Cerebrospinal Fluid-In Gradient of Cortical and Deep Gray Matter Damage in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach. METHODS: For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures. RESULTS: We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-p ≤ 0.016) and thalamic (FDR-p ≤ 0.048) layers, and in the outer caudate layer (FDR-p = 0.024). They showed lower R2* values in the outer cortical layer (FDR-p = 0.003) and in the outer thalamic layer (FDR-p = 0.046) and higher R2* values in all 3 caudate layers (FDR-p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-p ≤ 0.002) and thalamic (FDR-p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-p = 0.005), thalamic R2* (FDR-p = 0.004), and caudate MTR (FDR-p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (ß ≥ 0.08, all FDR-p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (ß = -0.26, FDR-p = 0.040). No correlations with choroid plexus volume were found. DISCUSSION: CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.

Is the Caudate, Putamen, and Globus Pallidus the Delusional Disorder's Trio? A Texture Analysis Study.

BACKGROUND: The neurobiological basis of delusional disorder is less explored through neuroimaging techniques than in other psychotic disorders. This study aims to provide information about the neural origins of delusional disorder (DD) by examining the neuroanatomical features of some basal nuclei with magnetic resonance imaging (MRI) texture analysis. MATERIALS AND METHODS: Twenty DD patients and 20 healthy individuals were included in the study. Globus pallidus, putamen, and caudate nuclei were selected individually with a region of interest (ROI) on the axial MRI images. The entire texture analysis algorithm applied to all selected ROIs was done with an in-house software. Nuclei on both sides were taken as separate samples. RESULTS: There were no significant differences between groups in terms of age and gender. The average "mean, median and maximum" values of all three nuclei were decreased in DD patients. The small putamen area and the differences detected in different tissue parameters for all three nuclei in delusional disorder patients indicate that they differ in delusional disorder from normal controls (p < 0.05). CONCLUSION: The differences detected in the texture parameters for all three nuclei indicate that there is something different in the DD from in the normal controls. Neuroimaging studies with larger samples and different techniques in the future may shed light on the etiology of delusional disorder.

Robust memory of face moral values is encoded in the human caudate tail: a simultaneous EEG-fMRI study.

Moral judgements about people based on their actions is a key component that guides social decision making. It is currently unknown how positive or negative moral judgments associated with a person's face are processed and stored in the brain for a long time. Here, we investigate the long-term memory of moral values associated with human faces using simultaneous EEG-fMRI data acquisition. Results show that only a few exposures to morally charged stories of people are enough to form long-term memories a day later for a relatively large number of new faces. Event related potentials (ERPs) showed a significant differentiation of remembered good vs bad faces over centerofrontal electrode sites (value ERP). EEG-informed fMRI analysis revealed a subcortical cluster centered on the left caudate tail (CDt) as a correlate of the face value ERP. Importantly neither this analysis nor a conventional whole-brain analysis revealed any significant coding of face values in cortical areas, in particular the fusiform face area (FFA). Conversely an fMRI-informed EEG source localization using accurate subject-specific EEG head models also revealed activation in the left caudate tail. Nevertheless, the detected caudate tail region was found to be functionally connected to the FFA, suggesting FFA to be the source of face-specific information to CDt. A further psycho-physiological interaction analysis also revealed task-dependent coupling between CDt and dorsomedial prefrontal cortex (dmPFC), a region previously identified as retaining emotional working memories. These results identify CDt as a main site for encoding the long-term value memories of faces in humans suggesting that moral value of faces activates the same subcortical basal ganglia circuitry involved in processing reward value memory for objects in primates.

Differential Roles of Key Brain Regions: Ventral Tegmental Area, Locus Coeruleus, Dorsal Raphe, Nucleus Accumbens, Caudate Nucleus, and Prefrontal Cortex in Regulating Response to Methylphenidate: Insights from Neuronal and Behavioral Studies in Freely Behaving Rats.

A total of 3102 neurons were recorded before and following acute and chronic methylphenidate (MPD) administration. Acute MPD exposure elicits mainly increases in neuronal and behavioral activity in dose-response characteristics. The response to chronic MPD exposure, as compared to acute 0.6, 2.5, or 10.0 mg/kg MPD administration, elicits electrophysiological and behavioral sensitization in some animals and electrophysiological and behavioral tolerance in others when the neuronal recording evaluations were performed based on the animals' behavioral responses, or amount of locomotor activity, to chronic MPD exposure. The majority of neurons recorded from those expressing behavioral sensitization responded to chronic MPD with further increases in firing rate as compared to the initial MPD responses. The majority of neurons recorded from animals expressing behavioral tolerance responded to chronic MPD with decreases in their firing rate as compared to the initial MPD exposures. Each of the six brain areas studied-the ventral tegmental area, locus coeruleus, dorsal raphe, nucleus accumbens, prefrontal cortex, and caudate nucleus (VTA, LC, DR, NAc, PFC, and CN)-responds significantly (p < 0.001) differently to MPD, suggesting that each one of the above brain areas exhibits different roles in the response to MPD. Moreover, this study demonstrates that it is essential to evaluate neuronal activity responses to psychostimulants based on the animals' behavioral responses to acute and chronic effects of the drug from several brain areas simultaneously to obtain accurate information on each area's role in response to the drug.

The tail of the caudate is sensitive to both gain and loss feedback during information integration categorization.

Although most category learning studies use feedback for training, little attention has been paid to how individuals utilize feedback implemented as gains or losses during categorization. We compared skilled categorization under three different conditions: Gain (earn points for correct answers), Gain and Loss (earn points for correct answers and lose points for wrong answers) and Correct or Wrong (accuracy feedback only). We also manipulated difficulty and point value, with near boundary stimuli having the highest number of points to win or lose, and stimuli far from the boundary having the lowest point value. We found that the tail of the caudate was sensitive to feedback condition, with highest activity when both Gain and Loss feedback were present and least activity when only Gain or accuracy feedback was present. We also found that activity across the caudate was affected by distance from the decision bound, with greatest activity for the near boundary high value stimuli, and lowest for far low value stimuli. Overall these results indicate that the tail of the caudate is sensitive not only to positive rewards but also to loss and punishment, consistent with recent animal research finding tail of the caudate activity in aversive learning.

Excessive left anterior hippocampal and caudate activation in schizophrenia underlie cognitive underperformance in a virtual navigation task.

We used a virtual navigation paradigm in a city environment to assess neuroanatomical correlates of cognitive deficits in schizophrenia spectrum disorders (SSD). We studied a total of N = 36 subjects: 18 with SSD and 18 matched unaffected controls. Participants completed 10 rapid, single-trial navigation tasks within the virtual city while undergoing functional magnetic resonance imaging (fMRI). All trials tested ability to find different targets seen earlier, during the passive viewing of a path around different city blocks. SSD patients had difficulty finding previously-encountered targets, were less likely to find novel shortcuts to targets, and more likely to attempt retracing of the path observed during passive viewing. Based on a priori region-of-interest analyses, SSD participants had hyperactivation of the left hippocampus when passively viewing turns, hyperactivation of the left caudate when finding targets, and hypoactivation of a focal area of the dorsolateral prefrontal cortex when targets were initially shown during passive viewing. We propose that these brain-behaviour relations may bias or reinforce stimulus-response navigation approaches in SSD and underlie impaired performance when allocentric spatial memory is required, such as when forming efficient shortcuts. This pattern may extend to more general cognitive impairments in SSD that could be used to design remediation strategies.

Identification of patients with internet gaming disorder via a radiomics-based machine learning model of subcortical structures in high-resolution T1-weighted MRI.

It is of vital importance to establish an objective and reliable model to facilitate the early diagnosis and intervention of internet gaming disorder (IGD). A total of 133 patients with IGD and 110 healthy controls (HCs) were included. We extracted radiomic features of subcortical structures in high-resolution T1-weighted MRI. Different combinations of four feature selection methods (analysis of variance, Kruskal-Wallis, recursive feature elimination and relief) and ten classification algorithms were used to identify the most robust combined models for distinguishing IGD patients from HCs. Furthermore, a nomogram incorporating radiomic signatures and independent clinical factors was developed. Calibration curve and decision curve analyses were used to evaluate the nomogram. The combination of analysis of variance selector and logistic regression classifier identified that the radiomic model constructed with 20 features from the right caudate nucleus and amygdala showed better IGD screening performance. The radiomic model produced good areas under the curves (AUCs) in the training, validation and test cohorts (AUCs of 0.961, 0.903 and 0.895, respectively). In addition, sex, internet addiction test scores and radiomic scores were included in the nomogram as independent risk factors for IGD. Analysis of the correction curve and decision curve showed that the clinical-radiomic model has good reliability (C-index: 0.987). The nomogram incorporating radiomic features of subcortical structures and clinical characteristics achieved satisfactory classification performance and could serve as an effective tool for distinguishing IGD patients from HCs.

Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus.

Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n = 399, dorsolateral prefrontal cortex: n = 377, and hippocampus: n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.

Comparative anatomy of the caudate nucleus in canids and felids: Associations with brain size, curvature, cross-sectional properties, and behavioral ecology.

The evolutionary history of canids and felids is marked by a deep time separation that has uniquely shaped their behavior and phenotype toward refined predatory abilities. The caudate nucleus is a subcortical brain structure associated with both motor control and cognitive, emotional, and executive functions. We used a combination of three-dimensional imaging, allometric scaling, and structural analyses to compare the size and shape characteristics of the caudate nucleus. The sample consisted of MRI scan data obtained from six canid species (Canis lupus lupus, Canis latrans, Chrysocyon brachyurus, Lycaon pictus, Vulpes vulpes, Vulpes zerda), two canid subspecies (Canis lupus familiaris, Canis lupus dingo), as well as three felids (Panthera tigris, Panthera uncia, Felis silvestris catus). Results revealed marked conservation in the scaling and shape attributes of the caudate nucleus across species, with only slight deviations. We hypothesize that observed differences in caudate nucleus size and structure for the domestic canids are reflective of enhanced cognitive and emotional pathways that possibly emerged during domestication.

External evaluation of a deep learning-based approach for automated brain volumetry in patients with huntington's disease.

A crucial step in the clinical adaptation of an AI-based tool is an external, independent validation. The aim of this study was to investigate brain atrophy in patients with confirmed, progressed Huntington's disease using a certified software for automated volumetry and to compare the results with the manual measurement methods used in clinical practice as well as volume calculations of the caudate nuclei based on manual segmentations. Twenty-two patients were included retrospectively, consisting of eleven patients with Huntington's disease and caudate nucleus atrophy and an age- and sex-matched control group. To quantify caudate head atrophy, the frontal horn width to intercaudate distance ratio and the intercaudate distance to inner table width ratio were obtained. The software mdbrain was used for automated volumetry. Manually measured ratios and automatically measured volumes of the groups were compared using two-sample t-tests. Pearson correlation analyses were performed. The relative difference between automatically and manually determined volumes of the caudate nuclei was calculated. Both ratios were significantly different between the groups. The automatically and manually determined volumes of the caudate nuclei showed a high level of agreement with a mean relative discrepancy of - 2.3 ± 5.5%. The Huntington's disease group showed significantly lower volumes in a variety of supratentorial brain structures. The highest degree of atrophy was shown for the caudate nucleus, putamen, and pallidum (all p < .0001). The caudate nucleus volume and the ratios were found to be strongly correlated in both groups. In conclusion, in patients with progressed Huntington's disease, it was shown that the automatically determined caudate nucleus volume correlates strongly with measured ratios commonly used in clinical practice. Both methods allowed clear differentiation between groups in this collective. The software additionally allows radiologists to more objectively assess the involvement of a variety of brain structures that are less accessible to standard semiquantitative methods.

Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo.

The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia.

Comparative Roles of the Caudate and Putamen in the Serial Order of Behavior: Effects of Striatal Glutamate Receptor Blockade on Variable versus Fixed Spatial Self-Ordered Sequencing in Marmosets.

Self-ordered sequencing is an important executive function involving planning and executing a series of steps to achieve goal-directed outcomes. The lateral frontal cortex is implicated in this behavior, but downstream striatal outputs remain relatively unexplored. We trained marmosets on a three-stimulus self-ordered spatial sequencing task using a touch-sensitive screen to explore the role of the caudate nucleus and putamen in random and fixed response arrays. By transiently blocking glutamatergic inputs to these regions, using intrastriatal CNQX microinfusions, we demonstrate that the caudate and putamen are both required for, but contribute differently to, flexible and fixed sequencing. CNQX into either the caudate or putamen impaired variable array accuracy, and infusions into both simultaneously elicited greater impairment. We demonstrated that continuous perseverative errors in variable array were caused by putamen infusions, likely due to interference with the putamen's established role in monitoring motor feedback. Caudate infusions, however, did not affect continuous errors, but did cause an upward trend in recurrent perseveration, possibly reflecting interference with the caudate's established role in spatial working memory and goal-directed planning. In contrast to variable array performance, while both caudate and putamen infusions impaired fixed array responding, the combined effects were not additive, suggesting possible competing roles. Infusions into either region individually, but not simultaneously, led to continuous perseveration. Recurrent perseveration in fixed arrays was caused by putamen, but not caudate, infusions. These results are consistent overall with a role of caudate in planning and flexible responding and the putamen in more rigid habitual or automatic responding.

Freesurfer Software Update Significantly Impacts Striatal Volumes in the Huntington's Disease Young Adult Study and Will Influence HD-ISS Staging.

Background: The Huntington's Disease Integrated Staging System (HD-ISS) defined disease onset using volumetric cut-offs for caudate and putamen derived from FreeSurfer 6 (FS6). The impact of the latest software update (FS7) on volumes remains unknown. The Huntington's Disease Young Adult Study (HD-YAS) is appropriately positioned to explore differences in FS bias when detecting early atrophy. Objective: Explore the relationships and differences between raw caudate and putamen volumes, calculated total intracranial volumes (cTICV), and adjusted caudate and putamen volumes, derived from FS6 and FS7, in HD-YAS. Methods: Images from 123 participants were segmented and quality controlled. Relationships and differences between volumes were explored using intraclass correlation (ICC) and Bland-Altman analysis. Results: Across the whole cohort, ICC for raw caudate and putamen was 0.99, cTICV 0.93, adjusted caudate 0.87, and adjusted putamen 0.86 (all p < 0.0005). Compared to FS6, FS7 calculated: i) larger raw caudate (+0.8%, p < 0.00005) and putamen (+1.9%, p < 0.00005), with greater difference for larger volumes; and ii) smaller cTICV (-5.1%, p < 0.00005), with greater difference for smaller volumes. The systematic and proportional difference in cTICV was greater than raw volumes. When raw volumes were adjusted for cTICV, these effects compounded (adjusted caudate +7.0%, p < 0.00005; adjusted putamen +8.2%, p < 0.00005), with greater difference for larger volumes. Conclusions: As new software is released, it is critical that biases are explored since differences have the potential to significantly alter the findings of HD trials. Until conversion factors are defined, the HD-ISS must be applied using FS6. This should be incorporated into the HD-ISS online calculator.

The relationship between oxidative stress markers and 1H-Magnetic resonance spectroscopy findings in obsessive compulsive disorder.

INTRODUCTION: The purpose of this study was to examine N-acetyl aspartate (NAA)/creatine (Cr) and glutamate, glutamine, and gamma-aminobutyric acid complex (Glx)/Cr levels in patients with obsessive compulsive disorder (OCD) and healthy controls' orbitofrontal cortex (OFC) and caudate nucleus (CN) by proton magnetic resonance spectroscopy (1H-MRS) method and to investigate their relationship with oxidative stress markers glutathione peroxidase (GPx) and superoxide dismutase (SOD). METHODS: This study included patients with OCD (n = 25) and healthy controls (n = 25) ranging in age from 18 to 65. We used the ELISA method to evaluate serum SOD and GPx levels. Levels of NAA/Cr and Glx/Cr in the orbitofrontal cortex and caudate nucleus were measured using the 1H-MRS method. RESULTS: Our study did not detect statistically significant differences in the orbitofrontal cortex Glx/Cr and NAA/Cr levels between the OCD patients and the control group. OCD patients exhibited a decrease in NAA/Cr levels, consistent with impaired neuronal integration, and an increase in Glx/Cr levels, consistent with hyperactivation, in the caudate nucleus compared to the control group. We observed a negative correlation between NAA/Cr levels in the caudate nucleus and the levels of SOD and GPx. CONCLUSIONS: Our study is the first to assess CN and OFC together in OCD patients using 3 T MR, investigating the relationship between neurometabolite concentrations and oxidative stress parameters. The negative correlation we observed between NAA/Cr levels and SOD and GPx in the caudate nucleus suggests that increased oxidative stress in this brain region in OCD patients may contribute to impaired neuronal integration and functionality.

Human striatal association megaclusters.

The striatum receives projections from multiple regions of the cerebral cortex consistent with the role of the basal ganglia in diverse motor, affective, and cognitive functions. Within the striatum, the caudate receives projections from association cortex, including multiple distinct regions of prefrontal cortex. Building on recent insights about the details of how juxtaposed cortical networks are specialized for distinct aspects of higher-order cognition, we revisited caudate organization using within-individual precision neuroimaging initially in two intensively scanned individuals (each scanned 31 times). Results revealed that the caudate has side-by-side regions that are coupled to at least five distinct distributed association networks, paralleling the organization observed in the cerebral cortex. We refer to these spatial groupings of regions as striatal association megaclusters. Correlation maps from closely juxtaposed seed regions placed within the megaclusters recapitulated the five distinct cortical networks, including their multiple spatially distributed regions. Striatal association megaclusters were explored in 15 additional participants (each scanned at least 8 times), finding that their presence generalizes to new participants. Analysis of the laterality of the regions within the megaclusters further revealed that they possess asymmetries paralleling their cortical counterparts. For example, caudate regions linked to the language network were left lateralized. These results extend the general notion of parallel specialized basal ganglia circuits with the additional discovery that, even within the caudate, there is fine-grained separation of multiple distinct higher-order networks that reflects the organization and lateralization found in the cerebral cortex.NEW & NOTEWORTHY An individualized precision neuroimaging approach reveals juxtaposed zones of the caudate that are coupled with five distinct networks in association cortex. The organization of these caudate zones recapitulates organization observed in the cerebral cortex and extends the notion of specialized basal ganglia circuits.

Optimizing Screening for Intrastriatal Interventions in Huntington's Disease Using Predictive Models.

BACKGROUND: Intrastriatal delivery of potential therapeutics in Huntington's disease (HD) requires sufficient caudate and putamen volumes. Currently, volumetric magnetic resonance imaging is rarely done in clinical practice, and these data are not available in large research cohorts such as Enroll-HD. OBJECTIVE: The objective of this study was to investigate whether predictive models can accurately classify HD patients who exceed caudate and putamen volume thresholds required for intrastriatal therapeutic interventions. METHODS: We obtained and merged data for 1374 individuals across three HD cohorts: IMAGE-HD, PREDICT-HD, and TRACK-HD/TRACK-ON. We imputed missing data for clinical variables with >72% non-missing values and used the model-building algorithm BORUTA to identify the 10 most important variables. A random forest algorithm was applied to build a predictive model for putamen volume >2500 mm3 and caudate volume >2000 mm3 bilaterally. Using the same 10 predictors, we constructed a logistic regression model with predictors significant at P < 0.05. RESULTS: The random forest model with 1000 trees and minimal terminal node size of 5 resulted in 83% area under the curve (AUC). The logistic regression model retaining age, CAG repeat size, and symbol digit modalities test-correct had 85.1% AUC. A probability cutoff of 0.8 resulted in 5.4% false positive and 66.7% false negative rates. CONCLUSIONS: Using easily obtainable clinical data and machine learning-identified initial predictor variables, random forest, and logistic regression models can successfully identify people with sufficient striatal volumes for inclusion cutoffs. Adopting these models in prescreening could accelerate clinical trial enrollment in HD and other neurodegenerative disorders when volume cutoffs are necessary enrollment criteria. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Topological alteration of the brain structural network in Parkinson's disease with apathy.

BACKGROUND: Apathy is a common neuropsychiatric manifestations in Parkinson's disease (PD), but neural network mechanisms still remain elusive. We aim to investigate the topological alteration of the brain structural network in PD with apathy. METHOD: In the present study, a total of 47 apathetic PD (aPD) patients, 37 non-apathetic PD (naPD) patients, and 40 healthy controls (HCs) were enrolled. Diffusion tensor imaging (DTI) in conjunction with graph-theoretic approaches were used to explore the alterations of topological properties of the WM structural network arising from apathy in PD. One-way analysis of covariance and post hoc analyses were performed to explore differences among the three groups. Correlations were ascertained to examine relationships between the Starkstein Apathy Scale (AS) scores and significantly different network metrics among the three groups. RESULTS: Both aPD and naPD patients remained small-world topology. However, compared with the naPD patients, aPD patients showed increased clustering coefficient (Cp) at the global level. At the regional level, aPD exhibited decreased nodal properties, mainly in the right dorsolateral prefrontal cortex (DLPFC), the right caudate nucleus (CAU), the right hippocampus, and the right superior parietal gyrus. Further, AS scores were negatively correlated with degree centrality of the right DLPFC (r = -0.254, p = 0.020) and the right CAU ( r = -0.357, p = 0.001) in the pooled patients with PD. CONCLUSIONS: The findings suggested that apathy in PD presented relatively optimized global topological properties of the brain structural network and disrupted topological organization of the regional network, particularly involving the fronto-striatal-limbic circuits. The altered topological properties of abnormal brain regions might be used to understand the physiopathologic mechanism of the neural network in aPD patients.

Corticostriatal activity related to performance during continuous de novo motor learning.

Corticostriatal regions play a pivotal role in visuomotor learning. However, less research has been done on how fMRI activity in their subregions is related to task performance, which is provided as visual feedback during motor learning. To address this, we conducted an fMRI experiment in which participants acquired a complex de novo motor skill using continuous or binary visual feedback related to performance. We found a highly selective response related to performance in the entire striatum in both conditions and a relatively higher response in the caudate nucleus for the binary feedback condition. However, the ventromedial prefrontal cortex (vmPFC) response was significant only for the continuous feedback condition. Furthermore, we also found functional distinction of the striatal subregions in random versus goal-directed motor control. These findings underscore the substantial effects of the visual feedback indicating performance on distinct corticostriatal responses, thereby elucidating its significance in reinforcement-based motor learning.

Ghrelin decreases sensitivity to negative feedback and increases prediction-error related caudate activity in humans, a randomized controlled trial.

The stomach-derived hormone ghrelin plays not only a role in feeding, starvation, and survival, but it has been suggested to also be involved in the stress response, in neuropsychiatric conditions, and in alcohol and drug use disorders. Mechanisms related to reward processing might mediate ghrelin's broader effects on complex behaviors, as indicated by animal studies and mostly correlative human studies. Here, using a within-subject double-blind placebo-controlled design with intravenous ghrelin infusion in healthy volunteers (n = 30), we tested whether ghrelin alters sensitivity to reward and punishment in a reward learning task. Parameters were derived from a computational model of participants' task behavior. The reversal learning task with monetary rewards was performed during functional brain imaging to investigate ghrelin effects on brain signals related to reward prediction errors. Compared to placebo, ghrelin decreased punishment sensitivity (t = -2.448, p = 0.021), while reward sensitivity was unaltered (t = 0.8, p = 0.43). We furthermore found increased prediction-error related activity in the dorsal striatum during ghrelin administration (region of interest analysis: t-values ≥ 4.21, p-values ≤ 0.044). Our results support a role for ghrelin in reward processing that extends beyond food-related rewards. Reduced sensitivity to negative outcomes and increased processing of prediction errors may be beneficial for food foraging when hungry but could also relate to increased risk taking and impulsivity in the broader context of addictive behaviors.