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Neurobiology of Disease Jun 2019Hypertension-induced microvascular brain injury is a major vascular contributor to cognitive impairment and dementia. We hypothesized that chronic hypoxia promotes the...
BACKGROUND
Hypertension-induced microvascular brain injury is a major vascular contributor to cognitive impairment and dementia. We hypothesized that chronic hypoxia promotes the hyperphosphorylation of tau and cell death in an accelerated spontaneously hypertensive stroke prone rat model of vascular cognitive impairment.
METHODS
Hypertensive male rats (n = 13) were fed a high salt, low protein Japanese permissive diet and were compared to Wistar Kyoto control rats (n = 5).
RESULTS
Using electron paramagnetic resonance oximetry to measure in vivo tissue oxygen levels and magnetic resonance imaging to assess structural brain damage, we found compromised gray (dorsolateral cortex: p = .018) and white matter (corpus callosum: p = .016; external capsule: p = .049) structural integrity, reduced cerebral blood flow (dorsolateral cortex: p = .005; hippocampus: p < .001; corpus callosum: p = .001; external capsule: p < .001) and a significant drop in cortical oxygen levels (p < .05). Consistently, we found reduced oxygen carrying neuronal neuroglobin (p = .008), suggestive of chronic cerebral hypoperfusion in high salt-fed rats. We also observed a corresponding increase in free radicals (NADPH oxidase: p = .013), p-Tau (pThr231) in dorsolateral cortex (p = .011) and hippocampus (p = .003), active interleukin-1β (p < .001) and neurodegeneration (dorsolateral cortex: p = .043, hippocampus: p = .044). Human patients with subcortical ischemic vascular disease, a type of vascular dementia (n = 38; mean age = 68; male/female ratio = 23/15) showed reduced hippocampal volumes and cortical shrinking (p < .05) consistent with the neuronal cell death observed in our hypertensive rat model as compared to healthy controls (n = 47; mean age = 63; male/female ratio = 18/29).
CONCLUSIONS
Our data support an association between hypertension-induced vascular dysfunction and the sporadic occurrence of phosphorylated tau and cell death in the rat model, correlating with patient brain atrophy, which is relevant to vascular disease.
Topics: Aged; Animals; Brain; Cell Hypoxia; Dementia, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Phosphorylation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; tau Proteins
PubMed: 30010004
DOI: 10.1016/j.nbd.2018.07.009 -
Frontiers in Neurology 2021Multiple studies have identified segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. It has been suggested that...
Multiple studies have identified segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. It has been suggested that in PD, preferential loss of dopamine in the posterior putamen may cause a major deficit in habitual control (mediated by the sensorimotor cortical-striatal loop), and the patients may therefore be forced into a progressive reliance on the goal-directed behavior (regulated by the associative cortical-striatal loop). Functional evidence supporting this point is scarce at present. This study aims to verify the functional connectivity changes within the sensorimotor, associative, and limbic cortical-striatal loops in PD. Resting-state fMRI of 70 PD patients and 30 controls were collected. Bilateral tripartite functional territories of basal ganglia and their associated cortical structures were chosen as regions of interest, including ventral striatum and ventromedial prefrontal cortex for limbic loop; dorsomedial striatum and dorsolateral prefrontal cortex for associative loop; dorsolateral striatum and sensorimotor cortex for sensorimotor loop. Pearson's correlation coefficients for each seed pair were calculated to obtain the functional connectivity. The relationships between functional connectivity and disease severity were further investigated. Functional connectivity between dorsolateral striatum and sensorimotor cortex is decreased in PD patients, and negatively correlated with disease duration; whereas functional connectivity between dorsomedial striatum and dorsolateral prefrontal cortex is also decreased but postitively correlated with disease duration. The functional connectivity within the sensorimotor loop is pathologically decreased in PD, while the altered connectivity within the associative loop may indicate a failed attempt to compensate for the loss of connectivity within the sensorimotor loop.
PubMed: 34764927
DOI: 10.3389/fneur.2021.720293 -
The Journal of Pain Sep 2023The ability to accurately predict pain is an adaptive feature in healthy individuals. However, in chronic pain, this mechanism may be selectively impaired and can lead...
The ability to accurately predict pain is an adaptive feature in healthy individuals. However, in chronic pain, this mechanism may be selectively impaired and can lead to increased anxiety and excessive avoidance behavior. Recently, we reported the first data demonstrating brain activation in fibromyalgia (FM) patients during conditioned pain responses, in which FM patients revealed a tendency to form new pain-related associations rather than extinguishing irrelevant ones. The aim of the present study was to extend our previous analysis, to elucidate potential neural divergences between subjects with FM (n = 65) and healthy controls (HCs) (n = 33) during anticipatory information (ie, prior to painful stimulus onset). Using functional magnetic resonance imaging (fMRI), the current analyses include 1) a congruently cued paradigm of low and high pain predictive cues, followed by 2) an incongruently cued paradigm where low and high pain predictive cues were followed by an identical mid-intensity painful pressure. During incongruently cued high-pain associations, FM exhibited reduced left dorsolateral prefrontal cortex (dlPFC) activation compared to HCs, which was followed by an altered subsequent pain experience in FM, as patients continued to rate the following painful stimuli as high, even though the pressure had been lowered. During congruently cued low pain anticipation, FM exhibited decreased right dlPFC activation compared to HCs, as well as decreased brain connectivity between brain regions implicated in cognitive modulation of pain (dlPFC) and nociceptive processing (primary somatosensory cortex/postcentral gyrus [S1] and supplementary motor area [SMA]/midcingulate cortex [MCC]). These results may reflect an important feature of validating low pain expectations in HCs and help elucidate behavioral reports of impaired safety processing in FM patients. PERSPECTIVE: FM exhibited a stronger conditioned pain response for high-pain associations, which was associated with reduced dlPFC activation during the incongruent trial. During (congruent and incongruent) low pain associations, FM dlPFC brain activation remained indifferent. Imbalances in threat and safety pain perception may be an important target for psychotherapeutic interventions.
Topics: Humans; Fibromyalgia; Dorsolateral Prefrontal Cortex; Pain Perception; Brain; Chronic Pain; Magnetic Resonance Imaging; Prefrontal Cortex
PubMed: 37354157
DOI: 10.1016/j.jpain.2023.05.006 -
Brain Sciences Jun 2022To investigate the intervention effect of orienteering exercises on the spatial memory ability of college students of different genders and its underlying mechanism.
OBJECTIVE
To investigate the intervention effect of orienteering exercises on the spatial memory ability of college students of different genders and its underlying mechanism.
METHODS
Forty-eight college students were randomly screened into experimental and control groups, 12 each of male and female, by SBSOD scale. The effects of 12 weeks of orienteering exercises on the behavioral performance and brain activation patterns during the spatial memory tasks of college students of different genders were explored by behavioral tests and the fNIRS technique.
RESULTS
After the orienteering exercise intervention in the experimental group, the male students had significantly greater correct rates and significantly lower reaction times than the female students; left and right dorsolateral prefrontal activation was significantly reduced in the experimental group, and the male students had a significantly greater reduction in the left dorsolateral prefrontal than the female students. The degree of activation in the left and right dorsolateral prefrontals of the male students and the right dorsolateral prefrontals of the female students correlated significantly with behavioral performance, and the functional coupling between the brain regions showed an enhanced performance.
DISCUSSION
Orienteering exercises improve the spatial memory ability of college students, more significantly in male students. The degree of activation of different brain regions correlated with behavioral performance and showed some gender differences.
PubMed: 35884661
DOI: 10.3390/brainsci12070852 -
Neural Regeneration Research May 2022Acupuncture has been shown to be effective on alcohol use disorder. However, the underlying mechanism remains poorly understood. To investigate the effects of Shenmen...
Acupuncture has been shown to be effective on alcohol use disorder. However, the underlying mechanism remains poorly understood. To investigate the effects of Shenmen (HT7) acupoint on brain activation induced by cue-elicited alcohol craving, 30 right-handed healthy light to moderate alcohol drinkers were recruited from the community. They were randomly assigned to undergo acupuncture either at HT7 (experimental acupoint, n = 15) or Jingqu (LU8, control acupoint, n = 15) acupoints. This randomized controlled study was performed in Daegu Haany University and Daegu-Gyeongbuk Medical Innovation Foundation, Republic of Korea. Recruitment and data collection were conducted from December 2018 to May 2019. The results showed that after acupuncture at HT7 acupoint, the activation of orbitofrontal cortex and dorsolateral prefrontal cortex was greatly increased, while the activation of dorsolateral prefrontal cortex was obviously reduced, and subject's craving for alcohol was reduced when he/she seeing alcohol-related video clips involving various alcohols (beer, wine, or soju) or drinking scenarios. Acupuncture at HT7 more greatly reduced subject's alcohol cravings than acupuncture at LU8 acupoint. These findings suggest that acupuncture can improve the self-control of mild to moderate social drinkers through the activation of the orbitofrontal cortex and dorsolateral prefrontal cortex, thereby reducing the craving for alcohol. The study protocol was approved by the Institutional Review Board of Daegu Haany University Korean Medicine Hospital, Republic of Korea (approval No. DHUMC-D-18026-PRO-02) on November 30, 2018.
PubMed: 34558533
DOI: 10.4103/1673-5374.324849 -
The Wnt/beta-catenin signaling pathway establishes neuroanatomical asymmetries and their laterality.Mechanisms of Development 2013The vertebrate brain is an immensely complex structure, which exhibits numerous morphological and functional asymmetries. The best described brain asymmetries are found... (Review)
Review
The vertebrate brain is an immensely complex structure, which exhibits numerous morphological and functional asymmetries. The best described brain asymmetries are found in the diencephalic epithalamus, where the habenulae and the dorso-laterally adjacent pineal complex are lateralized in many species. Research in the past decade has shed light on the establishment of the laterality of these structures as well as their asymmetry per se. In particular work in zebrafish (Danio rerio) has substantially contributed to our understanding, which genetic pathways are involved in these processes. The Wnt/beta-catenin pathway has turned out to play a pivotal role in the regulation of brain laterality and asymmetry and acts reiteratively during embryonic development.
Topics: Animals; Body Patterning; Functional Laterality; Gastrulation; Gene Expression Regulation, Developmental; Habenula; Pineal Gland; Wnt Proteins; Wnt Signaling Pathway; Zebrafish; Zebrafish Proteins; beta Catenin
PubMed: 23022991
DOI: 10.1016/j.mod.2012.09.002 -
Journal of Cognitive Neuroscience Jun 2019Two primary functions attributed to the hippocampus and prefrontal cortex (PFC) network are retaining the temporal and spatial associations of events and detecting...
Two primary functions attributed to the hippocampus and prefrontal cortex (PFC) network are retaining the temporal and spatial associations of events and detecting deviant events. It is unclear, however, how these two functions converge into one mechanism. Here, we tested whether increased activity with perceiving salient events is a deviant detection signal or contains information about the event associations by reflecting the magnitude of deviance (i.e., event saliency). We also tested how the deviant detection signal is affected by the degree of anticipation. We studied regional neural activity when people watched a movie that had varying saliency of a novel or an anticipated flow of salient events. Using intracranial electroencephalography from 10 patients, we observed that high-frequency activity (50-150 Hz) in the hippocampus, dorsolateral PFC, and medial OFC tracked event saliency. We also observed that medial OFC activity was stronger when the salient events were anticipated than when they were novel. These results suggest that dorsolateral PFC and medial OFC, as well as the hippocampus, signify the saliency magnitude of events, reflecting the hierarchical structure of event associations.
Topics: Adolescent; Adult; Aged; Anticipation, Psychological; Auditory Perception; Brain Waves; Electrocorticography; Female; Hippocampus; Humans; Male; Middle Aged; Motion Pictures; Prefrontal Cortex; Visual Perception; Young Adult
PubMed: 30883290
DOI: 10.1162/jocn_a_01392 -
Scientific Reports Jul 2016The striatum controls multiple cognitive aspects including motivation, reward perception, decision-making and motor planning. In particular, the dorsolateral striatum...
The striatum controls multiple cognitive aspects including motivation, reward perception, decision-making and motor planning. In particular, the dorsolateral striatum contributes to motor learning. Here we define an approach for investigating synaptic plasticity in mouse dorsolateral cortico-striatal circuitry and interrogate the relative contributions of neurotransmitter receptors and intracellular signaling components. Consistent with previous studies, we show that long-term potentiation (LTP) in cortico-striatal circuitry is facilitated by dopamine, and requires activation of D1-dopamine receptors, as well as NMDA receptors (NMDAR) and their calcium-dependent downstream effectors, including CaMKII. Moreover, we assessed the contribution of the protein kinase Cdk5, a key neuronal signaling molecule, in cortico-striatal LTP. Pharmacological Cdk5 inhibition, brain-wide Cdk5 conditional knockout, or viral-mediated dorsolateral striatal-specific loss of Cdk5 all impaired dopamine-facilitated LTP or D1-dopamine receptor-facilitated LTP. Selective loss of Cdk5 in dorsolateral striatum increased locomotor activity and attenuated motor learning. Taken together, we report an approach for studying synaptic plasticity in mouse dorsolateral striatum and critically implicate D1-dopamine receptor, NMDAR, Cdk5, and CaMKII in cortico-striatal plasticity. Furthermore, we associate striatal plasticity deficits with effects upon behaviors mediated by this circuitry. This approach should prove useful for the study of the molecular basis of plasticity in the dorsolateral striatum.
Topics: Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Corpus Striatum; Cyclin-Dependent Kinase 5; Dopamine; Learning; Locomotion; Long-Term Potentiation; Male; Mice; Receptors, Dopamine D1; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission
PubMed: 27443506
DOI: 10.1038/srep29812 -
Neuropsychiatric Disease and Treatment 2021Previous studies suggested a link between serotonergic neurotransmission and impaired insight in schizophrenia. In this study, we examined the relationship between...
Association Between Lack of Insight and Prefrontal Serotonin Transporter Availability in Antipsychotic-Free Patients with Schizophrenia: A High-Resolution PET Study with [C]DASB.
BACKGROUND
Previous studies suggested a link between serotonergic neurotransmission and impaired insight in schizophrenia. In this study, we examined the relationship between serotonin transporter (SERT) availability in regions of the prefrontal cortex (dorsolateral, ventrolateral, ventromedial, and orbitofrontal cortices) and insight deficits in antipsychotic-free patients with schizophrenia using high-resolution positron emission tomography (PET) with [C]DASB.
METHODS
Nineteen patients underwent [C]DASB PET and 7-Tesla magnetic resonance imaging scans. To assess SERT availability, the binding potential with respect to non-displaceable compartment (BP) was derived using the simplified reference tissue model. Patients' level of insight was assessed using the Insight and Treatment Attitude Questionnaire (ITAQ). The relationship between ITAQ scores and [C]DASB BP values was examined using the region-of-interest (ROI)- and voxel-based analyses with relevant variables as covariates. The prefrontal cortex and its four subregions were selected as a priori ROIs since the prefrontal cortex has been implicated as the critical neuroanatomical substrate of impaired insight in schizophrenia.
RESULTS
The ROI-based analysis revealed that the ITAQ illness insight dimension had significant negative correlations with the [C]DASB BP in the left dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ treatment insight dimension had significant negative correlations with the [C]DASB BP in the bilateral dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ total score showed significant negative correlations with the [C]DASB BP in the bilateral prefrontal cortex and three subregions (dorsolateral, ventrolateral, and orbitofrontal cortices). A supplementary voxel-based analysis corroborated a significant negative association between the ITAQ score and the [C]DASB BP in the prefrontal cortices.
CONCLUSION
Our study provides in vivo evidence of significant negative correlations between insight deficits and prefrontal SERT availability in patients with schizophrenia, suggesting significant involvement of prefrontal serotonergic signaling in impaired insight, one of the core symptoms of schizophrenia.
PubMed: 34707358
DOI: 10.2147/NDT.S336126 -
Frontiers in Neurology 2014
Review
PubMed: 24688482
DOI: 10.3389/fneur.2014.00032