Corticostriatal Functional Connectivity Research Articles

Atypicalities in the developmental trajectory of cortico-striatal functional connectivity in autism spectrum disorder.

Autism spectrum disorder has long been conceptualized as a disorder of "atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions)." However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6-30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.

Motor Symptom Lateralization Influences Cortico-Striatal Functional Connectivity in Parkinson's Disease.

Objective: The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI).Methods: Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation.Results: Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients.Conclusions: Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.

Inflammatory Signaling and Corticostriatal Functional Connectivity to Anticipated Valence and Salience of Reward and Threat Stimuli: An Investigation in Depressed vs. Non-Depressed Young Adults

Inflammatory Signaling and Corticostriatal Functional Connectivity to Anticipated Valence and Salience of Reward and Threat Stimuli: An Investigation in Depressed vs. Non-Depressed Young Adults

Structural and functional brain-wide alterations in A350V Iqsec2 mutant mice displaying autistic-like behavior

IQSEC2 is an X-linked gene that is associated with autism spectrum disorder (ASD), intellectual disability, and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V). Using high-resolution structural and functional MRI, we show that animals with the A350V mutation display increased whole-brain volume which was further found to be specific to the cerebral cortex and hippocampus. Moreover, using a data-driven approach we identify putative alterations in structure–function relations of the frontal, auditory, and visual networks in A350V mice. Examination of these alterations revealed an increase in functional connectivity between the anterior cingulate cortex and the dorsomedial striatum. We also show that corticostriatal functional connectivity is correlated with individual variability in social behavior only in A350V mice, as assessed using the three-chamber social preference test. Our results at the systems-level bridge the impact of previously reported changes in AMPA receptor trafficking to network-level disruption and impaired social behavior. Further, the A350V mouse model recapitulates similarly reported brain-wide changes in other ASD mouse models, with substantially different cellular-level pathologies that nonetheless result in similar brain-wide alterations, suggesting that novel therapeutic approaches in ASD that result in systems-level rescue will be relevant to IQSEC2 mutations.

Altered cortico-striatal functional connectivity in people with high levels of schizotypy: A longitudinal resting-state study.

Cortico-striatal functional connectivity has been implicated in the neuropathology of schizophrenia. However, the longitudinal relationship between the cortico-striatal connectivity and schizotypy remains unknown. We examined the resting-state fMRI connectivity in 27 individuals with a high level of schizotypy and 20 individuals with a low level of schizotypy at baseline and 18 months later. Correlations between changes in cortico-striatal connectivity and changes in schizotypy scores over time were examined. We found both increased and decreased cortico-striatal connectivity in individuals with a high level of schizotypy at baseline. Over time, these individuals showed improvement in both the negative and positive schizotypal domains. Changes in striatal-insula connectivity were positively correlated with changes in positive schizotypy from baseline to follow-up. Our results suggested impaired cortico-striatal connectivity in individuals with a high level of schizotypy. The dysconnectivity mainly involves the dorsal striatum. The connectivity between the dorsal striatum and the insula may be a putative marker for temporal changes in positive schizotypy.

Frontal Corticostriatal Functional Connectivity Reveals Task Positive and Negative Network Dysregulation in Relation to Adhd, Sex, and Inhibitory Control

Frontal Corticostriatal Functional Connectivity Reveals Task Positive and Negative Network Dysregulation in Relation to Adhd, Sex, and Inhibitory Control

Impaired cortico-striatal functional connectivity is related to trait impulsivity in unmedicated patients with obsessive-compulsive disorder

ObjectivesConvergent evidence has demonstrated that trait impulsivity, a key feature in obsessive-compulsive disorder (OCD), involves dysregulated frontal-striatal circuits. The present study aims to explore relationships between frontal-striatal circuits, trait impulsivity, and obsessive-compulsive symptoms. MethodsThirty-six unmedicated patients with OCD and 50 healthy controls (HCs) matched for age, sex, and years of education underwent a magnetic resonance imaging (MRI) procedure. Voxel-wise statistical parametric analysis was used to investigate the differences in resting-state functional connectivity between brain regions functionally connected to six pairs of a-priori defined striatal seed regions, between patients with OCD and HCs. Associations between frontal-striatal connectivity and both trait impulsivity and symptom severity of OCD were analyzed. ResultsThe results showed altered striatal functional connectivity in OCD group compared to HCs, including increased connectivity of dorsal caudate (DC)-orbitofrontal cortex (OFC), ventral striatum (VS)-OFC, VS-medial prefrontal cortex, and putamen-sensorimotor area, and decreased functional connectivity of DC-anterior cingulate cortex (ACC), putamen-ACC, and putamen-dorsolateral prefrontal cortex (DLPFC). Furthermore, the putamen-DLPFC connectivity was negatively correlated with attentional impulsivity in the OCD group, but showed a positive correlation in HCs. ConclusionsThe present findings suggested that dorsal cognitive circuits could reflect the level of inhibitory control, which is balanced with the impulsive drive in healthy controls, but breakdown in OCD. Our findings supported that DLPFC-putamen connectivity underlying trait impulsivity, which were involved in the pathophysiology of OCD. The findings have provided new insights into the neurobiological mechanisms of OCD.

Aberrant striatal coupling with default mode and central executive network relates to self-reported avolition and anhedonia in schizophrenia

BackgroundAvolition and anhedonia are common symptoms in schizophrenia and are related to poor long-term prognosis. There is evidence for aberrant cortico-striatal function and connectivity as neural substrate of avolition and anhedonia. However, it remains unclear how both relate to shared or distinct striatal coupling with large-scale intrinsic networks. Using resting state functional magnetic resonance imaging (rs-fMRI) this study investigated the association of large-scale cortico-striatal functional connectivity with self-reported and clinician-rated avolition and anhedonia in subjects with schizophrenia. MethodsSeventeen subjects with schizophrenia (SZ) and 28 healthy controls (HC) underwent rs-fMRI. Using Independent Component Analysis (ICA), we assessed Independent Components (ICs) reflecting intrinsic connectivity networks (ICNs), intra intrinsic functional connectivity within the ICs (intra-iFC), and intrinsic functional connectivity between different ICs (inter-iFC). Avolition and anhedonia were assessed using the Self Evaluation Scale for Negative Symptoms and the Brief Negative Symptom Scale. ResultsICA revealed three striatal components and six cortical ICNs. Both self-rated avolition and anhedonia correlated with increased inter-iFC between the caudate and posterior Default Mode Network (pDMN) and between the caudate and Central Executive Network (CEN). In contrast, clinician-rated avolition and anhedonia were not correlated with cortico-striatal connectivity. Group comparison revealed trend-wise decreased inter-iFC between the caudate and Salience Network (SN) in schizophrenia patients compared to HC. DiscussionSelf-rated, but not clinician-rated, avolition and anhedonia was associated with aberrant striatal coupling with the default mode and the central executive network. These findings suggest that self-reported and clinician-rated scores might capture different aspects of motivational and hedonic deficits in schizophrenia and therefore relate to different cortico-striatal functional abnormalities.

A multivariate analysis of the association between corticostriatal functional connectivity and psychosis-like experiences in the general community

Dysfunction of dorsal corticostriatal (CST) circuitry is thought to play an important role in psychosis. Here, we use multivariate analysis to characterize covariance between CST functional connectivity and psychosis-like experiences (PLEs) in non-clinical individuals. In 353 healthy adults (155 males), we use partial least squares (PLS) to identify latent variables (LV) describing covariance between seven PLE questionnaire measures and functional connectivity estimated between each of six striatal seed regions and the rest of the brain using multiband resting-state fMRI. Hypothesis-driven PLS of the dorsal caudate (DC) seed identified one significant LV, accounting for 23.88% of covariance, with loadings from nearly all PLE subscales. Cortical regions implicated in this LV comprise anterior cingulate and left dorsolateral prefrontal cortex. Lower connectivity between these cortical areas and the DC seed was associated with more severe PLEs. Using multivariate modeling, we identified an association between dorsal CST connectivity and PLEs in the general community that implicates similar brain regions to those identified in patient groups. Our results highlight that the severity of both positive/negative symptom-like PLEs is related with functional coupling between the DC and dorsolateral PFC, suggesting this neural circuit may play a role in mediating risk for general psychosis-related psychopathology.

Peripheral inflammation is associated with dysfunctional corticostriatal circuitry and executive dysfunction in bipolar disorder patients

Bipolar disorder (BD) has been linked to abnormal frontal and striatal function, and elevated inflammatory responses. However, the impact of peripheral inflammation on the corticostriatal functional connectivity (FC) remains obscure in BD. The current study aimed to explore the association between peripheral inflammation and corticostriatal connectivity in euthymic BD. We recruited 25 euthymic BD patients and 43 healthy controls (HCs) from the community. Resting state functional images were obtained using 3T magnetic resonance imaging (fMRI), and striatal seed-based whole-brain functional connectivity analyses were performed, with the fasting plasma high-sensitivity C-reactive protein (hs-CRP) level entered as a regressor of interest. The participants also completed the Wisconsin Card-Sorting Test (WCST) and the Continuous Performance Test (CPT). The euthymic BD group had a similar hs-CRP level to the HC group, but a significantly poorer cognitive performance. Compared with the HC group, a higher connectivity between the right dorsal caudal putamen (dcP) and the ventral lateral prefrontal cortex (vlPFC) in the BD group was significantly correlated with a higher hs-CRP level. Stronger dcP-vlPFC connectivity was correlated with a lower CPT unmasked d' in the BD group. BD patients might be particularly sensitive to the effects of inflammation on corticostriatal connectivity. The potentially greater sensitivity of BD patients to peripheral inflammation may differentially modulate the cognitive and reward related corticostriatal circuitry, which may contribute to the pathophysiology of cognitive-affective dysregulation in the euthymic state. Anti-inflammatory or other circuit-specific treatment is warranted for individualized treatment in BD.

The Neural Signature of Impaired Dual-Tasking in Idiopathic Rapid Eye Movement Sleep Behavior Disorder Patients.

The objective of this cross-sectional study was to determine the neural signature of dual-tasking deficits in idiopathic rapid eye movement sleep behavior disorder using a validated gait paradigm. Fifty-eight participants (28 controls; 30 idiopathic rapid eye movement sleep behavior disorder patients) were recruited; 52 participants had functional MRI scans as they performed a validated dual-task virtual reality gait paradigm using foot pedals. Forty-one participants completed single- and dual-task "overground walking" on a pressure sensor carpet. Idiopathic rapid eye movement sleep behavior disorder patients showed deficits in dual-tasking (i.e., greater mean step time) compared to controls during "overground walking." Functional MRI revealed that idiopathic rapid eye movement sleep behavior disorder patients had reduced blood-oxygen-level-dependent signal change in the dorsal caudate nucleus, and significantly different corticostriatal functional connectivity patterns from controls, when dual-tasking in high versus low cognitive load. While controls showed greater connectivity between frontoparietal and motor networks, idiopathic rapid eye movement sleep behavior disorder patients exhibited less change in this connectivity as a function of cognitive load. These findings demonstrate evidence of dual-task gait deficits in idiopathic rapid eye movement sleep behavior disorder patients, underpinned by disrupted corticostriatal connectivity. Minimal differences in the level of functional connectivity between dual-tasking conditions of high and low cognitive load suggest that idiopathic rapid eye movement sleep behavior disorder patients recruit cognitive networks to control gait even when the cognitive demands are low. This may indicate a compensatory strategy for early cognitive decline in idiopathic rapid eye movement sleep behavior disorder. © 2020 International Parkinson and Movement Disorder Society.

The Role of Sex Differences in Cortico-Striatal Functional Connectivity in Schizophrenia

The Role of Sex Differences in Cortico-Striatal Functional Connectivity in Schizophrenia

Obesogenic diet-associated C-reactive protein predicts reduced central dopamine and corticostriatal functional connectivity in female rhesus monkeys

Alterations in dopamine (DA) signaling and reductions in functional connectivity (FC; a measure of temporal correlations of activity between different brain regions) within dopaminergic reward pathways are implicated in the etiology of psychopathology and have been associated with increased concentrations of inflammatory markers, including C-reactive protein. Peripheral and central inflammatory cytokines that have been shown to disrupt DA signaling and corticostriatal FC are associated with C-reactive protein, an acute phase reactant that is used translationally as a marker of systemic inflammation. One factor that can significantly increase systemic inflammation to produce neuroadaptations in reward pathways is a diet that results in fat mass accumulation (e.g. obesogenic diet). The current study in female rhesus monkeys maintained in a standard laboratory chow (n = 18) or on obesogenic diet (n = 16) for 12-months tested the hypothesis that an obesogenic diet would alter central DA and homovanillic acid (HVA) concentrations, and be associated with increased CRP concentrations and decreased FC between corticostriatal regions at 12-months following dietary intervention. We specifically assessed FC between the nucleus accumbens (NAcc) and two sub-regions of the prefrontal cortex (PFC) previously associated with CRP concentrations, the ventromedial PFC (vmPFC) and the orbitofrontal cortex (OFC), which are also involved in emotional and motivational salience assessment, and in goal-directed behavior, impulse control and the salience/value of food, respectively. Results showed that CSF DA concentrations were decreased (p = 0.002), HVA:DA ratios were increased (p = 0.016), and body mass index was increased (p = 0.047) over the 12-months of consuming an obesogenic diet. At 12-months, females maintained in the obesogenic diet exhibited higher CRP concentrations than females consuming chow-only (p = 0.008). Linear regression analyses revealed significant CRP by dietary condition interactions on DA concentrations (β = −5.10; p = 0.017) and HVA:DA ratios (β = 5.14; p = 0.029). Higher CRP concentrations were associated with lower CSF DA concentrations (r = −0.69; p = 0.004) and greater HVA:DA ratios only in females maintained in the obesogenic dietary condition (r = 0.58; p = 0.024). Resting-state magnetic resonance neuroimaging (rs-fMRI) in a subset of females from each diet condition (n = 8) at 12-months showed that higher CRP concentrations were associated decreased FC between the NAcc and subregions of the prefrontal cortex (PFC; p’s < 0.05). Decreased FC between the NAcc and PFC subregions were also associated with lower concentrations of DA and greater HVA:DA ratios (p’s < 0.05). Overall, these data suggest that increased inflammatory signaling driving heightened CRP levels may mediate the adverse consequences of obesogenic diets on DA neurochemistry and corticostriatal connectivity.

Psychopathy and Corticostriatal Connectivity: The Link to Criminal Behavior in Methamphetamine Dependence.

Methamphetamine use and psychopathy are associated with criminal behavior; however, it is unclear how methamphetamine use and psychopathy interact to promote violent, economic and drug offenses. Abnormalities in corticostriatal functional connectivity are exhibited in both psychopathic and methamphetamine dependent individuals, which may contribute to criminal behavior through maladaptive and impulsive decision-making processes. This study shows that psychopathic traits contribute to weaker corticostriatal connectivity in methamphetamine dependence and contributes to an increase in criminal behavior. As the propensity to engage in criminal activity is dependent on a number of factors, a hierarchical regression identifies the contribution of the impulsive antisocial domain of psychopathy, anxiety, years of methamphetamine use and corticostriatal connectivity on different types of criminal offenses. Methamphetamine use and psychopathic traits reduce treatment responsiveness and increase the likelihood of recidivism, and it is therefore important to understand the factors underlying the propensity to engage in criminal behavior.

Functional Connectivity of the Striatum as a Neural Correlate of Symptom Severity in Patient with Obsessive-Compulsive Disorder.

ObjectiveIt is well established that the cortico-striato-thalamo-cortical (CSTC) circuit is implicated in the pathophysiology of obsessive- compulsive disorder (OCD). However, reports on corticostriatal functional connectivity (FC) in OCD have been inconsistent due to the structural and functional heterogeneity of the striatum. Therefore, in the present study, we investigated corticostriatal FC using a fine 12-seed striatal parcellation to overcome this heterogeneity and discover the neural correlates of symptoms in OCD patients. MethodsWe recruited 23 OCD patients and 23 healthy controls (HCs). Whole-brain FC based on striatal seeds was examined using resting-state functional magnetic resonance imaging data and compared across OCD patients and HCs. We conducted correlation analysis between FCs of striatal subregions with significant group differences and symptom severity scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Rating Scale for Depression, and Hamilton Rating Scale for Anxiety (HAM-A).ResultsCompared to HCs, patients demonstrated increased FC of the dorsal caudal putamen and ventral rostral putamen (VRP) with several cortical regions, such as the intracalcarine cortex, inferior frontal gyrus, supramarginal/angular gyrus (SMG/AG), and postcentral gyrus (PCG). Furthermore, FC between the VRP and SMG/AG and between the VRP and PCG was negatively correlated with scores on the Y-BOCS compulsive subscale and the HAM-A, respectively. ConclusionThese findings suggest that striatal subregions have strengthened FC with extensive cortical regions, which may reflect neural correlates of compulsive and anxious symptoms in OCD patients. These results contribute to an improved understanding of OCD pathophysiology by complementing the current evidence regarding striatal FC.

Corticostriatal functional connectivity of bothersome tinnitus in single-sided deafness

Subjective tinnitus is an auditory phantom perceptual disorder without an objective biomarker. Bothersome tinnitus in single-sided deafness (SSD) is particularly challenging to treat because the deaf ear can no longer be stimulated by acoustic means. We contrasted an SSD cohort with bothersome tinnitus (TIN; N = 15) against an SSD cohort with no or non-bothersome tinnitus (NO TIN; N = 15) using resting-state functional magnetic resonance imaging (fMRI). All study participants had normal hearing in one ear and severe or profound hearing loss in the other. We evaluated corticostriatal functional connectivity differences by placing seeds in the caudate nucleus and Heschl’s Gyrus (HG) of both hemispheres. The TIN cohort showed increased functional connectivity between the left caudate and left HG, and left and right HG and the left caudate. Within the TIN cohort, functional connectivity between the right caudate and cuneus was correlated with the Tinnitus Functional Index (TFI) relaxation subscale. And, functional connectivity between the right caudate and superior lateral occipital cortex, and the right caudate and anterior supramarginal gyrus were correlated with the TFI control subscale. These findings support a striatal gating model of tinnitus and suggest tinnitus biomarkers to monitor treatment response and to target specific brain areas for innovative neuromodulation therapies.

Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients.

Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced dyskinesia (LID).Method: To study the effect of clinically-determined anti-parkinsonian medications, 10 PD patients (5 with LID and 5 without LID) have been scanned with FDG-PET (a probe for glucose metabolism) and perfusion MRI (a probe for cerebral blood flow) both when they are ON and OFF medications. Patients additionally underwent resting state fMRI to detect changes in dopamine-mediated cortico-striatal connectivity. The degree of blood flow-glucose metabolism dissociation was quantified by comparing the FDG-PET and perfusion MRI data.Results: A significant interaction effect (imaging modality × medication; blood flow-glucose metabolism dissociation) has been found in the putamen (p = 0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen while mixed effects were observed in cerebral blood flow changes. This dissociation was especially predominant in patients with LID compared to those without. Unlike the prior study, this differentiation was not observed when cortico-striatal functional connectivity was assessed.Conclusion: We confirmed striatal neurovascular dissociation between FDG-PET and perfusion MRI in response to clinically determined anti-parkinsonian medication. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI), which may have the potential to be used as a biomarker for LID (correctly classifying 8 out 10 patients). For wider use of PHI, a larger validation study is warranted.

Nigrostriatal Dopaminergic Dysfunction and Altered Functional Connectivity in REM Sleep Behavior Disorder With Mild Motor Impairment.

Rapid eye movement sleep behavior disorder is parasomnia characterized by symptoms of dream enactment and loss of muscle atonia during rapid eye movement sleep. Mild motor impairment is present in some patients with rapid eye movement sleep behavior disorder and presumed to be a risk factor for conversion to synucleinopathies. The purpose of this study is to identify patients with mild motor impairment by evaluating finger tapping and to investigate its pathophysiology. Twenty-three patients with rapid eye movement sleep behavior disorder and 20 healthy control subjects were recruited in the present study. We accurately evaluated finger tapping including amplitude, peak open, and close speed with a magnetic sensing device and identified patients with mild motor impairment. Moreover, we performed 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane SPECT and resting state functional MRI. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake for each bilateral caudate, anterior putamen, and posterior putamen was calculated and the resting state functional connectivity of sensorimotor network was analyzed. Using finger tapping parameters, we identified eight patients with mild motor impairment. In patients with mild motor impairment, all finger tapping parameters were significantly impaired when compared to patients with normal motor function, while they exhibited no significant differences in Unified Parkinson's Disease Rating Scale part III score. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake in the right posterior putamen, bilateral anterior putamen, and caudate was significantly lower when compared to healthy controls or patients with rapid eye movement sleep behavior disorder with normal motor function. These patients also exhibited decreased cortico-striatal functional connectivity and increased cortico-cerebellar functional connectivity when compared to healthy controls or patients with normal motor function. Our results show that mild motor impairment in rapid eye movement sleep behavior disorder evaluated by finger tapping task presented mild nigrostriatal dopaminergic dysfunction as well as alterations in resting state sensorimotor network. Although longitudinal follow up is necessary, such patients may have higher risk of short-term conversion to synucleinopathies.

Functional Connectivity of the Striatum in Schizophrenia and Psychotic Bipolar Disorder

BackgroundThe striatum is abnormal in schizophrenia and possibly represents a common neurobiological mechanism underlying psychotic disorders. Resting-state functional magnetic resonance imaging studies have not reached a consensus regarding striatal dysconnectivity in schizophrenia, although these studies generally find impaired frontoparietal and salience network connectivity. The goal of the current study was to clarify the pattern of corticostriatal connectivity, including whether corticostriatal dysconnectivity is transdiagnostic and extends into psychotic bipolar disorder. MethodsWe examined corticostriatal functional connectivity in 60 healthy subjects and 117 individuals with psychosis, including 77 with a schizophrenia spectrum illness and 40 with psychotic bipolar disorder. We conducted a cortical seed–based region-of-interest analysis with follow-up voxelwise analysis for any significant results. Further, a striatum seed–based analysis was conducted to examine group differences in connectivity between the striatum and the whole cortex. ResultsCortical region-of-interest analysis indicated that overall connectivity of the salience network with the striatum was reduced in psychotic disorders, which follow-up voxelwise analysis localized to the left putamen. Striatum seed–based analyses showed reduced ventral rostral putamen connectivity with the salience network portion of the medial prefrontal cortex in both schizophrenia and psychotic bipolar disorder. ConclusionsThe current study found evidence of transdiagnostic corticostriatal dysconnectivity in both schizophrenia and psychotic bipolar disorder, including reduced salience network connectivity, as well as reduced connectivity between the putamen and the medial prefrontal cortex. Overall, the current study points to the relative importance of salience network hypoconnectivity in psychotic disorders.

Autism-associated Nf1 deficiency disrupts corticocortical and corticostriatal functional connectivity in human and mouse

Children with the autosomal dominant single gene disorder, neurofibromatosis type 1 (NF1), display multiple structural and functional changes in the central nervous system, resulting in neuropsychological cognitive abnormalities. Here we assessed the pathological functional organization that may underlie the behavioral impairments in NF1 using resting-state functional connectivity MRI. Coherent spontaneous fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional organization of corticocortical and corticostriatal networks in both NF1 pediatric patients and mice with a heterozygous mutation in the Nf1 gene (Nf1+/−). Children with NF1 demonstrated abnormal organization of cortical association networks and altered posterior-anterior functional connectivity in the default network. Examining the contribution of the striatum revealed that corticostriatal functional connectivity was altered. NF1 children demonstrated reduced functional connectivity between striatum and the frontoparietal network and increased striatal functional connectivity with the limbic network. Awake passive mouse functional connectivity MRI in Nf1+/− mice similarly revealed reduced posterior-anterior connectivity along the cingulate cortex as well as disrupted corticostriatal connectivity. The striatum of Nf1+/− mice showed increased functional connectivity to somatomotor and frontal cortices and decreased functional connectivity to the auditory cortex. Collectively, these results demonstrate similar alterations across species, suggesting that NF1 pathogenesis is linked to striatal dysfunction and disrupted corticocortical connectivity in the default network.