A network model of the modulation of gamma oscillations by NMDA receptors in cerebral cortex

Psychotic drugs such as ketamine induce symptoms close to schizophrenia, and stimulates the production of gamma oscillations, as also seen in patients, but the underlying mechanisms are still unclear. Here, we have used computational models of cortical networks generating gamma oscillations, and have integrated the action of drugs such as ketamine to partially block n-methyl-d-Aspartate (NMDA) receptors. The model can reproduce the modulation of gamma oscillations by NMDA-receptor antagonists, assuming that antagonists affect NMDA receptors predominantly on inhibitory interneurons. We next used the model to compare the responsiveness of the network to external stimuli, and found that when NMDA channnels are blocked an increase of Gamma power is observed altogether with an increase of network responsiveness. However, this responsiveness increase applies not only to gamma states, but also to synchronous states with no apparent gamma. We conclude that NMDA antagonists induce increased excitability state, which may or may not produce gamma oscillations, but the response to external inputs is exacerbated, which may explain phenomena such as altered perception or hallucinations.

Neural Oscillations and Networks in Processes Specific to Auditory Imagery

Auditory imagery is a cognitive process for generating sound in our mind. Despite the absence of external stimuli, neuroimaging studies have found overlapping neural activities within perception and imagery. While neuroimaging studies have revealed activities unique to auditory imagery, namely memory retrieval and mental manipulation, little is known about the functional oscillatory networks associated with these processes. Therefore, in this study, we aimed to distinguish between neural oscillations for memory retrieval and mental manipulation processes by building a novel experimental paradigm containing multiple imagery conditions with the goal of enabling the effective investigation of different oscillatory processes. We found that frontal and temporal gamma power was associated with mental manipulation, while frontotemporal delta phase coupling and delta-gamma phase-amplitude coupling were each associated with memory retrieval during auditory imagery. Moreover, we found that oscillations reflecting auditory-motor communication were associated with memory retrieval. Our results suggest the critical role of neural oscillations associated with imagery-specific processes and present evidence supporting the long-debated role of motor functions in auditory imagery. Our work thus adds dimension to the state of knowledge regarding functional networks within auditory imagery.

Early neural activity changes associated with visual conscious perception

The neural mechanisms of visual conscious perception have been investigated for decades. However, the spatiotemporal dynamics associated with the earliest neural responses following consciously perceived stimuli are still poorly understood. Using a dataset of intracranial EEG recordings, the current study aims to investigate the neural activity changes associated with the earliest stages of visual conscious perception. Subjects (N=10, 1,693 grey matter electrode contacts) completed a continuous performance task in which individual letters were presented in series and subjects were asked to press a button when they saw a target letter. Broadband gamma power (40-115Hz) dynamics were analyzed in comparison to baseline prior to stimulus and contrasted for target trials with button presses and non-target trials without button presses. Regardless of event type, we observed early gamma power changes within 30-150 ms from stimulus onset in a network including increases in bilateral occipital, fusiform, frontal (including frontal eye fields), and medial temporal cortex, increases in left lateral parietal-temporal cortex, and decreases in the right anterior medial occipital cortex. No significant differences were observed between target and non-target stimuli until >150 ms post-stimulus, when we saw greater gamma power increases in left motor and premotor areas, suggesting a possible role of these later signals in perceptual decision making and/or motor responses with the right hand. The early gamma power findings suggest a broadly distributed cortical visual detection network that is engaged at early times tens of milliseconds after signal transduction from the retina.

The hippocampus as the switchboard between perception and memory

Adaptive memory recall requires a rapid and flexible switch from external perceptual reminders to internal mnemonic representations. However, owing to the limited temporal or spatial resolution of brain imaging modalities used in isolation, the hippocampal–cortical dynamics supporting this process remain unknown. We thus employed an object-scene cued recall paradigm across two studies, including intracranial electroencephalography (iEEG) and high-density scalp EEG. First, a sustained increase in hippocampal high gamma power (55 to 110 Hz) emerged 500 ms after cue onset and distinguished successful vs. unsuccessful recall. This increase in gamma power for successful recall was followed by a decrease in hippocampal alpha power (8 to 12 Hz). Intriguingly, the hippocampal gamma power increase marked the moment at which extrahippocampal activation patterns shifted from perceptual cue toward mnemonic target representations. In parallel, source-localized EEG alpha power revealed that the recall signal progresses from hippocampus to posterior parietal cortex and then to medial prefrontal cortex. Together, these results identify the hippocampus as the switchboard between perception and memory and elucidate the ensuing hippocampal–cortical dynamics supporting the recall process.

Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice

Background Alzheimer’s disease (AD) is the most common cause of dementia, and is characterized by amyloid-β (Aβ) plaques and tauopathy. Reducing Aβ has been considered a major AD treatment strategy in pharmacological and non-pharmacological approaches. Impairment of gamma oscillations, which play an important role in perception and cognitive function, has been shown in mouse AD models and human patients. Recently, the therapeutic effect of gamma entrainment in AD mouse models has been reported. Given that ultrasound is an emerging neuromodulation modality, we investigated the effect of ultrasound stimulation pulsed at gamma frequency (40 Hz) in an AD mouse model. Methods We implanted electroencephalogram (EEG) electrodes and a piezo-ceramic disc ultrasound transducer on the skull surface of 6-month-old 5×FAD and wild-type control mice (n = 12 and 6, respectively). Six 5×FAD mice were treated with two-hour ultrasound stimulation at 40 Hz daily for two weeks, and the other six mice received sham treatment. Soluble and insoluble Aβ levels in the brain were measured by enzyme-linked immunosorbent assay. Spontaneous EEG gamma power was computed by wavelet analysis, and the brain connectivity was examined with phase-locking value and cross-frequency phase-amplitude coupling. Results We found that the total Aβ42 levels, especially insoluble Aβ42, in the treatment group decreased in pre- and infra-limbic cortex (PIL) compared to that of the sham treatment group. A reduction in the number of Aβ plaques was also observed in the hippocampus. There was no increase in microbleeding in the transcranial ultrasound stimulation (tUS) group. In addition, the length and number of microglial processes decreased in PIL and hippocampus. Encelphalographic spontaneous gamma power was increased, and cross-frequency coupling was normalized, implying functional improvement after tUS stimulation. Conclusion These results suggest that the transcranial ultrasound-based gamma-band entrainment technique can be an effective therapy for AD by reducing the Aβ load and improving brain connectivity.

Population receptive fields in non-human primates from whole-brain fMRI and large-scale neurophysiology in visual cortex in visual cortex

Population receptive field (pRF) modeling is a popular fMRI method to map the retinotopic organization of the human brain. While fMRI-based pRF-maps are qualitatively similar to invasively recorded single-cell receptive fields in animals, it remains unclear what neuronal signal they represent. We addressed this question in awake non-human primates comparing whole-brain fMRI and large-scale neurophysiological recordings in areas V1 and V4 of the visual cortex. We examined the fits of several pRF-models based on the fMRI BOLD-signal, multi-unit spiking activity (MUA) and local field potential (LFP) power in different frequency bands. We found that pRFs derived from BOLD-fMRI were most similar to MUA-pRFs in V1 and V4, while pRFs based on LFP gamma power also gave a good approximation. FMRI-based pRFs thus reliably reflect neuronal receptive field properties in the primate brain. In addition to our results in V1 and V4, the whole-brain fMRI measurements revealed retinotopic tuning in many other cortical and subcortical areas with a consistent increase in pRF-size with increasing eccentricity, as well as a retinotopically specific deactivation of default-mode network nodes similar to previous observations in humans.

The Consciousness State of Traditional Nidrâ Yoga/Modern Yoga Nidra: Phenomenological Characterization and Preliminary Insights from an EEG Study

Nidrâ yoga is an ancient yogic practice capable of inducing altered states of consciousness characterized by deep relaxation, strong concentration, acute self-awareness, and joy. In modern contemplative neuroscience language, it is known by the name yoga nidra, and few studies have investigated its phenomenological and psychophysiological effects. Six healthy volunteers (four females aged 31–74) performed 12 yoga nidra sessions guided by an expert during a 6-day retreat. Each session consisted of 10 minutes in a resting state (baseline) followed by 2 hours of yoga nidra. Psychometric data regarding dissociative experiences (Clinician Administered Dissociative States Scale) and the state of consciousness (Phenomenology of Consciousness Inventory) were collected after baseline and yoga nidra, while high-density EEG was recorded during the entire session. During nidra sessions, no sleep hallmarks (i.e., K-complexes and sleep spindles) were detected by the EEG in any subject. Psychometric data we re analyzed using a Wilcoxon signed-rank test corrected with the false discovery rate approach for multiple comparisons. Compared to baseline, yoga nidra practice was related to: (1) increased dissociative effects (p = 0.022); (2) perception of being in an altered state of consciousness (p = 0.026); (3) alterations in perceived body image (p = 0.022); (4) increased “meaningfulness” attributed to the experience (p = 0.026); (5) reduced rational thinking (p = 0.029); and (6) reduced volitional thought control (p = 0.026). First-person experience is discussed in relation to descriptive EEG power spectral density analysis, which was performed in one subject because of severe EEG artifacts in the other recordings; that subject showed, compared to baseline: (1) early increase of alpha and beta power, followed by a progressive widespread reduction; (2) widespread early increase of theta power, followed by a progressive reduction; and (3) widespread increase of gamma power in the latest stages. The present preliminary results enrich the knowledge of yoga nidra, elucidating its phenomenology and suggesting some psychophysiological correlates that future studies may address.

Baclofen-Associated Neurophysiologic Target Engagement Across Species in Fragile X Syndrome

Background: Fragile X Syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. Methods: In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABAB selective agonist racemic baclofen (RBAC). Results: In Fmr1 KO mice and in humans with FXS, baclofen use was synchronously associated with suppression of elevated gamma power and increase in theta power at rest. In the Frm1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted. Conclusions: Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field. Trial Registration: The human experiments are registered under NCT02998151.