Corticostriatal Connectivity Research Articles

Methylphenidate differentially alters corticostriatal connectivity after traumatic brain injury.

Traumatic brain injury commonly impairs attention and executive function, and disrupts the large-scale brain networks that support these cognitive functions. Abnormalities of functional connectivity are seen in corticostriatal networks, which are associated with executive dysfunction and damage to neuromodulatory catecholaminergic systems caused by head injury. Methylphenidate, a stimulant medication that increases extracellular dopamine and noradrenaline, can improve cognitive function following TBI. In this experimental medicine add-on study to a randomised, double-blind, placebo-controlled clinical trial, we test whether administration of methylphenidate alters corticostriatal network function and influences drug response. 43 moderate-severe traumatic brain injury patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. 28 patients were included in the neuropsychological and functional imaging analysis (4 females, mean age 40.9±12.7, range 20-65) and underwent functional MRI and neuropsychological assessment after each block. 123I-Ioflupane SPECT Dopamine Transporter (DAT) scans were performed, and specific binding ratios were extracted from caudate subdivisions. Functional connectivity and the relationship to cognition was compared between drug and placebo conditions. Methylphenidate increased caudate to anterior cingulate cortex functional connectivity compared to placebo and decreased connectivity from the caudate to default mode network. Connectivity within the default mode network was also decreased by methylphenidate administration and there was a significant relationship between caudate functional connectivity and DAT binding during methylphenidate administration. Methylphenidate significantly improved executive function in TBI patients, and this was associated with alterations in the relationship between executive function and right anterior caudate functional connectivity. Functional connectivity is strengthened to brain regions including the anterior cingulate that are activated when attention is focused externally. These results show that methylphenidate alters caudate interactions with cortical brain networks involved in executive control. In contrast, caudate functional connectivity reduces to default mode network regions involved in internally focused attention and that deactivate during tasks that require externally focused attention. These results suggest that the beneficial cognitive effects of methylphenidate may be mediated through its impact on the caudate. Methylphenidate differentially influences how the caudate interacts with large-scale functional brain networks that exhibit co-ordinated but distinct patterns of activity required for attentionally demanding tasks.

Cross-species striatal hubs: Linking anatomy to resting-state connectivity

Corticostriatal connections are essential for motivation, cognition, and behavioral flexibility. There is broad interest in using resting-state functional magnetic resonance imaging (rs-fMRI) to link circuit dysfunction in these connections with neuropsychiatric disorders. In this paper, we used tract-tracing data from non-human primates (NHPs) to assess the likelihood of monosynaptic connections being represented in rs-fMRI data of NHPs and humans. We also demonstrated that existing hub locations in the anatomical data can be identified in the rs-fMRI data from both species. To characterize this in detail, we mapped the complete striatal projection zones from 27 tract-tracer injections located in the orbitofrontal cortex (OFC), dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), ventrolateral PFC (vlPFC), and dorsal PFC (dPFC) of macaque monkeys. Rs-fMRI seeds at the same regions of NHP and homologous regions of human brains showed connectivity maps in the striatum mostly consistent with those observed in the tracer data. We then examined the location of overlap in striatal projection zones. The medial rostral dorsal caudate connected with all five frontocortical regions evaluated in this study in both modalities (tract-tracing and rs-fMRI) and species (NHP and human). Other locations in the caudate also presented an overlap of four frontocortical regions, suggesting the existence of different locations with lower levels of input diversity. Small retrograde tracer injections and rs-fMRI seeds in the striatum confirmed these cortical input patterns. This study sets the ground for future studies evaluating rs-fMRI in clinical samples to measure anatomical corticostriatal circuit dysfunction and identify connectional hubs to provide more specific treatment targets for neurological and psychiatric disorders.

Increased GluK1 Subunit Receptors in Corticostriatal Projection from the Anterior Cingulate Cortex Contributed to Seizure-Like Activities.

The corticostriatal connection plays a crucial role in cognitive, emotional, and motor control. However, the specific roles and synaptic transmissions of corticostriatal connection are less studied, especially the corticostriatal transmission from the anterior cingulate cortex (ACC). Here, a direct glutamatergic excitatory synaptic transmission in the corticostriatal projection from the ACC is found. Kainate receptors (KAR)-mediated synaptic transmission is increased in this corticostriatal connection both in vitro and in vivo seizure-like activities. GluK1 containing KARs and downstream calcium-stimulated adenylyl cyclase subtype 1 (AC1) are involved in the upregulation of KARs following seizure-like activities. Inhibiting the activities of ACC or its corticostriatal connection significantly attenuated pentylenetetrazole (PTZ)-induced seizure. Additionally, injection of GluK1 receptor antagonist UBP310 or the AC1 inhibitor NB001 both show antiepileptic effects. The studies provide direct evidence that KARs are involved in seizure activity in the corticostriatal connection and the KAR-AC1 signaling pathway is a potential novel antiepileptic strategy.

Changed ventral striatum structural covariance and grey matter volume in depression during a one-year follow-up

Empirical findings suggest reduced cortico-striatal structural connectivity in patients with major depressive disorder (MDD). However, the relationship between the abnormal structural covariance and one-year outcome of first-episode drug-naive patients has not been evaluated. This longitudinal study aimed to identify specific changes of ventral striatum-related brain structural covariance and grey matter volume in forty-two first-episode patients with major depression disorder compared with thirty-seven healthy controls at the baseline and the one-year follow-up conditions. At the baseline, patients showed decreased structural covariance between the left ventral striatum and the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus (MFG), right supplementary motor area (SMA) and left precentral gyrus and increased grey matter volume at the left fusiform and left parahippocampus. At the one-year follow-up, patients showed decreased structural covariance between the left ventral striatum and the right SFG, right MFG, left precentral gyrus and left postcentral gyrus, and increased structural covariance between the right ventral striatum and the right amygdala, right hippocampus, right parahippocampus, right superior temporal pole, right insula and right olfactory bulb and decreased volume at the left SMA compared with controls. These findings suggest that specific ventral striatum connectivity changes contribute to the early brain development of the MDD.

Functional near-infrared spectroscopy-based neurofeedback training targeting the dorsolateral prefrontal cortex induces changes in cortico-striatal functional connectivity

Due to its central role in cognitive control, the dorso–lateral prefrontal cortex (dlPFC) has been the target of multiple brain modulation studies. In the context of the present pilot study, the dlPFC was the target of eight repeated neurofeedback (NF) sessions with functional near infrared spectroscopy (fNIRS) to assess the brain responses during NF and with functional and resting state magnetic resonance imaging (task-based fMRI and rsMRI) scanning. Fifteen healthy participants were recruited. Cognitive task fMRI and rsMRI were performed during the 1st and the 8th NF sessions. During NF, our data revealed an increased activity in the dlPFC as well as in brain regions involved in cognitive control and self-regulation learning (pFWE < 0.05). Changes in functional connectivity between the 1st and the 8th session revealed increased connectivity between the posterior cingulate cortex and the dlPFC, and between the posterior cingulate cortex and the dorsal striatum (pFWE < 0.05). Decreased left dlPFC-left insula connectivity was also observed. Behavioural results revealed a significant effect of hunger and motivation on the participant control feeling and a lower control feeling when participants did not identify an effective mental strategy, providing new insights on the effects of behavioural factors that may affect the NF learning.

Neuroprotection by ADAM10 inhibition requires TrkB signaling in the Huntington’s disease hippocampus

Synaptic dysfunction is an early pathogenic event leading to cognitive decline in Huntington’s disease (HD). We previously reported that the active ADAM10 level is increased in the HD cortex and striatum, causing excessive proteolysis of the synaptic cell adhesion protein N-Cadherin. Conversely, ADAM10 inhibition is neuroprotective and prevents cognitive decline in HD mice. Although the breakdown of cortico-striatal connection has been historically linked to cognitive deterioration in HD, dendritic spine loss and long-term potentiation (LTP) defects identified in the HD hippocampus are also thought to contribute to the cognitive symptoms of the disease. The aim of this study is to investigate the contribution of ADAM10 to spine pathology and LTP defects of the HD hippocampus. We provide evidence that active ADAM10 is increased in the hippocampus of two mouse models of HD, leading to extensive proteolysis of N-Cadherin, which has a widely recognized role in spine morphology and synaptic plasticity. Importantly, the conditional heterozygous deletion of ADAM10 in the forebrain of HD mice resulted in the recovery of spine loss and ultrastructural synaptic defects in CA1 pyramidal neurons. Meanwhile, normalization of the active ADAM10 level increased the pool of synaptic BDNF protein and activated ERK neuroprotective signaling in the HD hippocampus. We also show that the ADAM10 inhibitor GI254023X restored LTP defects and increased the density of mushroom spines enriched with GluA1-AMPA receptors in HD hippocampal neurons. Notably, we report that administration of the TrkB antagonist ANA12 to HD hippocampal neurons reduced the beneficial effect of GI254023X, indicating that the BDNF receptor TrkB contributes to mediate the neuroprotective activity exerted by ADAM10 inhibition in HD. Collectively, these findings indicate that ADAM10 inhibition coupled with TrkB signaling represents an efficacious strategy to prevent hippocampal synaptic plasticity defects and cognitive dysfunction in HD.

Cortico-striatal white-matter connectivity underlies the ability to exert goal-directed control.

The balance between goal-directed and habitual control has been proposed to determine the flexibility of instrumental behaviour, in both humans and animals. This view is supported by neuroscientific studies that have implicated dissociable neural pathways in the ability to flexibly adjust behaviour when outcome values change. A previous Diffusion Tensor Imaging study provided preliminary evidence that flexible instrumental performance depends on the strength of parallel cortico-striatal white-matter pathways previously implicated in goal-directed and habitual control. Specifically, estimated white-matter strength between caudate and ventromedial prefrontal cortex correlated positively with behavioural flexibility, and posterior putamen-premotor cortex connectivity correlated negatively, in line with the notion that these pathways compete for control. However, the sample size of the original study was limited, and so far, there have been no attempts to replicate these findings. In the present study, we aimed to conceptually replicate these findings by testing a large sample of 205 young adults to relate cortico-striatal connectivity to performance on the slips-of-action task. In short, we found only positive neural correlates of goal-directed performance, including striatal connectivity (caudate and anterior putamen) with the dorsolateral prefrontal cortex. However, we failed to provide converging evidence for the existence of a neural habit system that puts limits on the capacity for flexible, goal-directed action. We discuss the implications of our findings for dual-process theories of instrumental action.

Oxytocin pathway gene variation and corticostriatal resting-state functional connectivity

Genetic variations in single nucleotide polymorphisms (SNPs) within oxytocin pathway genes have been linked to social behavior and neurodevelopmental conditions. However, the neurobiological mechanisms underlying these associations remain elusive. In this study, we investigated the relationship between variations of 10 SNPs in oxytocin pathway genes and resting-state functional connectivity among 55 independent components using a large sample from the UK Biobank (N ≈ 30,000). Our findings revealed that individuals with the GG genotype at rs4813627 within the oxytocin structural gene (OXT) exhibited weaker resting-state functional connectivity in the corticostriatal circuit compared to those with the GA/AA genotypes. Empirical evidence has linked the GG genotype at OXT rs4813627 with a behavioral tendency of insensitivity to others. These results inform the neural mechanisms by which oxytocin-related genetic factors can influence social behavior.

Shared and Specific Changes of Cortico-Striatal Functional Connectivity in Stable Mild Cognitive Impairment and Progressive Mild Cognitive Impairment.

Mild cognitive impairment (MCI), the prodromal stage of Alzheimer's disease, has two distinct subtypes: stable MCI (sMCI) and progressive MCI (pMCI). Early identification of the two subtypes has important clinical significance. We aimed to compare the cortico-striatal functional connectivity (FC) differences between the two subtypes of MCI and enhance the accuracy of differential diagnosis between sMCI and pMCI. We collected resting-state fMRI data from 31 pMCI patients, 41 sMCI patients, and 81 healthy controls. We chose six pairs of seed regions, including the ventral striatum inferior, ventral striatum superior, dorsal-caudal putamen, dorsal-rostral putamen, dorsal caudate, and ventral-rostral putamen and analyzed the differences in cortico-striatal FC among the three groups, additionally, the relationship between the altered FC within the MCI subtypes and cognitive function was examined. Compared to sMCI, the pMCI patients exhibited decreased FC between the left dorsal-rostral putamen and right middle temporal gyrus, the right dorsal caudate and right inferior temporal gyrus, and the left dorsal-rostral putamen and left superior frontal gyrus. Additionally, the altered FC between the right inferior temporal gyrus and right putamen was significantly associated with episodic memory and executive function. Our study revealed common and distinct cortico-striatal FC changes in sMCIs and pMCI across different seeds; these changes were associated with cognitive function. These findings can help us understand the underlying pathophysiological mechanisms of MCI and distinguish pMCI and sMCI in the early stage potentially.

Corticostriatal causality analysis in children and adolescents with attention-deficit/hyperactivity disorder.

The effective connectivity between the striatum and cerebral cortex has not been fully investigated in attention-deficit/hyperactivity disorder (ADHD). Our objective was to explore the interaction effects between diagnosis and age on disrupted corticostriatal effective connectivity and to represent the modulation function of altered connectivity pathways in children and adolescents with ADHD. We performed Granger causality analysis on 300 participants from a publicly available Attention-Deficit/Hyperactivity Disorder-200 dataset. By computing the correlation coefficients between causal connections between striatal subregions and other cortical regions, we estimated the striatal inflow and outflow connection to represent intermodulation mechanisms in corticostriatal pathways. Interactions between diagnosis and age were detected in the superior occipital gyrus within the visual network, medial prefrontal cortex, posterior cingulate gyrus, and inferior parietal lobule within the default mode network, which is positively correlated with hyperactivity/impulsivity severity in ADHD. Main effect of diagnosis exhibited a general higher cortico-striatal causal connectivity involving default mode network, frontoparietal network and somatomotor network in ADHD compared with comparisons. Results from high-order effective connectivity exhibited a disrupted information pathway involving the default mode-striatum-somatomotor-striatum-frontoparietal networks in ADHD. The interactions detected in the visual-striatum-default mode networks pathway appears to be related to the potential distraction caused by long-term abnormal information input from the retina in ADHD. Higher causal connectivity and weakened intermodulation may indicate the pathophysiological process that distractions lead to the impairment of motion planning function and the inhibition/control of this unplanned motion signals in ADHD.

Fatigue and perceived energy in a sample of older adults over 10 years: A resting state functional connectivity study of neural correlates

PurposeDeclining energy and increasing fatigue, common in older age, predict neurodegenerative conditions, but their neural substrates are not known. We examined brain resting state connectivity in relation to declining self-reported energy levels (SEL) and occurrence of fatigue over time. MethodsWe examined resting-state functional MRI in 272 community dwelling older adults participating in the Health Aging and Body Composition Study (mean age 83 years; 57.4 % female; 40.8 % Black) with measures of fatigue and SEL collected at regular intervals over the prior ten years. Functional connectivity (FC) between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with prior fatigue state (reporting fatigue at least once or never reporting fatigue), and with SEL decline (divided into stable or declining SEL groups) and adjusted for demographic, physical function, mood, cognition, and comorbidities. ResultsHigher cortico-striatal FC in the right limbic network was associated with lower odds of reporting fatigue (better) at least once during the study period (adjusted odds ratio [95 % confidence interval], p-value: (0.747 [0.582, 0.955], 0.020), independent of SEL. Higher cortico-striatal FC in the right executive network was associated with higher odds of declining SEL (worse) during the study period (adjusted odds ratio [95 % confidence interval], p-value: (1.31 [1.01, 1.69], 0.041), independent of fatigue. Associations with other networks were not significant. ConclusionsIn this cohort of older adults, the cortico-striatal functional connectivity of declining SEL appears distinct from that underlying fatigue. Studies to further assess the neural correlates of energy and fatigue, and their independent contribution to neurodegenerative conditions are warranted.

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats.

JOURNAL/nrgr/04.03/01300535-202504000-00031/figure1/v/2024-07-06T104127Z/r/image-tiff Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia. Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia. Currently, studies have reported increased oscillation power in cases of levodopa-induced dyskinesia. However, little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia. Furthermore, the role of the dopamine D3 receptor, which is implicated in levodopa-induced dyskinesia, in movement disorder-related changes in neural oscillations is unclear. We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson's disease. Furthermore, levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components, as well as bidirectional primary motor cortex (M1) ↔ dorsolateral striatum gamma flow. Administration of PD128907 (a selective dopamine D3 receptor agonist) induced dyskinesia and excessive gamma oscillations with a bidirectional M1 ↔ dorsolateral striatum flow. However, administration of PG01037 (a selective dopamine D3 receptor antagonist) attenuated dyskinesia, suppressed gamma oscillations and cortical gamma aperiodic components, and decreased gamma causality in the M1 → dorsolateral striatum direction. These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity, and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Familial effects account for association between chronic pain and past month smoking.

Smoking is associated with chronic pain, but it is not established whether smoking causes pain or if the link is due to familial effects. One proposed mechanism is that smoking strengthens maladaptive cortico-striatal connectivity, which contributes to pain chronification. We leveraged a twin design to assess direct effects of smoking on pain controlling for familial confounds, and whether cortico-striatal connectivity mediates this association. In a population-based sample of 692 twins (age = 28.83 years), we assessed past-month smoking frequency (n = 132 used in the past month), presence and severity of a current pain episode (n = 179 yes), and resting-state functional connectivity of the nucleus accumbens and medial prefrontal cortex (NAc-mPFC). Smoking was significantly associated with pain, but the association was not significantly mediated by NAc-mPFC connectivity. In a co-twin control model, smoking predicted which families had more pain but could not distinguish pain between family members. Pain risk was 43% due to additive genetic (A) and 57% due to non-shared environmental (E) influences. Past-month smoking frequency was 71% genetic and 29% non-shared environmental. Smoking and pain significantly correlated phenotypically (r = 0.21, p = 0.001) and genetically (rg = 0.51, p < 0.001), but not environmentally (re = -0.18, p = 0.339). Pain and smoking are associated; however, the association appears to reflect shared familial risk factors, such as genetic risk, rather than being causal in nature. The connectivity strength of the reward pathway was not related to concurrent pain and smoking in this sample. Smoking does not appear to directly cause chronic pain; rather, there may be shared biopsychosocial risk factors, including genetic influences, that explain their association. These findings can be integrated into future research to identify shared biological pathways of both chronic pain and smoking behaviours as a way to conceptualize pain chronification.

Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids.

Realizing the full potential of organoids and assembloids to model neural development and disease will require improved methods for long-term, minimally invasive recording of electrical activity. Current technologies, such as patch clamp, penetrating microelectrodes, planar electrode arrays and substrate-attached flexible electrodes, do not allow chronic recording of organoids in suspension, which is necessary to preserve architecture. Inspired by kirigami art, we developed flexible electronics that transition from a two-dimensional to a three-dimensional basket-like configuration with either spiral or honeycomb patterns to accommodate the long-term culture of organoids in suspension. Here we show that this platform, named kirigami electronics (KiriE), integrates with and enables chronic recording of cortical organoids for up to 120 days while preserving their morphology, cytoarchitecture and cell composition. We demonstrate integration of KiriE with optogenetic and pharmacological manipulation and modeling phenotypes related to a genetic disease. Moreover, KiriE can capture corticostriatal connectivity in assembloids following optogenetic stimulation. Thus, KiriE will enable investigation of disease and activity patterns underlying nervous system assembly.

Profiling functional networks identify activation of corticostriatal connectivity in ET patients after MRgFUS thalamotomy

BackgroundMR-guided focused ultrasound (MRgFUS) thalamotomy is a novel and effective treatment for medication-refractory tremor in essential tremor (ET), but how the brain responds to this deliberate lesion is not clear. ObjectiveThe current study aimed to evaluate the immediate and longitudinal alterations of functional networks after MRgFUS thalamotomy. MethodsWe retrospectively obtained preoperative and postoperative 30-day, 90-day, and 180-day data of 31 ET patients subjected with MRgFUS thalamotomy from 2018 to 2020. Their archived resting-state functional MRI data were used for functional network comparison as well as graph-theory metrics analysis. Both partial least squares (PLS) regression and linear regression were conducted to associate functional features to tremor symptoms. ResultsMRgFUS thalamotomy dramatically abolished tremors, while global functional network only sustained immediate fluctuation within one week after the surgery. Network-based statistics have identified a long-term enhanced corticostriatal subnetwork by comparison between 180-day and preoperative data (P = 0.019). Within this subnetwork, network degree, global efficiency and transitivity were significantly recovered in ET patients right after MRgFUS thalamotomy compared to the pre-operative timepoint (P < 0.05), as well as hemisphere lateralization (P < 0.001). The PLS main component significantly accounted for 33.68 % and 34.16 % of the total variances of hand tremor score and clinical rating scale for tremor (CRST)-total score (P = 0.037 and 0.027). Network transitivity of this subnetwork could serve as a reliable biomarker for hand tremor score control prediction at 180-day after the surgery (β = 2.94, P = 0.03). ConclusionMRgFUS thalamotomy promoted corticostriatal connectivity activation correlated with tremor improvement in ET patient after MRgFUS thalamotomy.

A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy.

In our brains, different neurons make appropriate connections; however, there remain few in vitro models of such circuits. We use an open microfluidic approach to build and study neuronal circuits in vitro in ways that fit easily into existing bio-medical workflows. Dumbbell-shaped circuits are built in minutes in standard Petri dishes; the aqueous phase is confined by fluid walls - interfaces between cell-growth medium and an immiscible fluorocarbon, FC40. Conditions are established that ensure post-mitotic neurons derived from human induced pluripotent stem cells (iPSCs) plated in one chamber of a dumbbell remain where deposited. After seeding cortical neurons on one side, axons grow through the connecting conduit to ramify amongst striatal neurons on the other - an arrangement mimicking unidirectional cortico-striatal connectivity. We also develop a moderate-throughput non-contact axotomy assay. Cortical axons in conduits are severed by a media jet; then, brain-derived neurotrophic factor and striatal neurons in distal chambers promote axon regeneration. As additional conduits and chambers are easily added, this opens up the possibility of mimicking complex neuronal networks, and screening drugs for their effects on connectivity.

Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions.

Understanding how the brain's macroscale dynamics are shaped by underlying microscale mechanisms is a key problem in neuroscience. In animal models, we can now investigate this relationship in unprecedented detail by directly manipulating cellular-level properties while measuring the whole-brain response using resting-state fMRI. Here, we focused on understanding how blood-oxygen-level-dependent (BOLD) dynamics, measured within a structurally well-defined striato-thalamo-cortical circuit in mice, are shaped by chemogenetically exciting or inhibiting D1 medium spiny neurons (MSNs) of the right dorsomedial caudate putamen (CPdm). We characterize changes in both the BOLD dynamics of individual cortical and subcortical brain areas, and patterns of inter-regional coupling (functional connectivity) between pairs of areas. Using a classification approach based on a large and diverse set of time-series properties, we found that CPdm neuromodulation alters BOLD dynamics within thalamic subregions that project back to dorsomedial striatum. In the cortex, changes in local dynamics were strongest in unimodal regions (which process information from a single sensory modality) and weakened along a hierarchical gradient towards transmodal regions. In contrast, a decrease in functional connectivity was observed only for cortico-striatal connections after D1 excitation. Our results show that targeted cellular-level manipulations affect local BOLD dynamics at the macroscale, such as by making BOLD dynamics more predictable over time by increasing its self-correlation structure. This contributes to ongoing attempts to understand the influence of structure-function relationships in shaping inter-regional communication at subcortical and cortical levels.

Disrupted functional connectivity of the striatum in patients with diffuse axonal injury: a resting-state functional MRI study.

Diffuse axonal injury (DAI) disrupts the integrity of white matter microstructure and affects brain functional connectivity, resulting in persistent cognitive, behavioral and affective deficits. Mounting evidence suggests that altered cortical-subcortical connectivity is a major contributor to cognitive dysfunction. The functional integrity of the striatum is particularly vulnerable to DAI, but has received less attention. This study aimed to investigate the alteration patterns of striatal subdivision functional connectivity. Twenty-six patients with DAI and 27 healthy controls underwent resting-state fMRI scans on a 3.0 T scanner. We assessed striatal subdivision functional connectivity using a seed-based analysis in DAI. Furthermore, a partial correlation was used to measure its clinical association. Compared to controls, patients with DAI showed decreased functional connectivity between the right inferior ventral striatum and right inferior frontal gyrus, as well as the right inferior parietal lobule, between the left inferior ventral striatum and right inferior frontal gyrus, between the right superior ventral striatum and bilateral cerebellar posterior lobe, between the bilateral dorsal caudal putamen and right anterior cingulate gyrus, and between the right dorsal caudal putamen and right inferior parietal lobule. Moreover, decreased functional connectivity was observed between the left dorsal caudate and the right cerebellar posterior lobe, while increased functional connectivity was found between the left dorsal caudate and right inferior parietal lobule. Correlation analyses showed that regions with functional connectivity differences in the DAI group correlated with multiple clinical scoring scales, including cognition, motor function, agitated behavior, and anxiety disorders. These findings suggest that abnormalities in cortico-striatal and cerebellar-striatal functional connectivity are observed in patients with DAI, enriching our understanding of the neuropathological mechanisms of post-injury cognitive disorders and providing potential neuroimaging markers for the diagnosis and treatment of DAI.

Corticostriatal Connectivity during Prosocial Decision-making Relates to Giving Behavior during Adolescence.

Prosocial behavior during adolescence becomes more differentiated based on the recipient of the action as well as the perceived value or benefit, relative to the cost to self, for the recipients. The current study investigated how functional connectivity of corticostriatal networks tracked the value of prosocial decisions as a function of target recipient (caregiver, friend, stranger) and age of the giver, and how they related to giving behavior. Two hundred sixty-one adolescents (9-15 and 19-20 years of age) completed a decision-making task in which they could give money to caregivers, friends, and strangers while undergoing fMRI. Results indicated that adolescents were more likely to give to others as the value of the prosocial decision (i.e., the difference between the benefit to other relative to the cost to self) increased; this effect was stronger for known (caregiver and friends) than unknown targets, and increased with age. Functional connectivity between the nucleus accumbens (NAcc) and OFC increased as the value of the prosocial decisions decreased for strangers, but not for known others, irrespective of choice. This differentiated NAcc-OFC functional connectivity during decision-making as a function of value and target also increased with age. Furthermore, regardless of age, individuals who evinced greater value-related NAcc-OFC functional connectivity when considering giving to strangers relative to known others showed smaller differentiated rates of giving between targets. These findings highlight the role of corticostriatal development in supporting the increasing complexity of prosocial development across adolescence.

Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan

Age-related alterations in D1-like dopamine receptor (D1DR) have distinct implications for human cognition and behavior during development and aging, but the timing of these periods remains undefined. Enabled by a large sample of invivo assessments (n= 180, age 20 to 80 years of age, 50% female), we discover that age-related D1DR differences pivot at approximately 40 years of age in several brain regions. Focusing on the most age-sensitive dopamine-rich region, we observe opposing pre- and post-forties interrelations among caudate D1DR, cortico-striatal functional connectivity, and memory. Finally, particularly caudate D1DR differences in midlife and beyond, but not in early adulthood, associate with manifestation of white matter lesions. The present results support a model by which excessive dopamine modulation in early adulthood and insufficient modulation in aging are deleterious to brain function and cognition, thus challenging a prevailing view of monotonic D1DR function across the adult lifespan.