Frontostriatal Systems Research Articles

The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view.

Behavioral disorders, with an average prevalence of 30-60% are important non-motor symptoms in amyotrophic lateral sclerosis (ALS) that have a negative impact on prognosis, management and quality of life, yet the underlying neurobiology is poorly understood. Among people with ALS, apathy, fatigue, anxiety, irritability and other behavioral symptoms are the most prominent, although less frequent than cognitive impairment. The present review explores the current understanding of behavioral changes in ALS with particular emphasis on our current knowledge about their structural and functional brain correlates, substantiating a multisystem degeneration with particular dysfunction of frontal-subcortical circuits and dysfunction of fronto-striatal, frontotemporal and other essential brain systems. The natural history of behavioral dysfunctions in ALS and their relationship to frontotemporal lobe degeneration (FTLD) are not fully understood, although they form a clinical continuum, suggesting a differential vulnerability of non-motor brain networks, ALS being considered a brain network disorder. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of behavioral impairment in ALS. Treatment of both ALS and co-morbid behavioral disorders is a multidisciplinary task, but whereas no causal or disease-modifying therapies for ALS are available, symptomatic treatment of a variety of behavioral symptoms plays a pivotal role in patient care, although the management of behavioral symptoms in clinical care still remains limited.

From compulsivity to compulsion: the neural basis of compulsive disorders.

Compulsive behaviour, an apparently irrational perseveration in often maladaptive acts, is a potential transdiagnostic symptom of several neuropsychiatric disorders, including obsessive-compulsive disorder and addiction, and may reflect the severe manifestation of a dimensional trait termed compulsivity. In this Review, we examine the psychological basis of compulsions and compulsivity and their underlying neural circuitry using evidence from human neuroimaging and animal models. Several main elements of this circuitry are identified, focused on fronto-striatal systems implicated in goal-directed behaviour and habits. These systems include the orbitofrontal, prefrontal, anterior cingulate and insular cortices and their connections with the basal ganglia as well as sensoriomotor and parietal cortices and cerebellum. We also consider the implications for future classification of impulsive-compulsive disorders and their treatment.

Distinct Topological Properties of the Reward Anticipation Network in Preadolescent Children With Binge Eating Disorder Symptoms

Few studies have considered the neural underpinnings of binge eating disorder (BED) in children, despite clinical and subclinical symptom presentation occurring in this age group. Symptom presentation at this age is of clinical relevance, as early onset of binge eating is linked to negative health outcomes. Studies in adults have highlighted dysfunction in the frontostriatal reward system as a potential candidate for binge eating pathophysiology, although the exact nature of such dysfunction is currently unclear. Data from 83 children (mean age 9.9 years, SD= 0.60) with symptoms of BED (57% girls) and 123 control participants (mean age 10.0 years, SD= 0.60) (52% girls) were acquired from the 4.0 baseline release of the Adolescent Brain Cognitive Development Study. Task-based graph theoretic techniques were used to analyze data from anticipation trials of the monetary incentive delay task. Network and nodal properties were compared between groups. The BED-S group showed alterations in topological properties associated with the frontostriatal subnetwork, such as reduced nodal efficiency in the superior frontal gyrus, nucleus accumbens, putamen, and in normal sex-difference patterns of these properties, such as diminished girls-greater-than-boys pattern of betweenness-centrality in nucleus accumbens observed in controls. Distinct network properties and sex-difference patterns in preadolescent children with BED-S suggest dysregulation in the reward system compared to those of matched controls. For the first time, these results quantify this dysregulation in terms of systems-level properties during anticipation of monetary reward and significantly inform the early and sex-related brain markers of BED symptoms. Binge eating disorder is the most common eating disorder. One factor that may contribute to binge eating is dysregulation of the reward system in the brain. This study analyzed brain activity during anticipation of monetary rewards in 83 youth with and 123 children without binge eating disorder symptoms from the Adolescent Brain Cognitive Development Study. The authors found specific alterations in the frontostriatal system, responsible for reward processing, in children with binge eating disorder symptoms, compared to the control group, suggesting dysregulation of the reward system.

Multimodal quantitative magnetic resonance imaging of the thalamus in tinnitus patients with different outcomes after sound therapy.

This study systematically investigated structural and functional alterations in the thalamus and its subregions using multimodal magnetic resonance imaging (MRI) and examined its clinical relevance in tinnitus patients with different outcomes after sound therapy (narrowband noise). In total, 60 patients with persistent tinnitus and 57 healthy controls (HCs) were recruited. Based on treatment efficacy, 28 patients were categorized into the effective group and 32 into the ineffective group. Five MRI measurements of the thalamus and its seven subregions, including gray matter volume, fractional anisotropy, fractional amplitude of low-frequency fluctuation, and functional connectivity (FC), were obtained for each participant and compared between the groups. Patients in both the groups exhibited widespread functional and diffusion abnormalities in the whole thalamus and several subregions, with more obvious changes observed in the effective group. All tinnitus patients had abnormal FC compared with the HCs; FC differences between the two patient groups were only observed in the striatal network, auditory-related cortex, and the core area of the limbic system. We combined the multimodal quantitative thalamic alterations and used it as an imaging indicator to evaluate prognosis before sound therapy and achieved a sensitivity of 71.9% and a specificity of 85.7%. Similar patterns of thalamic alterations were identified in tinnitus patients with different outcomes, with more obvious changes observed in the effective group. Our findings support the tinnitus generation hypothesis of frontostriatal gating system dysfunction. A combination of multimodal quantitative thalamic properties may be used as indicators to predict tinnitus prognosis before sound therapy.

Puberty contributes to adolescent development of fronto-striatal functional connectivity supporting inhibitory control

Adolescence is defined by puberty and represents a period characterized by neural circuitry maturation (e.g., fronto-striatal systems) facilitating cognitive improvements. Though studies have characterized age-related changes, the extent to which puberty influences maturation of fronto-striatal networks is less known. Here, we combine two longitudinal datasets to characterize the role of puberty in the development of fronto-striatal resting-state functional connectivity (rsFC) and its relationship to inhibitory control in 106 10–18-year-olds. Beyond age effects, we found that puberty was related to decreases in rsFC between the caudate and the anterior vmPFC, rostral and ventral ACC, and v/dlPFC, as well as with rsFC increases between the dlPFC and nucleus accumbens (NAcc) across males and females. Stronger caudate rsFC with the dlPFC and vlPFC during early puberty was associated with worse inhibitory control and slower correct responses, respectively, whereas by late puberty, stronger vlPFC rsFC with the dorsal striatum was associated with faster correct responses. Taken together, our findings suggest that certain fronto-striatal connections are associated with pubertal maturation beyond age effects, which, in turn are related to inhibitory control. We discuss implications of puberty-related fronto-striatal maturation to further our understanding of pubertal effects related to adolescent cognitive and affective neurodevelopment.

Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder.

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.

Focal electrical stimulation on an alcohol disorder model using magnetic resonance imaging-compatible chronic neural monopolar carbon fiber electrodes.

Neuromodulation interventions, such as Deep Brain Stimulation (DBS) and repeated transcranial magnetic stimulation (rTMS), are proposed as possible new complementary therapies to treat substance use disorders (SUD) such as alcohol use disorder (AUD). It is hypothesized that neuromodulation may induce neural plasticity in the reward and frontostriatal systems via electrical field induction, possibly reducing symptoms. Preclinical self-administration rodent models of AUD may help us gain insight into the effects of neuromodulation therapies on different pathology, as well as the neural mechanisms behind the positive effects. DBS, or any type of brain stimulation using intracranial electrodes in rodents, would benefit from the use of magnetic resonance imaging (MRI) to study the longitudinal effects and mechanisms of stimulation as well as novel targets, as it is a non-invasive technique that allows the analysis of structural and functional changes in the brain. To do this, there is a need for MRI-compatible electrodes that allow for MRI acquisition with minimal distortion of the magnetic field. In this protocol, we present a method for the construction and surgery of chronically implantable monopolar carbon electrodes for use in rats. Unlike conventional electrodes, carbon electrodes are resistant to high temperatures, flexible, and generate fewer artifacts in MRI compared to conventional ones. We validated its use by using a focal electrical stimulation high-frequency (20 Hz) protocol that lasted ∼10 sessions. We propose that this technique can also be used for the research of the neurophysiological bases of the neuromodulatory treatment in other preclinical substance use disorders (SUD) models.

Learning and memory : neurosciences perspectives

Learning is the process of acquiring new or modifyingexisting knowledge, skills, behaviors or preferences (Schachter et al., 2010)
 
 
 Memory is the faculty of encoding, storing and retreiving information (Squire, 2009)
 
 Basic forms of learning were demonstrated at earlier and earlier stages of development, including in utero (Blumberg et al., 2010, Kail and Spear, 1984)
 
 There are multiple brain learning/memory systems, age-specific ecological adaptions, and acquisition-vs.-expression of learning (Krasnegor et al., 1986, Shair et al., 1991, Spear and Campbell, 1979). 
 
 
 Rats show “infantile amnesia” (Campbell and Campbell, 1962, Campbell and Spear, 1972). The discovery that rodents show poor long-term memory for experiences occurring in infancy suggested that the human phenomenon has a biological basis. 
 
 The neurobiology of learning and memory during adolescence showed specific sex/gender effects (Spear, 2009, Raznahan 2019).
 
 There is a strong relationship between neurobiological and behavioral changes specifically during the adolescent period: alterations in fronto-striatal systems during adolescence impact risky decision making and vulnerability to social pressures, which may ultimately provide a framework for the development of reward-related learning abilities (DePasque & Galvan 2017).
 
 Involvement of NMDA glutamate receptors in impairments in fearextinction during adolescence, and how the role of NMDA receptorsmay differ during this stage of development compared to adults and juveniles (Baker and Richardson 2017). 
 
 The maturation of cortical noradrenergic systems contributes to executive function (Mokler and colleagues 2017). 
 
 

Charting the neural circuits disruption in inhibitory control and its subcomponents across psychiatric disorders: A neuroimaging meta-analysis

BackgroundInhibitory control, comprising cognitive inhibition and response inhibition, showed consistent deficits among several major psychiatric disorders. We aim to identify the trans-diagnostic convergence of neuroimaging abnormalities underlying inhibitory control across psychiatric disorders. MethodsInhibitory control tasks neuroimaging, including functional magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography articles published in PubMed and Web of Science before April 2020 comparing healthy controls with patients with several psychiatric disorders were searched. Results146 experiments on 2653 patients with different disorders and 2764 control participants were included. Coordinates of case-control differences coded by diagnosis and inhibitory control components were analyzed using activation likelihood estimation. A robust trans-diagnostic pattern of aberrant brain activation in the bilateral cingulate gyri extending to medial frontal gyri, right insula, bilateral lentiform nuclei, right inferior frontal gyrus, right precuneus extending to inferior parietal lobule, and right supplementary motor area were detected. Frontostriatal pathways are the commonly disrupted neural circuits in the inhibitory control across psychiatric disorders. Furthermore, Patients showed aberrant activation in the dorsal frontal inhibitory system in cognitive inhibition, while in the frontostriatal system in response inhibition across disorders. ConclusionConsistent with the Research Domain Criteria initiative, current findings show that psychiatric disorders may be productively formulated as a phenotype of trans-diagnostic neurocircuit disruption. Our results provide new insights for future research into mental disorders with inhibition-related dysfunctions.

Hierarchical Reinforcement Learning, Sequential Behavior, and the Dorsal Frontostriatal System.

To effectively behave within ever-changing environments, biological agents must learn and act at varying hierarchical levels such that a complex task may be broken down into more tractable subtasks. Hierarchical reinforcement learning (HRL) is a computational framework that provides an understanding of this process by combining sequential actions into one temporally extended unit called an option. However, there are still open questions within the HRL framework, including how options are formed and how HRL mechanisms might be realized within the brain. In this review, we propose that the existing human motor sequence literature can aid in understanding both of these questions. We give specific emphasis to visuomotor sequence learning tasks such as the discrete sequence production task and the M × N (M steps × N sets) task to understand how hierarchical learning and behavior manifest across sequential action tasks as well as how the dorsal cortical-subcortical circuitry could support this kind of behavior. This review highlights how motor chunks within a motor sequence can function as HRL options. Furthermore, we aim to merge findings from motor sequence literature with reinforcement learning perspectives to inform experimental design in each respective subfield.

Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior

RationaleCompulsivity often develops during childhood and is associated with elevated glutamate levels within the frontostriatal system. This suggests that anti-glutamatergic drugs, like memantine, may be an effective treatment.ObjectiveOur goal was to characterize the acute and chronic effect of memantine treatment on compulsive behavior and frontostriatal network structure and function in an adolescent rat model of compulsivity.MethodsJuvenile Sprague–Dawley rats received repeated quinpirole, resulting in compulsive checking behavior (n = 32; compulsive) or saline injections (n = 32; control). Eight compulsive and control rats received chronic memantine treatment, and eight compulsive and control rats received saline treatment for seven consecutive days between the 10th and 12th quinpirole/saline injection. Compulsive checking behavior was assessed, and structural and functional brain connectivity was measured with diffusion MRI and resting-state fMRI before and after treatment. The other rats received an acute single memantine (compulsive: n = 12; control: n = 12) or saline injection (compulsive: n = 4; control: n = 4) during pharmacological MRI after the 12th quinpirole/saline injection. An additional group of rats received a single memantine injection after a single quinpirole injection (n = 8).ResultsMemantine treatment did not affect compulsive checking nor frontostriatal structural and functional connectivity in the quinpirole-induced adolescent rat model. While memantine activated the frontal cortex in control rats, no significant activation responses were measured after single or repeated quinpirole injections.ConclusionsThe lack of a memantine treatment effect in quinpirole-induced compulsive adolescent rats may be partly explained by the interaction between glutamatergic and dopaminergic receptors in the brain, which can be evaluated with functional MRI.

What scans see when patients see defects: neuroimaging findings in body dysmorphic disorder.

Body dysmorphic disorder (BDD) is characterized by an individual's preoccupation with a perceived defect in their appearance which to others may be barely noticeable or even completely unnoticed. It confers significant disturbances of everyday functioning in affected persons. The present review study provides an overview of neuroimaging findings on BDD. Literature on three platforms, PubMed, Google Scholar and PsycArticles of APA PsycNet, was searched for studies on patients with BBD compared with healthy controls (HCs), with a focus on neuroimaging findings. Out of an initial yield of 414 articles, 23 fulfilled inclusion criteria and were reviewed. Among the most remarkable findings were functional abnormalities in visual processing, frontostriatal and limbic systems, reduced global efficiency of White Matter (WM) connectivity, reduced cortical thickness in temporal and parietal lobes, and correlations between these neuroimaging findings and clinical variables such as symptom severity and degree of insight. Structural, volumetric and functional neuroimaging findings in BDD affected persons may help shed light on the pathophysiology and neurobiological underpinnings of this condition. Future studies should further investigate the use of imaging findings as potential prognostic biomarkers of treatment efficacy and disease outcome.

Neurofunctional characteristics of executive control in older people with HIV infection:a comparison with Parkinson's disease.

Expression of executive dysfunctions is marked by substantial heterogeneity in people living with HIV infection (PLWH) and attributed to neuropathological degradation of frontostriatal circuitry with age and disease. We compared the neurophysiology of executive function in older PLWH and Parkinson's disease (PD), both affecting frontostriatal systems. Thirty-one older PLWH, 35 individuals with PD, and 28 older healthy controls underwent executive task-activated fMRI, neuropsychological testing, and a clinical motor exam. fMRI task conditions distinguished cognitive control operations, invoking a lateral frontoparietal network, and motor control operations, activating a cerebellar-precentral-medial prefrontal network. HIV-specific findings denoted a prominent sensorimotor hypoactivation during cognitive control and striatal hypoactivation during motor control related to CD4+ T cell count and HIV disease duration. Activation deficits overlapped for PLWH and PD, relative to controls, in dorsolateral frontal, medial frontal, and middle cingulate cortices for cognitive control, and in limbic, frontal, parietal, and cerebellar regions for motor control. Thus, despite well-controlled HIV infection, frontostriatal and sensorimotor activation deficits occurred during executive control in older PLWH. Overlapping activation deficits in posterior cingulate and hippocampal regions point toward similarities in mesocorticolimbic system aberrations among older PLWH and PD. The extent of pathophysiology in PLWH was associated with variations in immune system health, neural signature consistent with subclinical parkinsonism, and mild neurocognitive impairment. The failure to adequately engage these pathways could be an early sign for cognitive and motor functional decline in the aging population of PLWH.

Childhood ADHD, Going Beyond the Brain: A Meta-Analysis on Peripheral Physiological Markers of the Heart and the Gut.

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common neurodevelopmental disorder diagnosed in children. Questions regarding its increased diagnostic rates and pharmacological treatments in developing children have led to a more holistic review of the multi-system pathophysiology observed in ADHD. The dopaminergic neurotransmitter system, known for its influence on reward-motivated behaviors and motor control, and the frontostriatal systems, that mediate motor, cognition, and behavior, are associated with ADHD’s development. However, studies have shown that these neural systems do not wholly account for ADHD’s multilayered and heterogeneous symptom presentation. For instance, the literature suggests that emotional dysregulation, the inability to regulate one’s emotional responses to provoking stimuli, is associated with increased risk for social impairment in ADHD. A broader examination of physiological systems in children with ADHD has found potential markers in the heart-brain and gut-brain axes that correspond with certain behaviors associated with emotional dysregulation in recent studies. Hence, the purpose of this meta-analysis is to aggregate ten applicable published case studies and analyze task-related heart rate reactivity (HRR; n = 5 studies) and gut microbiota (n = 5 studies) data in children with and without ADHD. Data from a total of 531 youth with ADHD and 603 youth without ADHD revealed significant small and medium effect sizes for higher Chao1 levels and Actinobacteria levels in the ADHD group, respectively, but no evidence of altered task-related HRR. Thus, further research into multi-system psychophysiological measures of emotional dysregulation and ADHD is warranted. The clinical, empirical, and educational implications of these findings are discussed.Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021236819).

Generalizing effects of frontostriatal structural connectivity on self-esteem using predictive modeling

Determining the generalizability of biological mechanisms supporting psychological constructs is a central goal of cognitive neuroscience. Self-esteem is a popular psychological construct that is associated with a variety of measures of mental health and life satisfaction. Recently, there has been interest in identifying biological mechanisms that support individual differences in self-esteem. Understanding the biological basis of self-esteem requires identifying predictive biomarkers of self-esteem that generalize across groups of individuals. Previous research using diffusion magnetic resonance imaging has shown that self-esteem is related to the integrity of structural connections linking frontostriatal brain systems involved in self-referential processing and reward. However, these findings were based on a small, relatively homogeneous group of participants. In the current study, we used an out-of-sample predictive modeling approach to generalize the results of the previous study to an independent sample of participants more than twice the size of the original study. We found that both linear univariate and multivariate machine learning models trained on frontostriatal integrity from the original data significantly predicted self-esteem in the independent dataset. These findings underscore the relationship between self-esteem and frontostriatal connectivity and suggest these results are robust to differences in scanning acquisition, analytic methods, and participant demographics.

Neural and computational mechanisms of momentary fatigue and persistence in effort-based choice

From a gym workout, to deciding whether to persevere at work, many activities require us to persist in deciding that rewards are ‘worth the effort’ even as we become fatigued. However, studies examining effort-based decisions typically assume that the willingness to work is static. Here, we use computational modelling on two effort-based tasks, one behavioural and one during fMRI. We show that two hidden states of fatigue fluctuate on a moment-to-moment basis on different timescales but both reduce the willingness to exert effort for reward. The value of one state increases after effort but is ‘recoverable’ by rests, whereas a second ‘unrecoverable’ state gradually increases with work. The BOLD response in separate medial and lateral frontal sub-regions covaried with these states when making effort-based decisions, while a distinct fronto-striatal system integrated fatigue with value. These results provide a computational framework for understanding the brain mechanisms of persistence and momentary fatigue.

The neural substrates of risky rewards and losses in healthy volunteers and patient groups: a PET imaging study.

Risk is an essential trait of most daily decisions. Our behaviour when faced with risks involves evaluation of many factors including the outcome probabilities, the valence (gains or losses) and past experiences. Several psychiatric disorders belonging to distinct diagnostic categories, including pathological gambling and addiction, show pathological risk-taking and implicate abnormal dopaminergic, opioidergic and serotonergic neurotransmission. In this study, we adopted a transdiagnostic approach to delineate the neurochemical substrates of decision making under risk. We recruited 39 participants, including 17 healthy controls, 15 patients with pathological gambling and seven binge eating disorder patients, who completed an anticipatory risk-taking task. Separately, participants underwent positron emission tomography (PET) imaging with three ligands, [18F]fluorodopa (FDOPA), [11C]MADAM and [11C]carfentanil to assess presynaptic dopamine synthesis capacity and serotonin transporter and mu-opioid receptor binding respectively. Risk-taking behaviour when faced with gains positively correlated with dorsal cingulate [11C]carfentanil binding and risk-taking to losses positively correlated with [11C]MADAM binding in the caudate and putamen across all subjects. We show distinct neurochemical substrates underlying risk-taking with the dorsal cingulate cortex mu-opioid receptor binding associated with rewards and dorsal striatal serotonin transporter binding associated with losses. Risk-taking and goal-directed control appear to dissociate between dorsal and ventral fronto-striatal systems. Our findings thus highlight the potential role of pharmacological agents or neuromodulation on modifying valence-specific risk-taking biases.

Vocal TIC (Case from practice)

We examined an inpatient patient who was admitted to the Otorhinolaryngology Department of the ASMI clinics with complaints of involuntary movements in the form of grunting, during the day, ceasing at night during sleep. With the appointment of topiromat preparations (topepsil 100 mg / day), in addition to the taken tiapride (tiaprosan at a dosage of 200 mg / day), a decrease and disappearance of vocal tics was noted in several days. The described features inherent in vocal tics allow us to conclude that the combined use of anticonvulsants and tiapriides is effective in treating patients with extensive use of the frontostriatal systems.

Risks versus consequences of adolescent and young adult substance use: A focus on executive control.

This review examines the role of executive control processes in the liability for substance misuse and whether substance use, once initiated, leads to subsequent decrements as proposed by neurotoxicity models of substance use disorder (SUD). As indicated by a number of recent meta-analyses, executive control processes, which include working memory, cognitive flexibility and numerous aspects of attentional, behavioral and emotional control, are impaired in the context of active SUD. Longitudinal studies of behaviorally disinhibited children, individuals with familial risks for SUD, and twins within whom genetic versus environmental influences on behavior can be modeled robustly indicate that relatively poor control is a vulnerability factor for early substance use initiation, binge patterns of use, and subsequent SUD. Evidence of further declines in executive control, once substance use is initiated, is mixed, although a growing number of neuroimaging studies indicate that frontostriatal, frontolimbic, and frontocerebellar systems are altered as a consequence of use. Together these patterns suggest strategies for identifying children and adolescents at high risk for SUD, avenues through which substance-related neurotoxicities can be more reliably detected, and the need to structure prevention efforts in a manner that is developmentally appropriate and perhaps personalized to individual vulnerabilities.

Network-Specific Corticothalamic Dysconnection in Attention-Deficit Hyperactivity Disorder.

Functional connectivity (FC) is believed to be abnormal in attention-deficit hyperactivity disorder (ADHD). Most studies have focused on frontostriatal systems, and the role of the thalamic network in ADHD remains unclear. The current study used FC magnetic resonance imaging (fcMRI) to explore corticothalamic network properties and correlated network dysconnection with ADHD symptom severity. Eighteen adolescents with ADHD and 16 healthy controls aged 12 to 17 years underwent resting functional MRI scans, clinical evaluations, and 2 parent rating scales, namely the Swanson, Nolan, and Pelham IV scale and the Child Behavior Checklist. Six a priori cortical regions of interest were used to derive 6 networks: the dorsal default mode network, frontoparietal network, cingulo-opercular network (CON), primary sensorimotor network (SM1), primary auditory network, and primary visual network (V1). The corticothalamic connectivity for each network was calculated for each participant and then compared between the groups. We also compared the 2 scales with the network connectivity. The corticothalamic connectivity within the CON was significantly reduced (p < 0.05) among adolescents with ADHD compared with the controls. The corticothalamic dysconnection within the CON, SM1, and V1 networks negatively correlated with ADHD symptom severity. This network analysis indicates that corticothalamic dysconnection in ADHD involves the CON, SM1, and V1 networks and relates to symptom severity. The findings provide evidence of dysfunctional thalamus-related networks in ADHD.