Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Humans ; Pruritus ; Somatosensory Cortex ; Spinal Cord

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

OBJECTIVE: The aims of this study were to investigate the effects of daily low-dose tadalafil on cognitive function and to examine whether there was a change in cerebral blood flow (CBF) in patients with erectile dysfunction (ED) and mild cognitive impairment. METHODS: Male patients aged 50 to 75 years with at least three months of ED (International Index of Erectile Function [IIEF]-5 score ≤ 21) and mild cognitive impairment (Montreal Cognitive Assessment [MoCA] score ≤ 22) were included in the study. The subjects were prescribed a low-dose PDE5 inhibitor (tadalafil 5 mg) to be taken once daily for eight weeks. Changes in MoCA score and single-photon emission computed tomography (SPECT) study between the two time-points were assessed by paired t tests. RESULTS: Overall, 30 male patients were assigned to the treatment group in this study and 25 patients completed the eight-week treatment course. Five patients were withdrawn due to adverse events such as myalgia and dizziness. Mean baseline IIEF and MoCA scores were 7.52 ± 4.84 and 18.92 ± 1.78. After the eight-week treatment, mean IIEF and MoCA scores were increased to 12.92 ± 7.27 (p < 0.05) and 21.8 ± 1.71 (p < 0.05), respectively. Patients showed increased relative regional CBF in the postcentral gyrus, precuneus, and brainstem after tadalafil administration versus at baseline (p < 0.001). CONCLUSION: The results of this prospective clinical study suggest that daily use of tadalafil 5 mg increases some regional CBF and improves cognitive function in patients with ED and mild cognitive impairment.
Brain Stem ; Cerebrovascular Circulation ; Clinical Study ; Cognition ; Dizziness ; Erectile Dysfunction ; Humans ; Male ; Methylenebis(chloroaniline) ; Mild Cognitive Impairment ; Myalgia ; Parietal Lobe ; Perfusion ; Phosphodiesterase Inhibitors ; Prospective Studies ; Somatosensory Cortex ; Tadalafil ; Tomography, Emission-Computed

Absence seizures (AS) are generalized non-convulsive seizures characterized by a brief loss of consciousness and spike-and-wave discharges (SWD) in an electroencephalogram (EEG). A number of animal models have been developed to explain the mechanisms of AS, and thalamo-cortical networks are considered to be involved. However, the cortical foci have not been well described in mouse models of AS. This study aims to use a high density EEG in pathophysiologically different AS models to compare the spatiotemporal patterns of SWDs. We used two AS models: a pharmacologically induced model (gamma-hydroxybutyric acid, GHB model) and a transgenic model (phospholipase beta4 knock-out, PLCβ4 model). The occurrences of SWDs were confirmed by thalamic recordings. The topographical analysis of SWDs showed that the onset and propagation patterns were markedly distinguishable between the two models. In the PLCβ4 model, the foci were located within the somatosensory cortex followed by propagation to the frontal cortex, whereas in the GHB model, a majority of SWDs was initiated in the prefrontal cortex followed by propagation to the posterior cortex. In addition, in the GHB model, foci were also observed in other cortical areas. This observation indicates that different cortical networks are involved in the generation of SWDs across the two models.
Animals ; Electroencephalography ; Epilepsy, Absence ; Frontal Lobe ; Mice ; Models, Animal ; Prefrontal Cortex ; Seizures ; Somatosensory Cortex ; Unconsciousness

Obesity, an increasingly common problem in modern societies, results from energy intake chronically exceeding energy expenditure. This imbalance of energy can be triggered by the internal state of the caloric equation (homeostasis) and non-homeostatic factors, such as social, cultural, psychological, environmental factors or food itself. Nowadays, positron emission tomography (PET) radiopharmaceuticals have been examined to understand the cerebral control of food intake in humans. Using ¹⁵O–H₂ PET, changes in regional cerebral blood flow (rCBF) coupled to neuronal activity were reported in states of fasting, satiation after feeding, and sensory stimulation. In addition, rCBF in obese subjects showed a greater increase in insula, the primary gustatory cortex. ¹⁸F–fluorodeoxyglucose PET showed higher metabolic activity in postcentral gyrus of the parietal cortex and lower in prefrontal cortex and anterior cingulate cortex in obese subjects. In addition, dopamine receptor (DR) PET demonstrated lower DR availability in obese subjects, which might lead to overeating to compensate. Brain PET has been utilized to reveal the connectivity between obesity and brain. This could improve understanding of obesity and help develop a new treatment for obesity.
Brain ; Cerebrovascular Circulation ; Eating ; Electrons ; Energy Intake ; Energy Metabolism ; Fasting ; Gyrus Cinguli ; Humans ; Hyperphagia ; Neurons ; Obesity ; Parietal Lobe ; Positron-Emission Tomography ; Prefrontal Cortex ; Radiopharmaceuticals ; Receptors, Dopamine ; Satiation ; Somatosensory Cortex

PURPOSE: The prefrontal lobe, supplementary motor area, cerebellum, and basal ganglia are activated during gait. In addition, gait is controlled by nerves, such as the corticospinal tract (CST) and corticoreticular pathway (CRP). In this study, the presence of an injury to the CST and CRP was identified by diffusion tensor imaging and the characteristics of the gait pattern were investigated according to inferior cerebral artery infarction. METHODS: One patient and six control subjects of a similar age participated. A 69-year-old female patient had an injury to the left basal ganglia, insular gyrus, corona radiata, dorsolateral prefrontal cortex, and postcentral gyrus due to an inferior cerebral artery infarction. Diffusion tensor imaging (DTI) data was acquired 4 weeks after the stroke. The kinematic and spatio-temporal parameters of gait were collected using a three-dimensional gait analysis system. RESULTS: On 4 weeks DTI, the CST and CRP in the affected hemisphere did not show injury to the affected and unaffected hemisphere. Gait analysis showed that the cadence of spatio-temporal parameter was decreased significantly in the patient. The angle of the knee joint was decreased significantly in the affected and unaffected sides compared to the control group. CONCLUSION: The results of diffusion tensor imaging showed that although the patient was evaluated to be capable of an independent gait, the quality and quantity of gait might be reduced. This study could help better understand the gait ability analysis of stroke patients and the abnormal gait pattern of patients with a brain injury.
Aged ; Basal Ganglia ; Brain Injuries ; Cerebellum ; Cerebral Arteries ; Diffusion Tensor Imaging ; Female ; Gait* ; Humans ; Infarction ; Knee Joint ; Motor Cortex ; Prefrontal Cortex ; Pyramidal Tracts* ; Somatosensory Cortex ; Stroke*

BACKGROUND AND PURPOSE: To explore anatomic substrate of specific wandering patterns in patients with Alzheimer's disease (AD) by performing positron emission tomography with 18F fluorodeoxyglucose positron emission tomography (FDG PET). METHODS: Drug-naïve AD patients with wandering (n=80) and without wandering (n=262) were recruited. First, the specific pattern of wandering type was operationally classified according to specific wandering score and clinical assessment. Second, brain FDG PET was performed and fluorodeoxyglucose (FDG) uptake differences of specific brain regions according to wandering patterns were compared to those of non-wanderers. RESULTS: In patients with pacing pattern, FDG PET showed significant lower FDG uptake in both middle cingulum and left putamen cluster compared to non-wanderers. The right precuneus and supplementary motor area in patients with random pattern and left calcarine sulcus, right calcarine sulcus, right middle cingulum, and right post central gyrus in patients with lapping pattern had significantly lower FDG uptake compared to non-wanderers. CONCLUSIONS: This study showed that wandering in patients with AD had three distinct patterns. These specific patterns showed significant lower FDG uptake in specific brain areas compared to non-wanderers.
Alzheimer Disease* ; Brain ; Fluorodeoxyglucose F18 ; Humans ; Motor Cortex ; Occipital Lobe ; Parietal Lobe ; Positron-Emission Tomography ; Putamen ; Somatosensory Cortex

OBJECTIVE: Structural changes of brain areas have been reported in depressive disorder and suicidal behavior (SB), in which TPH1 also has been known as a promising candidate gene. We investigated gray matter volume (GMV) differences, TPH1 rs1800532 and rs1799913 polymorphisms previously found to be associated with depressive disorder and SB, and the relationship between the two markers. METHODS: Thirteen depressive disorder patients with suicidal attempts (SA) and twenty healthy controls were included. We examined GMV differences using a voxel-based morphometry and regions of interest analysis. Direct sequencing was used for genotyping. RESULTS: The patients showed significant GMV reduction in left cerebral region including middle frontal gyrus, inferior frontal gyrus, and anterior cingulate cortex; in right middle temporal gyrus; in left cerebellar tonsil; and in right cerebral region including precentral gyrus and postcentral gyrus (corrected p < 0.005). The right precentral and postcentral gyri GMV values of AA and CA genotypes patients were significantly decreased compared to those of CC genotype subjects (corrected p=0.040). CONCLUSION: These findings show the possibility that both GMV reductions and TPH1 rs1800532/rs1799913 A allele may be involved in the pathogenesis of depressive disorder patients with SA.
Alleles ; Brain ; Depressive Disorder* ; Frontal Lobe ; Genotype ; Gray Matter* ; Gyrus Cinguli ; Humans ; Palatine Tonsil ; Prefrontal Cortex ; Somatosensory Cortex ; Temporal Lobe

BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.
Brain ; Broca Area ; Caudate Nucleus ; Classification ; Dyspepsia ; Functional Neuroimaging ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Parahippocampal Gyrus ; Parietal Lobe ; Perfusion ; Prefrontal Cortex ; Sensation ; Somatosensory Cortex ; Visceral Pain ; Water