Brain Structures Research Articles

Neuroimaging Insights into Autism Spectrum Disorder: Structural and Functional Brain

Neuroimaging Insights into Autism Spectrum Disorder: Structural and Functional Brain

Optimasi Deteksi Tumor Otak Menggunakan Adaptive Multiscale Retinex dan YOLOV10 Pada Citra Digital

The incidence of brain tumors in Indonesia continues to rise annually, affecting both adults and children. Therefore, an effective detection system is required to differentiate MRI images showing the presence of brain tumors from those that do not. This distinction is crucial in the analysis and diagnosis of medical images. This study aims to optimize brain tumor detection in digital images by combining the Adaptive Multiscale Retinex (AMSR) method with the YOLOv10 algorithm. AMSR enhances the quality and contrast of brain images, making critical details more visible. The method adjusts the scale and intensity of image lighting to address uneven illumination and improve the visibility of brain structures. YOLOv10 is recognized for its speed and accuracy in real-time object detection. This algorithm employs deep learning techniques to identify and classify objects with high precision on enhanced brain image datasets. The model's performance was evaluated using metrics such as accuracy, sensitivity, specificity, and computation time. Results indicate that the combination of AMSR and YOLOv10 improves the accuracy and efficiency of brain tumor detection compared to conventional methods. The YOLOv10 model achieved a detection accuracy of 92%. This study provides significant contributions to early brain tumor detection technology, with important implications for the healthcare sector.

Distributed associations among white matter hyperintensities and structural brain networks with fluid cognition in healthy aging

AbstractWhite matter hyperintensities (WMHs) are associated with age-related cognitive impairment and increased risk of Alzheimer’s disease. However, the manner by which WMHs contribute to cognitive impairment is unclear. Using a combination of predictive modeling and network neuroscience, we investigated the relationship between structural white matter connectivity and age, fluid cognition, and WMHs in 68 healthy adults (18–78 years). Consistent with previous work, WMHs were increased in older adults and exhibited a strong negative association with fluid cognition. Extending previous work, using predictive modeling, we demonstrated that age, WMHs, and fluid cognition were jointly associated with widespread alterations in structural connectivity. Subcortical-cortical connections between the thalamus/basal ganglia and frontal and parietal regions of the default mode and frontoparietal networks were most prominent. At the network level, both age and WMHs were negatively associated with network density and communicability, and positively associated with modularity. Spatially, WMHs were most prominent in arterial zones served by the middle cerebral artery and associated lenticulostriate branches that supply subcortical regions. Finally, WMHs overlapped with all major white matter tracts, most prominently in tracts that facilitate subcortical-cortical communication and are implicated in fluid cognition, including the anterior thalamic-radiations and forceps minor. Finally, results of mediation analyses suggest that whole-brain WMH load influences age-related decline in fluid cognition. Thus, across multiple levels of analysis, we showed that WMHs were increased in older adults and associated with altered structural white matter connectivity and network topology involving subcortical-cortical pathways critical for fluid cognition.

Protocol for a pilot clinical trial of the senolytic drug combination Dasatinib Plus Quercetin to mitigate age-related health and cognitive decline in mental disorders

Background Major depressive disorder (MDD) and schizophrenia are linked to accelerated aging leading to reduced lifespan, health span and cognitive decline. Cellular senescence, in which cells lose proliferative capacity and develop a senescence-associated secretory phenotype (SASP), plays a role in this process. Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related health and cognitive decline. This pilot study aims to assess the feasibility and safety of D+Q in older adults with schizophrenia, schizoaffective disorder, and treatment-resistant depression (TRD). Methods This single-center study will recruit 30 participants total aged 50 years or older with schizophrenia/schizoaffective disorder or 60 years or older with TRD; the difference in age limits is because individuals with schizophrenia are biologically about 10 years older than general population owing to metabolic burden. Each participant will receive two consecutive days of 100 mg oral dasatinib plus 1250 mg oral quercetin at baseline and weeks one through three, (i.e., two days on, five days off) along with lifestyle risk management education. Questionnaires and assessments will measure health and cognitive function as well as psychiatric function at baseline, week 10, and one year. Magnetic Resonance Imaging (MRI) will measure structural and functional brain health at baseline and 10 weeks. Blood sampling for SASP testing will occur at seven time points: baseline, weeks one through four, week 10, and one year. Conclusion This pilot aims to evaluate the safety and feasibility of the senolytic regimen and D+Q’s potential to counteract accelerated aging in adults with schizophrenia/schizoaffective disorder and TRD. Trial registration Dasatinib Plus Quercetin for Accelerated Aging in Mental Disorders is registered on ClinicalTrials.gov: NCT05838560; posted May 1, 2023.

Distinct ventral hippocampal inhibitory microcircuits regulating anxiety and fear behaviors

In emotion research, anxiety and fear have always been interconnected, sharing overlapping brain structures and neural circuitry. Recent investigations, however, have unveiled parallel long-range projection pathways originating from the ventral hippocampus, shedding light on their distinct roles in anxiety and fear. Yet, the mechanisms governing the emergence of projection-specific activity patterns to mediate different negative emotions remain elusive. Here, we show a division of labor in local GABAergic inhibitory microcircuits of the ventral hippocampus, orchestrating the activity of subpopulations of pyramidal neurons to shape anxiety and fear behaviors in mice. These findings offer a comprehensive insight into how distinct inhibitory microcircuits are dynamically engaged to encode different emotional states.

Atrophy in the supramarginal gyrus associated with impaired cognitive inhibition in grieving Chinese Shidu parents

ABSTRACT Background: The loss of an only child, known as Shidu in China, is a profoundly distressing experience, often leading to Prolonged Grief Disorder (PGD). Despite its impact, the structural brain alterations associated with PGD, potentially influencing cognitive impairments in Shidu parents, remain understudied. Objective: This study aims to identify brain structural abnormalities related to prolonged grief and their relation with cognitive inhibition in Shidu parents. Methods: The study included 40 Shidu parents and 42 non-bereaved participants. Prolonged grief was evaluated using the Prolonged Grief Questionnaire (PG-13). We employed voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to assess brain structural alterations and their correlation with cognitive inhibition, as measured by Stroop interference scores. Results: Findings suggest that greater prolonged grief intensity correlates with reduced grey matter volume in the right amygdala and the left supramarginal gyrus (SMG). Additionally, enhanced amygdala-to-whole-brain structural connectivity showed a marginal association with prolonged grief, particularly with emotional-related symptoms. Furthermore, a decrease in SMG volume was found to mediate the relation between prolonged grief and Stroop Time Inference (TI) score, indicating an indirect effect of prolonged grief on cognitive inhibition. Conclusions: The study provides insight into the neural correlates of prolonged grief in Shidu parents, highlighting the SMG’s role in cognitive inhibition. These findings emphasise the need for comprehensive grief interventions to address the complex cognitive and emotional challenges faced by this unique bereaved population.

Investigating the genetic relationship of intracranial and subcortical brain volumes with depression and other psychiatric disorders

Abstract Depression is one of the most common mental health disorders worldwide, yet its neurobiological mechanisms remain poorly understood. Structural brain differences in subcortical limbic regions are thought to be implicated in the pathology of depression. We leveraged genome-wide association studies (GWAS) summary-level data to explore the molecular pathways underlying the relationship between genetic risk for depression and intracranial and subcortical brain volumes measured via magnetic resonance imaging. At the whole-genome level, we identified a negative genetic correlation (rG) between depression and the volume of the ventral diencephalon (rG = -0.08), which remained significant after adjusting for multiple testing. We observed nominal (P < 0.05) positive genetic correlations between depression and the volumes of the caudate nucleus (rG = 0.06) and the putamen (rG = 0.06), while hippocampal volume displayed a negative genetic correlation (rG = -0.06) with depression. Pairwise GWAS analyses uncovered 104 genome segments with genetic variants influencing the aetiology of depression and at least one brain volume at the local genetic level. Gene association analyses of these genomic segments suggest putative links with dopamine neurotransmission, mesocorticolimbic functional connectivity, GABAergic transmission, and the insulin signalling pathway. Sensitivity analyses showed that the volume of the ventral diencephalon is also negatively correlated with bipolar disorder and schizophrenia; however, most of the genes associated with depression and brain volumes are specific for depression and do not replicate when investigating bipolar disorder or schizophrenia with brain volumes. We observed negative phenotypic correlations between depression and intracranial and subcortical brain volumes. Overall, our findings contribute to our understanding of the neurobiology of depression and suggest that, besides the known role of the hippocampus, other subcortical structures might also play essential roles in the aetiology of depression.

The Potential Utility of Retinal Biomarkers to Index Central Nervous System Effects of Repetitive Blast Exposure in Military Personnel.

Military personnel exposed to blasts receive repeated subconcussive head impacts. Although these events typically do not cause immediate symptoms and do not lead to medical evaluation, the cumulative effects of subconcussive impacts can be significant and can include postconcussive symptoms, changes in brain structure and function, long-term cognitive dysfunction, depression, and chronic traumatic encephalopathy. Retinal measures such as thickness of retinal neural layers, density of retinal microvasculature, and strength of retinal neuronal firing are associated with cognitive function and brain structure and function in healthy populations and in neurodegenerative disease cohorts, and changes over time in retinal indices predict cognitive decline and brain atrophy in longitudinal studies in a range of medical populations. This commentary highlights the potential benefits of using retinal biomarkers in the routine screening and monitoring of brain health in warfighters and veterans. Retinal measures can be rapidly acquired (often in a matter of seconds) using methods that are inexpensive and noninvasive, and they can be collected with movable and often portable equipment that uses automated scoring routines that can be used for prediction and decision-making at the individual level. To date, however, retinal biomarkers have not been included in studies of blast overpressure exposures in military personnel. Despite this, preclinical and human evidence suggests that they could be among the most effective methods for tracking central nervous system damage in people exposed to repeated blasts. Retinal biomarkers could also contribute to brief test batteries to determine who is most at risk for long-term negative effects of future exposures. In addition, the sensitivity of retinal indices to blast exposure and mild traumatic brain injury suggests that they should be incorporated into research on strategies to minimize or prevent blast-related short- and long-term central nervous system changes in blast-exposed military personnel.

Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids

A hexanucleotide repeat expansion (HRE) in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Human brain imaging and experimental studies indicate early changes in brain structure and connectivity in C9-ALS/FTD, even before symptom onset. Because these early disease phenotypes remain incompletely understood, we generated iPSC-derived cerebral organoid models from C9-ALS/FTD patients, presymptomatic C9ORF72-HRE (C9-HRE) carriers, and controls. Our work revealed the presence of all three C9-HRE-related molecular pathologies and developmental stage-dependent size phenotypes in cerebral organoids from C9-ALS/FTD patients. In addition, single-cell RNA sequencing identified changes in cell type abundance and distribution in C9-ALS/FTD organoids, including a reduction in the number of deep layer cortical neurons and the distribution of neural progenitors. Further, molecular and cellular analyses and patch-clamp electrophysiology detected various changes in synapse structure and function. Intriguingly, organoids from all presymptomatic C9-HRE carriers displayed C9-HRE molecular pathology, whereas the extent to which more downstream cellular defects, as found in C9-ALS/FTD models, were detected varied for the different presymptomatic C9-HRE cases. Together, these results unveil early changes in 3D human brain tissue organization and synaptic connectivity in C9-ALS/FTD that likely constitute initial pathologies crucial for understanding disease onset and the design of therapeutic strategies.

From Brownian motion to virtual biopsy: a historical perspective from 40years of diffusion MRI.

Diffusion MRI was introduced in 1985, showing how the diffusive motion of molecules, especially water, could be spatially encoded with MRI to produce images revealing the underlying structure of biologic tissues at a microscopic scale. Diffusion is one of several Intravoxel Incoherent Motions (IVIM) accessible to MRI together with blood microcirculation. Diffusion imaging first revolutionized the management of acute cerebral ischemia by allowing diagnosis at an acute stage when therapies can still work, saving the outcomes of many patients. Since then, the field of diffusion imaging has expanded to the whole body, with broad applications in both clinical and research settings, providing insights into tissue integrity, structural and functional abnormalities from the hindered diffusive movement of water molecules in tissues. Diffusion imaging is particularly used to manage many neurologic disorders and in oncology for detecting and classifying cancer lesions, as well as monitoring treatment response at an early stage. The second major impact of diffusion imaging concerns the wiring of the brain (Diffusion Tensor Imaging, DTI), allowing to obtain from the anisotropic movement of water molecules in the brain white-matter images in 3 dimensions of the brain connections making up the Connectome. DTI has opened up new avenues of clinical diagnosis and research to investigate brain diseases, neurogenesis and aging, with a rapidly extending field of application in psychiatry, revealing how mental illnesses could be seen as Connectome spacetime disorders. Adding that water diffusion is closely associated to neuronal activity, as shown from diffusion fMRI, one may consider that diffusion MRI is ideally suited to investigate both brain structure and function. This article retraces the early days and milestones of diffusion MRI which spawned over 40years, showing how diffusion MRI emerged and expanded in the research and clinical fields, up to become a pillar of modern clinical imaging.

The posterior hypothalamic area as an independent generator of rhythmic theta oscillatory activity

Theta rhythm is one of the most prominent examples of rhythmic oscillatory activity in mammalian brain and it is generated mainly in structures of the limbic cortex, including the hippocampal formation. In the 1970s it was shown that theta rhythm may be also recorded in diencephalic region including the posterior hypothalamic nuclei and supramammillary nucleus, together considered as the posterior hypothalamic area (PHa). For decades it was stated that local posterior hypothalamic oscillatory activity is controlled by the descending inputs going to the PHa from the septohippocampal system. However, the latest studies indicated that theta rhythm can be recorded in deafferented PHa in vitro preparations which indicates that the posterior hypothalamic area should be considered as an independent of the other brain structures theta generator. In subsequent research the neurochemical and cellular basis of PHa theta were examined in both in vivo and in vitro conditions. In the light of multiple evidence obtained in these studies, it is the author’s intent to summarize the data concerning the role of the posterior hypothalamic area in hippocampal theta rhythm generation as well as the ability of that brain structure to independently generate theta rhythmicity.

Magnetic resonance imaging-based machine learning classification of schizophrenia spectrum disorders: a meta-analysis.

Recent advances in multivariate pattern recognition have fostered the search for reliable neuroimaging-based biomarkers in psychiatric conditions, including schizophrenia. These approaches consider the complex pattern of alterations in brain function and structure, overcoming the limitations of traditional univariate methods. To assess the reliability of neuroimaging-based biomarkers and the contribution of study characteristics in distinguishing individuals with schizophrenia spectrum disorder (SSD) from healthy controls (HCs), we conducted a systematic review of the studies that used multivariate pattern recognition for this objective. We systematically searched PubMed, Scopus, and Web of Science for studies on SSD classification using multivariate pattern analysis on magnetic resonance imaging data. We employed a bivariate random-effects meta-analytic model to explore the classification of sensitivity (SE) and specificity (SP) across studies while also evaluating the moderator effects of clinical and non-clinical variables. A total of 119 studies (with 12,723 patients with SSD and 13,196 HCs) were identified. The meta-analysis estimated a SE of 79.1% (95% confidence interval [CI], 77.1%-81.0%) and a SP of 80.0% (95% CI, 77.8%-82.0%). In particular, the Positive and Negative Syndrome Scale and the Global Assessment of Functioning scores, age, age of onset, duration of untreated psychosis, deep learning, algorithm type, features selection, and validation methods had significant effects on classification performance. Multivariate pattern analysis reliably identifies neuroimaging-based biomarkers of SSD, achieving ∼80% SE and SP. Despite clinical heterogeneity, discernible brain modifications effectively differentiate SSD from HCs. Classification performance depends on patient-related and methodological factors crucial for the development, validation, and application of prospective models in clinical settings.

Involvement of the cerebellum in structural connectivity enhancement in episodic migraine

BackgroundThe pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls.MethodsTo that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM.ResultsWe found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine.ConclusionsA distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.

Study of Eye Movements Abnormalities in Epilepsy

ABSTRACT Idiopathic epilepsy (IE), is a group of epileptic syndromes with no structural brain lesion, but with microstructural changes in neuronal networks leading to neuropsychological consequences. Therefore, the assessment of saccadic eye movements can provide insight into the integrity of cerebral networks as it involves large cortical and subcortical brain areas and circuitries. Describe saccadic eye movement abnormalities in patients with IE and correlate them with disease characteristics and antiseizure medication. Case–control study including IE patients followed in the Neurology Department of Razi University Hospital and healthy controls matched. Participants underwent a recording of saccadic eye movements. Pursuit, prosaccade, and anti-saccade tasks were performed. 115 patients and 98 matched healthy controls were included. The gender ratio (male to female) was 0.6. The mean age at onset was 16.3 ± 12 years. Diagnosed epileptic syndromes were juvenile myoclonic epilepsy (JME), epilepsy with generalized tonic-clonic seizures, childhood absence epilepsy, temporal lobe epilepsy, frontal lobe epilepsy, and rolandic epilepsy. Saccadic eye movements were impaired in 52.2% of our patients and significantly more altered in those with JME (p = .021). Prolonged horizontal saccades latencies were the most frequent eye movement abnormalities (32.1%), followed by altered horizontal smooth pursuit (22.6%). A positive correlation was found between age at eye movements recording, age at onset, disease duration, global cognitive impairment, and saccadic eye movements. However, no definite relationship was identified. Saccadic eye movement illustrates extending anatomic alterations in IE including frontal and temporoparietal cortical areas and cortico-subcortical circuits. Eye movement recording is a useful and reproducible tool in the assessment of epileptic patients and provides a better understanding of neuronal mechanisms in epilepsy.

Depression, brain structure and socioeconomic status: A UK Biobank study

BackgroundDepression results from interactions between biological, social, and psychological factors. Literature shows that depression is associated with abnormal brain structure, and that socioeconomic status (SES) is associated with depression and brain structure. However, limited research considers the interaction between each of these factors. MethodsMultivariate regression analysis was conducted using UK Biobank data on 39,995 participants to examine the relationship between depression and brain volume in 23 cortical regions for the whole sample and then separated by sex. It then examined whether SES affected this relationship. ResultsEight out of 23 brain areas had significant negative associations with depression in the whole population. However, these relationships were abolished in seven areas when SES was included in the analysis. For females, three regions had significant negative associations with depression when SES was not included, but only one when it was. For males, lower volume in six regions was significantly associated with higher depression without SES, but this relationship was abolished in four regions when SES was included. The precentral gyrus was robustly associated with depression across all analyses. LimitationsParticipants with conditions that could affect the brain were not excluded. UK Biobank is not representative of the general population which may limit generalisability. SES was made up of education and income which were not considered separately. ConclusionsSES affects the relationship between depression and cortical brain volume. Health practitioners and researchers should consider this when working with imaging data in these populations.

Structural brain correlates of sustained attention in healthy ageing: Cross-sectional findings from the LEISURE study

Sustained attention is important for maintaining cognitive function and autonomy during ageing, yet older people often show reductions in this domain. The role of the underlying neurobiology is not yet well understood, with most neuroimaging studies primarily focused on fMRI. Here, we utilise sMRI to investigate the relationships between age, structural brain volumes and sustained attention performance. Eighty-nine healthy older adults (50–84 years, Mage 65.5 (SD=8.4) years, 74 f) underwent MRI brain scanning and completed two sustained attention tasks: a rapid visual information processing (RVP) task and sustained attention to response task (SART). Independent hierarchical linear regressions demonstrated that greater volumes of white matter hyperintensities (WMH) were associated with worse RVP_A’ performance, whereas greater grey matter volumes were associated with better RVP_A’ performance. Further, greater cerebral white matter volumes were associated with better SART_d’ performance. Importantly, mediation analyses revealed that both grey and white matter volumes completely mediated the relationship between ageing and sustained attention. These results explain disparate attentional findings in older adults, highlighting the intervening role of brain structure.

Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders

Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM).A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.

Intermittent access to sugary drinks associated with fasting induces overeating and depressive-like behavior in female C57BL/6J mice

Binge eating disorder is the most prevalent eating disorder, affecting both sexes but more commonly found in women. Given the frequent co-occurrence of psychiatric disorders, this study aimed to establish a standardized experimental intermittent protocol to investigate overeating associated with depression. A 10-day protocol induced uncontrolled eating behavior in C57BL/6J female mice. The first experiment included the following groups: naive group (chow ad libitum), control group (chow and sucrose solution ad libitum), and fasting groups (16 and 20 h) exposed to an intermittent sucrose solution (10 %) and chow regimen. Subsequently, the feeding test, open field test, elevated plus maze test, tail suspension test, and light/dark conflict test were conducted. Furthermore, monoamine oxidase (MAO) A and B activities in brain structures and plasma corticosterone levels were assessed. Food overconsumption and depressive-like behavior were observed in both sucrose fasting groups, while risk-taking behaviors were specifically observed in the 20-hour fasting sucrose group. While both fasting sucrose groups caused reduced hippocampal MAO-A activity, only the F20 sucrose group inhibited MAO-B in the cortex and hypothalamus. Moreover, both fasting sucrose groups exhibited elevated corticosterone levels. In a separate design (Experiment 2), groups with 16 and 20 h of fasting alone (without sucrose) did not show the same behavioral results as the intermittent fasting sucrose groups, thus avoiding fasting bias. Based on these results, the 20-hour sucrose fasting group was chosen as the ideal protocol for mimicking overeating behavior associated with depression to investigate future therapeutic approaches for this comorbidity.

Sequential physical and cognitive training disrupts cocaine-context associations via multi-level stimulation of adult hippocampal neurogenesis

Cocaine-related contextual cues are a recurrent source of craving and relapse. Extinction of cue-driven cocaine seeking remains a clinical challenge, and the search for adjuvants is ongoing. In this regard, combining physical and cognitive training is emerging as a promising strategy that has shown synergistic benefits on brain structure and function, including enhancement of adult hippocampal neurogenesis (AHN), which has been recently linked to reduced maintenance of maladaptive drug seeking. Here, we examined whether this behavioral approach disrupts cocaine-context associations via improved AHN. To this aim, C57BL/6J mice (N = 37) developed a cocaine-induced conditioned place preference (CPP) and underwent interventions consisting of exercise and/or spatial working memory training. Bromodeoxyuridine (BrdU) was administered during early running sessions to tag a subset of new dentate granule cells (DGCs) reaching a critical window of survival during spatial learning. Once these DGCs became functionally mature (∼ 6 weeks-old), mice received extinction training before testing CPP extinction and reinstatement. We found that single and combined treatments accelerated CPP extinction and prevented reinstatement induced by a low cocaine priming (2 mg/kg). Remarkably, the dual-intervention mice showed a significant decrease of CPP after extinction relative to untreated animals. Moreover, combining the two strategies led to increased number and functional integration of BrdU+ DGCs, which in turn maximized the effect of spatial training (but not exercise) to reduce CPP persistence. Together, our findings suggests that sequencing physical and cognitive training may redound to decreased maintenance of cocaine-context associations, with multi-level stimulation of AHN as a potential underlying mechanism.

The importance of timing of socioeconomic disadvantage throughout development for depressive symptoms and brain structure

Prior studies have reported associations between socioeconomic disadvantage, brain structure and mental health outcomes, but the timing of these relations is not well understood. Using prospective longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC), this preregistered study examined whether socioeconomic disadvantage related differentially to depressive symptoms (n=3012–3530) and cortical and subcortical structures (n=460–733) in emerging adults, depending on the timing of exposure to socioeconomic disadvantage. Family income in early childhood and own income measured concurrently were both significantly related to depressive symptoms in emerging adulthood. Similar results were observed for perceived financial strain. In contrast, only family income in early childhood was associated with brain structure in emerging adulthood, with positive associations with intracranial volume and total and regional cortical surface area. The findings suggest that both objective and subjective aspects of one’s financial standing throughout development relate to depressive symptoms in adulthood, but that specifically early life family income is related to brain structural features in emerging adulthood. This suggests that associations between socioeconomic disadvantage and brain structure originate early in neurodevelopment, highlighting the role of timing of socioeconomic disadvantage.