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Abstract Background Dyslexia and Attention-deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders (estimates of 25–40% bidirectional comorbidity). Previous work has identified strong genetic and cognitive overlap between the disorders, but neural overlap is relatively unexplored. This study is a systematic meta-analysis of existing voxel-based morphometry studies to determine whether there is any overlap in the gray matter correlates of both disorders. Methods We conducted anatomic likelihood estimate (ALE) meta-analyses of voxel-based morphometry studies in which individuals with dyslexia (15 studies; 417 cases, 416 controls) or ADHD (22 studies; 898 cases, 763 controls) were compared to typically developing controls. We generated ALE maps for dyslexia vs. controls and ADHD vs. controls using more conservative (p

Background: Neuroimaging shows considerable promise in generating sensitive and objective outcome measures for therapeutic trials across a range of neurodegenerative conditions. For volumetric measures the current gold standard is manual delineation, which is unfeasible for samples sizes required for large clinical trials.Methods: Using a cohort of early Huntington’s disease (HD) patients (n = 46) and controls (n = 35), we compared the performance of four automated segmentation tools (FIRST, FreeSurfer, STEPS, MALP-EM) with manual delineation for generating cross-sectional caudate volume, a region known to be vulnerable in HD. We then examined the effect of each of these baseline regions on the ability to detect change over 15 months using the established longitudinal Caudate Boundary Shift Integral (cBSI) method, an automated longitudinal pipeline requiring a baseline caudate region as an input.Results: All tools, except Freesurfer, generated significantly smaller caudate volumes than the manually derived regions. Jaccard indices showed poorer levels of overlap between each automated segmentation and manual delineation in the HD patients compared with controls. Nevertheless, each method was able to demonstrate significant group differences in volume (p < 0.001). STEPS performed best qualitatively as well as quantitively in the baseline analysis. Caudate atrophy measures generated by the cBSI using automated baseline regions were largely consistent with those derived from a manually segmented baseline, with STEPS providing the most robust cBSI values across both control and HD groups.Conclusions: Atrophy measures from the cBSI were relatively robust to differences in baseline segmentation technique, suggesting that fully automated pipelines could be used to generate outcome measures for clinical trials.

Social interactions are a crucial aspect of human behaviour. Numerous neurophysiological studies have focused on socio-cognitive processes associated with the so-called theory of mind—the ability to attribute mental states to oneself and others. Theory of mind is closely related to social intelligence defined as a set of abilities that facilitate effective social interactions. Social intelligence encompasses multiple theory of mind components and can be measured by the Four Factor Test of Social Intelligence (the Guilford-Sullivan test). However, it is unclear whether the differences in social intelligence are reflected in structural brain differences. During the experiment, 48 healthy right-handed individuals completed the Guilford-Sullivan test. T1-weighted structural MRI images were obtained for all participants. Voxel-based morphometry analysis was performed to reveal grey matter volume differences between the two groups (24 subjects in each)—with high social intelligence scores and with low social intelligence scores, respectively. Participants with high social intelligence scores had larger grey matter volumes of the bilateral caudate. The obtained results suggest the caudate nucleus involvement in the neural system of socio-cognitive processes, reflected by its structural characteristics. [ABSTRACT FROM AUTHOR]

It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P =.01) but not in the ACC (n = 24, F = 0.02, P =.59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r =.42, P =.04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment. [ABSTRACT FROM AUTHOR]

Background: Neuroimaging shows considerable promise in generating sensitive and objective outcome measures for therapeutic trials across a range of neurodegenerative conditions. For volumetric measures the current gold standard is manual delineation, which is unfeasible for samples sizes required for large clinical trials. Methods: Using a cohort of early Huntington's disease (HD) patients (n = 46) and controls (n = 35), we compared the performance of four automated segmentation tools (FIRST, FreeSurfer, STEPS, MALP-EM) with manual delineation for generating cross-sectional caudate volume, a region known to be vulnerable in HD. We then examined the effect of each of these baseline regions on the ability to detect change over 15 months using the established longitudinal Caudate Boundary Shift Integral (cBSI) method, an automated longitudinal pipeline requiring a baseline caudate region as an input. Results: All tools, except Freesurfer, generated significantly smaller caudate volumes than the manually derived regions. Jaccard indices showed poorer levels of overlap between each automated segmentation and manual delineation in the HD patients compared with controls. Nevertheless, each method was able to demonstrate significant group differences in volume (p < 0.001). STEPS performed best qualitatively as well as quantitively in the baseline analysis. Caudate atrophy measures generated by the cBSI using automated baseline regions were largely consistent with those derived from a manually segmented baseline, with STEPS providing the most robust cBSI values across both control and HD groups. Conclusions: Atrophy measures from the cBSI were relatively robust to differences in baseline segmentation technique, suggesting that fully automated pipelines could be used to generate outcome measures for clinical trials. [ABSTRACT FROM AUTHOR]

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

We describe a 61-year-old woman with bilateral parkinsonism caused by unilateral infarction limited to the territory of the lenticulostriate arteries. Although dopamine transporter imaging with single-photon emission computed tomography (DaTSPECT) demonstrated reduced putaminal tracer binding concordant with the size and location of the vascular lesion, the specific binding ratio was within the normal range. Five months after onset, the patient was free from parkinsonism without the use of any antiparkinsonian agents. When patients show bilateral parkinsonism, it is important to consider infarction of the lenticulostriate arteries. Additionally, DaTSPECT might be useful for predicting the prognosis of parkinsonism caused by infarction.

Behavioral variant frontotemporal dementia and semantic dementia have been associated with striatal degeneration, but few studies have delineated striatal subregion volumes in vivo or related them to the clinical phenotype. We traced caudate, putamen, and nucleus accumbens on magnetic resonance images to quantify volumes of these structures in behavioral variant frontotemporal dementia, semantic dementia, Alzheimer disease, and healthy controls (n=12 per group). We further related these striatal volumes to clinical deficits and neuropathologic findings in a subset of patients. Behavioral variant frontotemporal dementia and semantic dementia showed significant overall striatal atrophy compared with controls. Moreover, behavioral variant frontotemporal dementia showed panstriatal degeneration, whereas semantic dementia featured a more focal pattern involving putamen and accumbens. Right-sided striatal atrophy, especially in the putamen, correlated with the overall behavioral symptom severity and with specific behavioral domains. At autopsy, patients with behavioral variant frontotemporal dementia and semantic dementia showed striking and severe tau or TAR DNA-binding protein of 43 kDa pathology, especially in ventral parts of the striatum. These results demonstrate that ventral striatum degeneration is a prominent shared feature in behavioral variant frontotemporal dementia and semantic dementia and may contribute to the social-emotional deficits common to both disorders.

Background: Objective biomarkers of cognitive vulnerabilities related to suicidal ideation (SI) may assist in early prevention in adolescents. Previously, we found that smaller gray matter volumes (GMVs) of the dorsal striatum prospectively predicted implicit SI, measured using a computerized implicit association test (IAT) assessing associations between "self" and "death," in a community sample of adolescents. Here, we sought to replicate these findings in an independent sample of depressed adolescents.Methods: 53 depressed adolescents who varied in severity of suicidal thoughts and behaviors completed high-resolution structural MRI. Caudate, putamen, and nucleus accumbens GMVs were estimated using FreeSurfer 6.0. Robust linear regressions were used to examine associations between striatal GMVs and implicit and explicit SI, covarying for sex, age, total intracranial volume, medication use, and depression severity. Significance was determined using Bonferroni correction. Finally, LASSO regression was used to identify which striatal GMV contributed most to prediction of implicit SI.Results: Smaller bilateral caudate and right nucleus accumbens GMVs were associated with higher IAT scores (all ps<0.001). Smaller putamen and nucleus accumbens GMVs were not associated with implicit or explicit SI. Our LASSO analysis indicated that right caudate GMV contributed most to the prediction of IAT scores.Conclusions: This study is the first to demonstrate that caudate GMVs are significantly associated with implicit self-associations with death in a sample of depressed adolescents. When considered with our previous work, smaller caudate GMVs may be a robust biomarker of implicit SI in adolescents, with clinical implications for early identification of youth at risk for engaging in suicidal behaviors. [ABSTRACT FROM AUTHOR]

Early initiation of antipsychotic treatment plays a crucial role in the management of first-episode schizophrenia (FES) patients, significantly improving their prognosis. However, limited attention has been given to the long-term effects of antipsychotic drug therapy on FES patients. In this research, we examined the changes in abnormal brain regions among FES patients undergoing long-term treatment using a dynamic perspective. A total of 98 participants were included in the data analysis, comprising 48 FES patients, 50 healthy controls, 22 patients completed a follow-up period of more than 6 months with qualified data. We processed resting-state fMRI data to calculate coefficient of variation of fractional amplitude of low-frequency fluctuations (CVfALFF), which reflects the brain regional activity stability. Data analysis was performed at baseline and after long-term treatment. We observed that compared with HCs, patients at baseline showed an elevated CVfALFF in the supramarginal gyrus (SMG), parahippocampal gyrus (PHG), caudate, orbital part of inferior frontal gyrus (IOG), insula, and inferior frontal gyrus (IFG). After long-term treatment, the instability in SMG, PHG, caudate, IOG, insula and inferior IFG have ameliorated. Additionally, there was a positive correlation between the decrease in dfALFF in the SMG and the reduction in the SANS total score following long-term treatment. In conclusion, FES patients exhibit unstable regional activity in widespread brain regions at baseline, which can be ameliorated with long-term treatment. Moreover, the extent of amelioration in SMG instability is associated with the amelioration of negative symptoms., 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 © 2024 Zhong, Liu, Wang, Yang, Chen, Lee, Wu and Yang.)

Major depressive disorder (MDD) is characterized by deficient reward functions in the brain. However, existing findings on functional alterations during reward anticipation, reward processing, and learning among MDD patients are inconsistent, and it was unclear whether a common reward system implicated in multiple reward functions is altered in MDD. Here we meta-analyzed 18 past studies that compared brain reward functions between adult MDD patients ( N = 477, mean age = 26.50 years, female = 59.40%) and healthy controls ( N = 506, mean age = 28.11 years, females = 55.58%), and particularly examined group differences across multiple reward functions. Jack-knife sensitivity and subgroup meta-analyses were conducted to test robustness of findings across patient comorbidity, task paradigm, and reward nature. Meta-regression analyses assessed the moderating effect of patient symptom severity and anhedonia scores. We found during reward anticipation, MDD patients showed lower activities in the lateral prefrontal-thalamus circuitry. During reward processing, patients displayed reduced activities in the right striatum and prefrontal cortex, but increased activities in the left temporal cortex. During reward learning, patients showed reduced activity in the lateral prefrontal-thalamic-striatal circuitry and the right parahippocampal-occipital circuitry but higher activities in bilateral cerebellum and the left visual cortex. MDD patients showed decreased activity in the right thalamus during both reward anticipation and learning, and in the right caudate during both reward processing and learning. Larger functional changes in MDD were observed among patients with more severe symptoms and higher anhedonia levels. The thalamic-striatal circuitry functional alterations could be the key neural mechanism underlying MDD patients overarching reward function deficiencies.

Neurogenesis decline with aging may be associated with brain atrophy. Subventricular zone neuron precursor cells possibly modulate striatal neuronal activity via the release of soluble molecules. Neurogenesis decay in the subventricular zone may result in structural alterations of brain regions connected to the caudate, particularly to its medial component. The aim of this study was to investigate how the functional organization of caudate networks relates to structural brain changes with aging. One hundred and fifty-two normal subjects were recruited: 52 young healthy adults (≤35 years old), 42 middle-aged (36 ≤ 60 years old) and 58 elderly subjects (≥60 years old). In young adults, stepwise functional connectivity was used to characterize regions that connect to the medial and lateral caudate at different levels of link-step distances. A statistical comparison between the connectivity of medial and lateral caudate in young subjects was useful to define medial and lateral caudate connected regions. Atrophy of medial and lateral caudate connected regions was estimated in young, middle-aged and elderly subjects using T 1 -weighted images. Results showed that middle-aged and elderly adults exhibited decreased stepwise functional connectivity at one-link step from the caudate, particularly in the frontal, parietal, temporal and occipital brain regions, compared to young subjects. Elderly individuals showed increased stepwise functional connectivity in frontal, parietal, temporal and occipital lobes compared to both young and middle-aged adults. Additionally, elderly adults displayed decreased stepwise functional connectivity compared to middle-aged subjects in specific parietal and subcortical areas. Moreover, in young adults, the medial caudate showed higher direct connectivity to the basal ganglia (left thalamus), superior, middle and inferior frontal and inferior parietal gyri (medial caudate connected region) relative to the lateral caudate. Considering the opposite contrast, lateral caudate showed stronger connectivity to the basal ganglia (right pallidum), orbitofrontal, rostral anterior cingulate and insula cortices (lateral caudate connected region) compared to medial caudate. In elderly subjects, the medial caudate connected region showed greater atrophy relative to the lateral caudate connected region. Brain regions linked to the medial caudate appear to be more vulnerable to aging than lateral caudate connected areas. The adjacency to the subventricular zone may, at least partially, explain these findings. Stepwise functional connectivity analysis can be useful to evaluate the role of the subventricular zone in network disruptions in age-related neurodegenerative disorders., Competing Interests: S.B. and E.C. receive or have received research supports from the Italian Ministry of Health. M.Z., G.R., G.S., C.C., L.C., M.B. and G.M. report no disclosures. M.F. is Editor-in-Chief of the Journal of Neurology and Associate Editor of Human Brain Mapping, Neurological Sciences and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. F.A. is Associate Editor of NeuroImage: Clinical, has received speaker honoraria from Biogen Idec, Italfarmaco, Roche, Zambon and Eli Lilly, and receives or has received research supports from the Italian Ministry of Health, the Italian Ministry of University and Research, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council, the EU Joint Programme – Neurodegenerative Disease Research (JPND), and Foundation Research on Alzheimer Disease (France)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray-matter volumes (GMVs) and structural covariance networks (SCNs) abnormalities in community-based older people preceding the conversion to physio-cognitive decline syndrome (PCDS)., Methods: Voxel-wise brain GMV and established SCNs were compared between PCDS and non-PCDS converters., Results: The study included 343 individuals (60.2 ± 6.9 years, 49.6% men) with intact cognitive and mobility functions. Over an average 5.6-year follow-up, 116 transitioned to PCDS. Identified regions with abnormal GMVs in PCDS converters were over cerebellum and caudate, which served as seeds for SCNs establishment. Significant differences in cerebellum-based (to right frontal pole and left middle frontal gyrus) and caudate-based SCNs (to right caudate putamen, right planum temporale, left precentral gyrus, right postcentral gyrus, and left parietal operculum) between converters and nonconverters were observed., Discussion: This study reveals early neuroanatomic changes, emphasizing the cerebellum's role, in dual cognitive and mobility impairments., Highlights: Neuroanatomic precursors of dual cognitive and mobility impairments are identified. Cerebellar GMV reductions and increased right caudate GMV precede the onset of PCDS. Altered cerebellum- and caudate-based SCNs drive PCDS transformation. This research establishes a foundation for understanding PCDS as a specific dementia syndrome., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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., (Copyright © 2024 Gould et al.)

Background: Post-stroke behavioral disinhibition (PSBD) is common in stroke survivors and often presents as impulsive, tactless or vulgar behavior. However, it often remains undiagnosed and thus untreated, even though it can lead to a longer length of stay in a rehabilitation facility. The proposed study will aim to evaluate the clinical, neuropsychological and magnetic resonance imaging (MRI) correlates of PSBD in a cohort of stroke survivors and describe its 12-month course., Methods: This prospective cohort study will recruit 237 patients and will be conducted at the Neurology Unit of the Prince of Wales Hospital. The project duration will be 24 months. The patients will be examined by multiple MRI methods, including diffusion-weighted imaging, within 1 week after stroke onset. The patients and their caregivers will receive a detailed assessment at a research clinic at 3, 9 and 15 months after stroke onset (T1, T2 and T3, respectively). The disinhibition subscale of the Frontal Systems Behavior Scale (FrSBe) will be completed by each subject and caregiver, and scores ≥65 will be considered to indicate PSBD.A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest (ROIs), together with other significant variables identified in the univariate analyses. For patients with PSBD at T 1 , the FrSBe disinhibition scores will be compared between the groups of patients with and without ROI infarcts, using covariance analysis. The demographic, clinical and MRI variables of remitters and non-remitters will be examined again at T 2 and T 3 by logistic regression., Discussion: This project will be the first MRI study on PSBD in stroke survivors. The results will shed light on the associations of lesions in the orbitofrontal cortex, anterior temporal lobe and subcortical brain structures with the risk of PSBD. The obtained data will advance our understanding of the pathogenesis and clinical course of PSBD in stroke, as well as other neurological conditions. The findings are thus likely to be applicable to the large population of patients with neurological disorders at risk of PSBD and are expected to stimulate further research in this field., 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 © 2024 Tang, Hui and Leung.)

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

This study tested the hypothesis that executive dysfunction, common in temporal lobe epilepsy (TLE), is associated with an abnormal frontostriatal network. Structural and diffusion tensor MR scans, the Wisconsin Card Sorting Test (WCST) targeting cognitive flexibility, and the Trail Making Test B examining parallel sequencing were obtained from 9 patients with left TLE and 17 healthy controls. The five major findings were: (1) Caudate volume is reduced on the left side in TLE. (2) The atrophy involves the dorsal and ventral head of the caudate. (3) These atrophic caudate regions have a corresponding high probability of connections to dorsal prefrontal, anterior cingulate, and orbitofrontal cortex. (4) Smaller caudate volumes are linked to greater numbers of WCST perseverative errors. (5) Reduced connections between caudate and dorsal prefrontal cortex correlated with poorer scores on the Trail Making Test B. The results suggest that atrophy in the dorsal head of the caudate might disrupt frontostriatal networks that are critical for executive functioning in TLE.

“Wanting”, a component of reward processing, is a motivational property that guides decision making in goal-oriented behavior. This includes behavior aiming at supporting relational bonds, even at the group level. Accordingly, group belongingness works as this motivational property, which is fundamentally different from romantic or maternal love. While primary rewards (or learned associations, such as money) have been largely used to study the conceptual framework associated with “wanting,” other cues triggering behavior, such as passionate motives, are less well-studied. We investigated the neural correlates of value estimation of a passion-driven incentive in neuropsychologically defined football fans. We asked the participants (n = 57) to compute the value of football tickets (the cues that trigger passionate behavior in this “tribal love” context). The trials were all different, comprising tickets for different matches. The participants had no restrictions on the amount to be introduced. This enabled a parametric functional magnetic resonance imaging design based on the explicit estimated value given by the participants in a trial-by-trial approach. Using a whole-brain approach (to prevent biased focus on value-related regions), only the activity in the ventral caudate and left anterior insula showed a critical relationship with the reported value. Higher normalized values led to more activity in the striatum and left insula. The parametric map shows that these regions encode the magnitude of incentive by indexing self-relevant value. Other regions were involved in value computation, such as the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex, but did not exhibit parametric patterns. The involvement of the nucleus accumbens in value estimation was only found in region of interest -based analysis, which emphasizes the role of the ventral caudate for the presently studied social “reinforcer” cue.

Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease.

Structural and functional brain alterations have been always observed in end-stage renal disease (ESRD) patients undergoing hemodialysis. The present study aimed to investigate the gray matter volume (GMV) changes in hemodialysis patients compared with those noted in healthy subjects, as well as explore the associated functional connectivity alterations based on the abnormal GMV regions. The experiments revealed the effects of regional morphometry aberrance on the brain functional integrity. A total of 46 hemodialysis patients (53.11 ± 1.58 years, 28 males) and 47 healthy subjects (55.57 ± 0.86 years, 22 males) were enrolled in the present study. All subjects underwent high-resolution T1-weighted imaging, resting-state functional MR imaging, and laboratory examinations were performed in hemodialysis patients. The GMV deficits were analyzed using voxel-based morphometry (VBM) and regions with GMV alteration were defined as seeds for functional connectivity analysis. Correlation analyses between significantly different regions and the results of the blood examination were further performed. We found that bilateral thalamus exhibited significantly increased volumes in the hemodialysis patients compared with those of the healthy subjects. However, the bilateral rectus, bilateral caudate, and bilateral temporal gyrus demonstrated significantly decreased volumes. When the regions with GMV alterations were defined as seeds, the hemodialysis patients exhibited decreased integrations in the thalamo-cortical network and within the basal-ganglia connection. The present study revealed the presence of different types of structural and functional brain impairments in hemodialysis patients.

Brain-Derived Neurotrophic Factor (BDNF) facilitates the formation of long-term potentiation (LTP) in hippocampus but whether this involves release from pre- vs. post- synaptic pools is unclear. We therefore tested if BDNF is essential for LTP in dorsal striatum, a structure in which the neurotrophin is present only in afferent terminals. Whole cell recordings were collected from medium spiny neurons in striatal slices prepared from adult mice. High frequency stimulation (HFS) of neocortical afferents produced a rapid and stable NMDA receptor-dependent potentiation. The ratio of AMPA to NMDA receptor-mediated components of the EPSPs was substantially increased after inducing potentiation, suggesting that potentiation involved post-synaptic changes. In accord with this, paired pulse response ratios, a measure of transmitter release kinetics, were reduced by elevated calcium but not by LTP. Infusion of the BDNF scavenger TrkB-Fc blocked the formation of potentiation, beginning with the second minute post-HFS, without reducing responses to HFS. These results suggest that presynaptic pools of BDNF can act within 2 minutes of HFS to support the formation of a post-synaptic form of LTP in striatum.

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

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

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

Background: Apathy is a prevalent and debilitating neuropsychiatric syndrome in Parkinson's disease (PD). However, its neural mechanisms are still unclear.Methods: Forty-six de novo, drug-naïve, non-demented PD patients without depressive or anxious symptoms, of whom 26 were apathetic (PD-A) and 20 were not (PD-NA) according to the Apathy Scale (AS), and 23 matched healthy control (HC) subjects were enrolled in this study. The regional homogeneity (ReHo) approach based on resting-state functional MRI on a 3-T MR system was used to investigate apathy related local brain activity.Results: Compared with both patients with PD-NA and HC subjects, patients with PD-A showed significantly lower ReHo values in the dorsal anterior cingulate cortex (ACC) and right caudate. Both the PD-A and PD-NA groups also demonstrated lower ReHo values in the right putamen compared to the HC group. Further correlation analyses revealed that AS scores were negatively correlated with the ReHo values in the dorsal ACC and right caudate in the pooled patients with PD.Limitations: The present results are preliminary due to the small sample size in the study.Conclusions: This study used ReHo for the first time to characterize "pure" apathy related regional spontaneous brain function within the frontostriatal circuits in PD. Our findings suggest that abnormal brain activity in the dorsal ACC and caudate may involve the pathological mechanisms of apathy in PD. [ABSTRACT FROM AUTHOR]

"Wanting", a component of reward processing, is a motivational property that guides decision making in goal-oriented behavior. This includes behavior aiming at supporting relational bonds, even at the group level. Accordingly, group belongingness works as this motivational property, which is fundamentally different from romantic or maternal love. While primary rewards (or learned associations, such as money) have been largely used to study the conceptual framework associated with "wanting," other cues triggering behavior, such as passionate motives, are less well-studied. We investigated the neural correlates of value estimation of a passion-driven incentive in neuropsychologically defined football fans. We asked the participants (n = 57) to compute the value of football tickets (the cues that trigger passionate behavior in this "tribal love" context). The trials were all different, comprising tickets for different matches. The participants had no restrictions on the amount to be introduced. This enabled a parametric functional magnetic resonance imaging design based on the explicit estimated value given by the participants in a trial-by-trial approach. Using a whole-brain approach (to prevent biased focus on value-related regions), only the activity in the ventral caudate and left anterior insula showed a critical relationship with the reported value. Higher normalized values led to more activity in the striatum and left insula. The parametric map shows that these regions encode the magnitude of incentive by indexing self-relevant value. Other regions were involved in value computation, such as the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex, but did not exhibit parametric patterns. The involvement of the nucleus accumbens in value estimation was only found in region of interest -based analysis, which emphasizes the role of the ventral caudate for the presently studied social "reinforcer" cue. [ABSTRACT FROM AUTHOR]

Structural and functional brain alterations have been always observed in end-stage renal disease (ESRD) patients undergoing hemodialysis. The present study aimed to investigate the gray matter volume (GMV) changes in hemodialysis patients compared with those noted in healthy subjects, as well as explore the associated functional connectivity alterations based on the abnormal GMV regions. The experiments revealed the effects of regional morphometry aberrance on the brain functional integrity. A total of 46 hemodialysis patients (53.11 ± 1.58 years, 28 males) and 47 healthy subjects (55.57 ± 0.86 years, 22 males) were enrolled in the present study. All subjects underwent high-resolution T1-weighted imaging, resting-state functional MR imaging, and laboratory examinations were performed in hemodialysis patients. The GMV deficits were analyzed using voxel-based morphometry (VBM) and regions with GMV alteration were defined as seeds for functional connectivity analysis. Correlation analyses between significantly different regions and the results of the blood examination were further performed. We found that bilateral thalamus exhibited significantly increased volumes in the hemodialysis patients compared with those of the healthy subjects. However, the bilateral rectus, bilateral caudate, and bilateral temporal gyrus demonstrated significantly decreased volumes. When the regions with GMV alterations were defined as seeds, the hemodialysis patients exhibited decreased integrations in the thalamo-cortical network and within the basal-ganglia connection. The present study revealed the presence of different types of structural and functional brain impairments in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Bilingualism has been said to improve cognition and even delay the onset of Alzheimer's disease (AD). This research aimed to investigate whether bilingualism leaves a neurophysiological trace even when people are highly educated. We expected bilinguals to present better preserved brain functional networks, which could be a trace of higher cognitive reserve. With this purpose, we conducted a magnetoencephalographic study with a group of healthy older adults. We estimated functional connectivity using phase-locking value and found five clusters in parieto-occipital regions in which bilinguals exhibited greater functional connectivity than monolinguals. These clusters included brain regions typically implicated in language processing. Furthermore, these functional changes correlated with caudate volumes (a key region in language shifting and control) in the bilingual sample. Interestingly, decreased Functional Connectivity between posterior brain regions had already been identified as an indicator of aging/preclinical AD but, according to our study, bilingualism seems to exert the opposite effect. [ABSTRACT FROM AUTHOR]

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

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS). While progressive resistance training (PRT) has been shown to reduce fatigue in persons with MS, it is not clear why these reductions occur. One hypothesis is that PRT may induce functional changes to the caudate, a region highly implicated in MS fatigue. The aim of the current study was to study the effects of PRT on overall fatigue impact and resting-state functional connectivity of the caudate in persons with MS reporting severe fatigue. Participants were semi-randomly assigned to either a 16-week home-based PRT (n = 5) or stretching control (n = 5) condition. Both groups demonstrated reductions in overall fatigue impact (main effect of time: F = .84, d = .65). Significant group × time interactions were found, with the PRT group demonstrating post-training increases in functional connectivity between the caudate and left inferior parietal (F = 66.0, p < .001), bilateral frontal (both p < .001), and right insula (F = 21.8, p = .002) regions compared to the stretching group. Furthermore, greater post-training increases in functional connectivity between the caudate and left inferior parietal region were associated with greater decreases in cognitive fatigue (r = -.52) specifically. This study provides initial evidence for the caudate as a potential neural substrate for the beneficial effects of PRT on fatigue in persons with MS. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate whether severity of cannabis dependence is associated with the neuroanatomy of key brain regions of the stress and reward brain circuits. Methods: To examine dependence-specific regional brain alterations, we compared the volumes of regions relevant to reward and stress, between high-dependence cannabis users (CD+, n = 25), low-dependence cannabis users (CD−, n = 20) and controls (n = 37). Results: Compared to CD− and/or controls, the CD+ group had lower cerebellar white matter and hippocampal volumes, and deflation of the right hippocampus head and tail. Conclusion: These findings provide initial support for neuroadaptations involving stress and reward circuits that are specific to high-dependence cannabis users. [ABSTRACT FROM AUTHOR]

The hippocampal and caudate networks interact to support episodic memory, but the relationship between hippocampal and caudate connectivity strength and episodic memory is unclear. In general, cognition is optimally supported when connectivity within a functional network dominates connectivity from other networks. For example, episodic memory may be optimally supported when the hippocampal and caudate networks express this pattern of connectivity, consistent with research showing that the two networks are organized competitively. Alternatively, episodic memory may be optimally supported when connectivity in both networks is more balanced, consistent with fMRI reports showing cooperation between networks. Using cross-sectional behavioral and resting state fMRI data from a diverse sample (N = 347; Ages 18–85), I tested the hypothesis that reduced hippocampal and caudate network dominance would be associated with reduced episodic memory across individuals and age. Consistent with this hypothesis, lower caudate network dominance in bilateral thalamic regions was associated with worse episodic memory regardless of age. Age-related differences in caudate network dominance in the pallidum and putamen were also associated with worse episodic memory performance, but through their shared variance with age. I found no evidence that network dominance was related to processing speed or executive function, or that hippocampal network dominance was relate to episodic memory performance. These results show that ongoing biological dynamics between the hippocampal and caudate networks throughout adulthood are related to episodic memory performance and support a growing literature specifying the role of the caudate network in episodic memory. • Hippocampal (HN) and caudate network (CN) dominance over each other was assessed. • Independent of age, lower thalamic CN dominance predicted worse episodic memory. • Age-related decline in striatal CN dominance predicted worse episodic memory. • HN and CN dominance were not related to processing speed or executive function. • Decline in HN dominance was not related to episodic memory. [ABSTRACT FROM AUTHOR]

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

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

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.

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.

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

Neuromodulation is a promising treatment modality for disorders of learning and memory, offering the possibility of precise alteration of disordered neural circuits. Studies to date have failed to identify an optimal target and stimulation paradigm. Six epilepsy patients with depth electrodes implanted for seizure localization participated in our study. We recorded local field potentials from implanted electrodes while subjects participated in an associative learning task requiring them to learn an association between presented images and a button press. Three subjects participated in stimulation sessions during which caudate or putamen stimulation was delivered for some images during feedback after correct responses. Caudate stimulation enhanced learning. Both caudate and dorsolateral prefrontal cortex demonstrated a beta power increase during the feedback period of the learning task that was greater following correct than incorrect trials. In dorsolateral prefrontal cortex, this difference increased with learning and persisted beyond the end of the feedback period. Caudate stimulation was associated with increased dorsolateral prefrontal cortex beta power following feedback. These findings suggest that temporally specific caudate stimulation is a promising neuromodulation strategy to improve learning in disorders of learning and memory. [ABSTRACT FROM AUTHOR]

Objective: Although not typical of Parkinson's disease (PD), caudate dopaminergic dysfunction can occur in early stages of the disease. However, its frequency and longitudinal implications in large cohorts of recently diagnosed patients remain to be established. We investigated the occurrence of caudate dopaminergic dysfunction in the very early phases of PD (<2 years from diagnosis) using 123I-FP-CIT single photon emission CT and determined whether it was associated with the presence or subsequent development of cognitive impairment, depression, sleep and gait problems.Methods: Patients with PD and healthy controls were identified from the Parkinson's Progression Markers Initiative (PPMI) database. We defined a clinically significant caudate dysfunction as 123I-FP-CIT binding <-2 SDs compared with the controls' mean and categorised three groups accordingly (no reduction, unilateral reduction, bilateral reduction). All statistical analyses were adjusted for mean putamen binding.Results: At baseline, 51.6% of 397 patients had normal caudate dopamine transporter binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate.Compared with those with a baseline normal caudate function, at the4-year follow-up patients with a baseline bilateral caudate involvement showed a higher frequency of cognitive impairment (p<0.001) and depression (p<0.001), and worse cognitive (p<0.001), depression (<0.05) and gait (<0.001) ratings. Significant caudate involvement was observed in 83.9% of the population after 4 years (unilateral 22.5%, bilateral 61.4%).Conclusions: Early significant caudate dopaminergic denervation was found in half of the cases in the PPMI series. Baseline bilateral caudate involvement was associated with increased risk of developing cognitive impairment, depression and gait problems over the next 4 years. [ABSTRACT FROM AUTHOR]

Fragile X-associated tremor ataxia syndrome is an inherited neurodegenerative disorder caused by premutation expansions (55-200 CGG repeats) of the FMR1 gene. There is accumulating evidence to suggest that early cognitive and brain imaging signs may be observed in some premutation carriers without motor signs of FXTAS, but few studies have examined the relationships between subcortical brain volumes and cognitive performance in this group. This study examined the relationships between caudate volume and select cognitive measures (executive function and information processing speed) in men at risk of developing FXTAS and controls with normal FMR1 alleles (<45 CGG repeats). The results showed that men with premutation alleles performed worse on measures of executive function and information processing speed, and had significantly reduced caudate volume, compared to controls. Smaller caudate volume in the premutation group was associated with slower processing speed. These findings provide preliminary evidence that early reductions in caudate volume may be associated with cognitive slowing in men with the premutation who do not present with cardinal motor signs of FXTAS. If confirmed in future studies with larger PM cohorts, these findings will have important implications for the identification of sensitive measures with potential utility for tracking cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives: With an increasing aging population, it is important to understand biological markers of aging. Subcortical volume is known to differ with age; additionally considering shape-related characteristics may provide a better index of age-related differences. Fractal dimensionality is more sensitive to age-related differences, but is borne out of mathematical principles, rather than neurobiological relevance. We considered four distinct measures of shape and how they relate to aging and fractal dimensionality: surface-to-volume ratio, sphericity, long-axis curvature, and surface texture. Methods: Structural MRIs from a combined sample of over 600 healthy adults were used to measure age-related differences in the structure of the thalamus, putamen, caudate, and hippocampus. For each, volume and fractal dimensionality were calculated, as well as four distinct shape measures. These measures were examined for their utility in explaining age-related variability in brain structure. Results: The four shape measures were able to account for 80%–90% of the variance in fractal dimensionality. Of the distinct shape measures, surface-to-volume ratio was the most sensitive biomarker. Conclusion: Though volume is often used to characterize inter-individual differences in subcortical structures, our results demonstrate that additional measures can be useful complements. Our results indicate that shape characteristics are useful biological markers of aging. [ABSTRACT FROM AUTHOR]

Successful behavioral inhibition involves both proactive and reactive inhibition, allowing people to prepare for restraining actions, and cancel their actions if the response becomes inappropriate. In the present study, we utilized the stop-signal paradigm to examine whole-brain contrasts and functional connectivity for proactive and reactive inhibition. The results of our functional magnetic resonance imaging (fMRI) data analysis show that the inferior frontal gyrus (IFG), the supplementary motor area (SMA), the subthalamic nucleus (STN), and the primary motor cortex (M1) were activated by both proactive and reactive inhibition. We then created 70 dynamic causal models (DCMs) representing the alternative hypotheses of modulatory effects from proactive and reactive inhibition in the IFG-SMA-STN-M1 network. Bayesian model selection (BMS) showed that causal connectivity from the IFG to the SMA was modulated by both proactive and reactive inhibition. To further investigate the possible brain circuits involved in behavioral control, including proactive inhibitory processes, we compared 13 DCMs representing the alternative hypotheses of proactive modulation in the dorsolateral prefrontal cortex (DLPFC)-caudate-IFG-SMA neural circuits. BMS revealed that the effective connectivity from the caudate to the IFG is modulated only in the proactive inhibition condition but not in the reactive inhibition. Together, our results demonstrate how fronto-basal ganglia pathways are commonly involved in proactive and reactive inhibitory control, with a "longer" pathway (DLPFC-caudate-IFG-SMA-STN-M1) playing a modulatory role in proactive inhibitory control, and a "shorter" pathway (IFG-SMA-STN-M1) involved in reactive inhibition. These results provide causal evidence for the roles of indirect and hyperdirect pathways in mediating proactive and reactive inhibitory control. [ABSTRACT FROM AUTHOR]

Objectives: Apathy is a debilitating symptom of Huntington's disease (HD) and manifests before motor diagnosis, making it an excellent therapeutic target in the preclinical phase of Huntington's disease (prHD). HD is a neurological genetic disorder characterized by cognitive and motor impairment, and psychiatric abnormalities. Apathy is not well characterized within the prHD. In previous literature, damage to the caudate and putamen has been correlated with increased apathy in other neurodegenerative and movement disorders. The objective of this study was to determine whether apathy severity in individuals with prHD is related to striatum volumes and cognitive control. We hypothesized that, within prHD individuals, striatum volumes and cognitive control scores would be related to apathy. Methods: We constructed linear mixed models to analyze striatum volumes and cognitive control, a composite measure that includes tasks assessing with apathy scores from 797 prHD participants. The outcome variable for each model was apathy, and the independent variables for the four separate models were caudate volume, putamen volume, cognitive control score, and motor symptom score. We also included depression as a covariate to ensure that our results were not solely related to mood. Results: Caudate and putamen volumes, as well as measures of cognitive control, were significantly related to apathy scores even after controlling for depression. Conclusions: The behavioral apathy expressed by these individuals was related to regions of the brain commonly associated with isolated apathy, and not a direct result of mood symptoms. [ABSTRACT FROM AUTHOR]

Highlights • Right anterior cingulate cortex, left caudate, and left amygdala volumes are associated with trust of neighbors. • Age, level of education, and race/ethnicity play a role in trust of neighbors. • Findings implicate importance of the salience network in formation of interpersonal trust. Abstract Trust is a fundamental part of human interpersonal relationships, and among other complex factors it is shown to be linked with demographic characteristics and specific regions of the brain. The authors utilized a large, community-based database gathered from the Dallas Heart Study to determine specific brain regions associated with an individual's trust in neighbors. A trust questionnaire was taken and regional brain volumes were determined from structural magnetic resonance imaging. Two analyses using logistic regressions in a training set and validation set were performed to investigate the association between measures of trust and bilateral brain region volumes and thickness. A total of 1527 participants were included in the final analysis. Right caudal anterior cingulate cortex thickness and left caudate volume were inversely correlated with neighbor trust, while left amygdala volume was positively correlated with neighbor trust. Greater age and higher level of education were positively correlated with neighbor trust. African Americans showed less neighbor trust than Caucasians and Hispanics. Anterior cingulate cortex, caudate, and amygdala are all integral parts of the salience network; thus, results of this study suggest that the salience network, the brain network responsible for functions such as communication and social behavior, may play a role in the formation of interpersonal trust. [ABSTRACT FROM AUTHOR]