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NeuroImage. Clinical 2022Cortical (e.g., Broca's area and Wernicke's area) and subcortical (e.g., putamen) language-related areas and executive control areas (e.g., inferior frontal gyrus (IFG),...
BACKGROUND AND HYPOTHESIS
Cortical (e.g., Broca's area and Wernicke's area) and subcortical (e.g., putamen) language-related areas and executive control areas (e.g., inferior frontal gyrus (IFG), dorsolateral prefrontal cortex (DLPFC)) show functional and structural dysconnectivity in long-term psychosis. We examined whether resting-state basal perfusion levels revealed selective pathophysiology (likely hypo- and hyper-activation) of language-related and executive areas in first-episode psychosis (FEP).
STUDY DESIGN
Basal resting-state perfusion was measured using pseudo-continuous Arterial Spin Labeling (pcASL). Relative cerebral blood flow (rCBF) was compared between 32 FEP and 34 matched healthy comparison (HC) individuals. Structural and functional MRI scans were acquired using a 3T Prisma scanner during the same session.
STUDY RESULTS
Whole-brain comparison of resting rCBF identified 8 clusters with significant between-group differences. Reduced rCBF was found in executive control areas in left and right IFG, right DLPFC, and right parietal cortex. Increased rCBF was found in left and right temporal cortex (including Wernicke's area), and left and right putamen. A positive correlation was observed between auditory hallucination severity and rCBF in the left putamen.
CONCLUSIONS
To the degree that perfusion implies activation, language and auditory processing areas in bilateral temporal lobe and putamen showed pathological hyper-activity, and cognitive control areas (IFG, DLPFC, right parietal) showed pathological hypo-activity in FEP at rest. Pathological basal activity was present across the range of symptom severity, suggesting it may be a common underlying pathology for psychosis that may be targeted with non-invasive brain stimulation to normalize resting activity levels.
Topics: Humans; Psychotic Disorders; Language; Brain Mapping; Temporal Lobe; Hallucinations; Magnetic Resonance Imaging
PubMed: 36451364
DOI: 10.1016/j.nicl.2022.103261 -
Human Brain Mapping Oct 2023Temporal lobe epilepsy (TLE) is associated with widespread brain alterations. Using quantitative susceptibility mapping (QSM) alongside transverse relaxation rate ( ),...
Temporal lobe epilepsy (TLE) is associated with widespread brain alterations. Using quantitative susceptibility mapping (QSM) alongside transverse relaxation rate ( ), we investigated regional brain susceptibility changes in 36 patients with left-sided (LTLE) or right-sided TLE (RTLE) secondary to hippocampal sclerosis, and 27 healthy controls (HC). We compared three susceptibility calculation methods to ensure image quality. Correlations of susceptibility and with age of epilepsy onset, frequency of focal-to-bilateral tonic-clonic seizures (FBTCS), and neuropsychological test scores were examined. Weak-harmonic QSM (WH-QSM) successfully reduced noise and removed residual background field artefacts. Significant susceptibility increases were identified in the left putamen in the RTLE group compared to the LTLE group, the right putamen and right thalamus in the RTLE group compared to HC, and a significant susceptibility decrease in the left hippocampus in LTLE versus HC. LTLE patients who underwent epilepsy surgery showed significantly lower left-versus-right hippocampal susceptibility. Significant changes were found between TLE and HC groups in the amygdala, putamen, thalamus, and in the hippocampus. Specifically, decreased R * was found in the left and right hippocampus in LTLE and RTLE, respectively, compared to HC. Susceptibility and were significantly correlated with cognitive test scores in the hippocampus, globus pallidus, and thalamus. FBTCS frequency correlated positively with ipsilateral thalamic and contralateral putamen susceptibility and with in bilateral globi pallidi. Age of onset was correlated with susceptibility in the hippocampus and putamen, and with in the caudate. Susceptibility and changes observed in TLE groups suggest selective loss of low-myelinated neurons alongside iron redistribution in the hippocampi, predominantly ipsilaterally, indicating QSM's sensitivity to local pathology. Increased susceptibility and in the thalamus and putamen suggest increased iron content and reflect disease severity.
Topics: Humans; Epilepsy, Temporal Lobe; Gray Matter; Brain Mapping; Functional Laterality; Hippocampus; Seizures; Magnetic Resonance Imaging
PubMed: 37493334
DOI: 10.1002/hbm.26432 -
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 -
Medical Physics Aug 2022Quantitative measures of dopamine transporter (DaT) uptake in caudate, putamen, and globus pallidus (GP) derived from dopamine transporter-single-photon emission...
BACKGROUND
Quantitative measures of dopamine transporter (DaT) uptake in caudate, putamen, and globus pallidus (GP) derived from dopamine transporter-single-photon emission computed tomography (DaT-SPECT) images have potential as biomarkers for measuring the severity of Parkinson's disease. Reliable quantification of this uptake requires accurate segmentation of the considered regions. However, segmentation of these regions from DaT-SPECT images is challenging, a major reason being partial-volume effects (PVEs) in SPECT. The PVEs arise from two sources, namely the limited system resolution and reconstruction of images over finite-sized voxel grids. The limited system resolution results in blurred boundaries of the different regions. The finite voxel size leads to TFEs, that is, voxels contain a mixture of regions. Thus, there is an important need for methods that can account for the PVEs, including the TFEs, and accurately segment the caudate, putamen, and GP, from DaT-SPECT images.
PURPOSE
Design and objectively evaluate a fully automated tissue-fraction estimation-based segmentation method that segments the caudate, putamen, and GP from DaT-SPECT images.
METHODS
The proposed method estimates the posterior mean of the fractional volumes occupied by the caudate, putamen, and GP within each voxel of a three-dimensional DaT-SPECT image. The estimate is obtained by minimizing a cost function based on the binary cross-entropy loss between the true and estimated fractional volumes over a population of SPECT images, where the distribution of true fractional volumes is obtained from existing populations of clinical magnetic resonance images. The method is implemented using a supervised deep-learning-based approach.
RESULTS
Evaluations using clinically guided highly realistic simulation studies show that the proposed method accurately segmented the caudate, putamen, and GP with high mean Dice similarity coefficients of ∼ 0.80 and significantly outperformed ( ) all other considered segmentation methods. Further, an objective evaluation of the proposed method on the task of quantifying regional uptake shows that the method yielded reliable quantification with low ensemble normalized root mean square error (NRMSE) < 20% for all the considered regions. In particular, the method yielded an even lower ensemble NRMSE of ∼ 10% for the caudate and putamen.
CONCLUSIONS
The proposed tissue-fraction estimation-based segmentation method for DaT-SPECT images demonstrated the ability to accurately segment the caudate, putamen, and GP, and reliably quantify the uptake within these regions. The results motivate further evaluation of the method with physical-phantom and patient studies.
Topics: Algorithms; Dopamine Plasma Membrane Transport Proteins; Humans; Magnetic Resonance Imaging; Parkinson Disease; Tomography, Emission-Computed, Single-Photon
PubMed: 35635327
DOI: 10.1002/mp.15778 -
Neurology International Mar 2021Although the putamen has a significant role in reward-seeking and motivated behaviors, including eating and food-seeking, minorities' diminished returns (MDRs) suggest...
INTRODUCTION
Although the putamen has a significant role in reward-seeking and motivated behaviors, including eating and food-seeking, minorities' diminished returns (MDRs) suggest that individual-level risk and protective factors have weaker effects for Non-Hispanic Black than Non-Hispanic White individuals. However, limited research is available on the relevance of MDRs in terms of the role of putamen functional connectivity on body mass index (BMI).
PURPOSE
Building on the MDRs framework and conceptualizing race and socioeconomic status (SES) indicators as social constructs, we explored racial and SES differences in the associations between putamen functional connectivity to the salience network and children's BMI.
METHODS
For this cross-sectional study, we used functional magnetic resonance imaging (fMRI) data of 6473 9-10-year-old Non-Hispanic Black and Non-Hispanic White children from the Adolescent Brain Cognitive Development (ABCD) study. The primary independent variable was putamen functional connectivity to the salience network, measured by fMRI. The primary outcome was the children's BMI. Age, sex, neighborhood income, and family structure were the covariates. Race, family structure, parental education, and household income were potential moderators. For data analysis, we used mixed-effect models in the overall sample and by race.
RESULTS
Higher right putamen functional connectivity to the salience network was associated with higher BMI in Non-Hispanic White children. The same association was missing for Non-Hispanic Black children. While there was no overall association in the pooled sample, a significant interaction was found, suggesting that the association between right putamen functional connectivity to the salience network and children's BMI was modified by race. Compared to Non-Hispanic White children, Non-Hispanic Black children showed a weaker association between right putamen functional connectivity to the salience network and BMI. While parental education and household income did not moderate our association of interest, marital status altered the associations between putamen functional connectivity to the salience network and children's BMI. These patterns were observed for right but not left putamen. Other/Mixed Race children also showed a pattern similar to Non-Hispanic Black children.
CONCLUSIONS
The association between right putamen functional connectivity to the salience network and children's BMI may depend on race and marital status but not parental education and household income. While right putamen functional connectivity to the salience network is associated with Non-Hispanic White children's BMI, Non-Hispanic Black children' BMI remains high regardless of their putamen functional connectivity to the salience network. This finding is in line with MDRs, which attributes diminished effects of individual-risk and protective factors for Non-Hispanic Black children to racism, stratification, and segregation.
PubMed: 33806587
DOI: 10.3390/neurolint13010009 -
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 -
Brain Sciences Dec 2022Dysfunction of the lenticular nucleus is thought to contribute to neurological symptoms in Wilson's disease (WD). However, very little is known about whether and how the...
Dysfunction of the lenticular nucleus is thought to contribute to neurological symptoms in Wilson's disease (WD). However, very little is known about whether and how the lenticular nucleus influences dystonia by interacting with the cerebral cortex and cerebellum. To solve this problem, we recruited 37 WD patients (20 men; age, 23.95 ± 6.95 years; age range, 12-37 years) and 37 age- and sex-matched healthy controls (HCs) (25 men; age, 25.19 ± 1.88 years; age range, 20-30 years), and each subject underwent resting-state functional magnetic resonance imaging (RS-fMRI) scans. The muscle biomechanical parameters and Unified Wilson Disease Rating Scale (UWDRS) were used to evaluate the level of dystonia and clinical representations, respectively. The lenticular nucleus, including the putamen and globus pallidus, was divided into 12 subregions according to dorsal, ventral, anterior and posterior localization and seed-based functional connectivity (FC) was calculated for each subregion. The relationships between FC changes in the lenticular nucleus with muscle tension levels and clinical representations were further investigated by correlation analysis. Dystonia was diagnosed by comparing all WD muscle biomechanical parameters with healthy controls (HCs). Compared with HCs, FC decreased from all subregions in the putamen except the right ventral posterior part to the middle cingulate cortex (MCC) and decreased FC of all subregions in the putamen except the left ventral anterior part to the cerebellum was observed in patients with WD. Patients with WD also showed decreased FC of the left globus pallidus primarily distributed in the MCC and cerebellum and illustrated decreased FC from the right globus pallidus to the cerebellum. FC from the putamen to the MCC was significantly correlated with psychiatric symptoms. FC from the putamen to the cerebellum was significantly correlated with muscle tension and neurological symptoms. Additionally, the FC from the globus pallidus to the cerebellum was also associated with muscle tension. Together, these findings highlight that lenticular nucleus-cerebellum circuits may serve as neural biomarkers of dystonia and provide implications for the neural mechanisms underlying dystonia in WD.
PubMed: 36671989
DOI: 10.3390/brainsci13010007 -
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 -
Scientific Reports Jan 2021Individuals with Rett syndrome (RTT) commonly demonstrate Parkinsonian features and dystonia at teen age; however, the pathological reason remains unclear. Abnormal iron...
Individuals with Rett syndrome (RTT) commonly demonstrate Parkinsonian features and dystonia at teen age; however, the pathological reason remains unclear. Abnormal iron accumulation in deep gray matter were reported in some Parkinsonian-related disorders. In this study, we investigated the iron accumulation in deep gray matter of RTT and its correlation with dystonia severity. We recruited 18 RTT-diagnosed participants with MECP2 mutations, from age 4 to 28, and 28 age-gender matched controls and investigated the iron accumulation by susceptibility weighted image (SWI) in substantia nigra (SN), globus pallidus (GP), putamen, caudate nucleus, and thalamus. Pearson's correlation was applied for the relation between iron accumulation and dystonia severity. In RTT, the severity of dystonia scales showed significant increase in subjects older than 10 years, and the contrast ratios of SWI also showed significant differences in putamen, caudate nucleus and the average values of SN, putamen, and GP between RTT and controls. The age demonstrated moderate to high negative correlations with contrast ratios. The dystonia scales were correlated with the average contrast ratio of SN, putamen and GP, indicating iron accumulation in dopaminergic system and related grey matter. As the first SWI study for RTT individuals, we found increased iron deposition in dopaminergic system and related grey matter, which may partly explain the gradually increased dystonia.
Topics: Adolescent; Adult; Brain Mapping; Case-Control Studies; Child; Child, Preschool; Dystonic Disorders; Female; Gray Matter; Humans; Iron; Iron Overload; Magnetic Resonance Imaging; Methyl-CpG-Binding Protein 2; Mutation; Rett Syndrome; Severity of Illness Index; Young Adult
PubMed: 33436916
DOI: 10.1038/s41598-020-80723-1 -
Frontiers in Aging Neuroscience 2022The efficacy of clinical interventions for post-stroke spasticity (PSS) has been consistently unsatisfactory, probably because lesions causing PSS may occur at different...
OBJECTIVE
The efficacy of clinical interventions for post-stroke spasticity (PSS) has been consistently unsatisfactory, probably because lesions causing PSS may occur at different locations in the brain, leaving the neuroanatomical substrates of spasticity unclear. Here, we investigated whether heterogeneous lesions causing PSS were localized to a common brain network and then identified the key nodes in this network.
METHODS
We used 32 cases of PSS and the Human Connectome dataset ( = 1,000), using a lesion network mapping method to identify the brain regions that were associated with each lesion in patients with PSS. Functional connectivity maps of all lesions were overlaid to identify common connectivity. Furthermore, a split-half replication method was used to evaluate reproducibility. Then, the lesion network mapping results were compared with those of patients with post-stroke non-spastic motor dysfunction ( = 29) to assess the specificity. Next, both sensitive and specific regions associated with PSS were identified using conjunction analyses, and the correlation between these regions and PSS was further explored by correlation analysis.
RESULTS
The lesions in all patients with PSS were located in different cortical and subcortical locations. However, at least 93% of these lesions (29/32) had functional connectivity with the bilateral putamen and globus pallidus. These connections were highly repeatable and specific, as compared to those in non-spastic patients. In addition, the functional connectivity between lesions and bilateral putamen and globus pallidus in patients with PSS was positively correlated with the degree of spasticity.
CONCLUSION
We identified that lesions causing PSS were localized to a common functional connectivity network defined by connectivity to the bilateral putamen and globus pallidus. This network may best cover the locations of lesions causing PSS. The putamen and globus pallidus may be potential key regions in PSS. Our findings complement previous neuroimaging studies on PSS, contributing to identifying patients with stroke at high risk for spasticity at an early stage, and may point to PSS-specific brain stimulation targets.
PubMed: 36389077
DOI: 10.3389/fnagi.2022.1011812