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The Journal of Neuroscience : the... May 2023Regional cellular heterogeneity is a fundamental feature of the human neocortex; however, details of this heterogeneity are still undefined. We used single-nucleus...
Regional cellular heterogeneity is a fundamental feature of the human neocortex; however, details of this heterogeneity are still undefined. We used single-nucleus RNA-sequencing to examine cell-specific transcriptional features in the dorsolateral PFC (DLPFC) and the subgenual anterior cingulate cortex (sgACC), regions implicated in major psychiatric disorders. Droplet-based nuclei-capture and library preparation were performed on replicate samples from 8 male donors without history of psychiatric or neurologic disorder. Unsupervised clustering identified major neural cell classes. Subsequent iterative clustering of neurons further revealed 20 excitatory and 22 inhibitory subclasses. Inhibitory cells were consistently more abundant in the sgACC and excitatory neuron subclusters exhibited considerable variability across brain regions. Excitatory cell subclasses also exhibited greater within-class transcriptional differences between the two regions. We used these molecular definitions to determine which cell classes might be enriched in loci carrying a genetic signal in genome-wide association studies or for differentially expressed genes in mental illness. We found that the heritable signals of psychiatric disorders were enriched in neurons and that, while the gene expression changes detected in bulk-RNA-sequencing studies were dominated by glial cells, some alterations could be identified in specific classes of excitatory and inhibitory neurons. Intriguingly, only two excitatory cell classes exhibited concomitant region-specific enrichment for both genome-wide association study loci and transcriptional dysregulation. In sum, by detailing the molecular and cellular diversity of the DLPFC and sgACC, we were able to generate hypotheses on regional and cell-specific dysfunctions that may contribute to the development of mental illness. Dysfunction of the subgenual anterior cingulate cortex has been implicated in mood disorders, particularly major depressive disorder, and the dorsolateral PFC, a subsection of the PFC involved in executive functioning, has been implicated in schizophrenia. Understanding the cellular composition of these regions is critical to elucidating the neurobiology underlying psychiatric and neurologic disorders. We studied cell type diversity of the subgenual anterior cingulate cortex and dorsolateral PFC of humans with no neuropsychiatric illness using a clustering analysis of single-nuclei RNA-sequencing data. Defining the transcriptomic profile of cellular subpopulations in these cortical regions is a first step to demystifying the cellular and molecular pathways involved in psychiatric disorders.
Topics: Humans; Male; Dorsolateral Prefrontal Cortex; Depressive Disorder, Major; Gyrus Cinguli; Prefrontal Cortex; Genome-Wide Association Study; Solitary Nucleus
PubMed: 37037607
DOI: 10.1523/JNEUROSCI.0830-22.2023 -
Cureus Mar 2021Introduction This study aimed to evaluate the clinical outcomes of 16 patients with capitellum and trochlea fractures that were treated using isolated headless...
Introduction This study aimed to evaluate the clinical outcomes of 16 patients with capitellum and trochlea fractures that were treated using isolated headless compression screws or a combination of dorsolateral locking plates and anterior-to-posterior screws. We also investigated the presence of lateral epicondyle fragments because this fragment is especially important when making decisions regarding the surgical approach and implants. Materials and methods We conducted a retrospective analysis of 16 patients with capitellum and trochlea fractures. Clinical, radiographic (based on CT scans), and elbow-specific outcomes, including the Mayo Elbow Performance Index (MEPI), were evaluated at a mean of 23.5 months postoperatively. Results The average MEPI scores in patients with Dubberley type A (non-posterior comminution) and type B (posterior comminution) fractures were 88 and 78, respectively (p=0.08). Headless compression screws were used in 10 cases of type A fracture and one case of type B fracture. A combination of dorsolateral locking plates and anterior-to-posterior screws was used in five cases of type B fracture. Hardware loosening was seen in one case of type B fracture with isolated screw fixation. The presence of a lateral epicondyle fragment was significantly associated with the type B group (6/6 patients; 100%). In contrast, patients in the type A group rarely had posterior comminution of the lateral epicondyle fragment (2/10 patients; 20%). Conclusions Capitellum and trochlea fractures with posterior comminution, which typically presented with lateral epicondylar fragments, were safely and effectively treated with a combination of dorsolateral locking plates and anterior-to-posterior screws through lateral approaches. Cases without posterior comminution were treated with headless compression screws with no complications. The Dubberley classification system provides helpful information to determine the fixation strategy.
PubMed: 33842118
DOI: 10.7759/cureus.13740 -
Psychological Medicine Apr 2023Repetitive transcranial magnetic stimulation has been employed to treat drug dependence, reduce drug use and improve cognition. The aim of the study was to analyze the...
BACKGROUND
Repetitive transcranial magnetic stimulation has been employed to treat drug dependence, reduce drug use and improve cognition. The aim of the study was to analyze the effectiveness of intermittent theta-burst stimulation (iTBS) on cognition in individuals with methamphetamine use disorder (MUD).
METHODS
This was a secondary analysis of 40 MUD subjects receiving left dorsolateral prefrontal cortex (L-DLPFC) iTBS or sham iTBS for 20 times over 10 days (twice-daily). Changes in working memory (WM) accuracy, reaction time, and sensitivity index were analyzed before and after active and sham rTMS treatment. Resting-state EEG was also acquired to identify potential biological changes that may relate to any cognitive improvement.
RESULTS
The results showed that iTBS increased WM accuracy and discrimination ability, and improved reaction time relative to sham iTBS. iTBS also reduced resting-state delta power over the left prefrontal region. This reduction in resting-state delta power correlated with the changes in WM.
CONCLUSIONS
Prefrontal iTBS may enhance WM performance in MUD subjects. iTBS induced resting EEG changes raising the possibility that such findings may represent a biological target of iTBS treatment response.
Topics: Humans; Dorsolateral Prefrontal Cortex; Transcranial Magnetic Stimulation; Memory, Short-Term; Prefrontal Cortex; Methamphetamine
PubMed: 37310309
DOI: 10.1017/S003329172100430X -
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 -
Journal of Affective Disorders Oct 2023Cardiovascular autonomic system (ANS) may be affected by altered neural activations in the brain. This systematic review and meta-analysis investigated potential effects... (Review)
Review
BACKGROUND
Cardiovascular autonomic system (ANS) may be affected by altered neural activations in the brain. This systematic review and meta-analysis investigated potential effects of repetitive transcranial magnetic stimulation (rTMS) protocols on cardiovascular ANS control.
METHODS
Through 19 qualified studies, we acquired 70 comparisons for data synthesis. Individual effect sizes were estimated by comparing changes in following cardiovascular ANS control variables between active and sham stimulation conditions: (a) blood pressure (BP), (b) heart rate (HR), and (c) heart rate variability (HRV). Moreover, two moderator variable analyses determined whether changes in cardiovascular ANS control were different based on (a) rTMS protocols (excitatory rTMS versus inhibitory rTMS) and (b) specific targeted cortical regions, respectively.
RESULTS
The random-effects model meta-analysis revealed significant improvements in cardiovascular ANS control after the rTMS protocols. Specifically, applying excitatory and inhibitory rTMS protocols significantly decreased values of BP and HR variables. For HRV variables, excitatory rTMS protocols showed significant positive effects. These improvements in cardiovascular ANS control were observed while applying either excitatory rTMS protocols to the left dorsolateral prefrontal cortex or inhibitory rTMS protocols to the right dorsolateral prefrontal cortex.
LIMITATIONS
Relatively small number of studies for inhibitory rTMS on the right dorsolateral prefrontal cortex were included in this meta-analysis.
CONCLUSION
These findings suggest that applying excitatory and inhibitory rTMS protocols on prefrontal cortical regions may be effective to improve cardiovascular ANS control.
PubMed: 37459970
DOI: 10.1016/j.jad.2023.07.039 -
Learning & Memory (Cold Spring Harbor,... Oct 2020Most experimental preparations demonstrate a role for dorsolateral striatum (DLS) in stimulus-response, but not outcome-based, learning. Here, we assessed DLS...
Most experimental preparations demonstrate a role for dorsolateral striatum (DLS) in stimulus-response, but not outcome-based, learning. Here, we assessed DLS involvement in a touchscreen-based reversal task requiring mice to update choice following a change in stimulus-reward contingencies. In vivo single-unit recordings in the DLS showed reversal produced a population-level shift from excited to inhibited neuronal activity prior to choices being made. The larger the shift, the faster mice reversed. Furthermore, optogenetic photosilencing DLS neurons during choice increased early reversal errors. These findings suggest dynamic DLS engagement may facilitate reversal, possibly by signaling a change in contingencies to other striatal and cortical regions.
Topics: Animals; Conditioning, Operant; Corpus Striatum; Discrimination Learning; Male; Mice; Mice, Inbred C57BL; Photic Stimulation; Reversal Learning
PubMed: 32934094
DOI: 10.1101/lm.051714.120 -
Journal of Neurochemistry Sep 2022A distinct population of dopamine neurons in the substantia nigra pars lateralis (SNL) has a unique projection to the most caudolateral (tail) region of the striatum....
A distinct population of dopamine neurons in the substantia nigra pars lateralis (SNL) has a unique projection to the most caudolateral (tail) region of the striatum. Here, using two electrochemical techniques to measure basal dopamine and electrically evoked dopamine release in anesthetized rats, we characterized this pathway, and compared it with the 'classic' nigrostriatal pathway from neighboring substantia nigra pars compacta (SNc) dopamine neurons to the dorsolateral striatum. We found that the tail striatum constitutes a distinct dopamine domain compared with the dorsolateral striatum, with consistently lower basal and evoked dopamine, and diverse dopamine release kinetics. Importantly, electrical stimulation of the SNL and SNc evoked dopamine release in entirely separate striatal regions; the tail and dorsolateral striatum, respectively. Furthermore, we showed that stimulation of the subthalamic nucleus (STN) evoked dopamine release exclusively in the tail striatum, likely via the SNL, consistent with previous anatomical evidence of STN afferents to SNL dopamine neurons. Our work identifies the STN as an important modulator of dopamine release in a novel dopamine pathway to the tail striatum, largely independent of the classic nigrostriatal pathway, which necessitates a revision of the basal ganglia circuitry with the STN positioned as a central integrator of striatal information.
Topics: Animals; Basal Ganglia; Corpus Striatum; Dopamine; Dopaminergic Neurons; Rats; Substantia Nigra; Subthalamic Nucleus
PubMed: 35869680
DOI: 10.1111/jnc.15677 -
Brain Research Sep 2022The evaluation of external and internal stimuli permits the ongoing actualization of choice-related information and, thus, the association between stimuli and outcomes....
The evaluation of external and internal stimuli permits the ongoing actualization of choice-related information and, thus, the association between stimuli and outcomes. This process is essential to decision-making as it allows constant adaptation to environmental changes in order to maximize gains and minimize losses. Reversal learning paradigms are used to study this process, which has been associated with prefrontal cortex activity (frontopolar, dorsolateral) in conjunction with posterior areas (parietal, temporal), due to their participation in integrating and processing the stimuli-reward relation. The aim of this study was to assess the cortical functionality associated with reversal learning during the decision-making process. The EEG activity of 22 young men was recorded while performing a decision-making task in a reversal learning condition compared to an initial learning condition. EEG data were analyzed during evaluation of the stimuli, before motor execution (formation of preferences), and during task feedback (outcome evaluation). The formation of preferences stage was characterized by a higher correlation of the alpha2 band between the parietal cortices. In the feedback stage of the reversal learning condition, a higher absolute power of the theta band in the left dorsolateral (F3), and a lower correlation of the alpha1 band between the right frontopolar and dorsolateral (Fp2-F4), as well as between the right frontopolar and temporal (Fp2-T4), were observed. The data obtained show that the EEG activity of the areas recorded changed in the evaluation of the stimuli information in the reversal learning condition during a decision-making task.
Topics: Decision Making; Humans; Male; Parietal Lobe; Prefrontal Cortex; Reversal Learning; Reward
PubMed: 35780864
DOI: 10.1016/j.brainres.2022.147998 -
Archives of Suicide Research : Official... 2022The current study investigated the neural correlates of non-suicidal self-injury (NSSI) and suicidal ideation across the dorsolateral prefrontal cortex. Two-hundred...
The current study investigated the neural correlates of non-suicidal self-injury (NSSI) and suicidal ideation across the dorsolateral prefrontal cortex. Two-hundred ninety-six undergraduates solved anagram tasks while being monitored by a functional near-infrared spectroscopy device, and completed a questionnaire assessing behaviors and symptoms. Repeated measures analysis of variance revealed location-specific changes in neural activity based on NSSI, suicidal ideation, task type, and cognitive demand. The presence of suicidal ideation was associated with specific patterns of neural activity, modified by sex and task type. Interestingly, participants who engaged in NSSI exhibited some deactivation of the dlPFC when faced with more difficult cognitive challenges. Future research on these processes may allow for noninvasive imaging techniques to help screen risk for suicidality and NSSI.
Topics: Dorsolateral Prefrontal Cortex; Humans; Risk Factors; Self-Injurious Behavior; Suicidal Ideation; Surveys and Questionnaires
PubMed: 32589862
DOI: 10.1080/13811118.2020.1779154 -
Frontiers in Aging Neuroscience 2023Previous research has primarily focused on the association between muscle strength and global cognitive function in older adults, while the connection between muscle...
OBJECTIVE
Previous research has primarily focused on the association between muscle strength and global cognitive function in older adults, while the connection between muscle strength and advanced cognitive function such as inhibition and working memory (WM) remains unclear. This study aimed to investigate the relationship among muscle strength, WM, and task-related cortex hemodynamics.
METHODS
We recruited eighty-one older adults. Muscle strength was measured using a grip and lower limb strength protocol. We measured the WM performance by using reaction time (RT) and accuracy (ACC) in the N-back task and the cortical hemodynamics of the prefrontal cortex (PFC) by functional near-infrared spectroscopy (fNIRS).
RESULTS
We found positive correlations between grip strength ( < 0.05), 30-s sit-up ( < 0.05) and ACC, negative correlation between grip strength ( < 0.05) and RT. Furthermore, we observed positive correlations between grip strength and the level of oxygenated hemoglobin (HbO) in dorsolateral prefrontal cortex, frontopolar area, ventrolateral prefrontal cortex ( < 0.05), and negative correlations between grip strength and the level of deoxygenated hemoglobin (Hb) in left dorsolateral prefrontal cortex, frontopolar area, left ventrolateral prefrontal cortex ( < 0.05). Additionally, we noticed positive correlations between RT and the level of Hb in left dorsolateral prefrontal cortex, right frontopolar area ( < 0.05), and negative correlations between RT and the level of HbO in left dorsolateral prefrontal cortex, frontopolar area ( < 0.05). However, the cortical hemodynamics did not mediate the relationship between muscle strength and WM performance (RT, ACC).
CONCLUSION
The grip strength of older adults predicted WM in the cross-section study. The level of hemodynamics in PFC can serve as a predictor of WM.
PubMed: 37876877
DOI: 10.3389/fnagi.2023.1243283