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Neuroscience Letters Jun 2024Brain somatic variants in SLC35A2, an intracellular UDP-galactose transporter, are commonly identified mutations associated with drug-resistant neocortical epilepsy and...
Brain somatic variants in SLC35A2, an intracellular UDP-galactose transporter, are commonly identified mutations associated with drug-resistant neocortical epilepsy and developmental brain malformations, including focal cortical dysplasia type I and mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). However, the causal effects of altered SLC35A2 function on cortical development remain untested. We hypothesized that focal Slc35a2 knockout (KO) or knockdown (KD) in the developing mouse cortex would disrupt cortical development and change network excitability. Through two independent studies, we used in utero electroporation (IUE) to introduce CRISPR/Cas9/targeted guide RNAs or short-hairpin RNAs into the embryonic mouse brain at day 14.5-15.5 to achieve Slc35a2 KO or KD, respectively, from neural precursor cells. Slc35a2 KO or KD caused disrupted radial migration of electroporated neurons evidenced by heterotopic cells located in lower cortical layers and in the sub-cortical white matter. Slc35a2 KO in neurons did not induce changes in oligodendrocyte number, importantly suggesting that the oligodendroglial hyperplasia observed in MOGHE originates from distinct cell autonomous effects of Slc35a2 mutations. Adult KO mice were implanted with EEG electrodes for 72-hour continuous recording. Spontaneous seizures were not observed in focal Slc35a2 KO mice, but there was reduced seizure threshold following pentylenetetrazol injection. Here we demonstrate that focal Slc35a2 KO or KD in vivo disrupts corticogenesis through altered neuronal migration and that KO leads to reduced seizure threshold. Together these results demonstrate a direct causal role for SLC35A2 in cortical development.
PubMed: 38909838
DOI: 10.1016/j.neulet.2024.137881 -
Psychiatry Research. Neuroimaging Jun 2024Transcranial magnetic stimulation (TMS) is an FDA-approved neuromodulation treatment for major depressive disorder (MDD), thought to work by altering dysfunctional brain... (Review)
Review
Transcranial magnetic stimulation (TMS) is an FDA-approved neuromodulation treatment for major depressive disorder (MDD), thought to work by altering dysfunctional brain connectivity pathways, or by indirectly modulating the activity of subcortical brain regions. Clinical response to TMS remains highly variable, highlighting the need for baseline predictors of response and for understanding brain changes associated with response. This systematic review examined brain connectivity features, and changes in connectivity features, associated with clinical improvement following TMS in MDD. Forty-one studies met inclusion criteria, including 1097 people with MDD. Most studies delivered one of two types of TMS to left dorsolateral prefrontal cortex and measured connectivity using resting-state functional MRI. The subgenual anterior cingulate cortex was the most well-studied brain region, particularly its connectivity with the TMS target or with the "executive control network" of brain regions. There was marked heterogeneity in findings. There is a need for greater understanding of how cortical TMS modulates connectivity with, and the activity of, subcortical regions, and how these effects change within and across treatment sessions.
PubMed: 38908353
DOI: 10.1016/j.pscychresns.2024.111846 -
BMC Surgery Jun 2024posterior pedicle screw fixation is common method, one of the most severe complications is iatrogenic vascular damage, no report investigated association of different...
BACKGROUND
posterior pedicle screw fixation is common method, one of the most severe complications is iatrogenic vascular damage, no report investigated association of different introversion angles (INTAs) and length of pedicle screw. The aims were to investigate the optimal introversion angle and length of pedicle screw for improving the safety of the operation, and to analyze the differences of vascular damage types at L1-S1.
METHODS
Lumbar CT imaging data from110 patients were analyzed by DICOM software, and all parameters were measured by new Cartesian coordinate system, INTAs (L1-L5:5°,10°,15°,S1: 0°, 5°,10°,15°), D (the distance between the origin (O) with anterior vertebral cortex (AVC)), D (the distance between AVC and the prevertebral great vessels (PGVs)), D (the distance between the O and PGVs). At different INTAs, D were divided into four grades: Grade III: D ≤ 3 mm, Grade II: 3 mm < D ≤ 5 mm, Grade I: D > 5 mm, and N: the not touching PGVs.
RESULTS
The optimal INTA was 5° at L1-L3, the left was 5° and the right was 15° at L4, and screw length was less than 50 mm at L1-L4. At L5, the left optimal INTA was 5° and the right was 10°, and screw length was less than 45 mm. The optimal INTA was 15° at S1, and screw length was less than 50 mm. However, screw length was less than 40 mm when the INTA was 0° or 5° at S1.
CONCLUSIONS
At L5-S1, the risk of vascular injury is the highest. INTA and length of the pedicle screw in lumbar operation are closely related. 3 mm interval of screw length may be more preferable to reduce vascular damage.
Topics: Humans; Pedicle Screws; Female; Male; Middle Aged; Lumbar Vertebrae; Aged; Vascular System Injuries; Adult; Spinal Fusion; Tomography, X-Ray Computed; Sacrum; Retrospective Studies
PubMed: 38907190
DOI: 10.1186/s12893-024-02483-3 -
Acta Psychologica Jun 2024Engaging in chasing, where an actor actively pursues a target, is considered a crucial activity for the development of social skills. Previous studies have focused...
Engaging in chasing, where an actor actively pursues a target, is considered a crucial activity for the development of social skills. Previous studies have focused predominantly on understanding the neural correlates of chasing from an observer's perspective, but the neural mechanisms underlying the real-time implementation of chasing action remain poorly understood. To gain deeper insights into this phenomenon, the current study employed functional near-infrared spectroscopy (fNIRS) techniques and a novel interactive game. In this interactive game, participants (N = 29) were tasked to engage in chasing behavior by controlling an on-screen character using a gamepad, with the goal of catching a virtual partner. To specifically examine the brain activations associated with the interactive nature of chasing, we included two additional interactive actions: following action of following the path of a virtual partner and free action of moving without a specific pursuit goal. The results revealed that chasing and following actions elicited activation in a broad and overlapping network of brain regions, including the temporoparietal junction (TPJ), medial prefrontal cortex (mPFC), premotor cortex (PMC), primary somatosensory cortex (SI), and primary motor cortex (M1). Crucially, these regions were found to be modulated by the type of interaction, with greater activation and functional connectivity during the chasing interaction than during the following and free interactions. These findings suggested that both the MNS, encompassing regions such as the PMC, M1 and SI, and the mentalizing system (MS), involving the TPJ and mPFC, contribute to the execution of online chasing actions. Thus, the present study represents an initial step toward future investigations into the roles of MNS and MS in real-time chasing interactions.
PubMed: 38905953
DOI: 10.1016/j.actpsy.2024.104363 -
PloS One 2024Visual processing relies on the identification of both local and global features of visual stimuli. While well investigated at the behavioral level, the underlying brain...
Visual processing relies on the identification of both local and global features of visual stimuli. While well investigated at the behavioral level, the underlying brain mechanisms are less clear, especially in the context of aging. Using fMRI, we aimed to investigate the neural correlates underlying local and global processing in early and late adulthood. We recruited 77 healthy adults aged 19-77 who completed a visual search task based on 2-level hierarchical stimuli made of squares and/or circles. Participants were instructed to detect a target (a square) at either a local (small) or global (large) level of a hierarchical geometrical form, in the presence or absence of other hierarchical geometrical forms (distractors). At the behavioral level, we revealed high accuracy for all participants, but older participants were slower to detect local targets, specifically in presence of distractors. At the brain level, while both local and global processing were associated with occipital activation, local processing also recruited the anterior insula and dorsal anterior cingulate cortex, that are core regions of the salience network. However, while the presence of distractors in the local condition elicited specifically stronger activation within the right anterior insula for the young group, it was not observed for older participants. In addition, older participants showed less activation than younger participants in the occipital cortex, especially for the most complex conditions. Our findings suggest that the brain correlates underlying local and global processing change with aging, especially for complex visual patterns. These results are discussed in terms of top-down reduction effects from the salience network on primary visual areas, that may lead to specific difficulties to process local visual details in older adults.
Topics: Humans; Adult; Male; Female; Middle Aged; Magnetic Resonance Imaging; Aged; Young Adult; Brain Mapping; Visual Perception; Photic Stimulation; Brain; Aging; Reaction Time; Occipital Lobe
PubMed: 38905236
DOI: 10.1371/journal.pone.0303796 -
Critical Care Explorations Jul 2024Microvascular autoregulation (MA) maintains adequate tissue perfusion over a range of arterial blood pressure (ABP) and is frequently impaired in critical illness. MA... (Observational Study)
Observational Study Comparative Study
Microvascular Autoregulation in Skeletal Muscle Using Near-Infrared Spectroscopy and Derivation of Optimal Mean Arterial Pressure in the ICU: Pilot Study and Comparison With Cerebral Near-Infrared Spectroscopy.
IMPORTANCE
Microvascular autoregulation (MA) maintains adequate tissue perfusion over a range of arterial blood pressure (ABP) and is frequently impaired in critical illness. MA has been studied in the brain to derive personalized hemodynamic targets after brain injury. The ability to measure MA in other organs is not known, which may inform individualized management during shock.
OBJECTIVES
This study determines the feasibility of measuring MA in skeletal muscle using near-infrared spectroscopy (NIRS) as a marker of tissue perfusion, the derivation of optimal mean arterial pressure (MAPopt), and comparison with indices from the brain.
DESIGN
Prospective observational study.
SETTING
Medical and surgical ICU in a tertiary academic hospital.
PARTICIPANTS
Adult critically ill patients requiring vasoactive support on the first day of ICU admission.
MAIN OUTCOMES AND MEASURES
Fifteen critically ill patients were enrolled. NIRS was applied simultaneously to skeletal muscle (brachioradialis) and brain (frontal cortex) while ABP was measured continuously via invasive catheter. MA correlation indices were calculated between ABP and NIRS from skeletal muscle total hemoglobin (MVx), muscle tissue saturation index (MOx), brain total hemoglobin (THx), and brain tissue saturation index (COx). Curve fitting algorithms derive the MAP with the lowest correlation index value, which is the MAPopt.
RESULTS
MAPopt values were successfully calculated for each correlation index for all patients and were frequently (77%) above 65 mm Hg. For all correlation indices, median time was substantially above impaired MA threshold (24.5-34.9%) and below target MAPopt (9.0-78.6%). Muscle and brain MAPopt show moderate correlation (MVx-THx r = 0.76, p < 0.001; MOx-COx r = 0.69, p = 0.005), with a median difference of -1.27 mm Hg (-9.85 to -0.18 mm Hg) and 0.05 mm Hg (-7.05 to 2.68 mm Hg).
CONCLUSIONS AND RELEVANCE
This study demonstrates, for the first time, the feasibility of calculating MA indices and MAPopt in skeletal muscle using NIRS. Future studies should explore the association between impaired skeletal muscle MA, ICU outcomes, and organ-specific differences in MA and MAPopt thresholds.
Topics: Humans; Spectroscopy, Near-Infrared; Muscle, Skeletal; Pilot Projects; Male; Prospective Studies; Female; Middle Aged; Intensive Care Units; Arterial Pressure; Homeostasis; Critical Illness; Aged; Adult; Microcirculation; Brain
PubMed: 38904977
DOI: 10.1097/CCE.0000000000001111 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024The locus coeruleus-norepinephrine system plays a key role in supporting brain health along the lifespan, notably through its modulatory effects on neuroinflammation....
The locus coeruleus-norepinephrine system plays a key role in supporting brain health along the lifespan, notably through its modulatory effects on neuroinflammation. Using ultra-high field diffusion magnetic resonance imaging, we examined whether microstructural properties (neurite density index and orientation dispersion index) in the locus coeruleus were related to those in cortical and subcortical regions, and whether this was modulated by plasma glial fibrillary acidic protein levels, as a proxy of astrocyte reactivity. In our cohort of 60 healthy individuals (30 to 85 yr, 50% female), higher glial fibrillary acidic protein correlated with lower neurite density index in frontal cortical regions, the hippocampus, and the amygdala. Furthermore, under higher levels of glial fibrillary acidic protein (above ~ 150 pg/mL for cortical and ~ 145 pg/mL for subcortical regions), lower locus coeruleus orientation dispersion index was associated with lower orientation dispersion index in frontotemporal cortical regions and in subcortical regions. Interestingly, individuals with higher locus coeruleus orientation dispersion index exhibited higher orientation dispersion index in these (sub)cortical regions, despite having higher glial fibrillary acidic protein levels. Together, these results suggest that the interaction between locus coeruleus-norepinephrine cells and astrocytes can signal a detrimental or neuroprotective pathway for brain integrity and support the importance of maintaining locus coeruleus neuronal health in aging and in the prevention of age-related neurodegenerative diseases.
Topics: Humans; Female; Male; Locus Coeruleus; Astrocytes; Aged; Middle Aged; Adult; Aged, 80 and over; Glial Fibrillary Acidic Protein; Magnetic Resonance Imaging; Cerebral Cortex; Brain; Diffusion Magnetic Resonance Imaging; Neurites
PubMed: 38904081
DOI: 10.1093/cercor/bhae261 -
Frontiers in Aging Neuroscience 2024Recent evidence suggests that anosognosia or unawareness of cognitive impairment in Alzheimer's Disease (AD) may be explained by a disconnection between brain regions...
BACKGROUND
Recent evidence suggests that anosognosia or unawareness of cognitive impairment in Alzheimer's Disease (AD) may be explained by a disconnection between brain regions involved in accessing and monitoring information regarding self and others. It has been demonstrated that AD patients with anosognosia have reduced connectivity within the default mode network (DMN) and that anosognosia in people with prodromal AD is positively associated with bilateral anterior cingulate cortex (ACC), suggesting a possible role of this region in mechanisms of awareness in the early phase of disease. We hypothesized that anosognosia in AD is associated with an imbalance between the activity of large-scale resting-state functional magnetic resonance imaging (fMRI) networks, in particular the DMN, the salience network (SN), and the frontoparietal network (FPN).
METHODS
Sixty patients with MCI and AD dementia underwent fMRI and neuropsychological assessment including the Anosognosia Questionnaire Dementia (AQ-D), a measure of anosognosia based on a discrepancy score between patient's and carer's judgments. After having applied Independent Component Analysis (ICA) to resting fMRI data we performed: (i) correlations between the AQ-D score and functional connectivity in the DMN, SN, and FPN, and (ii) comparisons between aware and unaware patients of the DMN, SN, and FPN functional connectivity.
RESULTS
We found that anosognosia was associated with (i) weak functional connectivity within the DMN, in posterior and middle cingulate cortex particularly, (ii) strong functional connectivity within the SN in ACC, and between the SN and basal ganglia, and (iii) a heterogenous effect concerning the functional connectivity of the FPN, with a weak connectivity between the FPN and PCC, and a strong connectivity between the FPN and ACC. The observed effects were controlled for differences in severity of cognitive impairment and age.
CONCLUSION
Anosognosia in the AD continuum is associated with a dysregulation of the functional connectivity of three large-scale networks, namely the DMN, SN, and FPN.
PubMed: 38903902
DOI: 10.3389/fnagi.2024.1415994 -
Frontiers in Psychiatry 2024Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate...
BACKGROUND
Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD).
METHODS
Mice were subjected to social isolation during postnatal days 21-35 (P21-P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression.
RESULTS
In adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found.
CONCLUSION
Our study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior.
PubMed: 38903649
DOI: 10.3389/fpsyt.2024.1403476 -
Frontiers in Neuroscience 2024Reward-seeking behavior is frequently associated with risk of punishment. There are two types of punishment: positive punishment, which is defined as addition of an...
Reward-seeking behavior is frequently associated with risk of punishment. There are two types of punishment: positive punishment, which is defined as addition of an aversive stimulus, and negative punishment, involves the omission of a rewarding outcome. Although the medial prefrontal cortex (mPFC) is important in avoiding punishment, whether it is important for avoiding both positive and negative punishment and how it contributes to such avoidance are not clear. In this study, we trained male mice to perform decision-making tasks under the risks of positive (air-puff stimulus) and negative (reward omission) punishment, and modeled their behavior with reinforcement learning. Following the training, we pharmacologically inhibited the mPFC. We found that pharmacological inactivation of mPFC enhanced the reward-seeking choice under the risk of positive, but not negative, punishment. In reinforcement learning models, this behavioral change was well-explained as an increase in sensitivity to reward, rather than a decrease in the strength of aversion to punishment. Our results suggest that mPFC suppresses reward-seeking behavior by reducing sensitivity to reward under the risk of positive punishment.
PubMed: 38903603
DOI: 10.3389/fnins.2024.1412509