The complexity of brain activity reflects its ability to process information, adapt to environmental changes, and transition between states. However, it remains unclear how schizophrenia (SZ) affects brain activity complexity, particularly its dynamic changes. This study aimed to investigate the abnormal patterns of brain activity complexity in SZ, their relationship with cognitive deficits, and the impact of antipsychotic medication. Forty-four drug-naive first-episode (DNFE) SZ patients and thirty demographically matched healthy controls (HC) were included. Functional MRI-based sliding window analysis was utilized for the first time to calculate weighted permutation entropy to characterize complex patterns of brain activity in SZ patients before and after 12 weeks of risperidone treatment. Results revealed reduced complexity in the caudate, putamen, and pallidum at baseline in SZ patients compared to HC, with reduced complexity in the left caudate positively correlated with Continuous Performance Test (CPT) and Category Fluency Test scores. After treatment, the complexity of the left caudate increased. Regions with abnormal complexity showed decreased functional connectivity, with complexity positively correlated with connectivity strength. We observed that the dynamic complexity of the brain exhibited the characteristic of spontaneous, recurring \"complexity drop\", potentially reflecting transient state transitions in the resting brain. Compared to HC, patients exhibited reduced scope, intensity, and duration of complexity drop, all of which improved after treatment. Reduced duration was negatively correlated with CPT scores and positively with clinical symptoms. The results suggest that abnormalities in brain activity complexity and its dynamic changes may underlie cognitive deficits and clinical symptoms in SZ patients. Antipsychotic treatment partially restores these abnormalities, highlighting their potential as indicators of treatment efficacy and biomarkers for personalized therapy.

OBJECTIVE: Antenatal corticosteroids (ACS) is a well-established treatment for women at risk of preterm birth that improves neonatal outcomes. However, several concerns have been raised regarding the potential long-term adverse effects of ACS on the offspring\'s developing brain. Here we investigated the association between ACS and subcortical segmental volumes in preterm infants at term-equivalent age.
METHODS: This retrospective observational study was conducted using the clinical data of preterm singleton infants born between 220/7 and 336/7 gestational weeks at Nagoya University Hospital in 2014-2020. Subcortical volumes of the bilateral thalami, caudate nuclei, putamens, pallidums, hippocampi, amygdalae, and nuclei accumbens were evaluated using an automated segmentation tool, Infant FreeSurfer, and compared between neonates exposed to a single course of ACS (n = 46) and those who were not (n = 13) by multiple linear regression analysis (covariates: postmenstrual age at magnetic resonance imaging, infant sex, and gestational age at birth). We compared each subcortical volume stratified by gestational age at birth (<28 vs. ≥28 gestational weeks).
RESULTS: Multivariate analyses revealed significantly smaller volumes in the bilateral amygdalae (left, p < 0.03; right, p < 0.03) and caudate nuclei (left, p < 0.03; right, p = 0.04) in neonates with ACS. Significantly smaller volumes in these regions were observed only in neonates born at 28 weeks of gestation or later.
CONCLUSIONS: ACS was associated with smaller volumes of the bilateral amygdalae and caudate nuclei at term-equivalent age. This association was observed exclusively in infants born at 28 weeks of gestation or later.

Primates must adapt to changing environments by optimizing their behavior to make beneficial choices. At the core of adaptive behavior is the orbitofrontal cortex (OFC) of the brain, which updates choice value through direct experience or knowledge-based inference. Here, we identify distinct neural circuitry underlying these two separate abilities. We designed two behavioral tasks in which two male macaque monkeys updated the values of certain items, either by directly experiencing changes in stimulus-reward associations, or by inferring the value of unexperienced items based on the task\'s rules. Chemogenetic silencing of bilateral OFC combined with mathematical model-fitting analysis revealed that monkey OFC is involved in updating item value based on both experience and inference. In vivo imaging of chemogenetic receptors by positron emission tomography allowed us to map projections from the OFC to the rostromedial caudate nucleus (rmCD) and the medial part of the mediodorsal thalamus (MDm). Chemogenetic silencing of the OFC-rmCD pathway impaired experience-based value updating, while silencing the OFC-MDm pathway impaired inference-based value updating. Our results thus demonstrate dissociable contributions of distinct OFC projections to different behavioral strategies, and provide new insights into the neural basis of value-based adaptive decision-making in primates.

Temporal discounting, in which the recipient of a reward perceives the value of that reward to decrease with delay in its receipt, is associated with impulsivity and psychiatric disorders such as depression. Here, we investigate the role of the serotonin 5-HT4 receptor (5-HT4R) in modulating temporal discounting in the macaque dorsal caudate nucleus (dCDh), the neurons of which have been shown to represent temporally discounted value. We first mapped the 5-HT4R distribution in macaque brains using positron emission tomography (PET) imaging and confirmed dense expression of 5-HT4R in the dCDh. We then examined the effects of a specific 5-HT4R antagonist infused into the dCDh. Blockade of 5-HT4R significantly increased error rates in a goal-directed delayed reward task, indicating an increase in the rate of temporal discounting. This increase was specific to the 5-HT4R blockade because saline controls showed no such effect. The results demonstrate that 5-HT4Rs in the dCDh are involved in reward-evaluation processes, particularly in the context of delay discounting, and suggest that serotonergic transmission via 5-HT4R may be a key component in the neural mechanisms underlying impulsive decisions, potentially contributing to depressive symptoms.

Suicide is the second leading cause of death in youth, and depression is a strong proximal predictor of adolescent suicide. It is important to identify psychological factors that may protect against suicide ideation in depressed adolescents. Self-compassion may be such a factor. Converging evidence indicates the inverse association between self-compassion and suicide ideation, but the neural mechanisms underlying their link remain unknown. Because self-referential caudate activity is associated with both self-compassion and suicide ideation, its functional connectivity might explain their relationship. In this study, we examined the relationship between self-compassion and caudate functional connectivity during self-appraisals, a typical self-referential paradigm, and their associations with suicide ideation in both depressed and healthy youth. In the scanner, 79 depressed youth and 36 healthy controls evaluated, from various perspectives, whether phrases they heard were self-descriptive. Self-compassion and suicide ideation were rated with self-report and interview-based measures. We found that self-compassion was associated with stronger left caudate functional connectivity with bilateral posterior superior temporal sulcus/temporoparietal junction, the left middle temporal gyrus (MTG), and the left middle occipital gyrus during positive versus negative self-appraisals. Stronger left caudate connectivity with the left MTG explained the association between higher self-compassion and lower suicide ideation, even controlling for non-suicide ideation depression severity, anxiety severity, and non-suicidal self-injurious behavior. The findings suggest that the left caudate to MTG connectivity during positive versus negative self-referential processing could be a biomarker to be targeted by neural stimulation interventions for reducing suicide ideation in depressed youth, combined with self-compassion interventions.

Degenerative lesions specific to the basal nuclei have not been described as a background finding in Beagle dogs. This report comprises a documentation of seven cases. In the context of a nonclinical safety studies, the authors suggest documenting the lesion descriptively as degeneration neuropil, basal nuclei, bilateral as it is characterized by (1) vacuolation, neuropil; (2) gliosis (astro- and/or microgliosis); and (3) demyelination. This novel lesion is considered a potential new background change for several reasons: (1) It occurred in animals from test item-treated and also vehicle-treated groups; (2) no dose dependency was observed; (3) in one of six affected test item-treated dogs, the given compound was shown not to penetrate the blood-brain barrier; and (4) statistical comparison between the proportions of affected dogs in the treatment and control groups did not yield a statistically significant difference. The etiology remains unknown and is subject to further investigations.

Caudate nucleus (CN) neurons in camels and humans were examined using modified Golgi impregnation methods. Neurons were classified based on soma morphology, dendritic characteristics, and spine distribution. Three primary neuron types were identified in both species: rich-spiny (Type I), sparsely-spiny (Type II), and aspiny (Type III), each comprising subtypes with specific features. Comparative analysis revealed significant differences in soma size, dendritic morphology, and spine distribution between camels and humans. The study contributes to our understanding of structural diversity in CN neurons and provides insights into evolutionary neural adaptations.

UNASSIGNED: Excessive daytime sleepiness (EDS) and caudate nucleus volume alterations have been linked to Alzheimer\'s disease (AD), but their relationship remains unclear under the context of subjective cognitive decline (SCD).
UNASSIGNED: This study aimed to investigate the relationship between EDS and caudate nucleus volume in patients with SCD.
UNASSIGNED: The volume of entire brain was measured in 170 patients with SCD, including 37 patients with EDS and 133 non-EDS, from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Participants underwent a comprehensive assessment battery, including neuropsychological and clinical evaluations, blood tests, genetic analysis for APOE ɛ4, and structural MRI scans analyzed using the fully automated segmentation tool, volBrain.
UNASSIGNED: Patients with EDS had significantly increased volume in the total and left caudate nucleus compared to non-EDS. The most significant cognitive behavioral factor associated with caudate nucleus volume in the EDS was the Auditory Verbal Learning Test-recognition.
UNASSIGNED: These findings suggest that EDS may be associated with alterations in caudate nucleus volume, particularly in the left hemisphere, in the context of SCD. Further research is necessary to understand the underlying mechanisms of this relationship and its implications for clinical management.

OBJECTIVE: To study the ultrastructure of microglia and neurons in contact with each other in the head of the caudate nucleus in continuous schizophrenia (CS) and paroxysmal-progressive schizophrenia (PPS) as compared to controls and to analyze correlations between the parameters of microglia and neurons in the control and schizophrenia groups.
METHODS: Post-mortem electron microscopic morphometric study of microglia and neurons in contact with each other was performed in the head of the caudate nucleus in 9 cases of CS, 10 cases of PPS and 20 controls without mental pathology. Group comparisons were made using analysis of covariance and Pearson correlation analysis.
RESULTS: The PPS group showed increased numerical density of microglia in young (≤50 years old) patients compared to elderly (>50 years old) controls and increased area of endoplasmic reticulum vacuoles in microglia in young patients compared to young controls. Decreased numerical density of microglia was found in the CS group compared to the PPS group (p<0.05), and increased volume fraction (Vv) and the number of lipofuscin granules in microglia were found in the CS group in elderly patients compared with young and elderly controls. In this group, negative correlations were revealed between the numerical density of microglia, microglia nuclear area and the duration of disease (r= -0.72, p=0.03; r= -0.8; p=0.01). Decreased Vv and the number of mitochondria in microglia and increased area and perimeter of neurons were revealed in both groups compared to the control group. In neurons, increased vacuole area was found in the PPS group and mitochondrial area in the NTS group compared to the control group. Correlation violations were found between the parameters of mitochondria in microglia and neurons in both PPS and CS groups and between the area of mitochondria in neurons and the area of vacuoles in microglia in the CS group compared to the control group.
CONCLUSIONS: Disturbed interactions between microglia and neurons in the caudate nucleus are associated with the types of course of schizophrenia and with microglial reactivity. They might be caused by the damage of energy metabolism in microglia in both types of schizophrenia course and by stress of endoplasmic reticulum in microglia in CS.
UNASSIGNED: Изучение ультраструктуры микроглии и нейронов, контактирующих друг с другом, в хвостатом ядре при непрерывнотекущей (НТШ) и приступообразно-прогредиентной (ППШ) шизофрении по сравнению с контролем и анализ корреляционных связей между параметрами микроглии и нейронов в контроле и при шизофрении.
UNASSIGNED: На аутопсийном материале проведено электронно-микроскопическое морфометрическое исследование микроглии и нейронов, контактирующих друг с другом, в головке хвостатого ядра в 9 случаях НТШ, 10 — ППШ и 20 контролях без психической патологии. Групповые сравнения проводили с помощью ковариационного анализа и корреляционного анализа Пирсона.
UNASSIGNED: В группе ППШ показаны повышенная численная плотность микроглии у молодых (≤50 лет) больных по сравнению с пожилыми (>50 лет) из группы контроля и площадь вакуолей эндоплазматического ретикулума в микроглии у молодых больных по сравнению с молодыми из группы контроля. В группе НТШ обнаружены сниженная численная плотность микроглии по сравнению с группой ППШ (p<0,05) и повышенные объемная фракция (Vv) и количество гранул липофусцина в микроглии у пожилых больных по сравнению с молодыми и пожилыми из группы контроля. В группе НТШ найдены отрицательные корреляции между численной плотностью микроглии, площадью ядра микроглии и длительностью болезни (r= –0,72, p=0,03; r= –0,8; p=0,01). В обеих группах больных обнаружены сниженные Vv и количество митохондрий в микроглии и повышенные площадь и периметр нейронов по сравнению с контрольной группой. В нейронах найдены повышенные площадь вакуолей в группе ППШ и площадь митохондрий в группе НТШ по сравнению с контрольной группой. Установлены нарушения корреляционных связей между параметрами митохондрий в микроглии и нейронах в группах ППШ и НТШ и между площадью митохондрий в нейронах и площадью вакуолей в микроглии в группе НТШ по сравнению с контрольной группой.
UNASSIGNED: Нарушенные взаимодействия между микроглией и нейронами в хвостатом ядре связаны с типами течения шизофрении и микроглиальной реактивностью. Они могут быть вызваны повреждением энергетического метаболизма в микроглии при обоих типах течения шизофрении и стрессом эндоплазматического ретикулума в микроглии при НТШ.

Brain iron increases in several neurodegenerative diseases are associated with disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron, systemic iron and inflammatory status. Brain magnetic resonance imaging (MRI) scans and blood plasma samples were collected from cognitively healthy females (n = 176, mean age = 61.4 ± 4.5 years, age range = 28-72 years) and males (n = 152, mean age = 62.0 ± 5.1 years, age range = 32-74 years). Regional brain iron was quantified using quantitative susceptibility mapping. To assess systemic iron, haematocrit, ferritin and soluble transferrin receptor were measured, and total body iron index was calculated. To assess systemic inflammation, C-reactive protein (CRP), neutrophil:lymphocyte ratio (NLR), macrophage colony-stimulating factor 1 (MCSF), interleukin 6 (IL6) and interleukin 1β (IL1β) were measured. We demonstrated that iron levels in the right hippocampus were higher in males compared with females, while iron in the right caudate was higher in females compared with males. There were no significant associations observed between subcortical iron levels and blood markers of iron and inflammatory status indicating that such blood measures are not markers of brain iron. These results suggest that brain iron may be regulated independently of blood iron and so directly targeting global iron change in the treatment of neurodegenerative disease may have differential impacts on blood and brain iron.