Resting-state EEG correlates of sustained attention in healthy ageing: Cross-sectional findings from the LEISURE study.

While structural and biochemical brain changes are well-documented in ageing, functional neuronal network differences, as indicated by electrophysiological markers, are less clear. Moreover, age-related changes in sustained attention and their associated electrophysiological correlates are still poorly understood. To address this, we analysed cross-sectional baseline electroencephalography (EEG) and cognitive data from the Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE). Participants were 96 healthy older adults, aged 50-84. We examined resting-state EEG periodic (individual alpha frequency [IAF], aperiodic-adjusted individual alpha power [aIAP]) and aperiodic (exponent and offset) activity, and their associations with age and sustained attention. Results showed associations between older age and slower IAF, but not aIAP or global aperiodic exponent and offset. Additionally, hierarchical linear regression revealed that after controlling for demographic variables, faster IAF was associated with better Sustained Attention to Response Task performance, and mediation analysis confirmed IAF as a mediator between age and sustained attention performance. These findings indicate that IAF may be an important marker of ageing, and a slower IAF may signal diminished cognitive processing capacity for sustained attention in older adults.

Structural brain correlates of sustained attention in healthy ageing: Cross-sectional findings from the LEISURE study.

Sustained attention is important for maintaining cognitive function and autonomy during ageing, yet older people often show reductions in this domain. The role of the underlying neurobiology is not yet well understood, with most neuroimaging studies primarily focused on fMRI. Here, we utilise sMRI to investigate the relationships between age, structural brain volumes and sustained attention performance. Eighty-nine healthy older adults (50-84 years, Mage 65.5 (SD=8.4) years, 74 f) underwent MRI brain scanning and completed two sustained attention tasks: a rapid visual information processing (RVP) task and sustained attention to response task (SART). Independent hierarchical linear regressions demonstrated that greater volumes of white matter hyperintensities (WMH) were associated with worse RVP_A' performance, whereas greater grey matter volumes were associated with better RVP_A' performance. Further, greater cerebral white matter volumes were associated with better SART_d' performance. Importantly, mediation analyses revealed that both grey and white matter volumes completely mediated the relationship between ageing and sustained attention. These results explain disparate attentional findings in older adults, highlighting the intervening role of brain structure.

Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.

The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning.

Chronotype and subjective sleep quality predict white matter integrity in young people with emerging mental disorders.

Protecting brain health is a goal of early intervention. We explored whether sleep quality or chronotype could predict white matter (WM) integrity in emerging mental disorders. Young people (N = 364) accessing early-intervention clinics underwent assessments for chronotype, subjective sleep quality, and diffusion tensor imaging. Using machine learning, we examined whether chronotype or sleep quality (alongside diagnostic and demographic factors) could predict four measures of WM integrity: fractional anisotropy (FA), and radial, axial, and mean diffusivities (RD, AD and MD). We prioritised tracts that showed a univariate association with sleep quality or chronotype and considered predictors identified by ≥80% of machine learning (ML) models as 'important'. The most important predictors of WM integrity were demographics (age, sex and education) and diagnosis (depressive and bipolar disorders). Subjective sleep quality only predicted FA in the perihippocampal cingulum tract, whereas chronotype had limited predictive importance for WM integrity. To further examine links with mood disorders, we conducted a subgroup analysis. In youth with depressive and bipolar disorders, chronotype emerged as an important (often top-ranking) feature, predicting FA in the cingulum (cingulate gyrus), AD in the anterior corona radiata and genu of the corpus callosum, and RD in the corona radiata, anterior corona radiata, and genu of corpus callosum. Subjective quality was not important in this subgroup analysis. In summary, chronotype predicted altered WM integrity in the corona radiata and corpus callosum, whereas subjective sleep quality had a less significant role, suggesting that circadian factors may play a more prominent role in WM integrity in emerging mood disorders.

Functional MRI of the Brainstem for Assessing Its Autonomic Functions: From Imaging Parameters and Analysis to Functional Atlas.

BACKGROUND: The brainstem is a crucial component of the central autonomic nervous (CAN) system. Functional MRI (fMRI) of the brainstem remains challenging due to a range of factors, including diverse imaging protocols, analysis, and interpretation. PURPOSE: To develop an fMRI protocol for establishing a functional atlas in the brainstem. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Ten healthy subjects (four males, six females). FIELD STRENGTH/SEQUENCE: Using a 3.0 Tesla MR scanner, we acquired T1-weighted images and three different fMRI scans using fMRI protocols of the optimized functional Imaging of Brainstem (FIBS), the Human Connectome Project (HCP), and the Adolescent Brain Cognitive Development (ABCD) project. ASSESSMENT: The temporal signal-to-noise-ratio (TSNR) of fMRI data was compared between the FIBS, HCP, and ABCD protocols. Additionally, the main normalization algorithms (i.e., FSL-FNIRT, SPM-DARTEL, and ANTS-SyN) were compared to identify the best approach to normalize brainstem data using root-mean-square (RMS) error computed based on manually defined reference points. Finally, a functional autonomic brainstem atlas that maps brainstem regions involved in the CAN system was defined using meta-analysis and data-driven approaches. STATISTICAL TESTS: ANOVA was used to compare the performance of different imaging and preprocessing pipelines with multiple comparison corrections (P ≤ 0.05). Dice coefficient estimated ROI overlap, with 50% overlap between ROIs identified in each approach considered significant. RESULTS: The optimized FIBS protocol showed significantly higher brainstem TSNR than the HCP and ABCD protocols (P ≤ 0.05). Furthermore, FSL-FNIRT RMS error (2.1 ± 1.22 mm; P ≤ 0.001) exceeded SPM (1.5 ± 0.75 mm; P ≤ 0.01) and ANTs (1.1 ± 0.54 mm). Finally, a set of 12 final brainstem ROIs with dice coefficient ≥0.50, as a step toward the development of a functional brainstem atlas. DATA CONCLUSION: The FIBS protocol yielded more robust brainstem CAN results and outperformed both the HCP and ABCD protocols. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

A short-interval longitudinal study of associations between psychological distress and hippocampal grey matter in early adolescence.

This study of Australian adolescents (N = 88, 12-13-years-old) investigated the relationship between hippocampal grey matter volume (GMV) and self-reported psychological distress (K10) at four timepoints, across 12 months. Participants were divided into two groups; those who had K10 scores between 10 and 15 for all four timepoints were categorised as "low distress" (i.e., control group; n = 38), while participants who had K10 scores of 16 or higher at least once over the year were categorised as "moderate-high distress" (n = 50). Associations were tested by GEE fitting of GMV and K10 measures at the same time point, and in the preceding and subsequent timepoints. Analyses revealed smaller preceding left GMV and larger preceding right GMV were associated with higher subsequent K10 scores in the "moderate-high distress" group. This was not observed in the control group. In contrast, the control group showed significant co-occurring associations (i.e., at the same TP) between GMV and K10 scores. The "moderate-high distress" group experienced greater variability in distress. These results suggest that GMV development in early adolescence is differently associated with psychological distress for those who experience "moderate-high distress" at some point over the year, compared to controls. These findings offer a novel way to utilise short-interval, multiple time-point longitudinal data to explore changes in volume and experience of psychological distress in early adolescents. The results suggest hippocampal volume in early adolescence may be linked to fluctuations in psychological distress.

Hippocampal subfield volumes predict treatment response to oral ketamine in people with suicidality.

Ongoing stress results in hippocampal neuro-structural alterations which produce pathological consequences, including depression and suicidality. Ketamine may ameliorate stress related illnesses, including suicidality, via neuroplasticity processes. This novel study sought to determine whether oral ketamine treatment specifically affects hippocampal (whole and subfield) volumes in patients with chronic suicidality and MDD. It was hypothesised that oral ketamine treatment would differentially alter hippocampal volumes in trial participants categorised as ketamine responders, versus those who were non-responders. Twenty-eight participants received 6 single, weekly doses of oral ketamine (0.5-3 mg/kg) and underwent MRI scans at pre-ketamine (week 0), post-ketamine (week 6), and follow up (week 10). Hippocampal subfield volumes were extracted using the longitudinal pipeline in FreeSurfer. Participants were grouped according to ketamine response status and then compared in terms of grey matter volume (GMV) changes, among 10 hippocampal regions, over 6 and 10 weeks. Mixed ANOVAs were used to analyse interactions between time and group. Post treatment analysis revealed a significant main effect of group for three left hippocampal GMVs as well in the left and right whole hippocampus. Ketamine acute responders (Week 6) showed increased GMVs in both left and right whole hippocampus and in three subfields compared to acute non-responders, across all three timepoints, suggesting that pre-treatment increased hippocampal GMVs (particularly left hemisphere) may be predictive biomarkers of acute treatment response. Future studies should further investigate the potential of hippocampal volumes as a biomarker of ketamine treatment response.

REducing Sleep Apnoea for the PrEvention of Dementia (REShAPED): Protocol for a multi-site feasibility randomised controlled trial.

There is accumulating evidence that has linked OSA with increased risk of cognitive decline and dementia. Here we present the protocol for an Australian, multi-site randomised controlled, parallel open-label trial which will evaluate the feasibility for a full-scale trial investigating the effects of treating OSA on cognitive decline in older adults at risk of dementia within memory clinic settings. We will randomise 180 older adults to either the treatment intervention group or control group for 2 years. Inclusion criteria include: 50-85 years; mild-severe OSA (defined average ODI ≥ 10 with 3% oxygen desaturation determined by wrist oximetry over two nights); and subjective cognitive complaints or mild cognitive impairment. The treatment intervention arm aims to achieve an optimal treatment response based on reducing hypoxic burden with either CPAP, mandibular advancement splint, positional therapy, or oxygen therapy. Furthermore, participants will receive up to 8 sessions which involve motivational interviewing, collaborative goal setting, and behavioural sleep management. The control arm will not receive OSA treatment as part of this trial, however there will be no OSA treatment restrictions, and any treatment will be documented. Primary outcomes are 1) acceptability based upon willingness of participants to be randomised; 2) alleviating hypoxic burden by reducing OSA severity; 3) tolerability of the trial burden based upon collection of outcomes over the 2-year follow-up. Secondary outcomes include safety and cognitive function. Outcomes will be collected at 0, 6 and 24-months. This feasibility study aims to will provide the basis for a larger longer-term trial of dementia prevention.

The Study of Ketamine for Youth Depression (SKY-D): study protocol for a randomised controlled trial of low-dose ketamine for young people with major depressive disorder.

BACKGROUND: Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD). METHODS: SKY-D is a double-masked, randomised controlled trial funded by the Australian Government's National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes. DISCUSSION: Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513 .

Oral ketamine may offer a solution to the ketamine conundrum.

Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative. Emerging evidence regarding the efficacy and tolerability of oral ketamine suggests that it may be a favourable route of administration, as it appears to obtain similarly beneficial treatment effects, but without the cost and medical resources required in parenteral dosing. The pharmacological effects may be due to the active metabolite norketamine, which has been found to be at substantially higher levels via oral dosing, most likely due to first-pass clearance. Despite bioavailability and peak plasma concentrations both being lower than when administered parenterally, evidence suggests that low-dose oral ketamine is clinically effective in treating pain. This may also be due to the actions of norketamine and therefore, its relevance to the mental health context is explored in this narrative review.

clusterBMA: Bayesian model averaging for clustering.

Various methods have been developed to combine inference across multiple sets of results for unsupervised clustering, within the ensemble clustering literature. The approach of reporting results from one 'best' model out of several candidate clustering models generally ignores the uncertainty that arises from model selection, and results in inferences that are sensitive to the particular model and parameters chosen. Bayesian model averaging (BMA) is a popular approach for combining results across multiple models that offers some attractive benefits in this setting, including probabilistic interpretation of the combined cluster structure and quantification of model-based uncertainty. In this work we introduce clusterBMA, a method that enables weighted model averaging across results from multiple unsupervised clustering algorithms. We use clustering internal validation criteria to develop an approximation of the posterior model probability, used for weighting the results from each model. From a combined posterior similarity matrix representing a weighted average of the clustering solutions across models, we apply symmetric simplex matrix factorisation to calculate final probabilistic cluster allocations. In addition to outperforming other ensemble clustering methods on simulated data, clusterBMA offers unique features including probabilistic allocation to averaged clusters, combining allocation probabilities from 'hard' and 'soft' clustering algorithms, and measuring model-based uncertainty in averaged cluster allocation. This method is implemented in an accompanying R package of the same name. We use simulated datasets to explore the ability of the proposed technique to identify robust integrated clusters with varying levels of separation between subgroups, and with varying numbers of clusters between models. Benchmarking accuracy against four other ensemble methods previously demonstrated to be highly effective in the literature, clusterBMA matches or exceeds the performance of competing approaches under various conditions of dimensionality and cluster separation. clusterBMA substantially outperformed other ensemble methods for high dimensional simulated data with low cluster separation, with 1.16 to 7.12 times better performance as measured by the Adjusted Rand Index. We also explore the performance of this approach through a case study that aims to identify probabilistic clusters of individuals based on electroencephalography (EEG) data. In applied settings for clustering individuals based on health data, the features of probabilistic allocation and measurement of model-based uncertainty in averaged clusters are useful for clinical relevance and statistical communication.

Excitatory and inhibitory neurometabolites in anorexia nervosa: A systematic review of proton magnetic resonance spectroscopy studies.

The dysregulation of excitatory and inhibitory neurotransmission is considered a pathological marker of Anorexia Nervosa (AN), however, no systematic evaluation of the proton Magnetic Resonance Spectroscopy (1H-MRS) literature has been conducted to date. Accordingly, we conducted a systematic review of neurometabolite differences between individuals with AN and healthy controls (HC). A comprehensive database search (until June 2023) identified seven studies meeting inclusion criteria. Samples included adolescents and adults with similar mean age (AN: 22.20 HC: 22.60), and female percentages (AN: 98%; HC: 94%). The review found a considerable need for improving study design and the reporting of MRS sequence parameters and analysis. Reduced glutamate concentrations in the ACC and OCC, and reduced Glx concentrations in the ACC were reported by one and two studies, respectively. Lastly, only one study to date has quantified GABA concentrations, with no significant differences found. In conclusion, there is currently insufficient evidence of excitatory and inhibitory neurometabolites changes in AN. As the 1H-MRS literature in AN increases, the key questions herein proposed must be revisited.

The LEISURE Study: A Longitudinal Randomized Controlled Trial Protocol for a Multi-Modal Lifestyle Intervention Study to Reduce Dementia Risk in Healthy Older Adults.

Dementia is understood to arise from a mixed etiology, enveloping chronic inflammatory and vascular impacts on the brain, driven by a constellation of modifiable risk factors which are largely mediated by lifestyle-related behaviors. These risk factors manifest over a prolonged preclinical period and account for up to 40% of the population attributable risk for dementia, representing viable targets for early interventions aimed at abating disease onset and progression. Here we outline the protocol for a 12-week randomized control trial (RCT) of a multimodal Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE), with longitudinal follow-up at 6-months and 24-months post-intervention. This trial integrates exercise, diet, sleep, and mindfulness to simultaneously target multiple different etiopathogenetic mechanisms and their interplay in a healthy older adult population (aged 50-85 years), and assesses dementia risk reduction as the primary endpoint. The LEISURE study is located in the Sunshine Coast region of Australia, which has one of the nation's highest proportions of adults aged over 50 years (36.4%), and corresponding dementia prevalence. This trial is novel in its inclusion of mindfulness and sleep as multidomain lifestyle targets, and in its comprehensive suite of secondary outcomes (based on psychological, physical health, sleep activity, and cognitive data) as well as exploratory neuroimaging (magnetic resonance imaging and electroencephalography) and molecular biology measures. These measures will provide greater insights into the brain-behavioral underpinnings of dementia prevention, as well as the predictors and impacts of the proposed lifestyle intervention. The LEISURE study was prospectively registered (ACTRN12620000054910) on 19 January 2020.

Insights into the neurobiology of suicidality: explicating the role of glutamatergic systems through the lens of ketamine.

Suicidality is a prevalent mental health condition, and managing suicidal patients is one of the most challenging tasks for health care professionals due to the lack of rapid-acting, effective psychopharmacological treatment options. According to the literature, suicide has neurobiological underpinnings that are not fully understood, and current treatments for suicidal tendencies have considerable limitations. To treat suicidality and prevent suicide, new treatments are required; to achieve this, the neurobiological processes underlying suicidal behavior must be thoroughly investigated. Although multiple neurotransmitter systems, particularly serotonergic systems, have been studied in the past, less has been reported in relation to disruptions in glutamatergic neurotransmission, neuronal plasticity, and neurogenesis that result from stress-related abnormalities of the hypothalamic-pituitary-adrenal system. Informed by the literature, which reports robust antisuicidal and antidepressive properties of subanaesthetic doses of ketamine, this review aims to provide an examination of the neurobiology of suicidality (and relevant mood disorders) with implications of pertinent animal, clinical, and postmortem studies. We discuss dysfunctions in the glutamatergic system, which may play a role in the neuropathology of suicidality and the role of ketamine in restoring synaptic connectivity at the molecular levels.

Precision Medicine for Brain Disorders: New and Emerging Approaches.

The brain is the most complex organ in the human body, making it susceptible to many abnormalities [...].

Self-reported Fatigue was Associated with Increased White-matter Alterations in Long-term Traumatic Brain Injury and Posttraumatic Stress Disorder Patients.

Fatigue is a long-lasting problem in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), with limited research that investigated the fatigue-related white-matter changes within TBI and/or PTSD cohorts. This exploratory cross-sectional study used diffusion tensor imaging (DTI) and neuropsychological data collected from 153 male Vietnam War veterans, as part of the Alzheimer's Disease Neuroimaging Initiative - Department of Defense, and were divided clinically into control veterans, PTSD, TBI, and with both TBI and PTSD (TBI + PTSD). The existence of fatigue was defined by the question "Do you often feel tired, fatigued, or sleepy during the daytime?". DTI data were compared between fatigue and non-fatigue subgroups in each clinical group using tract-based spatial statistics voxel-based differences. Fatigue was reported in controls (29.55%), slightly higher in TBI (52.17%, PBenf = 0.06), and significantly higher in both TBI + PTSD (66.67%, PBenf = 0.001) and PTSD groups (79.25%, PBenf < 0.001). Compared to non-fatigued subgroups, no white-matter differences were observed in the fatigued subgroups of control or TBI, while the fatigued PTSD subgroup only showed increased diffusivity measures (i.e., radial and axial), and the fatigued TBI + PTSD subgroup showed decreased fractional anisotropy and increased diffusivity measures (PFWE ≤ 0.05). The results act as preliminary findings suggesting fatigue to be significantly reported in TBI + PTSD and PTSD decades post-trauma with a possible link to white-matter microstructural differences in both PTSD and TBI + PTSD. Future studies with larger cohorts and detailed fatigue assessments would be required to identify the white-matter changes associated with fatigue in these cohorts.

Longitudinal associations between resting-state, interregional theta-beta phase-amplitude coupling, psychological distress, and wellbeing in 12-15-year-old adolescents.

Cross-frequency coupling between the phase of slower oscillatory activity and the amplitude of faster oscillatory activity in the brain (phase-amplitude coupling; PAC), is a promising new biological marker for mental health. Prior research has demonstrated that PAC is associated with mental health. However, most research has focused on within-region theta-gamma PAC in adults. Our recent preliminary study found increased theta-beta PAC was associated with increased psychological distress in 12 year olds. It is important to investigate how PAC biomarkers relate to mental health and wellbeing in youth. Thus, in this study, we investigated longitudinal associations between interregional (posterior-anterior cortex) resting-state theta-beta PAC (Modulation Index [MI]), psychological distress and wellbeing in N = 99 adolescents (aged 12-15 years). In the right hemisphere, there was a significant relationship, whereby increased psychological distress was associated with decreased theta-beta PAC and psychological distress increased with increased age. In the left hemisphere, there was a significant relationship, whereby decreased wellbeing was associated with decreased theta-beta PAC and wellbeing scores decreased with increased age. This study presents novel findings demonstrating longitudinal relationships between interregional, resting-state theta-beta PAC and mental health and wellbeing in early adolescents. This EEG marker may facilitate improved early identification of emerging psychopathology.

Novel ketamine and zinc treatment for anorexia nervosa and the potential beneficial interactions with the gut microbiome.

Anorexia nervosa (AN) is a severe illness with diverse aetiological and maintaining contributors including neurobiological, metabolic, psychological, and social determining factors. In addition to nutritional recovery, multiple psychological and pharmacological therapies and brain-based stimulations have been explored; however, existing treatments have limited efficacy. This paper outlines a neurobiological model of glutamatergic and γ-aminobutyric acid (GABA)-ergic dysfunction, exacerbated by chronic gut microbiome dysbiosis and zinc depletion at a brain and gut level. The gut microbiome is established early in development, and early exposure to stress and adversity contribute to gut microbial disturbance in AN, early dysregulation to glutamatergic and GABAergic networks, interoceptive impairment, and inhibited caloric harvest from food (e.g., zinc malabsorption, competition for zinc ions between gut bacteria and host). Zinc is a key part of glutamatergic and GABAergic networks, and also affects leptin and gut microbial function; systems dysregulated in AN. Low doses of ketamine in conjunction with zinc, could provide an efficacious combination to act on NMDA receptors and normalise glutamatergic, GABAergic and gut function in AN.

Objective sleep measures in chronic fatigue syndrome patients: A systematic review and meta-analysis.

Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report disrupted and unrefreshing sleep in association with worsened fatigue symptoms. However, the nature and magnitude of sleep architecture alteration in ME/CFS is not known, with studies using objective sleep measures in ME/CFS generating contradictory results. The current manuscript aimed to review and meta-analyse of case-control studies with objective sleep measures in ME/CSF. A search was conducted in PubMed, Scopus, Medline, Google Scholar, and Psychoinfo databases. After review, 24 studies were included in the meta-analysis, including 20 studies with 801 adults (ME/CFS = 426; controls = 375), and 4 studies with 477 adolescents (ME/CFS = 242; controls = 235), who underwent objective measurement of sleep. Adult ME/CFS patients spend longer time in bed, longer sleep onset latency, longer awake time after sleep onset, reduced sleep efficiency, decreased stage 2 sleep, more Stage 3, and longer rapid eye movement sleep latency. However, adolescent ME/CFS patients had longer time in bed, longer total sleep time, longer sleep onset latency, and reduced sleep efficiency. The meta-analysis results demonstrate that sleep is altered in ME/CFS, with changes seeming to differ between adolescent and adults, and suggesting sympathetic and parasympathetic nervous system alterations in ME/CFS.