Common Neurobiological Mechanisms Research Articles

Dynamic changes in seizure state and anxiety-like behaviors during pentylenetetrazole kindling in rats

IntroductionExcessive anxiety is a mental disorder, and its treatment involves the use of benzodiazepines, a class of drugs that enhance the effects of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor. Anxiety disorders are frequent comorbidities in patients with epilepsy, and it has been speculated that anxiety disorders and epileptic seizures share common neurobiological mechanisms. However, conflicting results regarding anxiolytic and anxiogenic effects have been reported in animal models of epilepsy induced by pentylenetetrazole (PTZ) injections, and the causes of this discrepancy are unknown. We hypothesized that anxiety-like behaviors would change dynamically according to the changes in epilepsy susceptibility that occur during the PTZ kindling process. Therefore, we attempted to change anxiety-like behaviors bidirectionally depending on the number of PTZ injections. MethodsAdult male rats were injected with PTZ 20 times every other day, and stages of seizure onset were classified according to the Racine staging system. Anxiety-like behaviors were measured after 10 and 20 injections. The control group was injected with an equal volume of saline solution. Anxiety-like behaviors were investigated using the open-field, light/dark transition, elevated plus maze, and social interaction tests. ResultsBimodal changes in seizure stage were observed in response to PTZ kindling. The increase in the seizure stage was transiently suppressed after 10 injections, and this decrease in epileptic sensitivity disappeared after 20 injections. However, none of the rats reached a fully kindled state after 20 PTZ injections. After 10 PTZ injections, anxiety-like behaviors decreased compared with those of the control group in the open field, light/dark transition, and elevated plus-maze tests. The anxiolytic effects correlated with the seizure stage in individual rats. After 20 PTZ injections, anxiety-like behaviors returned to control levels. ConclusionPTZ kindling induced bimodal changes in the seizure stage. Anxiety-like behaviors decreased with transient decrease in epileptic sensitivity and returned to control levels with the disappearance of these states. These findings suggest a common neurobiological mechanism underlying anxiety disorders and epileptic seizures. In addition, the discrepancy in the previous studies, in which anxiety levels increase or decrease in PTZ-kindled animals, may be due to examination at different phases of the kindling process.

ВЛИЯНИЕ ИНФОРМАЦИОННОГО СТРЕССА НА ПСИХИЧЕСКОЕ ЗДОРОВЬЕ НАСЕЛЕНИЯ

The abundance of diverse information accompanied by information noise can be an additional and powerful stressor, especially if the assimilation and processing of this information is carried out in a time-limited environment. Information streams created by gadgets, reflecting the activity of a person in social networks, his communications, his news sources, are not a harmless source of leisure and recreation. They require the inclusion of sensory systems and central nervous system structures, which are very energy-intensive. Manifestations of information fatigue are clinically similar to stress symptoms, and have common neurobiological mechanisms based on adaptation to changes or new challenges. The emergence of new phenomena of interaction with information space and technogenic environment (FOMO) reflects the influence of information transmitted by gadgets on the mental health of the population. Cognitive flexibility, goal-setting, will-based control, priority-setting, and gadget-detox (gadget regulation and informed information consumption) are all necessary skills for successful interaction with and operation of information flows.

Obesity and depression: Review on common neurobiological mechanisms and identification of potential drug targets.

IntroductionThis review aimed to identify common pathophysiological mechanisms that exist between depression and obesity, as well as pharmacological strategies used in clinical trials and animal models. It is necessary to carry out larger studies that integrate the multiple neurobiological processes of these phenomena and the search for therapeutic targets that affect these pathways.ObjectivesConduct a literature review on the common neurobiological aspects that exist between depression and obesity. Compare pharmacological and therapeutic strategies in the management of depressive patients by means of common neurobiological mechanisms.MethodsWe used the Pubmed search engine to search for the keywords: ((depression and obesity) OR (common pathways for depression and obesity) OR (therapeutic targets for depression and obesity) OR (neurobiology of depression and obesity) OR (treatments for depression and obesity))Once the predefined screening was carried out, 68 studies were identified. 54 articles were left for review and analysis. At the end of the review, 25 studies were discarded, including 29 studies with relevance to the objectives described in the study. These articles were selected when they provided information with adequate, concrete and specific reasoning towards the scientific and methodological elements of the review.Results Table 1: Findings related to the NEGR1 gene and its involvement in processes associated with alterations associated with depression and obesity. Table 2: Findings of inflammation associated with depression and obesity in clinical trials and animal models.Image:Image 2:ConclusionsAlterations in the NEGR1 gene, inflammatory markers, HPA axis and microbiota demonstrate multiple pathophysiological mechanisms in the clinical pictures associated with obesity and depression.Infliximab, pioglitazone, ondansentron, BVT.2733 and palmitoylethanolamide showed anti-inflammatory regulatory effects with reduction in depressive symptoms and multiple anti-inflammatory markers.Animal models for obesity and depression present ample and reliable evidence regarding the use of drugs that direct their therapeutic profile towards the pathophysiological mechanisms involved in pathologies involving depressive and metabolic disorders.Disclosure of InterestNone Declared

Common neurobiological mechanisms underlying anosognosia and neuropsychiatric symptoms across the Alzheimer’s disease spectrum

AbstractBackgroundBoth loss of awareness for cognitive decline (a.k.a. anosognosia) and neuropsychiatric symptoms (NPS) are common symptoms in Alzheimer’s disease (AD) and have been associated with AD pathology. Recent studies have shown a co‐occurrence between these symptoms across the AD spectrum, suggesting shared underlying neurophysiological processes, especially within the default mode network (DMN). Here, we investigated the relationship between NPS and altered awareness and the structural integrity (as assessed with diffusion tensor imaging, DTI) of brain regions supporting the DMN in participants with and without amyloid pathology.MethodsThree‐hundred participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent an amyloid positron emission tomography (PET), using 18F‐AV45 (florbetapir), and were classified into two groups: amyloid‐positive (A+) and negative (A‐). Individual mean fractional anisotropy (FA) was calculated from tracts overlapping the DMN regions. An awareness index was computed using the discrepancy between Everyday Cognition questionnaire scores from participants and informants. The Neuropsychiatric Inventory Total Score was used to assess the informant‐reported NPS. We compared amyloid groups on demographics and our different measures of interest. Pearson correlations were used to determine associations between measures of interest in each amyloid group. A multivariate multiple regression (MMR) model was performed to determine whether structural brain integrity predicts altered awareness and NPS jointly.ResultsA+ participants were significantly older (74 ± 7 vs. 72 ± 7 for A‐), more impaired (CDR global), and showed lower awareness and diffusion, and greater NPS (all p<0.001, see Table 1). Significant correlations were found between the FA, NPS, and awareness measures in A+ participants, with decreased FA associated with decreased awareness and more NPS. The MMR confirmed these associations between FA, awareness and NPS (p<0.02, see Table 2). The Pillai test revealed that the DTI effect jointly contributed to both models. No significant relationships were observed in the A‐ group.ConclusionOur results show that, in amyloid‐positive individuals across the AD spectrum, decreased awareness and increased NPS were related to decreased structural integrity of the DMN. This supports the hypothesis of common neurobiological mechanisms underlying anosognosia and NPS in AD.

Longitudinal cortical thinning is associated with cognitive decline in MCI and Alzheimer’s disease in the Korean population

AbstractUndAlzheimer’s disease (AD) is characterized by cognitive dysfunction likely secondary to progressive neurodegeneration in the brain. However, to what extent regional cortical thickness (CT) changes are related to cognitive decline in the Asian population remains unclear.MethodWe measured CT using Freesurfer v6 from T1‐weighted magnetic resonance imaging (MRI) data in 603 Korean participants, including 71 young and 288 old cognitively unimpaired (CU young and CU old), 149 with mild cognitive impairment (MCI), and 92 AD from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE). Cognitive function of each participant was quantified by the MMSE. MRI and cognitive data were acquired at baseline (n = 603) and a 2‐year follow‐up visit (n = 380). Linear mixed‐effect models were used to estimate diagnosis group, time, and group‐by‐time interaction effects on CT measurements, with age, sex, and education as covariates. Pearson’s correlations between CT measurements and MMSE total score were computed, corrected for multiple comparisons by false discovery rate (FDR).ResultAt baseline, CU old participants had lower CT values than CU young participants in the inferior parietal cortex and frontal and parietal regions. In comparison with CU old participants, MCI and AD showed widespread lower CT values, more pronounced in the medial temporal lobe (i.e., the entorhinal cortex and parahippocampal gyrus), inferior temporal cortex, medial prefrontal cortex, and medial parietal cortex (i.e., the posterior cingulate cortex and precuneus), with AD lower than MCI in these regions. These regions also showed the most longitudinal atrophy in both AD and MCI over 2 years. AD patients showed faster and more widespread atrophy patterns than MCI and CU old participants. We identified significant (PFDR<0.05) positive linear correlations between cognitive decline and regional CT measurements, particularly in regions showing significant cortical thinning across time.ConclusionIn this study, we replicated the typical cross‐sectional and longitudinal brain atrophy patterns, and relationships with cognitive decline in an Asian cohort. Our findings support the generalizability of atrophy patterns in MCI and AD, suggesting common neurobiological mechanisms underlying AD symptoms across different ethnoracial populations.

Increased Inhibition May Contribute to Maintaining Normal Network Function in the Ventral Hippocampus of a Fmr1-Targeted Transgenic Rat Model of Fragile X Syndrome.

A common neurobiological mechanism in several neurodevelopmental disorders, including fragile X syndrome (FXS), is alterations in the balance between excitation and inhibition in the brain. It is thought that in the hippocampus, as in other brain regions, FXS is associated with increased excitability and reduced inhibition. However, it is still not known whether these changes apply to both the dorsal and ventral hippocampus, which appear to be differently involved in neurodegenerative disorders. Using a Fmr1 knock-out (KO) rat model of FXS, we found increased neuronal excitability in both the dorsal and ventral KO hippocampus and increased excitatory synaptic transmission in the dorsal hippocampus. Interestingly, synaptic inhibition is significantly increased in the ventral but not the dorsal KO hippocampus. Furthermore, the ventral KO hippocampus displays increased expression of the α1GABAA receptor subtype and a remarkably reduced rate of epileptiform discharges induced by magnesium-free medium. In contrast, the dorsal KO hippocampus displays an increased rate of epileptiform discharges and similar expression of α1GABAA receptors compared with the dorsal WT hippocampus. Blockade of α5GABAA receptors by L-655,708 did not affect epileptiform discharges in any genotype or hippocampal segment, and the expression of α5GABAA receptors did not differ between WT and KO hippocampus. These results suggest that the increased excitability of the dorsal KO hippocampus contributes to its heightened tendency to epileptiform discharges, while the increased phasic inhibition in the Fmr1-KO ventral hippocampus may represent a homeostatic mechanism that compensates for the increased excitability reducing its vulnerability to epileptic activity.

Comorbidity of schizophrenia and alcoholism in the modern paradigm of outpatient psychiatric care

The comorbidity of alcohol disorder and schizophrenia or schizoaffective disorder is a complex and multifaceted problem that has a significant impact on the quality of life of patients and the complexity of medical care. This article discusses the common neurobiological mechanisms that explain the high rates of co-occurrence of these disorders, as well as the consequences of such comorbidity for patients and the healthcare system. Additionally, potential ways to optimize the treatment of these patients are being considered.

Pain neuroscience education improves post-traumatic stress disorder, disability, and pain self-efficacy in veterans and service members with chronic low back pain: Preliminary results from a randomized controlled trial with 12-month follow-up

ABSTRACT Post-traumatic stress disorder (PTSD) and chronic low back pain (CLBP) are frequently co-morbid. Some research suggests that PTSD and CLBP may share common neurobiological mechanisms related to stress. Traditional biomedical education may be ineffective for PTSD and CLBP, especially when co-morbid. The purpose of this study is to determine if pain neuroscience education (PNE) is more effective than traditional education in reducing PTSD, disability, pain, and maladaptive beliefs in patients with CLBP. Participants with CLBP and possible PTSD/PTSD-symptoms were recruited for this study. Participants were randomly allocated to a PNE group or a traditional education group. The intervention included 30 minutes of education followed by a standardized exercise program once a week for 4-weeks with a 4 and 8-week follow-up and healthcare utilization assessed at 12-months. Forty-eight participants consented for this research study with 39 allocated to treatment (PNE n = 18, traditional n = 21). PNE participants were more likely to achieve a clinically meaningful reduction in PTSD symptoms and disability at short-term follow-up. At 12-months, the PNE group utilized healthcare with 76% lower costs. In participants with CLBP, PNE may reduce hypervigilance toward pain and improve PTSD symptoms. Participants who received PNE were more confident body-tissues were safe to exercise. These beliefs about pain could contribute to a decrease in perceived disability and healthcare consumption for CLBP.

The BrainDrugs-epilepsy study: A prospective open-label cohort precision medicine study in epilepsy

IntroductionThe BrainDrugs-Epilepsy Study is part of the established Lundbeck Foundation funded BrainDrugs research alliance (braindrugs.nru.dk). The study aims to identify biomarkers of treatment outcome as well as cognitive and psychiatric comorbidity in patients with a first epileptic seizure and epilepsy. Our goal is to provide a patient-level prediction of treatment response. MethodsIn a prospective cohort study design, we will consecutively include a total of 200 patients who have experienced their first epileptic seizure and 150 newly diagnosed patients with epilepsy (≥ 16 years old). We will systematically collect data at baseline and one, three, and five years after inclusion. Neuropsychiatric and neuropsychological assessments will be combined with electroencephalography (EEG) and neuroimaging tools such as Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) brain scans using the synaptic vesicle glycoprotein 2A-binding radioligand [11C]-UCB-J. After completing the baseline investigations, patients diagnosed with epilepsy start anti-seizure medication (ASM) treatment with either lamotrigine or levetiracetam. Patients will be monitored every three months. For daily monitoring, we will use a mobile app. Our clinical endpoints are 1) ASM treatment response, 2) development of a second seizure/epilepsy diagnosis, 3) psychiatric symptoms, 4) cognitive disturbances, and 5) quality of life. DiscussionWe hypothesize that seizures, cognitive impairment, and psychiatric symptoms share common neurobiological mechanisms that can be identified using MRI, PET, and EEG. We will assess how these biomarkers change over time and in response to treatment, providing novel insights into disease trajectories in the first years of epilepsy. Clinical trial registrationNCT05450822. Retrospectively registered July 5, 2022 (https://clinicaltrials.gov/ct2/results?term=NCT05450822&Search=Search).

GluA2-lacking AMPA receptors in the nucleus accumbens core and shell contribute to the incubation of oxycodone craving in male rats.

One of the most challenging issues in the treatment of substance use disorder, including misuse of opioids such as oxycodone, is persistent vulnerability to relapse, often triggered by cues or contexts previously associated with drug use. In rats, cue-induced craving progressively intensifies ('incubates') during withdrawal from extended-access self-administration of several classes of misused drugs, including the psychostimulants cocaine and methamphetamine. For these psychostimulants, incubation is associated with strengthening of excitatory synapses in the nucleus accumbens (NAc) through incorporation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors that lack the GluA2 subunit and are therefore Ca2+ -permeable (CP-AMPARs). Once CP-AMPAR upregulation occurs, their stimulation is required for expression of incubation. It is not known if a similar mechanism contributes to incubation of oxycodone craving. Using male rats, we established that incubation occurs by withdrawal day (WD) 15 and persists through WD30. Then, using cell-surface biotinylation, we found that surface levels of the AMPAR subunit GluA1 but not GluA2 are elevated in NAc core and shell of oxycodone rats on WD15, although this wanes by WD30. Next, using intra-NAc injection of the selective CP-AMPAR antagonist Naspm before a seeking test, we demonstrate that CP-AMPAR blockade in either subregion decreases oxycodone seeking on WD15 or WD30 (after incubation), but not WD1, and has no effect in saline self-administering animals. The Naspm results suggest CP-AMPARs persist in synapses through WD30 even if total cell surface levels wane. These results suggest that a common neurobiological mechanism contributes to expression of incubation of craving for oxycodone and psychostimulants.

NEURONAL CORRELATES OF HYPERALGESIA AND SOMATIC SIGNS OF HEROIN WITHDRAWAL IN MALE AND FEMALE MICE.

Opioid withdrawal involves the manifestation of motivational and somatic symptoms. However, the brain structures that are involved in the expression of different opioid withdrawal signs remain unclear. We induced opioid dependence by repeatedly injecting escalating heroin doses in male and female C57BL/6J mice. We assessed hyperalgesia during spontaneous heroin withdrawal and somatic signs of withdrawal that was precipitated by the preferential μ-opioid receptor antagonist naloxone. Heroin-treated mice exhibited significantly higher hyperalgesia and somatic signs than saline-treated mice. Following behavioral assessment, we measured regional changes in brain activity by automated the counting of c-Fos expression (a marker of cellular activity). Using Principal Component Analysis, we determined the association between behavior (hyperalgesia and somatic signs of withdrawal) and c-Fos expression in different brain regions. Hyperalgesia was associated with c-Fos expression in the lateral hypothalamus, central nucleus of the amygdala, ventral tegmental area, parabrachial nucleus, dorsal raphe (DR), and locus coeruleus (LC). Somatic withdrawal was associated with c-Fos expression in the paraventricular nucleus of the thalamus, lateral habenula, DR, and LC. Thus, hyperalgesia and somatic withdrawal signs were each associated with c-Fos expression in unique sets of brain areas. The expression of c-Fos in the DR and LC was associated with both hyperalgesia and somatic withdrawal. Understanding common neurobiological mechanisms of acute and protracted opioid withdrawal may help identify new targets for treating this salient aspect of opioid use disorder.

N-Oleoyl Glycine and Its Derivatives Attenuate the Acquisition and Expression of Cocaine-Induced Behaviors.

Introduction: The endocannabinoid system (ECS) plays a key modulatory role during synaptic plasticity and homeostatic processes in the brain and plays an important role in the neurobiological processes underlying drug addiction. Impaired endocannabinoid (eCB) signaling contributes to dysregulated synaptic plasticity, increased stress responsivity, and craving that propel addiction. Therefore, we hypothesized that boosting the ECS by exogenous administration of selective eCBs will attenuate cocaine-induced behaviors. Materials and Methods: The behavioral paradigms included psychomotor sensitization (PS) and conditioned place preference (CPP). Liquid chromatography-mass spectrometry analysis was used for quantitative profiling of eCBs in mouse brain. Results: We first measured the levels of eCBs in different brain areas of the reward system following chronic cocaine treatment. We found that following daily administration of cocaine, the levels of N-oleoyl glycine (OlGly) were significantly elevated in the nucleus accumbens (NAc) in a region-specific manner. We next tested whether administration of OlGly will attenuate cocaine-induced behaviors. We found that administration of OlGly during withdrawal, but not during acquisition of PS, attenuated the expression of cocaine sensitization. In addition, the administration of OlGly during the acquisition of cocaine CPP, but not during withdrawal, attenuated the expression of cocaine-conditioned reward. To enhance the stability of OlGly and its duration of action, two methylated derivatives of OlGly were synthesized, the monomethylated OlGly (HU-595) and dimethylated OlGly (HU-596). We found that the effect of administration of HU-595 or HU-596 during cocaine conditioning did not differ from the OlGly-induced decrease in the expression of CPP. Conclusion: Our findings suggest that the ECS is involved in the common neurobiological mechanisms underlying the development and expression of cocaine reward and drug-seeking. Boosting the ECS exogenously has beneficial effects against cocaine-induced behaviors.

Applying dimensional psychopathology: transdiagnostic prediction of executive cognition using brain connectivity and inflammatory biomarkers.

The association between executive dysfunction, brain dysconnectivity, and inflammation is a prominent feature across major psychiatric disorders (MPDs), schizophrenia, bipolar disorder, and major depressive disorder. A dimensional approach is warranted to delineate their mechanistic interplay across MPDs. This single site study included a total of 1543 participants (1058 patients and 485 controls). In total, 1169 participants underwent diffusion tensor and resting-state functional magnetic resonance imaging (745 patients and 379 controls completed the Wisconsin Card Sorting Test). Fractional anisotropy (FA) and regional homogeneity (ReHo) assessed structural and functional connectivity, respectively. Pro-inflammatory cytokine levels [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] were obtained in 325 participants using blood samples collected with 24 h of scanning. Group differences were determined for main measures, and correlation and mediation analyses and machine learning prediction modeling were performed. Executive deficits were associated with decreased FA, increased ReHo, and elevated IL-1β and IL-6 levels across MPDs, compared to controls. FA and ReHo alterations in fronto-limbic-striatal regions contributed to executive deficits. IL-1β mediated the association between FA and cognition, and IL-6 mediated the relationship between ReHo and cognition. Executive cognition was better predicted by both brain connectivity and cytokine measures than either one alone for FA-IL-1β and ReHo-IL-6. Transdiagnostic associations among brain connectivity, inflammation, and executive cognition exist across MPDs, implicating common neurobiological substrates and mechanisms for executive deficits in MPDs. Further, inflammation-related brain dysconnectivity within fronto-limbic-striatal regions may represent a transdiagnostic dimension underlying executive dysfunction that could be leveraged to advance treatment.

Disordered Decision Making: A Cognitive Framework for Apathy and Impulsivity in Huntington's Disease.

A caregiver's all‐too‐familiar narrative ‐ “He doesn't think through what he does, but mostly he does nothing.” Apathy and impulsivity, debilitating and poorly understood, commonly co‐occur in Huntington's disease (HD). HD is a neurodegenerative disease with manifestations bridging clinical neurology and psychiatry. In addition to movement and cognitive symptoms, neurobehavioral disturbances, particularly apathy and impulsivity, are prevalent features of HD, occurring early in the disease course, often worsening with disease progression, and substantially reducing quality of life. Treatments remain limited, in part because of limited mechanistic understanding of these behavioral disturbances. However, emerging work within the field of decision‐making neuroscience and beyond points to common neurobiological mechanisms underpinning these seemingly disparate problems. These insights bridge the gap between underlying disease pathology and clinical phenotype, offering new treatment strategies, novel behavioral and physiological biomarkers of HD, and deeper understanding of human behavior. In this review, we apply the neurobiological framework of cost‐benefit decision making to the problems of apathy and impulsivity in HD. Through this decision‐making lens, we develop a mechanistic model that elucidates the occurrence of these behavioral disturbances and points to potential treatment strategies and crucial research priorities. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Connectivity Patterns Evoked by Fearful Faces Demonstrate Reduced Flexibility Across a Shared Dimension of Adolescent Anxiety and Depression

Adolescents experiencing anxiety or depression exhibit cognitive biases favoring the processing of negative emotional information. It remains unknown whether common neurobiological processes underlie these biases across anxiety and depression. Here, brain imaging was acquired from typical, anxious, and depressed adolescents during an emotional-interference task. Functional connectivity patterns were assessed while adolescents were cued to attend to or ignore faces. Results revealed a shared dimension of anxious and depressive symptoms was associated with reduced changes in connectivity patterns between conditions in which adolescents needed to ignore or attend to fearful faces. These findings were exclusive to fearful faces and observed only for functional connections with a primary face-representation area (fusiform gyrus). Results suggested a failure to flexibly adapt communication patterns with sensory-representation areas in the presence of negative emotional information, which may reflect a common neurobiological mechanism explaining biases favoring such information shared among adolescent anxiety and depression.

Hassle Faced with Induced Mania in Elderly Female While Treating for Obsessive-Compulsive Symptoms

Obsessive-compulsive disorder (OCD) is one of the most frequently associated comorbidities in bipolar disorder. While this presents a challenge in understanding the phenomenology and also the treatment aspect of cooccurrence of mania with OCD. The index case is of an elderly female who presented with obsessive-compulsive (OC) symptoms and while on treatment had mania episodes. The mania episodes presented challenges while managing underlying OC symptoms. The common neurobiological mechanism for the comorbid illness and treatment lacunae are discussed.

Clinical Considerations in Internet and Video Game Addiction Treatment.

In order to address etiologic, clinical, and treatment strategies applicable to Internet and video game addiction (IVGA), a working definition of addiction is presented and unique aspects of Internet and screen use disorders and addictive patterns are discussed. Addictions share common neurobiological mechanisms, cause, triggers, and behavioral sequelae-often presenting with similar symptomatology-although severity and impairment vary widely. This article reviews etiologic and neurobiological antecedents to Internet and video game addiction.

Assessment of automated craving across substances and across cultures: stability-analysis of the Craving Automated Scale (CAS)

Background The transition from hedonic to compulsive use in Substance Use Disorders (SUD) is a critical point in SUD progression and hence relevant for assessment and treatment. To measure the habitual patterns of substance consumption, the Craving Automated Scales (CAS) for alcohol (CAS-A), substances (CAS-S) and cigarette smoking (CAS-CS) were developed and introduced to different countries. In this study, we aimed to investigate the structural stability of CAS across substances and cultures. Methods This study analyzed the CAS-scores of a sample of 370 participants in Germany, China and the UK, including 262 opioid-users, 65 smokers and 43 alcohol-users. We performed stability analyses to check the stability (i. e. factorial invariance) of factor solutions. Based on confirmed stability of the general factor (gfactor) solution and the calculations rule obtained in the previous validation of CAS-alcohol (CAS-A), the factor structures of CAS-A, CAS-S and CAS-CS were compared. Results The gfactor solutions based on calculations rule shows good stability, with the mean stability coefficients of 0.990 and 0.977 for CAS-S and CAS-CS respectively. The gfactor patterns were similar for CAS-A, CAS-S and CAS-CS, as well as across samples (Germany, China and the UK), with most factor-loadings larger than 0.7. Based on these findings, CAS-S and CAS-CS were also associated with established clinical measures of SUD. Conclusions Our findings suggest the two-gfactor solution based on a proposed calculation rule has a high stability across substances and cultures. This could be in line with common neurobiological mechanisms underlying habitual substance use. Moreover, comparing CAS with established clinical tools suggests that CAS might assess the automated behavior in substance consumption in a more sophisticated way.

Aging Enhances Neural Activity in Auditory, Visual, and Somatosensory Cortices: The Common Cause Revisited.

In humans, age-related declines in vision, hearing, and touch coincide with changes in amplitude and latency of sensory-evoked potentials. These age-related differences in neural activity may be related to a common deterioration of supra-modal brain areas (e.g., PFC) that mediate activity in sensory cortices or reflect specific sensorineural impairments that may differ between sensory modalities. To distinguish between these two possibilities, we measured neuroelectric brain activity while 37 young adults (18-30 years, 18 males) and 35 older adults (60-88 years, 20 males) were presented with a rapid randomized sequence of lateralized auditory, visual, and somatosensory stimuli. Within each sensory domain, we compared amplitudes and latencies of sensory-evoked responses, source activity, and functional connectivity (via phase-locking value) between groups. We found that older adults' early sensory-evoked responses were greater in amplitude than those of young adults in all three modalities, which coincided with enhanced source activity in auditory, visual, and somatosensory cortices. Older adults also showed stronger neural synchrony than young adults between superior prefrontal and sensory cortices; and in older adults, the degree of phase synchrony was positively correlated with the magnitude of source activity in sensory areas. Critically, older adults who showed enhanced neural activity in one sensory domain also showed enhanced activity in other modalities. Together, these findings support the common cause hypothesis of aging and highlight the role of prefrontal regions in exerting top-down control over sensory cortices.SIGNIFICANCE STATEMENT A prominent theory of aging posits that age-related declines in sensory processing across domains are related to a single common neurobiological mechanism. However, the neural evidence supporting this common cause hypothesis has remained elusive. Our study revealed robust age-related changes in three sensory domains across a range of neural metrics. Importantly, older adults who showed increased neural activity within one sensory domain also showed enhanced neural activity in the other two sensory modalities. No such relation among activity in sensory cortices was observed in young adults. Age-related increases in neural activity in sensory cortices coincided with enhanced neural synchrony between the PFC and sensory cortices, underlining the importance of the PFC in regulating sensory processing.

A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta‐analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1‐weighted structural MRI scans. Mass univariate meta‐analyses revealed more‐concave‐than‐convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more‐convex‐than‐concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta‐analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.