Orexin neurons are generally more dynamic, with about 2/3rds of them activated before and during self-initiated running, and most activated by sensory stimulation across sensory modalities. MCH neurons are activated in a more select manner, for example upon self-paced investigation of novel objects and by certain other novel stimuli. We discuss optogenetic and chemogenetic manipulations of orexin and MCH neurons, which combined with pharmacological blockade of orexin and MCH receptors, imply that these rapid LH dynamics shape fundamental cognitive and motor processes due to orexin and MCH neuropeptide actions in the awake brain. Finally, we contemplate whether the awake control of psychomotor brain functions by orexin and MCH are distinct from their "arousal" effects.
Depression induces an early onset of Parkinson's disease (PD), aggravates dyskinesia and cognitive impairment, and accelerates disease progression. However, it is very difficult to identify and diagnose PD with depression (PDD) in the early clinical stage. Few studies have suggested that the changes in neural networks are associated with PDD, while degree centrality (DC) has been documented to be effective in detecting brain network changes.

The objectives of this study are to explore DC changes between patients with PDD and without depression (PDND) and to find the key brain hubs involved with depression in PD patients.

One hundred and four PD patients and 54 healthy controls (HCs) underwent brain resting-state functional magnetic resonance imaging. The Data Processing and Analysis of Brain Imaging and Resting-State Functional Magnetic Resonance Data Analysis Toolkit were used for processing and statistical analysis. The DC value of each frequency band was calculated. One-way analysis of variance and a fusiform gyrus, and left caudate nucleus in the traditional frequency band (0.01-0.08 Hz) compared to PDND patients. PDND patients displayed more abnormal functions in the basal ganglia in the slow-4 frequency band.

The DC changes in PDD and PDND are frequency dependent and frequency specific. The medial frontal gyrus, SMA, and limbic system may be the key hubs for depression in PD.
The DC changes in PDD and PDND are frequency dependent and frequency specific. The medial frontal gyrus, SMA, and limbic system may be the key hubs for depression in PD.Traumatic brain injury (TBI) results in complex pathological reactions, where the initial lesion is followed by secondary inflammation and edema. Our laboratory and others have reported that angiotensin receptor blockers (ARBs) have efficacy in improving recovery from traumatic brain injury in ****. Treatment of **** with a subhypotensive dose of the ARB candesartan results in improved functional recovery, and reduced pathology (lesion volume, inflammation and gliosis). In order to gain a better understanding of the molecular mechanisms through which candesartan improves recovery after controlled cortical impact injury (CCI), we performed transcriptomic profiling on brain regions after injury and drug treatment. We examined RNA expression in the ipsilateral hippocampus, thalamus and hypothalamus at 3 or 29 days post injury (dpi) treated with either candesartan (0.1 mg/kg) or vehicle. RNA was isolated and analyzed by bulk mRNA-seq. Gene expression in injured and/or candesartan treated brain region was comparedcifically in the hippocampus. Our results suggest that candesartan has broad actions in the brain after injury and affects different processes at acute and chronic times after injury. These data should assist in elucidating the beneficial effect of candesartan on recovery from TBI.Spinal cord injury (SCI) impairs mobility and often results in complications like intractable neuropathic pain. A multi-approach management of this chronic pain condition has been encouraged, but little has been explored of the field. Here, we focus on the effect and underlying mechanism of environmental enrichment (EE), which promotes voluntary social and physical activities, combined with a clinical analgesic, ketamine, on SCI-induced neuropathic pain as well as motor dysfunction. We performed T13 spinal hemisection in rats, which induced unilateral motor impairment and neuropathic pain-like behaviors in the hindlimb. Treatment regimen started a week after SCI, which consists of ketamine administration (30 mg kg-1 day-1; intramuscular) for 10 days, or EE housing for 20 days, or their combination. Paw withdrawal response to mechanical and thermal stimuli, motor function, burrowing behaviors, and body weight was monitored. Spinal segments at T13 lesion and L4-L6 were collected for histopathological and protein analyses. The joint treatment of EE and ketamine provided greater relief of pain-like behaviors and locomotor recovery than did either paradigm alone. These improvements were associated with reduced cavitation area, astrogliosis, and perilesional phosphorylation of glutamate N-methyl-D-aspartate receptor (NMDAR). Concurrently, lumbar spinal analysis of NMDAR-linked excitatory markers in hypersensitization showed reduced activation of NMDAR, mitogen-activated protein kinase (MAPK) family, nuclear factor (NF)-κB, interleukin (IL)-1β signaling, and restored excitatory amino acid transporter 2 level. Our data support a better therapeutic efficacy of the combination, EE, and ketamine, in the attenuation of neuropathic pain and motor recovery by reducing spinal glutamatergic activation, signifying a potential multifaceted neurorehabilitation strategy to improve SCI patient outcome.Sustained attention is the ability to continually concentrate on task-relevant information, even in the presence of distraction. https://www.selleckchem.com/products/indy.html Understanding the neural mechanisms underlying this ability is critical for comprehending attentional processes as well as neuropsychiatric disorders characterized by attentional deficits, such as attention deficit hyperactivity disorder (ADHD). In this study, we aimed to investigate how trait-like critical oscillations during rest relate to the P300 evoked potential-a biomarker commonly used to assess attentional deficits. We measured long-range temporal correlations (LRTC) in resting-state EEG oscillations as index for criticality of the signal. In addition, the attentional performance of the subjects was assessed as reaction time variability (RTV) in a continuous performance task following an oddball paradigm. P300 amplitude and latencies were obtained from EEG recordings during this task. We found that, after controlling for individual variability in task performance, LRTC were positively associated with P300 amplitudes but not latencies.
Orexin neurons are generally more dynamic, with about 2/3rds of them activated before and during self-initiated running, and most activated by sensory stimulation across sensory modalities. MCH neurons are activated in a more select manner, for example upon self-paced investigation of novel objects and by certain other novel stimuli. We discuss optogenetic and chemogenetic manipulations of orexin and MCH neurons, which combined with pharmacological blockade of orexin and MCH receptors, imply that these rapid LH dynamics shape fundamental cognitive and motor processes due to orexin and MCH neuropeptide actions in the awake brain. Finally, we contemplate whether the awake control of psychomotor brain functions by orexin and MCH are distinct from their "arousal" effects. Depression induces an early onset of Parkinson's disease (PD), aggravates dyskinesia and cognitive impairment, and accelerates disease progression. However, it is very difficult to identify and diagnose PD with depression (PDD) in the early clinical stage. Few studies have suggested that the changes in neural networks are associated with PDD, while degree centrality (DC) has been documented to be effective in detecting brain network changes. The objectives of this study are to explore DC changes between patients with PDD and without depression (PDND) and to find the key brain hubs involved with depression in PD patients. One hundred and four PD patients and 54 healthy controls (HCs) underwent brain resting-state functional magnetic resonance imaging. The Data Processing and Analysis of Brain Imaging and Resting-State Functional Magnetic Resonance Data Analysis Toolkit were used for processing and statistical analysis. The DC value of each frequency band was calculated. One-way analysis of variance and a fusiform gyrus, and left caudate nucleus in the traditional frequency band (0.01-0.08 Hz) compared to PDND patients. PDND patients displayed more abnormal functions in the basal ganglia in the slow-4 frequency band. The DC changes in PDD and PDND are frequency dependent and frequency specific. The medial frontal gyrus, SMA, and limbic system may be the key hubs for depression in PD. The DC changes in PDD and PDND are frequency dependent and frequency specific. The medial frontal gyrus, SMA, and limbic system may be the key hubs for depression in PD.Traumatic brain injury (TBI) results in complex pathological reactions, where the initial lesion is followed by secondary inflammation and edema. Our laboratory and others have reported that angiotensin receptor blockers (ARBs) have efficacy in improving recovery from traumatic brain injury in mice. Treatment of mice with a subhypotensive dose of the ARB candesartan results in improved functional recovery, and reduced pathology (lesion volume, inflammation and gliosis). In order to gain a better understanding of the molecular mechanisms through which candesartan improves recovery after controlled cortical impact injury (CCI), we performed transcriptomic profiling on brain regions after injury and drug treatment. We examined RNA expression in the ipsilateral hippocampus, thalamus and hypothalamus at 3 or 29 days post injury (dpi) treated with either candesartan (0.1 mg/kg) or vehicle. RNA was isolated and analyzed by bulk mRNA-seq. Gene expression in injured and/or candesartan treated brain region was comparedcifically in the hippocampus. Our results suggest that candesartan has broad actions in the brain after injury and affects different processes at acute and chronic times after injury. These data should assist in elucidating the beneficial effect of candesartan on recovery from TBI.Spinal cord injury (SCI) impairs mobility and often results in complications like intractable neuropathic pain. A multi-approach management of this chronic pain condition has been encouraged, but little has been explored of the field. Here, we focus on the effect and underlying mechanism of environmental enrichment (EE), which promotes voluntary social and physical activities, combined with a clinical analgesic, ketamine, on SCI-induced neuropathic pain as well as motor dysfunction. We performed T13 spinal hemisection in rats, which induced unilateral motor impairment and neuropathic pain-like behaviors in the hindlimb. Treatment regimen started a week after SCI, which consists of ketamine administration (30 mg kg-1 day-1; intramuscular) for 10 days, or EE housing for 20 days, or their combination. Paw withdrawal response to mechanical and thermal stimuli, motor function, burrowing behaviors, and body weight was monitored. Spinal segments at T13 lesion and L4-L6 were collected for histopathological and protein analyses. The joint treatment of EE and ketamine provided greater relief of pain-like behaviors and locomotor recovery than did either paradigm alone. These improvements were associated with reduced cavitation area, astrogliosis, and perilesional phosphorylation of glutamate N-methyl-D-aspartate receptor (NMDAR). Concurrently, lumbar spinal analysis of NMDAR-linked excitatory markers in hypersensitization showed reduced activation of NMDAR, mitogen-activated protein kinase (MAPK) family, nuclear factor (NF)-κB, interleukin (IL)-1β signaling, and restored excitatory amino acid transporter 2 level. Our data support a better therapeutic efficacy of the combination, EE, and ketamine, in the attenuation of neuropathic pain and motor recovery by reducing spinal glutamatergic activation, signifying a potential multifaceted neurorehabilitation strategy to improve SCI patient outcome.Sustained attention is the ability to continually concentrate on task-relevant information, even in the presence of distraction. https://www.selleckchem.com/products/indy.html Understanding the neural mechanisms underlying this ability is critical for comprehending attentional processes as well as neuropsychiatric disorders characterized by attentional deficits, such as attention deficit hyperactivity disorder (ADHD). In this study, we aimed to investigate how trait-like critical oscillations during rest relate to the P300 evoked potential-a biomarker commonly used to assess attentional deficits. We measured long-range temporal correlations (LRTC) in resting-state EEG oscillations as index for criticality of the signal. In addition, the attentional performance of the subjects was assessed as reaction time variability (RTV) in a continuous performance task following an oddball paradigm. P300 amplitude and latencies were obtained from EEG recordings during this task. We found that, after controlling for individual variability in task performance, LRTC were positively associated with P300 amplitudes but not latencies.
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