Abstract Early-life stress (ELS), such as parental neglect or abuse, predisposes an individual to develop mental disorders. Disease hallmarks include heightened amygdala reactivity and impaired prefrontal cortex-amygdala functional interactions, already during childhood and adolescence. However, which cellular and circuit mechanisms underlie these hallmarks, as well as the altered developmental trajectory of prefrontal-amygdala networks, is poorly understood. Here we performed simultaneous in vivo local-field potential and multi-unit recordings under light urethane anaesthesia in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) of male and female pre-juvenile or adolescent mice, exposed to a resource scarcity model of ELS. We find a developmentally transient low-theta (3-5 Hz) oscillatory hypercoupling within mPFC-BLA networks in pre-juvenile ELS males which seems to result from a precocious development of coupling strength after ELS. In the mPFC, neuronal spiking activity was decreased in pre-juvenile males and the local theta entrainment of spike firing disrupted. In BLA, both sexes showed an increase in firing activity in a subpopulation of neurons after ELS, also confirmed by an increase in ΔFosB-positive neurons in BLA, which we identified to be non-GABAergic. Directed interactions, i.e. the ability to entrain spike firing in mPFC to the theta rhythm in BLA and vice versa, were also impaired predominantly in pre-juvenile males after ELS, while females showed a milder phenotype. These early sex-dependent impairments in the functional development of prefrontal-amygdala circuits may promote aberrant development of emotional behaviours after ELS and may predispose to a disease phenotype later on.

Impact of mobile phone use on the brain activity: Audio call vs video call.

Binding multisensory information into episodic memory depends partly on the timing of the hippocampal theta rhythm which provides time windows for synaptic modification. In humans, theta rhythmic sensory stimulation (RSS) enhances episodic memory when the stimuli are synchronised across the visual and auditory domain compared to when they are out-of-synchrony. However, recent studies show mixed evidence if the improvement in episodic memory is the result of modulating hippocampal theta activity. In the current study, we investigated whether pre-stimulus brain state could explain part of this variance in the neural and behavioural effects induced by the RSS, via recording 24 participants' brain activity with MEG during a multisensory theta RSS memory paradigm. Our findings suggest that pre-stimulus alpha power modulates entrainment strength in sensory regions, which in turn predicts subsequent memory formation. These findings suggest that for non-invasive brain stimulation tools to be effective it is crucial to consider brain-state dependent effects.

The theta rhythm synchronizes neural activity in the processes of attention and memory. However, the mechanisms of synchronization of neural activity during theta rhythm generation are not known. We propose a mathematical model explaining the distribution of the CA1 field neurons over the theta rhythm phase. We examined a network consisting of 10 types of inhibitory cells: (PV) parvalbumin and (CCK) cholecystokinin basket cells, axo-axonal, bistratified, neurogliaform, perforant path-associated, interneuronal-specific (subtypes R-O and RO-O), Ivy and OLM neurons. The network received four excitatory inputs from the CA3 field, the medial entorhinal cortex, and two types of local pyramidal neurons of the CA1 field. We have shown that it is possible to fit the parameters of connections in the model that neurons form experimentally observed phase relationships relative to the theta rhythm. For most types of neurons, excitatory inputs add up and give a maximum near the peak of discharges in the theta cycle. The peak of inhibitory inputs falls on the opposite phase of the theta rhythm, due to this, activity slows down from the opposite phase of the theta rhythm. The model steadily reproduces the phase relations over the entire frequency range of the theta rhythm for most types of interneurons.

The medial septum modulates hippocampal oscillations, including ripples, which are critical for memory consolidation. While the role of the medial septum in theta rhythms is well-established, its specific contribution to hippocampal ripple activity remains poorly understood. This study sought to investigate the relationship between medial septal activity and hippocampal ripples in vivo. This study aimed to characterize the in-vivo membrane potential dynamics of putative medial septal neuron subtypes and their contribution to hippocampal ripples in awake mice. We performed in-vivo whole-cell patch-clamp recordings from medial septal neurons in head-fixed, awake mice, while simultaneously acquiring hippocampal local field potentials. Medial septal neurons were classified into glutamatergic, cholinergic, and GABAergic subtypes using hierarchical clustering based on their intrinsic electrophysiological properties. We analyzed the firing rates and subthreshold membrane potential dynamics of these neurons during hippocampal ripple events and examined their correlations with ripple parameters (duration, frequency, and power). Our results revealed subtype-specific responses. Notably, putative glutamatergic neurons exhibited a slight decrease in firing rate, yet displayed a pronounced depolarization of their membrane potential approximately 100 ms before ripple onset, peaking at the initiation of ripples. This depolarization was inversely correlated with subsequent ripple amplitude and power. In addition, membrane hyperpolarization was positively correlated with ripple duration. These findings elucidate the contribution of glutamatergic medial septal neurons to hippocampal ripple dynamics and suggest a tightly regulated interaction between the medial septum and hippocampus in shaping ripple activity.

Prior EEG research has shown that during working memory, alpha (8 to 14 Hz) and theta (4 to 8 Hz) oscillations tend to form a 2:1 frequency ratio. According to the Binary Hierarchy Brain Body Oscillation Theory (BHBBOT), a recent model grounded in mathematical analysis, this cross-frequency configuration reflects enhanced connectivity between brain regions generating these rhythms. However, this prediction has not yet been empirically tested. In this study, we leveraged high density EEG, source localization and connectivity metrics derived from Information Theory (IT) and the Theory of Weakly Coupled Oscillators (TWCO) to examine whether the previously observed alpha-theta cross-frequency dynamics during working memory are accompanied by changes in connectivity. Our results show that a significant increase in the proportion of 2:1 ratios between regions generating frontal theta and parietal alpha rhythms was accompanied by relative decreases in connectivity, as revealed by both IT and TWCO metrics. Furthermore, phase synchrony between these two regions was significantly reduced during working memory and correlated negatively with behavioral performance. In conclusion, our results show that the increased occurrence of 2:1 alpha:theta cross-frequency ratios during working memory reflects functional segregation (rather than integration) and therefore directly challenges some of the predictions of the BHBBOT.

Now you recall it, now you don't: Working memory performance fluctuates with a theta rhythm.

The enjoyment of music involves a complex interplay between brain perceptual areas and the reward network. While previous studies have shown that musical liking is related to an enhancement of synchronization between the right temporal and frontal brain regions via theta frequency band oscillations, the underlying mechanisms of this interaction remain elusive. Specifically, a causal relationship between theta oscillations and musical pleasure has yet to be shown. In the present study, we address this question by using transcranial alternating current stimulation (tACS). Twenty-four participants underwent three different sessions where they received tACS over the right auditory cortex before listening to and rating a set of melodies selected to vary in familiarity and complexity. In the target session, participants received theta stimulation, while in the other two sessions, they received beta and sham stimulation, serving as controls. We recorded brain activity using EEG during task performance to confirm the effects of tACS on oscillatory activity. Results revealed that compared with sham, theta, but not beta, stimulation resulted in higher liking ratings specifically for unfamiliar music with low complexity. In addition, we found increased theta connectivity between the right temporal and frontal electrodes for these stimuli when they were most liked after theta stimulation but not after beta stimulation. These findings support a causal and frequency-specific relationship between music hedonic judgments and theta oscillatory mechanisms that synchronize the right temporal and frontal areas. These mechanisms play a crucial role in different cognitive processes supported by frontotemporal loops, such as auditory working memory and predictive processing, which are fundamental to music reward processing.

Objective: To investigate the characteristics of theta rhythm functional connectivity and their clinical implications in patients with Meniere's disease. Methods: A cross-sectional study was conducted. Patients diagnosed with Meniere's disease along with matched healthy controlsat the Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital between August 2020 and January 2024 were enrolled. Phase-locking value (PLV) was used to calculate theta-band functional connectivity between brain regions in source space. Intergroup differences of the functional connectivity were compared, and its correlations with clinical characteristics were analyzed. Results: The study included 32 Meniere's disease patients (9 males and 23 female) with a mean age of (54.8±11.9) years, along with 29 healthy controls (7 males and 22 females) with a mean age of (56.7±14.5) years. Compared with the healthy controls, Meniere's disease patients exhibited enhanced theta functional connectivity within a network centered on the paracentral lobule and cingulate gyrus (all P<0.05). This enhanced connectivity between the medial/paracingulate gyri and the paracentral lobule positively correlated with the severity of subjective symptoms (r=0.355, P=0.046) and scores on the anxiety-autonomic symptom subscale (r=0.402, P=0.023). However, no statistically significant correlation was found with hearing levels or dynamic posturography scores (all P>0.05). Conclusions: Patients with Meniere's disease demonstrate enhanced theta rhythm functional connectivity involving the paracentral lobule and cingulate gyrus. This neural signature is dissociated from hearing loss and overall balance performance but is linked to subjective anxiety and autonomic symptoms.

BackgroundHealthy aging and cognitive decline in Alzheimer's Disease (AD) and its precursor, Mild Cognitive Impairment (MCI), are linked to changes in resting‐state EEG power spectral density (PSD). Theta band (3‐7 Hz) power decreases with normal aging but increases with cognitive decline. However, frequency content does not always indicate true oscillatory activity. Oscillations reflect power concentration at a specific frequency, appearing as peaks in the frequency domain and visible rhythms in the time domain. Rhythmicity analysis quantifies oscillation persistence (percentage of time observed) independently of power. This study examined Theta power and Theta rhythms in healthy controls (HC) versus individuals with MCI/AD.MethodParticipants included 32 AD, 88 MCI, and 115 and age‐ matched HC, who completed 5‐minutes of resting‐state eyes‐closed EEG at their baseline visit. PSD was computed for one‐second epochs. Relative Theta power was defined as the proportion of total power in the Theta band, averaging across epochs. Theta rhythm duration was defined as the percentage of epochs with Theta oscillations. Baseline differences and longitudinal changes were analyzed for a subset of participants: 28 MCI and 5 AD with at least one follow‐up visit, and 25 HC with at least two follow‐ups.ResultAt baseline, the MCI/AD group exhibited significantly higher relative Theta power (p <0.01, df=233, ES=0.35 at T6) and a greater Theta rhythm duration (p <0.01, df=231, ES=0.41 at T6) compared to HC. Longitudinally, HC exhibited a significant reduction in Theta power by the second follow‐up (p <0.05, df=24, ES=0.51 at Cz), with no significant changes in Theta rhythms duration. In contrast, MCI/AD showed a significant increase in Theta rhythm duration (and not power) at first follow‐up visit (p < 0.05, df =32, ES=0.30 at T3).ConclusionTheta power and Theta rhythm duration are both linked to cognitive decline in MCI and AD but differ from healthy aging patterns. While Theta power reflects age‐related changes, Theta rhythms duration may serve as a specific biomarker for disease progression in MCI and AD. These findings support the value of Rhythmicity analysis in EEG‐based biomarkers of cognitive decline.

The cannabinoid 1-receptor (CB1R) is found in particularly high levels in the hippocampus (HPC). Increased CB1R density and binding are observed in patients with schizophrenia, and epidemiological studies suggest that regular cannabis use during adolescence is a risk factor for the disease. CB1R was shown to interfere with neuronal network oscillations and to impair sensory gating and memory function. Neuronal oscillations are essential in multiple cognitive functions, and their impairment was documented in neurological and psychiatric diseases. The aim of this study was to investigate how adolescent pre-treatment with the CB1R-selective agonist CP-55940 may lead to abnormalities in theta synchronization in adulthood. Rats were pre-treated with CP-55940 or vehicle during adolescence (daily injections in PND 32–36 or PND 42–46). They were then tested in adulthood (PND over 70) under urethane anesthesia. Hippocampal theta rhythm was elicited by brainstem stimulation at five intensity levels 1 hour before and up to 5 h after injection. We found a significant decrease in elicited theta power after CP-55940 in adult rats, which was aggravated further in rats pre-treated in adolescence with the CB1R agonist. The effect was significantly larger in rats pre-treated during early adolescence (PND 32–36) compared to the group pre-treated during late adolescence (PND 42–46). We conclude that (1) exposure to cannabis during adolescence leads to increased sensitivity to CB1R agonist in adulthood, and (2) early adolescence, a critical period for development of HPC networks generating theta rhythms, is particularly prone to this sensitivity.

Background: Cognitive impairment in older adults is commonly associated with increased slow-wave EEG activity and reduced alpha–beta activity. Ginkgo biloba extract (EGb 761®) has been reported to exert neuroprotective, vasomodulatory and neurotransmission-enhancing effects. Objective: To evaluate the effects of 30-day supplementation with Ginkgo biloba (240 mg/day) on neuropsychological performance and EEG spectral activity in older adults with cognitive impairment. Methods: A pre-experimental repeated-measures design was applied. Five participants (50–70 years old) with MMSE scores 14–24 and no depression were included. Neuropsychological assessment was conducted using the Barcelona Test (TB-r), and EEG recordings were obtained at baseline, day 1, day 15 and day 30. Spectral bands (delta, theta, alpha, beta) and cognitive domain performance were analyzed. Results: Cognitive improvement was significant in attention, naming, categorical evocation, delayed verbal memory and visual memory. EEG showed initial predominance of slow activity, with progressive normalization. At day 15, delta and theta waves decreased while alpha–beta increased. By day 30, alpha–beta activity increased by nearly 50%, with reduction of pathological slow-wave activity across all regions. Conclusions: Thirty-day supplementation with Ginkgo biloba (240 mg/day) improved cognitive performance and shifted EEG activity toward a more functional alpha–beta profile, suggesting modulation of neuroelectrical activity in older adults with cognitive impairment.

Anxiety represents a prevalent yet under-recognised, non-motor manifestation of Parkinson's disease (PD), affecting approximately one-third of patients globally while remaining substantially underdiagnosed, with detection rates of only 50%. This comprehensive review synthesises current evidence on anxiety in PD, emphasising regional Indian data and emerging therapeutic interventions. Epidemiological studies reveal marked geographical disparities, with Indian prevalence ranging from 14.1 per 100,000 in rural Kashmir to 328.3 per 100,000 in Mumbai, and projections indicating 2.8 million cases by 2050. The pathophysiology involves progressive degeneration of dopaminergic, noradrenergic, and serotonergic circuits within frontal-basal ganglia networks, with early raphe nucleus and locus coeruleus involvement often preceding motor symptoms. Electrophysiological investigations demonstrate significant correlations between theta wave activity (4-8 Hertz [Hz]) in basal ganglia structures and anxiety severity, providing novel therapeutic targets. Current assessment relies on gold-standard instruments including the Movement Disorder Society-unified Parkinson's disease rating scale (MDS-UPDRS) and Parkinson's anxiety scale (PAS), though systematic screening remains inadequately implemented. Therapeutic approaches encompass selective serotonin reuptake inhibitors as first-line pharmacological agents, cognitive behavioural therapy, and lifestyle modifications, though PD-specific evidence remains limited. Emerging adaptive deep brain stimulation technologies represent a paradigmatic shift toward precision neuromodulation, utilising closed-loop systems that monitor anxiety-specific neural oscillations and adjust stimulation parameters in real-time. Future directions include large-scale epidemiological investigations, biomarker development, culturally sensitive treatment approaches, and integrated care models combining neurological, psychiatric, and rehabilitation services. This review emphasises the urgent need for improved recognition and evidence-based management while highlighting the transformative potential of precision medicine approaches incorporating genetic profiling and artificial intelligence-driven optimisation.

Place field dynamics in retrosplenial cortex compared to hippocampus.

Background/Objectives: Excessive smartphone use may negatively affect cognitive functions, including attention. While sensorimotor rhythm, beta, and theta waves have been linked to concentration, the electroencephalography (EEG) frequency band that most reliably serves as a neurophysiological marker of concentration is unclear. Therefore, we aimed to evaluate the effects of glucose tablet candy ingestion on attention following smartphone use in healthy adults. Methods: A randomized, double-blind, placebo-controlled crossover trial was conducted in 16 healthy adults aged 18–39 years. Participants performed a 30 min smartphone-based information search task. Attention was assessed before and after the task using the Cognitrax test battery, and participants ingested either a glucose tablet candy (containing 26 g of glucose) or a placebo (no glucose) between tests. EEG was performed during attention tests using a patch-type device. Subjective sensations, including attention, fatigue, and mental clarity (clear-headedness), were evaluated using a visual analog scale (VAS). The primary outcome was attention test scores, and secondary outcomes included EEG power and VAS ratings. Results: Glucose tablet candy ingestion after smartphone use significantly improved mean correct response time and error response scores in part 2 of the four-part continuous performance test, a subtest within Cognitrax, compared to that with the placebo. Additionally, glucose intake significantly attenuated the decrease in right prefrontal beta EEG power observed with the placebo. Improvements were also observed in self-reported physical fatigue and mental clarity on the VAS following glucose ingestion. Conclusions: The ingestion of the glucose (26 g) tablet candy improved sustained attention after smartphone use in healthy adults aged 18–39 years and was associated with changes in brain activity. These results suggest that the glucose tablet candy may help counteract the decline in concentration following cognitively demanding smartphone use.

ABSTRACTHippocampal theta and gamma rhythms are often viewed as discrete channels supporting distinct cognitive operations. In particular, “gamma multiplexing” models propose that slow and fast gamma bands independently encode separate information streams or memory processes. Here, we present an alternative view: hippocampal oscillations form an interdependent process, governed by an energy cascade akin to turbulent flow across scales. In this framework, large‐amplitude, low‐frequency rhythms drive energy transfer to higher‐frequency oscillations, rather than acting as isolated carriers of segregated information. Using laminar local field potential recordings in freely moving mice, we show that optogenetic inactivation of the medial entorhinal cortex or CA1 reduces theta power, leading to proportional reductions across the entire gamma spectrum (60–100 Hz). These data support the perspective that the putative ‘slow gamma’ component (30–50 Hz) potentially reflects higher‐order theta harmonics rather than a distinct, independent rhythm. Moreover, locally generated gamma remains tightly coupled to theta, supporting an interdependent frequency spectrum modulated by network excitation. These findings challenge gamma multiplexing models and instead support an energy cascade framework, in which hippocampal gamma emerges from hierarchical, theta‐driven oscillatory dynamics. Recognizing gamma as part of an interdependent, turbulence‐like process reconciles contradictions in prior research and redefines how hippocampal oscillations contribute to cognition.

IntroductionPost-stroke spasticity affects 25%−40% of survivors, causing pain and functional impairment. Current non-invasive treatments target either central or peripheral pathways alone. This neglects the critical imbalance between spastic agonists and antagonists. We designed this protocol to address this gap through dual-site peripheral theta-burst stimulation.MethodsThis single-center, three-arm, sham-controlled, single-blind randomized controlled trial enrolled 54 stroke survivors (aged 40–80, 3–12 months post-stroke, Modified Ashworth Scale score ≥1). Participants were randomized in a 1:1:1 ratio to receive a 10-session intervention over 2 weeks (5 days/week). Each session consisted of stimulation followed by 30 min of conventional physical therapy. The stimulation protocols were: Group 1: active iTBS over extensor carpi radialis longus + sham cTBS over flexor carpi radialis; Group 2: sham iTBS + active cTBS; Group 3: active iTBS + active cTBS. Stimulation was delivered using a MagTD stimulator at 110%−120% of the peripheral motor threshold (mean 38.4% maximum stimulator output), with 600 pulses per session (50 Hz burst frequency, 5 Hz theta rhythm).Anticipated resultsWe hypothesize that Group 3 (combined stimulation) will yield the greatest reduction in spasticity (MAS decrease ≥ 1) and the most significant improvements in upper-limb function (FMA-UE, ARAT) compared to Groups 1 and 2. These clinical gains are expected to correlate with neurophysiological changes (MEP amplitude, cortical silent period), supporting the central-peripheral synergy model.DiscussionThis protocol tests a novel dual-site pTBS paradigm. Positive findings would provide preliminary evidence for network-based rehabilitation. This could inform larger trials and potentially transform post-stroke spasticity management.

Ibogalogs improve spatial and recognition memory in rodents through a mechanism involving 5-HT2A receptor activation-enhanced NMDA receptor activity in hippocampal pyramidal CA1 neurons.

Top-down regulation of subcortical regions by hippocampal long-range inhibition.

This article aims to analyse the issue of human expertise in line with the assumptions of anthropo- centric linguistics of specialist languages. The first chapter is dedicated to knowledge generation, based on the results of neurobiological research. Biophysiologically, neural activation takes the form of so-called neural oscillations. As a result of mutual modulation of brain waves – gamma waves are usually modulated by theta waves (theta-gamma nesting) - an oscillation pattern (nesting) specific to information processing at the phoneme and syllable level is created. The nesting of oscillatory pattern for phonemic and syllabic processes allows us to assume how cognitive load is reduced in the process of text production. The process of nesting/mutual modulation of neural oscillations corresponds by structural analogy to linguistic models that mirror the actual stages of text understanding and text production. Mutual relations between phonemic (non-semantic) and grammatical (semantic) interpretation of language expressions, emerging in the process of text un- derstanding/ production to create meaning, reflect mutual relations between neural oscillations, which results in the effect of nesting. In both cases, the emergence of these relations can be described with regard to the mechanism of selective pressure.