Neurobiological Substrates Research Articles

The hierarchical taxonomy of psychopathology and the search for neurobiological substrates of mental illness: A systematic review and roadmap for future research.

Understanding the neurobiological mechanisms involved in psychopathology has been hindered by the limitations of categorical nosologies. The Hierarchical Taxonomy of Psychopathology (HiTOP) is an alternative dimensional system for characterizing psychopathology, derived from quantitative studies of covariation among diagnoses and symptoms. HiTOP provides more promising targets for clinical neuroscience than traditional psychiatric diagnoses and can facilitate cumulative integration of existing research. We systematically reviewed 164 human neuroimaging studies with sample sizes of 194 or greater that have investigated dimensions of psychopathology classified within HiTOP. Replicated results were identified for constructs at five different levels of the hierarchy, including the overarching p-factor, the externalizing superspectrum, the thought disorder and internalizing spectra, the distress subfactor, and the depression symptom dimension. Our review highlights the potential of dimensional clinical neuroscience research and the usefulness of HiTOP while also suggesting limitations of existing work in this relatively young field. We discuss how HiTOP can be integrated synergistically with neuroscience-oriented, transdiagnostic frameworks developed by the National Institutes of Health, including the Research Domain Criteria, Addictions Neuroclinical Assessment, and the National Institute on Drug Abuse's Phenotyping Assessment Battery, and how researchers can use HiTOP to accelerate clinical neuroscience research in humans and other species. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Uncovering neural substrates across Alzheimer's disease stages using contrastive variational autoencoder.

Alzheimer's disease is the most common major neurocognitive disorder. Although currently, no cure exists, understanding the neurobiological substrate underlying Alzheimer's disease progression will facilitate early diagnosis and treatment, slow disease progression, and improve prognosis. In this study, we aimed to understand the morphological changes underlying Alzheimer's disease progression using structural magnetic resonance imaging data from cognitively normal individuals, individuals with mild cognitive impairment, and Alzheimer's disease via a contrastive variational autoencoder model. We used contrastive variational autoencoder to generate synthetic data to boost the downstream classification performance. Due to the ability to parse out the nonclinical factors such as age and gender, contrastive variational autoencoder facilitated a purer comparison between different Alzheimer's disease stages to identify the pathological changes specific to Alzheimer's disease progression. We showed that brain morphological changes across Alzheimer's disease stages were significantly associated with individuals' neurofilament light chain concentration, a potential biomarker for Alzheimer's disease, highlighting the biological plausibility of our results.

Differential gene expression and chromatin accessibility in the medial prefrontal cortex associated with individual differences in rat behavioral models of opioid use disorder.

Opioid use disorder (OUD) is a neuropsychological disease that has a devastating impact on public health. Substantial individual differences in vulnerability exist, the neurobiological substrates of which remain unclear. To address this question, we investigated genome-wide gene transcription (RNA-seq) and chromatin accessibility (ATAC-seq) in the medial prefrontal cortex (mPFC) of male and female rats exhibiting differential vulnerability in behavioral paradigms modeling different phases of OUD: Withdrawal-Induced Anhedonia (WIA), Demand, and Reinstatement. Ingenuity Pathway Analysis (IPA) of RNA-seq revealed greater changes in canonical pathways in Resilient (vs. Saline) rats in comparison to Vulnerable (vs. Saline) rats across 3 paradigms, suggesting brain adaptations that might contribute to resilience to OUD across its trajectory. Analyses of gene networks and upstream regulators implicated processes involved in oligodendrocyte maturation and myelination in WIA, neuroinflammation in Demand, and metabolism in Reinstatement. Motif analysis of ATAC-seq showed changes in chromatin accessibility to a small set of transcription factor (TF) binding sites as a function either of opioid exposure (i.e., morphine versus saline) generally or of individual vulnerability specifically. Some of these were shared across the 3 paradigms and others were unique to each. In conclusion, we have identified changes in biological pathways, TFs, and their binding motifs that vary with paradigm and OUD vulnerability. These findings point to the involvement of distinct transcriptional and epigenetic mechanisms in response to opioid exposure, vulnerability to OUD, and different stages of the disorder.

A longitudinal MRI analysis reveals altered brain connectivity and microstructural changes in a transgenic mouse model of Alzheimer's disease

Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuropathological changes, yet the underlying neurobiological mechanisms remain elusive. Here, we employed a multimodal longitudinal neuroimaging approach, using anatomical and functional sequences on a high field magnetic resonance imaging (MRI) preclinical scanner, to investigate alterations in brain connectivity and white matter microstructure in a transgenic mouse model of AD (J20) when compared to wild-type (WT) littermates. Functional connectivity analysis revealed distinct network disruptions in J20 mice, primarily involving connections between posterior and anterior brain regions; importantly, a significant interaction between group and age highlighted an exacerbation of these connectivity changes with advancing age in J20 mice. In addition, significant reductions in fractional anisotropy (FA) were observed in the corpus callosum of J20 mice compared to WT, indicative of microstructural alterations consistent with white matter pathology. The observed alterations in brain connectivity and microstructure provide valuable insights into the spatiotemporal processes underlying AD-related decline and underscore the utility of multimodal neuroimaging in elucidating the neurobiological substrates of AD pathology in animal models.

Serotonin drives aggression and social behaviors of laboratory male mice in a semi-natural environment.

Aggression is an adaptive social behavior crucial for the stability and prosperity of social groups. When uncontrolled, aggression leads to pathological violence that disrupts group structure and individual wellbeing. The comorbidity of uncontrolled aggression across different psychopathologies makes it a potential endophenotype of mental disorders with the same neurobiological substrates. Serotonin plays a critical role in regulating impulsive and aggressive behaviors. Mice lacking in brain serotonin, due to the ablation of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in serotonin synthesis, could serve as a potential model for studying pathological aggression. Home cage monitoring allows for the continuous observation and quantification of social and non-social behaviors in group-housed, freely-moving mice. Using an ethological approach, we investigated the impact of central serotonin ablation on the everyday expression of social and non-social behaviors and their correlations in undisturbed, group-living Tph2-deficient and wildtype mice. By training a machine learning algorithm on behavioral time series, "allogrooming", "struggling at feeder", and "eating" emerged as key behaviors dissociating one genotype from the other. Although Tph2-deficient mice exhibited characteristics of pathological aggression and reduced communication compared to wildtype animals, they still demonstrated affiliative huddle behaviors to normal levels. Altogether, such a distinct and dynamic phenotype of Tph2-deficient mice influenced the group's structure and the subsequent development of its hierarchical organization. These aspects were analyzed using social network analysis and the Glicko rating methods. This study demonstrates the importance of the ethological approach for understanding the global impact of pathological aggression on various aspects of life, both at the individual and group levels. Home cage monitoring allows the observation of the natural behaviors of mice in a semi-natural habitat, providing an accurate representation of real-world phenomena and pathological mechanisms. The results of this study provide insights into the neurobiological substrate of pathological aggression and its potential role in complex brain disorders.

Subtyping drug-free first-episode major depressive disorder based on cortical surface area alterations

BackgroundMajor depressive disorder (MDD) is recognized as a complex and heterogeneous metal illness, characterized by diverse clinical symptoms and variable treatment outcomes. Previous studies have repeatedly reported alterations in brain morphology in MDD, but findings vary across sample characteristics. Whether this neurobiological substrate could stratify MDD into more homogeneous clinical subgroups thus improving personalized medicine remains unknown. MethodsWe included 65 drug-free patients with first-episode MDD and 66 healthy controls (HCs) and collected their structural MRI data. We performed the surface reconstruction and calculated cortical surface area using Freesurfer. The surface area of 34 Gy matter regions in each hemisphere based on the Desikan-Killiany atlas were extracted for each participant and subtyping results were obtained with the Louvain community detection algorithm. The demographic and clinical characteristics were then compared between MDD subgroups. ResultsTwo subgroups defined by distinct patterns of cortical surface area were identified in first-episode MDD. Subgroup 1 exhibited a significant reduction in surface area across nearly the entire cortex compared to subgroup 2 and HCs, whereas subgroup 2 demonstrated increased surface area than HCs. Further, subgroup 1 exhibited a higher proportion of females, and higher severity of anxiety symptoms compared to subgroup 2. LimitationsThe relatively small sample size. ConclusionsThis study identified two neurobiologically subgroups with distinct alterations in cortical surface area among drug-free patients with first-episode MDD. Our results highlight the promise of in delineating morphological heterogeneity within MDD, particularly in relation to the severity of anxiety symptoms.

Visual hallucinations in Parkinson's disease: spotlight on central cholinergic dysfunction.

Visual hallucinations are a common non-motor feature of Parkinson's disease and have been associated with accelerated cognitive decline, increased mortality and early institutionalisation. Despite their prevalence and negative impact on patient outcomes, the repertoire of treatments aimed at addressing this troubling symptom is limited. Over the last two decades, significant contributions have been made in uncovering the pathological and functional mechanisms of visual hallucinations, bringing us closer to the development of a comprehensive neurobiological framework. Convergent evidence now suggests that degeneration within the central cholinergic system may play a significant role in the genesis and progression of visual hallucinations. Here, we outline how cholinergic dysfunction may serve as a potential unifying neurobiological substrate underlying the multifactorial and dynamic nature of visual hallucinations. Drawing upon previous theoretical models, we explore the impact that alterations in cholinergic neurotransmission has on the core cognitive processes pertinent to abnormal perceptual experiences. We conclude by highlighting that a deeper understanding of cholinergic neurobiology and individual pathophysiology may help to improve established and emerging treatment strategies for the management of visual hallucinations and psychotic symptoms in Parkinson's disease.

A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease

A combination of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) at non-psychoactive doses was previously demonstrated to reduce cognitive decline in APP/PS1 mice, an animal model of Alzheimer's disease (AD). However, the neurobiological substrates underlying these therapeutic properties of Δ9-THC and CBD are not fully understood. Considering that dysregulation of glutamatergic activity contributes to cognitive impairment in AD, the present study evaluates the hypothesis that the combination of these two natural cannabinoids might reverse the alterations in glutamate dynamics within the hippocampus of this animal model of AD. Interestingly, our findings reveal that chronic treatment with Δ9-THC and CBD, but not with any of them alone, reduces extracellular glutamate levels and the basal excitability of the hippocampus in APP/PS1 mice. These effects are not related to significant changes in the function and structure of glutamate synapses, as no relevant changes in synaptic plasticity, glutamate signaling or in the levels of key components of these synapses were observed in cannabinoid-treated mice. Our data instead indicate that these cannabinoid effects are associated with the control of glutamate uptake and/or to the regulation of the hippocampal network. Taken together, these results support the potential therapeutic properties of combining these natural cannabinoids against the excitotoxicity that occurs in AD brains.

Unraveling the Boundaries, Overlaps, and Connections between Schizophrenia and Obsessive-Compulsive Disorder (OCD).

Schizophrenia (SCZ) and obsessive-compulsive disorder (OCD) typically have distinct diagnostic criteria and treatment approaches. SCZ is characterized by delusions, hallucinations, disorganized speech, and cognitive impairments, while OCD involves persistent, intrusive thoughts (obsessions) and repetitive behaviors (compulsions). The co-occurrence of these disorders increases clinical complexity and poses significant challenges for diagnosis and treatment. Epidemiological studies indicate a significant overlap, with prevalence rates of comorbid OCD in SCZ patients ranging from 12% to 25%, which is higher than in the general population. Etiological hypotheses suggest shared genetic, neurobiological, and environmental factors, with genetic studies identifying common loci and pathways, such as glutamatergic and dopaminergic systems. Neuroimaging studies reveal both overlapping and distinct neural abnormalities, indicating shared and unique neurobiological substrates. Environmental factors, like early life stressors and urbanicity, also contribute to the comorbidity. The overlapping clinical features of both disorders complicate diagnosis. Treatment approaches include combining SSRIs with antipsychotics and cognitive behavioral therapy (CBT). The complexity of SCZ and OCD comorbidity underscores the need for a dimensional, spectrum-based perspective on psychiatric disorders, alongside traditional categorical approaches, to improve diagnosis and treatment outcomes.

Early protein restriction in rats induces anhedonia in adult offspring: A key role of BDNF-TrkB signaling in the nucleus accumbens shell

Clinical evidence suggests that early malnutrition promotes symptoms related to psychiatric disorders later in life. Nevertheless, the molecular mechanisms underpinning nutritional injury induce depression remains unknown. The purpose of the present study was to evaluate whether perinatal protein restriction increases vulnerability to developing depressive-like behavior in adulthood by focusing on anhedonia, a core symptom of depression. To this, male adult Wistar rats submitted to a protein restriction schedule at perinatal age (PR-rats), were subjected to the sucrose preference test (SPT), the novel object recognition test (NORT), the forced swim test (FST), and the elevated plus maze (EPM), and compared to animals fed with a normoprotein diet. To investigate neurobiological substrates linked to early protein undernutrition-facilitated depressive-like behavior, we assessed the levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the nucleus accumbens (NAc), and evaluated the reversal of anhedonic-like behavior by infusing ANA-12. We found that early malnutrition decreased sucrose preference, impaired performance in the NORT and increased immobility time in the FST. Furthermore, perinatal protein-restriction-induced anhedonia correlated with increased BDNF and p-TrkB protein levels in the NAc, a core structure in the reward circuit linked with anhedonia. Finally, bilateral infusion of the TrkB antagonist ANA-12 into the NAc shell ameliorated a reduced sucrose preference in the PR-rats.Altogether, these findings revealed that protein restriction during pregnancy and lactation facilitates depressive-like behavior later in life and may increase the risk of developing anhedonia by altering BDNF-TrkB in the NAc shell.

Hominin musical sound production: palaeoecological contexts and self domestication

In this article we seek to integrate theories of music origins and dance with hominin fossil anatomy and the paleoecological contexts of hominin evolution. Based on the association between rhythm in music, dance and locomotion, we propose that early bipedal hominins may have evolved neurobiological substrates different from other great apes due to the rhythmic aspects of bipedal walking and running. Combined with the emancipation of the hands resulting from erect posture, we propose that the neurobiological changes necessary for technological innovation, cultural practices and human musical abilities may have evolved, at least in incipient form, much earlier than previously thought. The consequent ability to synchronize movement and sound production may have also proved beneficial as early bipedal hominins ventured out of late Miocene and early Pliocene woodland and forested habitats and into more open habitats with increased predation risk. We also postulate that, along with bipedalism, paedomorphic morphogenesis of the skull at the base of the hominin clade was a necessary prerequisite for the evolution of vocal modulation and singing in later varieties of hominin. To date research into the evolution of music and dance has yet to be integrated with the fossil and paleoecological evidence of early hominin evolution. This paper seeks to fill this lacuna in the extant literature on human evolution. We also suggest that autocatalytic feedback loops evolving synergistically with hominin erect posture, skull and hand morphology, neurochemical processes and the self-domestication syndrome, have been operative from early hominins some 6 Ma to the present. We document this process by reference to primatological, ethnographic, neurochemical and archaeological data.

Children and Young Adults with Epilepsy Exhibit an Interictal Autonomic Dysfunction: A Prospective Exploratory Study.

Dysautonomic disorders are an increasingly studied group of conditions, either as isolated diseases or associated with other neurological disorders. There is growing interest in understanding how dysautonomia affects people with epilepsy, who may report autonomic symptoms before, during and after seizures. Furthermore, autonomic abnormalities appear to play a role in sudden unexpected death in epilepsy, likely contributing to the increased mortality rate described in epilepsy. To better understand the association between epilepsy and dysautonomia, we explored electrochemical skin conductance in a group of 18 children and young adults with epilepsy compared to 15 age- and sex-matched healthy controls by the SudoscanTM test. We found a significant difference in terms of electrochemical skin conductance, suggesting that people with epilepsy suffer significantly reduced conductance in small nerve fibers. Within patients, values were significantly different according to the type of epilepsy and to neuroimaging results, with lower conductance values in epilepsies of unknown origin and in patients with morphological abnormalities of the brain. Using a non-invasive test, we identified altered conductance of small sympathetic nerve fibers in children and young adults with epilepsy, suggesting underlying dysautonomia. Further studies are needed to investigate this association and to clarify its neurobiological substrates.

GPT-based normative models of brain sMRI correlate with dimensional psychopathology

Abstract Generative Pre-trained Transformer (GPT) models have been widely used for language tasks with surprising results. Furthermore, neuroimaging studies using deep generative normative modeling show promise in detecting brain abnormalities from brain structural MRI (sMRI). Meanwhile, psychiatric disorders are typically diagnosed through clinical assessment, which is particularly challenging in children and adolescents who present early symptoms or are in the early stages of the disease. Brain biomarkers research may contribute to the complex task of disentangling typical neurodevelopment from emergent psychiatric disorders. Here, we investigate whether a GPT-based normative architecture can detect psychiatric symptoms and disorders from brain sMRI of youths. The studied datasets contain measures of dimensional psychopathology: Brazilian High-Risk Cohort Study (BHRCS, n = 737) and Adolescent Brain Cognitive Development (ABCD, n = 11,031), and scores and diagnostic of psychiatric disorders: Attention Deficit Hyperactivity Disorder (ADHD-200, n = 922) and Autism Brain Imaging Data Exchange II (ABIDE-II, n = 580). We examined the associations of all brain regions with: the Child Behavior Checklist (CBCL) symptom groups, ADHD scores, and Autism Spectrum Disorder (ASD) diagnosis. Results showed the whole-brain typicality likelihood as correlated with social problems (ABCD test set) and ASD diagnosis (ABIDE-II dataset). Analysis by brain regions linked different areas to several CBCL scales, ADHD scores, and ASD diagnostic. This is the first successful study assessing all dimensional groups of CBCL symptoms, from all brain regions, based exclusively on sMRI. The normative models based on GPT are promising to investigate the gap between the phenotypes of psychiatric conditions and their neurobiological substrates.

Alzheimer’s-linked axonal changes accompany elevated antidromic action potential failure rate in aged mice

Alzheimer’s disease (AD) affects both grey and white matter (WM), but considerably more is known about the former. Interestingly, WM disruption has been consistently observed and thoroughly described using imaging modalities, particularly MRI which has shown WM functional disconnections between the hippocampus and other brain regions during AD pathogenesis when early neurodegeneration and synapse loss are also evident. Nonetheless, high-resolution structural and functional analyses of WM during AD pathogenesis remain scarce. Given the importance of the myelinated axons in the WM for conveying information across brain regions, such studies will provide valuable information on the cellular drivers and consequences of WM disruption that contribute to the characteristic cognitive decline of AD. Here, we employed a multi-scale approach to investigate hippocampal WM disruption during AD pathogenesis and determine whether hippocampal WM changes accompany the well-documented grey matter losses. Our data indicate that ultrastructural myelin disruption is elevated in the alveus in human AD cases and increases with age in 5xFAD mice. Unreliable action potential propagation and changes to sodium channel expression at the node of Ranvier co-emerged with this deterioration. These findings provide important insight to the neurobiological substrates and functional consequences of decreased WM integrity and are consistent with the notion that hippocampal disconnection contributes to cognitive changes in AD.

In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat

In addition to extracellular amyloid plaques, intracellular neurofibrillary tau tangles, and inflammation, cognitive and emotional affect perturbations are characteristic of Alzheimer's disease (AD). The cognitive and emotional domains impaired by AD include several forms of decision making (such as intertemporal choice), blunted motivation (increased apathy), and impaired executive function (such as working memory and cognitive flexibility). However, the interaction between these domains of the mind and their supporting neurobiological substrates at prodromal stages of AD, or whether these interactions can be predictive of AD severity (individual variability), remain unclear. In this study, we employed a battery of cognitive and emotional tests in the young adult (5–7 mo) transgenic Fisher-344 AD (TgF344-AD; TgAD) rat model of AD. We also assessed whether markers of inflammation or AD-like pathology in the prelimbic cortex (PrL) of the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), or nucleus accumbens (NAc), all structures that directly support the aforementioned behaviors, were predictive of behavioral deficits. We found TgAD rats displayed maladaptive decision making, greater apathy, and impaired working memory that was indeed predicted by AD-like pathology in the relevant brain structures, even at an early age. Moreover, we report that the BLA is an early epicenter of inflammation, and notably, AD-like pathology in the PrL, BLA, and NAc was predictive of BLA inflammation. These results suggest that operant-based battery testing may be sensitive enough to determine pathology trajectories, including neuroinflammation, from early stages of AD.

Role of microglia in stress-induced alcohol intake in female and male mice.

Rates of alcohol use disorder (AUD) have escalated in recent years, with a particular increase among women. Women are more susceptible to stress-induced alcohol drinking, and preclinical data suggest that stress can increase alcohol intake in female rodents; however, a comprehensive understanding of sex-specific neurobiological substrates underlying this phenomenon is still emerging. Microglia, the resident macrophages of the brain, are essential for reshaping neuronal processes, and microglial activity contributes to overall neuronal plasticity. We investigated microglial dynamics and morphology in limbic brain structures of male and female mice following exposure to stress, alcohol or both challenges. In a modified paradigm of intermittent binge drinking (repeated "drinking in the dark"), we determined that female, but not male, mice increased their alcohol consumption after exposure to a physical stressor and re-exposure trials in the stress-paired context. Ethanol (EtOH) drinking and stress altered a number of microglial parameters, including overall number, in subregions of the amygdala and hippocampus, with effects that were somewhat more pronounced in female mice. We used the CSF1R antagonist PLX3397 to deplete microglia in female mice to determine whether microglia contribute to stress-induced escalation of EtOH intake. We observed that microglial depletion attenuated stress-induced alcohol intake with no effect in the unstressed group. These findings suggest that microglial activity can contribute to alcohol intake under stressful conditions, and highlight the importance of evaluating sex-specific mechanisms that could result in tailored interventions for AUD in women.

Oscillation-Specific Nodal Differences in Parkinson's Disease Patients with Anxiety.

Parkinson's disease (PD) is a common neurodegenerative disorder that is predominantly known for its motor symptoms but is also accompanied by non-motor symptoms, including anxiety. The underlying neurobiological substrates and brain network changes associated with comorbid anxiety in PD require further exploration. An analysis of oscillation-specific nodal properties in patients with and without anxiety was conducted using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory. We used a band-pass filtering approach to differentiate oscillatory frequency bands for subsequent functional connectivity (FC) and graph analyses. The study included 68 non-anxiety PD (naPD) patients, 62 anxiety PD (aPD) patients, and 64 healthy controls (NC). Analyses of nodal betweenness centrality (BC), degree centrality (DC), and efficiency were conducted across multiple frequency bands. The findings indicated no significant differences in BC among naPD, aPD, and NC within the 0.01-0.08 Hz frequency range. However, we observed a specific reduction in BC at narrower frequency ranges in aPD patients, as well as differing patterns of change in DC and efficiency, which are believed to reflect the neurophysiological bases of anxiety symptoms in PD. Differential oscillation-specific nodal characteristics have been identified in PD patients with anxiety, suggesting potential dysregulations in brain network dynamics. These findings emphasize the complexity of brain network alterations in anxiety-associated PD and identify oscillatory frequencies as potential biomarkers. The study highlights the importance of considering oscillatory frequency bands in the analysis of brain network changes.

Association between hearing ability and cortical morphology in the elderly: multiparametric mapping, cognitive relevance, and neurobiological underpinnings

Hearing impairment is a common condition in the elderly. However, a comprehensive understanding of its neural correlates is still lacking. We recruited 284 elderly adults who underwent structural MRI, magnetic resonance spectroscopy, audiometry, and cognitive assessments. Individual hearing abilities indexed by pure tone average (PTA) were correlated with multiple structural MRI-derived cortical morphological indices. For regions showing significant correlations, mediation analyses were performed to examine their role in the relationship between hearing ability and cognitive function. Finally, the correlation maps between hearing ability and cortical morphology were linked with publicly available connectomic gradient, transcriptomic, and neurotransmitter maps. Poorer hearing was related to cortical thickness (CT) reductions in widespread regions and gyrification index (GI) reductions in the right Area 52 and Insular Granular Complex. The GI in the right Area 52 mediated the relationship between hearing ability and executive function. This mediating effect was further modulated by glutamate and N-acetylaspartate levels in the right auditory region. The PTA-CT correlation map followed microstructural connectomic hierarchy, were related to genes involved in certain biological processes (e.g., glutamate metabolic process), cell types (e.g., excitatory neurons and astrocytes), and developmental stages (i.e., childhood to young adulthood), and covaried with dopamine receptor 1, dopamine transporter, and fluorodopa. The PTA-GI correlation map was related to 5-hydroxytryptamine receptor 2a. Poorer hearing is associated with cortical thinning and folding reductions, which may be engaged in the relationship between hearing impairment and cognitive decline in the elderly and have different neurobiological substrates. See the Acknowledgements section.

Personality disorders in people with epilepsy: a review.

Epileptologists and psychiatrists have long observed a correlation between epilepsy and personality disorders (PDs) in their clinical practice. We conducted a comprehensive PubMed search looking for evidence on PDs in people with epilepsy (PwE). Out of over 600 results obtained without applying any time restriction, we selected only relevant studies (both analytical and descriptive) limited to English, Italian, French and Spanish languages, with a specific focus on PDs, rather than traits or symptoms, thus narrowing our search down to 23 eligible studies. PDs have been investigated in focal epilepsy (predominantly temporal lobe epilepsy - TLE), juvenile myoclonic epilepsy (JME) and psychogenic non-epileptic seizures (PNES), with heterogeneous methodology. Prevalence rates of PDs in focal epilepsy ranged from 18 to 42% in surgical candidates or post-surgical individuals, with Cluster C personality disorders or related traits and symptoms being most common. In JME, prevalence rates ranged from 8 to 23%, with no strong correlation with any specific PDs subtype. In PNES, prevalence rates ranged from 30 to 60%, with a notable association with Cluster B personality disorders, particularly borderline personality disorder. The presence of a PD in PwE, irrespective of subtype, complicates treatment management. However, substantial gaps of knowledge exist concerning the neurobiological substrate, effects of antiseizure medications and epilepsy surgery on concomitant PDs, all of which are indeed potential paths for future research.

Within-subject reliability of brain networks during advanced meditation: An intensively sampled 7 Tesla MRI case study.

Advanced meditation such as jhana meditation can produce various altered states of consciousness (jhanas) and cultivate rewarding psychological qualities including joy, peace, compassion, and attentional stability. Mapping the neurobiological substrates of jhana meditation can inform the development and application of advanced meditation to enhance well-being. Only two prior studies have attempted to investigate the neural correlates of jhana meditation, and the rarity of adept practitioners has largely restricted the size and extent of these studies. Therefore, examining the consistency and reliability of observed brain responses associated with jhana meditation can be valuable. In this study, we aimed to characterize functional magnetic resonance imaging (fMRI) reliability within a single subject over repeated runs in canonical brain networks during jhana meditation performed by an adept practitioner over 5 days (27 fMRI runs) inside an ultra-high field 7 Tesla MRI scanner. We found that thalamus and several cortical networks, that is, the somatomotor, limbic, default-mode, control, and temporo-parietal, demonstrated good within-subject reliability across all jhanas. Additionally, we found that several other relevant brain networks (e.g., attention, salience) showed noticeable increases in reliability when fMRI measurements were adjusted for variability in self-reported phenomenology related to jhana meditation. Overall, we present a preliminary template of reliable brain areas likely underpinning core neurocognitive elements of jhana meditation, and highlight the utility of neurophenomenological experimental designs for better characterizing neuronal variability associated with advanced meditative states.