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Hyperdirect insula-basal-ganglia pathway and adult-like maturity of global brain responses predict inhibitory control in children.

ABSTRACT: Inhibitory control is fundamental to children's self-regulation and cognitive development. Here we investigate cortical-basal ganglia pathways underlying inhibitory control in children and their adult-like maturity. We first conduct a comprehensive meta-analysis of extant neurodevelopmental studies of inhibitory control and highlight important gaps in the literature. Second, we examine cortical-basal ganglia activation during inhibitory control in children ages 9-12 and demonstrate the formation of an adult-like inhibitory control network by late childhood. Third, we develop a neural maturation index (NMI), which assesses the similarity of brain activation patterns between children and adults, and demonstrate that higher NMI in children predicts better inhibitory control. Fourth, we show that activity in the subthalamic nucleus and its effective connectivity with the right anterior insula predicts children's inhibitory control. Fifth, we replicate our findings across multiple cohorts. Our findings provide insights into cortical-basal ganglia circuits and global brain organization underlying the development of inhibitory control.

SUBMITTER: Cai W

PROVIDER: S-EPMC6805945 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Basal ganglia plus insula damage yields stronger disruption of smoking addiction than basal ganglia damage alone.

Project description:IntroductionThe main objective of this study was to elucidate the importance of the basal ganglia (BG) and insula (INS) for nicotine addiction and smoking behavior.MethodsWe used a lesion study examining the effects of BG and INS damage on changes in smoking behavior and nicotine dependence over time in a prospective manner. We studied whether combined BG and INS damage yields more substantial disruption of smoking and nicotine dependence than damage to the BG alone and compared with damage to other brain regions outside the BG and INS (brain-damaged comparison [BDC] group). We obtained neuroanatomical and behavioral data for 63 neurological patients with stroke at 1 month after onset and at 3-, 6-, and 12-month follow-ups. All patients were smokers at lesion onset.ResultsThe BG and BG + INS groups had significantly higher and more sustained rates of smoking cessation than patients with damage elsewhere. By 12 months after onset, only 14.3% of the patients in the BDC group were classified as nonsmokers. In the BG group, 37% were not smoking by the 12-month follow-up, and in the BG + INS group, smoking cessation was even more pronounced, as 75% of this group was not smoking at the 12-month epoch.ConclusionsThe findings show that damage to the BG alone can cause disruption of smoking addiction, and when BG damage is combined with INS damage, the disruption increases. The latter finding is consistent with the proposal that the INS has a key role in smoking addiction.

| S-EPMC3954424 | biostudies-literature

Lateralized Deficits of Disgust Processing After Insula-Basal Ganglia Damage.

Project description:A growing body of evidence suggests a role of the insular cortex (IC) and the basal ganglia (BG) in the experience, expression, and recognition of disgust. However, human lesion research, probing this structure-function link, has yielded rather disparate findings in single cases of unilateral and bilateral damage to these areas. Comparative group approaches are needed to elucidate whether disgust-related deficits specifically follow damage to the IC-BG system, or whether there might be a differential hemispheric contribution to disgust processing. We examined emotional processing by means of a comprehensive emotional test battery in four patients with left- and four patients with right-hemispheric lesions to the IC-BG system as well as in 19 healthy controls. While single tests did not provide clear-cut separations of patient groups, composite scores indicated selective group effects for disgust. Importantly, left-lesioned patients presented attenuated disgust composites, while right-lesioned patients showed increased disgust composites, as compared to each other and controls. These findings propose a left-hemispheric basis of disgust, potentially due to asymmetrical representations of autonomic information in the human forebrain. The present study provides the first behavioral evidence of hemispheric lateralization of a specific emotion in the human brain, and contributes to neurobiological models of disgust.

| S-EPMC7347022 | biostudies-literature

Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

Project description:A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.

| S-EPMC4194444 | biostudies-literature

Adult-Onset Isolated Hemichorea Revealing Iatrogenic Hypoparathyroidism and Bilateral Basal Ganglia Calcification.

Project description:Isolated hemichorea (HC) in adults has a relatively restricted differential diagnosis including stroke of contralateral basal ganglia nuclei, nonketotic hyperglycemia, and basal ganglia toxoplasmosis in HIV infection. Hypoparathyroidism-related basal ganglia calcification can potentially cause neurological problems, including movement disorders, that are usually bilateral in keeping with bilateral symmetric lesions. We report a patient with video-documented isolated, adult-onset HC due to iatrogenic hypoparathyroidism and bilateral basal ganglia calcification. A 47-year-old woman presented with isolated adult-onset HC of 2 years' duration as the presenting and only neurological feature of hypoparathyroidism and bilateral extensive basal ganglia calcification, 20 years after thyroidectomy-induced hypoparathyroidism. Significant improvement in the unilateral hyperkinesia was noted after correction of hypocalcemia and hypoparathyroidism at 3 months. Isolated HC in adults is a rare presenting feature of hypoparathyroidism with bilateral basal ganglia calcification and is treatable with correction of the underlying metabolic abnormality. In all cases with a movement disorder and brain calcification, hypoparathyroidism should be actively sought as this treatable condition must not be missed.

| S-EPMC6839308 | biostudies-literature

Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors.

Project description:The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) will have specific effects on locomotion: the SNr inhibiting locomotion and the GPe enhancing it. In this manuscript, we use in vivo optogenetics to show that a projection-defined neural subpopulation within each structure exerts non-canonical effects on locomotion. These non-canonical subpopulations are defined by their projection to the pedunculopontine nucleus (PPN) and mediate opposing effects on reward. To understand how these structures differentially modulate the PPN, we use ex vivo whole-cell recording with optogenetics to comprehensively dissect the SNr and GPe connections to regionally- and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes, but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence.

| S-EPMC11326182 | biostudies-literature

Deciphering the distinct transcriptomic and gene regulatory map in adult macaque basal ganglia cells.

Project description:BackgroundThe basal ganglia are a complex of interconnected subcortical structures located beneath the mammalian cerebral cortex. The degeneration of dopaminergic neurons in the basal ganglia is the primary pathological feature of Parkinson's disease. Due to a lack of integrated analysis of multiomics datasets across multiple basal ganglia brain regions, very little is known about the regulatory mechanisms of this area.FindingsWe utilized high-throughput transcriptomic and epigenomic analysis to profile over 270,000 single-nucleus cells to create a cellular atlas of the basal ganglia, characterizing the cellular composition of 4 regions of basal ganglia in adult macaque brain, including the striatum, substantia nigra (SN), globus pallidum, and amygdala. We found a distinct epigenetic regulation on gene expression of neuronal and nonneuronal cells across regions in basal ganglia. We identified a cluster of SN-specific astrocytes associated with neurodegenerative diseases and further explored the conserved and primate-specific transcriptomics in SN cell types across human, macaque, and mouse. Finally, we integrated our epigenetic landscape of basal ganglia cells with human disease heritability and identified a regulatory module consisting of candidate cis-regulatory elements that are specific to medium spiny neurons and associated with schizophrenia.ConclusionsIn general, our macaque basal ganglia atlas provides valuable insights into the comprehensive transcriptome and epigenome of the most important and populous cell populations in the macaque basal ganglia. We have identified 49 cell types based on transcriptomic profiles and 47 cell types based on epigenomic profiles, some of which exhibit region specificity, and characterized the molecular relationships underlying these brain regions.

| S-EPMC10716911 | biostudies-literature

An interpretable multiparametric radiomics model of basal ganglia to predict dementia conversion in Parkinson's disease.

Project description:Cognitive impairment in Parkinson's disease (PD) severely affects patients' prognosis, and early detection of patients at high risk of dementia conversion is important for establishing treatment strategies. We aimed to investigate whether multiparametric MRI radiomics from basal ganglia can improve the prediction of dementia development in PD when integrated with clinical profiles. In this retrospective study, 262 patients with newly diagnosed PD (June 2008-July 2017, follow-up >5 years) were included. MRI radiomic features (n = 1284) were extracted from bilateral caudate and putamen. Two models were developed to predict dementia development: (1) a clinical model-age, disease duration, and cognitive composite scores, and (2) a combined clinical and radiomics model. The area under the receiver operating characteristic curve (AUC) were calculated for each model. The models' interpretabilities were studied. Among total 262 PD patients (mean age, 68 years ± 8 [standard deviation]; 134 men), 51 (30.4%), and 24 (25.5%) patients developed dementia within 5 years of PD diagnosis in the training (n = 168) and test sets (n = 94), respectively. The combined model achieved superior predictive performance compared to the clinical model in training (AUCs 0.928 vs. 0.894, P = 0.284) and test set (AUCs 0.889 vs. 0.722, P = 0.016). The cognitive composite scores of the frontal/executive function domain contributed most to predicting dementia. Radiomics derived from the caudate were also highly associated with cognitive decline. Multiparametric MRI radiomics may have an incremental prognostic value when integrated with clinical profiles to predict future cognitive decline in PD.

| S-EPMC10468504 | biostudies-literature

Vocal babbling in songbirds requires the basal ganglia-recipient motor thalamus but not the basal ganglia.

Project description:Young songbirds produce vocal "babbling," and the variability of their songs is thought to underlie a process of trial-and-error vocal learning. It is known that this exploratory variability requires the "cortical" component of a basal ganglia (BG) thalamocortical loop, but less understood is the role of the BG and thalamic components in this behavior. We found that large bilateral lesions to the songbird BG homolog Area X had little or no effect on song variability during vocal babbling. In contrast, lesions to the BG-recipient thalamic nucleus DLM (medial portion of the dorsolateral thalamus) largely abolished normal vocal babbling in young birds and caused a dramatic increase in song stereotypy. These findings support the idea that the motor thalamus plays a key role in the expression of exploratory juvenile behaviors during learning.

| S-EPMC3118735 | biostudies-literature

miR-9 regulates basal ganglia-dependent developmental vocal learning and adult vocal performance in songbirds.

Project description:miR-9 is an evolutionarily conserved miRNA that is abundantly expressed in Area X, a basal ganglia nucleus required for vocal learning in songbirds. Here, we report that overexpression of miR-9 in Area X of juvenile zebra finches impairs developmental vocal learning, resulting in a song with syllable omission, reduced similarity to the tutor song, and altered acoustic features. miR-9 overexpression in juveniles also leads to more variable song performance in adulthood, and abolishes social context-dependent modulation of song variability. We further show that these behavioral deficits are accompanied by downregulation of FoxP1 and FoxP2, genes that are known to be associated with language impairments, as well as by disruption of dopamine signaling and widespread changes in the expression of genes that are important in circuit development and functions. These findings demonstrate a vital role for miR-9 in basal ganglia function and vocal communication, suggesting that dysregulation of miR-9 in humans may contribute to language impairments and related neurodevelopmental disorders.

| S-EPMC5800847 | biostudies-literature

A disynaptic basal ganglia connection to the inferior olive: potential for basal ganglia influence on cerebellar learning.

Project description:Recent studies have shown that the cerebellum and the basal ganglia are interconnected at subcortical levels. However, a subcortical basal ganglia connection to the inferior olive (IO), being the source of the olivocerebellar climbing fiber system, is not known. We have used classical tracing with CTb, retrograde transneuronal infection with wildtype rabies virus, conditional tracing with genetically modified rabies virus, and examination of material made available by the Allen Brain Institute, to study potential basal ganglia connections to the inferior olive in rats and mice. We show in both species that parvalbumin-positive, and therefore GABAergic, neurons in the entopeduncular nucleus, representing the rodent equivalent of the internal part of the globus pallidus, innervate a group of cells that surrounds the fasciculus retroflexus and that are collectively known as the area parafascicularis prerubralis. As these neurons supply a direct excitatory input to large parts of the inferior olivary complex, we propose that the entopeduncular nucleus, as a main output station of the basal ganglia, provides an inhibitory influence on olivary excitability. As such, this connection may influence olivary involvement in cerebellar learning and/or could be involved in transmission of reward properties that have recently been established for olivocerebellar signaling.

| S-EPMC10196041 | biostudies-literature

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