Near-death experience (NDE) is a transcendent mental event of uncertain etiology that arises on the cusp of biological death. Since the discovery of NDE in the mid-1970s, multiple neuroscientific theories have been developed in an attempt to account for it in strictly materialistic or reductionistic terms. Therefore, in this conception, NDE is at most an extraordinary hallucination without any otherworldly, spiritual, or supernatural denotations. During the last decade or so, a number of animal and clinical studies have emerged which reported that about the time of death, there may be a surge of high frequency electroencephalogram (EEG) at a time when cortical electrical activity is otherwise at a very low ebb. This oscillatory rhythm falls within the range of the enigmatic brain wave-labelled gamma-band activity (GBA). Therefore, it has been proposed that this brief, paradoxical, and perimortem burst of the GBA may represent the neural foundation of the NDE. This study examines three separate but related questions concerning this phenomenon. The first problem pertains to the electrogenesis of standard GBA and the extent to which authentic cerebral activity has been contaminated by myogenic artifacts. The second problem involves the question of whether agents that can mimic NDE are also underlain by GBA. The third question concerns the electrogenesis of the surge in GBA itself. It has been contended that this is neither cortical nor myogenic in origin. Rather, it arises in a subcortical (amygdaloid) location but is recorded at the cortex via volume conduction, thereby mimicking standard GBA. Although this surge of GBA contains genuine electrophysiological activity and is an intriguing and provocative finding, there is little evidence to suggest that it could act as a kind of neurobiological skeleton for a phenomenon such as NDE.

N-methyl-D-aspartate (NMDA) receptor antagonists are widely used to pharmacologically model schizophrenia and have been recently established in the treatment of treatment-resistant major depression demonstrating that the pharmacology of this substance class is complex. Cortical gamma oscillations, a rhythmic neuronal activity associated with cognitive processes, are increased in schizophrenia and deteriorated in depressive disorders and are increasingly used as biomarker in these neuropsychiatric diseases. The opposite use of NMDA receptor antagonists in schizophrenia and depression raises the question how their effects are in accordance with the observed disease pathophysiology and if these effects show a consequent sex-specificity. In this study in rats, we investigated the effects of subchronic (14 days) intraperitoneal injections of the NMDA receptor antagonist MK-801 at a subanesthetic daily dose of 0.2 mg/kg on the behavioral phenotype of adult female and male rats and on pharmacologically induced gamma oscillations measured ex vivo from the hippocampus. We found that MK-801 treatment leads to impaired recognition memory in the novel object recognition test, increased stereotypic behavior and reduced grooming, predominantly in female rats. MK-801 also increased the peak power of hippocampal gamma oscillations induced by kainate or acetylcholine only in female rats, without affecting the peak frequency of the oscillations. The findings indicate that blockade of NMDA receptors enhances gamma oscillations predominantly in female rats and this effect is associated with behavioral changes in females. The results are in accordance with clinical electrophysiological findings and highlight the importance of hippocampal gamma oscillations as a biomarker in schizophrenia and depression.

Most patients with schizophrenia (SCZ) do not exhibit violent behaviors and are more likely to be victims rather than perpetrators of violent acts. However, a subgroup of forensic detainees with SCZ exhibit tendencies to engage in criminal violations. Although numerous models have been proposed, ranging from substance use, serotonin transporter gene, and cognitive dysfunction, the molecular underpinnings of violence in SCZ patients remains elusive. Lithium and clozapine have established anti-aggression properties and recent studies have linked low cholesterol levels and ultraviolet (UV) radiation with human aggression, while vitamin D3 reduces violent behaviors. A recent study found that vitamin D3, omega-3 fatty acids, magnesium, and zinc lower aggression in forensic population. In this review article, we take a closer look at aryl hydrocarbon receptor (AhR) and the dysfunctional lipidome in neuronal membranes, with emphasis on cholesterol and vitamin D3 depletion, as sources of aggressive behavior. We also discuss modalities to increase the fluidity of neuronal double layer via membrane lipid replacement (MLR) and natural or synthetic compounds. This article is part of the Special Issue on \"Personality Disorders\".

Brain rhythms provide the timing for recruitment of brain activity required for linking together neuronal ensembles engaged in specific tasks. The γ-oscillations (30 to 120 Hz) orchestrate neuronal circuits underlying cognitive processes and working memory. These oscillations are reduced in numerous neurological and psychiatric disorders, including early cognitive decline in Alzheimer\'s disease (AD). Here, we report on a potent brain-permeable small molecule, DDL-920 that increases γ-oscillations and improves cognition/memory in a mouse model of AD, thus showing promise as a class of therapeutics for AD. We employed anatomical, in vitro and in vivo electrophysiological, and behavioral methods to examine the effects of our lead therapeutic candidate small molecule. As a novel in central nervous system pharmacotherapy, our lead molecule acts as a potent, efficacious, and selective negative allosteric modulator of the γ-aminobutyric acid type A receptors most likely assembled from α1β2δ subunits. These receptors, identified through anatomical and pharmacological means, underlie the tonic inhibition of parvalbumin (PV) expressing interneurons (PV+INs) critically involved in the generation of γ-oscillations. When orally administered twice daily for 2 wk, DDL-920 restored the cognitive/memory impairments of 3- to 4-mo-old AD model mice as measured by their performance in the Barnes maze. Our approach is unique as it is meant to enhance cognitive performance and working memory in a state-dependent manner by engaging and amplifying the brain\'s endogenous γ-oscillations through enhancing the function of PV+INs.

Research suggests a potential of gamma oscillation entrainment for enhancing memory in Alzheimer\'s disease and healthy subjects. Gamma entrainment can be accomplished with oscillatory electrical, but also sensory stimulation. However, comparative studies between sensory stimulation and transcranial alternating current stimulation (tACS) effects on memory processes are lacking. This study examined the effects of rhythmic gamma auditory stimulation (rAS) and temporal gamma-tACS on verbal long-term memory (LTM) and working memory (WM) in 74 healthy individuals. Participants were assigned to two groups according to the stimulation techniques (rAS or tACS). Memory was assessed in three experimental blocks, in which each participant was administered with control, 40, and 60 Hz stimulation in counterbalanced order. All interventions were well-tolerated, and participants reported mostly comparable side effects between real stimulation (40 and 60 Hz) and the control condition. LTM immediate and delayed recall remained unaffected by stimulations, while immediate recall intrusions decreased during 60 Hz stimulation. Notably, 40 Hz interventions improved WM compared to control stimulations. These results highlight the potential of 60 and 40 Hz temporal cortex stimulation for reducing immediate LTM recall intrusions and improving WM performance, respectively, probably due to the entrainment of specific gamma oscillations in the auditory cortex. The results also shed light on the comparative effects of these neuromodulation tools on memory functions, and their potential applications for cognitive enhancement and in clinical trials.

Major burdens for patients suffering from stroke are cognitive co-morbidities and epileptogenesis. Neural network disinhibition and deficient inhibitive pulses for fast network activities may result from impaired presynaptic release of the inhibitory neurotransmitter GABA. To test this hypothesis, a cortical photothrombotic stroke was induced in Sprague Dawley rats, and inhibitory currents were recorded seven days later in the peri-infarct blood-brain barrier disrupted (BBBd) hippocampus via patch-clamp electrophysiology in CA1 pyramidal cells (PC). Miniature inhibitory postsynaptic current (mIPSC) frequency was reduced to about half, and mIPSCs decayed faster in the BBBd hippocampus. Furthermore, the paired-pulse ratio of evoked GABA release was increased at 100 Hz, and train stimulations with 100 Hz revealed that the readily releasable pool (RRP), usually assumed to correspond to the number of tightly docked presynaptic vesicles, is reduced by about half in the BBBd hippocampus. These pathophysiologic changes are likely to contribute significantly to disturbed fast oscillatory activity, like cognition-associated gamma oscillations or sharp wave ripples and epileptogenesis in the BBBd hippocampus.

OBJECTIVE: Electroencephalography (EEG) measures of visual evoked potentials (VEPs) provide a targeted approach for investigating neural circuit dynamics. This study separately analyses phase-locked (evoked) and non-phase-locked (induced) gamma responses within the VEP to comprehensively investigate circuit differences in autism.
METHODS: We analyzed VEP data from 237 autistic and 114 typically developing (TD) children aged 6-11, collected through the Autism Biomarkers Consortium for Clinical Trials (ABC-CT). Evoked and induced gamma (30-90 Hz) responses were separately quantified using a wavelet-based time-frequency analysis, and group differences were evaluated using a permutation-based clustering procedure.
RESULTS: Autistic children exhibited reduced evoked gamma power but increased induced gamma power compared to TD peers. Group differences in induced responses showed the most prominent effect size and remained statistically significant after excluding outliers.
CONCLUSIONS: Our study corroborates recent research indicating diminished evoked gamma responses in children with autism. Additionally, we observed a pronounced increase in induced power. Building upon existing ABC-CT findings, these results highlight the potential to detect variations in gamma-related neural activity, despite the absence of significant group differences in time-domain VEP components.
CONCLUSIONS: The contrasting patterns of decreased evoked and increased induced gamma activity in autistic children suggest that a combination of different EEG metrics may provide a clearer characterization of autism-related circuitry than individual markers alone.

The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer\'s Disease (AD) and to testing new drugs, with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments, such as non-invasive stimulation techniques on AD neuropathology and symptoms. Among the different non-invasive brain stimulation approaches, transcranial alternating current stimulation (tACS) is gaining particular attention due to its ability to externally control gamma oscillations. Here, we outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD, applied specifically at 40 Hz frequency, and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials.

Auditory neural networks in the brain naturally entrain to rhythmic stimuli. Such synchronization is an accessible index of local network performance as captured by EEG. Across species, click trains delivered ∼ 40 Hz show strong entrainment with primary auditory cortex (Actx) being a principal source. Imaging studies have revealed additional cortical sources, but it is unclear if they are functionally distinct. Since auditory processing evolves hierarchically, we hypothesized that local synchrony would differ between between primary and association cortices. In female SD rats (N = 12), we recorded 40 Hz click train-elicited gamma oscillations using epidural electrodes situated at two distinct sites; one above the prefrontal cortex (PFC) and another above the Actx, after dosing with saline (1 ml/kg, sc) or the NMDA antagonist, MK801 (0.025, 0.05 or 0.1 mpk), in a blocked crossover design. Post-saline, both regions showed a strong 40 Hz auditory steady state response (ASSR). The latencies for the N1 response were ∼ 16 ms (Actx) and ∼ 34 ms (PFC). Narrow band (38-42 Hz) gamma oscillations appeared rapidly (<40 ms from stim onset at Actx but in a more delayed fashion (∼200 ms) at PFC. MK801 augmented gamma synchrony at Actx while dose-dependently disrupting at the PFC. Event-related gamma (but not beta) coherence, an index of long-distance connectivity, was disrupted by MK801. In conclusion, local network gamma synchrony in a higher order association cortex performs differently from that of the primary auditory cortex. We discuss these findings in the context of evolving sound processing across the cortical hierarchy.

It is known that Temporal Information Processing (TIP) underpins our cognitive functioning. Previous research has focused on the relationship between TIP efficiency and oscillatory brain activity, especially the gamma rhythm; however, non-oscillatory (aperiodic or 1/f) brain activity has often been missed. Recent studies have identified the 1/f component as being important for the functioning of the brain. Therefore, the current study aimed to verify whether TIP efficiency is associated with specific EEG resting state cortical activity patterns, including oscillatory and non-oscillatory (aperiodic) brain activities. To measure individual TIP efficiency, we used two behavioral tasks in which the participant judges the order of two sounds separated by millisecond intervals. Based on the above procedure, participants were classified into two groups with high and low TIP efficiency. Using cluster-based permutation analyses, we examined between-group differences in oscillatory and non-oscillatory (aperiodic) components across the 1-90 Hz range. The results revealed that the groups differed in the aperiodic component across the 30-80 Hz range in fronto-central topography. In other words, participants with low TIP efficiency exhibited higher levels of aperiodic activity, and thus a flatter frequency spectrum compared to those with high TIP efficiency. We conclude that participants with low TIP efficiency display higher levels of \'neural noise\', which is associated with poorer quality and speed of neural processing.