Frontostriatal Circuits Research Articles

Right inferior frontal gyrus theta-burst stimulation reduces smoking behaviors and strengthens fronto-striatal-limbic resting-state functional connectivity: a randomized crossover trial.

Functional and anatomical irregularities in the right inferior frontal gyrus (rIFG), a ventrolateral prefrontal region that mediates top-down inhibitory control over prepotent behavioral responding, are implicated in the ongoing maintenance of nicotine dependence (ND). However, there is little research on the effects of neuromodulation of the rIFG on smoking behavior, inhibitory control, and resting-state functional connectivity (rsFC) among individuals with ND. In this double-blind, crossover, theta-burst stimulation (TBS) study, adults with ND (N = 31; female: n = 15) completed a baseline session and were then randomized to two counterbalanced sessions of functionally neuronavigated TBS to the rIFG: continuous TBS (cTBS) on 1 day and intermittent TBS (iTBS) on another. Differences in cigarette cravings, smoking, and fronto-striatal-limbic rsFC were assessed. Relative to baseline, cTBS significantly reduced appetitive and withdrawal cravings immediately after treatment. The effects of cTBS on withdrawal craving persisted for 24 h, as well as produced a reduction in smoking. Furthermore, cTBS significantly strengthened rsFC between the rIFG pars opercularis and subcallosal cingulate (fronto-striatal circuit), and between the rIFG pars opercularis and the right posterior parahippocampal gyrus (fronto-limbic circuit). At post-24 h, cTBS-induced increase in fronto-striatal rsFC was significantly associated with less appetitive craving, while the increase in fronto-limbic rsFC was significantly associated with less withdrawal craving and smoking. These findings warrant further investigation into the potential value of rIFG cTBS to attenuate smoking behavior among individuals with ND.

Early-life seizures alter habit behavior formation and fronto-striatal circuit dynamics

Obsessive compulsive disorder (OCD) can occur comorbidly with epilepsy; both are complex, disruptive disorders that lower quality of life. Both OCD and epilepsy are disorders of hyperexcitable circuits, but it is unclear whether common circuit pathology may underlie the co-occurrence of these two neuropsychiatric disorders. Here, we induced early-life seizures (ELS) in rats to examine habit formation as a model for compulsive behaviors. Compulsive, repetitive behaviors in OCD utilize the same circuitry as habit formation. We hypothesized that rats with ELS could be more susceptible to habit formation than littermate controls, and that altered behavior would correspond to altered signaling in fronto-striatal circuits that underlie decision-making and action initiation. Here, we show instead that rats with ELS were significantly less likely to form habit behaviors compared with control rats. This behavioral difference corresponded with significant alterations to temporal coordination within and between brain regions that underpin the action to habit transition: 1) phase coherence between the lateral orbitofrontal cortex and dorsomedial striatum (DMS) and 2) theta-gamma coupling within DMS. Finally, we used cortical electrical stimulation as a model of transcranial magnetic stimulation (TMS) to show that temporal coordination of fronto-striatal circuits in control and ELS rats are differentially susceptible to potentiating and suppressive stimulation, suggesting that altered underlying circuit physiology may lead to altered response to therapeutic interventions such as TMS.

Associations of lesion location, structural disconnection, and functional diaschisis with depressive symptoms post stroke.

Post-stroke depressive symptoms (PSDS) are common and relevant for patient outcome, but their complex pathophysiology is ill understood. It likely involves social, psychological and biological factors. Lesion location is a readily available information in stroke patients, but it is unclear if the neurobiological substrates of PSDS are spatially localized. Building on previous analyses, we sought to determine if PSDS are associated with specific lesion locations, structural disconnection and/or localized functional diaschisis. In a prospective observational study, we examined 270 patients with first-ever stroke with the Hospital Anxiety and Depression Scale (HADS) around 6 months post-stroke. Based on individual lesion locations and the depression subscale of the HADS we performed support vector regression lesion-symptom mapping, structural-disconnection-symptom mapping and functional lesion network-symptom-mapping, in a reanalysis of this previously published cohort to infer structure-function relationships. We found that depressive symptoms were associated with (i) lesions in the right insula, right putamen, inferior frontal gyrus and right amygdala and (ii) structural disconnection in the right temporal lobe. In contrast, we found no association with localized functional diaschisis. In addition, we were unable to confirm a previously described association between depressive symptom load and a network damage score derived from functional disconnection maps. Based on our results, and other recent lesion studies, we see growing evidence for a prominent role of right frontostriatal brain circuits in PSDS.

Interaction of Person-Affect-Cognition-Execution (I-PACE) Model on Addictive Behavior

AbstractsIntroductions: Adiction is a pattern of substance abuse behavior characterized by overuse of the substance (compulsive use), the safety of its availability, and a high likelihood of relapse after discontinuation. There are 3 (three) stages of addiction, those are a stage of internal change, lifestyle change, and life breakdown. Objectives: This study aims to explore the I-PACE concepts about its components and their relation with the emergence of addictive usage of certain internet services including gaming, online gambling, pornography addiction, online shopping, and social networking. Methods: This study is a literature review that collects from various source of scientific journals related to the psychiatric management of the disorder. Several studies from the international database Pubmed Central including textbooks review papers, comments, and editorials are reviewed to evaluate I-PACE concepts concerning the components and their interaction with addictive behavior. Results: The findings show that the I-PACE model which includes the P component (person), the A component (affective), the C component (cognitive), and the E component (executive function) explains the disruption in a person’s decision-making. The anatomy of the frontostriatal circuit, notably between the ventral striatum, amygdala, and dorsolateral prefrontal area, is particularly significant for the early stages of the addictive process and the dorsal striatum for the latter stages. Conclusions: Interactions between components that occur in certain situations will result in addictive behavior due to the formation of satisfaction and compensation related to that behavior .

Regulation of social interaction in mice by a frontostriatal circuit modulated by established hierarchical relationships

Social hierarchies exert a powerful influence on behavior, but the neurobiological mechanisms that detect and regulate hierarchical interactions are not well understood, especially at the level of neural circuits. Here, we use fiber photometry and chemogenetic tools to record and manipulate the activity of nucleus accumbens-projecting cells in the ventromedial prefrontal cortex (vmPFC-NAcSh) during tube test social competitions. We show that vmPFC-NAcSh projections signal learned hierarchical relationships, and are selectively recruited by subordinate mice when they initiate effortful social dominance behavior during encounters with a dominant competitor from an established hierarchy. After repeated bouts of social defeat stress, this circuit is preferentially activated during social interactions initiated by stress resilient individuals, and plays a necessary role in supporting social approach behavior in subordinated mice. These results define a necessary role for vmPFC-NAcSh cells in the adaptive regulation of social interaction behavior based on prior hierarchical interactions.

Spontaneous Brain Activity Alterations in First-Episode Psychosis: A Meta-analysis of Functional Magnetic Resonance Imaging Studies.

Several studies have shown that spontaneous brain activity, including the total and fractional amplitude of low-frequency fluctuations (LFF) and regional homogeneity (ReHo), is altered in psychosis. Nonetheless, neuroimaging results show a high heterogeneity. For this reason, we gathered the extant literature on spontaneous brain activity in first-episode psychosis (FEP), where the effects of long-term treatment and chronic disease are minimal. A systematic research was conducted on PubMed, Scopus, and Web of Science to identify studies exploring spontaneous brain activity and local connectivity in FEP estimated using functional magnetic resonance imaging. 20 LFF and 15 ReHo studies were included. Coordinate-Based Activation Likelihood Estimation Meta-Analyses stratified by brain measures, age (adolescent vs adult), and drug-naïve status were performed to identify spatially-convergent alterations in spontaneous brain activity in FEP. We found a significant increase in LFF in FEP compared to healthy controls (HC) in the right striatum and in ReHo in the left striatum. When pooling together all studies on LFF and ReHo, spontaneous brain activity was increased in the bilateral striatum and superior and middle frontal gyri and decreased in the right precentral gyrus and the right inferior frontal gyrus compared to HC. These results were also replicated in the adult and drug-naïve samples. Abnormalities in the frontostriatal circuit are present in early psychosis independently of treatment status. Our findings support the view that altered frontostriatal can represent a core neural alteration of the disorder and could be a target of treatment.

Distributed processing for value-based choice by prelimbic circuits targeting anterior-posterior dorsal striatal subregions in male mice

Fronto-striatal circuits have been implicated in cognitive control of behavioral output for social and appetitive rewards. The functional diversity of prefrontal cortical populations is strongly dependent on their synaptic targets, with control of motor output mediated by connectivity to dorsal striatum. Despite evidence for functional diversity along the anterior-posterior striatal axis, it is unclear how distinct fronto-striatal sub-circuits support value-based choice. Here we found segregated prefrontal populations defined by anterior/posterior dorsomedial striatal target. During a feedback-based 2-alternative choice task, single-photon imaging revealed circuit-specific representations of task-relevant information with prelimbic neurons targeting anterior DMS (PL::A-DMS) robustly modulated during choices and negative outcomes, while prelimbic neurons targeting posterior DMS (PL::P-DMS) encoded internal representations of value and positive outcomes contingent on prior choice. Consistent with this distributed coding, optogenetic inhibition of PL::A-DMS circuits strongly impacted choice monitoring and responses to negative outcomes while inhibition of PL::P-DMS impaired task engagement and strategies following positive outcomes. Together our data uncover PL populations engaged in distributed processing for value-based choice.

Differential Associations of Mobility With Fronto-Striatal Integrity and Lesion Load in Older Adults With and Without Multiple Sclerosis

Background Mobility impairment is common in older persons with multiple sclerosis (MS), and further compounded by general age-related mobility decline but its underlying brain substrates are poorly understood. Objective Examine fronto-striatal white matter (WM) integrity and lesion load as imaging correlates of mobility outcomes in older persons with and without MS. Methods Fifty-one older MS patients (age 64.9 ± 3.7 years, 29 women) and 50 healthy, matched controls (66.2 ± 3.2 years, 24 women), participated in the study, which included physical and cognitive test batteries and 3T MRI imaging session. Primary imaging measures were fractional anisotropy (FA) and WM lesion load. The relationship between mobility impairment, defined using a validated short physical performance battery cutoff score, and neuroimaging measures was assessed with stratified logistic regression models. FA was extracted from six fronto-striatal circuits (left/right): dorsal striatum (dStr)-to-anterior dorsolateral prefrontal cortex (aDLPFC), dStr-to-posterior DLPFC, and ventral striatum (vStr)-to-ventromedial prefrontal cortex (VMPFC). Results Mobility impairment was significantly associated with lower FA in two circuits, left dStr-aDLPFC (P = .003) and left vStr-VMPFC (P = .004), in healthy controls but not in MS patients (P > .20), for fully adjusted regression models. Conversely, in MS patients but not in healthy controls, mobility impairment was significantly associated with greater lesion volume (P < .02). Conclusions Comparing older persons with and without MS, we provide compelling evidence of a double dissociation between the presence of mobility impairment and two neuroimaging markers of white matter integrity, fronto-striatal fractional anisotropy, and whole brain lesion load.

Differential neural processing of value during decision-making in adults with attention-deficit/hyperactivity disorder and healthy controls.

Risk-taking behaviours are observed among adults with attention-deficit/hyperactivity disorder (ADHD). We sought to evaluate altered neural processing of stimuli values associated with risk-taking decision behaviour, distinct from learning requirements, among adults with ADHD. Overall, 32 adults with ADHD and 32 healthy controls without ADHD underwent a lottery choice task in a functional magnetic resonance imaging (fMRI) experiment. Participants accepted or rejected stakes with explicit information about variable probabilities of winning or losing points at different magnitudes. Outcomes were independent across trials, circumventing reward learning. Data analysis explored group differences in neurobehavioural responses to stimuli values during choice decision-making processing and outcome feedback. Compared with healthy controls, adults with ADHD had slower response times and tended to accept more stakes with a middle-to-low probability of winning. Adults with ADHD had evidence of lower dorsolateral prefrontal cortex (DLPFC) activity and reduced sensitivity in the ventromedial prefrontal cortex (VMPFC) region of interest in response to linear changes in probability, compared with healthy controls. Lower DLPFC responses were associated with lower VMPFC probability sensitivity and greater risk-taking among healthy controls but not adults with ADHD. Compared with health controls, adults with ADHD showed higher responses to loss outcomes in the putamen and hippocampus. Assessments of real-life decision behaviours are required to further validate the experimental findings. Our findings explore tonic and phasic neural processing of value-related information that modulates risk-taking behaviours among adults with ADHD. Dysregulated neural computation of the values of behavioural actions and outcomes in the frontostriatal circuits may underlie decision processing distinct from reward learning differences among adults with ADHD. NCT02642068.

Stress degrades working memory-related frontostriatal circuit function.

Goal-directed behavior is dependent on neuronal activity in the prefrontal cortex (PFC) and extended frontostriatal circuitry. Stress and stress-related disorders are associated with impaired frontostriatal-dependent cognition. Our understanding of the neural mechanisms that underlie stress-related cognitive impairment is limited, with the majority of prior research focused on the PFC. To date, the actions of stress across cognition-related frontostriatal circuitry are unknown. To address this gap, the current studies examined the effects of acute noise-stress on the spiking activity of neurons and local field potential oscillatory activity within the dorsomedial PFC (dmPFC) and dorsomedial striatum (dmSTR) in rats engaged in a test of spatial working memory. Stress robustly suppressed responses of both dmPFC and dmSTR neurons strongly tuned to key task events (delay, reward). Additionally, stress strongly suppressed delay-related, but not reward-related, theta and alpha spectral power within, and synchrony between, the dmPFC and dmSTR. These observations provide the first demonstration that stress disrupts the neural coding and functional connectivity of key task events, particularly delay, within cognition-supporting dorsomedial frontostriatal circuitry. These results suggest that stress-related degradation of neural coding within both the PFC and striatum likely contributes to the cognition-impairing effects of stress.

Altered Associations Between Motivated Performance and Frontostriatal Functional Connectivity During Reward Anticipation in Schizophrenia.

The neuronal mechanisms that underlie deficits in effort cost computation in schizophrenia (SZ) are poorly understood. Given the role of frontostriatal circuits in valence-oriented motivation, we hypothesized that these circuits are either dysfunctional in SZ or do not appropriately predict behavior in SZ when task conditions are difficult and good performance is rewarded. A total of 52 people with recent onset SZ-spectrum disorders and 48 healthy controls (HCs) performed a 3T fMRI task with 2 valence conditions (rewarded vs neutral) and 2 difficulty conditions. Frontostriatal connectivity was extracted during the cue (anticipatory) phase. Individual behavior was fit using a drift-diffusion model, allowing the performance parameter, drift rate (DR), to vary between task conditions. Three models were examined: A group × condition model of DR, a group × condition model of connectivity, and a regression model of connectivity predicting DR depending on group and condition. DRs showed the expected positive correlation with accuracy and a negative association with reaction time. The SZ group showed a deficit in DR but did not differ in overall connectivity or show a valence-specific deficit in connectivity. Significant group × valence × difficulty interactions, however, were observed on the relationship between right dorsolateral prefrontal (DLPFC)-striatal connectivity and DR (DLPFC-Caudate: F = 10.92, PFDR = .004; DLPFC-Putamen: F = 5.14, PFDR = .048) driven by more positive relationships between DR and connectivity during cues for the difficult-rewarded condition in HCs compared to SZ. These findings suggest that frontostriatal connectivity is less predictive of performance in SZ when task difficulty is increased and a reward incentive is applied.

Functional connectivity between pre-supplementary motor area and inferior parietal lobule associated with impaired motor response inhibition in first-degree relatives of patients with obsessive-compulsive disorder.

Previous studies have suggested that specific fronto-striatal circuits are associated with impaired motor response inhibition in patients with obsessive-compulsive disorder (OCD) and their relatives. However, no study has investigated the underlying resting-state network associated with motor response inhibition in the unaffected first-degree relatives of patients with OCD. We measured motor response inhibition using stop-signal task, and obtained resting-state fMRI in 23 first-degree relatives and 52 healthy control participants. We explored the group differences in the functional network from seed regions-of-interest (ROIs) associated with motor response inhibition abilities. We used the inferior frontal gyrus (IFG) and pre-supplementary motor area (pre-SMA) as seed-ROIs. A significant group difference was observed in functional connectivity between the pre-SMA and inferior parietal lobule. In the relative group, reduced functional connectivity between these areas was associated with a longer stop-signal reaction time. Additionally, relatives showed significantly greater functional connectivity between the IFG and SMA, precentral, and postcentral areas. Our results could provide new insights into the resting-state neural activity of the pre-SMA underlying impaired motor response inhibition of unaffected first-degree relatives. In addition, our results suggested that relatives have an altered connectivity of the sensorimotor region, similar to that of patients with OCD shown in previous literature.

Exposure to a sensory functional ingredient in the pig model modulates the blood-oxygen-level dependent brain responses to food odor and acute stress during pharmacological MRI in the frontostriatal and limbic circuits.

In the present study, we examined the effects of a supplementation with a sensory functional ingredient (FI, D16729, Phodé, France) containing vanillin, furaneol, diacetyl and a mixture of aromatic fatty acids on the behavioural and brain responses of juvenile pigs to acute stress. Twenty-four pigs were fed from weaning with a standard granulated feed supplemented with the functional ingredient D16729 (FS animals, N = 12) or a control formulation (CT animals, N = 12). After a feed transition (10 days after weaning), the effects of FI were investigated on eating behaviour during two-choice feed preference tests. Emotional reactivity to acute stress was then investigated during openfield (OF), novel suddenly moving object (NSO), and contention tests. Brain responses to the FI and the two different feeds' odour, as well as to an acute pharmacological stressor (injection of Synacthen®) were finally investigated with functional magnetic resonance imaging (fMRI). FS animals tended to spend more time above the functional feed (p = 0.06) and spent significantly more time at the periphery of the arena during NSO (p < 0.05). Their latency to contact the novel object was longer and they spent less time exploring the object compared to CT animals (p < 0.05 for both). Frontostriatal and limbic responses to the FI were influenced by previous exposure to FI, with higher activation in FS animals exposed to the FI feed odor compared to CT animals exposed to a similarly familiar feed odor without FI. The pharmacological acute stress provoked significant brain activations in the prefrontal and thalamic areas, which were alleviated in FS animals that also showed more activity in the nucleus accumbens. Finally, the acute exposure to FI in naive animals modulated their brain responses to acute pharmacological stress. Overall, these results showed how previous habituation to the FI can modulate the brain areas involved in food pleasure and motivation while alleviating the brain responses to acute stress.

Abnormal functional connectivity of the frontostriatal circuits in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with an increased incidence of cognitive and emotional disorders. Previous studies have indicated that the frontostriatal circuits play a significant role in brain disorders. However, few studies have investigated functional connectivity (FC) abnormalities in the frontostriatal circuits in T2DM. We aimed to investigate the abnormal functional connectivity (FC) of the frontostriatal circuits in patients with T2DM and to explore the relationship between abnormal FC and diabetes-related variables. Twenty-seven patients with T2DM were selected as the patient group, and 27 healthy peoples were selected as the healthy controls (HCs). The two groups were matched for age and sex. In addition, all subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological evaluation. Seed-based FC analyses were performed by placing six bilateral pairs of seeds within a priori defined subdivisions of the striatum. The functional connection strength of subdivisions of the striatum was compared between the two groups and correlated with each clinical variable. Patients with T2DM showed abnormalities in the FC of the frontostriatal circuits. Our findings show significantly reduced FC between the right caudate nucleus and left precentral gyrus (LPCG) in the patients with T2DM compared to the HCs. The FC between the prefrontal cortex (left inferior frontal gyrus, left frontal pole, right frontal pole, and right middle frontal gyrus) and the right caudate nucleus has a significant positive correlation with fasting blood glucose (FBG). The results showed abnormal FC of the frontostriatal circuits in T2DM patients, which might provide a new direction to investigate the neuropathological mechanisms of T2DM.

PO083 / #526 STEREOTACTICALLY GUIDED BRAIN MODULATION OF THE FRONTOSTRIATAL CIRCUITS FOR HUNTINGTON’S DISEASE: CURRENT STATE: E-POSTER VIEWING

In light of the lack of disease-modifying therapies, stereotactically assisted intracranial therapies targeting the pallidal area (globus pallidus) and the frontostriatal circuits, such as deep-brain stimulation (DBS), stereotactic lesioning (pallidotomy), and brain-grafting approaches (DNA-targeting approach, zinc-finger transcription factors, CRISPR/Cas9, and posttranscriptional RNA targeting), have gained increased recognition for the treatment of otherwise drug-refractory Huntington’s disease (HD)-associated chorea (HD-C), dystonia (HD-Dy), and parkinsonism (HD-P).

Transdiagnostic profiles of behaviour and communication relate to academic and socioemotional functioning and neural white matter organisation.

Behavioural and language difficulties co-occur in multiple neurodevelopmental conditions. Our understanding of these problems has arguably been slowed by an overreliance on study designs that compare diagnostic groups and fail to capture the overlap across different neurodevelopmental disorders and the heterogeneity within them. We recruited a large transdiagnostic cohort of children with complex needs (N = 805) to identify distinct subgroups of children with common profiles of behavioural and language strengths and difficulties. We then investigated whether and how these data-driven groupings could be distinguished from a comparison sample (N = 158) on measures of academic and socioemotional functioning and patterns of global and local white matter connectome organisation. Academic skills were assessed via standardised measures of reading and maths. Socioemotional functioning was captured by the parent-rated version of the Strengths and Difficulties Questionnaire. We identified three distinct subgroups of children, each with different levels of difficulties in structural language, pragmatic communication, and hot and cool executive functions. All three subgroups struggled with academic and socioemotional skills relative to the comparison sample, potentially representing three alternative but related developmental pathways to difficulties in these areas. The children with the weakest language skills had the most widespread difficulties with learning, whereas those with more pronounced difficulties with hot executive skills experienced the most severe difficulties in the socioemotional domain. Each data-driven subgroup could be distinguished from the comparison sample based on both shared and subgroup-unique patterns of neural white matter organisation. Children with the most pronounced deficits in language, cool executive, or hot executive function were differentiated from the comparison sample by altered connectivity in predominantly thalamocortical, temporal-parietal-occipital, and frontostriatal circuits, respectively. These findings advance our understanding of commonly co-morbid behavioural and language problems and their relationship to behavioural outcomes and neurobiological substrates.

Neuropsychological, neuropsychiatric, and clinical correlates of affective and cognitive theory of mind in Parkinson's disease: A meta-analysis.

Theory of mind (ToM) is the ability to infer others' mental (Cognitive) and emotional (Affective) states, both being impaired in Parkinson's disease (PD). However, the clinical, neuropsychological, and neuropsychiatric features underlying Affective and Cognitive ToM deficits in PD are unclear. Therefore, we performed a meta-analytic study to test whether PD demographical, clinical, neuropsychological, or neuropsychiatric changes related differently to both ToM processes. A systematic literature search was performed up to January 2022, including a total of 31 studies following our search terms. Data from each study were obtained from demographic (age, education), clinical (disease duration, Hoehn & Yahr staging system, Unified Parkinson's Disease Rating Scale-III, levodopa equivalent daily dose), neuropsychological (global cognitive functioning, memory subdomains, executive functions subdomains, processing speed/complex attention/working memory, visuospatial and constructional abilities, and language), and neuropsychiatric (depression, apathy, anxiety) variables. Affective ToM impairment in PD was related to lower educational level and global cognition, deficits of generativity, decision making, attention/working memory, and language. Conversely, Cognitive ToM deficits were associated with advanced age, poorer global cognition, executive dysfunctions, and language impairments. Medication moderated the relationship between attention/working memory and Cognitive ToM, whereas age moderated the association of Affective ToM with language. No significant associations were found between ToM deficits and patients' neuropsychiatric or clinical states. These findings clarify the neuropsychological and clinical features that explain ToM deficits in PD. Possibly, our results suggest the need to explore the complex neural networks involving frontostriatal and temporoparietal circuits behind changes in social cognition in PD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pre-operative cognitive burden as predictor of motor outcome following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

The interrelationship between neurocognitive impairments and motor functions was observed in patients with advanced Parkinson's disease (PD). This study was conducted to identify pre-operative neurocognitive and clinical predictors of short-term motor outcome following subthalamic nucleus deep brain stimulation (STN-DBS). All consecutive PD patients who were eligible for bilateral STN-DBS from 2009 to 2019 were evaluated before and at 1year following surgery. Standard motor evaluation and neurocognitive tests including global cognition, memory, executive functions (attention and category fluency), confrontational speech, visuospatial abilities, and mood were conducted at baseline. The post-operative STN-DBS effects were assessed at 1year following the surgery. Multiple regression analysis was applied to identify baseline independent predictors of post-operative STN-DBS effect. A total of 82 patients were analyzed. It was found that younger age at operation, higher levodopa responsiveness at baseline based on UPDRS-III total score, and better baseline verbal delayed memory and category fluency predicted post-operative motor outcome at 1year following STN-DBS (F = 9.639, p < 0.001, R2 = .340). Our findings demonstrated the role of baseline cognitive burden, especially cognitive processes related to frontostriatal circuits, was significant clinical predictors of short-term motor outcomes following STN-DBS. Profile analysis of neurocognitive functions at baseline is recommended.

Learning to read Chinese promotes two cortico-subcortical pathways: The development of thalamo-occipital and fronto-striatal circuits.

Learning to read may result in network reorganization in the developing brain. The thalamus and striatum are two important subcortical structures involved in learning to read. It remains unclear whether the thalamus and striatum may form two independent cortico-subcortical reading pathways during reading acquisition. In this prospective longitudinal study, we aimed to identify whether there may be two independent cortico-subcortical reading pathways involving the thalamus and striatum and to examine the longitudinal predictions between these two cortico-subcortical pathways and reading development in school-age children using cross-lagged panel modeling. A total of 334 children aged 6–12 years completed two reading assessments and resting functional imaging scans at approximately 12-month intervals. The results showed that there were two independent cortico-subcortical pathways, the thalamo-occipital and fronto-striatal circuits. The former may be part of a visual pathway and was predicted longitudinally by reading ability, and the prediction was stronger in children in lower grades and weaker in children in higher grades. The latter may be part of a cognitive pathway related to attention, memory, and reasoning, which was bidirectionally predicted with reading ability, and the predictive effect gradually increasing with reading development. These results extend previous findings on the relationship between functional connectivity and reading competence in children, highlighting the dynamic relationships between the thalamo-occipital and fronto-striatal circuits and reading acquisition.

Fronto-striatal connectivity patterns account for the impact of methylphenidate on choice impulsivity among healthy adults

Choice impulsivity depicts a preference towards smaller-sooner rewards over larger-delayed rewards, and is often assessed using a delay discounting (DD) task. Previous research uncovered the prominent role of dopaminergic signaling within fronto-striatal circuits in mediating choice impulsivity. Administration of methylphenidate (MPH), an indirect dopaminergic agonist, was shown to reduce choice impulsivity in animals and pathological populations, although significant inter-individual variability in these effects was reported. Whether MPH impacts choice impulsivity among healthy individuals, and whether variability in the impact of MPH is related to fronto-striatal activation and connectivity patterns, has yet to be assessed. Here, fifty-seven healthy young adults completed the DD task twice during fMRI scans, after acute administration of either MPH (20 mg) or placebo, in a randomized double-blind placebo-controlled design. Acute MPH administration was found to reduce choice impulsivity at the group level, yet substantial variability in this behavioral response was observed. MPH was also found to increase activation in the bilateral putamen and the right caudate, and to enhance functional connectivity between the left putamen and medial prefrontal cortex (mPFC), particularly during non-impulsive choices. Notably, the more putamen-mPFC functional connectivity increased during non-impulsive choices following MPH administration, the less an individual was likely to make impulsive choices. These findings reveal, for the first time in healthy adults, that acute MPH administration is associated with reduced choice impulsivity and increased striatal activation and fronto-striatal connectivity; and furthermore, that the magnitude of MPH-induced change in fronto-striatal connectivity may account for individual differences in the impact of MPH on impulsive behavior.