Frontostriatal Networks Research Articles

Behavioral disorders in Parkinson disease: current view.

Patients with Parkinson disease (PD) frequently experience several behavioral symptoms, such as anxiety, apathy, irritability, agitation, impulsive control and obsessive-compulsive or REM sleep behavior disorders, which can cause severe psychosocial problems and impair quality of life. Occurring in 30-70% of PD patients, these symptoms can manifest at early stages of the disease, sometimes even before the appearance of classic motor symptoms, while others can develop later. Behavioral changes in PD show distinct patterns of brain atrophy, dopaminergic and serotonergic deterioration, altered neuronal connectivity in frontostriatal, corticolimbic, default mode and other networks due to a cascade linking molecular pathologies and deficits in multiple behavior domains. The changes suggest a multi-system neurodegenerative process in the context of a specific α-synucleinopathy inducing a variety of biochemical and functional changes, the neurobiological basis and clinical relevance of which await further elucidation. This paper is intended to review the recent literature with focus on the main behavioral disturbances in PD patients, their epidemiology, clinical features, risk factors, animal models, neuroimaging findings, pathophysiological backgrounds, and treatment options of these deleterious lesions.

Gamma frequency connectivity in fronto-striatal networks associated with social preference is reduced with traumatic brain injury

Gamma frequency connectivity in fronto-striatal networks associated with social preference is reduced with traumatic brain injury

Frontostriatal salience network expansion in individuals in depression

Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset1. Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals2–4, but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.

Gray matter matters: Cognitive stability and flexibility in schizophrenia spectrum disorder.

Cognitive dysfunction constitutes a core characteristic of schizophrenia spectrum disorders (SZ). Specifically, deficits in updating generative models (i.e., cognitive flexibility) and shielding against distractions (i.e., cognitive stability) are considered critical contributors to cognitive impairment in these patients. Here, we examined the structural integrity of frontostriatal networks and their associations with reduced cognitive stability and flexibility in SZ patients. In a sample of 21 patients diagnosed with SZ and 22 healthy controls, we measured gray matter volume (GMV) using structural MRI. Further, cognitive stability and flexibility were assessed using a switch-drift paradigm, quantifying the successful ignoring of distracters and detection of rule switches. Compared to controls, patients showed significantly smaller GMV in the whole brain and three predefined regions of interest: the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), and caudate nucleus (CN). Notably, GMV in these areas positively correlated with correct rule-switch detection but not with ignoring rule-compatible drifts. Further, the volumetric differences between SZ patients and controls were statistically explainable by considering the behavioral performance in the switch-drift task. Our results indicate that morphological abnormalities in frontostriatal networks are associated with deficient flexibility in SZ patients and highlight the necessity of minimizing neurodevelopmental and progressive brain atrophy in this population.

Task-induced deactivation dysfunction during reward processing is associated with low self-esteem in a possible subtype of major depression.

Low self-esteem is a frequent symptom in major depressive disorder (MDD). This functional magnetic resonance imaging study investigated whether MDD patients with low self-esteem show a distinct neural pathophysiology. Previous studies linked low self-esteem to reduced task-induced deactivation of the pregenual anterior cingulate cortex (pgACC) as a part of the default mode network, and to reduced connectivity between pgACC and reward system. Goya-Maldonado etal. identified an MDD subtype with pgACC and ventral striatal overactivations during reward processing. We hypothesized that this subtype might be characterized by low self-esteem. Eighty-three MDD patients performed the desire-reason dilemma task and completed the Rosenberg Self-Esteem Scale (RSES). Brain activity during bottom-up reward processing was regressed upon the RSES scores, controlling for depression severity measured by the Montgomery-Åsberg Depression Rating Scale. To corroborate the findings, we compared self-esteem scores between patient subgroups with impaired task-induced deactivation (n=31) and with preserved task-induced deactivation (n=31) of the pgACC. Consistent with our a priori hypothesis, activity in a bilateral fronto-striatal network including pgACC and ventral striatum correlated negatively with RSES scores, also when controlling for depression severity. In the additional analysis, patients with impaired task-induced pgACC deactivation showed lower self-esteem (t (52.82)=-2.27; p=.027, d=0.58) compared to those with preserved task-induced pgACC deactivation. We conclude that low self-esteem in MDD patients is linked to a task-induced deactivation dysfunction of the pgACC. Our findings suggest that a previously described possible subtype of MDD with pgACC and ventral striatal overactivations during reward processing is clinically characterized by low self-esteem.

The yes–no reversal phenomenon in patients with primary progressive apraxia of speech

Patients who have a yes–no reversal respond “yes” when they mean no and vice versa. The unintentional response can be made both verbally and with gestures (e.g., head shake or nod, thumbs up or down). Preliminary reports associate this phenomenon with 4-repeat tauopathies including primary progressive apraxia of speech (PPAOS), nonfluent/agrammatic primary progressive aphasia, and corticobasal syndrome; however, the significance and timing of this symptom relative to others are not well understood. Whereas some accounts associate yes–no reversals with other binary reversals (e.g., up/down, hot/cold) and attribute the reversals to disturbances of selection within the language system, others implicate more general inhibitory control processes. Here, we compared clinical and neuroimaging findings across 30 patients with PPAOS (apraxia of speech in the absence of aphasia), 15 of whom had a yes–no reversal complaint and 15 who did not. The two groups did not differ on any of the language or motor speech measures; however, patients who had the yes–no reversal received lower scores on the Frontal Assessment Battery and motor assessments. They also had greater hypometabolism in the left supplementary motor area and bilateral caudate nuclei on [18F]-fluorodeoxyglucose PET, but only the right caudate nucleus cluster survived correction for multiple comparisons. We interpret these results to suggest that the yes–no reversal phenomenon is associated with cognitive abilities that are supported by the frontostriatal network; more specifically, impaired response inhibition.

Mindfulness-based cognitive therapy neurobiology in treatment-resistant obsessive-compulsive disorder: A domain-related resting-state networks approach

Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes —the precuneus and the frontopolar cortex— were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.

Pramipexole restores behavioral inhibition in highly impulsive rats through a paradoxical modulation of frontostriatal networks

Impulse control disorders (ICDs), a wide spectrum of maladaptive behaviors which includes pathological gambling, hypersexuality and compulsive buying, have been recently suggested to be triggered or aggravated by treatments with dopamine D2/3 receptor agonists, such as pramipexole (PPX). Despite evidence showing that impulsivity is associated with functional alterations in corticostriatal networks, the neural basis of the exacerbation of impulsivity by PPX has not been elucidated. Here we used a hotspot analysis to assess the functional recruitment of several corticostriatal structures by PPX in male rats identified as highly (HI), moderately impulsive (MI) or with low levels of impulsivity (LI) in the 5-choice serial reaction time task (5-CSRTT). PPX dramatically reduced impulsivity in HI rats. Assessment of the expression pattern of the two immediate early genes C-fos and Zif268 by in situ hybridization subsequently revealed that PPX resulted in a decrease in Zif268 mRNA levels in different striatal regions of both LI and HI rats accompanied by a high impulsivity specific reduction of Zif268 mRNA levels in prelimbic and cingulate cortices. PPX also decreased C-fos mRNA levels in all striatal regions of LI rats, but only in the dorsolateral striatum and nucleus accumbens core (NAc Core) of HI rats. Structural equation modeling further suggested that the anti-impulsive effect of PPX was mainly attributable to the specific downregulation of Zif268 mRNA in the NAc Core. Altogether, our results show that PPX restores impulse control in highly impulsive rats by modulation of limbic frontostriatal circuits.

Neuroradiological changes in patients with attention deficit hyperactivity disorder: Presentation of 3 cases and literature update

Introduction: Attention deficit/hyperactivity disorder (ADHD) is thought to be caused by structural and functional abnormalities in the frontal-striatal circuitry of the brain. The dorsolateral prefrontal cortex, caudate, pallidum, corpus callosum, and cerebellum all have significantly smaller volumes in children with ADHD. According to recent reports, other cortical and cerebellar regions generally suffer impairment. Case Series: Multiple nodes of dysfunction at the frontostriatal and mesocorticolimbic networks in attention-deficit/hyperactivity disorder (ADHD) have been identified through functional neuroimaging studies. We present a group of three ADHD patients and review the clinical findings and potential connections to neuroimaging tests. DISCUSSION: Adults with ADHD have different brain volume patterns in the areas of the brain responsible for attention and executive function. Conclusion: Among other neuroradiological findings, the ADHD patients in the current study showed changes in the frontal and prefrontal cortex, thickening of the corpus callosum, and elevated levels of glutamine and glutamate in the cerebellum. New studies are required to understand better the clinical finding with potential neuroanatomical and functional changes. Attention-deficit/hyperactivity disorder, brain, and neuroimage are keywords.

Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder — study protocol for a randomized clinical trial

BackgroundAnhedonia and other deficits in reward- and motivation-related processing in psychiatric patients, including patients with major depressive disorder (MDD), represent a high unmet medical need. Neurobiologically, these deficits in MDD patients are mainly associated with low dopamine function in a frontostriatal network. In this study, alterations in brain activation changes during reward processing and at rest in MDD patients compared with healthy subjects are explored and the effects of a single low dose of the dopamine D2 receptor antagonist amisulpride are investigated.MethodsThis is a randomized, controlled, double-blind, single-dose, single-center parallel-group clinical trial to assess the effects of a single dose of amisulpride (100 mg) on blood-oxygenation-level-dependent (BOLD) responses during reward- and motivation-related processing in healthy subjects (n = 60) and MDD patients (n = 60). Using functional magnetic resonance imaging (fMRI), BOLD responses are assessed during the monetary incentive delay (MID) task (primary outcome). Exploratory outcomes include BOLD responses and behavioral measures during the MID task, instrumental learning task, effort-based decision-making task, social incentive delay task, and probabilistic reward task as well as changes in resting state functional connectivity and cerebral blood flow.DiscussionThis study broadly covers all aspects of reward- and motivation-related processing as categorized by the National Institute of Mental Health Research Domain Criteria and is thereby an important step towards precision psychiatry. Results regarding the immediate effects of a dopaminergic drug on deficits in reward- and motivation-related processing not only have the potential to significantly broaden our understanding of underlying neurobiological processes but might eventually also pave the way for new treatment options.Trial registrationClinicalTrials.gov NCT05347199. April 12, 2022.

4 Resting State Functional Connectivity Impairments Implicate CNS Mechanisms Underlying Chronic Pain and Depression in Gulf War Veterans’ Illness

Objective:Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW veterans’ illness (GWVI). GWVI is a poorly understood chronic medical condition, characterized by symptoms indicative of brain function deficits in multiple domains. Among the symptoms of brain impairment GWVI-related chronic headaches and body muscle and joint pain conditions (GWVI-HAP) are the most debilitating, affecting around 64% of the GWVI veterans. Further, depression carries a very high co-morbid rate (>50%) in patients with chronic pain, including GWVI-HAP. In this preliminary study, we examined the integrity of brain function networks in a group of GWI-HAP veterans, with resting state fMRI (rsfMRI).Participants and Methods:Data from the first twenty-two GWVI-HAP veterans from two ongoing parallel clinical trials was examined. Of these 14 subjects (GWVI-HAP-DM) had mild depression (Hamilton Rating Scale for Depression (HSRD < 13); and 8 subjects (GWVI-HAP-DS) had moderate to severe depression (HSRD > 14). Written informed consent was obtained from all participants in the protocol approved by the local Institutional Review Board. RsfMRI data was acquired on a Siemens 3T Prisma-Fit MRI scanner using a 10-minute whole-brain high resolution simultaneous multi-slice (SMS) gradient echo echo-planar imaging (EPI) sequence: TR/TE/FA = 2.2 sec/ 27 msec/80°, and analyzed with well-established image processing pipelines. Functional connectivity (FC) to different regions implicated in depression and chronic pain was assessed with seed-based correlation analysis. Between group differences in FC were obtained with 2-sample t-tests.Results:GWVI-HAP-DS group exhibited significantly (p < 0.05) reduced FC compared to GWVI-HAP-DM between frontal lobe (medial (mPFC), and dorsolateral (dlPFC) prefrontal cortex) and the striatum. This indicates that malfunction of fronto-striatal circuits could be a source of the increased chronic pain and depression seen in veterans with GWVI- HAP-DS. Dysregulation of fronto-striatal networks has been implicated in major depressive disorder as well as many chronic pain conditions. In addition, FC between mPFC, and salience network (SN; anterior insula and dorsal anterior cingulate) and limbic (subgenual and ventral anterior cingulate) regions were also reduced in GWVI-HAP-DS. Similarly, mPFC and SN also exhibited reduced FC to pain processing regions (posterior insula, centromedian thalamus and cerebellum). These FC impairments could reflect greater deficits in regulation of and salience attribution to emotions and nociception in the GWVI-HAP-DS group. Finally, GWVI-HAP-DS also exhibited reduced FC between nodes of the default mode network. DMN impairments also have been observed in many depressive and chronic pain conditions.Conclusions:The results of this preliminary analysis implicate impairments in cognitive control of emotion and nociception as a mechanism underlying the enhanced chronic pain and depression observed in GWVI-HAP veterans, especially those with moderate to severe depression. A fuller picture of deficits in FC in brain function networks is expected to emerge as more GWI-HAP subjects of both groups along with age matched healthy controls are examined in this ongoing project. Better understanding of impairments in these networks in GWI-HAP will benefit the rehabilitation of veterans with GWI-HAP.

Poor response to methylphenidate is associated with a smaller dorsal attentive network in adult Attention-Deficit/Hyperactivity Disorder (ADHD)

Stimulants, such as methylphenidate (MPH), are effective in treating attention-deficit/hyperactivity disorder (ADHD), but there is individual variability in response, especially in adults. To improve outcomes, we need to understand the factors associated with adult treatment response. This longitudinal study investigated whether pre-treatment anatomy of the fronto-striatal and fronto-parietal attentional networks was associated with MPH treatment response. 60 adults with ADHD underwent diffusion brain imaging before starting MPH treatment, and response was measured at two months. We tested the association between brain anatomy and treatment response by using regression-based approaches; and compared the identified anatomical characteristics with those of 20 matched neurotypical controls in secondary analyses. Finally, we explored whether combining anatomical with clinical and neuropsychological data through machine learning provided a more comprehensive profile of factors associated with treatment response. At a group level, a smaller left dorsal superior longitudinal fasciculus (SLF I), a tract responsible for the voluntary control of attention, was associated with a significantly lower probability of being responders to two-month MPH-treatment. The association between the volume of the left SLF I and treatment response was driven by improvement on both inattentive and hyperactive/impulsive symptoms. Only non-responders significantly differed from controls in this tract metric. Finally, our machine learning approach identified clinico-neuropsychological factors associated with treatment response, such as higher cognitive performance and symptom severity at baseline. These novel findings add to our understanding of the pathophysiological mechanisms underlying response to MPH, pointing to the dorsal attentive network as playing a key role.

Cortical paired associative stimulation shows impaired plasticity of inhibition networks as a function of chronic alcohol use.

Response inhibition - or the ability to withhold a suboptimal response - relies on the efficacy of fronto-striatal networks, and is impaired in neuropsychiatric disorders including addiction. Cortical paired associative stimulation (cPAS) is a form of transcranial magnetic stimulation (TMS) which can strengthen neuronal connections via spike-timing-dependent plasticity mechanisms. Here, we used cPAS targeting the fronto-striatal inhibitory network to modulate performance on a response inhibition measure in chronic alcohol use. Fifty-five participants (20 patients with a formal alcohol use disorder (AUD) diagnosis (26-74 years, 6[30%] females) and 20 matched healthy controls (HCs) (27-73 years, 6[30%] females) within a larger sample of 35 HCs (23-84 years, 11[31.4%] females) underwent two randomized sessions of cPAS 1-week apart: right inferior frontal cortex stimulation preceding right presupplementary motor area stimulation by either 4 ms (excitation condition) or 100 ms (control condition), and were subsequently administered the Stop Signal Task (SST) in both sessions. HCs showed decreased stop signal reaction time in the excitation condition (t(19) = -3.01, p = 0.007, [CIs]:-35.6 to -6.42); this facilitatory effect was not observed for AUD (F(1,31) = 9.57, p = 0.004, CIs: -68.64 to -14.11). Individually, rates of SST improvement were substantially higher for healthy (72%) relative to AUD (13.6%) groups (OR: 2.33, p = 0.006, CIs:-3.34 to -0.55). In line with previous findings, cPAS improved response inhibition in healthy adults by strengthening the fronto-striatal network through putative long-term potentiation-like plasticity mechanisms. Furthermore, we identified a possible marker of impaired cortical excitability, and, thus, diminished capacity for cPAS-induced neuroplasticity in AUD with direct implications to a disorder-relevant cognitive process.

Gamma-Aminobutyric Acid and Glutamate Concentrations in the Striatum and Anterior Cingulate Cortex Not Found to Be Associated with Cognitive Flexibility.

Behavioral flexibility and goal-directed behavior heavily depend on fronto-striatal networks. Within these circuits, gamma-aminobutyric acid (GABA) and glutamate play an important role in (motor) response inhibition, but it has remained largely unclear whether they are also relevant for cognitive inhibition. We hence investigated the functional role of these transmitters for cognitive inhibition during cognitive flexibility. Healthy young adults performed two paradigms assessing different aspects of cognitive flexibility. Magnetic resonance spectroscopy (MRS) was used to quantify GABA+ and total glutamate/glutamine (Glx) levels in the striatum and anterior cingulate cortex (ACC) referenced to N-acetylaspartate (NAA). We observed typical task switching and backward inhibition effects, but striatal and ACC concentrations of GABA+/NAA and Glx/NAA were not associated with cognitive flexibility in a functionally relevant manner. The assumption of null effects was underpinned by Bayesian testing. These findings suggest that behavioral and cognitive inhibition are functionally distinct faculties, that depend on (at least partly) different brain structures and neurotransmitter systems. While previous studies consistently demonstrated that motor response inhibition is modulated by ACC and striatal GABA levels, our results suggest that the functionally distinct cognitive inhibition required for successful switching is not, or at least to a much lesser degree, modulated by these factors.

The association between brain serotonin transporter binding and impulsivity and aggression in healthy individuals

The serotonin system plays a critical role in the modulation of impulsive aggression. Although serotonin transporters (SERT) are key in modulating synaptic serotonin levels, few studies have investigated the role of SERT levels in human impulsive aggression. The aim of this study was to investigate whether brain SERT levels are associated with trait impulsive aggression. We included 148 healthy individuals (mean age 29.3 ± 13.0, range 18–80 years, 91 females) who had undergone positron emission positron (PET) examinations with the SERT tracer [11C]DASB and filled in self-report questionnaires of trait aggression, trait impulsivity and state aggression. We evaluated the association between cerebral SERT binding (BPND) and trait impulsive aggression in a latent variable model, with one latent variable (LVSERT) modelled from SERT BPND in frontostriatal and frontolimbic networks implicated in impulsive aggression, and another latent variable (LVIA) modelled from various trait measures of impulsivity and aggression. The LVSERT was not significantly associated with the LVIA (p = 0.8). Post-hoc univariate analyses did not reveal any significant associations between regional SERT levels and trait aggression, trait impulsivity or state aggression, but we found that state aggression at the day of PET scan was significantly lower in LA/LA homozygotes vs S-carriers of the 5-HTTLPR gene (p = 0.008). We conclude that brain SERT binding was not related to variations in trait impulsive aggression or state aggression. Our findings do not support that SERT is involved in mediating the serotonergic effects on aggression and impulsivity, at least not in individuals with non-pathological levels of impulsive aggression.

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case–control study

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales. Our sample consisted of 178 ADHD cases, 103 unaffected siblings, and 173 controls (total N = 454; 8–29 years), for whom genome-wide genotyping was available. PRS-ADHD was constructed using the PRSice-2 software. We found PRS-ADHD to be associated with ADHD symptom severity, a slower and more variable response to Go-stimuli, and altered brain activation during response inhibition in several regions of the bilateral fronto-striatal network. Mean reaction time and intra-individual reaction time variability mediated the association of PRS-ADHD with ADHD symptoms (total, inattention, hyperactivity-impulsivity), and activity in the left temporal pole and anterior parahippocampal gyrus during failed inhibition mediated the relationship of PRS-ADHD with hyperactivity-impulsivity. Our findings indicate that PRS-ADHD are related to ADHD severity on a spectrum of clinical, sub-threshold, and normal levels; more importantly, we show a shared genetic etiology of ADHD and behavioral and neural correlates of response inhibition. Given the modest sample size of our study, future studies with higher power are warranted to explore mediation effects, suggesting that genetic liability to ADHD may adversely affect attention regulation on the behavioral level and point to a possible response inhibition-related mechanistic pathway from PRS-ADHD to hyperactivity-impulsivity.

The Effect of Efavirenz on Reward Processing in Asymptomatic People Living with HIV: A Randomized Controlled Trial.

Functional magnetic resonance imaging (fMRI) studies have demonstrated that HIV-infection affects the fronto-striatal network. It has not been examined what impact efavirenz (EFV), an antiretroviral drug notorious for its neurocognitive effects, has on the reward system: a key subcomponent involved in depressive and apathy symptoms. Therefore, this study aims to investigate the effect of EFV on reward processing using a monetary incentive delay (MID) task. In this multicenter randomized controlled trial, asymptomatic adult participants stable on emtricitabine/tenofovirdisoproxil fumarate (FTC/TDF)/EFV were randomly assigned in a 2:1 ratio to switch to FTC/TDF/rilpivirine (RPV) (n = 30) or continue taking FTC/TDF/EFV (n = 13). At baseline and 12 weeks after therapy switch, both groups performed an MID task. Behavior and functional brain activity related to reward anticipation and reward outcome were assessed with blood-oxygen-level-dependent fMRI. Both groups were matched for age, education level, and time since HIV diagnosis and on EFV. At the behavioral level, both groups had faster response times and better response accuracy during rewarding versus nonrewarding trials, with no improvement resulting from switching FTC/TDF/EFV to FTC/TDF/RPV. No significant change in activation related to reward anticipation in the ventral striatum was found after switching therapy. Both groups had significantly higher activation levels over time, consistent with a potential learning effect. Similar activity related to reward outcome in the orbitofrontal cortex was found. Discontinuing FTC/TDF/EFV was not found to improve activity related to reward anticipation in asymptomatic people living with HIV, with similar cortical functioning during reward outcome processing. It is therefore likely that EFV does not affect motivational control. Further research is needed to determine whether EFV affects motivational control in HIV populations with different characteristics.

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.

Investigation of white matter functional networks underlying different behavioral profiles in attention-deficit/hyperactivity disorder.

Cortical functional network alterations have been widely accepted as the neural basis of attention-deficit/hyperactivity disorder (ADHD). Recently, white matter has also been recognized as a novel neuroimaging marker of psychopathology and has been used as a complement to cortical functional networks to investigate brain-behavior relationships. However, disorder-specific features of white matter functional networks (WMFNs) are less well understood than those of gray matter functional networks. In the current study, we constructed WMFNs using a new strategy to characterize behavior-related network features in ADHD. We recruited 46 drug-naïve boys with ADHD and 46 typically developing (TD) boys, and used clustering analysis on resting-state functional magnetic resonance imaging data to generate WMFNs in each group. Intrinsic activity within each network was extracted, and the associations between network activity and behavior measures were assessed using correlation analysis. Nine WMFNs were identified for both ADHD and TD participants. However, boys with ADHD showed a splitting of the inferior corticospinal-cerebellar network and lacked a cognitive control network. In addition, boys with ADHD showed increased activity in the dorsal attention network and somatomotor network, which correlated positively with attention problems and hyperactivity symptom scores, respectively, while they presented decreased activity in the frontoparietal network and frontostriatal network in association with poorer performance in response inhibition, working memory, and verbal fluency. We discovered a dual pattern of white matter network activity in drug-naïve ADHD boys, with hyperactive symptom-related networks and hypoactive cognitive networks. These findings characterize two distinct types of WMFN in ADHD psychopathology.

Altered dynamic functional connectivity of striatal-cortical circuits in Juvenile Myoclonic Epilepsy

ObjectiveTo investigate whether the dynamic functional connectivity (dFC) of striatal-cortical circuits changes in juvenile myoclonic epilepsy (JME). MethodsThe resting-state EEG-fMRI and the sliding-window approach were adopted to explore the dynamic striatal-cortical circuitry in thirty JME patients compared with 30 well-matched health controls (HCs). Six pairs of striatal seeds were selected as regions of interests. The correlation analysis was performed to reveal the relationship between the altered dFC variability and clinical variables in JME group. ResultsJME patients exhibited increased dFC variability mainly involved in fronto-striatal and striatal-thalamic networks; decreased dFC variability between striatum subdivisions and default mode network (DMN) regions compared with HCs (p<0.05, GRF corrected). In addition, the hypervariability between left ventral-rostral putamen and left medial superior frontal gyrus was positively (r= 0.493, p=0.008) correlated with the mean frequency score of myoclonic seizures in JME group. ConclusionJME presented altered dFC variability in striatal-cortical circuits. The pattern of altered circuits showed increased variability in fronto-striatal and striatal-thalamic networks and decreased variability in striatal-DMN. These results provide novel information about the dynamic neural striatal-cortical circuitry of JME.