Frontocingulate-parietal-limbic circuits associated with both ruminative brooding and self-regulatory processes

Background: Subjective cognitive impairments are frequent, but poorly understood in patients with chronic fatigue. We hypothesized that maladaptive metacognitive beliefs at baseline were associated with baseline subjective cognitive impairments, that they predict subjective cognitive impairments at treatment termination, and that a reduction in maladaptive metacognitive beliefs was associated with less subjective cognitive impairments at treatment termination, independent of changes in fatigue, pain, insomnia, depression, and anxiety.Methods: In this non-controlled study, patients (n = 137) on sick leave due to chronic fatigue received a 3.5-week inpatient RTW rehabilitation program. Of these patients 69 (50.4%) was referred with a ICPC-2 diagnosis of chronic fatigue. Patients completed questionnaires about metacognitive beliefs, somatic complaints, psychological complaints, and cognitive impairments before and after treatment. To test the hypotheses we performed paired t-tests of change, as well as seven hierarchical linear regressions.Results: Results showed that baseline maladaptive metacognitive beliefs were significantly associated with subjective cognitive impairments at baseline, controlling for symptoms. Score on baseline metacognitive beliefs did not predict impairments post-treatment. Testing specific maladaptive beliefs, pre-treatment scores on cognitive confidence were associated with subjective cognitive impairments both pre and post-treatment, controlling for symptoms. Post-treatment metacognitive beliefs and post-treatment cognitive confidence were associated with post-treatment subjective cognitive impairments, controlling for pre-treatment impairments and pre-treatment metacognitive beliefs, as well as pre and post-scores on symptom measures.Conclusion: This study reports associations between maladaptive metacognitive beliefs and subjective cognitive impairments in patients with chronic fatigue. Targeting metacognitive beliefs could prove an effective therapeutic intervention for subjective cognitive impairments in these patients.

Epilepsy is a chronic brain disease with dysfunctional brain networks, and electroencephalography (EEG) is an important tool for epileptogenic zone (EZ) identification, with rich information about frequencies. Different frequency oscillations have different contributions to brain function, and cross-frequency coupling (CFC) has been found to exist within brain regions. Cross-channel and inter-channel analysis should be both focused because they help to analyze how epilepsy networks change and also localize the EZ. In this paper, we analyzed long-term stereo-electroencephalography (SEEG) data from 17 patients with temporal lobe epilepsy. Single-channel and cross-channel CFC features were combined to establish functional brain networks, and the network characteristics under different periods and the localization of EZ were analyzed. It was observed that theta–gamma phase amplitude coupling (PAC) within the electrodes in the seizure region increased during the ictal (p < 0.05). Theta–gamma and delta–gamma PAC of cross-channel were enhanced in the early and mid-late ictal, respectively. It was also found that there was a strong cross-frequency coupling state between channels of EZ in the functional network during the ictal, along with a more regular network than interictal. The accuracy rate of EZ localization was 82.4%. Overall, the combination of single-channel and multi-channel cross-band coupling analysis can help identify seizures and localize EZ for temporal lobe epilepsy. Rhythmic coupling reveals a relationship between the functional network and the seizure status of epilepsy.

Fronto-subthalamic phase synchronization and cross-frequency coupling during conflict processing

Early adolescent psychological distress and cognition, correlates of resting-state EEG, interregional phase-amplitude coupling.

Subjective cognitive decline exhibits alterations of resting-state phase-amplitude coupling in precuneus

An increasing number of studies pays attention to cross-frequency coupling in neuronal oscillations network, as it is considered to play an important role in exchanging and integrating of information. In this study, two generalized algorithms, phase-amplitude coupling-evolution map approach and phase-amplitude coupling-conditional mutual information which have been developed and applied originally in an identical rhythm, are generalized to measure cross-frequency coupling. The effectiveness of quantitatively distinguishing the changes of coupling strength from the measurement of phase-amplitude coupling (PAC) is demonstrated based on simulation data. The data suggest that the generalized algorithms are able to effectively evaluate the strength of PAC, which are consistent with those traditional approaches, such as PAC-PLV and PAC-MI. Experimental data, which are local field potentials obtained from anaesthetized SD rats, have also been analyzed by these two generalized approaches. The data show that the theta-low gamma PAC in the hippocampal CA3-CA1 network is significantly decreased in the glioma group compared to that in the control group. The results, obtained from either simulation data or real experimental signals, are consistent with that of those traditional approaches PAC-MI and PAC-PLV. It may be considered as a proper indicator for the cross frequency coupling in sub-network, such as the hippocampal CA3 and CA1.

This study aimed to determine whether patients with disorders of consciousness (DoC) could experience neural entrainment to individualized music, which explored the cross-modal influences of music on patients with DoC through phase-amplitude coupling (PAC). Furthermore, the study assessed the efficacy of individualized music or preferred music (PM) versus relaxing music (RM) in impacting patient outcomes, and examined the role of cross-modal influences in determining these outcomes. Thirty-two patients with DoC [17 with vegetative state/unresponsive wakefulness syndrome (VS/UWS) and 15 with minimally conscious state (MCS)], alongside 16 healthy controls (HCs), were recruited for this study. Neural activities in the frontal-parietal network were recorded using scalp electroencephalography (EEG) during baseline (BL), RM and PM. Cerebral-acoustic coherence (CACoh) was explored to investigate participants' abilitiy to track music, meanwhile, the phase-amplitude coupling (PAC) was utilized to evaluate the cross-modal influences of music. Three months post-intervention, the outcomes of patients with DoC were followed up using the Coma Recovery Scale-Revised (CRS-R). HCs and patients with MCS showed higher CACoh compared to VS/UWS patients within musical pulse frequency (p = 0.016, p = 0.045; p < 0.001, p = 0.048, for RM and PM, respectively, following Bonferroni correction). Only theta-gamma PAC demonstrated a significant interaction effect between groups and music conditions (F (2,44) = 2.685, p = 0.036). For HCs, the theta-gamma PAC in the frontal-parietal network was stronger in the PM condition compared to the RM (p = 0.016) and BL condition (p < 0.001). For patients with MCS, the theta-gamma PAC was stronger in the PM than in the BL (p = 0.040), while no difference was observed among the three music conditions in patients with VS/UWS. Additionally, we found that MCS patients who showed improved outcomes after 3 months exhibited evident neural responses to preferred music (p = 0.019). Furthermore, the ratio of theta-gamma coupling changes in PM relative to BL could predict clinical outcomes in MCS patients (r = 0.992, p < 0.001). Individualized music may serve as a potential therapeutic method for patients with DoC through cross-modal influences, which rely on enhanced theta-gamma PAC within the consciousness-related network.

The phantom sound of tinnitus can be an extremely debilitating condition. The thalamocortical dysrhythmia (TCD) hypothesis is a feature of subjective tinnitus; however, its consistency in characterizing different types of tinnitus remains unclear. We compared theta-beta/gamma coupling in multichannel EEG recordings from subjects with bothersome tinnitus (BT), non-bothersome tinnitus (NBT), and healthy controls (HC). Additionally, we used these EEG features to distinguish BT from NBT by employing the k-nearest neighbor (KNN) model. Theta-beta/gamma phase-amplitude coupling (PAC) was enhanced in the auditory cortex of both BT and NBT groups compared to HC. In contrast, theta-beta/gamma PAC was specifically enhanced in the cingulate gyrus and parahippocampal gyrus in the BT group. Notably, theta-gamma PAC in the orbitofrontal cortex was attenuated in the BT group and showed a negative correlation with their THI scores. By integrating theta-beta/gamma PAC into a machine learning algorithm, up to 92% of BT patients were accurately identified. TCD in BT patients was characterized by enhanced theta-beta/gamma PAC in the auditory cortex, cingulate gyrus, and parahippocampal gyrus and attenuated theta-gamma PAC in the orbitofrontal cortex. The latter was significantly negatively correlated with THI scores. These PAC features, which could objectively distinguish BT patients by machine learning, may support the specificity of PAC features in tinnitus characterization.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem, and spinal cord. Despite decades of research, ALS remains incurable, challenging to diagnose, and of extremely rapid progression. A unifying feature of sporadic and familial forms of ALS is cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, and is sufficient to trigger neurodegeneration in rodents. Using electrocorticography in the Sod1G86R and FusΔNLS/+ ALS mouse models and standard electroencephalography recordings in patients with sporadic ALS, we demonstrate a deficit in theta-gamma phase-amplitude coupling (PAC) in ALS. In mice, PAC deficits started before symptom onset, and in patients, PAC deficits correlated with the rate of disease progression. Using mass spectrometry analyses of CNS neuropeptides, we identified a presymptomatic reduction of noradrenaline (NA) in the motor cortex of ALS mouse models, further validated by in vivo two-photon imaging in behaving SOD1G93A and FusΔNLS/+ mice, that revealed pronounced reduction of locomotion-associated NA release. NA deficits were also detected in postmortem tissues from patients with ALS, along with transcriptomic alterations of noradrenergic signaling pathways. Pharmacological ablation of noradrenergic neurons with DSP-4 reduced theta-gamma PAC in wild-type mice and administration of a synthetic precursor of NA augmented theta-gamma PAC in ALS mice. Our findings suggest theta-gamma PAC as means to assess and monitor cortical dysfunction in ALS and warrant further investigation of the NA system as a potential therapeutic target.

Differential phase-amplitude coupling in nucleus accumbens and orbitofrontal cortex reflects decision-making during a delay discounting task

Increased theta-low gamma phase-amplitude coupling in resting electroencephalography after intermittent theta burst stimulation

ObjectiveResting-state EEG (rsEEG) provides insights into neural mechanisms underlying memory by reflecting intrinsic brain activity. This study tested whether rsEEG spectral power and theta-gamma phase-amplitude coupling (PAC) can predict memory performance in healthy adults.MethodsTwenty-four healthy adults participated in two rsEEG recording sessions, followed by memory tests assessing multimodal Working Memory (WM), Immediate Recall (IR), and Delayed Recall (DR). The predictive value of rsEEG spectral power across frequency bands and theta-gamma PAC was analyzed in relation to memory performance.ResultsHigh-gamma (h-γ, 51–100 Hz) power significantly predicted IR and DR, accounting for over 43% of the variance. Temporal and frontal h-γ power positively correlated with memory performance, while posterior h-γ power showed a negative correlation. Temporal low-gamma (30–49 Hz) power positively predicted DR, and posterior and frontal theta power was significantly linked to IR. Other frequency bands showed marginal associations, and theta-gamma PAC had limited predictive value.ConclusionsSpontaneous gamma activity emerged as a key predictor of memory performance in healthy adults, highlighting the role of brain networks in encoding and retrieval processes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11571-025-10313-2.

Working memory (WM) is the active retention and processing of information over a few seconds and is considered an essential component of cognitive function. The reduced WM capacity is a common feature in many diseases, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), mild cognitive impairment (MCI), and Alzheimer's disease (AD). The theta-gamma neural code is an essential component of memory representations in the multi-item WM. A large body of studies have examined the association between cross-frequency coupling (CFC) across the cerebral cortices and WM performance; electrophysiological data together with the behavioral results showed the associations between CFC and WM performance. The oscillatory entrainment (sensory, non-invasive electrical/magnetic, and invasive electrical) remains the key method to investigate the causal relationship between CFC and WM. The frequency-tuned non-invasive brain stimulation is a promising way to improve WM performance in healthy and non-healthy patients with cognitive impairment. The WM performance is sensitive to the phase and rhythm of externally applied stimulations. CFC-transcranial-alternating current stimulation (CFC-tACS) is a recent approach in neuroscience that could alter cognitive outcomes. The studies that investigated (1) the association between CFC and WM and (2) the brain stimulation protocols that enhanced WM through modulating CFC by the means of the non-invasive brain stimulation techniques have been included in this review. In principle, this review can guide the researchers to identify the most prominent form of CFC associated with WM processing (e.g., theta/gamma phase-amplitude coupling), and to define the previously published studies that manipulate endogenous CFC externally to improve WM. This in turn will pave the path for future studies aimed at investigating the CFC-tACS effect on WM. The CFC-tACS protocols need to be thoroughly studied before they can be considered as therapeutic tools in patients with WM deficits.

Background: Autism is predominantly idiopathic, while many syndromic forms have also been identified. Fragile X Syndrome (FXS) is the most common syndromic form of autism and intellectual disability. No effective approaches currently exist for reducing the negative impact of autism or FXS symptoms, and drug development has suffered many failures in clinical trials, which were based on promising preclinical findings. Thus, effective translational biomarkers that bridge animal and human studies are urgently needed. Both autism and FXS are developmentally dynamic and sexually dimorphic regarding prevalence, clinical presentations and neural mechanisms. Recently, electroencephalography (EEG) has been proposed as a low-cost translational biomarker in neurodevelopmental conditions. However, there is still a dearth of EEG research in autism, especially in research using animal models. Hypothesis: EEG profiles in mouse models of idiopathic and syndromic autism vary depending on sex, age, and genetic background. Methods: We compared the BTBR model of idiopathic autism with the control B6 mice, as well as the fmr1 knockout model of FXS and syndromic autism with the control wildtype mice. A custom-made stand-alone Open-Source Electrophysiology Recording system for Rodents (OSERR) was used for EEG recording. Results: We found absolute EEG power in the beta and gamma frequency bands was increased in juvenile male BTBR mice, while relative theta power was increased and relative alpha power decreased. In the FXS model on a FVB genetic background, we confirmed previous findings of an increase in the absolute gamma power in the male mice. Detailed analysis in the females indicated that in both juvenile and adult animals, increases in the alpha and beta power were present besides an increase in the gamma power, compared with age-matched wildtype controls. Additionally, both wildtype and FXS model had increased absolute and relative gamma power in adult females compared with juvenile females. Furthermore, we analyzed phase-amplitude cross frequency coupling between gamma frequency (30–100 Hz) and theta-alpha frequency (4–12 Hz), to quantify the modulation of gamma oscillation amplitude by the phase of the theta-alpha frequency. Our results indicated that this phase-amplitude coupling was increased in the female FXS model, similar to the findings in the FXS patients. Additionally, both wildtype and FXS model had increased coupling in adult females compared with juvenile females. We also recorded EEG in the female FXS model on a B6 genetic background and observed that relative EEG power was deceased in alpha frequency but increased in gamma frequency, while phase-amplitude coupling was similar, compared with wildtype controls. Lastly, we observed that these EEG phenotypes were stable when recorded in different arenas, including home cage, open field arena, and light-dark arena, for all female groups tested. Discussion and Conclusion: Together, our findings revealed a consistent and robust increase in the gamma power in mouse models of both idiopathic and syndromic autism, and this includes female FXS models. In addition, we identified changes in the EEG signal that depended on sex, developmental stage, and genetic background. Collectively, our findings support further investigation of EEG signal as translational biomarkers in neurodevelopmental conditions, while factors including sex, developmental stage, and genetic background should be incorporated into the design and interpretation of such studies. University of Calgary Veterinary Medicine, Alberta Children's Hospital Research Foundation, FRAXA Research Foundation, NSERC of Canada, CIHR of Canada, Alberta Student Aid This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Objectives: Maladaptive beliefs about emotions (e.g., believing emotions are uncontrollable or useless) are theorised to contribute to emotion regulation difficulties and psychological distress. Despite growing interest, limited research has examined maladaptive emotion beliefs in clinical populations. This study investigated the psychometric properties and latent profiles of the Emotion Beliefs Questionnaire (EBQ) in a clinical sample. Methods: A sample of 385 adults undergoing psychotherapy completed the EBQ alongside measures of emotion regulation difficulties (Perth Emotion Regulation Competency Inventory) and psychological distress (Depression, Anxiety, Stress Scale-21). Results: Confirmatory factor analyses supported a three-factor model distinguishing beliefs about emotional controllability and the usefulness of positive and negative emotions. The EBQ demonstrated strong internal consistency and convergent and incremental validity. Latent Profile Analysis identified six distinct profiles of emotion beliefs, which were differentially associated with emotion regulation difficulties and psychological distress. Notably, the two profiles characterised by the highest levels of maladaptive emotion beliefs had the highest levels of emotion regulation difficulties and psychological distress. Conclusions: These findings underscore the heterogeneity of emotion belief patterns in clinical populations and highlight the importance of assessing belief combinations rather than isolated dimensions, which can help with more personalised therapeutic interventions. This study contributes to a more nuanced understanding of emotion beliefs in psychopathology and supports the use of the EBQ as a psychometrically sound tool with clinical samples.