Frontal Gamma Research Articles

Hybrid framework of fatigue: connecting motivational control and computational moderators to gamma oscillations.

There is a need to develop a comprehensive account of time-on-task fatigue effects on performance (i.e., the vigilance decrement) to increase predictive accuracy. We address this need by integrating three independent accounts into a novel hybrid framework. This framework unites (1) a motivational system balancing goal and comfort drives as described by an influential cognitive-energetic theory with (2) accumulating microlapses from a recent computational model of fatigue, and (3) frontal gamma oscillations indexing fluctuations in motivational control. Moreover, the hybrid framework formally links brief lapses (occurring over milliseconds) to the dynamics of the motivational system at a temporal scale not otherwise described in the fatigue literature. EEG and behavioral data was collected from a brief vigilance task. High frequency gamma oscillations were assayed, indexing effortful controlled processes with motivation as a latent factor. Binned and single-trial gamma power was evaluated for changes in real- and lagged-time and correlated with behavior. Functional connectivity analyses assessed the directionality of gamma power in frontal-parietal communication across time-on-task. As a high-resolution representation of latent motivation, gamma power was scaled by fatigue moderators in two computational models. Microlapses modulated transitions from an effortful controlled state to a minimal-effort default state. The hybrid models were compared to a computational microlapse-only model for goodness-of-fit with simulated data. Findings suggested real-time high gamma power exhibited properties consistent with effortful motivational control. However, gamma power failed to correlate with increases in response times over time, indicating electrophysiology and behavior relations are insufficient in capturing the full range of fatigue effects. Directional connectivity affirmed the dominance of frontal gamma activity in controlled processes in the frontal-parietal network. Parameterizing high frontal gamma power, as an index of fluctuating relative motivational control, produced results that are as accurate or superior to a previous microlapse-only computational model. The hybrid framework views fatigue as a function of a energetical motivational system, managing the trade-space between controlled processes and competing wellbeing needs. Two gamma computational models provided compelling and parsimonious support for this framework, which can potentially be applied to fatigue intervention technologies and related effectiveness measures.

Resting Frontal Gamma Power is Associated with Both Expressive Language and Non-verbal Cognitive Abilities in Young Autistic Children.

Previous research links resting frontal gamma power to key developmental outcomes in young neurotypical (NT) children and infants at risk for language impairment. However, it remains unclear whether gamma power is specifically associated with language or with more general cognitive abilities among young children diagnosedwith autism spectrum disorder (ASD). The current study evaluates differences in resting frontal gamma power between young autistic and NT children and tests whether gamma power is uniquely associated with individual differences in expressive language, receptive language and non-verbal cognitive abilities in autistic and NT children. Participants included 48 autistic children and 58 age- and sex-matched NT children (ages 22-60months). Baseline electroencephalography (EEG) recordings were acquired from each participant. Children also completed the Mullen Scales of Early Learning (MSEL). We found thatfrontal gamma power at rest did not differ between autistic and NT children. Among autistic children, reduced frontal gamma power was significantly associated with both higher expressive language skills and higher non-verbal cognitive skills, controlling for age and sex. The interaction between frontal gamma power and diagnostic status no longer explained unique variance in expressive language skills after controlling for variance associated with non-verbal cognitive skills across autistic and NT children. Together, these findings suggest that reduced gamma power is associated with both better expressive language and non-verbal cognitive skills among young autistic children. Moreover, associations between high frequency neural activity and cognition are not specific to verbal abilities but reflect neural mechanisms associated with general higher-order cognitive abilities in ASD.

Leyi Mental Training: Bridging Ancient Wisdom and Modern Science to Reduce Anxiety via Altered Brain Dynamics

Leyi is a set of physical and mental cultivation methods established by Professor Changle Zhou after many years of practice. It combines modern psychological adjustment and Chinese ancient Buddhist practice methods, including relaxation, breathing, meditation, koan, and cognitive regulation. Its purpose is to achieve the state of enlightenment (a high-level ideology in Buddhism). More than ten years of practical experience has proved that Leyi Mental Training can improve people's physical and mental health, especially most participants reported that their anxiety reduced after training. Before and after the training, we recorded the participants' EEG during the task of judging emotional pictures and administered the POMS Scale to them after the task. The results showed that their anxiety subscale scores were significantly reduced after training, and the accompanying brain activity was that the power of frontal gamma was reduced considerably. Studies have found that frontal gamma power is related to DMN activity, and a decrease in frontal gamma power indicates a reduction of internal network activity. We speculate that this may be because Leyi's training changed the way of self-referential processing, which in turn affected the activities of the internal network, which may be one of the brain mechanisms for reducing anxiety

Gamma Power as an Index of Sustained Attention in Simulated Vigilance Tasks.

Performance on the psychomotor vigilance test (PVT; Dinges & Powell, 1985)-a common index of sustained attention-is affected by the opposing forces of fatigue and sustained effort, where reaction times and error rates typically increase across trials and are sometimes offset by additional efforts deployed toward the end of the task (i.e., an "end-spurt"; cf. Bergum & Klein, 1961). In ACT-R (Adaptive Control of Thought-Rational; Anderson etal., 2004), these influences on task performance have been modeled as latent variables that are inferred from performance (e.g., Jongman, 1998; Veksler & Gunzelmann, 2018) without connections to directly observable variables. We propose the use of frontal gamma (γ) spectral power as a direct measure of vigilant effort and demonstrate its efficacy in modeling performance on the PVT in both the aggregate and inindividuals.

Mindset awareness and management protocols using real-time frontal gamma asymmetry

Mindset awareness and management protocols using real-time frontal gamma asymmetry

Frontal midline theta rhythm and gamma activity measured by sheet-type wearable EEG device.

The current study measured the frontal midline theta rhythm (Fmθ), which appears in the frontal midline region during the attentional focus state, using the sheet-type wearable electroencephalograph (EEG) device HARU-1, and examined the modulation of frontal gamma band activity by cognitive tasks. We measured the frontal EEG of 20 healthy subjects using HARU-1 for 2 min during the rest eyes-closed condition and simple mental calculation task condition, respectively. Statistical analyses were conducted using permutation testing based on t-test and cluster analysis to compare the results between the resting state and the task condition. Twelve of 20 subjects showed Fmθ during the task condition. The 12 subjects with Fmθ showed significantly higher activity of the theta and gamma bands, and significantly low activity of the alpha band during the task condition compared to the resting condition. In the eight subjects without Fmθ were significantly low activity of the alpha and beta bands and no significant activity in the theta and gamma band activity during the task condition compared to the resting condition. These results indicate that it is possible to measure Fmθ using HARU-1. A novel finding was the gamma band activity appearing with Fmθ in the left and right frontal forehead regions, suggesting that it reflects the function of the prefrontal cortex in working memory tasks.

Electrophysiological correlates of dispositional mindfulness: A quantitative and complexity EEG study.

While growing evidence supports that dispositional mindfulness relates to psychological health and cognitive enhancement, to date there have been only a few attempts to characterize its neural underpinnings. In the present study, we aimed at exploring the electrophysiological (EEG) signature of dispositional mindfulness using quantitative and complexity measures of EEG during resting state and while performing a learning task. Hundred twenty participants were assessed with the Five Facet Mindfulness Questionnaire and underwent 5min eyes-closed resting state and 5min at task EEG recording. We hypothesized that high mindfulness individuals would show patterns of brain activity related to (a) lower involvement of the default mode network (DMN) at rest (reduced frontal gamma power) and (b) a state of 'task readiness' reflected in a more similar pattern from rest to task (reduced overall q-EEG power at rest but not at task), as compared to their low mindfulness counterparts. Dispositional mindfulness was significantly linked to reduced frontal gamma power at rest and lower overall power during rest but not at task. In addition, we found a trend towards higher entropy during task performance in mindful individuals, which has recently been reported during mindfulness meditation. Altogether, our results add to those from expert meditators to show that high (dispositional) mindfulness seems to have a specific electrophysiological pattern characteristic of less involvement of the DMN and mind-wandering processes.

Gamma Oscillations and Potassium Channel Modulation in Schizophrenia: Targeting GABAergic Dysfunction.

Impairments in gamma-aminobutyric acid (GABAergic) interneuron function lead to gamma power abnormalities and are thought to underlie symptoms in people with schizophrenia. Voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels on GABAergic interneurons are critical to the generation of gamma oscillations suggesting that targeting Kv3.1/3.2 could augment GABAergic function and modulate gamma oscillation generation. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on resting state frontal gamma power in people with schizophrenia. We found a significant positive correlation between frontal resting gamma (35-45 Hz) power (n = 22, r = 0.613, P < .002) and positive and negative syndrome scale (PANSS) positive symptom severity. We also found a significant reduction in frontal gamma power (t13 = 3.635, P = .003) from baseline in patients who received AUT00206. This provides initial evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address gamma oscillation abnormalities in schizophrenia.

Decreased frontal gamma activity in Alzheimer’s disease patients

Decreased frontal gamma activity in Alzheimer’s disease patients

Developments in Transcranial Magnetic Stimulation to Study Human Cognition.

Developments in Transcranial Magnetic Stimulation to Study Human Cognition.

The effect of ketamine and D-cycloserine on the high frequency resting EEG spectrum in humans

RationalePreclinical studies indicate that high-frequency oscillations, above 100 Hz (HFO:100–170 Hz), are a potential translatable biomarker for pharmacological studies, with the rapid acting antidepressant ketamine increasing both gamma (40–100 Hz) and HFO.ObjectivesTo assess the effect of the uncompetitive NMDA antagonist ketamine, and of D-cycloserine (DCS), which acts at the glycine site on NMDA receptors on HFO in humans.MethodsWe carried out a partially double-blind, 4-way crossover study in 24 healthy male volunteers. Each participant received an oral tablet and an intravenous infusion on each of four study days. The oral treatment was either DCS (250 mg or 1000 mg) or placebo. The infusion contained 0.5 mg/kg ketamine or saline placebo. The four study conditions were therefore placebo-placebo, 250 mg DCS-placebo, 1000 mg DCS-placebo, or placebo-ketamine.ResultsCompared with placebo, frontal midline HFO magnitude was increased by ketamine (p = 0.00014) and 1000 mg DCS (p = 0.013). Frontal gamma magnitude was also increased by both these treatments. However, at a midline parietal location, only HFO were increased by DCS, and not gamma, whilst ketamine increased both gamma and HFO at this location. Ketamine induced psychomimetic effects, as measured by the PSI scale, whereas DCS did not increase the total PSI score. The perceptual distortion subscale scores correlated with the posterior low gamma to frontal high beta ratio.ConclusionsOur results suggest that, at high doses, a partial NMDA agonist (DCS) has similar effects on fast neural oscillations as an NMDA antagonist (ketamine). As HFO were induced without psychomimetic effects, they may prove a useful drug development target.

Novel EEG-Based Neurofeedback System Targeting Frontal Gamma Activity of Schizophrenia Patients to Improve Working Memory.

Patients with schizophrenia (SCZ) exhibit working memory (WM) deficits that are associated with deficient dorsal-lateral prefrontal cortical activity, including decreased frontal gamma power. We thus hypothesized that training SCZ patients to increase frontal gamma activity would improve their WM performance. We administered electroencephalographic (EEG) neurofeedback (NFB) to 31 participants with SCZ for 12 weeks (24 sessions), which provides real-time visual and auditory feedback related to frontal gamma activity. The EEG-NFB training significantly improved EEG markers of optimal working memory, e.g., frontal P3 amplitude and gamma power. Based on these promising results, we developed a novel, EEGLAB/MATLAB-based brain-computer interface (BCI) that delivers F3-F4 gamma coherence NFB with a dynamic threshold to SCZ patients randomized in a double-blind, placebo-controlled clinical trial. The BCI significantly increased F3-F4 gamma coherence after 12 weeks (24 sessions) of training, according to data from the first 12 subjects ( n=6 /group) who completed gamma- or placebo-NFB training.

Decreased Frontal Gamma Activity in Alzheimer Disease Patients.

ObjectiveIn Alzheimer disease (AD) animal models, synaptic dysfunction has recently been linked to a disorder of high‐frequency neuronal activity. In patients, a clear relation between AD and oscillatory activity remains elusive. Here, we attempt to shed light on this relation by using a novel approach combining transcranial magnetic stimulation and electroencephalography (TMS‐EEG) to probe oscillatory activity in specific hubs of the frontoparietal network in a sample of 60 mild‐to‐moderate AD patients.MethodsSixty mild‐to‐moderate AD patients and 21 age‐matched healthy volunteers (HVs) underwent 3 TMS‐EEG sessions to assess cortical oscillations over the left dorsolateral prefrontal cortex, the precuneus, and the left posterior parietal cortex. To investigate the relations between oscillatory activity, cortical plasticity, and cognitive decline, AD patients underwent a TMS‐based neurophysiological characterization and a cognitive evaluation at baseline. The latter was repeated after 24 weeks to monitor clinical evolution.ResultsAD patients showed a significant reduction of frontal gamma activity as compared to age‐matched HVs. In addition, AD patients with a more prominent decrease of frontal gamma activity showed a stronger impairment of long‐term potentiation–like plasticity and a more pronounced cognitive decline at subsequent follow‐up evaluation at 24 weeks.InterpretationOur data provide novel evidence that frontal lobe gamma activity is dampened in AD patients. The current results point to the TMS‐EEG approach as a promising technique to measure individual frontal gamma activity in patients with AD. This index could represent a useful biomarker to predict disease progression and to evaluate response to novel pharmacological therapies. ANN NEUROL 2022;92:464–475

Frontal Metabolites and Alzheimer's Disease Biomarkers in Healthy Older Women and Women Diagnosed with Mild Cognitive Impairment.

Women account for two thirds of the prevalence and incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Evidence suggest that sex may differently influence the expression of proteins amyloid-beta (Aβ1-42) and tau, for which early detection is crucial in prevention of the disease. We investigated the effect of aging and cerebrospinal fluid (CSF) levels of Aβ1-42 and tau on frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) in a cohort of cognitively normal older women and women with MCI. 3T single-voxel MRS was performed on the medial frontal cortex, using Point Resolved Spectroscopy (PRESS) and Mescher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) in 120 women (age range 50-85). CSF samples of Aβ1-42 and tau and scores of general cognition were also obtained. Levels of frontal gamma aminobutyric acid (GABA+) were predicted by age, independently of disease and CSF biomarkers. Importantly, levels of GABA+ were reduced in MCI patients. Additionally, we found that levels of N-acetylaspartate relative to myo-inositol (tNAA/mI) predicted cognition in MCI patients only and were not related to CSF biomarkers. This study is the first to demonstrate a strong association between frontal GABA+ levels and neurological aging in a sample consisting exclusively of healthy older women with various levels of CSF tau and Aβ1-42 and women with MCI. Importantly, our results show no correlation between CSF biomarkers and MRS metabolites in this sample.

Targeting Frontal Gamma Activity with Neurofeedback to Improve Working Memory in Schizophrenia.

Optimal working memory (WM), the mental ability to internally maintain and manipulate task-relevant information, requires coordinated activity of dorsal-lateral prefrontal cortical (DLPFC) neurons. More specifically, during delay periods of tasks with WM features, DLPFC microcircuits generate persistent, stimulus-specific higher-frequency (e.g., gamma) activity. This activity largely depends on recurrent connections between parvalbumin positive inhibitory interneurons and pyramidal neurons in more superficial DLPFC layers. Due to the size and organization of pyramidal neurons (especially apical dendrites), local field potentials generated by DLPFC microcircuits are strong enough to pass outside the skull and can be detected using electroencephalography (EEG). Since patients with schizophrenia (SCZ) exhibit both DLPFC and WM abnormalities, EEG markers of DLPFC microcircuit activity during WM may serve as effective biomarkers or treatment targets. In this review, we summarize converging evidence from primate and human studies for a critical role of DLPFC microcircuit activity during WM and in the pathophysiology of SCZ. We also present a meta-analysis of studies available in PubMed specifically comparing frontal gamma activity between participants with SCZ and healthy controls, to determine whether frontal gamma activity may be a valid biomarker or treatment target for patients with SCZ. We summarize the complex cognitive and neurophysiologic processes contributing to neural oscillations during tasks with WM features, and how such complexity has stalled the development of neurophysiologic biomarkers and treatment targets. Finally, we summarize promising results from early reports using neuromodulation to target DLPFC neural activity and improve cognitive function in participants with SCZ, including a study from our team demonstrating that gamma-EEG neurofeedback increases frontal gamma power and WM performance in participants with SCZ. From the evidence discussed in this review, we believe the emerging field of neuromodulation, which includes extrinsic (electrical or magnetic stimulation) and intrinsic (EEG neurofeedback) modalities, will, in the coming decade, provide promising treatment options targeting specific neurophysiologic properties of specific brain areas to improve cognitive and behavioral health for patients with SCZ.

Detection of Stroke-Induced Visual Neglect and Target Response Prediction Using Augmented Reality and Electroencephalography.

We aim to build a system incorporating electroencephalography (EEG) and augmented reality (AR) that is capable of identifying the presence of visual spatial neglect (SN) and mapping the estimated neglected visual field. An EEG-based brain-computer interface (BCI) was used to identify those spatiospectral features that best detect participants with SN among stroke survivors using their EEG responses to ipsilesional and contralesional visual stimuli. Frontal-central delta and alpha, frontal-parietal theta, Fp1 beta, and left frontal gamma were found to be important features for neglect detection. Additionally, temporal analysis of the responses shows that the proposed model is accurate in detecting potentially neglected targets. These targets were predicted using common spatial patterns as the feature extraction algorithm and regularized discriminant analysis combined with kernel density estimation for classification. With our preliminary results, our system shows promise for reliably detecting the presence of SN and predicting visual target responses in stroke patients with SN.

Identification of an optimal dose of intravenous ketamine for late-life treatment-resistant depression: a Bayesian adaptive randomization trial.

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) seven days after a 40 minute intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and effects on cortical excitation/inhibition (E/I) ratio using resting electroencephalography gamma and alpha power, were also determined. Thirty-three medication-free U.S. military veterans (mean age 62; range: 55 – 72; 10 female) with LL-TRD were randomized double-blind. The trial was terminated when dose superiority was established. All interventions were safe and well-tolerated. Pre-specified decision-rules terminated KET 0.1 (N=4) and KET 0.25 (N=5) for inferiority. Posterior probability was 0.89 that day-seven treatment response was superior for KET 0.5 (N=11; response rate = 70%) compared to MID (N=13; response rate = 46%). Persistent treatment response at day 28 was superior for KET 0.5 (response rate = 82%) compared to MID (response rate = 37%). KET 0.5 had high posterior probability of increased frontal gamma power (posterior probability = 0.99) and decreased posterior alpha power (0.89) during infusion, suggesting an acute increase in E/I ratio. These results suggest that 0.5 mg/kg is an effective initial IV ketamine dose in LL-TRD, although further studies in individuals older than 75 are required.

Relationships between frontal metabolites and Alzheimer's disease biomarkers in cognitively normal older adults

Elevated expression of β-amyloid (Aβ1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aβ1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.

Gamma Oscillations Index Sustained Attention in a Brief Vigilance Task

Sustained attention is an essential behavior in life, but often leads to performance decrements with time. Computational accounts of sustained attention suggest this is due to brief disruptions in goal-directed processing, or microlapses. Decreases in gamma spectral power are a potential candidate for indexing microlapses and discriminating between low and high performers in sustained attention tasks, while increases in beta, alpha, and theta power are expected to exhibit compensatory effort to offset fatigue. The current study tests these hypotheses in a 10-minute Psychomotor Vigilance Test, a context that eliminates confounds with measuring gamma frequencies. 34 participants ( Mage = 22.60; SDage = 4.08) volunteered in the study. Results suggested frontal gamma power declined with time-on-task, indicating reduction in central cognition. Beta power increased with time-on-task, suggesting compensatory effort; however, alpha and theta power did not increase. Additionally, gamma power discriminated between low and high performers, potentially suggesting motivational differences between the groups.

Violation of rhythmic expectancies can elicit late frontal gamma activity nested in theta oscillations.

Rhythm processing involves building expectations according to the hierarchical temporal structure of auditory events. Although rhythm processing has been addressed in the context of predictive coding, the properties of the oscillatory response in different cortical areas are still not clear. We explored the oscillatory properties of the neural response to rhythmic incongruence and the cross‐frequency coupling between multiple frequencies to further investigate the mechanisms underlying rhythm perception. We designed an experiment to investigate the neural response to rhythmic deviations in which the tone either arrived earlier than expected or the tone in the same metrical position was omitted. These two manipulations modulate the rhythmic structure differently, with the former creating a larger violation of the general structure of the musical stimulus than the latter. Both deviations resulted in an MMN response, whereas only the rhythmic deviant resulted in a subsequent P3a. Rhythmic deviants due to the early occurrence of a tone, but not omission deviants, seemed to elicit a late high gamma response (60–80 Hz) at the end of the P3a over the left frontal region, which, interestingly, correlated with the P3a amplitude over the same region and was also nested in theta oscillations. The timing of the elicited high‐frequency gamma oscillations related to rhythmic deviation suggests that it might be related to the update of the predictive neural model, corresponding to the temporal structure of the events in higher‐level cortical areas.