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Background and purpose: Radiotherapy (RT) is an adjuvant treatment option for glioma patients. Side effects include tissue atrophy, which might be a contributing factor to neurocognitive decline after treatment. The goal of this study was to determine potential atrophy of the hippocampus, amygdala, thalamus, putamen, pallidum and caudate nucleus in glioma patients having undergone magnetic resonance imaging (MRI) before and after RT. Materials and methods: Subcortical volumes were measured using T1-weighted MRI from patients before RT (N = 91) and from longitudinal follow-ups acquired in three-monthly intervals (N = 349). The volumes were normalized to the baseline values, while excluding structures touching the clinical target volume (CTV) or abnormal tissue seen on FLAIR imaging. A multivariate linear effects model was used to determine if time after RT and mean RT dose delivered to the corresponding structures were significant predictors of tissue atrophy. Results: The hippocampus, amygdala, thalamus, putamen, and pallidum showed significant atrophy after RT as function of both time after RT and mean RT dose delivered to the corresponding structure. Only the caudate showed no dose or time dependant atrophy. Conversely, the hippocampus was the structure with the highest atrophy rate of 5.2 % after one year and assuming a mean dose of 30 Gy. Conclusion: The hippocampus showed the highest atrophy rates followed by the thalamus and the amygdala. The subcortical structures here found to decrease in volume indicative of radiosensitivity should be the focus of future studies investigating the relationship between neurocognitive decline and RT. © 2022 The Authors

Iron homeostasis is important for maintaining normal physiological brain functioning. In two independent samples, we investigate the link between iron concentration in the basal ganglia (BG) and implicit sequence learning (ISL). In Study 1, we used quantitative susceptibility mapping and task-related fMRI to examine associations among regional iron concentration measurements, brain activation, and ISL in younger and older adults. In Study 2, we examined the link between brain iron and ISL using a metric derived from fMRI in an age-homogenous sample of older adults. Three main findings were obtained. First, BG iron concentration was positively related to ISL in both studies. Second, ISL was robust for both younger and older adults, and performance-related activation was found in fronto-striatal regions across both age groups. Third, BG iron was positively linked to task-related BOLD signal in fronto-striatal regions. This is the first study investigating the relationship among brain iron accumulation, functional brain activation, and ISL, and the results suggest that higher brain iron concentration may be linked to better neurocognitive functioning in this particular task.

Contains fulltext : 292515.pdf (Publisher’s version ) (Open Access) It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.

Type 2 diabetes (T2D) can result in a number of comorbidities involving various organs including heart, eye, kidney and even the brain. However, little is known about the molecular basis of T2D associated brain disorders. In this study, we performed a comprehensive transcriptomic analysis in a total of 304 T2D samples and 608 matched control samples from thirteen distinct brain regions. We observed prominent difference among transcriptomic profiles of diverse brain regions in T2D. The most striking change was found in caudate with thousands of T2D-associated genes identified, followed by hippocampus, while nearly no transcriptomic change was observed in other brain regions. Functional analysis of T2D-associated genes revealed impaired synaptic functions and an association with neurodegenerative diseases. Co-expression analysis of caudate transcriptomic profiles unveiled a core regional specific module that was disorganized in T2D. Sub-modules consisting of regional markers were enriched in T2D risk single nucleotide polymorphisms (SNPs) and implied a causal link with T2D. Hub genes of this module include NSF and ADD2, the former of which has been associated with T2D and neurogenerative diseases. Thus, our work provides useful information for further studies in T2D associated brain disorders.

Highlights • Working memory (WM). • Load versus Complexity. • ADHD. • FMRI. • Working Memory Striatum and Cerebellum., Working memory (WM) deficits are key in attention deficit hyperactivity disorder (ADHD). Nevertheless, WM is not universally impaired in ADHD. Additionally, the neural basis for WM deficits in ADHD has not been conclusively established, with regions including the prefrontal cortex, cerebellum, and caudate being implicated. These contradictions may be related to conceptualizations of WM capacity, such as load (amount of information) versus operational-complexity (maintenance-recall or manipulation). For instance, relative to neurotypical (NT) individuals, complex WM operations could be impaired in ADHD, while simpler operations are spared. Alternatively, all operations may be impaired at higher loads. Here, we compared the impact of these two components of WM capacity: load and operational-complexity, between ADHD and NT, behaviorally and neurally. We hypothesized that the impact of WM load would be greater in ADHD, and the neural activation would be altered. Participants (age-range 12–23 years; 50 ADHD (18 females); 82 NT (41 females)) recalled three or four objects (load) in forward or backward order (operational-complexity) during functional magnetic resonance imaging scanning. The effects of diagnosis and task were compared on performance and neural engagement. Behaviorally, we found significant interactions between diagnosis and load, and between diagnosis, load, and complexity. Neurally, we found an interaction between diagnosis and load in the right striatum, and between diagnosis and complexity in the right cerebellum and left occipital gyrus. The ADHD group displayed hypo-activation compared to NT group during higher load and greater complexity. This informs mechanisms of functional problems related to WM in adolescents and young adults with ADHD (e.g., academic performance) and remedial interventions (e.g., WM-training).

Palatable food can trigger appetitive responses, such as salivation and approach tendencies. Though evolutionarily functional, these conditioned responses can encourage overeating and obesity when food is abundant. The current study examines the neural correlates of ‘denovo’ Pavlovian appetitive conditioning, pairing one class of unknown objects (conditioned stimuli, CS) with their sweet taste (unconditioned stimulus, US) during a single trial. To do so, 23 participants consumed unknown (marzipan) objects of one particular color (CS+) while only interacting with control stimuli of different color and shape (CS-). After this single-trial conditioning procedure, participants viewed and rated images of the marzipan figures and the control objects during functional magnetic resonance imaging (fMRI). Relative to the CS-, the CS+ elicited stronger activation in the dorsal striatum, a brain region associated with cue-reward coupling. Furthermore, conditioning effects in subjective ‘craving’, defined as increased palatability and desire to eat, were observed, and these were positively related to conditioning effects in the amygdala, a brain region associated with the need-dependent value of a reward. Thus, the study identified reward-related brain regions involved in single-trial appetitive learning, thereby providing a potential mechanism that contributes to the etiology of food craving. These findings might help to understand clinically relevant food cravings in individuals with eating or weight related concerns and might support the development of extinction based treatments.

The intrinsic function of the human brain is dynamic, giving rise to numerous behavioral subtypes that fluctuate distinctively at multiple timescales. One of the key dynamical processes that takes place in the brain is the interaction between core-periphery brain regions, which undergoes constant fluctuations associated with developmental time frames. Core-periphery dynamical changes associated with macroscale brain network dynamics span multiple timescales and may lead to atypical behavior and clinical symptoms. For example, recent evidence suggests that brain regions with shorter intrinsic timescales are located at the periphery of brain networks (e.g., sensorimotor hand, face areas) and are implicated in perception and movement. On the contrary, brain regions with longer timescales are core hub regions. These hubs are important for regulating interactions between the brain and the body during self-related cognition and emotion. In this review, we summarize a large body of converging evidence derived from time-resolved fMRI studies in autism to characterize atypical core-periphery brain dynamics and how they relate to core and contextual sensory and cognitive profiles.

Background: Childhood obesity has become a global epidemic and the etiology of maladaptive ingestive behavior in children warrants further research. Mounting evidence suggests that the caudate is associated with body weight gain and obesity in adults. In adolescents, however, how caudate related neural networks are associated with body weight gain is unclear because their central nervous systems are still developing. Objectives: The current longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) study was conducted to investigate the hypothesis that caudate-related neural networks have a role in weight gain in adolescents. Methods: The study included 20 healthy adolescents with a mean age of 17.5 ± 2.0 years and a mean body mass index of 20.6 ± 2.1 who underwent baseline rs-fMRI then follow-up rs-fMRI approximately 1 year later. Body mass index (BMI) was measured at both timepoints. Seed-based functional connectivity analysis was utilized to analyze caudate-related functional connectivity (FC) using the caudate as a seed. Associations between caudate-related FC and BMI at baseline were assessed, as were associations between change in BMI and caudate-related FC between baseline and follow-up. Results: At baseline, greater caudate-lateral prefrontal cortex FC was correlated with lower BMI (family-wise error-corrected p < 0.05). Compared to the baseline, increased FC in the caudate-lateral prefrontal cortex at follow up were negatively associated with increased BMI (p < 0.05). Conclusion: Given that the lateral prefrontal cortex and caudate are associated with inhibitory control, the caudate-lateral prefrontal cortex FC may have a preventive effect on weight gain in adolescents. The results of the current study suggest that developing inhibitory control would lead to the prevention of childhood obesity.

Background Serum neurofilament light chain (sNfL) levels are associated with relapses, MRI lesions, and brain volume in multiple sclerosis (MS). Objective To explore the value of early serum neurofilament light (sNfL) measures in prognosticating 10-year regional brain volumes in MS. Methods Patients with MS enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital (CLIMB) study within five years of disease onset who had annual blood samples from years 1–10 (n = 91) were studied. sNfL was measured with a single molecule array (SIMOA) assay. We quantified global cortical thickness and normalized deep gray matter (DGM) volumes (fractions of the thalamus, caudate, putamen, and globus pallidus) from high-resolution 3 T MRI at 10 years. Correlations between yearly sNfL levels and 10-year MRI outcomes were assessed using linear regression models. Results sNfL levels from years 1 and 2 were associated with 10-year thalamus fraction. Early sNfL levels were not associated with 10-year putamen, globus pallidus or caudate fractions. At 10 years, cortical thickness was not associated with early sNfL levels, but was weakly correlated with total DGM fraction. Conclusions Early sNfL levels correlate with 10-year thalamic volume, supporting its role as a prognostic biomarker in MS.

Excessive daytime sleepiness (EDS) is one of the earliest and most common non-motor symptoms of PD, substantially impacting on patient's quality of life. Using the Parkinson's Progression Markers Initiative database, we performed a case-control study to investigate whether dopaminergic deficit is associated with the development of EDS using dopaminergic specific single photon emission computed tomography (SPECT) molecular imaging of dopamine transporters (DAT). We enrolled 84 early de novo PD patients with EDS and 84 without EDS, who were matched for age, gender, age of diagnosis, years of education and disease duration. We assessed and compared semi-quantified [123I]FP-CIT SPECT, and motor and non-motor features among these two groups, alongside exploring the clinical and imaging correlates of EDS and the predictive significance of these markers in the development of EDS. PD patients with EDS had worse non-motor (MDS-UPDRS Part-I, P

Background Idiopathic normal pressure hydrocephalus (iNPH) is an important and treatable cause of neurologic impairment. Diagnosis is complicated due to symptoms overlapping with other age related disorders. The pathophysiology underlying iNPH is not well understood. We explored FDG-PET abnormalities in iNPH patients in order to determine if FDG-PET may serve as a biomarker to differentiate iNPH from common neurodegenerative disorders. Methods We retrospectively compared 18F-FDG PET-CT imaging patterns from seven iNPH patients (mean age 74 ± 6 years) to age and sex matched controls, as well as patients diagnosed with clinical Alzheimer's disease dementia (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD), and behavioral variant frontotemporal dementia (bvFTD). Partial volume corrected and uncorrected images were reviewed separately. Results Patients with iNPH, when compared to controls, AD, DLB/PDD, and bvFTD, had significant regional hypometabolism in the dorsal striatum, involving the caudate and putamen bilaterally. These results remained highly significant after partial volume correction. Conclusions In this study, we report a FDG-PET pattern of hypometabolism in iNPH involving the caudate and putamen with preserved cortical metabolism. This pattern may differentiate iNPH from degenerative diseases and has the potential to serve as a biomarker for iNPH in future studies. These findings also further our understanding of the pathophysiology underlying the iNPH clinical presentation., Highlights • The pathophysiology of iNPH is poorly understood. • Clinical biomarkers for diagnosis and prediction of shunt outcome are needed. • iNPH patients have striatal hypometabolism on FDG-PET. • Striatal hypometabolism helps explain the clinical presentation of iNPH. • FDG-PET is a useful tool for differentiating iNPH from other degenerative disorders.

Rationale: Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment.Objectives: The objective of this study was to investigate the association between CB use and dependence, and the volumes of brain regions critically involved in goal-directed learning and behaviour—the orbitofrontal cortex (OFC) and caudate.Methods: In the largest multi-site structural imaging study of CB users vs healthy controls (HC), 140 CB users and 121 HC were recruited from four research sites. Group differences in OFC and caudate volumes were investigated between HC and CB users and between 70 dependent (CB-dep) and 50 non-dependent (CB-nondep) users. The relationship between quantity of CB use and age of onset of use and caudate and OFC volumes was explored.Results: CB users (consisting of CB-dep and CB-nondep) did not significantly differ from HC in OFC or caudate volume. CB-dep compared to CB-nondep users exhibited significantly smaller volume in the medial and the lateral OFC. Lateral OFC volume was particularly smaller in CB-dep females, and reduced volume in the CB-dep group was associated with higher monthly cannabis dosage.Conclusions: Smaller medial OFC volume may be driven by CB dependence-related mechanisms, while smaller lateral OFC volume may be due to ongoing exposure to cannabinoid compounds. The results highlight a distinction between cannabis use and dependence and warrant examination of gender-specific effects in studies of CB dependence.

Several studies have demonstrated through resting-state functional magnetic resonance imaging (fMRI) that functional connectivity changes are important in the recovery from Bell's palsy (BP); however, these studies have only focused on the cortico-cortical connectivity. It is unclear how corticostriatal connectivity relates to the recovery process of patients with BP. In the present study, we evaluated the relationship between longitudinal changes of caudate-based functional connectivity and longitudinal changes of facial performance in patients with intractable BP. Twenty-one patients with intractable BP underwent resting-state fMRI as well as facial behavioral assessments prior to treatment (PT) and at the middle stage of treatment (MT); and 21 age- and sex-matched healthy controls (HC) were recruited and received the same protocol. The caudate was divided into dorsal and ventral sub-regions and separate functional connectivity was calculated. Compared with HC, patients with intractable BP at the PT stage showed decreased functional connectivity of both the dorsal and ventral caudate mainly distributed in the somatosensory network, including the bilateral precentral gyrus (MI), left postcentral gyrus, media frontal gyrus, and superior temporal gyrus (STG). Alternatively, patients in the MT stage showed decreased functional connectivity primarily distributed in the executive network and somatosensory network, including the bilateral cingulate cortex (CC), left anterior cingulate cortex (LACC), inferior prefrontal gyrus (IFG), MI, STG, and paracentral lobe. The longitudinal changes in functional connectivity of both the dorsal and ventral caudate were mainly observed in the executive network, including the right ACC, left CC, and IFG. Functional connectivity changes in the right ACC and left IFG were significantly correlated with changes in facial behavioral performance. These findings indicated that corticostriatal connectivity changes are associated with recovery from BP.

Bolitoglossa mombachoensis is an endemic neotropical salamander of the Mombacho Volcano, Nicaragua. Canopy communities within the tropics are hubs for biodiversity, and many tropical plethodontids have a foraging preference for epiphytic plants, such as bromeliads, which provide moist microclimates for shelter, foraging, and nesting. Habitat loss continues to be the biggest threat to amphibians worldwide. This species is highly dependent on nocturnal arboreal climbing. We describe their plant preference, which extends beyond bromeliads, and their arboreal dependence used for refuge and foraging. Foraging behavior is constricted to nighttime, plant availability, geography, and altitude.

Depression can occur before the onset of motor symptoms in Parkinson's disease (PD) patients. The pathophysiology of depression in PD involves various brain regions and relevant functional circuits. This study investigated whether there exist distinctive patterns of presynaptic monoamine transporter densities in the basal ganglia depending on the degree of depression in patients with PD. A total of 123 early and drug-naïve PD patients were enrolled. Their affective status was evaluated by the Montgomery–Asberg Depression Rating Scale (MADRS), and subjects were subgrouped into one of the following three groups according to their MADRS scores: no depression, mild depression, and moderate-to-severe depression. All patients underwent positron emission tomography (PET) using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane. The PET images were normalized, and differences in the regional standardized uptake value ratios (SUVRs) for each side of the caudate, putamen, globus pallidus, thalamus, and ventral striatum were analyzed and compared between the three groups. A trend analysis was performed across the groups to discern any associations between SUVR values of the basal ganglia and depression severity. The SUVR values of the caudate, anterior caudate nuclei, and ventral striatum declined as MADRS increased. The SUVR values of the striatum showed an inverse dose-dependent trend of antero- and ventroposterior gradient across the groups. This result indirectly revealed the involvement of the associative and limbic circuitry of the brain that are modulated by monoamines in early PD with depression. This might suggest an in vivo causal relationship between the ventral striatum, caudate and depression.

ObjectiveAlthough not typical of Parkinson’s disease (PD), caudate dopaminergic dysfunction can occur in early stages of the disease. However, its frequency and longitudinal implications in large cohorts of recently diagnosed patients remain to be established. We investigated the occurrence of caudate dopaminergic dysfunction in the very early phases of PD (123I-FP-CIT single photon emission CT and determined whether it was associated with the presence or subsequent development of cognitive impairment, depression, sleep and gait problems.MethodsPatients with PD and healthy controls were identified from the Parkinson’s Progression Markers Initiative (PPMI) database. We defined a clinically significant caudate dysfunction as 123I-FP-CIT binding ResultsAt baseline, 51.6% of 397 patients had normal caudate dopamine transporter binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate.Compared with those with a baseline normal caudate function, at the4-year follow-up patients with a baseline bilateral caudate involvement showed a higher frequency of cognitive impairment (pConclusionsEarly significant caudate dopaminergic denervation was found in half of the cases in the PPMI series. Baseline bilateral caudate involvement was associated with increased risk of developing cognitive impairment, depression and gait problems over the next 4 years.

Background: Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood. Considering the recent explanation of establishing SoA from the standpoint of associative learning, the “agency network” may include not only the insula and inferior parietal lobule but also the striatum. We hypothesized that aberrant SoA in schizophrenia is based on a deficit in the “agency network.” Methods: Functional magnetic resonance imaging data were acquired while patients with schizophrenia (n = 15) and matched controls (n = 15) performed our adaptation method of agency attribution task on a trial-by-trial basis to assess participants' explicit experience of the temporal causal relationship between an action and an external event with temporal biases. Analysis of functional connectivity was done using the right supramarginal gyrus and the right middle frontal gyrus as seed regions. Results: In healthy controls, analyses revealed increased activation of the right inferior parietal lobule (mainly the supramarginal gyrus), right insula, and right middle frontal gyrus as an activation of the agency condition. We defined activated Brodmann areas shown in the agency condition of healthy controls as the seed region for connectivity analysis. The connectivity analysis revealed lower connectivity between the head of the left caudate nucleus and right supramarginal gyrus in the patients compared to healthy controls. Conclusions: This dysconnectivity of the agency network in schizophrenia may lead to self-disturbance through deficits in associative learning of SoA. These findings may explain why pathological function of the striatum in schizophrenia leads to self-disturbance.

Unidirectional connections from the cortex to the matrix of the corpus striatum initiate the cortico-basal ganglia (BG)-thalamocortical loop, thought to be important in momentary action selection and in longer-term fine tuning of behavioural repertoire; a discrete set of striatal compartments, striosomes, has the complementary role of registering or anticipating reward that shapes corticostriatal plasticity. Re-entrant signals traversing the cortico-BG loop impact predominantly frontal cortices, conveyed through topographically ordered output channels; by contrast, striatal input signals originate from a far broader span of cortex, and are far more divergent in their termination. The term ‘disclosed loop’ is introduced to describe this organisation: a closed circuit that is open to outside influence at the initial stage of cortical input. The closed circuit component of corticostriatal afferents is newly dubbed ‘operative’, as it is proposed to establish the bid for action selection on the part of an incipient cortical action plan; the broader set of converging corticostriatal afferents is described as contextual. A corollary of this proposal is that every unit of the striatal volume, including the long, C-shaped tail of the caudate nucleus, should receive a mandatory component of operative input, and hence include at least one area of BG-recipient cortex amongst the sources of its corticostriatal afferents. Individual operative afferents contact twin classes of GABAergic striatal projection neuron (SPN), distinguished by their neurochemical character, and onward circuitry. This is the basis of the classic direct and indirect pathway model of the cortico-BG loop. Each pathway utilises a serial chain of inhibition, with two such links, or three, providing positive and negative feedback, respectively. Operative co-activation of direct and indirect SPNs is, therefore, pictured to simultaneously promote action, and to restrain it. The balance of this rival activity is determined by the contextual inputs, which summarise the external and internal sensory environment, and the state of ongoing behavioural priorities. Notably, the distributed sources of contextual convergence upon a striatal locus mirror the transcortical network harnessed by the origin of the operative input to that locus, thereby capturing a similar set of contingencies relevant to determining action. The disclosed loop formulation of corticostriatal and subsequent BG loop circuitry, as advanced here, refines the operating rationale of the classic model and allows the integration of more recent anatomical and physiological data, some of which can appear at variance with the classic model. Equally, it provides a lucid functional context for continuing cellular studies of SPN biophysics and mechanisms of synaptic plasticity.

Iron is an essential micronutrient for healthy brain function and development. Because of the importance of iron in the brain, iron deficiency results in widespread and lasting effects on behavior and cognition. We measured iron in the basal ganglia of young children using a novel MRI method, quantitative susceptibility mapping, and examined the association of brain iron with age and cognitive performance. Participants were a community sample of 39 young children recruited from pediatric primary care who were participating in a five-year longitudinal study of child brain development and anxiety disorders. The children were ages 7 to 11 years old (mean age: 9.5 years old) at the time of the quantitative susceptibility mapping scan. The Differential Abilities Scale was administered when the children were 6 years old to provide a measure of general intelligence and verbal (receptive and expressive), non-verbal, and spatial performance. Magnetic susceptibility values, which are linearly related to iron concentration in iron-rich areas, were extracted from regions of interest within iron-rich deep gray matter nuclei from the basal ganglia, including the caudate, putamen, substantia nigra, globus pallidus, and thalamus. Controlling for scan age, there was a significant positive association between iron in the basal ganglia and spatial IQ, with this effect being driven by iron in the right caudate We also replicated previous findings of a significant positive association between iron in the bilateral basal ganglia and age. Our finding of a positive association between spatial IQ and mean iron in the basal ganglia, and in the caudate specifically, suggests that iron content in specific regions of the iron-rich deep nuclei of the basal ganglia influences spatial intelligence. This provides a potential neurobiological mechanism linking deficits in spatial abilities reported in children who were severely iron deficient as infants to decreased iron within the caudate.

Objectives: To identify activation changes assessed in functional magnetic resonance imaging (fMRI) studies of obsessive–compulsive disorder (OCD) through Activation Likelihood Estimate meta-analysis. Methods: We included 28 peer-reviewed standard stereotactic space studies assessing adult OCD patients (OCDpts) vs. healthy controls (HCs) with fMRI during executive task performance. Results: In within-group analyses, HCs showed task-related activations in bilateral inferior frontal gyri, right middle frontal gyrus, right inferior parietal lobule, right claustrum, bilateral cingulate gyri, and left caudate body. OCDpts showed task-related left-sided activations in the superior, medial, and inferior frontal gyri, and thalamus, and bilateral activations in the middle frontal gyri, inferior parietal lobule, and insular cortices. Subtraction analysis showed increased left middle frontal gyrus activation in OCDpts. In between-groups analyses, OCDpts hypoactivated the right caudate body, left putamen, left ACC, and right medial and middle frontal gyri. Right caudate hypoactivation persisted also after applying Family‐wise error algorithms. Conclusions: This meta-analysis confirms that during executive functioning OCDpts show a functional deficit of the right caudate body, which could represent a major neural functional correlate of their illness.

Background Studies of pre-and post-treatment striatal volume in schizophrenia have reported conflicting results. Materials and methods We assessed dorsal striatal (caudate and putamen) volumes bilaterally in 22 never-treated, non-substance-abusing patients with first-episode schizophrenia or schizophreniform disorder and 23 healthy controls matched for age, sex and educational status. Patients received either risperidone or flupenthixol long acting injection and were compared by structural MRI with controls at weeks 0, 4 and 13. T1-weighted data on a 3T MRI scanner were obtained and images were reconstructed using FreeSurfer. Treatment outcome was assessed by changes in psychopathology, insight, functionality, cognitive performance and motor symptoms. Results Caudate, but not putamen volumes was significantly larger in patients bilaterally at baseline (P = 0.01). Linear mixed effects repeated measures found no significant group × time interactions for any of the regions. Caudate volume was not significantly associated with improvements in psychotic symptoms. Also, the findings of a regression model were inconsistent insofar as larger caudate volume was associated with less improvement in depression scores, greater improvement in functionality and greater improvement in verbal learning but less improvement in reasoning and problem solving (left caudate) and composite cognitive score (right caudate). Conclusions The increased caudate volumes prior to treatment are contrary to previous reports in never-treated patients with first-episode schizophrenia, and together with our failure to demonstrate volume changes related to acute treatment, call into question previous proposals that enlarged caudate volume is a consequence of antipsychotic treatment.

Author(s): Hwang, Soonjo; Meffert, Harma; VanTieghem, Michelle R; Sinclair, Stephen; Bookheimer, Susan Y; Vaughan, Brigette; Blair, RJR | Abstract: ObjectivePrior functional magnetic resonance imaging (fMRI) work has revealed that children/adolescents with disruptive behavior disorders (DBDs) show dysfunctional reward/non-reward processing of non-social reinforcements in the context of instrumental learning tasks. Neural responsiveness to social reinforcements during instrumental learning, despite the importance of this for socialization, has not yet been previously investigated.MethodsTwenty-nine healthy children/adolescents and 19 children/adolescents with DBDs performed the fMRI social/non-social reinforcement learning task. Participants responded to random fractal image stimuli and received social and non-social rewards/non-rewards according to their accuracy.ResultsChildren/adolescents with DBDs showed significantly reduced responses within the caudate and posterior cingulate cortex (PCC) to non-social (financial) rewards and social non-rewards (the distress of others). Connectivity analyses revealed that children/adolescents with DBDs have decreased positive functional connectivity between the ventral striatum (VST) and the ventromedial prefrontal cortex (vmPFC) seeds and the lateral frontal cortex in response to reward relative to non-reward, irrespective of its sociality. In addition, they showed decreased positive connectivity between the vmPFC seed and the amygdala in response to non-reward relative to reward.ConclusionThese data indicate compromised reinforcement processing of both non-social rewards and social non-rewards in children/adolescents with DBDs within core regions for instrumental learning and reinforcement-based decision- making (caudate and PCC). In addition, children/adolescents with DBDs show dysfunctional interactions between the VST, vmPFC, and lateral frontal cortex in response to rewarded instrumental actions potentially reflecting disruptions in attention to rewarded stimuli.

Suicidal ideation (SI), a potent risk factor for suicide attempts, increases in adolescence. While alterations in dopaminergic functioning have been implicated in suicidal acts—particularly in adults—we do not know whether morphological alterations in dopamine-rich regions of the brain, such as the striatum, are vulnerability factors for the emergence of SI in adolescents. At baseline, a community sample of 152 adolescents (89 female; mean age: 11.41 ± 1.01 years) completed a magnetic resonance imaging (MRI) scan that was used to estimate gray matter volumes (GMVs) of three striatal structures: caudate, nucleus accumbens and putamen. At a 24 month follow-up session, participants completed a self-report measure of SI frequency [Suicidal Ideation Questionnaire (SIQ)] and the death version of the Implicit Association Test (IAT). Robust linear regression models were conducted to predict SIQ and IAT scores from striatal GMV. Bilateral putamen and left caudate GMV significantly predicted IAT scores (all Ps 0.05). Our finding of reduced dorsal striatal GMV predicting implicit SI may indicate that downstream dopaminergic dysfunction is implicated in the development of overt suicidal behaviors. Self-reported SI was not associated with striatal GMV, suggesting that biological correlates of suicide risk may correlate specifically with objective measurements of SI in adolescents.

s Background Speech recognition under noisy “cocktail-party” environments involves multiple perceptual/cognitive processes, including target detection, selective attention, irrelevant signal inhibition, sensory/working memory, and speech production. Compared to health listeners, people with schizophrenia are more vulnerable to masking stimuli and perform worse in speech recognition under speech-on-speech masking conditions. Although the schizophrenia-related speech-recognition impairment under “cocktail-party” conditions is associated with deficits of various perceptual/cognitive processes, it is crucial to know whether the brain substrates critically underlying speech detection against informational speech masking are impaired in people with schizophrenia. Methods Using functional magnetic resonance imaging (fMRI), this study investigated differences between people with schizophrenia (n = 19, mean age = 33 ± 10 years) and their matched healthy controls (n = 15, mean age = 30 ± 9 years) in intra-network functional connectivity (FC) specifically associated with target-speech detection under speech-on-speech-masking conditions. Results The target-speech detection performance under the speech-on-speech-masking condition in participants with schizophrenia was significantly worse than that in matched healthy participants (healthy controls). Moreover, in healthy controls, but not participants with schizophrenia, the strength of intra-network FC within the bilateral caudate was positively correlated with the speech-detection performance under the speech-masking conditions. Compared to controls, patients showed altered spatial activity pattern and decreased intra-network FC in the caudate. Conclusions In people with schizophrenia, the declined speech-detection performance under speech-on-speech masking conditions is associated with reduced intra-caudate functional connectivity, which normally contributes to detecting target speech against speech masking via its functions of suppressing masking-speech signals.

Significance Humans can learn to trust through direct social experiences. In our everyday lives, however, we constantly meet new people where judgments of trustworthiness are blind to reputation. In these cases, what drives decisions to trust? We find a simple learning mechanism observed across species—stimulus generalization—is deployed in complex social learning environments: Individuals distrust strangers who implicitly resemble those known to be untrustworthy. These behavioral findings were mirrored at the neural level, revealing that the amygdala and caudate selectively encode the transfer of social value during moral learning. The results demonstrate a mechanism that draws on prior learning to reduce the uncertainty associated with strangers, ultimately facilitating potentially adaptive decisions to trust, or withhold trust from, unfamiliar others., How do humans learn to trust unfamiliar others? Decisions in the absence of direct knowledge rely on our ability to generalize from past experiences and are often shaped by the degree of similarity between prior experience and novel situations. Here, we leverage a stimulus generalization framework to examine how perceptual similarity between known individuals and unfamiliar strangers shapes social learning. In a behavioral study, subjects play an iterative trust game with three partners who exhibit highly trustworthy, somewhat trustworthy, or highly untrustworthy behavior. After learning who can be trusted, subjects select new partners for a second game. Unbeknownst to subjects, each potential new partner was parametrically morphed with one of the three original players. Results reveal that subjects prefer to play with strangers who implicitly resemble the original player they previously learned was trustworthy and avoid playing with strangers resembling the untrustworthy player. These decisions to trust or distrust strangers formed a generalization gradient that converged toward baseline as perceptual similarity to the original player diminished. In a second imaging experiment we replicate these behavioral gradients and leverage multivariate pattern similarity analyses to reveal that a tuning profile of activation patterns in the amygdala selectively captures increasing perceptions of untrustworthiness. We additionally observe that within the caudate adaptive choices to trust rely on neural activation patterns similar to those elicited when learning about unrelated, but perceptually familiar, individuals. Together, these findings suggest an associative learning mechanism efficiently deploys moral information encoded from past experiences to guide future choice.

OBJECTIVESWith an increasing aging population, it is important to gain a better understanding of biological markers of aging. Subcortical volume is known to differ with age; additionally considering shape-related characteristics may provide a better index of age-related differences in subcortical structure. Recently fractal dimensionality has been shown to be more sensitive to age-related differences, but this measure is borne out of mathematical principles, rather than quantifying a neurobiologically relevant characteristic directly. We considered four distinct measures of shape and how they relate to aging and fractal dimensionality: surface-to-volume ratio, sphericity, long-axis curvature, and surface texture.METHODSStructural MRIs from two samples, with a combined sample size of over 600 healthy adults across the adult lifespan, were used to measure age-related differences in the structure of the thalamus, putamen, caudate, and hippocampus. For each structure, volume and fractal dimensionality were calculated, as well as each of the four distinct shape measures. These measures were then examined in their utility in explaining age-related variability in brain structure.RESULTSThe four shape measures were able to account for 80-90% of the variance in fractal dimensionality, indicating that these measures were sensitive to the same shape characteristics. Of the distinct shape measures, surface-to-volume ratio was the most sensitive aging biomarker.CONCLUSIONThough volume is often used to characterize inter-individual differences in subcortical structures, our results demonstrate that additional measures can be useful complements to volumetry. Our results indicate that shape characteristics of subcortical structures are useful biological markers of healthy aging.

Aging comes along with reduced gray matter (GM) volume in several cerebral areas and with cognitive performance decline in different cognitive domains. Moreover, regional GM volume is linked to specific cognitive sub processes in older adults. However, it remains unclear which regional changes in older individuals are directly associated with decreased cognitive performance. Moreover, most of the studies on this topic focused on hippocampal and prefrontal brain regions and their relation to memory and executive functioning. Interestingly, there are only a few studies that reported an association between striatal brain volume and cognitive performance. This is insofar surprising that striatal structures are (1) highly affected by age and (2) involved in different neural circuits that serve intact cognition. To address these issues, voxel-based morphometry (VBM) was used to analyze GM volume in 18 younger and 18 older adults. Moreover, several neuropsychological tests from different neuropsychological test batteries were applied to assess a broad range of cognitive domains. Older adults showed less GM volume than younger adults within frontal, striatal, and cerebellar brain regions. In the group of older adults, significant correlations were found between striatal GM volume and memory performance and between prefrontal/temporal GM volume and executive functioning. The only direct overlap between brain regions associated with regional atrophy and cognitive performance in older adults was found for the right caudate: older adults showed reduced caudate volume relative to younger adults. Moreover, caudate volume was positively correlated with associative memory accuracy in older adults and older adults showed poorer performances than younger adults in the respective associative memory task. Taken together, the current findings indicate the relevance of the caudate for associative memory decline in the aging brain.

Highlights • The options of treatment for caudate tumors are presented. • Treatment of caudate tumors by left-sided approach is proposal. • Better results with left-sided approach are discussed. • Selection of patients with tumors in caudate lobe for left-sided approach is important., Introduction The caudate lobe is a distinct liver lobe and surgical resection requires expertise and precise anatomic knowledge. Left-sided approach was described for resection of small tumors originated in the Spiegel lobe but now the procedure has been performed even for tumors more than five centimeters. The aim of this study is to present three cases of tumor of caudate lobe underwent isolated lobectomy by left-sided approach. Presentation of case Three patients with metastasis of colorectal cancer, carcinoma hepatocellular and metastasis of neuroendocrine tumor underwent resection. After modified Makuuchi incision, early control of short hepatic e short portal veins before hepatectomy was performed. The operative time was 200, 270 and 230 min respectively. No blood transfusion was used and no postoperative complications were observed. The length of stay was 7, 11 and 5 days respectively. Discussion Some approaches have been described to access and resect tumors of the caudate lobe, including the left-sided approach, right-sided approach, combined left- and right-sided approach and the anterior transhepatic approach. For liver resection in patients with malignant disease, parenchymal preservation is important in order to avoid postoperative liver failure or due to the risk of second hepatectomy. In these patients isolated caudate lobectomy is a safe option. Conclusion Isolated caudate lobectomy is a feasible procedure. Left-sided approach can be preformed even for tumors larger than 5 cm.

Journal article First episode psychosis (FEP) has been associated with structural brain changes, largely identified by volumetric analyses. Advances in neuroimaging processing have made it possible to measure geometric properties that may identify subtle structural changes not appreciated by a measure of volume alone. In this study we adopt complementary methods of assessing the structural integrity of grey matter in FEP patients and assess whether these relate to patient clinical and functional outcome at 3year follow-up. 1.5Tesla T1-weighted Magnetic Resonance (MR) images were acquired for 46 patients experiencing their first episode of psychosis and 46 healthy controls. Cerebral cortical thickness and local gyrification index (LGI) were investigated using FreeSurfer software. Volume and shape of the hippocampus, caudate and lateral ventricles were assessed using manual tracing and spherical harmonics applied for shape description. A cluster of cortical thinning was identified in FEP compared to controls; this was located in the right superior temporal gyrus, sulcus, extended into the middle temporal gyrus (lateral temporal cortex - LTC). Bilateral caudate volumes were significantly lower in FEP relative to controls and the right caudate also displayed regions of shape deflation in the FEP group. No significant structural abnormalities were identified in cortical LGI or hippocampal or lateral ventricle volume/shape. Neither LTC nor caudate abnormalities were related to change in symptom severity or global functioning 3years later. LTC and caudate abnormalities are present at the first episode of psychosis but do not appear to directly affect clinical or functional outcome. peer-reviewed

Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4's connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific., National Institute of Mental Health (U.S.). Intramural Research Program, National Institutes of Health (U.S.) (Grant R01EY017292)

Our brains represent spatial information in egocentric (self-based) or allocentric (landmark-based) coordinates. Rodent studies have demonstrated a critical role for the caudate in egocentric navigation and the hippocampus in allocentric navigation. We administered tests of egocentric and allocentric working memory to individuals with premotor Huntington’s disease (pmHD), which is associated with early caudate nucleus atrophy, and controls. Each test had 80 trials during which subjects were asked to remember 2 locations over 1-sec delays. The only difference between these otherwise identical tests was that locations could only be coded in self-based or landmark-based coordinates. We applied a multiatlas-based segmentation algorithm and computed point-wise Jacobian determinants to measure regional variations in caudate and hippocampal volumes from 3 T MRI. As predicted, the pmHD patients were significantly more impaired on egocentric working memory. Only egocentric accuracy correlated with caudate volumes, specifically the dorsolateral caudate head, right more than left, a region that receives dense efferents from dorsolateral prefrontal cortex. In contrast, only allocentric accuracy correlated with hippocampal volumes, specifically intermediate and posterior regions that connect strongly with parahippocampal and posterior parietal cortices. These results indicate that the distinction between egocentric and allocentric navigation applies to working memory. The dorsolateral caudate is important for egocentric working memory, which can explain the disproportionate impairment in pmHD. Allocentric working memory, in contrast, relies on the hippocampus and is relatively spared in pmHD.

Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD., Highlights • We used MRI techniques to assess the connectivity in language networks in AS. • Grey-matter heterogeneity of MR images correlated with volume of caudate in AS. • Hence, caudate nuclei were used as seed ROIs in connectivity analyses: PPI, DCM. • Grey-matter heterogeneity differently tuned caudate connectivity in AS, controls. • DCM of language circuitry featured bottom-up models in AS and top-down in controls.

Individuals in the early stage of intense romantic love show many symptoms of substance and non-substance or behavioral addictions, including euphoria, craving, tolerance, emotional and physical dependence, withdrawal and relapse. We have proposed that romantic love is a natural (and often positive) addiction that evolved from mammalian antecedents by four million years ago as a survival mechanism to encourage hominin pair-bonding and reproduction, seen cross-culturally today in Homo sapiens. Brain scanning studies using functional magnetic resonance imaging (fMRI) support this view: feelings of intense romantic love engage regions of the brain’s reward system, specifically dopamine-rich regions, including the ventral tegmental area, also activated during drug and/or behavioral addiction. Thus, because the experience of romantic love shares reward pathways with a range of substance and behavioral addictions, it may influence the drug and/or behavioral addiction response. Indeed, a study of overnight abstinent smokers has shown that feelings of intense romantic love attenuate brain activity associated with cigarette cue-reactivity. Could socially rewarding experiences be therapeutic for drug and/or behavioral addictions? We suggest that self expanding experiences like romance and expanding one’s knowledge, experience and self-perception, may also affect drug and/or behavioral addiction behaviors. Further, because feelings of romantic love can progress into feelings of calm attachment, and because attachment engages more plastic forebrain regions, there is a rationale for therapies that may help substance and/or behavioral addiction by promoting activation of these forebrain systems through long-term, calm, positive attachments to others, including group therapies. Addiction is considered a negative (harmful) disorder that appears in a population subset; while romantic love is often a positive (as well as negative) state experienced by almost all humans. Thus, researchers have not categorized romantic love as a chemical or behavioral addiction. But by embracing data on romantic love, it’s classification as an evolved, natural, often positive but also powerfully negative addiction, and its neural similarity to many substance and non-substance addictive states, clinicians may develop more effective therapeutic approaches to alleviate a range of the addictions, including heartbreak--an almost universal human experience that can trigger stalking, clinical depression, suicide, homicide and other crimes of passion.

We have previously shown that patients with Parkinson's disease (PD) perseverate in their choice of action relative to healthy controls, and that this is affected by dopaminergic medication (Hughes LE, Barker RA, Owen AM, Rowe JB. 2010. Parkinson's disease and healthy aging: Independent and interacting effects on action selection. Hum Brain Mapp. 31:1886-1899). To understand further the neural basis of these phenomena, we used a new task that manipulated the options to repeat responses. Seventeen patients with idiopathic PD were studied both "on" and "off" dopaminergic medication and 18 healthy adults were scanned twice as controls. All subjects performed a right-handed 3-choice button press task, which controlled the availability of repeatable responses. The frequency of choosing to repeat a response (a form of perseveration) in patients was related to dopamine therapy and disease severity as a "U-shaped" function. For repetitive trials, this "U-shaped" relationship was also reflected in the BOLD response in the caudate nuclei and ventrolateral prefrontal cortex. Our results support a U-shaped model of optimized cortico-striatal circuit function and clearly demonstrate that flexibility in response choice is modulated by an interaction of dopamine and disease severity.

Dopamine D2 receptor hyperactivity has been implicated in the development of psychogenic polydipsia in schizophrenic patients. Repeated treatment with dopamine agonists, including the D2/D3 agonist quinpirole, has been shown to induce hyperdipsia in a number of animal models. Despite these observations, obtained with systemic administrations, little attempt has been made to investigate where in the brain dopamine agonists act to induce hyperdipsia.The present study investigates the effects of repeated intra-caudate infusions of quinpirole on the intake of water by rats tested under free-drinking conditions.Rats with bilateral cannulae placed into the anterior, central or posterior caudate received quinpirole microinfusions (1 μg/side) for five consecutive days in their home cage. Water intake was measured 15 and 60 min after the treatment.When injected in the central caudate, quinpirole increased water intake, and this effect progressively increased over sessions, indicating the development of sensitization. When injected in the posterior caudate, the dipsogenic effect of quinpirole was less intense and did not undergo sensitization. The infusion of quinpirole in the anterior caudate did not affect drinking.The present study shows that caudate D2/3 receptors play an important role in the development of quinpirole-induced hyperdipsia, an animal model of psychotic polydipsia.

The human striatum has been previously implicated in the processing of positive reinforcement, but less is known about its role in processing negative reinforcement. In this experiment, participants learn specific approach or avoidance responses, mediated by positive and negative reinforcers respectively to investigate how affective learning and associated neural activity are influenced by the motivational context in which learning occurs. The paradigm was divided into two discrete sessions, where participants could either earn monetary rewards (approach sessions) or avoid monetary losses (avoid sessions) based on successful learning. Specifically, a conditioned cue predicted the chance to win or avoid losing money contingent on a correct button press (pre-learning trials), which upon learning led to the delivery of rewards or termination of losses (post-learning trials). Skin conductance responses (SCRs) and subjective ratings confirmed a learning effect (greater SCRs pre vs. post-learning) irrespective of reinforcer valence. Concurrently, activity in the ventral striatum was characterized by a similar learning effect, with greater responses during pre-learning. Interestingly, such learning effect was enhanced in the presence of a negative reinforcer, as suggested by an interaction between learning phase and session, highlighting the influence negative reinforcers can have on striatal circuits involved in learning and motivated behavior.

The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10⁻⁶) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.

Pain modulation is an integral function of the nervous system. It is needed to adapt to chronic stimuli. To gain insights into pain suppression mechanisms, two studies concerning the suppression of the feeling of pain with different stimulation modalities (heat vs. electrical stimuli) but using the same stimulation paradigms were compared: 15 subjects each had been stimulated on both hands under the instruction to suppress the feeling of pain. Anterior insula and DLPFC activation was seen in both single modality studies and seems to be a common feature of pain suppression, as it is absent in the interaction analyses presented here. During the task to suppress the feeling of pain, there were no consistent activations stronger under thermostimulation. But during electrostimulation, there was significantly stronger activation than during thermal stimulation in the caudate nu- cleus bilaterally and in the contralateral posterior insula. This may be attributed to the higher sensory-discriminative con- tent and more demand on subjective rating and suppression of the painful electrical stimulus, compared to thermostimula- tion. The caudate nucleus seems to play an important role not only in the motor system but also in the modulation of the pain experience.

Metabotropic glutamate receptors (mGluRs) are densely expressed in the limbic system of the mammalian brain. Increasing evidence suggests a critical role of mGluRs in the pathogenesis of various mental illnesses, including drug abuse and addiction. In this study, we investigated the effect of psychostimulant, cocaine, on protein expression of a specific mGluR subtype, mGluR8, in the rat forebrain in vivo. A rabbit antibody against the extracellular N-terminus of mGluR8 was developed to detect changes in mGluR8 proteins in immunoblot assays. With this antibody, we found that acute systemic injection of cocaine reduced mGluR8 protein levels in the striatum. The reduction of mGluR8 proteins was rapid and transient as it was induced 25 min after cocaine injection and returned to the normal level by 6 h. No significant change in mGluR8 protein levels in the prefrontal cortex and the hippocampus was observed following cocaine administration. These data demonstrate that protein expression of mGluR8 is subject to the modulation by dopamine stimulation. Acute exposure to cocaine results in a dynamic and region-specific downregulation of mGluR8 expression in the striatum. © 2008 Elsevier Ireland Ltd. All rights reserved.

We have explored genome-wide expression of genes related to glycobiology in exon 1 transgenic Huntington's disease (HD) mice using a custom-designed GLYCOv2 chip and Affymetrix microarray analyses. We validated, using quantitative real-time PCR, abnormal expression levels of genes encoding glycosyltransferases in the striatum of R6/1 transgenic mice, as well as in postmortem caudate from human HD subjects. Many of these genes show differential regional expression within the CNS, as indicated by in situ hybridization analysis, suggesting region-specific regulation of this system in the brain. We further show disrupted patterns of glycolipids (acidic and neutral lipids) and/or ganglioside levels in both the forebrain of the R6/1 transgenic mice and caudate samples from human HD subjects. These findings reveal novel disruptions in glycolipid/ganglioside metabolic pathways in the pathology of HD and suggest that the development of new targets to restore glycosphingolipid balance may act to ameliorate some symptoms of HD.

Music is often used to regulate emotions and mood. Typically, music conveys and induces emotions even when one does not attend to them. Studies on the neural substrates of musical emotions have, however, only examined brain activity when subjects have focused on the emotional content of the music. Here we address with functional magnetic resonance imaging (fMRI) the neural processing of happy, sad, and fearful music with a paradigm in which 56 subjects were instructed to either classify the emotions (explicit condition) or pay attention to the number of instruments playing (implicit condition) in 4-s music clips. In the implicit vs. explicit condition, stimuli activated bilaterally the inferior parietal lobule, premotor cortex, caudate, and ventromedial frontal areas. The cortical dorsomedial prefrontal and occipital areas activated during explicit processing were those previously shown to be associated with the cognitive processing of music and emotion recognition and regulation. Moreover, happiness in music was associated with activity in the bilateral auditory cortex, left parahippocampal gyrus, and supplementary motor area, whereas the negative emotions of sadness and fear corresponded with activation of the left anterior cingulate and middle frontal gyrus and down-regulation of the orbitofrontal cortex. Our study demonstrates for the first time in healthy subjects the neural underpinnings of the implicit processing of brief musical emotions, particularly in frontoparietal, dorsolateral prefrontal, and striatal areas of the brain. (C) 2016 Elsevier Ltd. All rights reserved.

Value-based decision-making involves an assessment of the value of items available and the actions required to obtain them. The basal ganglia are highly implicated in action selection and goal-directed behavior [1-4], and the striatum in particular plays a critical role in arbitrating between competing choices [5-9]. Previous work has demonstrated that neural activity in the caudate nucleus is modulated by task-relevant action values [6, 8]. Nonetheless, how value is represented and maintained in the striatum remains unclear since decision-making in these tasks relied on spatially lateralized responses, confounding the ability to generalize to a more abstract choice task [6, 8, 9]. Here, we investigate striatal value representations by applying caudate electrical stimulation in macaque monkeys (n= 3) to bias decision-making in a task that divorces the value of a stimulus from motor action. Electrical microstimulation is known to induce neural plasticity [10,11], and caudate microstimulation in primates has been shown to accelerate associative learning [12, 13]. Our results indicate that stimulation paired with a particular stimulus increases selection of that stimulus, and this effect was stimulus dependent and action independent. The modulation of choice behavior using microstimulation was best modeled as resulting from changes in stimulus value. Caudate neural recordings (n= 1) show that changes in value-coding neuron activity arestimulus value dependent. We argue that caudate microstimulation can differentially increase stimulus values independent of action, and unilateral manipulations of value are sufficient to mediate choice behavior. These results support potential future applications of microstimulation to correct maladaptive plasticity underlying dysfunctional decision-making related to neuropsychiatric conditions.

Summary Activity in striatal direct- and indirect-pathway spiny projection neurons (SPNs) is critical for proper movement. However, little is known about the spatiotemporal organization of this activity. We investigated the spatiotemporal organization of SPN ensemble activity in mice during self-paced, natural movements using microendoscopic imaging. Activity in both pathways showed predominantly local but also some long-range correlations. Using a novel approach to cluster and quantify behaviors based on continuous accelerometer and video data, we found that SPN ensembles active during specific actions were spatially closer and more correlated overall. Furthermore, similarity between different actions corresponded to the similarity between SPN ensemble patterns, irrespective of movement speed. Consistently, the accuracy of decoding behavior from SPN ensemble patterns was directly related to the dissimilarity between behavioral clusters. These results identify a predominantly local, but not spatially compact, organization of direct- and indirect-pathway SPN activity that maps action space independently of movement speed., Highlights • Direct- and indirect-pathway SPNs show locally biased spatiotemporal organization • SPNs active during a particular behavior are more correlated and spatially closer • SPN ensembles encode action identity independently of movement speed • Distance between behaviors corresponds to distance between SPN ensemble patterns, Klaus, Martins et al. image neural activity from direct- and indirect-pathway neurons of dorsal striatum during self-paced, natural behaviors. They find that striatal neurons form ensembles that are spatiotemporally organized and map action space independently of movement speed.

Basal ganglia (BG) abnormalities are implicated in the pathophysiology of autism spectrum disorder (ASD). However, studies measuring the volume of the entire BG in individuals with ASD have reported discrepant findings, and no study conducted volume measurement of the entire substructures of the BG (the caudate, putamen, nucleus accumbens, and globus pallidus) in individuals with ASD. We delineated the BG substructures and measured their volumes in 29 adults with ASD without intellectual disabilities and 29 age- and gender-matched typically developed adult controls. We acquired T1-weighted anatomical images and performed semi-automated delineation and volume measurements of the above-mentioned subregions. Total cerebral volumes, sex, and ages were partialed out. Compared with controls, the putamen was significantly larger in the ASD group. The increased volume of the putamen found in high-functioning adults with ASD suggests that structural or histological abnormalities of the putamen may underlie the pathologies of ASD such as repetitive and stereotyped behaviors and impaired social interactions.

The basal ganglia have traditionally been viewed as motor processing nuclei; however, functional neuroimaging evidence has implicated these structures in more complex cognitive and affective processes that are fundamental for a range of human activities. Using quantitative meta-analysis methods we assessed the functional subdivisions of basal ganglia nuclei in relation to motor (body and eye movements), cognitive (working-memory and executive), affective (emotion and reward) and somatosensory functions in healthy participants. We document affective processes in the anterior parts of the caudate head with the most overlap within the left hemisphere. Cognitive processes showed the most widespread response, whereas motor processes occupied more central structures. On the basis of these demonstrated functional roles of the basal ganglia, we provide a new comprehensive topographical model of these nuclei and insight into how they are linked to a wide range of behaviors.© 2012 Wiley Periodicals, Inc.

Lin Wu,1,2,* Yue Zhang,3,* Fuqing Zhou,1,2,* Lei Gao,2 Laichang He,1,2 Xianjun Zeng,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, 2Jiangxi Province Medical Imaging Research Institute, 3Department of Radiology, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, People’s Republic of China *These authors contributed equally tothis work Background and purpose: Neuroimaging studies of relapsing–remitting multiple sclerosis (RRMS) have found structural disconnection and large-scale neural network dysfunction. However, few studies have explored the local brain activity of RRMS patients in the resting state. Patients and methods: In this study, regional homogeneity (ReHo) and resting-state functional connectivity (FC) were used to investigate intra- and interregional synchronized activity in 22 patients with RRMS and 22 matched healthy controls (HCs). Results: Compared with HCs, patients with RRMS showed significantly decreased ReHo in the left insula and right caudate. Through further seed-based FC analysis, we found decreased FC between the left insula and left precentral gyrus in patients with RRMS compared with HCs, as well as increased FC between the right caudate and right dorsolateral prefrontal cortex. Pearson’s correlation analysis showed that a decreased ReHo value in the left insula was associated with an increased total white matter lesion loads (TWMLL) score (r=-0.594, P=0.004) or a worsened paced auditory serial addition test score (r=0.536, P=0.010). No other significant correlations were observed between the FC value (left insula - left precentral gyrus) and clinical scores (P=0.246–0.982). The ReHo value of the right caudate was negatively correlated with disease duration (r=-0.526, P=0.012) and with the TWMLL score (r=-0.596, P=0.003). Moreover, a positive correlation was observed between the FC value (right caudate - right dorsolateral prefrontal cortex) and the TWMLL score (r=0.523, P=0.012) or the modified fatigue impact scale-5 score (r=0.608, P=0.003). Conclusion: Together, these findings suggest that the insula with regional dysfunction involves disconnection with sensorimotor regions, and demyelinating lesion-related intra- and interregional dysfunction in the caudate is associated with the impact of fatigue on cognitive control functions. Abnormal synchronization of intra- and interregional activity in the insula and caudate may play important roles in the pathology of RRMS. Keywords: relapsing–remitting multiple sclerosis, functional MRI, resting state, regional homogeneity, functional connectivity, caudate, insula

Introduction The dopamine-type-1 receptor has been implicated in major depressive disorder (MDD) by clinical and preclinical evidence from neuroimaging, post-mortem and behavioral studies. To date, however, selective in vivo assessment of D1-receptors has been limited to the striatum in MDD-samples manifesting anger attacks. We employed the PET radioligand, [11C]NNC-112, to selectively assess D1-receptor binding in extrastriatal and striatal regions in a more generalized sample of MDD-subjects. Methods The [11C]NNC-112 nondisplaceable binding-potential (BPND) was assessed using PET in 18 unmedicated, currently-depressed subjects with MDD and 19 healthy controls, and compared between groups using MRI-based region-of-interest analysis. Results The mean D1-receptor BPND was reduced (14%) in the left middle caudate of the MDD group relative to control group (p

Adenosine A2A antagonists can exert antiparkinsonian effects in animal models. Recent experiments studied the ability of MSX-3 (an adenosine A2A antagonist) to reverse the locomotor suppression and tremor produced by dopamine antagonists in rats. MSX-3 reversed haloperidol-induced suppression of locomotion, and reduced the tremulous jaw movements induced by haloperidol, pimozide, and reserpine. Infusions of MSX-3 into the nucleus accumbens core increased locomotion in haloperidol-treated rats, but there were no effects of infusions into the accumbens shell or ventrolateral neostriatum. In contrast, MSX-3 injected into the ventrolateral neostriatum reduced pimozide-induced tremulous jaw movements. Dopamine/adenosine interactions in different striatal subregions are involved in distinct aspects of motor function. © 2008 Elsevier Ltd. All rights reserved.

In the dorsal striatum, there are two major populations of medium spiny projection neurons. One population is positive for dynorphin mRNA (DYN+), and these cells project preferentially to the substantia nigra, forming the so-called 'direct pathway'. A second population is positive for enkephalin mRNA (ENK+), and these cells influence the substantia nigra indirectly, via the globus pallidus and subthalamic nucleus. Psychostimulant drugs, such as amphetamine and cocaine, are reported to induce immediate early genes (IEGs) in only one subpopulation of dorsal striatal projection neurons, DYN+ cells. However, this apparent selectivity appears to be a function of environmental context. We found that when given in the animal's home cage, amphetamine and cocaine increased expression of the IEG, c-fos, almost exclusively in DYN+ cells. However, when given in a novel environment, amphetamine and cocaine increased c-fos mRNA in both DYN+ and ENK+ cells. Furthermore, amphetamine and cocaine increased c-fos mRNA expression in the subthalamic nucleus when administered in the novel environment, but not when given at home. We conclude that the neural circuitry engaged by psychostimulant drugs, and their ability to induce specific patterns of gene expression, are determined by the environmental context in which they are experienced. This may be related to the ability of environmental novelty to facilitate psychostimulant drug-induced neuroplasticity.

Drinking in the rat occurs in bursts of rapid licking, a high frequency rhythmic behavior controlled by a neural clock located in the brain stem. We found that 3.0 mg/kg amphetamine increased the speed of licking and shifted to the left the frequency distribution of inter-lick intervals. Repeated amphetamine treatments result in long-lasting sensitization to this effect. Thus, it appears possible to produce enduring changes in the activity of a biological interval clock (or 'stopwatch') by manipulating catecholaminergic transmission. These findings may be important for an understanding of the neural basis of normal and pathological timing behavior.