BACKGROUND: Having multiple previous generations with depression in the family increases offspring risk for psychopathology. Parental depression has been associated with smaller subcortical brain volumes in their children, but whether two prior generations with depression is associated with further decreases is unclear.
METHODS: Using two independent cohorts, 1) a Three-Generation Study (TGS, N = 65) with direct clinical interviews of adults and children across all three generations, and 2) the Adolescent Brain Cognitive Development Study (ABCD, N = 10,626) of 9-10 year-old children with family history assessed by a caregiver, we tested whether having more generations of depression in the family was associated with smaller subcortical volumes (using structural MRI).
RESULTS: In TGS, caudate, pallidum and putamen showed decreasing volumes with higher familial risk for depression. Having a parent and a grandparent with depression was associated with decreased volume compared to having no familial depression in these regions. Putamen volume was associated with depression at eight-year follow-up. In ABCD, smaller pallidum and putamen were associated with family history, which was driven by parental depression, regardless of grandparental depression.
CONCLUSIONS: Discrepancies between cohorts could be due to interview type (clinical or self-report) and informant (individual or common informant), sample size or age. Future analyses of follow-up ABCD waves will be able to assess whether effects of grandparental depression on brain markers become more apparent as the children enter young adulthood.
CONCLUSIONS: Basal ganglia regional volumes are significantly smaller in offspring with a family history of depression in two independent cohorts.

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

Movement and muscle control are crucial for the survival of all free-living organisms. This study aimed to explore differential patterns of cortical and subcortical activation across different stages of muscle control using functional magnetic resonance imaging (fMRI). An event-related design was employed. In each trial, participants (n = 10) were instructed to gently press a button with their right index finger, hold it naturally for several seconds, and then relax the finger. Neural activation in these temporally separated stages was analyzed using a General Linear Model. Our findings revealed that a widely distributed cortical network, including the supplementary motor area and insula, was implicated not only in the pressing stage, but also in the relaxation stage, while only parts of the network were involved in the steady holding stage. Moreover, supporting the direct/indirect pathway model of the subcortical basal ganglia, their substructures played distinct roles in different stages of muscle control. The caudate nucleus exhibited greater involvement in muscle contraction, whereas the putamen demonstrated a stronger association with muscle relaxation; both structures were implicated in the pressing stage. Furthermore, the subthalamic nucleus was exclusively engaged during the muscle relaxation stage. We conclude that even the control of simple muscle movements involves intricate automatic higher sensory-motor integration at a neural level, particularly when coordinating relative muscle movements, including both muscle contraction and muscle relaxation; the cortical and subcortical regions assume distinct yet coordinated roles across different stages of muscle control.

Studies of the development and asymmetry of the corpus striatum and thalamus in early childhood are rare. Studies investigating these structures across the lifespan have not presented their changes during childhood and adolescence in detail. For these reasons, this study investigated the effect of age and sex factors on the development and asymmetry of the corpus striatum and thalamus in the 1-18 age group. In this retrospective study, we included 652 individuals [362 (56%) males] aged 1-18 years with normal brain MRI between 2012 and 2021. Absolute and relative volumes of the corpus striatum and thalamus were obtained by segmentation of three-dimensional T1-weighted MRIs with volBrain1.0. We created age-specific volume data and month-based development models with the help of SPSS (ver.28). The corpus striatum and thalamus had cubic absolute volumetric developmental models. The relative volume of the caudate and thalamus (only males) is consistent with the decreasing \"growth\" model, the others with the decreasing cubic model. The absolute volumes of the males\' bilateral corpus striatum and thalamus and the relative volumes of the caudate and thalamus of the females were significantly larger (P < 0.05). The caudate showed right > left lateralization; putamen, globus pallidus, and thalamus showed left > right lateralization.

Obsessive-compulsive symptoms (OCS) are relatively common during adolescence although most individuals do not meet diagnostic criteria for obsessive-compulsive disorder (OCD). Nonetheless, OCS during adolescence are associated with comorbid psychopathologies and behavioral problems. Heightened levels of environmental stress and greater functional connectivity between the somatomotor network and putamen have been previously associated with elevated OCS in OCD patients relative to healthy controls. However, the interaction of these factors within the same sample of individuals has been understudied. This study examined somatomotor-putamen resting state connectivity, stress, and their interaction on OCS in adolescents from 9-12 years of age. Participants (n = 6386) were drawn from the ABCD Study 4.0 release. Multilevel modeling was used to account for nesting in the data and to assess changes in OCS in this age range. Stress moderated the association between somatomotor-putamen connectivity and OCS (β = 0.35, S.E. = 0.13, p = 0.006). Participants who reported more stress than their average and had greater somatomotor-left putamen connectivity reported more OCS, whereas participants who reported less stress than their average and had greater somatomotor-left putamen connectivity reported less OCS. These data suggest that stress differentially affects the direction of association between somatomotor-putamen connectivity and OCS. Individual differences in the experience or perception of stress may contribute to more OCS in adolescents with greater somatomotor-putamen connectivity.

We investigated the feasibility of using a dopamine transporter (DaT) tracer ligand ([123I]FP-CIT) along with novel multi-pinhole brain collimators for dynamic brain single photon emission computed tomography (SPECT) in suspected Parkinson\'s disease patients. Thirteen patients underwent dynamic tracer acquisitions before standard imaging. Uptake values were corrected for partial volume effects. Specific binding ratio (SBRcalc) was calculated, reflecting binding potential relative to non-displaceable binding (BPND) in the cortex. Additional pharmacokinetic parameters (BPND, R1, k2) were estimated using the simplified reference tissue model, revealing differences between Kahraman low-score (LS) and high-score (HS) groups. Results showed increasing striatal tracer uptake until 100 min post-injection, with consistent values afterward. Uptake and SBRcalc ratios matched visual assessment. LS patients had lower putamen than caudate nucleus tracer uptake, decreased BPND values, while R1 and k2 values were comparable to HS patients. In conclusion, dynamic multi-pinhole SPECT using DaT tracer with the extraction of pharmacokinetic parameters is feasible and could help enable early differentiation of reduced and normal DaT values.

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

To investigate the association between neuropsychiatric symptoms (NPS) and nutritional status, and explore their shared regulatory brain regions on the Alzheimer\'s disease (AD) continuum.
A longitudinal, observational cohort study.
Data were collected from the Chinese Imaging, Biomarkers, and Lifestyle study between June 1, 2021 and December 31, 2022.
Overall, 432 patients on the AD continuum, including amnestic mild cognitive impairment and AD dementia, were assessed at baseline, and only 165 patients completed the (10.37 ± 6.08) months\' follow-up.
The Mini-Nutritional Assessment (MNA) and Neuropsychiatric Inventory (NPI) were used to evaluate nutritional status and NPS, respectively. The corrected cerebral blood flow (cCBF) measured by pseudo-continuous arterial spin labeling of the dietary nutrition-related brain regions was analyzed. The association between the NPS at baseline and subsequent change in nutritional status and the association between the changes in the severity of NPS and nutritional status were examined using generalized linear mixed models.
Increased cCBF in the left putamen was associated with malnutrition, general NPS, affective symptoms, and hyperactivity (P < 0.05). The presence of general NPS (β = -1.317, P = 0.003), affective symptoms (β = -1.887, P < 0.001), and appetite/eating disorders (β = -1.714, P < 0.001) at baseline were associated with a decline in the MNA scores during follow-up. The higher scores of general NPI (β = -0.048), affective symptoms (β = -0.181), and appetite/eating disorders (β = -0.416; all P < 0.001) were longitudinally associated with lower MNA scores after adjusting for confounding factors.
We found that baseline NPS were predictors of a decline in nutritional status on the AD continuum. The worse the severity of affective symptoms and appetite/eating disorders, the poorer the nutritional status. Furthermore, abnormal perfusion of the putamen may regulate the association between malnutrition and NPS, which suggests their potentially common neural regulatory basis.

UNASSIGNED: In typical patients with multiple system atrophy with predominant parkinsonism (MSA-P) levodopa is ineffective. However, there are some of these patients who respond well to levodopa treatment. Levodopa efficacy in MSA-P patients is thought to be related to the degree of putaminal damage, but the pathological causation between the putaminal involvement and levodopa efficacy has not been established in detail.
UNASSIGNED: This study aimed to evaluate the neuropathological features of the nigrostriatal dopaminergic system in a \"levodopa-responsive\" MSA-P patient in comparison with \"levodopa-unresponsive\" conventional MSA-P patients.
UNASSIGNED: Clinicopathological findings were assessed in a 53-year-old Japanese man with MSA who presented with asymmetric parkinsonism, levodopa response, and later wearing-off phenomenon. During autopsy, the nigrostriatal pathology of presynaptic and postsynaptic dopaminergic receptor density and α-synuclein status were investigated. The other two patients with MSA-P were examined using the same pathological protocol.
UNASSIGNED: Four years after the onset, the patient died of sudden cardiopulmonary arrest. On autopsy, numerous α-synuclein-positive glial cytoplasmic inclusions in the basal ganglia, pons, and cerebellum were identified. The number of neurons in the putamen and immunoreactivity for dopamine receptors were well-preserved. In contrast, significant neuronal loss and decreased dopamine receptor immunoreactivity in the putamen were observed in the \"levodopa-unresponsive\" MSA-P control patients. These putaminal pathology results were consistent with the findings of premortem magnetic resonance imaging (MRI). All three patients similarly exhibited severe neuronal loss in the substantia nigra and decreased immunoreactivity for dopamine transporter.
UNASSIGNED: Levodopa responsiveness in patients with MSA-P may be corroborated by the normal putamen on MRI and the preserved postsynaptic nigrostriatal dopaminergic system on pathological examination. The results presented in this study may provide a rationale for continuation of levodopa treatment in patients diagnosed with MSA-P.

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