Gamma-band Responses Research Articles

GABA metabolism and its role in gamma-band oscillatory activity during auditory processing: An MRS and EEG study.

Gamma-aminobutyric acid (GABA) and glutamate are believed to have inhibitory and exhibitory neuromodulatory effects that regulate the brain's response to sensory perception. Furthermore, frequency-specific synchronization of neuronal excitability within the gamma band (30-80 Hz) is attributable to a homeostatic balance between excitation and inhibition. However, our understanding of the physiological mechanism underlying gamma rhythms is based on animal models. Investigations of the relationship between GABA concentrations, glutamate concentrations, and gamma band activity in humans were mostly restricted to the visual cortex and are conflicting. Here, we performed a multimodal imaging study combining magnetic resonance spectroscopy (MRS) with electroencephalography (EEG) in the auditory cortex. In 14 healthy subjects, we investigated the impact of individual differences in GABA and glutamate concentration on gamma band response (GBR) following auditory stimulus presentation. We explored the effects of bulk GABA on the GBR across frequency (30-200 Hz) and time (-200 to 600 ms) and found no significant relationship. Furthermore, no correlations were found between gamma peak frequency or power measures and metabolite concentrations (GABA, glutamate, and GABA/glutamate ratio). These findings suggest that, according to MRS measurements, and given the auditory stimuli used in this study, GABA and glutamate concentrations are unlikely to play a significant role in the inhibitory and excitatory drive in the generation of gamma band activity in the auditory cortex. Hum Brain Mapp 38:3975-3987, 2017. © 2017 Wiley Periodicals, Inc.

SA74. Visual Cortex Gamma-Band Power is Reduced in Individuals at Ultra-High Risk for Schizophrenia: An MEG Study

Abstract Background: Emerging evidence suggests that schizophrenia (ScZ) is associated with aberrant neural oscillatory activity, in particular at γ-band frequencies (>30 Hz). Our group has reported several studies showing impaired generation of high-gamma band oscillatory activity (~50–120 Hz) in chronic ScZ patients as well as in unmedicated patients with first-episode psychosis (FEP). Currently, however, it is unclear whether gamma-band activity is already impaired in individuals at Ultra High Risk (UHR) for schizophrenia. The current MEG study investigates this question, using a visual task that is known to induce strong high-γ band activity over visual cortical areas. Methods: MEG data were recorded, while 50 UHR and 30 healthy control (CON) participants performed an inward moving grating task. Participants fixated on sine-wave circular gratings and detected (by button-press) acceleration of inward movement, occurring at an unpredictable moment during trial presentation. MEG analysis focused on frequency domain reconstructed MEG data collected from central nodes placed in 80 (sub)cortical regions defined within the AAL-atlas, using LCMV beamformer source-analysis algorithms to optimally suppress both sensor-level noise sources and contributions from neighboring brain areas. Results: Independent of group (i.e., across all participants), 14 AAL-atlas-derived regions in the visual cortex showed significantly increased sustained gamma-band (53–63 Hz) and significantly decreased sustained alpha-band (8–12 Hz) activity during stimulus presentation, compared to baseline activity (False-Discovery-Rate corrected for multiple comparisons). Subsequently tested group effects (UHRs vs. CONs) across these 14 visual regions and across a time interval between 200 and 1200 ms postgrating onset revealed significantly decreased gamma-band responses for UHR, but no group differences in alpha-band responses. In addition, UHR participants’ performance was characterized by elevated error rates, compared to CON participants. Conclusion: Gamma-band visual-cortex responses during perception are already impaired in individuals at UHR for psychosis development and therefore represent a potential candidate biomarker for psychosis prediction.

Time course of gamma-band oscillation associated with face processing in the inferior occipital gyrus and fusiform gyrus: A combined fMRI and MEG study.

Debate continues over whether the inferior occipital gyrus (IOG) or the fusiform gyrus (FG) represents the first stage of face processing and what role these brain regions play. We investigated this issue by combining functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in normal adults. Participants passively observed upright and inverted faces and houses. First, we identified the IOG and FG as face-specific regions using fMRI. We applied beamforming source reconstruction and time-frequency analysis to MEG source signals to reveal the time course of gamma-band activations in these regions. The results revealed that the right IOG showed higher gamma-band activation in response to upright faces than to upright houses at 100 ms from the stimulus onset. Subsequently, the right FG showed greater gamma-band response to upright faces versus upright houses at around 170 ms. The gamma-band activation in the right IOG and right FG was larger in response to inverted faces than to upright faces at the later time window. These results suggest that (1) the gamma-band activities occurs rapidly first in the IOG and next in the FG and (2) the gamma-band activity in the right IOG at later time stages is involved in configuration processing for faces. Hum Brain Mapp 38:2067-2079, 2017. © 2017 Wiley Periodicals, Inc.

Attentional capture by physically salient stimuli in the gamma frequency is associated with schizophrenia symptoms

Objectives: Aberrant salience mainly is attributed to excessive dopaminergic processing in the ventral striatum. Increased gamma power during sensory processing of physical salience has been shown to be associated with positive trait schizotypy. In the present study, this is assessed in patients with schizophrenia.Methods: The early evoked visual gamma-band response (GBR) at 40 Hz was assessed for a schizophrenia patient group (N = 22) and a matched healthy control group (N = 22) applying EEG time-frequency analysis. The GBR was assessed for two conditions within a visual detection paradigm: a target with or without a physically salient distracter and evaluated in relation to the PANSS.Results: A 2 × 2 ANOVA revealed a significant main effect of condition and a trend interaction of group and condition for the GBR, with highest power for schizophrenia patients in the physically salient distracter condition. Moreover, evoked GBR power in this condition was correlated with positive (r = 0.664; P = 0.001**) and disorganised (r = 0.618; P = 0.002**) schizophrenia symptoms.Conclusions: Evoked GBR power during processing of physical salience in schizophrenia was associated with positive symptoms. We suggest that abnormal processing of physically salient stimuli might be involved in the pathophysiological genesis of positive symptoms.

Superior orientation discrimination and increased peak gamma frequency in autism spectrum conditions.

While perception is recognized as being atypical in individuals with autism spectrum conditions (ASC), the underlying mechanisms for such atypicality are unclear. Here we test the hypothesis that individuals with ASC will show enhanced orientation discrimination compared with neurotypical observers. This prediction is based both on anecdotal report of superior discriminatory skills in ASC and also on evidence in the auditory domain that some individuals with ASC have superior pitch discrimination. In order to establish whether atypical perception might be mediated by an imbalance in the ratio of neural excitation and inhibition (E:I ratio), we also measured peak gamma frequency, which provides an indication of neural inhibition levels. Using a rigorous thresholding method, we found that orientation discrimination thresholds for obliquely oriented stimuli were significantly lower in participants with ASC. Using EEG to measure the visually induced gamma band response, we also found that peak gamma frequency was higher in participants with ASC, relative to a well-matched control group. These novel results suggest that neural inhibition may be increased in the occipital cortex of individuals with ASC. Implications for existing theories of an imbalance in the E:I ratio of ASC are discussed.

ID 431 – A novel method for the diagnosis of photosensitive epilepsy based on the phase-locking of evoked gamma-band magnetoencephalographic oscillatory brain responses

Larger size and higher spatial frequency of grating stimuli have been shown not only to maximally modulate early gamma-band visual cortical responses but also to provoke seizures in photosensitive epilepsy. Occipital brain magnetic field (MEG) oscillatory responses were evoked upon static grating pattern subthreshold stimuli in 12 patients with photosensitive epilepsy and 2 matched control groups, one with epilepsy but no photosensitivity and the other healthy controls. The continuous wavelet transform (CWT) was employed to characterize the time–frequency energy dynamics and phase-locking of the early evoked gamma-band oscillatory responses (eGBR). The photosensitive epilepsy group showed statistically significantly increased phase-locking of the gamma-band responses (eGBR) of the striate visual cortex in the (40–70 Hz) × (25–300 ms) and in the (25–30 Hz) × (300–600 ms) time–frequency windows with respect to the healthy controls. Photosensitive epilepsy seems to be characterized by altered phase synchronization dynamics at a higher frequency range (a-frequency band) compared to healthy controls. Our results indicate that photosensitive epilepsy is driven by the large-scale phase-locking of the underlying striatal visual cortical unit oscillators in specific “photosensitive” frequency components (dynamic phase-attractor theory of epilepsy). Our method could provide a novel diagnostic tool in safely detecting, investigating and assessing response to treatment in photosensitive epilepsy.

Gamma oscillations in V1 are correlated with GABA(A) receptor density: A multi-modal MEG and Flumazenil-PET study.

High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABAA receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABAA receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABAA receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABAA-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABAA receptors, has been related to psychiatric disorders including schizophrenia and depression.

Salience in a social landscape: electrophysiological effects of task-irrelevant and infrequent vocal change

In a dynamically changing social environment, humans have to face the challenge of prioritizing stimuli that compete for attention. In the context of social communication, the voice is the most important sound category. However, the existing studies do not directly address whether and how the salience of an unexpected vocal change in an auditory sequence influences the orientation of attention. In this study, frequent tones were interspersed with task-relevant infrequent tones and task-irrelevant infrequent vocal sounds (neutral, happy and angry vocalizations). Eighteen healthy college students were asked to count infrequent tones. A combined event-related potential (ERP) and EEG time-frequency approach was used, with the focus on the P3 component and on the early auditory evoked gamma band response, respectively. A spatial-temporal principal component analysis was used to disentangle potentially overlapping ERP components. Although no condition differences were observed in the 210-310 ms window, larger positive responses were observed for emotional than neutral vocalizations in the 310-410 ms window. Furthermore, the phase synchronization of the early auditory evoked gamma oscillation was enhanced for happy vocalizations. These findings support the idea that the brain prioritizes the processing of emotional stimuli, by devoting more attentional resources to salient social signals even when they are not task-relevant.

Reduced early auditory evoked gamma-band response in ketamine model of schizophrenia

Reduced early auditory evoked gamma-band response in ketamine model of schizophrenia

Reduced early auditory evoked gamma-band response in ketamine model of schizophrenia

Reduced early auditory evoked gamma-band response in ketamine model of schizophrenia

Distributed attention is implemented through theta-rhythmic gamma modulation

When subjects monitor a single spatial location, target detection depends on the pre-target phase of an ~8 Hz brain rhythm. When multiple locations are monitored, performance decrements suggest a division of the 8 Hz rhythm over the number of locations. This suggests that different locations are sequentially sampled. Indeed, when subjects monitor two locations, performance benefits alternate at a 4 Hz rhythm. These performance alternations followed a reset of attention to one location. Although resets are common and important events for attention, it is unknown, whether in the absence of resets, ongoing attention operates rhythmically. Here, we examined whether spatially specific attentional sampling can be revealed by ongoing pre-target brain rhythms. Specifically, visually induced gamma-band activity plays a role in spatial attention and therefore, we hypothesized that performance can be predicted by a theta-rhythmic gamma modulation. Brain rhythms were assessed with MEG, while subjects monitored bilateral grating stimuli for a unilateral target. The corresponding contralateral gamma-band responses were subtracted from each other to isolate spatially-selective, target-related fluctuations. The resulting lateralized-gamma activity (LGA) showed opposite 4 Hz phases prior to detected versus missed targets. The 4 Hz phase of pre-target LGA accounted for a 14% modulation in performance. These findings suggest that spatial attention is an ongoing theta-rhythmic sampling process, with each sampling cycle implemented through gamma-band synchrony. This extends previous findings by demonstrating that in the case of distributed attention, gamma-band synchrony is shaped by the slower sampling rhythm that governs performance benefits.

Distributed Attention Is Implemented through Theta-Rhythmic Gamma Modulation

When subjects monitor a single location, visual target detection depends on the pre-target phase of an ∼8 Hz brain rhythm. When multiple locations are monitored, performance decrements suggest a division of the 8 Hz rhythm over the number of locations, indicating that different locations are sequentially sampled. Indeed, when subjects monitor two locations, performance benefits alternate at a 4 Hz rhythm. These performance alternations were revealed after a reset of attention to one location. Although resets are common and important events for attention, it is unknown whether, in the absence of resets, ongoing attention samples stimuli in alternation. Here, we examined whether spatially specific attentional sampling can be revealed by ongoing pre-target brain rhythms. Visually induced gamma-band activity plays a role in spatial attention. Therefore, we hypothesized that performance on two simultaneously monitored stimuli can be predicted by a 4 Hz modulation of gamma-band activity. Brain rhythms were assessed with magnetoencephalography (MEG) while subjects monitored bilateral grating stimuli for a unilateral target event. The corresponding contralateral gamma-band responses were subtracted from each other to isolate spatially selective, target-related fluctuations. The resulting lateralized gamma-band activity (LGA) showed opposite pre-target 4 Hz phases for detected versus missed targets. The 4 Hz phase of pre-target LGA accounted for a 14.5% modulation in performance. These findings suggest that spatial attention is a theta-rhythmic sampling process that is continuously ongoing, with each sampling cycle being implemented through gamma-band synchrony.

EEG-Informed fMRI Reveals a Disturbed Gamma-Band-Specific Network in Subjects at High Risk for Psychosis.

Objectives. Abnormalities of oscillatory gamma activity are supposed to reflect a core pathophysiological mechanism underlying cognitive disturbances in schizophrenia. The auditory evoked gamma-band response (aeGBR) is known to be reduced across all stages of the disease. The present study aimed to elucidate alterations of an aeGBR-specific network mediated by gamma oscillations in the high-risk state of psychosis (HRP) by means of functional magnetic resonance imaging (fMRI) informed by electroencephalography (EEG). Methods. EEG and fMRI were simultaneously recorded from 27 HRP individuals and 26 healthy controls (HC) during performance of a cognitively demanding auditory reaction task. We used single trial coupling of the aeGBR with the corresponding blood oxygen level depending response (EEG-informed fMRI). Results. A gamma-band–specific network was significantly lower active in HRP subjects compared with HC (random effects analysis, P < .01, Bonferroni-corrected for multiple comparisons) accompanied by a worse task performance. This network involved the bilateral auditory cortices, the thalamus and frontal brain regions including the anterior cingulate cortex, as well as the bilateral dorsolateral prefrontal cortex. Conclusions. For the first time we report a reduced activation of an aeGBR-specific network in HRP subjects brought forward by EEG-informed fMRI. Because the HRP reflects the clinical risk for conversion to psychotic disorders including schizophrenia and the aeGBR has repeatedly been shown to be altered in patients with schizophrenia the results of our study point towards a potential applicability of aeGBR disturbances as a marker for the prediction of transition of HRP subjects to schizophrenia.

Localization of neural efficiency of the mathematically gifted brain through a feature subset selection method.

Based on the neural efficiency hypothesis and task-induced EEG gamma-band response (GBR), this study investigated the brain regions where neural resource could be most efficiently recruited by the math-gifted adolescents in response to varying cognitive demands. In this experiment, various GBR-based mental states were generated with three factors (level of mathematical ability, task complexity, and short-term learning) modulating the level of neural activation. A feature subset selection method based on the sequential forward floating search algorithm was used to identify an "optimal" combination of EEG channel locations, where the corresponding GBR feature subset could obtain the highest accuracy in discriminating pairwise mental states influenced by each experiment factor. The integrative results from multi-factor selections suggest that the right-lateral fronto-parietal system is highly involved in neural efficiency of the math-gifted brain, primarily including the bilateral superior frontal, right inferior frontal, right-lateral central and right temporal regions. By means of the localization method based on single-trial classification of mental states, new GBR features and EEG channel-based brain regions related to mathematical giftedness were identified, which could be useful for the brain function improvement of children/adolescents in mathematical learning through brain-computer interface systems.

Generators and Connectivity of the Early Auditory Evoked Gamma Band Response.

High frequency oscillations in the gamma range are known to be involved in early stages of auditory information processing in terms of synchronization of brain regions, e.g., in cognitive functions. It has been shown using EEG source localisation, as well as simultaneously recorded EEG-fMRI, that the auditory evoked gamma-band response (aeGBR) is modulated by attention. In addition to auditory cortex activity a dorsal anterior cingulate cortex (dACC) generator could be involved. In the present study we investigated aeGBR magnetic fields using magnetoencephalography (MEG). We aimed to localize the aeGBR sources and its connectivity features in relation to mental effort. We investigated the aeGBR magnetic fields in 13 healthy participants using a 275-channel CTF-MEG system. The experimental paradigms were two auditory choice reaction tasks with different difficulties and demands for mental effort. We performed source localization with eLORETA and calculated the aeGBR lagged phase synchronization between bilateral auditory cortices and frontal midline structures. The eLORETA analysis revealed sources of the aeGBR within bilateral auditory cortices and in frontal midline structures of the brain including the dACC. Compared to the control condition the dACC source activity was found to be significantly stronger during the performance of the cognitively demanding task. Moreover, this task involved a significantly stronger functional connectivity between auditory cortices and dACC. In accordance with previous EEG and EEG-fMRI investigations, our study confirms an aeGBR generator in the dACC by means of MEG and suggests its involvement in the effortful processing of auditory stimuli.

EEG biomarkers of target engagement, therapeutic effect, and disease process.

Studies suggest that abnormalities in glutamate and GABA signaling contribute to deficits in schizophrenia and related conditions and that these neurochemical abnormalities produce changes in electroencephalographic (EEG) indices, including event-related potentials and event-related power within specific frequency ranges. Furthermore, clinical studies suggest that a subset of EEG biomarkers is associated with symptoms. This review addresses the relationship between EEG and behavior in preclinical models of N-methyl-d-aspartate (NMDA)-receptor hypofunction, as well as how these models can be used to screen therapies. Data from schizophrenia patients are juxtaposed with data from animal models, and EEG and behavioral data from mice with disruption of NMDA receptors in excitatory and/or inhibitory neurons are then compared to the pattern observed in schizophrenia. Also discussed are results following exposure to potential therapeutic agents, including GABAB agonists. Furthermore, evidence demonstrates that elevated resting gamma power is associated with deficits in social interactions. Consistent with elevated baseline noise, excitatory neurons from transgenic mice show increased intrinsic excitability in in vitro-slice patch-clamp studies across model systems. GABAB receptor agonists reduce this excitability, improve gamma-band responses, and reverse behavioral deficits in mice. Data suggest that baseline gamma power is associated with social function and GABAB agonists may be useful for schizophrenia. Translational EEG biomarkers reflect target engagement and can contribute to the design of more efficient drug trials, likely accelerating the development of new therapeutics for central nervous system disorders.

Reduced auditory evoked gamma band response and cognitive processing deficits in first episode schizophrenia

Objectives. Gamma-band oscillations (e.g., the early auditory evoked gamma-band response, aeGBR) have been suggested to mediate cognitive and perceptual processes by driving the synchronization of local neuronal populations. Reduced aeGBR is a consistent finding in patients with schizophrenia and high-risk subjects, and has been proposed to represent an endophenotype for the illness. However, it is still unclear whether this reduction represents a deficit in sensory or cognitive processes, or a combination of the two. The present study investigated this question by manipulating the difficulty of an auditory reaction task in patients with first-episode schizophrenia and healthy controls. Methods. A 64-channel EEG was recorded in 23 patients with first-episode schizophrenia and 22 healthy controls during two conditions of an auditory reaction task: an easy condition that merely required low-level vigilance, and a difficult condition that placed significant demands on attention and working memory. Results. In contrast to healthy controls, patients failed to increase aeGBR power and phase-locking in the difficult condition. In patients, aeGBR power and phase-locking indices were associated with working memory deficits. Conclusions. The observed results confirm the applicability of aeGBR disturbances as a stable endophenotype of schizophrenia, and suggest a cognitive, rather than sensory, deficit at their origin.

Increased gamma oscillations evoked by physically salient distracters are associated with schizotypy.

Over the last decade, there has been growing interest in aberrant salience as a precursor of positive symptoms in schizophrenia. The present study investigates the neurophysiology of attentional capture by salient stimuli in the visual modality. Evoked oscillatory activity in the gamma frequency range (40Hz) was assessed during visual processing of physically salient distracters and evaluated in relation to schizotypy and its positive, negative and disorganized dimension. The early evoked visual gamma-band response (GBR) was assessed for 24 healthy participants using EEG time-frequency analysis. Physical salience was constituted by colored stimuli diverting from an ongoing baseline condition. schizotypal personality traits were measured by the schizotypal personality questionnaire (SPQ; Raine in Schizophr Bull 17:555-564, 1991). The early evoked visual GBR was significantly pronounced in the physically salient distracter condition. GBR signal power was significantly correlated with positive schizotypal personality traits (r=0.588; p=0.024*). Our results indicate that the early evoked GBR in visual processing of physically salient distracters is associated with schizotypy. These findings refer to the phenomenology of aberrant salience by bridging the gap to neurophysiological research on early sensory selection and attentional capture in the schizophrenia spectrum.

Individual musical tempo preference correlates with EEG beta rhythm.

Every individual has a preferred musical tempo, which peaks slightly above 120 beats per minute and is subject to interindividual variation. The preferred tempo is believed to be associated with rhythmic body movements as well as motor cortex activity. However, a long-standing question is whether preferred tempo is determined biologically. To uncover the neural correlates of preferred tempo, we first determined an individual's preferred tempo using a multistep procedure. Subsequently, we correlated the preferred tempo with a general EEG timing parameter as well as perceptual and motor EEG correlates-namely, individual alpha frequency, auditory evoked gamma band response, and motor beta activity. Results showed a significant relation between preferred tempo and the frequency of motor beta activity. These findings suggest that individual tempo preferences result from neural activity in the motor cortex, explaining the interindividual variation.

Peak frequency of induced gamma-band response to simple stimulus predicts individual switch rate for perceptual rivalry tasks.

The peak frequency of an induced gamma-band response to a simple stimulus is known to vary across individuals (Muthukumaraswamy et al., 2010) and is thought to be shaped by differences in the extent of inhibitory connections in visual cortex (Brunel & Wang, 2003). In support of this, peak gamma frequency has been found to predict individual levels of resting state GABA in visual cortex (Edden et al., 2009; Muthukumaraswamy eta l., 2009). Also varying reliably across normal populations is the rate of alternation for perceptual rivalry tasks including binocular rivalry and monocular pattern rivalry (Carter & Pettigrew, 2003; Miller et al., 2010). Models of perceptual rivalry include mutual inhibition as a constraint on switching dynamics (e.g., Wilson 2003), but do the differences in switch rate reflect individual differences in cortical inhibition? If so, individual switch rate should be inversely correlated with peak gamma frequency, yet this prediction has not been tested. We used magnetoencephalography (MEG) to compare the peak gamma-band frequency of neuromagnetic responses of 12 healthy adults (6 female) to the onset of simple grating stimuli with their individual switch rates for binocular and monocular rivalry tasks. We computed Morlet wavelet analyses for left and right V1, V2, and MT+ of individual source data based on minimum norm estimates for each participant. Peak frequency was determined for three latency ranges: evoked (10-150ms), early induced (200-450ms) and late induced (500-800ms). Results show significant inverse correlations between peak frequency of early induced gamma in V1 and switch rate for both rivalry tasks, compatible with models that propose inhibitory connections in visual cortex are crucial for tuning gamma-band frequency as well as perceptual alternation rate. Our study suggests that subtle variations of behavior in a normal population can directly advance our understanding of visual function by encouraging models at increasingly finer scales. Meeting abstract presented at VSS 2014