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Developmental Science Sep 2018The goal of the present study was to examine differences in cortical thickness, cortical surface area, and subcortical volume between bilingual children who are highly...
The goal of the present study was to examine differences in cortical thickness, cortical surface area, and subcortical volume between bilingual children who are highly proficient in two languages (i.e., English and Spanish) and bilingual children who are mainly proficient in one of the languages (i.e., Spanish). All children (N = 49) learned Spanish as a native language (L1) at home and English as a second language (L2) at school. Proficiency of both languages was assessed using the standardized Woodcock Language Proficiency Battery. Five-minute high-resolution anatomical scans were acquired with a 3-Tesla scanner. The degree of discrepancy between L1 and L2 proficiency was used to classify the children into two groups: children with balanced proficiency and children with unbalanced proficiency. The groups were comparable on language history, parental education, and other variables except English proficiency. Values of cortical thickness and surface area of the transverse STG, IFG-pars opercularis, and MFG, as well as subcortical volume of the caudate and putamen, were extracted from FreeSurfer. Results showed that children with balanced bilingualism had thinner cortices of the left STG, left IFG, left MFG and a larger bilateral putamen, whereas unbalanced bilinguals showed thicker cortices of the same regions and a smaller putamen. Additionally, unbalanced bilinguals with stronger foreign accents in the L2 showed reduced surface areas of the MFG and STS bilaterally. The results suggest that balanced/unbalanced bilingualism is reflected in different neuroanatomical characteristics that arise from biological and/or environmental factors.
Topics: Adolescent; Age Factors; Broca Area; Caudate Nucleus; Child; Female; Hispanic or Latino; Humans; Language; Language Development; Learning; Male; Multilingualism; Putamen
PubMed: 29480569
DOI: 10.1111/desc.12654 -
Biological Psychiatry Jan 2023Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals with these illnesses also have major disruptions in sleep...
BACKGROUND
Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals with these illnesses also have major disruptions in sleep and circadian rhythms, and disturbances of sleep and circadian rhythms can precipitate or exacerbate psychotic symptoms. Psychosis is associated with the striatum, though to our knowledge, no study to date has directly measured molecular rhythms and determined how they are altered in the striatum of subjects with psychosis.
METHODS
We performed RNA sequencing and both differential expression and rhythmicity analyses to investigate diurnal alterations in gene expression in human postmortem striatal subregions (nucleus accumbens, caudate, and putamen) in subjects with psychosis (n = 36) relative to unaffected comparison subjects (n = 36).
RESULTS
Across regions, we found differential expression of immune-related transcripts and a substantial loss of rhythmicity in core circadian clock genes in subjects with psychosis. In the nucleus accumbens, mitochondrial-related transcripts had decreased expression in subjects with psychosis, but only in those who died at night. Additionally, we found a loss of rhythmicity in small nucleolar RNAs and a gain of rhythmicity in glutamatergic signaling in the nucleus accumbens of subjects with psychosis. Between-region comparisons indicated that rhythmicity in the caudate and putamen was far more similar in subjects with psychosis than in matched comparison subjects.
CONCLUSIONS
Together, these findings reveal differential and rhythmic gene expression differences across the striatum that may contribute to striatal dysfunction and psychosis in psychotic disorders.
Topics: Humans; Psychotic Disorders; Circadian Rhythm; Corpus Striatum; Putamen; Gene Expression
PubMed: 36302706
DOI: 10.1016/j.biopsych.2022.08.013 -
Brain : a Journal of Neurology Apr 2022The striatal dopaminergic deficit in Parkinson's disease exhibits a typical pattern, extending from the caudal and dorsal putamen at onset to its more rostral region as...
The striatal dopaminergic deficit in Parkinson's disease exhibits a typical pattern, extending from the caudal and dorsal putamen at onset to its more rostral region as the disease progresses. Clinically, upper-limb onset of cardinal motor features is the rule. Thus, according to current understanding of striatal somatotopy (i.e. the lower limb is dorsal to the upper limb) the assumed pattern of early dorsal striatal dopaminergic denervation in Parkinson's disease does not fit with an upper-limb onset. We have examined the topography of putaminal denervation in a cohort of 23 recently diagnosed de novo Parkinson's disease patients and 19 age-/gender-matched healthy subjects assessed clinically and by 18F-DOPA PET; 15 patients were re-assessed after 2 years. There was a net upper-limb predominance of motor features at onset. Caudal denervation of the putamen was confirmed in both the more- and less-affected hemispheres and corresponding hemibodies. Spatial covariance analysis of the most affected hemisphere revealed a pattern of 18F-DOPA uptake rate deficit that suggested focal dopamine loss starting in the posterolateral and intermediate putamen. Functional MRI group-activation maps during a self-paced motor task were used to represent the somatotopy of the putamen and were then used to characterize the decline in 18F-DOPA uptake rate in the upper- and lower-limb territories. This showed a predominant decrement in both hemispheres, which correlated significantly with severity of bradykinesia. A more detailed spatial analysis revealed a dorsoventral linear gradient of 18F-DOPA uptake rate in Parkinson's disease patients, with the highest putamen denervation in the caudal intermediate subregion (dorsoventral plane) compared to healthy subjects. The latter area coincides with the functional representation of the upper limb. Clinical motor assessment at 2-year follow-up showed modest worsening of parkinsonism in the primarily affected side and more noticeable increases in the upper limb in the less-affected side. Concomitantly, 18F-DOPA uptake rate in the less-affected putamen mimicked that recognized on the most-affected side. Our findings suggest that early dopaminergic denervation in Parkinson's disease follows a somatotopically related pattern, starting with the upper-limb representation in the putamen and progressing over a 2-year period in the less-affected hemisphere. These changes correlate well with the clinical presentation and evolution of motor features. Recognition of a precise somatotopic onset of nigrostriatal denervation may help to better understand the onset and progression of dopaminergic neurodegeneration in Parkinson's disease and eventually monitor the impact of putative therapies.
Topics: Child, Preschool; Corpus Striatum; Denervation; Dihydroxyphenylalanine; Dopamine; Humans; Parkinson Disease; Putamen
PubMed: 35349639
DOI: 10.1093/brain/awab378 -
Movement Disorders : Official Journal... Jul 2018Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective treatment for the motor symptoms of PD. However, chronic oral levodopa treatment can lead to various motor and nonmotor complications because of nonphysiological pulsatile dopaminergic stimulation in the brain. Examinations of autopsy cases with PD have revealed a decreased number of dendritic spines of striatal neurons. Animal models of PD have revealed altered density and morphology of dendritic spines of neurons in various brain regions after dopaminergic denervation or dopaminergic denervation plus levodopa treatment, indicating altered synaptic transmission. Recent studies using rodent models have reported dendritic spine head enlargement in the caudate-putamen, nucleus accumbens, primary motor cortex, and prefrontal cortex in cases where chronic levodopa treatment following dopaminergic denervation induced dyskinesia-like abnormal involuntary movement. Hypertrophy of spines results from insertion of alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid receptors into the postsynaptic membrane. Such spine enlargement indicates hypersensitivity of the synapse to excitatory inputs and is compatible with a lack of depotentiation, which is an electrophysiological hallmark of levodopa-induced dyskinesia found in the corticostriatal synapses of dyskinetic animals and the motor cortex of dyskinetic PD patients. This synaptic plasticity may be one of the mechanisms underlying the priming of levodopa-induced complications such as levodopa-induced dyskinesia and dopamine dysregulation syndrome. Drugs that could potentially prevent spine enlargement, such as calcium channel blockers, N-methyl-D-aspartate receptor antagonists, alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid receptor antagonists, and metabotropic glutamate receptor antagonists, are candidates for treatment of levodopa-induced complications in PD. © 2017 International Parkinson and Movement Disorder Society.
Topics: Animals; Antiparkinson Agents; Caudate Nucleus; Dendritic Spines; Dopaminergic Neurons; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease; Putamen
PubMed: 28880414
DOI: 10.1002/mds.27172 -
Addiction Biology Mar 2021The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely...
The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely implicated in the etiological processes of substance use disorders (SUD). Here, we aimed to identify robust and reliable associations between KTN1 SNPs and SUD across multiple samples. We examined the associations between SUD and KTN1 SNPs in four independent population-based or family-based samples (n = 10,209). The potential regulatory effects of the risk alleles on the putamen GMVs, the effects of alcohol, nicotine, marijuana and cocaine on KTN1 mRNA expression, and the relationship between KTN1 mRNA expression and SUD were explored. We found that a total of 23 SNPs were associated with SUD across at least two independent samples (1.4 × 10 ≤ p ≤ 0.049), including one SNP (rs12895072) across three samples (8.8 × 10 ≤ p ≤ 0.049). Four other SNPs were significantly or suggestively associated with SUD only in European-Australians (4.8 × 10 ≤ p ≤ 0.058). All of the SUD-risk alleles of these 27 SNPs increased (β > 0) the putamen GMVs and represented major alleles (f > 0.5) in Europeans. Twenty-two SNPs were potentially biologically functional. Alcohol, nicotine and cocaine significantly affected the KTN1 mRNA expression, and the KTN1 mRNA was differentially expressed between nicotine or cocaine dependent and control subjects. We concluded that there was a replicable and robust relationship among the KTN1 variants, KTN1 mRNA expression, putamen GMVs, molecular effects of substances, and SUD, suggesting that some risk KTN1 alleles might increase kinectin 1 expression in the putamen, altering putamen structures and functions, and leading to SUD.
Topics: Alcoholism; Alleles; Australia; Comorbidity; Female; Genetic Predisposition to Disease; Gray Matter; Humans; Male; Marijuana Abuse; Membrane Proteins; Polymorphism, Single Nucleotide; Putamen; RNA, Messenger; Substance-Related Disorders; Tobacco Use Disorder; White People
PubMed: 32115811
DOI: 10.1111/adb.12888 -
Biological Psychiatry Dec 2022The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how...
BACKGROUND
The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression.
METHODS
The study includes 115 second- and third-generation offspring at high or low risk for depression based on the presence or absence of major depressive disorder in the first generation. Offspring were followed longitudinally using semistructured clinical interviews blinded to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (N-acetylaspartate/creatine ratio), and functional MRI activity modulated by valence and arousal components of a mood induction task, respectively.
RESULTS
After adjusting for covariates, the high-risk individuals had lower putamen volume (standardized betas, β- = -0.17, β- = -0.15, ps = .002), N-acetylaspartate/creatine ratio (β-= -0.40, β-= -0.37, ps < .0001), and activation modulated by valence (β- = -0.22, β- = -0.27, ps < .05) than low-risk individuals. Volume differences were greater at younger ages, and N-acetylaspartate/creatine ratio differences were greater at older ages. Lower putamen volume also predicted major depressive disorder episodes up to 8 years after the scan (β- = -0.72, p = .013; β- = -0.83, p = .037). Magnetic resonance spectroscopy and task functional MRI measures were modestly correlated (0.27 ≤ r ≤ 0.33).
CONCLUSIONS
Findings demonstrate abnormalities in putamen structure and function in individuals at high risk for major depressive disorder. Future studies should focus on this region as a potential biomarker for depressive illness, noting meanwhile that differences attributable to family history may peak at different ages based on which MRI modality is being used to assay them.
Topics: Humans; Putamen; Depressive Disorder, Major; Creatine; Depression; Genetic Predisposition to Disease; Prospective Studies; Magnetic Resonance Imaging; Multimodal Imaging
PubMed: 36038379
DOI: 10.1016/j.biopsych.2022.06.035 -
Neuropsychopharmacology : Official... Nov 2022Dysregulation of frontal cortical inputs to the striatum is foundational in the neural basis of substance use disorder (SUD). Neuroanatomical and electrophysiological...
Dysregulation of frontal cortical inputs to the striatum is foundational in the neural basis of substance use disorder (SUD). Neuroanatomical and electrophysiological data increasingly show that striatal nodes receive appreciable input from numerous cortical areas, and that the combinational properties of these multivariate "connectivity profiles" play a predominant role in shaping striatal activity and function. Yet, how abnormal configuration of striatal connectivity profiles might contribute to SUD is unknown. Here, we implemented a novel "connectivity profile analysis" (CPA) approach using resting-state functional connectivity data to facilitate detection of different types of connectivity profile "misconfiguration" that may reflect distinct forms of aberrant circuit plasticity in SUD. We examined 46 nicotine-dependent smokers and 33 non-smokers and showed that both dorsal striatum (DS) and ventral striatum (VS) connectivity profiles with frontal cortex were misconfigured in smokers-but in doubly distinct fashions. DS misconfigurations were stable across sated and acute abstinent states (indicative of a "trait" circuit adaptation) whereas VS misconfigurations emerged only during acute abstinence (indicative of a "state" circuit adaptation). Moreover, DS misconfigurations involved abnormal connection strength rank order arrangement, whereas VS misconfigurations involved abnormal aggregate strength. We found that caudal ventral putamen in smokers uniquely displayed multiple types of connectivity profile misconfiguration, whose interactive magnitude was linked to dependence severity, and that VS misconfiguration magnitude correlated positively with withdrawal severity during acute abstinence. Findings underscore the potential for approaches that more aptly model the neurobiological composition of corticostriatal circuits to yield deeper insights into the neural basis of SUD.
Topics: Brain Mapping; Corpus Striatum; Humans; Magnetic Resonance Imaging; Neural Pathways; Nicotine; Putamen; Substance-Related Disorders; Ventral Striatum
PubMed: 35752682
DOI: 10.1038/s41386-022-01366-6 -
Schizophrenia Research Nov 2022The aim of this paper is to summarize ultrastructural evidence for glutamatergic dysregulation in several linked regions in postmortem schizophrenia brain. Following a...
The aim of this paper is to summarize ultrastructural evidence for glutamatergic dysregulation in several linked regions in postmortem schizophrenia brain. Following a brief summary of glutamate circuitry and how synapses are identified at the electron microscopic (EM) level, we will review EM pathology in the cortex and basal ganglia. We will include the effects of antipsychotic drugs and the relation of treatment response. We will discuss how these findings support or confirm other postmortem findings as well as imaging results. Briefly, synaptic and mitochondrial density in anterior cingulate cortex was decreased in schizophrenia, versus normal controls (NCs), in a selective layer specific pattern. In dorsal striatum, increases in excitatory synaptic density were detected in caudate matrix, a compartment associated with cognitive and motor function, and in the putamen patches, a region associated with limbic function and in the core of the nucleus accumbens. Patients who were treatment resistant or untreated had significantly elevated numbers of excitatory synapses in limbic striatal areas in comparison to NCs and responders. Protein levels of vGLUT2, found in subcortical glutamatergic neurons, were increased in the nucleus accumbens in schizophrenia. At the EM level, schizophrenia subjects had an increase in density of excitatory synapses in several areas of the basal ganglia. In the substantia nigra, the protein levels of vGLUT2 were elevated in untreated patients compared to NCs. The density of inhibitory synapses was decreased in schizophrenia versus NCs. In schizophrenia, glutamatergic synapses are differentially affected depending on the brain region, treatment status, and treatment response.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Synapses; Corpus Striatum; Putamen
PubMed: 32014360
DOI: 10.1016/j.schres.2020.01.016 -
NeuroImage. Clinical 2018Preliminary evidence from postmortem studies of X-linked dystonia-parkinsonism (XDP) suggests tissue loss may occur first and/or most severely in the striatal striosome...
Preliminary evidence from postmortem studies of X-linked dystonia-parkinsonism (XDP) suggests tissue loss may occur first and/or most severely in the striatal striosome compartment, followed later by cell loss in the matrix compartment. However, little is known about how this relates to pathogenesis and pathophysiology. While MRI cannot visualize these striatal compartments directly in humans, differences in relative gradients of afferent cortical connectivity across compartments (weighted toward paralimbic versus sensorimotor cortex, respectively) can be used to infer potential selective loss in vivo. In the current study we evaluated relative connectivity of paralimbic versus sensorimotor cortex with the caudate and putamen in 17 individuals with XDP and 17 matched controls. Although caudate and putamen volumes were reduced in XDP, there were no significant reductions in either "matrix-weighted", or "striosome-weighted" connectivity. In fact, paralimbic connectivity with the putamen was elevated, rather than reduced, in XDP. This was driven most strongly by elevated putamen connectivity with the anterior insula. There was no relationship of these findings to disease duration or striatal volume, suggesting insula and/or paralimbic connectivity in XDP may develop abnormally and/or increase in the years before symptom onset.
Topics: Adult; Brain Mapping; Case-Control Studies; Cerebral Cortex; Cohort Studies; Dystonic Disorders; Female; Functional Laterality; Genetic Diseases, X-Linked; Humans; Image Processing, Computer-Assisted; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways; Putamen; Severity of Illness Index
PubMed: 29527488
DOI: 10.1016/j.nicl.2017.10.025 -
Proceedings of the National Academy of... Jan 2021The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). Each of these structures have some overlapping and some distinct functions...
The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). Each of these structures have some overlapping and some distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a "time-of-death" approach to identify diurnal rhythms in RNA transcripts in human cortical regions. Here, we identify molecular rhythms across the three striatal subregions collected from postmortem human brain tissue in subjects without psychiatric or neurological disorders. Core circadian clock genes are rhythmic across all three regions and show strong phase concordance across regions. However, the putamen contains a much larger number of significantly rhythmic transcripts than the other two regions. Moreover, there are many differences in pathways that are rhythmic across regions. Strikingly, the top rhythmic transcripts in NAc (but not the other regions) are predominantly small nucleolar RNAs and long noncoding RNAs, suggesting that a completely different mechanism might be used for the regulation of diurnal rhythms in translation and/or RNA processing in the NAc versus the other regions. Further, although the NAc and putamen are generally in phase with regard to timing of expression rhythms, the NAc and caudate, and caudate and putamen, have several clusters of discordant rhythmic transcripts, suggesting a temporal wave of specific cellular processes across the striatum. Taken together, these studies reveal distinct transcriptome rhythms across the human striatum and are an important step in helping to understand the normal function of diurnal rhythms in these regions and how disruption could lead to pathology.
Topics: Brain; Circadian Clocks; Circadian Rhythm; Humans; Nucleus Accumbens; Putamen; Transcriptome; Ventral Striatum
PubMed: 33372142
DOI: 10.1073/pnas.2016150118