Individual Stability of Pain- and Touch-Related Neuronal Gamma Oscillations

Background: The processing of brief pain and touch stimuli has been associated with an increase of neuronal oscillations in the gamma range (40-90 Hz). However, some studies report divergent gamma effects across single participants. Methods: In two repeated sessions we recorded gamma responses to pain and touch stimuli using EEG. Individual gamma responses were extracted from EEG channels and from ICA components that contain a strong gamma amplitude. Results: We observed gamma responses in the majority of the participants. If present, gamma synchronisation was always bound to a component that contained a laser-evoked response. We found a broad variety of individual cortical processing: some participants showed a clear gamma effect, others did not exhibit any gamma. For both modalities, the effect was reproducible between sessions. In addition, participants with a strong gamma response showed a similar time-frequency pattern across sessions. Conclusions: Our results indicate that current measures of reproducibility of research results do not reflect the complex reality of the diverse individual processing pattern of applied pain and touch. The present findings raise the question of whether we would find similar quantitatively different processing patterns in other domains in neuroscience: group results would be replicable but the overall effect is driven by a subgroup of the participants.

Deficient auditory gamma-BOLD coupling in schizophrenia is related to sensory gating deficits

Background: Schizophrenia is associated with aberrant gamma band power, hypothesized to reflect imbalance in the excitation-inhibition (E/I) ratio and undermine neural signal efficiency. Relationships between resting-state gamma, E/I balance, and regional hemodynamics from the fMRI BOLD signal are unknown. Methods: We recorded simultaneous EEG-fMRI at rest, with eyes open, in people with schizophrenia (n= 57) and people without a psychiatric diagnosis (n= 46) and identified gamma and aperiodic EEG parameters associated with E/I balance. Measures from all EEG channels were entered into a whole-brain, parametric modulation analysis followed by statistical correction for multiple comparisons. Sensory gating was assessed using the Sensory Gating Inventory, and psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. Results: Across groups, gamma power modestly predicts a steeper aperiodic slope (greater inhibition), without group differences in either gamma power or aperiodic slope. In schizophrenia, gamma-BOLD coupling was reduced in bilateral auditory regions of the superior temporal gyri and inversely correlated with sensory gating deficits and symptom severity. Analysis of the spectral features of scanner sounds revealed distinct peaks in the gamma range, reflecting a rapidly repeating scanner pulse sound present throughout the resting state recording. Conclusion: Regional hemodynamic support for putative inhibitory and excitatory contributions to resting EEG are aberrant in SZ. Deficient gamma coupling to auditory BOLD may reflect impaired gating of fMRI-scanner sound.

Focal gamma activity in frontal control regions revealed using intraoperative electrocorticography

How the frontal cortex is anatomically and functionally organized to control cognition remains puzzling. Numerous non-invasive brain imaging studies relate cognitive control to a localized set of frontal regions, part of a wider fronto-parietal network (FPN), that show increases in functional MRI (fMRI) signal during the performance of multiple cognitively demanding tasks. Lesions implicating frontal control regions lead to disorganized behaviour. However, the fMRI BOLD signal is an indirect measure of neuronal activity and represents evidence from a single modality. This has led to limited clinical translation of fMRI findings e.g. to guide the surgical resection of brain tumours. Here we sought supporting evidence for lateral frontal control regions using electrocorticography (ECoG). We recorded electrophysiological activity from electrodes placed on the lateral frontal cortex in patients undergoing awake craniotomy for glioma resection. During surgery, patients performed two verbal executive-related counting tasks with a difficulty level manipulation, closely adapting difficulty manipulations in fMRI studies of cognitive control. We performed spectral analysis focusing on the gamma range (30-250 Hz) due to mounting evidence of its value as an index of local cortical processing. Comparing hard versus easy demands revealed circumscribed frontal regions with power increases in the gamma range. This contrasted with spatially distributed power decreases in the beta range (12-30 Hz). Further, electrodes showing significant gamma power increases were more likely to occur within a canonical fMRI-defined FPN and showed stronger gamma power increases compared to electrodes outside the FPN, even at the single patient level. Reinforcing the need for careful task manipulation, an easy versus baseline comparison, which includes factors such as speech output, produced gamma changes over a wider area. Thus, using similar task difficulty manipulations, ECoG and fMRI signals converged on delineating lateral frontal control regions. These findings open the door for extending clinical functional mapping to the domain of cognitive control during awake neurosurgery.

Altered low frequency brain rhythms precede changes in gamma power during tauopathy

Alzheimer's disease and other dementias are associated with disruptions of electrophysiological brain activity, including low frequency and gamma rhythms. Many of these dementias are also associated with the malfunction of the membrane associated protein tau. Tauopathy disrupts neuronal function and the stability of synapses and is a key driver of neurodegeneration. Here we ask how brain rhythms are affected by tauopathy, at different stages of its progression. We performed local field potential recordings from visual cortex of rTg4510 and control animals at early stages of neurodegeneration (5 months) and at a more advanced stage where pathology is evident (8 months). We measured brain activity in the presence or absence of external visual stimulation, and while monitoring pupil diameter and locomotion to establish animal behavioural states. At 5 months, before substantial pathology, we found an increase in low frequency rhythms during resting state in tauopathic animals. This was because tauopathic animals entered intermittent periods of increased neural synchronisation, where activity across a wide band of low frequencies was strongly correlated. At 8 months, when the degeneration was more advanced, the increased synchronisation and low frequency power was accompanied by a reduction in power in the gamma range, with diverse effects across different components of the gamma rhythm. Our results indicate that slower rhythms are impaired earlier than gamma rhythms in tauopathy, suggesting that electrophysiological measurements can indicate both the presence and progression of tauopathic degeneration.

The Blazar OJ 287 Jet from Parsec to Kiloparsec Scales

The curved shape of the kiloparsec-scale jet of the blazar OJ 287 is analyzed in the framework of the precession of the central engine, on the existence on which a large number of studies over the past decades are based. The data necessary for the analysis on the kiloparsec-scale jet velocity and angle with the line of sight are obtained based on two competing assumptions about the X-ray emission mechanism of the OJ 287 jet. Namely, there were both the inverse Compton scattering of the cosmic microwave background under the assumption of relativistic kiloparsec-scale jet and the inverse Compton scattering of the central source radiation. For the latter one, we showed that the expected flux from the kiloparsec-scale jet in the gamma range does not exceed the limit set for it according to Fermi-LAT data. We found that only the period of the kiloparsec-scale jet helix, estimated in the framework of the inverse Compton scattering of the central source radiation, agrees with the precession period of the central engine, determined from the modulation of the peak values of 12‑year optical flares.

Orientation of Temporal Interference for Non-invasive Deep Brain Stimulation in Epilepsy

In patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on non-penetrating surface electrodes, namely an orientation-tunable form of temporally interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of Pulse-width-modulation of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally invasive temporally interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue and overcoming several limitations of other non-invasive stimulation methods in epilepsy, such as transcranial magnetic stimulation (TMS).

The visual cortex produces gamma band echo in response to broadband visual flicker

The aim of this study is to uncover the network dynamics of the human visual cortex by driving it with a broadband random visual flicker. We here applied a broadband flicker (1–720 Hz) while measuring the MEG and then estimated the temporal response function (TRF) between the visual input and the MEG response. This TRF revealed an early response in the 40–60 Hz gamma range as well as in the 8–12 Hz alpha band. While the gamma band response is novel, the latter has been termed the alpha band perceptual echo. The gamma echo preceded the alpha perceptual echo. The dominant frequency of the gamma echo was subject-specific thereby reflecting the individual dynamical properties of the early visual cortex. To understand the neuronal mechanisms generating the gamma echo, we implemented a pyramidal-interneuron gamma (PING) model that produces gamma oscillations in the presence of constant input currents. Applying a broadband input current mimicking the visual stimulation allowed us to estimate TRF between the input current and the population response (akin to the local field potentials). The TRF revealed a gamma echo that was similar to the one we observed in the MEG data. Our results suggest that the visual gamma echo can be explained by the dynamics of the PING model even in the absence of sustained gamma oscillations.

Individual Resonant Frequencies at Low-Gamma Range and Cognitive Processing Speed

Brain electrophysiological activity within the low gamma frequencies (30–80 Hz) has been proposed to reflect information encoding and transfer processes. The 40-Hz auditory steady-state response (40-Hz ASSR) is frequently discussed in relation to changed cognitive processing in neuropsychiatric disorders. However, the relationship between ASSRs and cognitive functioning still remains unclear. Most of the studies assessed the single frequency ASSR, while the individual resonance frequency in the gamma range (30–60 Hz), also called individual gamma frequency (IGF), has received limited attention thus far. Nevertheless, IGF potentially might better reflect individual network characteristics than standardly utilized 40-Hz ASSRs. Here, we focused on the processing speed across different types of cognitive tasks and explored its relationship with responses at 40 Hz and at IGFs in an attempt to uncover how IGFs relate to certain aspects of cognitive functioning. We show that gamma activity is related to the performance speed on complex cognitive task tapping planning and problem solving, both when responses at 40 Hz and at IGFs were evaluated. With the individualized approach, the observed associations were found to be somewhat stronger, and the association seemed to primarily reflect individual differences in higher-order cognitive processing. These findings have important implications for the interpretation of gamma activity in neuropsychiatric disorders.

Hippocampal gamma-band oscillopathy in a mouse model of Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability arising from the loss of fragile X mental retardation protein (FMRP), a protein that plays a central role in neuronal function and plasticity. FXS patients show sensory hypersensitivity, hyperarousal and hippocampus-dependent learning deficits that can be recapitulated in the FMR1 KO mice. Enhanced metabotropic glutamate receptor (mGluR) signaling and muscarinic acetylcholine receptor (mAChR) signaling in the FMR1 KO mouse are implicated as the primary causes of the disease pathogenesis. Furthermore, glutamatergic kainate receptor (KAR) function is reduced in the cortex of the FMR1 KO mice. Of note, activation of these signaling pathways leads to slow gamma-range oscillations in the hippocampus in vitro and abnormal gamma oscillations have been reported in FMR1 KO mice and patients with FXS. Thus, we hypothesized that aberrant activation of these receptors leads to the observed gamma oscillopathy. We recorded gamma oscillations induced by either cholinergic agonist carbachol (CCh), mGluR1/5 agonist Dihydroxyphenylglycine (DHPG) or ionotropic glutamatergic agonist KA from the hippocampal CA3 in WT and FMR1 KO mice in vitro. We show a specific increase in the power of DHPG- and CCh-induced gamma oscillations and reduction in the synchronicity of gamma oscillations induced by KA. We further elucidate an aberrant spiking activity during CCh-induced and kainate-induced gamma oscillations which may underlie the altered gamma oscillation synchronization in the FMR1 KO mice. Last, we also noted a reduced incidence of spontaneously-occurring hippocampal sharp wave-ripple events. Our study provides further evidence for aberrant hippocampal rhythms in the FMR1 KO mice and identifies potential signaling pathways underlying gamma band oscillopathy in FXS.

Gamma-Range Auditory Steady-State Responses and Cognitive Performance: A Systematic Review

The auditory steady-state response (ASSR) is a result of entrainment of the brain’s oscillatory activity to the frequency and phase of temporally modulated stimuli. Gamma-range ASSRs are utilized to observe the dysfunctions of brain-synchronization abilities in neuropsychiatric and developmental disorders with cognitive symptoms. However, the link between gamma-range ASSRs and cognitive functioning is not clear. We systematically reviewed existing findings on the associations between gamma-range ASSRs and cognitive functions in patients with neuropsychiatric or developmental disorders and healthy subjects. The literature search yielded 1597 articles. After excluding duplicates and assessing eligibility, 22 articles were included. In healthy participants, the gamma-range ASSR was related to cognitive flexibility and reasoning as measured by complex tasks and behavioral indicators of processing speed. In patients with schizophrenia, the studies that reported correlations found a higher ASSR to be accompanied by better performance on short-term memory tasks, long-term/semantic memory, and simple speeded tasks. The main findings indicate that individual differences in the gamma-range ASSR reflect the level of attentional control and the ability to temporary store and manipulate the information, which are necessary for a wide range of complex cognitive activities, including language, in both healthy and impaired populations.