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Abstract Flow Proneness - FP (i.e., dispositional tendency to experience flow) is subjectively different across individuals. An earlier study demonstrated that FP is correlated with the availability of dopamine receptors in the dorsal striatum including the caudate and the putamen. However, it remains unclear whether FP is associated with gray matter volume variations in the brain. The neuro-anatomical basis of FP has been investigated for the first time in the present study. We conducted a cross-sectional study with a high number of healthy employed Japanese adults (n = 680). We measured FP in different domains of everyday life (work, household maintenance, and leisure time) using a Japanese translation of a Swedish flow proneness questionnaire. We investigated gray matter volume using optimized voxel-based morphometry. As hypothesized, we found a significant region in the dorsal striatum. Our results indicate that an increase in gray matter volume in the right caudate is associated with an increase in overall FP in everyday life. However, the resulting correlation was relatively small (0.13). We discuss the potential reasons underlying these findings. Our findings might have further implications for flow research and well-being. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: It remains to be clarified whether penetration of the caudate nucleus increases the risk of cognitive decline in patients with Parkinson's disease (PD) undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN).Methods: A retrospective analysis of pre/postoperative neuropsychological changes was performed with 46 consecutive patients with PD who underwent DBS of the STN. In particular, to evaluate the possible relationship between cognitive changes and DBS lead trajectories, repeated-measures ANCOVAs were conducted to analyze the effects of group (23 patients with vs 23 patients without penetration of the caudate nucleus) and time (T0 vs T1) for each neuropsychological test.Results: A statistically significant main effect of time was observed in the Trail Making Test - Part B (TMT-B), as well as in both the phonemic and semantic (F [1, 44] = 35.59, p < 0.001, PrtEta2 = 0.447) verbal fluency tasks, and the results suggested postoperative cognitive decline. However, no significant interaction effects of time and group were observed. The results indicated that the extent of the decline was comparable between the caudate and non-caudate penetration groups, and no relationship was found between cognitive changes and caudate penetration.Conclusion: Although postoperative cognitive decline was observed in some attentional-executive functions, which were assessed by the verbal fluency and TMT-B tasks, the trajectory passing through the caudate appeared not to increase the risk of cognitive decline in patients with PD undergoing DBS of the STN. [ABSTRACT FROM AUTHOR]

Background: Aberrant functional connectivity (FC) is increasingly implicated in the clinical phenomenology of schizophrenia. This study focused on the FC of the cortico-striatal network, which is thought to be disrupted in schizophrenia and to contribute to its clinical manifestations. Methods: We used simultaneous resting-state functional magnetic resonance imaging (rsfMRI) and electroencephalography (EEG) recordings to investigate FC in patients with schizophrenia. The study included 20 patients with schizophrenia and 20 healthy controls (HCs). Simultaneously recorded rsfMRI and EEG data were collected with an MR-compatible amplifier, and rsfMRI data were analyzed with the CONN toolbox to calculate FC. The study focused on the caudate, which was defined as the seed. We also performed between-group comparisons of standardized low-resolution electromagnetic tomography intracortical lagged coherence for each EEG frequency band. Results: Compared to HCs, patients with schizophrenia showed enhanced FC between the caudate nucleus and the posterior cingulate cortex, temporal, and occipital regions on rsfMRI. It is thus possible that HCs have negative FC between these regions, whereas patients with schizophrenia have non-negative FC. The EEG results showed no significant differences in oscillations or in FC between the groups in any frequency band in any region. Conclusions: Increased FC in the caudate may represent aberrant between-network FC resulting from the disruption of segregation between networks. [ABSTRACT FROM AUTHOR]

The claustrum is structurally connected with many cortical areas.A major hurdle standing in the way of understanding claustrum function is the difficulty in assessing the global functional connectivity (FC) of this structure. The primary issues lie in the inability to isolate claustrum signal from the adjacent insular cortex (Ins), caudate/putamen (CPu), and endopiriform nucleus (Endo). To address this issue, we used (7T) fMRI in the rat and describe a novel analytic method to study claustrum without signal contamination from the surrounding structures. Using this approach, we acquired claustrum signal distinct from Ins, CPu, and Endo, and used this claustrum signal to determine whole brain resting state functional connectivity (RSFC). Claustrum RSFC was distinct from the adjacent structures and displayed extensive connections with sensory cortices and the cingulate cortex, consistent with known structural connectivity of the claustrum. These results suggest fMRI and improved analysis can be combined to accurately assay claustrum function. [ABSTRACT FROM AUTHOR]

Background: Online gaming has become a popular leisure activity, in which males more frequently develop Internet gaming disorder (IGD) compared to females. However, gender-related neurocognitive differences have largely not been systematically investigated in IGD. Methods: Cue-elicited-craving tasks were performed before game playing and immediately after deprivation operationalized as a forced break from gaming when the Internet was disconnected. Ninety-nine subjects with IGD (27 males and 22 females) or recreational game use (RGU; 27 males and 23 females) provided functional MRI and subjective data. Analyses investigating effects of group (IGD and RGU) × gender (male and female) at different times (pre-gaming, post-gaming, and post-pre) on cue-elicited craving and brain responses were performed. Correlations between brain responses and subjective measures were calculated. Results: In pre-, post-, and post-pre tests, significant gender-by-group interactions (p < .001, cluster size > 15 voxels) were observed in the left dorsolateral prefrontal cortex (DLPFC). Further analyses of the DLPFC cluster showed that in post-pre comparisons, results were related to less engagement of the DLPFC in IGD, especially in females. In addition, at posttest, significant interactions were observed in the caudate, as females with IGD showed greater activation as compared to those with RGU. Discussion: The results raise the possibility that women with RGU may show better executive control than men when facing gaming cues, which may provide resiliency against developing IGD; however, once they develop IGD, their gaming may impair their executive control and enhance their cravings for gaming, which may make it more difficult to quit gaming. [ABSTRACT FROM AUTHOR]

• Neuroimaging of the caudate in relation to metabolic syndrome score (MetS). • Microstructure at 4.5 and functional activity at 7.5 years correlated with MetS. • Functional activity fully mediates the link between microstructure and MetS. • Inhibitory control is not a mediator for caudate functional activity and MetS. Metabolic syndrome score in children assesses the risk of developing cardiovascular disease in future. We aim to probe the role of the caudate in relation to the metabolic syndrome score. Furthermore, using both functional and structural neuroimaging, we aim to examine the interplay between functional and structural measures. A longitudinal birth cohort study with functional and structural neuroimaging data obtained at 4.5, 6.0 and 7.5 years and metabolic syndrome scores at 8.0 years was used. Pearson correlation and linear regression was used to test for correlation fractional anisotropy (FA) and fractional amplitude of low frequency fluctuations (fALFF) of the caudate with metabolic syndrome scores. Mediation analysis was used to test if later brain measures mediated the relation between earlier brain measures and metabolic syndrome scores. Inhibitory control was also tested as a mediator of the relation between caudate brain measures and metabolic syndrome scores. FA at 4.5 years and fALFF at 7.5 years of the left caudate was significantly correlated with metabolic syndrome scores. Post-hoc mediation analysis showed that fALFF at 7.5 years fully mediated the relation between FA at 4.5 years and metabolic syndrome scores. Inhibitory control was significantly correlated with fALFF at 7.5 years, but did not mediate the relation between fALFF at 7.5 years and metabolic syndrome scores. We found that variations in caudate microstructure at 4.5 years predict later variation in functional activity at 7.5 years. This later variation in functional activity fully mediates the relation between microstructural changes in early childhood and metabolic syndrome scores at 8.0 years. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging was conducted on six children and adolescents with fetal alcohol syndrome and seven matched normal controls. Detailed volumetric analyses demonstrated significant reductions in the cerebral vault, basal ganglia, and diencephalon in the children with fetal alcohol syndrome, compared with control children. In addition, the volume of the cerebellar vault was smaller than controls in 4 of the 6 children with fetal alcohol syndrome, although the group difference did not reach significance. When the basal ganglia were divided into the caudate and lenticular nuclei, both of these regions were significantly reduced in the children with fetal alcohol syndrome. Finally, when the overall reduction in brain size was controlled, the proportional volume of the basal ganglia and, more specifically, the caudate nucleus was reduced in the children with fetal alcohol syndrome. These results may relate to behavioral findings in both humans and animals exposed to alcohol prenatally.

Decades of research have established the importance of the hippocampus for episodic and spatial memory. In spatial navigation tasks, the role of the hippocampus has been classically juxtaposed with the role of the dorsal striatum, the latter of which has been characterized as a system important for implementing stimulus-response and action-outcome associations. In many neuroimaging paradigms, this has been explored through contrasting way finding and route-following behavior. The distinction between the contributions of the hippocampus and striatum to spatial navigation has been supported by extensive literature. Convergent research has also underscored the fact that these different memory systems can interact in dynamic ways and contribute to a broad range of navigational scenarios. For example, although familiar routes may often be navigable based on stimulus-response associations, hippocampal episodic memory mechanisms can also contribute to egocentric route-oriented memory, enabling recall of context-dependent sequences of landmarks or the actions to be made at decision points. Additionally, the literature has stressed the importance of subdividing the striatum into functional gradients—with more ventral and medial components being important for the behavioral expression of hippocampal-dependent spatial memories. More research is needed to reveal how networks involving these regions process and respond to dynamic changes in memory and control demands over the course of navigational events. In this Perspective article, we suggest that a critical direction for navigation research is to further characterize how hippocampal and striatal subdivisions interact in different navigational contexts.

Mild traumatic brain injury (mild TBI) is associated with dysfunctional brain network and accumulating evidence is pointing to the caudate as a vulnerable hub region. However, little is known about the longitudinal changes in the caudate-based resting-state functional connectivity following mild TBI. In the current study, 50 patients with mild TBI received resting-state functional magnetic resonance imaging as well as neuropsychological assessments within 7 days post-injury (acute phase) and 1 month later (subacute phase). Thirty-six age- and gender- matched healthy controls underwent the same protocol. The caudate was segmented into the dorsal and ventral sub-regions based on their related functionally distinct neural circuits and separate functional connectivity was investigated. Results indicated that patients with mild TBI at acute phase exhibited reduced left dorsal caudate-based functional connectivity with ventral lateral prefrontal cortex, dorsal anterior cingulate cortex, and inferior parietal lobule, which mainly distributed in the cognitive control network, and reduced right ventral caudate-based functional connectivity with the dorsal lateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and bilateral ventral anterior cingulate cortex (vACC), which mainly distributed in the executive network and emotional processing network. Furthermore, patients with mild TBI presented the reduced functional connectivity between the left dorsal caudate and the ventral lateral prefrontal cortex (vlPFC) compared with healthy controls at acute phase while this difference became no significance and return to the normal level following 1 month post-injury subacute phase. Similarly, the functional connectivity between the right ventral caudate and anterior cingulate cortex (both dorsal and ventral part) showed the reduced strength in patients compared with healthy controls only at the acute phase but presented no significant difference at subacute phase following mild TBI. Along the same line, patients with mild TBI presented the impaired performance on the information processing speed and more complaints on the pain impact index at acute phase compared with healthy controls but showed no significant difference at the follow-up 1 month post-injury subacute phase. The longitudinal changes of caudate-based dysfunction connectivity could serve as a neuroimaging biomarker following patients with mild TBI, with the evidence that the abnormal caudate-based functional connectivity at acute phase have returned to the normal level accompanying with the recovery of the neuropsychological syndromes following patients with mild TBI at subacute phase.

Objective: Anatomical taxonomy is a practical tool that has successfully guided clinical decision-making for patients with brain arteriovenous malformations and brainstem cavernous malformations (CMs). Deep CMs are similarly complex lesions that are difficult to access and highly variable in size, shape, and position. The authors propose a novel taxonomy for deep CMs in the basal ganglia based on clinical presentation (syndromes) and anatomical location., Methods: The taxonomy system was developed and applied to an extensive 2-surgeon experience over 19 years (2001-2019). Lesions involving the basal ganglia were identified and subtyped on the basis of the predominant superficial presentation identified on preoperative MRI. Three subtypes of basal ganglia CMs were defined: caudate (31, 57%), putaminal (16, 30%), and pallidal (7, 13%). Neurological outcomes were assessed using the modified Rankin Scale (mRS). Postoperative mRS scores ≤ 2 were defined as a favorable outcome, and scores > 2 were defined as a poor outcome. Clinical and surgical characteristics and neurological outcomes were compared among subtypes., Results: Fifty-four basal ganglia lesions were identified in 54 patients. Each basal ganglia CM subtype was associated with a recognizable constellation of neurological symptoms. The most common symptoms at presentation were severe or worsening headaches (25, 43%), mild hemiparesis (13, 24%), seizures (7, 13%), and dysmetria or ataxia (6, 11%). Patients with caudate CMs were the most likely to present with headaches and constitutional symptoms. Patients with putaminal CMs were the most likely to present with hemibody sensory deficits and dysmetria or ataxia. Patients with pallidal CMs were the most likely to present with mild hemiparesis and visual field deficits. A single surgical approach was preferred (> 80% of cases) for each basal ganglia subtype: caudate (contralateral transcallosal-transventricular, 28/31, 90%), putaminal (transsylvian-anterior transinsular, 13/16, 81%), and pallidal (transsylvian supracarotid-infrafrontal, 7/7, 100%). Most patients with follow-up had stable or improved mRS scores postoperatively (94%, 44/47); mRS scores of > 2 at final follow-up did not differ among the 3 basal ganglia subtypes., Conclusions: The study confirms the authors' hypothesis that this taxonomy for basal ganglia CMs meaningfully guides the selection of surgical approach and resection strategy. Furthermore, the proposed taxonomy can increase the diagnostic acumen at the patient bedside, help identify optimal surgical approaches, enhance the consistency of clinical communications and publications, and improve patient outcomes.

Background: Stress-related gastrointestinal bleeding (SRGB) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH), and it can present challenges in patient care and treatment. The aim of this study was to explore the clinical significance of the caudate Hounsfield unit (HU) value in the Alberta Stroke Program Early CT (ASPECT) score for predicting SRGB in patients with aSAH., Methods: We retrospectively analyzed the data of 531 aSAH patients admitted to our institution between 2019 and 2022. Potential predictors of SRGB were identified using multivariate Cox regression analysis. We used a restricted cubic spline (RCS) to evaluate whether there is a nonlinear relationship between the right caudate HU value and SRGB. MaxStat analysis (titled as maximally selected rank statistics) was performed to identify the optimal cutoff point for the right caudate HU value. Another Kaplan-Meier method with the log-rank test was used to analyze the right caudate HU value in predicting the occurrence of SRGB., Results: The incidence rate of SRGB was 17.9%. In the multivariate Cox regression analysis, the right caudate HU value was an independent predictor of SRGB [Hazard ratio (HR) = 0.913; 95% confidence interval (CI): 0.847-0.983, and p  = 0.016]. The RCS indicated that the incidence of developing SRGB reduces with increasing right caudate HU values (nonlinear p  = 0.78). The optimal cut-off value of the right caudate HU was 25.1., Conclusion: Among aSAH patients, lower right caudate HU values indicated a higher risk of developing SRGB. Our findings provide further evidence for the relationship between the gastrointestinal system and the brain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Yuan, Li, Lin, Chen, Yang, Han, Li, Jia, Zhou, Zhang, Li, Li, Zhao, Hao, Chen and Zhao.)

Introduction: Pain catastrophizing, a measure of an individual's negative emotional and cognitive appraisals of pain, has been included as a key treatment target in many psychological interventions for pain. However, the neural correlates of pain catastrophizing have been understudied. Prior neuroimaging evidence suggests that adults with pain show altered reward processing throughout the mesocorticolimbic reward circuitry., Methods: In this study, we tested the association between Pain Catastrophizing Scale (PCS) scores and neural activation to the Monetary Incentive Delay (MID) reward neuroimaging task in 94 adults reporting a range of pain, insomnia, and mood symptoms., Results: Results indicated that PCS score but not pain intensity was significantly associated with blunted activation in the caudate and putamen in response to feedback of successful vs. unsuccessful trials on the MID task. Mediation analyses indicated that PCS score fully mediated the relationship between depression symptoms and reward activation., Discussion: These findings provide evidence that pain catastrophizing is independently associated with altered striatal function apart from depression symptoms and pain intensity. Thus, in individuals experiencing pain and/or co- morbid conditions, reward dysfunction is directly related to pain catastrophizing., Competing Interests: AE has received research grant support to her institution from Pfizer Inc, Forum Pharmaceuticals, and GK, consultation fees from Charles River Analytics, and honoraria for advisory work from Pfizer, and Kaurna Pharmaceuticals in the past 5 years for work unrelated to this project. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Cooke, Edwards, Wheeler, Schmitt, Nielsen, Streck, Schuster, Potter, Evins and Gilman.)

Objective: Prior 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. Methods: Twenty-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. Results: Children/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. Conclusion: These 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. [ABSTRACT FROM AUTHOR]

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 < 0.03). No other associations were significant (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. [ABSTRACT FROM AUTHOR]

Nest building behavior in the pregnant rabbit ( Oryctolagus cuniculus ) can serve as a model for compulsions in obsessive compulsive disorder (OCD). Previous work showed that the “straw carrying” phase of nest building (during which the rabbit repeatedly collects straw in its mouth, carries it into the nest box and deposits it there, and then returns to collect more) is associated with increased c-FOS expression (a marker of neuronal activity) in the orbitofrontal, anterior cingulate, and piriform cortices. In the present study, we quantified c-FOS expression in the caudate and putamen, as well as in the primary motor, somatosensory, and prefrontal cortices of: (1) pregnant rabbits given straw (PREG + STRAW); pregnant rabbits not given straw (PREG); (3) estrous rabbits given straw (ESTROUS + STRAW); and (4) estrous rabbits not given straw (ESTROUS). We found that straw carrying was associated with increased c-FOS expression in the dorsal putamen, ventral caudate, primary motor cortex, and somatosensory cortex. Additionally, a correlational analysis of PREG + STRAW animals revealed that these regions, along with the premotor and prelimbic cortices, were significantly intercorrelated with respect to c-FOS expression, suggesting their “coactivation” during repetitive straw carrying. By contrast, behavioral interactions of non-pregnant (ESTROUS) rabbits with straw (e.g., sniffing, nibbling it) were associated with a distinct pattern of c-FOS expression that included the medial and ventral putamen. c-FOS expression in PREG + STRAW rabbits is similar to patterns of regional brain activity in OCD patients exposed to obsession-provoking stimuli, as well as to those observed in healthy human mothers responding to infant-associated stimuli. [ABSTRACT FROM AUTHOR]

Increasing animal models as well as brain imaging studies among human suggest an association between substance-related impulsivity in decision-making and decreased function of dorsal striatum. However, the resting-state intrinsic functional organization of dorsal striatum underlying food-choice impulsivity remains unknown. To address this issue, we used resting-state functional MRI (rs-fMRI) to measure brain activity among adult females. Subjects underwent the food rating task, during which they rated each food item according to their subjective perception of its taste (from Dislike it very much to Like it very much), its long term effect on health (from very unhealthy to very healthy) and decision strength to eat it (from Strong no to Strong yes). Behaviorally, impulsivity in food-choice was indexed by the decision strength of the palatable high-calorie food rather than of the low-caloric food. Results on rs-fMRI showed that greater impulsivity in food-related decision-making was inversely correlated with spontaneous regional homogeneity in the dorsal striatum (dorsal caudate), as well as the resting-state functional connectivity (rs-FC) between the dorsal caudate seed and the rostral putamen. Furthermore, the caudate-putamen rs-FC inversely predicted BMI change at six-month follow-up. These findings may suggest the insensitivity to reward signals in dorsal caudate in decision-making coupled with an imbalance between goal-directed behaviors (modulated by dorsal caudate) and habitual actions (modulated by putamen) underlying impulsivity and future weight gain. In sum, these findings extend our understanding on the neural basis of food-related impulsivity, and provide evidence for the dorsal striatum as one of the landmarks in over eating and weight change. [ABSTRACT FROM AUTHOR]

The present work studies the possible relation of parkinsonism and fronto-caudate dysconnectivity, as well as its relation to cognition in schizophrenia patients. We assessed parkinsonism using Simpson-Angus scale and prefronto-caudate connectivity using diffusion magnetic resonance in 22 schizophrenia patients (11 first-episodes) and 14 healthy controls. Fractional anisotropy was calculated for the white matter tracts directly linking rostral middle prefrontal (RMPF) and superior medial prefrontal (SMPF) regions with caudate nucleus. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia Scale (BACS). Total parkinsonism scores were negatively related to fractional anisotropy in the right SMPF-caudate tract in patients, which was also found in the first-episode patients alone, but not in controls. Parkinsonism was also inversely associated in patients to performance in social cognition, verbal memory, working memory and performance speed tests. In conclusion, our data support the involvement of fronto-striatal dysconnectivity in parkinsonism in schizophrenia. [ABSTRACT FROM AUTHOR]

Dopaminergic neuromodulation is critically important for brain and cognitive integrity. The DRD2/ANKK1 Taq1A polymorphism is associated with striatal dopamine (DA) D2 receptor availability. Some previous studies have found that the A allele of the Taq1A polymorphism influences brain structure, but the results are inconsistent, likely due to population heterogeneity and small sample sizes. We investigated the genetic effect on caudate volume in a large sample of older adults without dementia. Results show that A-allele carriers have smaller caudate volume compared to non-carriers in relatively older adults (n = 167; Mage = 77.8 years), whereas the genotype did not influence caudate volume in a younger age group (n = 220; Mage = 62.8 years). Cognitive performance was not significantly affected by the DRD2 gene. Our findings extend previous observations by showing magnified genetic effects on brain volume in old age, and provide evidence for a link between a DA-related genetic polymorphism and grey matter volume in a brain region within the nigrostriatal dopaminergic pathway. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mild TBI) is associated with dysfunctional brain network and accumulating evidence is pointing to the caudate as a vulnerable hub region. However, little is known about the longitudinal changes in the caudate-based resting-state functional connectivity following mild TBI. In the current study, 50 patients with mild TBI received resting-state functional magnetic resonance imaging as well as neuropsychological assessments within 7 days post-injury (acute phase) and 1 month later (subacute phase). Thirty-six age- and gender- matched healthy controls underwent the same protocol. The caudate was segmented into the dorsal and ventral sub-regions based on their related functionally distinct neural circuits and separate functional connectivity was investigated. Results indicated that patients with mild TBI at acute phase exhibited reduced left dorsal caudate-based functional connectivity with ventral lateral prefrontal cortex, dorsal anterior cingulate cortex, and inferior parietal lobule, which mainly distributed in the cognitive control network, and reduced right ventral caudate-based functional connectivity with the dorsal lateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and bilateral ventral anterior cingulate cortex (vACC), which mainly distributed in the executive network and emotional processing network. Furthermore, patients with mild TBI presented the reduced functional connectivity between the left dorsal caudate and the ventral lateral prefrontal cortex (vlPFC) compared with healthy controls at acute phase while this difference became no significance and return to the normal level following 1 month post-injury subacute phase. Similarly, the functional connectivity between the right ventral caudate and anterior cingulate cortex (both dorsal and ventral part) showed the reduced strength in patients compared with healthy controls only at the acute phase but presented no significant difference at subacute phase following mild TBI. Along the same line, patients with mild TBI presented the impaired performance on the information processing speed and more complaints on the pain impact index at acute phase compared with healthy controls but showed no significant difference at the follow-up 1 month post-injury subacute phase. The longitudinal changes of caudate-based dysfunction connectivity could serve as a neuroimaging biomarker following patients with mild TBI, with the evidence that the abnormal caudate-based functional connectivity at acute phase have returned to the normal level accompanying with the recovery of the neuropsychological syndromes following patients with mild TBI at subacute phase. [ABSTRACT FROM AUTHOR]

Reward outcomes are available in many diverse situations and all involve choice. If there are multiple outcomes each rewarding, then decisions regarding relative value lead to choosing one over another. Important factors related to choice context should be encoded and utilized for this form of adaptive choosing. These factors can include the number of alternatives, the pacing of choice behavior and the possibility to reverse one’s choice. An essential step in understanding if the context of choice is encoded is to directly compare choice with a context in which choice is absent. Neural activity in orbitofrontal cortex and striatum encodes potential value parameters related to reward quality and quantity as well as relative preference. We examined how neural activations in these brain regions are sensitive to choice situations and potentially involved in a prediction for the upcoming outcome selection. Neural activity was recorded and compared between a two-choice spatial delayed response task and an imperative ‘one-option’ task. Neural activity was obtained that extended from the instruction cue to the movement similar to previous work utilizing the identical imperative task. Orbitofrontal and striatal neural responses depended upon the decision about the choice of which reward to collect. Moreover, signals to predictive instruction cues that precede choice were selective for the choice situation. These neural responses could reflect chosen value with greater information on relative value of individual options as well as encode choice context itself embedded in the task as a part of the post-decision variable. [ABSTRACT FROM AUTHOR]

Introduction: The current study was designed to determine whether the degree of presynaptic striatal dopamine depletion can predict the later development of freezing of gait (FOG) in Parkinson's disease (PD).Methods: This retrospective cohort study included 390 de novo patients with PD without FOG at baseline. The participants were divided into tertiles according to the baseline dopamine transporter (DAT) uptake of each striatal subregion, and the cumulative risk of FOG was compared using the Kaplan-Meier method. Cox proportional hazard models were used to assess the predictive power of DAT uptake of striatal subregions for the development of FOG.Results: During a median follow-up period of 4.0 years, 143 patients with PD (36.7%) developed FOG. The severe reduction group of DAT uptake in the caudate nucleus and putamen had a significantly higher incidence of FOG than that of the mild and moderate reduction groups. Multivariate Cox regression analyses showed that DAT uptakes in the caudate nucleus (hazard ratio [HR] 0.551; 95% confidence interval [CI] 0.392-0.773; p = 0.001) and putamen (HR 0.441; 95% CI 0.214-0.911; p = 0.027) predicted the development of FOG. In addition, male sex, higher postural instability and gait difficulty score, and a lower Montreal Cognitive Assessment score were also significant predictors of FOG.Conclusion: Our finding suggests that presynaptic striatal dopaminergic denervation predicts the later development of FOG in de novo patients with PD, which may provide reliable insight into the mechanism of FOG in terms of nigrostriatal involvement. [ABSTRACT FROM AUTHOR]

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-known neuropeptide with strong neurotrophic and neuroprotective effects. PACAP exerts its protective actions via three G protein-coupled receptors: the specific Pac1 receptor (Pac1R) and the Vpac1/Vpac2 receptors, the neuroprotective effects being mainly mediated by the Pac1R. The protective role of PACAP in models of Parkinson’s disease and other neurodegenerative diseases is now well-established in both in vitro and in vivo studies. PACAP and its receptors occur in the mammalian brain, including regions associated with Parkinson’s disease. PACAP receptor upregulation or downregulation has been reported in several injury models or human diseases, but no data are available on alterations of receptor expression in Parkinson’s disease. The model closest to the human disease is the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced macaque model. Therefore, our present aim was to evaluate changes in Pac1R expression in basal ganglia related to Parkinson’s disease in a macaque model. Monkeys were rendered parkinsonian with MPTP, and striatum, pallidum, and cortex were evaluated for Pac1R immunostaining. We found that Pac1R immunosignal was markedly reduced in the caudate nucleus, putamen, and internal and external parts of the globus pallidus, while the immunoreactivity remained unchanged in the cortex of MPTP-treated parkinsonian monkey brains. This decrease was attenuated in some brain areas in monkeys treated with l-DOPA. The strong, specific decrease of the PACAP receptor immunosignal in the basal ganglia of parkinsonian macaque monkey brains suggests that the PACAP/Pac1R system may play an important role in the development/progression of the disease. [ABSTRACT FROM AUTHOR]

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 [ 123 I]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  < 0.001) and motor (MDS-UPRDS Part-II, P  = 0.005) experiences of daily living, as well as worse autonomic (SCOPA-AUT, P  < 0.0001) and cognitive (MoCA P  = 0.05) function, depression (GDS, P  = 0.002), and reduced caudate DAT ([ 123 I]FP-CIT, P  = 0.024) compared to PD patients without EDS. Lower caudate [ 123 I]FP-CIT values correlated with higher EDS scores ( r  = −0.192, P  = 0.013). Among patients without EDS, 47 PD patients (56%) developed EDS over a median follow-up of 36 months. Cox multivariate analysis, including all clinical and imaging data available, revealed that abnormal caudate [ 123 I]FP-CIT uptake ( P  = 0.030) and disease duration ( P  = 0.018) were predictors for the development of EDS. Although our findings indicate that dopaminergic deficits in the caudate may be associated to EDS in patients with PD, the pathophysiological causality is debateable, given that dopamine caudate denervation may covary with dopaminergic involvement at other targets and with non-dopaminergic involvement. [ABSTRACT FROM AUTHOR]

In this study, we examined the cellular distribution of encephalopsin (opsin 3; OPN3) expression in the striatum of non-human primates. In addition, because of our long standing interest in Parkinson’s disease and neuroprotection, we examined whether parkinsonian (MPTP; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) insult and/or photobiomodulation (670 nm) had any impact on encephalopsin expression in this key area of the basal ganglia. Striatal sections of control naïve monkeys, together with those that were either MPTP- and/or photobiomodulation-treated were processed for immunohistochemistry. Our results revealed two populations of striatal interneurones that expressed encephalopsin, one of which was the giant, choline acetyltransferase-containing, cholinergic interneurones. The other population had smaller somata and was not cholinergic. Neither cell group expressed the calcium-binding protein, parvalbumin. There was also rich encephalopsin expression in a set of terminals forming striosome-like patches across the striatum. Finally, we found that neither parkinsonian (MPTP) insult nor photobiomodulation had any effect on encephalopsin expression in the striatum. In summary, our results revealed an extensive network of encephalopsin containing structures throughout the striatum, indicating that external light is in a position to influence a range of striatal activities at both the interneurone and striosome level. [ABSTRACT FROM AUTHOR]

One in 12 adults suffer with alcohol use disorder (AUD). Studies suggest the younger the age in which alcohol consumption begins the higher the probability of being diagnosed with AUD. Binge/excessive alcohol drinking involves a transition from flexible to inflexible behavior likely involving the dorsal striatum (caudate and putamen nuclei). A major focus of this study was to examine the effect of age of drinking onset on subsequent chronic, voluntary ethanol intake and dorsal striatal circuitry. Data from rhesus monkeys (n = 45) that started drinking as adolescents, young adults or mature adults confirms an age-related risk for heavy drinking. Striatal neuroadaptations were examined using whole-cell patch clamp electrophysiology to record AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABA A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) from medium-sized spiny projection neurons located in the caudate or putamen nuclei. In controls, greater GABAergic transmission (mIPSC frequency and amplitude) was observed in the putamen compared to the caudate. With advancing age, in the absence of ethanol, an increase in mIPSC frequency concomitant with changes in mIPSC amplitude was observed in both regions. Chronic ethanol drinking decreased mIPSC frequency in the putamen regardless of age of onset. In the caudate, an ethanol drinking-induced increase in mIPSC frequency was only observed in monkeys that began drinking as young adults. Glutamatergic transmission did not differ between the dorsal striatal subregions in controls. With chronic ethanol drinking there was a decrease in the postsynaptic characteristics of rise time and area of mEPSCs in the putamen but an increase in mEPSC frequency in the caudate. Together, the observed changes in striatal physiology indicate a combined disinhibition due to youth and ethanol leading to abnormally strong activation of the putamen that could contribute to the increased risk for problem drinking in younger drinkers. [ABSTRACT FROM AUTHOR]

The clinical features of parkinsonism in carbon monoxide (CO) intoxication have been associated with striatal-related neuronal networks. As parkinsonian and neuropsychiatric features are both related to presynaptic dopaminergic integrity, the aim of this study was to explore the clinical significance of 99mTc TRODAT-1 in grading neurobehavioral scores and parkinsonian severity in CO intoxication. We enrolled 64 patients with CO intoxication, including 29 with parkinsonism (parkinsonism[+] group) and 35 without (parkinsonism[−] group). All of the patients received 99mTc TRODAT-1 neuroimaging evaluations, comprehensive neurobehavioral tests and assessments of the severity of parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS)-part III motor score. Univariate and multivariate regression analyses were used to test the predictive factors and scores for a diagnosis of parkinsonism and its severity. The parkinsonism(+) group had significantly lower cognitive scores and higher neuropsychiatric total scores compared with the parkinsonism(−) group, both of which were independently related to the severity of parkinsonism. 99mTc TRODAT-1 regional caudate signals were correlated with tremors at rest, action or postural tremors of the hands, bradykinesia and hypokinesia, and visuospatial, verbal fluency, abstract thinking and digit backwards scores. Scores of the neurobehavioral tests and UPDRS items were highly correlated (p < 0.01). Our results validated the initial hypothesis in that neurobehavioral deficits and parkinsonian symptoms were highly related. This association was independent of demographic factors and initial carboxyhemoglobin level. Within the presynaptic dopaminergic circuit, the clinical role of the caudate in mediating the clinical symptoms in CO intoxication may outweigh the putamen. [ABSTRACT FROM AUTHOR]

Background Nicotine improves attention and processing speed in individuals with schizophrenia. Few studies have investigated the effects of nicotine on cognitive control. Prior functional magnetic resonance imaging (fMRI) research demonstrates blunted activation of dorsal anterior cingulate cortex (dACC) and rostral anterior cingulate cortex (rACC) in response to error and decreased post-error slowing in schizophrenia. Methods Participants with schizophrenia (n = 13) and healthy controls (n = 12) participated in a randomized, placebo-controlled, crossover study of the effects of transdermal nicotine on cognitive control. For each drug condition, participants underwent fMRI while performing the stop signal task where participants attempt to inhibit prepotent responses to "go (motor activation)" signals when an occasional "stop (motor inhibition)" signal appears. Error processing was evaluated by comparing "stop error" trials (failed response inhibition) to "go" trials. Resting-state fMRI data were collected prior to the task. Results Participants with schizophrenia had increased nicotine-induced activation of right caudate in response to errors compared to controls (DRUG × GROUP effect: pcorrected < 0.05). Both groups had significant nicotine-induced activation of dACC and rACC in response to errors. Using right caudate activation to errors as a seed for resting-state functional connectivity analysis, relative to controls, participants with schizophrenia had significantly decreased connectivity between the right caudate and dACC/bilateral dorsolateral prefrontal cortices. Conclusions In sum, we replicated prior findings of decreased post-error slowing in schizophrenia and found that nicotine was associated with more adaptive (i.e., increased) post-error reaction time (RT). This proof-of-concept pilot study suggests a role for nicotinic agents in targeting cognitive control deficits in schizophrenia. [ABSTRACT FROM AUTHOR]

Behavioral inhibition (BI) is an early temperamental profile characterized by negative reactivity to novelty, withdrawal from social situations, and increased risk for social anxiety. Previous research associated BI assessed in early childhood to striatal hypersensitivity in mid-to-late adolescence. The present study examined this association among 10 year-olds, characterized with BI at ages 24 and 36 months on measures of temperamental reactivity. Participants (n = 40) were studied at age 10 using a reward processing task during functional magnetic resonance imaging (fMRI). Child- and maternal-report of social anxiety symptoms was collected at ages 10 and 13. Findings indicate greater caudate activation and stronger striatal connectivity in high, compared to low, behaviorally inhibited children. Caudate activation related to social anxiety symptoms at both ages. These findings suggest that enhanced striatal responsivity reliably manifests among high behaviorally inhibited children as early as age 10. This may reflect hyper-sensitivity to reward or excessive motivation to avoid errors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundCommonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain.MethodsTwenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex).ResultsUsable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies.ConclusionsPatients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances. [ABSTRACT FROM PUBLISHER]

Dorsal striatum, principally comprising of caudate and putamen, is well-known to support motor function but also various higher-order cognitive functions. This is enabled by developing short- and long-range connections to distributed cortical regions throughout the life span, but few studies have examined developmental changes from young children to adults in the same cohort. Here we investigated the development of dorsal-striatal network in a large (n = 476), single-site sample of healthy subjects 3–42 years of age in three groups (children, adolescence, adults). The results showed that the connectivity within the striatum and to sensorimotor regions was established at an early stage of life and remained strong in adolescence, supporting that sensory-seeking behaviours and habit formation are important learning mechanisms during the developmental periods. This connectivity diminished with age, as many behaviours become more efficient and automated. Adolescence demonstrated a remarkable transition phase where the connectivity to dorsolateral prefrontal cortex emerged but connectivity to the dorsomedial prefrontal and posterior brain, which belong to the ventral attentional and default mode networks, was only seen in adults. This prolonged maturation in between-network integration may explain the behavioural characteristics of adolescents in that they exhibit elaborated cognitive performance but also demonstrate high risk-taking behaviours. • Connectivity within-striatum and to sensorimotor region remained through adolescence. • Connectivity to dorsolateral prefrontal cortex emerged in adolescence. • Connectivity to attentional and default mode networks was not found until adulthood. [ABSTRACT FROM AUTHOR]

Anatomically distinct areas within the basal ganglia encode flexible- and stable-value memories for visual objects (Hikosaka et al., 2014), but an important question remains: do they receive inputs from the same or different brain areas or neurons? To answer this question, we first located flexible and stable value-coding areas in the caudate head (CDh) and caudate tail (CDt) of two rhesus macaque monkeys, and then injected different retrograde tracers into these areas of each monkey. We found that CDh and CDt received different inputs from several cortical and subcortical areas including temporal cortex, prefrontal cortex, cingulate cortex, amygdala, claustrum and thalamus. Superior temporal cortex and inferior temporal cortex projected to both CDh and CDt, with more CDt-projecting than CDh-projecting neurons. In superior temporal cortex and dorsal inferior temporal cortex, layers 3 and 5 projected to CDh while layers 3 and 6 projected to CDt. Prefrontal and cingulate cortex projected mostly to CDh bilaterally, less to CDt unilaterally. A cluster of neurons in the basolateral amygdala projected to CDt. Rostral-dorsal claustrum projected to CDh while caudal-ventral claustrum projected to CDt. Within the thalamus, different nuclei projected to either CDh or CDt. The medial centromedian nucleus and lateral parafascicular nucleus projected to CDt while the medial parafascicular nucleus projected to CDh. The inferior pulvinar and lateral dorsal nuclei projected to CDt. The ventral anterior and medial dorsal nuclei projected to CDh. We found little evidence of neurons projecting to both CDh and CDt across the brain. These data suggest that CDh and CDt can control separate functions using anatomically separate circuits. Understanding the roles of these striatal projections will be important for understanding how value memories are created and stored.

Autism Spectrum Disorder (ASD) is characterized by impairments in language and social–emotional cognition. Yet, findings of emotion recognition from affective prosody in individuals with ASD are inconsistent. This study investigated emotion recognition and neural processing of affective prosody in high-functioning adults with ASD relative to neurotypical (NT) adults. Individuals with ASD showed mostly typical brain activation of the fronto-temporal and subcortical brain regions in response to affective prosody. Yet, the ASD group showed a trend towards increased activation of the right caudate during processing of affective prosody and rated the emotional intensity lower than NT individuals. This is likely associated with increased attentional task demands in this group, which might contribute to social–emotional impairments.

Anatomically distinct areas within the basal ganglia encode flexible- and stable-value memories for visual objects (Hikosaka et al., 2014), but an important question remains: do they receive inputs from the same or different brain areas or neurons? To answer this question, we first located flexible and stable value-coding areas in the caudate head (CDh) and caudate tail (CDt) of two rhesus macaque monkeys, and then injected different retrograde tracers into these areas of each monkey. We found that CDh and CDt received different inputs from several cortical and subcortical areas including temporal cortex, prefrontal cortex, cingulate cortex, amygdala, claustrum and thalamus. Superior temporal cortex and inferior temporal cortex projected to both CDh and CDt, with more CDt-projecting than CDh-projecting neurons. In superior temporal cortex and dorsal inferior temporal cortex, layers 3 and 5 projected to CDh while layers 3 and 6 projected to CDt. Prefrontal and cingulate cortex projected mostly to CDh bilaterally, less to CDt unilaterally. A cluster of neurons in the basolateral amygdala projected to CDt. Rostral-dorsal claustrum projected to CDh while caudal-ventral claustrum projected to CDt. Within the thalamus, different nuclei projected to either CDh or CDt. The medial centromedian nucleus and lateral parafascicular nucleus projected to CDt while the medial parafascicular nucleus projected to CDh. The inferior pulvinar and lateral dorsal nuclei projected to CDt. The ventral anterior and medial dorsal nuclei projected to CDh. We found little evidence of neurons projecting to both CDh and CDt across the brain. These data suggest that CDh and CDt can control separate functions using anatomically separate circuits. Understanding the roles of these striatal projections will be important for understanding how value memories are created and stored. [ABSTRACT FROM AUTHOR]

Although the activation of the prefrontal cortex (PFC) and the striatum had been found in smoking cue induced craving task, whether and how the functional interactions and white matter integrity between these brain regions contribute to craving processing during smoking cue exposure remains unknown. Twenty-five young male smokers and 26 age- and gender-matched nonsmokers participated in the smoking cue-reactivity task. Craving related brain activation was extracted and psychophysiological interactions (PPI) analysis was used to specify the PFC-efferent pathways contributed to smoking cue-induced craving. Diffusion tensor imaging (DTI) and probabilistic tractography was used to explore whether the fiber connectivity strength facilitated functional coupling of the circuit with the smoking cue-induced craving. The PPI analysis revealed the negative functional coupling of the left dorsolateral prefrontal cortex (DLPFC) and the caudate during smoking cue induced craving task, which positively correlated with the craving score. Neither significant activation nor functional connectivity in smoking cue exposure task was detected in nonsmokers. DTI analyses revealed that fiber tract integrity negatively correlated with functional coupling in the DLPFC-caudate pathway and activation of the caudate induced by smoking cue in smokers. Moreover, the relationship between the fiber connectivity integrity of the left DLPFC-caudate and smoking cue induced caudate activation can be fully mediated by functional coupling strength of this circuit in smokers. The present study highlighted the left DLPFC-caudate pathway in smoking cue-induced craving in smokers, which may reflect top-down prefrontal modulation of striatal reward processing in smoking cue induced craving processing. Hum Brain Mapp 38:4644-4656, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Recent empirical findings have suggested that imbalanced neural networks may underlie the pathophysiology of major depressive disorder (MDD). However, the contribution of the superior temporal gyrus (STG) and the caudate nucleus to its pathophysiology remains unclear.Methods: Functional magnetic resonance imaging (MRI) date were acquired from 40 patients with first-episode drug-naive MDD and 36 matched healthy controls during wakeful rest. We used whole-brain voxel-wise statistical maps to quantify within-group resting state functional connectivity (RSFC) and between-group differences of bilateral caudate and STG seeds.Results: Compared with healthy controls, first-episode MDD patients were found to have reduced connectivity between the ventral caudate and several brain regions including the superior frontal gyrus (SFG), the superior parietal lobule (SPL) and the middle temporal gyrus (MTG), as well as increased connectivity with the cuneus. We also found increased connectivity between the left STG and the precuneus, the angular gyrus and the cuneus. Moreover, we found that increased anhedonia severity was correlated with the magnitude of ventral caudate functional connectivity with the cuneus and the MTG in MDD patients.Limitations: Due to our small sample size, we did not correct the statistical threshold in the correlation analyses between clinical variables and connectivity abnormalities.Conclusions: The present study suggests that anhedonia is mainly associated with altered ventral caudate-cortical connectivity and highlights the importance of the ventral caudate in the neurobiology of MDD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Patients with schizophrenia (SCZ) tend to sample less information when making a decision, jumping to conclusions (JTC) without sufficient evidence. This “JTC bias” may be a trait marker of the disease and may not improve with antipsychotic treatment. We conducted a double-blind, placebo-controlled trial to test whether intranasal oxytocin could reduce JTC in stable, medicated patients with SCZ and healthy controls (HCs). We also explored whether striatal volume, clinical symptoms, and baseline social functioning (SF) was related to JTC performance. Methods Forty-three male, medicated SCZ patients (Mean Age: 40.81 ± 11.44) and sixteen HCs (Mean Age: 30.38 ± 9.85) participated in a double-blind, placebo-controlled, cross-over study. Participants completed the Beads Task on two separate visits (minimum 20 days apart). Participants were randomized to receive either intranasal oxytocin (50IU in solution) or intranasal placebo (saline). Twenty of the SCZ patients and all sixteen HCs also provided T1 MRIs (3-T). Results Patients with SCZ took fewer draws to decision (DTD) than HCs ( t (57) = 2.78, p = 0.007). Oxytocin did not significantly change DTD in patients ( t (42) = −1.11, p = 0.27), nor in HCs ( t (15) = −0.62, p = 0.55). Exploratory analyses found ventral caudate volumes were negatively correlated with DTD ( r (18) = −0.50, p = 0.03) in patients. Moreover, oxytocin was more likely to improve JTC in patients with lower baseline SF. However, these exploratory findings did not survive correction for multiple comparisons. Conclusions We replicate increased JTC in SCZ. However, acute intranasal oxytocin did not modify JTC. Future studies with larger samples should explore how brain morphology and SF are related to JTC performance in patients with SCZ. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Intracranial application of red to infrared light, known also as photobiomodulation (PBM), has been shown to improve locomotor activity and to neuroprotect midbrain dopaminergic cells in rodent and monkey models of Parkinson's disease. In this study, we explored whether PBM has any influence on the number of tyrosine hydroxylase (TH)cells and the expression of GDNF (glial-derived neurotrophic factor) in the striatum. Striatal sections of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice and monkeys and 6-hydroxydopamine (6OHDA)-lesioned rats that had PBM optical fibres implanted intracranially (or not) were processed for immunohistochemistry (all species) or western blot analysis (monkeys). In our MPTP monkey model, which showed a clear loss in striatal dopaminergic terminations, PBM generated a striking increase in striatal TH cell number, 60% higher compared to MPTP monkeys not treated with PBM and 80% higher than controls. This increase was not evident in our MPTP mouse and 6OHDA rat models, both of which showed minimal loss in striatal terminations. In monkeys, the increase in striatal TH cell number in MPTP-PBM cases was accompanied by similar increases in GDNF expression, as determined from western blots, from MPTP and control cases. In summary, these results offer insights into the mechanisms by which PBM generates its beneficial effects, potentially with the use of trophic factors, such as GDNF. [ABSTRACT FROM AUTHOR]

Brain mechanisms underpinning attention deficit/hyperactivity disorder (ADHD) are incompletely understood. The adolescent spontaneously hypertensive rat (SHR) is a widely studied preclinical model that expresses several of the key behavioral features associated with ADHD. Yet, little is known about large-scale functional connectivity patterns in the SHR, and their potential similarity to those of humans with ADHD. Using an approach comparable to human studies, magnetic resonance imaging in the awake animal was performed to identify whole-brain intrinsic neural connectivity patterns. An independent components analysis of resting-state functional connectivity demonstrated many common components between the SHR and both Wistar Kyoto and Sprague-Dawley control strains, but there was a divergence in other networks. In the SHR, three functional networks involving the striatum had only weak correlations with networks in the two control strains. Conversely, networks involving the visual cortex that was present in both control strains had only weak correlations with networks in the SHR. The implication is that the patterns of brain activity differ between the SHR and the other strains, suggesting that brain connectivity patterns in this animal model of ADHD may provide insights into the neural basis of ADHD. Brain connectivity patterns might also serve to identify brain circuits that could be targeted for the manipulation and evaluation of potential therapeutic options. [ABSTRACT FROM AUTHOR]

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. [ABSTRACT FROM AUTHOR]

Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT2A receptor activity is altered in autism, while recent work indicates that systemic 5HT2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Huntington’s disease (HD) is a debilitating genetic disorder characterized by motor, cognitive and psychiatric abnormalities associated with neuropathological decline. HD pathology is the result of an extended chain of CAG (cytosine, adenine, guanine) trinucleotide repetitions in the HTT gene. Clinical diagnosis of HD requires the presence of an otherwise unexplained extrapyramidal movement disorder in a participant at risk for HD. Over the past 15 years, evidence has shown that cognitive, psychiatric, and subtle motor dysfunction is evident decades before traditional motor diagnosis. This study examines the relationships among subcortical brain volumes and measures of emerging disease phenotype in prodromal HD, before clinical diagnosis. Methods: The dataset includes 34 cognitive, motor, psychiatric, and functional variables and five subcortical brain volumes from 984 prodromal HD individuals enrolled in the PREDICT HD study. Using cluster analyses, seven distinct clusters encompassing cognitive, motor, psychiatric, and functional domains were identified. Individual cluster scores were then regressed against the subcortical brain volumetric measurements. Results: Accounting for site and genetic burden (the interaction of age and CAG repeat length) smaller caudate and putamen volumes were related to clusters reflecting motor symptom severity, cognitive control, and verbal learning. Conclusions: Variable reduction of the HD phenotype using cluster analysis revealed biologically related domains of HD and are suitable for future research with this population. Our cognitive control cluster scores show sensitivity to changes in basal ganglia both within and outside the striatum that may not be captured by examining only motor scores. (JINS, 2017, 23, 159–170) [ABSTRACT FROM AUTHOR]