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AJNR. American Journal of Neuroradiology Jun 2024Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy-subject...
BACKGROUND AND PURPOSE
Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy-subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and silent word generation language paradigms using a large sample of patients with brain tumors.
MATERIALS AND METHODS
The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. 317 patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI dataset of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap map in Montreal Neurological Institute standard space. Wilcoxon signed-rank test was used to determine significant difference in the maximum Dice coefficient for our atlas compared to a meta-analysis-based template with respect to expert-delineated primary language area activations.
RESULTS
Probabilities of activating left anterior primary language area and left posterior primary language area in temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in left anterior primary language area (0.351 and 0.326, respectively, P < .05) and left posterior primary language area in temporal lobe (0.274 and 0.244, respectively, P < .005).
CONCLUSIONS
Brain tumor patient-and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients than the meta-analysis-based template.
ABBREVIATIONS
SENT = sentence completion, LETT = letter fluency, CAT = category fluency, PLA = primary language area, aPLA = anterior PLA, pPLAT = posterior PLA in the temporal lobe, pPLAP = posterior PLA in the parietal lobe, SMA = supplementary motor area, DLPFC = dorsolateral prefrontal cortex, BTLA = basal temporal language area.
PubMed: 38889968
DOI: 10.3174/ajnr.A8383 -
Sleep deprivation increases the generalization of perceptual and concept-based fear: An fNIRS study.Journal of Anxiety Disorders Jun 2024Insufficient sleep can initiate or exacerbate anxiety by triggering excessive fear generalization. In this study, a de novo paradigm was developed and used to examine...
Insufficient sleep can initiate or exacerbate anxiety by triggering excessive fear generalization. In this study, a de novo paradigm was developed and used to examine the neural mechanisms governing the effects of sleep deprivation on processing perceptual and concept-based fear generalizations. A between-subject design was adopted, wherein a control group (who had a typical night's sleep) and a one-night sleep deprivation group completed a fear acquisition task at 9:00 PM on the first day and underwent a generalization test the following morning at 7:00 AM. In the fear acquisition task, navy blue and olive green were used as perceptual cues (P+ and P-, respectively), while animals and furniture items were used as conceptual cues (C+ and C-, respectively). Generalization was tested for four novel generalized categories (C+P+, C+P-, C-P+, and C-P-). Shock expectancy ratings, skin conductance responses, and functional near-infrared spectroscopy were recorded during the fear acquisition and generalization processes. Compared with the group who had a typical night's sleep, the sleep deprived group showed higher shock expectancy ratings (especially for P+ and C-), increased oxygenated hemoglobin in the dorsolateral prefrontal cortex, and increased activation in the triangular inferior frontal gyrus during the generalization test. These findings suggest that sleep deprivation increases the generalization of threat memories, thus providing insights into the overgeneralization characteristics of anxiety and fear-related disorders.
PubMed: 38889495
DOI: 10.1016/j.janxdis.2024.102892 -
Proceedings of the National Academy of... Jul 2024Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function...
Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position mitochondria both as targets and drivers of psychosocial experiences. On the one hand, chronic stress exposure and mood states may alter multiple aspects of mitochondrial biology; on the other hand, functional variations in mitochondrial OxPhos capacity may alter social behavior, stress reactivity, and mood. But are psychosocial exposures and subjective experiences linked to mitochondrial biology in the human brain? By combining longitudinal antemortem assessments of psychosocial factors with postmortem brain (dorsolateral prefrontal cortex) proteomics in older adults, we find that higher well-being is linked to greater abundance of the mitochondrial OxPhos machinery, whereas higher negative mood is linked to lower OxPhos protein content. Combined, positive and negative psychosocial factors explained 18 to 25% of the variance in the abundance of OxPhos complex I, the primary biochemical entry point that energizes brain mitochondria. Moreover, interrogating mitochondrial psychobiological associations in specific neuronal and nonneuronal brain cells with single-nucleus RNA sequencing (RNA-seq) revealed strong cell-type-specific associations for positive psychosocial experiences and mitochondria in glia but opposite associations in neurons. As a result, these "mind-mitochondria" associations were masked in bulk RNA-seq, highlighting the likely underestimation of true psychobiological effect sizes in bulk brain tissues. Thus, self-reported psychosocial experiences are linked to human brain mitochondrial phenotypes.
Topics: Humans; Mitochondria; Male; Oxidative Phosphorylation; Female; Brain; Aged; Stress, Psychological; Middle Aged; Prefrontal Cortex; Neurons; Proteomics; Affect
PubMed: 38889126
DOI: 10.1073/pnas.2317673121 -
IScience Jun 2024The dorsolateral striatum (DLS) is important for performing actions persistently, even when it becomes suboptimal, reflecting a function that is reflexive and habitual....
The dorsolateral striatum (DLS) is important for performing actions persistently, even when it becomes suboptimal, reflecting a function that is reflexive and habitual. However, there are also ways in which persistent behaviors can result from a more prospective, planning mode of behavior. To help tease apart these possibilities for DLS function, we trained animals to perform a lever press for reward and then inhibited the DLS in key test phases: as the task shifted from a 1-press to a 3-press rule (upshift), as the task was maintained, as the task shifted back to the one-press rule (downshift), and when rewards came independent of pressing. During DLS inhibition, animals always favored their initially learned strategy to press just once, particularly so during the free-reward period. DLS inhibition surprisingly changed performance speed bidirectionally depending on the task shifts. DLS inhibition thus encouraged habitual behavior, suggesting it could normally help adapt to changing conditions.
PubMed: 38883824
DOI: 10.1016/j.isci.2024.110044 -
Scientific Reports Jun 2024Children with attention deficit/hyperactivity disorder (ADHD) typically exhibit difficulties in emotion regulation. It has been shown that the dorsolateral prefrontal...
Children with attention deficit/hyperactivity disorder (ADHD) typically exhibit difficulties in emotion regulation. It has been shown that the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) are crucially involved in these deficient processes. In this study, we aimed to explore the impact of electrical stimulation over the left dlPFC and right vmPFC on emotion regulation in children with ADHD. Twenty-four children with ADHD completed the Emotional Go/No-Go and Emotional 1-Back tasks while undergoing transcranial direct current stimulation (tDCS) in three separate sessions, each with a different electrode placement: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation. During both real tDCS conditions, the accuracy of pre-potent inhibitory control and working memory performance improved, but not speed. This study provides evidence that the left dlPFC and the right vmPFC are involved in emotion regulation in ADHD.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Transcranial Direct Current Stimulation; Child; Male; Female; Emotional Regulation; Prefrontal Cortex; Memory, Short-Term; Emotions; Dorsolateral Prefrontal Cortex; Adolescent
PubMed: 38880826
DOI: 10.1038/s41598-024-64886-9 -
Journal of Affective Disorders Jun 2024Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the...
BACKGROUND
Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD.
METHODS
Positron emission tomography (PET) with [F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25).
RESULTS
Consistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r≥0.904, p≤0.005) and attention (r≥0.809, p≤0.028).
LIMITATIONS
The modest sample size is the primary limitation.
CONCLUSIONS
Deficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights.
PubMed: 38876317
DOI: 10.1016/j.jad.2024.06.025 -
Human Movement Science Jun 2024Transcranial direct current stimulation (tDCS) and high-intensity interval training (HIIT) have been demonstrated to enhance inhibitory control and working memory (WM)...
Transcranial direct current stimulation (tDCS) and high-intensity interval training (HIIT) have been demonstrated to enhance inhibitory control and working memory (WM) performance in healthy adults. However, the potential benefits of combining these two interventions have been rarely explored and remain largely speculative. This study aimed to explore the effects of acute HIIT combined with dual-site tDCS over the dorsolateral prefrontal cortex (DLPFC, F3 and F4) on inhibitory control and WM in healthy young adults. Twenty-five healthy college students (20.5 ± 1.3 years; 11 females) were recruited to complete HIIT + tDCS, HIIT + sham-tDCS, rest + tDCS, and rest + sham-tDCS (CON) sessions in a randomized crossover design. tDCS or sham-tDCS was conducted after completing HIIT or a rest condition of the same duration. The Stroop and 2-back tasks were used to evaluate the influence of this combined intervention on cognitive tasks involving inhibitory control and WM performance in post-trials, respectively. Response times (RTs) of the Stroop task significantly improved in the HIIT + tDCS session compared to the CON session across all conditions (all p values <0.05), in the HIIT + tDCS session compared to the rest + tDCS session in the congruent and neutral conditions (all p values <0.05), in the HIIT + sham-tDCS session compared to the CON session in the congruent and neutral conditions (all p values <0.05), in the HIIT + sham-tDCS session compared to the rest + tDCS session in the congruent condition (p = 0.015). No differences were found between sessions in composite score of RT and accuracy in the Stroop task (all p values >0.05) and in the 2-back task reaction time and accuracy (all p values >0.05). We conclude that acute HIIT combined with tDCS effectively improved inhibitory control but it failed to yield cumulative benefits on inhibitory control and WM in healthy adults. These preliminary findings help to identify beneficial effects of combined interventions on cognitive performance and might guide future research with clinical populations.
PubMed: 38875731
DOI: 10.1016/j.humov.2024.103240 -
ELife Jun 2024Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and...
Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it's unclear whether they exist during developmental EMT. Neural crest cells (NCC) are an embryonic progenitor cell population that gives rise to numerous cell types and tissues in vertebrates, and their formation and delamination is a classic example of developmental EMT. However, whether intermediate states also exist during NCC EMT and delamination remains unknown. Through single-cell RNA sequencing of mouse embryos, we identified intermediate NCC states based on their transcriptional signature and then spatially defined their locations in situ in the dorsolateral neuroepithelium. Our results illustrate the importance of cell cycle regulation and functional role for the intermediate stage marker in facilitating mammalian cranial NCC delamination and may provide new insights into mechanisms regulating pathological EMP.
Topics: Neural Crest; Animals; Epithelial-Mesenchymal Transition; Mice; Single-Cell Analysis
PubMed: 38873887
DOI: 10.7554/eLife.92844 -
Journal of Psychopathology and Clinical... Jun 2024Childhood externalizing psychopathology is heterogeneous. Symptom variability in conduct disorder (CD), oppositional defiant disorder (ODD),...
Childhood externalizing psychopathology is heterogeneous. Symptom variability in conduct disorder (CD), oppositional defiant disorder (ODD), attention-deficit/hyperactivity disorder (ADHD), and callous-unemotional (CU) traits designate different subgroups of children with externalizing problems who have specific treatment needs. However, CD, ODD, ADHD, and CU traits are highly comorbid. Studies need to generate insights into shared versus unique risk mechanisms, including through the use of functional magnetic resonance imaging (fMRI). In this study, we tested whether symptoms of CD, ODD, ADHD, and CU traits were best represented within a bifactor framework, simultaneously modeling shared (i.e., general externalizing problems) and unique (i.e., symptom-specific) variance, or through a four-correlated factor or second-order factor model. Participants ( = 11,878, age, = 9 years) were from the Adolescent Brain and Cognitive Development Study. We used questionnaire and functional magnetic resonance imaging data (emotional N-back task) from the baseline assessment. A bifactor model specifying a general externalizing and specific CD, ODD, ADHD, and CU traits factors demonstrated the best fit. The four-correlated and second-order factor models both fit the data well and were retained for analyses. Across models, reduced right amygdala activity to fearful faces was associated with more general externalizing problems and reduced dorsolateral prefrontal cortex activity to fearful faces was associated with higher CU traits. ADHD scores were related to greater right nucleus accumbens activation to fearful and happy faces. Results give insights into risk mechanisms underlying comorbidity and heterogeneity within externalizing psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38869879
DOI: 10.1037/abn0000923 -
Neuroscience Bulletin Jun 2024Within the prefrontal-cingulate cortex, abnormalities in coupling between neuronal networks can disturb the emotion-cognition interactions, contributing to the...
Within the prefrontal-cingulate cortex, abnormalities in coupling between neuronal networks can disturb the emotion-cognition interactions, contributing to the development of mental disorders such as depression. Despite this understanding, the neural circuit mechanisms underlying this phenomenon remain elusive. In this study, we present a biophysical computational model encompassing three crucial regions, including the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and ventromedial prefrontal cortex. The objective is to investigate the role of coupling relationships within the prefrontal-cingulate cortex networks in balancing emotions and cognitive processes. The numerical results confirm that coupled weights play a crucial role in the balance of emotional cognitive networks. Furthermore, our model predicts the pathogenic mechanism of depression resulting from abnormalities in the subgenual cortex, and network functionality was restored through intervention in the dorsolateral prefrontal cortex. This study utilizes computational modeling techniques to provide an insight explanation for the diagnosis and treatment of depression.
PubMed: 38869704
DOI: 10.1007/s12264-024-01246-7