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Clinical Parkinsonism & Related... 2023Most commonly, hemichorea associated with nonketotic and ketotic hyperglycemia resolves with normalization of blood glucose. Herein, we present a case of hyperosmolar...
Most commonly, hemichorea associated with nonketotic and ketotic hyperglycemia resolves with normalization of blood glucose. Herein, we present a case of hyperosmolar hyperglycemic left hemichoreoathetosis-hemidystonia that has persisted for over 1 year. The subject presented to the emergency room with dysarthria and manifested left hemichoreoathetosis-hemidystonia within 36 h of admission. Initial computed tomography (CT) showed hyperdensity in the right putamen and left caudate. Magnetic resonance imaging (MRI) showed T1 hyperintensity within the right putamen. Failure to detect these classic imaging abnormalities during hospitalization resulted in a delayed etiologic diagnosis. Modest symptomatic improvement in the severity of hemichoreoathetosis-hemidystonia has been noted with low dose tetrabenazine.
PubMed: 37927362
DOI: 10.1016/j.prdoa.2023.100221 -
Journal of Huntington's Disease 2023Huntington's disease (HD) is a genetic neurodegenerative disease caused by trinucleotide repeat CAG expansions in the human HTT gene. Early onset juvenile HD (JHD) in...
BACKGROUND
Huntington's disease (HD) is a genetic neurodegenerative disease caused by trinucleotide repeat CAG expansions in the human HTT gene. Early onset juvenile HD (JHD) in children is the most severe form of the disease caused by high CAG repeat numbers of the HTT gene.
OBJECTIVE
To gain understanding of human HD mechanisms hypothesized to involve dysregulated proteomes of brain regions that regulate motor and cognitive functions, this study analyzed the proteomes of human JHD cortex and putamen brain regions compared to age-matched controls.
METHODS
JHD and age-matched control brain tissues were assessed for CAG repeat numbers of HTT by PCR. Human brain JHD brain cortex regions of BA4 and BA6 with the putamen region (n = 5) were analyzed by global proteomics, compared to age-matched controls (n = 7). Protein interaction pathways were assessed by gene ontology (GO), STRING-db, and KEGG bioinformatics.
RESULTS
JHD brain tissues were heterozygous for one mutant HTT allele containing 60 to 120 CAG repeats, and one normal HTT allele with 10 to 19 CAG repeats. Proteomics data for JHD brain regions showed dysregulated mitochondrial energy pathways and changes in synaptic systems including peptide neurotransmitters. JHD compared to control proteomes of cortex and putamen displayed (a) proteins present only in JHD, (b) proteins absent in JHD, and (c) proteins that were downregulated or upregulated.
CONCLUSIONS
Human JHD brain cortex and putamen regions display significant dysregulation of proteomes representing deficits in mitochondrial and synaptic neurotransmission functions. These findings advance understanding of JHD brain molecular mechanisms associated with HD disabilities.
Topics: Child; Humans; Putamen; Proteome; Huntington Disease; Neurodegenerative Diseases; Brain; Neuropeptides
PubMed: 38108356
DOI: 10.3233/JHD-230577 -
Cerebral Cortex (New York, N.Y. : 1991) Oct 2023Inhibition is a core executive cognitive function. However, the neural correlates of non-motor inhibitory control are not well understood. We investigated this question...
Inhibition is a core executive cognitive function. However, the neural correlates of non-motor inhibitory control are not well understood. We investigated this question using functional Magnetic Resonance Imaging (fMRI) and a simple Count Go/NoGo task (n = 23), and further explored the causal relationships between activated brain regions. We found that the Count NoGo task activated a distinct pattern in the subcortical basal ganglia, including bilateral ventral anterior/lateral nucleus of thalamus (VA/VL), globus pallidus/putamen (GP/putamen), and subthalamic nucleus (STN). Stepwise regressions and mediation analyses revealed that activations in these region(s) were modulated differently by only 3 cortical regions i.e. the right inferior frontal gyrus/insula (rIFG/insula), along with left IFG/insula, and anterior cingulate cortex/supplementary motor area (ACC/SMA). The activations of bilateral VA/VL were modulated by both rSTN and rIFG/insula (with rGP/putamen as a mediator) independently, and the activation of rGP/putamen was modulated by ACC/SMA, with rIFG/insula as a mediator. Our findings provide the neural correlates of inhibitory control of counting and causal relationships between them, and strongly suggest that both indirect and hyperdirect pathways of the basal ganglia are involved in the Count NoGo condition.
Topics: Magnetic Resonance Imaging; Brain Mapping; Brain; Subthalamic Nucleus; Executive Function
PubMed: 37724423
DOI: 10.1093/cercor/bhad336 -
Neuroscience Apr 2020We aimed to clarify the mechanisms of neural plasticity involved in language. We hypothesized that alterations which occur in bilinguals could reflect the mechanisms of...
We aimed to clarify the mechanisms of neural plasticity involved in language. We hypothesized that alterations which occur in bilinguals could reflect the mechanisms of acquisition of a second language and simulate neural plasticity related to language. We compared spatial characteristics of story listening-related hemodynamic modulations and subcortical fiber networks between monolinguals and bilinguals. Participants were Japanese monolinguals and Japanese-English bilinguals whose first language was Japanese. We divided bilinguals into early and late bilinguals depending on whether the age of acquisition was before after 7 years of age. We applied intergroup analysis to investigate the following: (1) blood oxygen level-dependent response (BOLD) responses during story listening by block-based fMRI; (2) number of fibers (NOFs) between specific edges by DTI. Both bilingual samples showed larger BOLD responses (BRs) in the right putamen and bilateral superior temporal gyri compared to the Japanese monolinguals in fMRI. Late bilinguals demonstrated bigger BRs in the right anterior temporal lobe and left medial parietal lobe than early bilinguals. Early bilinguals showed a higher NOFs between the right putamen and precentral gyrus than monolinguals and late bilinguals in DTI. Late bilinguals showed a lower NOFs between the left superior temporal gyrus and supramarginal gyrus than monolinguals and early bilinguals. Early bilinguals reinforce the subcortical fiber network between the right putamen and precentral gyrus, and activate the right putamen to gain alternative language function. We conclude that these key cerebral regions and subcortical fiber networks could contribute to the neural plasticity of language.
Topics: Child; Connectome; Humans; Japan; Language; Magnetic Resonance Imaging; Multilingualism
PubMed: 32027993
DOI: 10.1016/j.neuroscience.2020.01.030 -
Life (Basel, Switzerland) Dec 2022The objective of this study was to analyze the neurostructural abnormalities of brain areas responsible for the acquisition and maintenance of fear in small animal...
The objective of this study was to analyze the neurostructural abnormalities of brain areas responsible for the acquisition and maintenance of fear in small animal phobia by comparing gray matter volume (GMV) in individuals with phobia and non-fearful controls. Structural magnetic resonance imaging was obtained from 62 adults (79% female) assigned to one of two groups: 31 were diagnosed with small animal phobia and 31 were non-fearful controls. To investigate structural alterations, a whole-brain voxel-based morphometry analysis was conducted to compare the GMV of the brain areas involved in fear between both groups. The results indicated that individuals with a small animal specific phobia showed smaller GMV in cortical regions, such as the orbitofrontal (OFC) and medial frontal cortex, and greater GMV in the putamen than non-fearful controls. These brain areas are responsible for avoidant behavior (putamen) and emotional regulation processes or inhibitory control (prefrontal cortex (PFC)), which might suggest a greater vulnerability of phobic individuals to acquiring non-adaptive conditioned responses and emotional dysregulation. The findings provide preliminary support for the involvement of structural deficits in OFC and medial frontal cortex in phobia, contributing to clarify the neurobiological substrates for phobias.
PubMed: 36676068
DOI: 10.3390/life13010119 -
Frontiers in Neuroscience 2021Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker...
Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan). We retrospectively identified 47 patients (17 Alzheimer's dementia, 10 idiopathic Parkinson's disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores. DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right < 0.01, putamen right < 0.05, left < 0.05) and between pNfH and putamen (right < 0.05; left < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results. We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases.
PubMed: 34924923
DOI: 10.3389/fnins.2021.690013 -
Aging Cell Jul 2023Age is a major risk factor for neurodegenerative diseases. Shortening of leucocyte telomeres with advancing age, arguably a measure of "biological" age, is a known...
Age is a major risk factor for neurodegenerative diseases. Shortening of leucocyte telomeres with advancing age, arguably a measure of "biological" age, is a known phenomenon and epidemiologically correlated with age-related disease. The main mechanism of telomere shortening is cell division, rendering telomere length in post-mitotic cells presumably stable. Longitudinal measurement of human brain telomere length is not feasible, and cross-sectional cortical brain samples so far indicated no attrition with age. Hence, age-related changes in telomere length in the brain and the association between telomere length and neurodegenerative diseases remain unknown. Here, we demonstrate that mean telomere length in the putamen, a part of the basal ganglia, physiologically shortens with age, like leukocyte telomeres. This was achieved by using matched brain and leukocyte-rich spleen samples from 98 post-mortem healthy human donors. Using spleen telomeres as a reference, we further found that mean telomere length was brain region-specific, as telomeres in the putamen were significantly shorter than in the cerebellum. Expression analyses of genes involved in telomere length regulation and oxidative phosphorylation revealed that both region- and age-dependent expression pattern corresponded with region-dependent telomere length dynamics. Collectively, our results indicate that mean telomere length in the human putamen physiologically shortens with advancing age and that both local and temporal gene expression dynamics correlate with this, pointing at a potential mechanism for the selective, age-related vulnerability of the nigro-striatal network.
Topics: Humans; Putamen; Cross-Sectional Studies; Telomere Shortening; Risk Factors; Telomere
PubMed: 37129365
DOI: 10.1111/acel.13861 -
The European Journal of Neuroscience Jan 2022Repetitive transcranial magnetic stimulation (rTMS) holds the ability to modulate the connectivity within the stimulated network. However, whether and how the rTMS... (Randomized Controlled Trial)
Randomized Controlled Trial
Repetitive transcranial magnetic stimulation (rTMS) holds the ability to modulate the connectivity within the stimulated network. However, whether and how the rTMS targeted over the primary motor cortex (M1) could affect the connectivity within the sensorimotor network (SMN) is not fully elucidated. Hence, in this study, we investigated the after-effects of rTMS over left M1 at different frequencies on connectivity within SMN. Forty-five healthy participants were recruited and randomly divided into three groups according to rTMS frequencies (high-frequency [HF], 3 Hz; low-frequency [LF], 1 Hz; and SHAM). Participants received 1-Hz, 3-Hz or sham stimulation and underwent two functional magnetic resonance imaging (fMRI) scanning sessions before and after rTMS intervention. Using resting-state functional connectivity (FC) approach, we found that high- and low-frequency rTMS had opposing effects on FC within the SMN, especially for connectivity with subcortical regions (i.e., putamen, thalamus and cerebellum). Specifically, the reductions in connectivity between cortical and subcortical regions within cortico-basal ganglia thalamo-cortical circuits and the cognitive loop of cerebellum, and increased connectivity between cortical and subdivisions within the sensorimotor loop of cerebellum were observed after high-frequency rTMS intervention, whereas the thalamus and cognitive cerebellum subdivisions exhibited increased connectivity, and sensorimotor cerebellum subdivisions showed decreased connectivity with stimulated target after low-frequency stimulation. Collectively, these findings demonstrated the alterations of connectivity within SMN after rTMS intervention at different frequencies and may help to understand the mechanisms of rTMS treatment for movement disorders associated with deficits in subcortical regions such as Parkinson's disease, Huntington's disease and Tourette's syndrome.
Topics: Cerebellum; Humans; Magnetic Resonance Imaging; Parkinson Disease; Putamen; Transcranial Magnetic Stimulation
PubMed: 34905661
DOI: 10.1111/ejn.15571 -
Cerebral Cortex (New York, N.Y. : 1991) Nov 2022The morphological development of the fetal striatum during the second trimester has remained poorly described. We manually segmented the striatum using 7.0-T MR images...
The morphological development of the fetal striatum during the second trimester has remained poorly described. We manually segmented the striatum using 7.0-T MR images of the fetal specimens ranging from 14 to 22 gestational weeks. The global development of the striatum was evaluated by volume measurement. The absolute volume (Vabs) of the caudate nucleus (CN) increased linearly with gestational age, while the relative volume (Vrel) showed a quadratic growth. Both Vabs and Vrel of putamen increased linearly. Through shape analysis, the changes of local structure in developing striatum were specifically demonstrated. Except for the CN tail, the lateral and medial parts of the CN grew faster than the middle regions, with a clear rostral-caudal growth gradient as well as a distinct "outside-in" growth gradient. For putamen, the dorsal and ventral regions grew obviously faster than the other regions, with a dorsal-ventral bidirectional developmental pattern. The right CN was larger than the left, whereas there was no significant hemispheric asymmetry in the putamen. By establishing the developmental trajectories, spatial heterochrony, and hemispheric dimorphism of human fetal striatum, these data bring new insight into the fetal striatum development and provide detailed anatomical references for future striatal studies.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, Second; Corpus Striatum; Caudate Nucleus; Putamen; Sex Characteristics
PubMed: 35078212
DOI: 10.1093/cercor/bhab532 -
Brain : a Journal of Neurology Apr 2023The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is...
The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.
Topics: Humans; Magnetic Resonance Imaging; Prefrontal Cortex; Obsessive-Compulsive Disorder; Nucleus Accumbens; Putamen; Brain Mapping
PubMed: 36380526
DOI: 10.1093/brain/awac425