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Cerebral Cortex Communications 2020Ventrolateral frontal area 44 is implicated in inhibitory motor functions and facilitating prefrontal control over vocalization. The contribution of corticostriatal...
Ventrolateral frontal area 44 is implicated in inhibitory motor functions and facilitating prefrontal control over vocalization. The contribution of corticostriatal circuits to area 44 functions is unclear, as prior investigation of area 44 projections to the striatum-a central structure in motor circuits-is limited. Here, we used anterograde and retrograde tracing in macaques to map the innervation zone of area 44 corticostriatal projections, quantify their strengths, and evaluate their convergence with corticostriatal projections from other frontal cortical regions. First, whereas terminal fields from a rostral area 44 injection site were found primarily in the central caudate nucleus, those from a caudal area 44 injection site were found primarily in the ventrolateral putamen. Second, amongst sampled injection sites, area 44 input as a percentage of total frontal cortical input was highest in the ventral putamen at the level of the anterior commissure. Third, area 44 projections converged with orofacial premotor area 6VR and other motor-related projections (in the putamen), and with nonmotor prefrontal projections (in the caudate nucleus). Findings support the role of area 44 as an interface between motor and nonmotor functional domains, possibly facilitated by rostral and caudal area 44 subregions with distinct corticostriatal connectivity profiles.
PubMed: 33283184
DOI: 10.1093/texcom/tgaa079 -
EJNMMI Research Jun 2022We hypothesised that the radiomics signature, which includes texture information of dopamine transporter single-photon emission computed tomography (DAT-SPECT) images...
BACKGROUND
We hypothesised that the radiomics signature, which includes texture information of dopamine transporter single-photon emission computed tomography (DAT-SPECT) images for Parkinson's disease (PD), may assist semi-quantitative indices. Herein, we constructed a radiomics signature using DAT-SPECT-derived radiomics features that effectively discriminated PD from healthy individuals and evaluated its classification performance.
RESULTS
We analysed 413 cases of both normal control (NC, n = 101) and PD (n = 312) groups from the Parkinson's Progression Markers Initiative database. Data were divided into the training and two test datasets with different SPECT manufacturers. DAT-SPECT images were spatially normalised to the Montreal Neurologic Institute space. We calculated 930 radiomics features, including intensity- and texture-based features in the caudate, putamen, and pallidum volumes of interest. The striatum uptake ratios (SURs) of the caudate, putamen, and pallidum were also calculated as conventional semi-quantification indices. The least absolute shrinkage and selection operator was used for feature selection and construction of the radiomics signature. The four classification models were constructed using a radiomics signature and/or semi-quantitative indicator. Furthermore, we compared the classification performance of the semi-quantitative indicator alone and the combination with the radiomics signature for the classification models. The receiver operating characteristics (ROC) analysis was used to evaluate the classification performance. The classification performance of SUR was higher than that of other semi-quantitative indicators. The radiomics signature resulted in a slightly increased area under the ROC curve (AUC) compared to SUR in each test dataset. When combined with SUR and radiomics signature, all classification models showed slightly higher AUCs than that of SUR alone.
CONCLUSION
We constructed a DAT-SPECT image-derived radiomics signature. Performance analysis showed that the current radiomics signature would be helpful for the diagnosis of PD and has the potential to provide robust diagnostic performance.
PubMed: 35759054
DOI: 10.1186/s13550-022-00910-1 -
Brain and Behavior May 2022Abnormal brain network connectivity is strongly implicated in the pathogenesis of schizophrenia. The striatum, consisting of the caudate and putamen, is the major...
Abnormal brain network connectivity is strongly implicated in the pathogenesis of schizophrenia. The striatum, consisting of the caudate and putamen, is the major treatment target for antipsychotics, the primary treatments for schizophrenia; however, there are few studies on the functional connectivity (FC) of striatum in drug-naive early-onset schizophrenia (EOS) patients. We examined the FC values of the caudate nucleus and putamen with whole brain by resting-state functional magnetic resonance imaging (RS-fMRI) and the associations with indices of clinical severity. Patients demonstrated abnormal FC between subregions of the putamen and both the visual network (left middle occipital gyrus) and default mode network (bilateral anterior cingulate, left superior frontal, and right middle frontal gyri). Furthermore, FC between dorsorostral putamen and left superior frontal gyrus correlated with both positive symptom subscore and total score on the Positive and Negative Syndrome Scale (PANSS). These findings demonstrate abnormal FC between the striatum and other brain areas even in the early stages of schizophrenia, supporting neurodevelopmental disruption in disease etiology and expression.
Topics: Brain; Brain Mapping; Corpus Striatum; Humans; Magnetic Resonance Imaging; Schizophrenia
PubMed: 35384392
DOI: 10.1002/brb3.2535 -
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 -
CNS Neuroscience & Therapeutics Feb 2020Impairment of basal ganglia (BG)-thalamo-cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns...
OBJECTIVE
Impairment of basal ganglia (BG)-thalamo-cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns of putamen among PD subtypes and healthy control (HC) and explored their clinical significance.
METHODS
A total of 16 patients with tremor-dominant (TD) PD, 23 patients with postural instability and gait difficulty-dominant (PIGD) PD, and 31 HC that underwent functional magnetic resonance imaging were observed. Voxel-wise FC analysis was performed by computing correlation between bilateral putamen and other voxels within the brain. Correlation analysis was performed between FC strength and clinical symptoms.
RESULTS
Compared with PIGD group, TD group showed increased FC between left putamen and right cerebellum lobule VI and cerebellum crus I, then we compared the cerebellum FC difference among the three groups. The cerebellum lobule VI FC difference was mainly involved in motor related cortex, and the cerebellum crus I FC difference was related to cognition areas. While compared with HC, TD and PIGD groups both had significant FC difference brain areas correlated with motor and cognition symptoms. The connectively of putamen and right cerebellum lobules VI and I showed positive correlation with tremor and Montreal Cognitive Assessment degree of scores, respectively. The connectivity of putamen and sensorimotor cortex had negative correlation with PIGD scores.
CONCLUSIONS
The altered connectivity of BG-cortical circuit in patients with PD was related to PIGD symptoms. Motor and cognitive impairments declined slower in patients with TD PD, which may be related to increased functional connectivity between putamen and cerebellum.
Topics: Aged; Cerebellum; Cognition Disorders; Female; Gait Disorders, Neurologic; Humans; Magnetic Resonance Imaging; Male; Mental Status and Dementia Tests; Middle Aged; Motor Cortex; Neural Pathways; Parkinson Disease; Putamen; Tremor
PubMed: 31730272
DOI: 10.1111/cns.13259 -
Cells Aug 2020Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons from the substantia nigra (SN) that project to the dorsal striatum (caudate-putamen). To...
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons from the substantia nigra (SN) that project to the dorsal striatum (caudate-putamen). To better understand the molecular mechanisms underlying PD, we performed combined lipid profiling and RNA sequencing of SN and putamen samples from PD patients and age-matched controls. SN lipid analysis pointed to a neuroinflammatory component and included elevated levels of the endosomal lipid Bis (Monoacylglycero)Phosphate 42:8, while two of the three depleted putamen lipids were saturated sphingomyelin species. Remarkably, we observed gender-related differences in the SN and putamen lipid profiles. Transcriptome analysis revealed that the top-enriched pathways among the 354 differentially expressed genes (DEGs) in the SN were "protein folding" and "neurotransmitter transport", and among the 261 DEGs from putamen "synapse organization". Furthermore, we identified pathways, e.g., "glutamate signaling", and genes, encoding, e.g., an angiotensin receptor subtype or a proprotein convertase, that have not been previously linked to PD. The identification of 33 genes that were common among the SN and putamen DEGs, which included the α-synuclein paralog β-synuclein, may contribute to the understanding of general PD mechanisms. Thus, our proof-of-concept data highlights new genes, pathways and lipids that have not been explored before in the context of PD.
Topics: Aged; Aged, 80 and over; Female; Gene Expression Profiling; Humans; Lipids; Male; Parkinson Disease; Putamen; Substantia Nigra
PubMed: 32858884
DOI: 10.3390/cells9091966 -
NeuroImage. Clinical 2022Compulsive behaviors in obsessive-compulsive disorder (OCD) have been suggested to result from an imbalance in cortico-striatal connectivity. However, the nature of this...
BACKGROUND
Compulsive behaviors in obsessive-compulsive disorder (OCD) have been suggested to result from an imbalance in cortico-striatal connectivity. However, the nature of this impairment, the relative involvement of different striatal areas, their imbalance in genetically related but unimpaired individuals, and their relationship with cognitive dysfunction in OCD patients, remain unknown.
METHODS
In the current study, striatal (i.e., caudate and putamen) whole-brain connectivity was computed in a sample of OCD patients (OCD, n = 62), unaffected first-degree relatives (UFDR, n = 53) and healthy controls (HC, n = 73) by ROI-based resting-state functional magnetic resonance imaging (rs-fMRI). A behavioral task switch paradigm outside of the scanner was also performed to measure cognitive flexibility in OCD patients.
RESULTS
There were significantly increased strengths (Z-transformed Pearson correlation coefficient) in caudate connectivity in OCD patients. A significant correlation between the two types of connectivity strengths in the relevant regions was observed only in the OCD patient group. Furthermore, the caudate connectivity of patients was negatively associated with their task-switch performance.
CONCLUSIONS
The imbalance between the caudate and putamen connectivity, arising from the abnormal increase of caudate activity, may serve as a clinical characteristic for obsessive-compulsive disorder.
Topics: Brain Mapping; Corpus Striatum; Humans; Magnetic Resonance Imaging; Neural Pathways; Obsessive-Compulsive Disorder; Putamen
PubMed: 35717885
DOI: 10.1016/j.nicl.2022.103083 -
Schizophrenia Research Feb 2021Auditory hallucinations are a debilitating symptom of schizophrenia. Effective treatment is limited because the underlying neural mechanisms remain unknown. Our study...
Auditory hallucinations are a debilitating symptom of schizophrenia. Effective treatment is limited because the underlying neural mechanisms remain unknown. Our study investigates how local and long-range functional connectivity is associated with auditory perceptual disturbances (APD) in schizophrenia. APD was assessed using the Auditory Perceptual Trait and State Scale. Resting state fMRI data were collected for N=99 patients with schizophrenia. Local functional connectivity was estimated using regional homogeneity (ReHo) analysis; long-range connectivity was estimated using resting state functional connectivity (rsFC) analysis. Mediation analyses tested whether local (ReHo) connectivity significantly mediated associations between long-distance rsFC and APD. Severity of APD was significantly associated with reduced ReHo in left and right putamen, left temporoparietal junction (TPJ), and right hippocampus-pallidum. Higher APD was also associated with reduced rsFC between the right putamen and the contralateral putamen and auditory cortex. Local and long-distance connectivity measures together explained 40.3% of variance in APD (P < 0.001), with the strongest predictor being the left TPJ ReHo (P < 0.001). Additionally, TPJ ReHo significantly mediated the relationship between right putamen - left putamen rsFC and APD (Sobel test, P = 0.001). Our findings suggest that both local and long-range functional connectivity deficits contribute to APD, emphasizing the role of striatum and auditory cortex. Considering the translational impact of these circuit-based findings within the context of prior clinical trials to treat auditory hallucinations, we propose a model in which correction of both local and long-distance functional connectivity deficits may be necessary to treat auditory hallucinations.
Topics: Auditory Cortex; Hallucinations; Humans; Magnetic Resonance Imaging; Schizophrenia; Temporal Lobe
PubMed: 33493774
DOI: 10.1016/j.schres.2020.11.052 -
Parkinsonism & Related Disorders Apr 2021Microstructural integrity of the middle cerebellar peduncle (MCP) and the putamen captured by diffusion-tensor imaging (DTI) is differentially affected in the...
INTRODUCTION
Microstructural integrity of the middle cerebellar peduncle (MCP) and the putamen captured by diffusion-tensor imaging (DTI) is differentially affected in the parkinsonian and cerebellar variants of multiple system atrophy (MSA-P, MSA-C) compared to Parkinson's disease (PD). The current study applied DTI and tractography in order to 1) characterize the distribution of DTI metrics along the tracts of the MCP and from the putamen in MSA variants, and 2) evaluate the usefulness of combining these measures for the differential diagnosis of MSA-P against PD in the clinical setting.
METHODS
Twenty-nine MSA patients (MSA-C, n = 10; MSA-P, n = 19), with a mean disease duration of 2.8 ± 1.7 years, 19 PD patients, and 27 healthy controls (HC) were included in the study. Automatized tractography with a masking procedure was employed to isolate the MCP tracts. DTI measures along the tracts of the MCP and within the putamen were acquired and jointly used to classify MSA vs. PD, and MSA-P vs. PD. Putamen volume was additionally tested as classification feature in post hoc analyses.
RESULTS
DTI measures within the MCP and putamen showed significant alterations in MSA variants compared to HC and PD. Classification accuracy for MSA vs. PD and MSA-P vs PD using diffusion measures was 91.7% and 89.5%, respectively. When replacing the putaminal DTI measure by a normalized measure of putamen volume classification accuracy improved to 95.8% and 94.7%, respectively.
CONCLUSION
Multimodal information from MCP tractography and putamen volume yields excellent diagnostic accuracy to discriminate between early-to-moderately advanced patients with MSA and PD.
Topics: Aged; Diagnosis, Differential; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Middle Cerebellar Peduncle; Multiple System Atrophy; Parkinson Disease; Putamen; Sensitivity and Specificity
PubMed: 33713904
DOI: 10.1016/j.parkreldis.2021.02.027 -
Molecular Therapy : the Journal of the... Dec 2022Direct putaminal infusion of adeno-associated virus vector (serotype 2) (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene was...
Direct putaminal infusion of adeno-associated virus vector (serotype 2) (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene was studied in a phase I clinical trial of participants with advanced Parkinson's disease (PD). Convection-enhanced delivery of AAV2-GDNF with a surrogate imaging tracer (gadoteridol) was used to track infusate distribution during real-time intraoperative magnetic resonance imaging (iMRI). Pre-, intra-, and serial postoperative (up to 5 years after infusion) MRI were analyzed in 13 participants with PD treated with bilateral putaminal co-infusions (52 infusions in total) of AAV2-GDNF and gadoteridol (infusion volume, 450 mL per putamen). Real-time iMRI confirmed infusion cannula placement, anatomic quantification of volumetric perfusion within the putamen, and direct visualization of off-target leakage or cannula reflux (which permitted corresponding infusion rate/cannula adjustments). Serial post-treatment MRI assessment (n = 13) demonstrated no evidence of cerebral parenchyma toxicity in the corresponding regions of AAV2-GDNF and gadoteridol co-infusion or surrounding regions over long-term follow-up. Direct confirmation of key intraoperative safety and efficacy parameters underscores the safety and tissue targeting value of real-time imaging with co-infused gadoteridol and putative therapeutic agents (i.e., AAV2-GDNF). This delivery-imaging platform enhances safety, permits delivery personalization, improves therapeutic distribution, and facilitates assessment of efficacy and dosing effect.
Topics: Humans; Parkinson Disease; Magnetic Resonance Imaging
PubMed: 35957524
DOI: 10.1016/j.ymthe.2022.08.003