Thalamic medial dorsal nucleus atrophy in medial temporal lobe epilepsy: A VBM meta-analysis

Purpose: Medial temporal lobe epilepsy (MTLE) is associated with MTLE network pathology within and beyond the hippocampus. The purpose of this meta-analysis was to identify consistent MTLE structural change to guide subsequent targeted analyses of these areas. Methods: We performed an anatomic likelihood estimation (ALE) meta-analysis of 22 whole-brain voxel-based morphometry experiments from 11 published studies. We grouped these experiments in three ways. We then constructed a meta-analytic connectivity model (MACM) for regions of consistent MTLE structural change as reported by the ALE analysis. Key findings: ALE reported spatially consistent structural change across VBM studies only in the epileptogenic hippocampus and the bilateral thalamus; within the thalamus, the medial dorsal nucleus of the thalamus (MDN thalamus) represented the greatest convergence (Pb0.05 corrected for multiple comparisons). The subsequent MACM for the hippocampus and ipsilateral MDN thalamus demonstrated that the hippocampus and ipsilateral MDN thalamus functionally co-activate and are nodes within the same network, suggesting that MDN thalamic damage could result from MTLE network excitotoxicity. Significance: Notwithstanding our large sample of studies, these findings aremore restrictive thanprevious reports and demonstrate the utility of our inclusion filters and of recently modified meta-analyticmethods in approximating clinical relevance. Thalamic pathology is commonly observed in animal and human studies, suggesting it could be a clinically useful indicator. Thalamus-specific research as a clinical marker awaits further investigation

Progranulin is Neurotrophic In Vivo and Protects against a Mutant TDP-43 Induced Axonopathy

Mislocalization, aberrant processing and aggregation of TAR DNA-binding protein 43 (TDP-43) is found in the neurons affected by two related diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal lobe dementia (FTLD). These TDP-43 abnormalities are seen when TDP-43 is mutated, such as in familial ALS, but also in FTLD, caused by null mutations in the progranulin gene. They are also found in many patients with sporadic ALS and FTLD, conditions in which only wild type TDP-43 is present. The common pathological hallmarks and symptomatic cross over between the two diseases suggest that TDP-43 and progranulin may be mechanistically linked. In this study we aimed to address this link by establishing whether overexpression of mutant TDP-43 or knock-down of progranulin in zebrafish embryos results in motor neuron phenotypes and whether human progranulin is neuroprotective against such phenotypes. Mutant TDP-43 (A315T mutation) induced a motor axonopathy characterized by short axonal outgrowth and aberrant branching, similar, but more severe, than that induced by mutant SOD1. Knockdown of the two zebrafish progranulin genes, grna and grnb, produced a substantial decrease in axonal length, with knockdown of grna alone producing a greater decrease in axonal length than grnb. Progranulin overexpression rescued the axonopathy induced by progranulin knockdown. Interestingly, progranulin also rescued the mutant TDP-43 induced axonopathy, whilst it failed to affect the mutant SOD1-induced phenotype. TDP-43 was found to be nuclear in all conditions described. The findings described here demonstrate that progranulin is neuroprotective in vivo and may have therapeutic potential for at least some forms of motor neuron degeneration

Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations

Background Whereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through meta-analytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations. Methods We first conducted a coordinate-based meta-analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta-analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural?functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding. Results Across studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural?functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural-behavioral implications, we observed that the left insula?s task-based, functional interactions with multiple other structurally impacted regions were linked with pain perception, the right cerebellum?s interactions with other regions were associated with overt body movements, interactions between the parahippocampus and thalamus were linked with memory processes, and interactions between medial PFC regions were associated with face processing. Conclusions Collectively, these findings emphasize brain regions (e.g., ventromedial PFC, insula, thalamus) critically linked with cigarette smoking, suggest neuroimaging paradigms warranting additional consideration among smokers (e.g., pain processing), and highlight regions in need of further elucidation in addiction (e.g., cerebellum). Electronic supplementary material The online version of this article (doi:10.1186/s12993-016-0100-5) contains supplementary material, which is available to authorized users

Functional Activation and Effective Connectivity Differences in Adolescent Marijuana Users Performing a Simulated Gambling Task

Background. Adolescent marijuana use is associated with structural and functional differences in forebrain regions while performing memory and attention tasks. In the present study, we investigated neural processing in adolescent marijuana users experiencing rewards and losses. Fourteen adolescents with frequent marijuana use (\u3e5 uses per week) and 14 nonuser controls performed a computer task where they were required to guess the outcome of a simulated coin flip while undergoing magnetic resonance imaging. Results. Across all participants, ?Wins? and ?Losses? were associated with activations including cingulate, middle frontal, superior frontal, and inferior frontal gyri and declive activations. Relative to controls, users had greater activity in the middle and inferior frontal gyri, caudate, and claustrum during ?Wins? and greater activity in the anterior and posterior cingulate, middle frontal gyrus, insula, claustrum, and declive during ?Losses.? Effective connectivity analyses revealed similar overall network interactions among these regions for users and controls during both ?Wins? and ?Losses.? However, users and controls had significantly different causal interactions for 10 out of 28 individual paths during the ?Losses? condition. Conclusions. Collectively, these results indicate adolescent marijuana users have enhanced neural responses to simulated monetary rewards and losses and relatively subtle differences in effective connectivity

The BrainMap strategy for standardization, sharing, and meta-analysis of neuroimaging data

<p>Abstract</p> <p>Background</p> <p>Neuroimaging researchers have developed rigorous community data and metadata standards that encourage meta-analysis as a method for establishing robust and meaningful convergence of knowledge of human brain structure and function. Capitalizing on these standards, the BrainMap project offers databases, software applications, and other associated tools for supporting and promoting quantitative coordinate-based meta-analysis of the structural and functional neuroimaging literature.</p> <p>Findings</p> <p>In this report, we describe recent technical updates to the project and provide an educational description for performing meta-analyses in the BrainMap environment.</p> <p>Conclusions</p> <p>The BrainMap project will continue to evolve in response to the meta-analytic needs of biomedical researchers in the structural and functional neuroimaging communities. Future work on the BrainMap project regarding software and hardware advances are also discussed.</p

Extended Functional Connectivity of Convergent Structural Alterations Among Individuals with PTSD: A Neuroimaging Meta-Analysis

Background: Post-traumatic stress disorder (PTSD) is a debilitating disorder defined by the onset of intrusive, avoidant, negative cognitive or affective, and/or hyperarousal symptoms after witnessing or experiencing a traumatic event. Previous voxel-based morphometry studies have provided insight into structural brain alterations associated with PTSD with notable heterogeneity across these studies. Furthermore, how structural alterations may be associated with brain function, as measured by task-free and task-based functional connectivity, remains to be elucidated. Methods: Using emergent meta-analytic techniques, we sought to first identify a consensus of structural alterations in PTSD using the anatomical likelihood estimation (ALE) approach. Next, we generated functional profiles of identified convergent structural regions utilizing resting-state functional connectivity (rsFC) and meta-analytic co-activation modeling (MACM) methods. Finally, we performed functional decoding to examine mental functions associated with our ALE, rsFC, and MACM brain characterizations. Results: We observed convergent structural alterations in a single region located in the medial prefrontal cortex. The resultant rsFC and MACM maps identified functional connectivity across a widespread, whole-brain network that included frontoparietal and limbic regions. Functional decoding revealed overlapping associations with attention, memory, and emotion processes. Conclusions: Consensus-based functional connectivity was observed in regions of the default mode, salience, and central executive networks, which play a role in the tripartite model of psychopathology. Taken together, these findings have important implications for understanding the neurobiological mechanisms associated with PTSD

Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study

Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits

Effects of a peer-led Walking In ScHools intervention (the WISH study) on physical activity levels of adolescent girls: a cluster randomised pilot study.

School-based interventions may be effective at increasing levels of physical activity (PA) among adolescents; however, there is a paucity of evidence on whether walking can be successfully promoted to increase PA in this age group. This pilot study aimed to assess the effects of a 12-week school-based peer-led brisk walking programme on levels of school-time PA post intervention

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts