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Abstract Functional magnetic resonance imaging in rodents holds great potential for advancing our understanding of brain networks. Unlike the human community, there remains no standardized resource in rodents for image processing, analysis and quality control, posing significant reproducibility limitations. Our software platform, Rodent Automated Bold Improvement of EPI Sequences, is a pipeline designed to address these limitations for preprocessing, quality control, and confound correction, along with best practices for reproducibility and transparency. We demonstrate the robustness of the preprocessing workflow by validating performance across multiple acquisition sites and both mouse and rat data. Building upon a thorough investigation into data quality metrics across acquisition sites, we introduce guidelines for the quality control of network analysis and offer recommendations for addressing issues. Taken together, this software platform will allow the emerging community to adopt reproducible practices and foster progress in translational neuroscience.

Abstract In the past, the cerebellum has been best known for its crucial role in motor function. However, increasingly more findings highlight the importance of cerebellar contributions in cognitive functions and neurodevelopment. Using a total of 7240 neuroimaging scans from 4862 individuals, we describe and provide detailed, openly available models of cerebellar development in childhood and adolescence (age range: 6–17 years), an important time period for brain development and onset of neuropsychiatric disorders. Next to a traditionally used anatomical parcellation of the cerebellum, we generated growth models based on a recently proposed functional parcellation. In both, we find an anterior-posterior growth gradient mirroring the age-related improvements of underlying behavior and function, which is analogous to cerebral maturation patterns and offers evidence for directly related cerebello-cortical developmental trajectories. Finally, we illustrate how the current approach can be used to detect cerebellar abnormalities in clinical samples.

Coincident with the legalisation of cannabis in many nations, rates of cannabis use during pregnancy have increased. Like prior investigations on smoking and alcohol, understanding how prenatal cannabis exposure (PCE) impacts offspring outcomes across the lifespan will be critical for informing choices for pregnant people, clinicians, and policy makers alike. A thorough characterization of the life-long impacts is especially urgent for supporting all of these stakeholders in the decision-making process. While studies in humans bring forth the most direct information, it can be difficult to parse the impact of PCE from confounding variables. Laboratory studies in animal models can provide experimental designs that allow for causal inferences to be drawn, however there can be challenges in designing experiments with external validity in mirroring real-world exposure, as well as challenges translating results from the laboratory back to the clinic. In this literature review, we first highlight what is known about patterns of cannabis use during pregnancy. We then seek to lay out updates to the current understanding of the impact of PCE on offspring development informed by both human and nonhuman animal experiments. Finally we highlight opportunities for information exchange among the laboratory, clinic, and policy, identifying gaps to be filled by future research.

Deep brain stimulation has been investigated as a potential treatment for cognitive impairments in Alzheimer’s disease. Here the authors carry out post hoc analysis of multi-center cohorts to investigate the anatomical and functional correlates of effective deep brain stimulation, and find that stimulating circuit of Papez, fornix and bed nucleus of the stria terminalis, and a multi-region functional network, were associated with clinical improvement.

Abstract Cholinergic dysfunction has been implicated in the pathophysiology of psychosis and psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here, we examined microstructural neuroimaging measures of the cholinergic nuclei in patients with untreated psychosis (~31 weeks of psychosis, 0.05). Case-control differences in qT1 and AxD were observed in the Ch1-3, with increased qT1 (reflecting reduced myelin content) and AxD (reflecting reduced axonal integrity). We found clinical correlates between left NBM qT1 with manic symptom severity, and AxD with negative symptom burden in FEP. Intracortical and subcortical myelin maps were derived and correlated with BF myelin. BF-cortical and BF-subcortical myelin correlations demonstrate known projection patterns from the BF. Using data from the Allen Human Brain Atlas, cholinergic nuclei showed significant enrichment for schizophrenia and depression-related genes. Cell-type specific enrichment indicated enrichment for cholinergic neuron markers as expected. Further relating the neuroimaging correlations to transcriptomics demonstrated links with cholinergic receptor genes and cell type markers of oligodendrocytes and cholinergic neurons, providing biological validity to the measures. These results provide genetic, neuroimaging, and clinical evidence for cholinergic dysfunction in schizophrenia.

Our current understanding of litter variability in neurodevelopmental studies using mice may limit translation of neuroscientific findings. Higher variance of measures across litters than within, often termed intra-litter likeness, may be attributable to both pre- and postnatal environment. This study aimed to assess the litter-effect within behavioral assessments (2 timepoints) and anatomy using T1-weighted magnetic resonance images across 72 brain region volumes (4 timepoints) (36 C57bl/6J inbred mice; 7 litters: 19F/17M). Between-litter comparisons of brain and behavioral measures and their associations were evaluated using univariate and multivariate techniques. A power analysis using simulation methods was then performed on modeled neurodevelopment and to evaluate trade-offs between number-of-litters, number-of-mice-per-litter, and sample size. Our results show litter-specific developmental effects, from the adolescent period to adulthood for brain structure volumes and behaviors, and for their associations in adulthood. Our power simulation analysis suggests increasing the number-of-litters in experimental designs to achieve the smallest total sample size necessary for detecting different rates of change in specific brain regions. Our results demonstrate how litter-specific effects may influence development and that increasing the litters to the total sample size ratio should be strongly considered when designing neurodevelopmental studies.

Brain maturation studies typically examine relationships linking a single morphometric feature with cognition, behavior, age, or other demographic characteristics. However, the coordinated spatiotemporal arrangement of morphological features across development and their associations with behavior are unclear. Here, we examine covariation across multiple cortical features (cortical thickness [CT], surface area [SA], local gyrification index [GI], and mean curvature [MC]) using magnetic resonance images from the NIMH developmental cohort (ages 5–25). Neuroanatomical covariance was examined using non-negative matrix factorization (NMF), which decomposes covariance resulting in a parts-based representation. Cross-sectionally, we identified six components of covariation which demonstrate differential contributions of CT, GI, and SA in hetero- vs. unimodal areas. Using this technique to examine covariance in rates of change to identify longitudinal sources of covariance highlighted preserved SA in unimodal areas and changes in CT and GI in heteromodal areas. Using behavioral partial least squares (PLS), we identified a single latent variable (LV) that recapitulated patterns of reduced CT, GI, and SA related to older age, with limited contributions of IQ and SES. Longitudinally, PLS revealed three LVs that demonstrated a nuanced developmental pattern that highlighted a higher rate of maturational change in SA and CT in higher IQ and SES females. Finally, we situated the components in the changing architecture of cortical gradients. This novel characterization of brain maturation provides an important understanding of the interdependencies between morphological measures, their coordinated development, and their relationship to biological sex, cognitive ability, and the resources of the local environment.

Abstract Relatives of individuals with schizophrenia have a higher risk of developing the illness compared to the general population. Thus, youth at familial high risk (FHR) offer a unique opportunity to identify neuroimaging-based endophenotypes of psychosis. Previous studies have identified lower amygdalo-hippocampal volume in FHR, as well as lower verbal memory and emotion recognition. However, whether these phenotypes increase the risk of transition to psychosis remains unclear. To determine if individuals who develop psychosis have abnormal neurodevelopmental trajectories of the amygdala and hippocampus, we investigated longitudinal changes of these structures in a unique cohort of 82 youth FHR and 56 healthy controls during a 3-year period. Ten individuals from the FHR group converted to psychosis. Longitudinal changes were compared using linear mixed-effects models. Group differences in verbal memory and emotion recognition performance at baseline were also analyzed. Surface-based morphometry measures revealed variation in amygdalar shape (concave shape of the right dorsomedial region) in those who converted to psychosis. Significantly lower emotion recognition performance at baseline was observed in converters. Percent trial-to-trial transfer on the verbal learning task was also significantly impaired in FHR, independently of the conversion status. Our results identify abnormal shape development trajectories in the dorsomedial amygdala and lower emotion recognition abilities as phenotypes of transition to psychosis. Our findings illustrate potential markers for early identification of psychosis, aiding prevention efforts in youth at risk of schizophrenia.

The cerebellum's involvement in cognitive, affective and motor functions is mediated by connections to different regions of the cerebral cortex. A distinctive feature of cortico-cerebellar loops that has been demonstrated in the animal work is a topographic organization that is preserved across its corticopontine, pontocerebellar, and cerebello-thalmo-cortical segments. Here we used tractography derived from diffusion imaging data to characterize the connections between the pons and the individual lobules of the cerebellum and generate a parcellation of the pons and middle cerebellar peduncle based on the pattern of connectivity. We identified a rostral to caudal gradient in the pons, similar to that observed in the animal work, such that rostral regions were preferentially connected to cerebellar lobules involved in non-motor, and caudal regions with motor regions. These findings advance our fundamental understanding of the cerebellum, and the parcellations we generated provide context for future research into the pontocerebellar tract's involvement in health and disease.

Abstract The habenula is a small epithalamic structure with widespread connections to multiple cortical, subcortical and brainstem regions. It has been identified as the central structure modulating the reward value of social interactions, behavioral adaptation, sensory integration and circadian rhythm. Autism spectrum disorder (ASD) is characterized by social communication deficits, restricted interests, repetitive behaviors, and is frequently associated with altered sensory perception and mood and sleep disorders. The habenula is implicated in all these behaviors and results of preclinical studies suggest a possible involvement of the habenula in the pathophysiology of this disorder. Using anatomical magnetic resonance imaging and automated segmentation we show that the habenula is significantly enlarged in ASD subjects compared to controls across the entire age range studied (6–30 years). No differences were observed between sexes. Furthermore, support-vector machine modeling classified ASD with 85% accuracy (model using habenula volume, age and sex) and 64% accuracy in cross validation. The Social Responsiveness Scale (SRS) significantly differed between groups, however, it was not related to individual habenula volume. The present study is the first to provide evidence in human subjects of an involvement of the habenula in the pathophysiology of ASD.

Recent research found that the combination of masculine gender identity and gynephilia was associated with cortical T1 relaxation time, which is considered to reflect gray matter density. We hypothesized that mean diffusivity (MD), a diffusion tensor imaging metric that reflects the degree to which water movement is free versus constrained, in combination with T1 relaxation time would provide further insight regarding cortical tissue characteristics. MD and T1 relaxation time were measured in 76 cortical regions in 15 adolescents assigned female at birth who experience gender dysphoria (GD AFAB) and were not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12–17 years). Sexual orientation was represented by the degree of androphilia–gynephilia and the strength of sexual attraction. In multivariate analyses, cortical T1 relaxation time showed a weak but statistically significant positive association with MD across the cortex, suggesting that macromolecule-rich cortical tissue also tends to show water movement that is somewhat more constrained. In further multivariate analyses, in several left frontal, parietal, and temporal regions, the combination of shorter T1 relaxation time and faster MD was associated with older age and greater gynephilia in GD AFAB individuals and cisgender boys and with stronger attractions in cisgender boys only. Thus, for these cortical regions in these groups, older age, gynephilia, and stronger attractions (cisgender boys only) were associated with macromolecule-rich tissue in which water movement was freer—a pattern that some prior research suggests is associated with greater cell density and size. Overall, this study indicates that investigating T1 relaxation time and MD together can further inform how cortical gray matter tissue characteristics relate to age and psychosexuality.

The sources of inter- and intra-individual variability in age-related cognitive decline remain poorly understood. We examined the association between 20-year trajectories of cognitive decline and multimodal brain structure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 ±4.9 years) and late-life (mean age = 67.7 ± 4.9). Using non-negative matrix factorization, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two latent variables describing distinct brain-cognition associations. The first describes variations in 5 structural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid-life performance in fluency and memory, but retention of multiple abilities. Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9). This data-driven approach highlights brain-cognition relationships wherein individuals degrees of cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with markers of cortical structure.

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain’s intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys.

Abstract Acute exposure to cannabis has been associated with an array of cognitive alterations, increased risk for neuropsychiatric illness, and other neuropsychiatric sequelae including the emergence of acute psychotic symptoms. However, the brain alterations associating cannabis use and these behavioral and clinical phenotypes remains disputed. To this end, neuroimaging can be a powerful technique to non-invasively study the impact of cannabis exposure on brain structure and function in both humans and animal models. While chronic exposure studies provide insight into how use may be related to long-term outcomes, acute exposure may reveal interesting information regarding the immediate impact of use and abuse on brain circuits. Understanding these alterations could reveal the connection with symptom dimensions in neuropsychiatric disorders and, more specifically with psychosis. The purpose of the present review is to: 1) provide an update on the findings of pharmacological neuroimaging studies examining the effects of administered cannabinoids and 2) focus the discussion on studies that examine the sensitive window for the emergence of psychosis. Current literature indicates that cannabis exposure has varied effects on the brain, with the principal compounds in cannabis (delta-9-tetrahydrocannabinol and cannabidiol) altering activity across different brain regions. Importantly, we also discovered critical gaps in the literature, particularly regarding sex-dependent responses and long-term effects of chronic exposure. Certain networks often characterized as dysregulated in psychosis, like the default mode network and limbic system, were also impacted by THC exposure, identifying areas of particular interest for future work investigating the potential relationship between the two.

Abstract Our sensory systems provide complementary information about the multimodal objects and events that are the target of perception in everyday life. Professional musicians’ specialization in the auditory domain is reflected in the morphology of their brains, which has distinctive characteristics, particularly in areas related to auditory and audio-motor activity. Here, we combined diffusion tensor imaging (DTI) with a behavioral measure of visually induced gain in pitch discrimination, and we used measures of cortical thickness (CT) correlations to assess how auditory specialization and musical expertise are reflected in the structural architecture of white and grey matter relevant to audiovisual processing. Across all participants (n = 45), we found a correlation (p < 0.001) between reliance on visual cues in pitch discrimination and the fractional anisotropy (FA) in the left inferior fronto-occipital fasciculus (IFOF), a structure connecting visual and auditory brain areas. Group analyses also revealed greater cortical thickness correlation between visual and auditory areas in non-musicians (n = 28) compared to musicians (n = 17), possibly reflecting musicians’ auditory specialization (FDR

Abstract Maternal nutritional programming by caloric exposure during pregnancy and lactation results in long-term behavioral modification in the offspring. Here, we characterized the effect of maternal caloric exposure on synaptic and brain morphological organization and its effects on depression-like behavior susceptibility in rats’ offspring. Female Wistar rats were exposed to chow or cafeteria (CAF) diet for 9 weeks (pre-pregnancy, pregnancy, and lactation) and then switched to chow diet after weaning. By postnatal day 60, the male Wistar rat offspring were tested for depressive-like behavior using operational conditioning, novelty suppressed feeding, sucrose preference, and open-field test. Brain macro and microstructural morphology were analyzed using magnetic resonance imaging deformation-based morphometry (DBM) and western blot, immunohistochemistry for NMDA and AMPA receptor, synaptophysin and myelin, respectively. We found that the offspring of mothers exposed to CAF diet displayed deficient motivation showing decrease in the operant conditioning, sucrose preference, and suppressed feeding test. Macrostructural DBM analysis showed reduction in the frontomesocorticolimbic circuit volume including the nucleus accumbens (NAc), hippocampus, and prefrontal cortex. Microstructural analysis revealed reduced synaptic terminals in hippocampus and NAc, whereas increased glial fibrillary acidic protein in hippocampus and lateral hypothalamus, as well as a decrease in the hippocampal cell number and myelin reduction in the dentate gyrus and hilus, respectively. Also, offspring exhibited increase of the GluR1 and GLUR2 subunits of AMPA receptor, whereas a decrease in the mGluR2 expression in hippocampus. Our findings reveal that maternal programming might prime depression-like behavior in the offspring by modulating macro and micro brain organization of the frontomesocorticolimbic circuit.

Kiesow et al. use deep learning to identify partially overlapping subnetworks in the human social brain at the population level. They also demonstrate that the learned subnetwork representations can be used to predict social traits.

The striatum is a major subcortical connection hub that has been heavily implicated in a wide array of motor and cognitive functions. Here, we developed a normative multimodal, data-driven microstructural parcellation of the striatum using non-negative matrix factorization (NMF) based on multiple magnetic resonance imaging-based metrics (mean diffusivity, fractional anisotropy, and the ratio between T1- and T2-weighted structural scans) from the Human Connectome Project Young Adult dataset (n = 329 unrelated participants, age range: 22–35, F/M: 185/144). We further explored the biological and functional relationships of this parcellation by relating our findings to motor and cognitive performance in tasks known to involve the striatum as well as demographics. We identified 5 spatially distinct striatal components for each hemisphere. We also show the gain in component stability when using multimodal versus unimodal metrics. Our findings suggest distinct microstructural patterns in the human striatum that are largely symmetric and that relate mostly to age and sex. Our work also highlights the putative functional relevance of these striatal components to different designations based on a Neurosynth meta-analysis.

Abstract Introduction Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence. Methods Our international working group, funded by the EU Joint Programme–Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption. Results This progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures. Discussion A harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.

Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices (“Prisma Upgrade protocol”) and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence (“vNav protocol”). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT and amygdala, globus pallidus, hippocampus, and striatum volumes, were observed. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement.

The hippocampus has been extensively studied in various neuropsychiatric disorders throughout the lifespan. However, inconsistent results have been reported with respect to which subfield volumes are most related to age. Here, we investigate whether these discrepancies may be explained by experimental design differences that exist between studies. Multiple datasets were used to collect 1690 magnetic resonance scans from healthy individuals aged 18–95 years old. Standard T1-weighted (T1w; MPRAGE sequence, 1 mm3 voxels), high-resolution T2-weighted (T2w; SPACE sequence, 0.64 mm3 voxels) and slab T2-weighted (Slab; 2D turbo spin echo, 0.4 × 0.4 × 2 mm3 voxels) images were included. The MAGeT Brain algorithm was used for segmentation of the hippocampal grey matter (GM) subfields and peri-hippocampal white matter (WM) subregions. Linear mixed-effect models and Akaike information criterion were used to examine linear, second or third order natural splines relationship between hippocampal volumes and age. We demonstrated that stratum radiatum/lacunosum/moleculare and fornix subregions expressed the highest relative volumetric decrease, while the cornus ammonis 1 presented a relative volumetric preservation of its volume with age. We also found that volumes extracted from slab images demonstrated different age-related relationships compared to volumes extracted from T1w and T2w images. The current work suggests that although T1w, T2w and slab derived subfield volumetric outputs are largely homologous, modality choice plays a meaningful role in the volumetric estimation of the hippocampal subfields.

Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.

Scientific research aims to bring forward innovative ideas and constantly challenges existing knowledge structures and stereotypes. However, women, ethnic and cultural minorities, as well as individuals with disabilities, are systematically discriminated against or even excluded from promotions, publications, and general visibility. A more diverse workforce is more productive, and thus discrimination has a negative impact on science and the wider society, as well as on the education, careers, and well-being of individuals who are discriminated against. Moreover, the lack of diversity at scientific gatherings can lead to micro-aggressions or harassment, making such meetings unpleasant, or even unsafe environments for early career and underrepresented scientists.At the Organization for Human Brain Mapping (OHBM), we recognized the need for promoting underrepresented scientists and creating diverse role models in the field of neuroimaging. To foster this, the OHBM has created a Diversity and Inclusivity Committee (DIC). In this article, we review the composition and activities of the DIC that have promoted diversity within OHBM, in order to inspire other organizations to implement similar initiatives.Activities of the committee over the past four years have included (a) creating a code of conduct, (b) providing diversity and inclusivity education for OHBM members, (c) organizing interviews and symposia on diversity issues, and (d) organizing family-friendly activities and providing childcare grants during the OHBM annual meetings.We strongly believe that these activities have brought positive change within the wider OHBM community, improving inclusivity and fostering diversity while promoting rigorous, ground-breaking science. These positive changes could not have been so rapidly implemented without the enthusiastic support from the leadership, including OHBM Council and Program Committee, and the OHBM Special Interest Groups (SIGs), namely the Open Science, Student and Postdoc, and Brain-Art SIGs. Nevertheless, there remains ample room for improvement, in all areas, and even more so in the area of targeted attempts to increase inclusivity for women, individuals with disabilities, members of the LGBTQ+ community, racial/ethnic minorities, and individuals of lower socioeconomic status or from low and middle-income countries.Here, we present an overview of the DIC's composition, its activities, future directions and challenges. Our goal is to share our experiences with a wider audience to provide information to other organizations and institutions wishing to implement similar comprehensive diversity initiatives. We propose that scientific organizations can push the boundaries of scientific progress only by moving beyond existing power structures and by integrating principles of equity and inclusivity in their core values.

Providing the appropriate quantity and quality of food needed for both the mother’s well-being and the healthy development of the offspring is crucial during pregnancy. However, the macro- and micronutrient intake also impacts the body’s regulatory supersystems of the mother, such as the immune, endocrine, and nervous systems, which ultimately influence the overall development of the offspring. Of particular importance is the association between unhealthy maternal diet and neurodevelopmental disorders in the offspring. Epidemiological studies have linked neurodevelopmental disorders like autism spectrum disorders, attention-deficit-hyperactivity disorder, and schizophrenia, to maternal immune activation (MIA) during gestation. While the deleterious consequences of diet-induced MIA on offspring neurodevelopment are increasingly revealed, neuroinflammation is emerging as a key underlying mechanism. In this review, we compile the evidence available on how the mother and offspring are both impacted by maternal dietary imbalance. We specifically explore the various inflammatory and anti-inflammatory effects of dietary components and discuss how changes in inflammatory status can prime the offspring brain development toward neurodevelopmental disorders. Lastly, we discuss research evidence on the mechanisms that sustain the relationship between maternal dietary imbalance and offspring brain development, involving altered neuroinflammatory status in the offspring, as well as genetic to cellular programming notably of microglia, and the evidence that the gut microbiome may act as a key mediator.

Objectives: Lateral geniculate nucleus (LGN) volume is reduced after optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD). We aimed at a longitudinal assessment of LGN volume in NMOSD. Methods: Twenty-nine patients with aquaporin 4-IgG seropositive NMOSD (age: 47.8 ± 14.6 years (y), female: n = 27, history of ON (NMO-ON): n = 17, median time since ON: 3[1.2–12.1]y) and 18 healthy controls (HC; age: 39.3 ± 15.8y; female: n = 13) were included. Median follow-up was 4.1[1.1–4.7]y for patients and 1.7[0.9–3.2]y for HC. LGN volume was measured using a multi-atlas-based approach of automated segmentation on 3 Tesla magnetic resonance images. Retinal optical coherence tomography and probabilistic tractography of the optic radiations (OR) were also performed. Results: At baseline, NMO-ON patients had lower LGN volumes (395.4 ± 48.9 mm3) than patients without ON (NMO-NON: 450.7 ± 55.6 mm3; p = 0.049) and HC (444.5 ± 61.5 mm3, p = 0.025). LGN volume was associated with retinal neuroaxonal loss and microstructural OR damage. Longitudinally, there was no change in LGN volumes in the absence of ON, neither in all patients (B = −0.6, SE = 1.4, p = 0.670), nor in NMO-ON (B = −0.8, SE = 1.6, p = 0.617) and NMO-NON (B = 1.7, SE = 3.5, p = 0.650). However, in four patients with new ON during follow-up, LGN volume was reduced at last visit (median time since ON: 2.6 [1.8–3.9] y) compared to the measurement before ON (352 ± 52.7 vs. 371.1 ± 55.9 mm3; t = −3.6, p = 0.036). Conclusion: Although LGN volume is reduced after ON in NMOSD, this volume loss is not progressive over longer follow-up or independent of ON. Thus, our findings -at least in this relatively small cohort- do not support occult neurodegeneration of the afferent visual pathway in NMOSD.

Background: Although there is some evidence for a normalization of brain structure following exposure to ADHD medication, literature on the effects of duration and dose of continued use on the brain is scarce. Here, we investigated the association between cumulative exposure to medication (range 1 week to 4.69 years) and cortical structures and subcortical volumes in a clinical sample of children with ADHD taking medication (n = 109). To the best of our knowledge, this is the first structural MRI study investigating the effects of cumulative exposure to medication on subregional volumes in children treated for ADHD. Methods: Cumulative exposure to ADHD medication (CEM) was defined as the product of duration on medication (days) and dose (mg/day), yielding the area under the curve (total mg). Cortical thickness and surface area measurements (CIVET-1.1.12), and subcortical volumes in 51 regions (MAGeT-Brain) were analyzed using general linear modelling. Results: Significant effects of CEM were found in two subregions of the left hippocampus, the CA1 (df = 95; q = 0.003) and the strata radiatum/lacunosum/moleculare (df = 95; q = 0.003). Specifically, higher CEM was associated with smaller volumes within these subregions. No effects of medication exposure were detected on cortical thickness or surface area. Conclusions: Although this study is cross-sectional, the results found within this sample of children show that prolonged ADHD medication use at higher doses is significantly associated with smaller hippocampus volumes in specific subregions. More research is required to determine whether these results are reproduced in other samples of children of ADHD, and further, whether these are beneficial or off-target effects of the medication.

To move Alzheimer Disease (AD) research forward it is essential to collect data from large cohorts, but also make such data available to the global research community. We describe the creation of an open science dataset from the PREVENT-AD (PResymptomatic EValuation of Experimental or Novel Treatments for AD) cohort, composed of cognitively unimpaired older individuals with a parental or multiple-sibling history of AD. From 2011 to 2017, 386 participants were enrolled (mean age 63 years old ± 5) for sustained investigation among whom 349 have retrospectively agreed to share their data openly. Repositories are findable through the unified interface of the Canadian Open Neuroscience Platform and contain up to five years of longitudinal imaging data, cerebral fluid biochemistry, neurosensory capacities, cognitive, genetic, and medical information. Imaging data can be accessed openly at https://openpreventad.loris.ca while most of the other information, sensitive by nature, is accessible by qualified researchers at https://registeredpreventad.loris.ca. In addition to being a living resource for continued data acquisition, PREVENT-AD offers opportunities to facilitate understanding of AD pathogenesis.

Men and women tend to differ in the age of first alcohol consumption, transition into disordered drinking, and the prevalence of alcohol use disorder. Here, we use a unique longitudinal dataset to test for potentially predispositonal sex-biases in brain organization prior to initial alcohol exposure. Our study combines measures of subcortical morphometry gathered in alcohol naive individuals during childhood (mean age: 9.43 years, SD = 2.06) with self-report measures of alcohol use in the same individuals an average of 17 years later (N = 81, 46 males, 35 females). We observe that pediatric amygdala and hippocampus volume both show sex-biased relationships with adult drinking. Specifically, females show a stronger association between subcortical volumetric reductions in childhood and peak drinking in adulthood as compared to males. Detailed analysis of subcortical shape localizes these effects to the rostro-medial hippocampus and basolateral amygdala subnuclei. In contrast, we did not observe sex-specific associations between striatal anatomy and peak alcohol consumption. These results are consistent with a model in which organization of the amygdala and hippocampus in childhood is more relevant for subsequent patterns of peak alcohol use in females as compared to males. Differential neuroanatomical precursors of alcohol use in males and females could provide a potential developmental basis for well recognized sex-differences in alcohol use behaviors.. Thus, our findings not only indicate that brain correlates of human alcohol consumption are manifest long before alcohol initiation, but that some of these correlates are not equivalent between males and females.

Prenatal exposure to maternal immune activation (MIA) is a risk factor for a variety of neurodevelopmental and psychiatric disorders. The timing of MIA-exposure has been shown to affect adolescent and adult offspring neurodevelopment, however, less is known about these effects in the neonatal period. To better understand the impact of MIA-exposure on neonatal brain development in a mouse model, we assess neonate communicative abilities with the ultrasonic vocalization task, followed by high-resolution ex vivo magnetic resonance imaging (MRI) on the neonatal (postnatal day 8) mouse brain. Early exposed offspring displayed decreased communicative ability, while brain anatomy appeared largely unaffected, apart from some subtle alterations. By integrating MRI and behavioural assays to investigate the effects of MIA-exposure on neonatal neurodevelopment we show that offspring neuroanatomy and behaviour are only subtly affected by both early and late exposure. This suggests that the deficits often observed in later stages of life may be dormant, not yet developed in the neonatal period, or not as easily detectable using a cross-sectional approach.

Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.

In this work we use non-negative matrix factorization to identify patterns of microstructural variance in the human hippocampus. We utilize high-resolution structural and diffusion magnetic resonance imaging data from the Human Connectome Project to query hippocampus microstructure on a multivariate, voxelwise basis. Application of non-negative matrix factorization identifies spatial components (clusters of voxels sharing similar covariance patterns), as well as subject weightings (individual variance across hippocampus microstructure). By assessing the stability of spatial components as well as the accuracy of factorization, we identified 4 distinct microstructural components. Furthermore, we quantified the benefit of using multiple microstructural metrics by demonstrating that using three microstructural metrics (T1-weighted/T2-weighted signal, mean diffusivity and fractional anisotropy) produced more stable spatial components than when assessing metrics individually. Finally, we related individual subject weightings to demographic and behavioural measures using a partial least squares analysis. Through this approach we identified interpretable relationships between hippocampus microstructure and demographic and behavioural measures. Taken together, our work suggests non-negative matrix factorization as a spatially specific analytical approach for neuroimaging studies and advocates for the use of multiple metrics for data-driven component analyses.

The amygdala and hippocampus are two adjacent allocortical structures implicated in sex-biased and developmentally-emergent psychopathology. However, the spatiotemporal dynamics of amygdalo-hippocampal development remain poorly understood in healthy humans. The current study defined trajectories of volume and shape change for the amygdala and hippocampus by applying a multi-atlas segmentation pipeline (MAGeT-Brain) and semi-parametric mixed-effects spline modeling to 1,529 longitudinally-acquired structural MRI brain scans from a large, single-center cohort of 792 youth (403 males, 389 females) between the ages of 5 and 25 years old. We found that amygdala and hippocampus volumes both follow curvilinear and sexually dimorphic growth trajectories. These sex-biases were particularly striking in the amygdala: males showed a significantly later and slower adolescent deceleration in volume expansion (at age 20 years) than females (age 13 years). Shape analysis localized significant hot-spots of sex-biased anatomical development in sub-regional territories overlying rostral and caudal extremes of the CA1/2 in the hippocampus, and the centromedial nuclear group of the amygdala. In both sexes, principal components analysis revealed close integration of amygdala and hippocampus shape change along two main topographically-organized axes – low vs. high areal expansion, and early vs. late growth deceleration. These results (i) bring greater resolution to our spatiotemporal understanding of amygdalo-hippocampal development in healthy males and females, and (ii) uncover focal sex-differences in the structural maturation of the brain components that may contribute to differences in behavior and psychopathology that emerge during adolescence.

Animal whole-brain functional magnetic resonance imaging (fMRI) provides a non-invasive window into brain activity. A collection of associated methods aims to replicate observations made in humans and to identify the mechanisms underlying the distributed neuronal activity in the healthy and disordered brain. Animal fMRI studies have developed rapidly over the past years, fueled by the development of resting-state fMRI connectivity and genetically encoded neuromodulatory tools. Yet, comparisons between sites remain hampered by lack of standardization. Recently, we highlighted that mouse resting-state functional connectivity converges across centers, although large discrepancies in sensitivity and specificity remained. Here, we explore past and present trends within the animal fMRI community and highlight critical aspects in study design, data acquisition, and post-processing operations, that may affect the results and influence the comparability between studies. We also suggest practices aimed to promote the adoption of standards within the community and improve between-lab reproducibility. The implementation of standardized animal neuroimaging protocols will facilitate animal population imaging efforts as well as meta-analysis and replication studies, the gold standards in evidence-based science.

White matter pathways that surround the hippocampus comprise its afferent and efferent connections, and are therefore crucial in mediating the function of the hippocampus. We recently demonstrated a role for the hippocampus in both spatial memory and olfactory identification in humans. In the current study, we focused our attention on the fimbria-fornix white matter bundle and investigated its relationship with spatial memory and olfactory identification. We administered a virtual navigation task and an olfactory identification task to 55 young healthy adults and measured the volume of the fimbria-fornix. We found that the volume of the right fimbria-fornix and its subdivisions is correlated with both navigational learning and olfactory identification in those who use hippocampus-based spatial memory strategies, and not in those who use caudate nucleus-based navigation strategies. These results are consistent with our recent finding that spatial memory and olfaction rely on similar neural networks and structures.

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a mouse default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. RSN spatial specificity was enhanced in datasets acquired at higher field strength, with cryoprobes, in ventilated animals, and under medetomidine-isoflurane combination sedation. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

Olfaction, the sense of smell, may have originally evolved to aid navigation in space, but there is no direct evidence of a link between olfaction and navigation in humans. Here the authors show that olfaction and spatial memory abilities are correlated and rely on similar brain regions in humans.

Parkinson׳s disease (PD) is a neurodegenerative disease that primarily affects the motor functions of the patients. Research and surgical treatment of PD (e.g., deep brain stimulation) often require human brain atlases for structural identification or as references for anatomical normalization. However, two pitfalls exist for many current atlases used for PD. First, most atlases do not represent the disease-specific anatomy as they are based on healthy young subjects. Second, subcortical structures, such as the subthalamic nucleus (STN) used in deep brain stimulation procedures, are often not well visualized. The dataset described in this Data in Brief is a population-averaged atlas that was made with 3 T MRI scans of 25 PD patients, and contains 5 image contrasts: T1w (FLASH & MPRAGE), T2*w, T1–T2* fusion, phase, and an R2* map. While the T1w, T2*w, and T1–T2* fusion templates provide excellent anatomical details for both cortical and sub-cortical structures, the phase and R2* map contain bio-chemical features. Probabilistic tissue maps of whiter matter, grey matter, and cerebrospinal fluid are provided for the atlas. We also manually segmented eight subcortical structures: caudate nucleus, putamen, globus pallidus internus and externus (GPi & GPe), thalamus, STN, substantia nigra (SN), and the red nucleus (RN). Lastly, a co-registered histology-derived digitized atlas containing 123 anatomical structures is included. The dataset is made freely available at the MNI data repository accessible through the link http://nist.mni.mcgill.ca/?p=1209.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

Introduction: The amygdala is a brain structure involved in emotional regulation. Studies have shown that larger amygdala volumes are associated with behavioral disorders. Prenatal maternal depression is associated with structural changes in the amygdala, which in turn, is predictive of an increase in behavioral problems. Girls may be particularly vulnerable. However, it is not known whether disaster-related prenatal maternal stress (PNMS), or which aspect of the maternal stress experience (i.e., objective hardship, subjective distress, and cognitive appraisal), influences amygdala volumes. Nor is it known whether amygdala volumes mediate the effect of PNMS on behavioral problems in girls and boys.Aims: To assess whether aspects of PNMS are associated with amygdala volume, to determine whether timing of exposure moderates the effect, and to test whether amygdala volume mediates the association between PNMS and internalizing and externalizing problems in 11½ year old children exposed in utero, to varying levels of disaster-related PNMS.Methods: Bilateral amygdala volumes (AGV) and total brain volume (TBV) were acquired using magnetic resonance imaging, from 35 boys and 33 girls whose mothers were pregnant during the January 1998 Quebec Ice Storm. The mothers' disaster-related stress was assessed in June 1998. Child internalizing and externalizing problems were assessed at 11½ years using the Child Behavior Checklist (CBCL). Hierarchical regression analyses and mediation analyses were conducted on boys and girls separately, controlling for perinatal and postnatal factors.Results: In boys, subjective distress was associated with larger right AGV/TBV when mothers where exposed during late pregnancy, which in turn explained higher levels of externalizing behavior. However, when adjusting for postnatal factors, the effect was no longer significant. In girls, later gestational exposure to the ice storm was associated with larger AGV/TBV, but here, higher levels of objective PNMS were associated with more externalizing problems, which was, in part, mediated by larger AGV/TBV. No effects were detected on internalizing behaviors.Conclusion: These results suggest that the effects of PNMS on amygdala development and externalizing symptoms, as assessed in boys and girls in early adolescence, can be influenced by the timing of the stress in pregnancy, and the particular aspect of the mother's stress experience.

Obesity is recognized as a significant risk factor for Alzheimer's disease (AD). Studies have supported that obesity accelerates AD-related pathophysiology and memory impairment in mouse models of AD. However, the nature of the brain structure-behaviour relationship mediating this acceleration remains unclear. In this manuscript we evaluated the impact of adolescent obesity on the brain morphology of the triple transgenic mouse model of AD (3xTg) and a non-transgenic control model of the same background strain (B6129s) using longitudinally acquired structural magnetic resonance imaging (MRI). At 8 weeks of age, animals were placed on a high-fat diet (HFD) or an ingredient-equivalent control diet (CD). Structural images were acquired at 8, 16, and 24 weeks. At 25 weeks, animals underwent the novel object recognition (NOR) task and the Morris water maze (MWM) to assess short-term non-associative memory and spatial memory, respectively. All analyses were carried out across four groups: B6129s-CD and -HFD and 3xTg-CD and -HFD. Neuroanatomical changes in MRI-derived brain morphology were assessed using volumetric and deformation-based analyses. HFD-induced obesity during adolescence exacerbated brain volume alterations by adult life in the 3xTg mouse model in comparison to control-fed mice and mediated volumetric alterations of select brain regions, such as the hippocampus. Further, HFD-induced obesity aggravated memory in all mice, lowering certain memory measures of B6129s control mice to the level of 3xTg mice maintained on a CD. Moreover, decline in the volumetric trajectories of hippocampal regions for all mice were associated with the degree of spatial memory impairments on the MWM. Our results suggest that obesity may interact with the brain changes associated with AD-related pathology in the 3xTg mouse model to aggravate brain atrophy and memory impairments and similarly impair brain structural integrity and memory capacity of non-transgenic mice. Further insight into this process may have significant implications in the development of lifestyle interventions for treatment of AD.

Mu opioid receptor (MOR) activation facilitates reward processing and reduces pain, and brain networks underlying these effects are under intense investigation. Mice lacking the MOR gene (MOR KO mice) show lower drug and social reward, enhanced pain sensitivity and altered emotional responses. Our previous neuroimaging analysis using Resting-state (Rs) functional Magnetic Resonance Imaging (fMRI) showed significant alterations of functional connectivity (FC) within reward/aversion networks in these mice, in agreement with their behavioral deficits. Here we further used a structural MRI approach to determine whether volumetric alterations also occur in MOR KO mice. We acquired anatomical images using a 7-Tesla MRI scanner and measured deformation-based morphometry (DBM) for each voxel in subjects from MOR KO and control groups. Our analysis shows marked anatomical differences in mutant animals. We observed both local volumetric contraction (striatum, nucleus accumbens, bed nucleus of the stria terminalis, hippocampus, hypothalamus and periacqueducal gray) and expansion (prefrontal cortex, amygdala, habenula, and periacqueducal gray) at voxel level. Volumetric modifications occurred mainly in MOR-enriched regions and across reward/aversion centers, consistent with our prior FC findings. Specifically, several regions with volume differences corresponded to components showing highest FC changes in our previous Rs-fMRI study, suggesting a possible function-structure relationship in MOR KO-related brain differences. In conclusion, both Rs-fMRI and volumetric MRI in live MOR KO mice concur to disclose functional and structural whole-brain level mechanisms that likely drive MOR-controlled behaviors in animals, and may translate to MOR-associated endophenotypes or disease in humans.

BackgroundCurrent neuroscience literature has related treatment with aripiprazole to improved memory performance and subcellular changes in the hippocampus.AimsTo explore the volumetric changes in hippocampal grey matter in people with a first episode of psychosis (FEP) treated with second-generation antipsychotics.MethodBaseline and 1-year follow-up magnetic resonance images were obtained. Hippocampal volumes were estimated by using FreeSurfer and MAGeT-Brain. Subgroups included: aripiprazole (n=13), olanzapine (n=12), risperidone/paliperidone (n=24), refused-antipsychotics (n=13) and controls (n=44).ResultsAripiprazole subgroup displayed significant increases in bilateral hippocampal volume compared with all other subgroups (FreeSurfer: all P's

Sex differences have been widely observed in clinical presentation, functional outcome and neuroanatomy in individuals with a first-episode of psychosis, and chronic patients suffering from schizophrenia. However, little is known about sex differences in the high-risk stages for psychosis. The present study investigated sex differences in cortical and subcortical neuroanatomy in individuals at clinical high risk (CHR) for psychosis and healthy controls (CTL), and the relationship between anatomy and clinical symptoms in males at CHR. Magnetic resonance images were collected in 26 individuals at CHR (13 men) and 29 CTLs (15 men) to determine total and regional brain volumes and morphology, cortical thickness, and surface area (SA). Clinical symptoms were assessed with the brief psychiatric rating scale. Significant sex-by-diagnosis interactions were observed with opposite directions of effect in male and female CHR subjects relative to their same-sex controls in multiple cortical and subcortical areas. The right postcentral, left superior parietal, inferior parietal supramarginal, and angular gyri [

Introduction: The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. Methods: First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. Results: The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations in comparison to manually derived gold standards (mean Dice's Kappa > 0.79 and Euclidean distance

There has been a distinct shift in neuroimaging from localization of function into a more network based approach focused on connectivity. While fMRI has proven very fruitful for this, the hemodynamic signal is inherently slow which limits the temporal resolution of fMRI-only connectivity measures. The brain, however, works on a time scale of milliseconds. This study utilized concurrent transcranial magnetic stimulation (TMS)-fMRI in a novel way to obtain measures of dynamic connectivity by measuring changes in fMRI signal amplitude in regions distal to the site of stimulation following differing TMS onset times. Seventeen healthy subjects completed an associative memory encoding task known to involve the DLPFC, viewing pairs of objects which could be semantically related or unrelated. Three pulses of 10 Hz repetitive TMS were applied over the left DLPFC starting either at 200, 600, or 1000 ms after stimulus onset. Associations for related pairs were better remembered than unrelated pairs in a post-scan cued recall test. Differences in neural activity were assessed across different TMS onsets, separately for related and unrelated pairs. Time specific TMS effects were observed in several regions, including those associated with higher-level processing (lateral frontal, anterior cingulate), visual areas (occipital), and regions involved in semantic processing (e.g., left mid-temporal and medial frontal). Activity in the frontal cortex was decreased at 200 ms post-stimulus for unrelated pairs, and 1000 ms post-stimulus for related pairs. This suggests differences in the timing across conditions in which the DLFPC interacts with other PFC regions, consistent with the notion that the DLPFC is facilitating extended semantic processing for related items. This study demonstrates that time-varying TMS onset inside the MRI can be used to reliably measure fast dynamic connectivity with a temporal resolution in the hundreds of milliseconds.

Previous studies in nonhuman primates and cats have shown that the pulvinar receives input from various cortical and subcortical areas involved in vision. Although the contribution of the pulvinar to human vision remains to be established, anatomical tracer and electrophysiological animal studies on cortico-pulvinar circuits suggest an important role of this structure in visual spatial attention, visual integration, and higher-order visual processing. Because methodological constraints limit investigations of the human pulvinar's function, its role could, up to now, only be inferred from animal studies. In the present study, we used an innovative imaging technique, Diffusion Tensor Imaging (DTI) tractography, to determine cortical and subcortical connections of the human pulvinar. We were able to reconstruct pulvinar fiber tracts and compare variability across subjects in vivo. Here we demonstrate that the human pulvinar is interconnected with subcortical structures (superior colliculus, thalamus, and caudate nucleus) as well as with cortical regions (primary visual areas (area 17), secondary visual areas (area 18, 19), visual inferotemporal areas (area 20), posterior parietal association areas (area 7), frontal eye fields and prefrontal areas). These results are consistent with the connectivity reported in animal anatomical studies.