The secondary motor cortex (M2) encodes choice-related information and plays an important role in cue-guided actions. M2 neurons innervate the dorsal striatum (DS), which also contributes to decision-making behavior, yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear. Using mice performing a visual Go/No-Go task, we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm (FA) rate to the reward-irrelevant No-Go stimulus. The choice signal of M2 neurons correlated with behavioral performance, and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS. By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs, we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus, and inactivating their early responses increased the FA rate. These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.
Mice ; Animals ; Motor Cortex ; Corpus Striatum/physiology* ; Neostriatum ; Neurons/physiology* ; Reaction Time

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum

BACKGROUND AND PURPOSE: There is accumulating evidence that epilepsy is caused by network dysfunction. We evaluated the hub reorganization of subcortical structures in patients with focal epilepsy using graph theoretical analysis based on diffusion-tensor imaging (DTI). In addition, we investigated differences in the values of diffusion tensors and scalars, fractional anisotropy (FA), and mean diffusivity (MD) of subcortical structures between patients with focal epilepsy and healthy subjects. METHODS: One hundred patients with focal epilepsy and normal magnetic resonance imaging (MRI) findings and 80 age- and sex-matched healthy subjects were recruited prospectively. All subjects underwent DTI to obtain data suitable for graph theoretical analysis. We investigated the differences in the node strength, cluster coefficient, eigenvector centrality, page-rank centrality measures, FA, and MD of subcortical structures between patients with epilepsy and healthy subjects. RESULTS: After performing multiple corrections, the cluster coefficient and the eigenvector centrality of the globus pallidus were higher in patients with epilepsy than in healthy subjects (p=0.006 and p=0.008, respectively). In addition, the strength and the page-rank centrality of the globus pallidus tended to be higher in patients with epilepsy than in healthy subjects (p=0.092 and p=0.032, respectively). The cluster coefficient of the putamen was lower in patients with epilepsy than in healthy subjects (p=0.004). The FA values of the caudate nucleus and thalamus were significantly lower in patients with epilepsy than in healthy subjects (p=0.009 and p=0.007, respectively), whereas the MD value of the thalamus was higher than that in healthy subjects (p=0.005). CONCLUSIONS: We discovered the presence of hub reorganization of subcortical structures in focal epilepsy patients with normal MRI findings, suggesting that subcortical structures play a pivotal role as a hub in the epilepsy network. These findings further reinforce the idea that epilepsy is a network disease.
Anisotropy ; Caudate Nucleus ; Connectome ; Diffusion ; Epilepsies, Partial* ; Epilepsy ; Globus Pallidus ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Prospective Studies ; Putamen ; Thalamus

BACKGROUND AND PURPOSE: We aimed to determine the association between the annual changes in dopamine transporter (DAT) availability as measured by 123I-ioflupane (123I-FP-CIT) single-photon-emission computed tomography and single-nucleotide polymorphisms (SNPs) known to be risk factors in Parkinson's disease (PD). METHODS: In total, 150 PD patients were included from the Parkinson's Progression Markers Initiative database. Specific SNPs that are associated with PD were selected for genotyping. SNPs that were not in Hardy-Weinberg equilibrium or whose minor allele frequency was less than 0.05 were excluded. Twenty-three SNPs met the inclusion criteria for this study. The Kruskal-Wallis test was used to compare annual percentage changes in DAT availability for three subgroups of SNP. RESULTS: None of the 23 SNPs exerted a statistically significant effect (p < 0.0022) on the decline of DAT availability in PD patients. However, we observed trends of association (p < 0.05) between three SNPs of two genes with the annual percentage change in DAT availability: 1) rs199347 on the putamen (p=0.0138), 2) rs356181 on the caudate nucleus (p=0.0105), and 3) rs3910105 on the caudate nucleus (p=0.0374). A post-hoc analysis revealed that DAT availability was reduced the most for 1) the putamen in the CC genotype of rs199347 (vs. CT, p=0.0199; vs. TT, p=0.0164), 2) the caudate nucleus in the TT genotype of rs356181 (vs. CC, p=0.0081), and 3) the caudate nucleus in the CC genotype of rs3910105 (vs. TT, p=0.0317). CONCLUSIONS: Significant trends in the associations between three SNPs and decline of DAT availability in PD patients have been discovered.
Caudate Nucleus ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Gene Frequency ; Genotype ; Humans ; Parkinson Disease* ; Polymorphism, Single Nucleotide ; Putamen ; Risk Factors ; Tomography, Emission-Computed, Single-Photon

OBJECTIVE: Dysphagia is a common consequence of stroke with a negative effect on the clinical outcome. Given these potential outcomes, it is important to identify the precursors to dysphagia after stroke. The aims of this study were to identify lesions associated with dysphagia after an ischemic supratentorial stroke using voxel-based lesion symptom mapping (VLSM) and compare the difference in the lesion pattern between the oral and pharyngeal phase dysphagia. METHODS: Stroke patients who met the following inclusion criteria were screened retrospectively between January 2012 and November 2014: a first-ever stroke, supratentorial lesion and who underwent brain MRI and functional dysphagia scale (FDS) from videofluoroscopic swallowing study (VFSS). Finally, the MRI data of 83 patients were analyzed. Statistical maps of the lesion contribution related to dysphagia were generated using VLSM. RESULTS: VLSM showed that FDS was associated with damage to the putamen, caudate, insula, frontal precentral gyrus, and inferior frontal gyrus. The lesions were distributed more widely in the left than right hemisphere. Lesions correlated with the FDS oral score were distributed mainly in the frontal lobe and insula. Otherwise, the associated lesion with the FDS pharyngeal score was mainly the basal ganglia. CONCLUSION: In these results, lesions that correlated with dysphagia were distributed more widely in the left hemisphere, reflecting the possibility of lateralization of the swallowing function. Oral phase dysphagia was associated with left frontal lobe and insula; the lesion correlated with the cognitive function or apraxia. On the other hand, VLSM revealed the lesions associated with pharyngeal dysphagia to be the basal ganglia, which is a structure that plays a role in the automatic motor control network.
Apraxias ; Basal Ganglia ; Brain ; Brain Mapping ; Cognition ; Deglutition ; Deglutition Disorders ; Frontal Lobe ; Hand ; Humans ; Magnetic Resonance Imaging ; Neuroanatomy ; Prefrontal Cortex ; Putamen ; Retrospective Studies ; Stroke

OBJECTIVE: To investigate association between lesion location on magnetic resonance imaging (MRI) performed after an infarction and the duration of dysphagia in middle cerebral artery (MCA) infarction. METHODS: A videofluoroscopic swallowing study was performed for 59 patients with dysphagia who were diagnosed as cerebral infarction of the MCA territory confirmed by brain MRI. Lesions were divided into 11 regions of interest: primary somatosensory cortex, primary motor cortex, supplementary motor cortex, anterior cingulate cortex, orbitofrontal cortex, parieto-occipital cortex, insular cortex, posterior limb of the internal capsule (PLIC), thalamus, basal ganglia (caudate nucleus), and basal ganglia (putamen). Recovery time was defined as the period from the first day of L-tube feeding to the day that rice porridge with thickening agent was prescribed. Recovery time and brain lesion patterns were compared and analyzed. RESULTS: The mean recovery time of all patients was 26.71±16.39 days. The mean recovery time was 36.65±15.83 days in patients with PLIC lesions and 32.6±17.27 days in patients with caudate nucleus lesions. Only these two groups showed longer recovery time than the average recovery time for all patients. One-way analysis of variance for recovery time showed significant differences between patients with and without lesions in PLIC and caudate (p<0.001). CONCLUSION: Injury to both PLIC and caudate nucleus is associated with longer recovery time from dysphagia.
Basal Ganglia ; Brain ; Caudate Nucleus ; Cerebral Cortex ; Cerebral Infarction ; Deglutition ; Deglutition Disorders ; Extremities ; Gyrus Cinguli ; Humans ; Infarction ; Infarction, Middle Cerebral Artery ; Internal Capsule ; Magnetic Resonance Imaging ; Middle Cerebral Artery ; Motor Cortex ; Prefrontal Cortex ; Somatosensory Cortex ; Thalamus

BACKGROUND AND PURPOSE: Various features of the cerebral cortex and white matter have been extensively investigated in migraine with aura (MwA), but the morphological characteristics of subcortical structures have been largely neglected. The aim of this study was to identify possible differences in subcortical structures between MwA patients and healthy subjects (HS), and also to determine the correlations between the characteristics of migraine aura and the volumes of subcortical structures. METHODS: Thirty-two MwA patients and 32 HS matched by sex and age were analyzed in this study. Regional subcortical brain volumes were automatically calculated using the FSL/FMRIB Image Registration and Segmentation Tool software (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Glossary). A general linear model analysis was used to investigate differences in the volume of subcortical structures between the MwA patients and HS. A partial correlation test was used to assess correlations between the volume of subcortical structures and characteristics of MwA. RESULTS: The volumes of the right globus pallidus, left globus pallidus, and left putamen were significantly smaller in MwA patients than in HS (mean±SD): 1,427±135 mm³ vs. 1,557±136 mm³ (p<0.001), 1,436±126 mm³ vs. 1,550±139 mm³ (p=0.001), and 4,235±437 mm³ vs. 4,522±412 mm³ (p=0.006), respectively. There were no significant relationships between subcortical structures and clinical parameters. CONCLUSIONS: These findings suggest that both the globus pallidi and left putamen play significant roles in the pathophysiology of the MwA. Future studies should determine the cause-and-effect relationships, since these could not be discriminated in this study due to its cross-sectional design.
Basal Ganglia ; Brain ; Cerebral Cortex ; Epilepsy ; Globus Pallidus ; Healthy Volunteers ; Humans ; Linear Models ; Migraine Disorders ; Migraine with Aura ; Putamen ; White Matter

OBJECTIVE: Ample evidence has suggested that age at onset of Parkinson's disease (PD) is associated with heterogeneous clinical features in individuals. We hypothesized that this may be attributed to different patterns of nigrostriatal dopamine loss. METHODS: A total of 205 consecutive patients with de novo PD who underwent 18F-FP-CIT PET scans (mean follow-up duration, 6.31 years) were divided into three tertile groups according to their age at onset of parkinsonian motor symptoms. Striatal dopamine transporter (DAT) availability was compared between the old- (n = 73) and young-onset (n = 66) groups. In addition, the risk of developing freezing of gait (FOG) and longitudinal requirements for dopaminergic medications were examined. RESULTS: The old-onset PD group (mean age at onset, 72.66 years) exhibited more severe parkinsonian motor signs than the young-onset group (52.58 years), despite comparable DAT availability in the posterior putamen; moreover, the old-onset group exhibited more severely decreased DAT availability in the caudate than the young-onset group. A Cox regression model revealed that the old-onset PD group had a higher risk for developing FOG than the young-onset group [hazard ratio 2.523, 95% confidence interval (1.239–5.140)]. The old-onset group required higher doses of dopaminergic medications for symptom control than the young-onset group over time. CONCLUSION: The present study demonstrated that the old-onset PD group exhibited more severe dopamine loss in the caudate and were more likely to develop gait freezing, suggesting that age at onset may be one of the major determinants of the pattern of striatal dopamine depletion and progression of gait disturbance in PD.
Age of Onset ; Dopamine Plasma Membrane Transport Proteins ; Dopamine ; Follow-Up Studies ; Freezing ; Gait ; Humans ; Parkinson Disease ; Positron-Emission Tomography ; Putamen ; Weather

OBJECTIVE: It is unclear whether the decline in dopamine transporters (DAT) differs among idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with different levels of olfactory impairment. This study aimed to characterize DAT changes in relation to nonmotor features in iRBD patients by olfactory loss. METHODS: This prospective cohort study consisted of three age-matched groups: 30 polysomnography-confirmed iRBD patients, 30 drug-naïve Parkinson's disease patients, and 19 healthy controls without olfactory impairment. The iRBD group was divided into two groups based on olfactory testing results. Participants were evaluated for reported prodromal markers and then underwent 18F-FP-CIT positron emission tomography and 3T MRI. Tracer uptakes were analyzed in the caudate, anterior and posterior putamen, substantia nigra, and raphe nuclei. RESULTS: Olfactory impairment was defined in 38.5% of iRBD patients. Mild parkinsonian signs and cognitive functions were not different between the two iRBD subgroups; however, additional prodromal features, constipation, and urinary and sexual dysfunctions were found in iRBD patients with olfactory impairment but not in those without. Tracer uptake showed significant group differences in all brain regions, except the raphe nuclei. The iRBD patients with olfactory impairment had uptake reductions in the anterior and posterior putamen, caudate, and substantia nigra (p < 0.016 in all, adjusted for age), which ranged from 0.6 to 0.8 of age-normative values. In contrast, those without olfactory impairment had insignificant changes in all regions ranging above 0.8. CONCLUSION: There was a clear distinction in DAT loss and nonmotor profiles by olfactory status in iRBD.
Brain ; Cognition ; Cohort Studies ; Constipation ; Dopamine Plasma Membrane Transport Proteins ; Dopamine ; Humans ; Magnetic Resonance Imaging ; Parkinson Disease ; Positron-Emission Tomography ; Prospective Studies ; Putamen ; Raphe Nuclei ; REM Sleep Behavior Disorder ; Sleep, REM ; Smell ; Substantia Nigra

OBJECTIVE: This study examined the efficacy of the white matter (WM) to gray matter (GM) signal intensity ratio (SIR) in predicting the clinical prognosis of cardiac arrest patients. METHODS: Thirty-one patients who were resuscitated from cardiac arrest and underwent brain magnetic resonance imaging (MRI) were investigated retrospectively. Thirty one subjects with normal brain MRI findings served as the controls. The signal intensities (SI) were measured on T2-weighted image (T2WI). The circular regions of measurement (2–10 mm²) were placed over the regions of interest, and the average signals in GM and WM were recorded in the caudate nucleus (CN), putamen, anterior limb of the internal capsule, corpus callosum (CC), and in the cortex and WM of the frontal lobe. Cerebral performance category (CPC) 1–2 were classified as a good prognosis, and CPC 3–5 were classified as a poor prognosis. RESULTS: Most combinations of the SIR of WM to GM and most SIs of GM, except the frontal cortex, were significantly different between the two groups. On the other hand, the SI of WM was insignificant between both groups. In receiver operating characteristic (ROC) curve analysis, the SIR of the CC to CN had an area under the ROC curve (AUROC) of 1.00 for a cut-off value of 1.59 (sensitivity, 100%; specificity, 100%), the SIR of the CC to putamen had also an AUROC of 1.00 for a cut-off value of 1.43 (sensitivity, 100%; specificity, 100%). CONCLUSION: The SIR of WM to GM measured on a T2WI is related to the neurological outcome after a cardiac arrest.
Brain ; Caudate Nucleus ; Coma ; Corpus Callosum ; Extremities ; Frontal Lobe ; Gray Matter ; Hand ; Heart Arrest ; Humans ; Internal Capsule ; Magnetic Resonance Imaging ; Prognosis ; Putamen ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; White Matter