas, whereas visually driven HFOs involved the larger areas including the more rostral sites. Neither spectral frequency band nor amplitude of spontaneous occipital HFOs significantly differed from those of epileptogenic HFOs. Spontaneous occipital HFOs were strongly locked to the phase of delta activity, but the strength of δ‐phase coupling decayed from 1 to 3 Hz. Conversely, epileptogenic extraoccipital HFOs were locked to the phase of delta activity about equally in the range from 1 to 3 Hz. The occipital cortex spontaneously generates physiological HFOs which may stand out on electrocorticography traces as prominently as pathological HFOs arising from elsewhere; this observation should be taken into consideration during presurgical evaluation. Coupling of spontaneous delta and HFOs may increase the understanding of significance of δ‐oscillations during slow‐wave sleep. Further studies are warranted to determine whether δ‐phase coupling distinguishes physiological from pathological HFOs or simply differs across anatomical locations. Hum Brain Mapp , 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90310/1/21233_ftp.pd