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Dissecting diagnostic heterogeneity in depression by integrating neuroimaging and genetics.

Wed, 08/12/2020 - 21:39

Dissecting diagnostic heterogeneity in depression by integrating neuroimaging and genetics.

Neuropsychopharmacology. 2020 Aug 11;:

Authors: Buch AM, Liston C

Abstract
Depression is a heterogeneous and etiologically complex psychiatric syndrome, not a unitary disease entity, encompassing a broad spectrum of psychopathology arising from distinct pathophysiological mechanisms. Motivated by a need to advance our understanding of these mechanisms and develop new treatment strategies, there is a renewed interest in investigating the neurobiological basis of heterogeneity in depression and rethinking our approach to diagnosis for research purposes. Large-scale genome-wide association studies have now identified multiple genetic risk variants implicating excitatory neurotransmission and synapse function and underscoring a highly polygenic inheritance pattern that may be another important contributor to heterogeneity in depression. Here, we review various sources of phenotypic heterogeneity and approaches to defining and studying depression subtypes, including symptom-based subtypes and biology-based approaches to decomposing the depression syndrome. We review "dimensional," "categorical," and "hybrid" approaches to parsing phenotypic heterogeneity in depression and defining subtypes using functional neuroimaging. Next, we review recent progress in neuroimaging genetics (correlating neuroimaging patterns of brain function with genetic data) and its potential utility for generating testable hypotheses concerning molecular and circuit-level mechanisms. We discuss how genetic variants and transcriptomic profiles may confer risk for depression by modulating brain structure and function. We conclude by highlighting several promising areas for future research into the neurobiological underpinnings of heterogeneity, including efforts to understand sexually dimorphic mechanisms, the longitudinal dynamics of depressive episodes, and strategies for developing personalized treatments and facilitating clinical decision-making. Fig. 1 APPROACHES TO PARSING HETEROGENEITY IN DEPRESSION.: Schematic illustrating two data-driven approaches to parsing heterogeneity in depression described in the text using a "top-down" symptom-based approach (right, blue) or a "bottom-up" brain-based mechanistic approach (left, green). The goals of both approaches are to advance our understanding of neurobiological mechanisms underlying depression-related symptoms and behaviors and to develop new tools for informing diagnosis and treatment decisions. Fig. 2 TRANSDIAGNOSTIC PSYCHOPATHOLOGY BRAIN CONNECTIVITY-BEHAVIOR DIMENSIONS.: a Schematic of the analytical pipeline depicting the calculation of functional connectivity matrices from the Pearson correlations between the average BOLD fMRI signals for each of 264 spherical regions of interest (ROI) and every other ROI. Sparse canonical correlation (sCCA) was used to define linear combinations of clinical symptoms across a range of psychiatric diagnoses (lower panel) that were maximally correlated with linear combinations of functional connectivity. Psychopathology domains: psychotic and subthreshold symptoms (PSY), depression (DEP), mania (MAN), suicidality (SUI), attention-deficit hyperactivity disorder (ADD), oppositional defiant disorder (ODD), conduct disorder (CON), obsessive-compulsive disorder (OCD), separation anxiety (SEP), generalized anxiety disorder (GAD), specific phobias (PHB), mental health treatment (TRT), panic disorder (PAN), post-traumatic stress disorder (PTSD). ROI communities: somatosensory/motor network (SMT), cingulo-opercular network (COP), auditory network (AUD), default mode network (DMN), visual network (VIS), fronto-parietal network (FPT), salience network (SAL), subcortical network (SBC), ventral attention network (VAT), dorsal attention network (DAT), cerebellar. b-e Four brain-behavior dimensions of psychopathology were identified that captured individual differences in clinical symptoms. Scatter plots depict brain connectivity and clinical dimension scores, which are linear combinations of functional connectivity features and psychiatric symptoms. b Dimension 1 described mood-related symptoms, e.g. feeling sad. c Dimension 2 described psychosis-related symptoms, e.g. auditory hallucinations. d Dimension 3 described fear-related symptoms, e.g. fear of traveling. e Dimension 4 described externalizing behavior and related symptoms, e.g. trouble following instructions. f-i Network module connectivity patterns associated with each brain connectivity-behavior dimension. Heatmaps depict the magnitude and direction of correlation change to each brain-behavior dimension score (positively- or negatively correlated) in the following functional networks: default mode network (DMN), visual network (VIS), fronto-parietal network (FPT), salience network (SAL), ventral attention network (VAT), dorsal attention network (DAT). Abbreviations: a.u., arbitrary units. Figure adapted with permission from ref. [88]. Fig. 3 BRAIN CONNECTIVITY-BEHAVIOR DIMENSIONS OF DEPRESSION DEFINE NOVEL DEPRESSION SUBTYPES THAT PREDICT TREATMENT RESPONSE TO TMS.: a Four rsfMRI-based subtypes of depression, identified through hierarchical clustering on latent brain-behavior dimensions (canonical connectivity-symptom components), exhibit distinct patterns of atypical functional connectivity. Heatmaps depict the z score from a Wilcoxon rank sum test for differences between the functional connectivity of depressed subjects in each subtype and of healthy controls. b The four subtypes were associated with distinct clinical symptom profiles as indexed by item-level responses to the Hamilton Depression Rating Scale. c Boxplots depicting subtype differences in depression severity. d-e Patients in Subtypes 1 and 3 were more likely to respond to rTMS targeting the dorsomedial prefrontal cortex, compared to patients in Subtypes 2 and 4. f Distinct functional connectivity patterns prior to treatment in rTMS-responders vs. nonresponders. Heatmap depicts functional connectivity features that were significantly different in responders, including connectivity between the dorsomedial prefrontal target and the left dorsolateral prefrontal cortex and left amygdala. Figure adapted with permission from Ref. [98]. ACC anterior cingulate cortex; amyg amygdala; a.u. arbitrary units; COTC cingulo-opercular task-control network; DAN dorsal attention network; DLPFC dorsolateral prefrontal cortex; DMN default-mode network; DMPFC dorsomedial prefrontal cortex; FPTC frontoparietal task-control network; GP globus pallidus; HAMD Hamilton Depression Rating Scale; HC hippocampus; lat PFC lateral prefrontal cortex; LIMB limbic; M1 primary motor cortex; NAcc nucleus accumbens; OFC orbitofrontal cortex; PCC posterior cingulate cortex; PPC posterior parietal cortex; precun precuneus; rTMS repetitive transcranial magnetic stimulation; rsfMRI resting state functional MRI; SM primary sensorimotor cortex (M1 or S1); SS1 primary somatosensory cortex; SN salience network; subC subcortical; thal, thalamus; VAN ventral attention network; vis visual cortex; VLPFC ventrolateral prefrontal cortex; vStr ventral striatum; n.s. not significant. Fig. 4 INTEGRATING NEUROIMAGING AND GENETIC DATA TO UNCOVER INTERMEDIATE ENDOPHENOTYPES AND NOVEL DEPRESSION SUBGROUPS.: Schematic of how combining neuroimaging with genetic data can be used to parse heterogeneity in depression and uncover subgroups within the depressed population. Polygenic variation may manifest in intermediate behavior-related brain circuits that can give rise to distinct depression subgroups. The polygenic effects of risk variants on circuit dysfunction, cognition, behavior, and clinical symptoms may interact with each other. Genes indicated are examples of candidate depression risk variants from Table 3 with the known variation and locus in the genome indicated and depicted on the chromosome strand in yellow. 1. Indicates examples of brain circuits known to be dysfunctional in depression. 2. Lists examples of cognitive processes and behaviors that are altered in depression, possibly as a direct or indirect consequence of genetic risk variants. 3. Lists clinical symptoms of depression that may result directly or indirectly from dysfunction in depression brain circuits. The double-sided arrows indicate the bi-directional relationships between 1, 2, and 3 that may modulate the expression of intermediate phenotypes. Fig. 5 POLYGENIC RISK SCORES FOR ANHEDONIA PREDICT PSYCHIATRIC NEUROIMAGING PHENOTYPES AND SPATIAL PATTERNS OF GENE EXPRESSION FOR SCHIZOPHRENIA RISK GENES PREDICT SCHIZOTYPY-ASSOCIATED MYELINATION.: a-c Polygenic risk scores (PRS) for anhedonia were associated with a. regional volumes of cortical and subcortical regions of interest, b tract-specific fractional anisotropy (measure of axonal integrity and myelination), and c tract-specific mean diffusivity (measures of structural integrity in the intra- and extracellular space, neuropil, and global CSF). d Partial least squares (PLS) analysis linear combinations of genes whose spatial expression patterns co-localized with schizotypy-associated myelination patterns as indexed by an MRI magnetization transfer measure. Genes with larger "PLS1 weight" values were more important predictors of the spatial distribution of SRM myelination. e Positively weighted PLS1 genes were associated with genes known to be down-regulated in schizophrenia ("Gandal Down-Reg" and "Fromer Down-Reg"), neuron cell types, and increased SRM myelination. f Negatively weighted PLS1 genes were associated with genes known to be up-regulated in schizophrenia ("Gandal Up-Reg" and "Fromer Up-Reg"), decreased SRM myelination, and astrocyte, microglia, and neuron cell types. FDR false discovery rate; PLS partial least squares; SRM schizotypy-related magnetization; Up/Down-Reg Up/Down-Regulated. Figure adapted with permission from refs. [155] (a-c) and [160] (d-f).

PMID: 32781460 [PubMed - as supplied by publisher]

Anterior insular network disconnection and cognitive impairment in Parkinson's disease.

Wed, 08/12/2020 - 21:39

Anterior insular network disconnection and cognitive impairment in Parkinson's disease.

Neuroimage Clin. 2020 Jul 25;28:102364

Authors: Fathy YY, Hepp DH, de Jong FJ, Geurts JJG, Foncke EMJ, Berendse HW, van de Berg WDJ, Schoonheim MM

Abstract
BACKGROUND: The insula is a central brain hub involved in cognition and affected in Parkinson's disease (PD). The aim of this study was to assess functional connectivity (FC) and betweenness centrality (BC) of insular sub-regions and their relationship with cognitive impairment in PD.
METHODS: Whole-brain 3D-T1, resting-state functional MRI and a battery of cognitive tests (CAMCOG) were included for 53 PD patients and 15 controls. The insular cortex was segmented into ventral (vAI) and dorsal (dAI) anterior and posterior sub-regions. Connectivity between insular sub-regions and resting-state networks was assessed and related to cognition; BC was used to further explore nodes associated with cognition.
RESULTS: Cognitive performance was significantly lower in PD patients compared to controls (p < 0.01) and was associated with FC of the dAI with default mode network (DMN) (adjusted R2 = 0.37, p < 0.001). In controls, cognitive performance was positively related to FC of the dAI with the fronto-parietal network (FPN) only (adjusted R2 = 0.5, p = 0.003). Regionally, FC of the dAI with the anterior cingulate cortex (ACC) was significantly reduced in PD (F(1,65) = 11, p = 0.002) and correlated with CAMCOG (r = 0.4, p = 0.001). DMN and FPN showed increased BC in PD which correlated with cognition and reduced connectivity of dAI with the ACC (rs = -0.33, p = 0.014 and rs = -0.44, p = 0.001 respectively).
CONCLUSIONS: These results highlight the relevance of the insula in cognitive dysfunction in PD. Disconnection of the dAI with ACC was related to altered centrality in the DMN and FPN only in patients. Disturbance in this network triad appears to be particularly relevant for cognitive impairment in PD.

PMID: 32781423 [PubMed - as supplied by publisher]

Intrinsic brain activity changes in temporal lobe epilepsy patients revealed by regional homogeneity analysis.

Wed, 08/12/2020 - 21:39

Intrinsic brain activity changes in temporal lobe epilepsy patients revealed by regional homogeneity analysis.

Seizure. 2020 Aug 05;81:117-122

Authors: Zhao B, Yang B, Tan Z, Hu W, Sang L, Zhang C, Wang X, Wang Y, Liu C, Mo J, Shao X, Zhang J, Zhang K

Abstract
PURPOSE: Temporal lobe epilepsy is increasingly being recognized as a disorder associated with brain networks extending outside the seizure onset zone. In the current study, we aim to clarify regional functional changes using a regional homogeneity method.
METHODS: We retrospectively included resting-state fMRI data from 14 left and 18 right temporal lobe epilepsy patients. Data from the control group were acquired from an open dataset. Regional homogeneity was calculated, and a two-sample t-test was performed to compare the left and right temporal lobe epilepsy groups with the control group.
RESULTS: Compared with the healthy control group, the left temporal lobe epilepsy group showed increased regional homogeneity in the left anterior and middle cingulate cortex, and putamen; right inferior frontal gyrus; bilateral temporal lobe and precentral gyrus and decreased regional homogeneity in the left superior parietal gyrus, cuneus and inferior occipital gyrus; right inferior parietal lobule and bilateral rectus. The right temporal lobe epilepsy group showed increased regional homogeneity in the left middle cingulate cortex, precuneus, precentral and postcentral gyrus; right insula and bilateral temporal lobe and decreased regional homogeneity in the left cuneus and superior occipital gyrus; right supramarginal gyrus, fusiform gyrus, lingual gyrus, inferior occipital gyrus and putamen; and the bilateral rectus.
CONCLUSION: Regional homogeneity measurements provide evidence supporting that temporal lobe epilepsy is a complex network disease. Functional disruption of temporal lobe epilepsy at the brain region level was revealed, which may provide novel insights for any potential diagnostic and therapeutic approaches.

PMID: 32781401 [PubMed - as supplied by publisher]

Functional dissection of prenatal drug effects on baby brain and behavioral development.

Wed, 08/12/2020 - 21:39
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Functional dissection of prenatal drug effects on baby brain and behavioral development.

Hum Brain Mapp. 2020 Aug 11;:

Authors: Salzwedel A, Chen G, Chen Y, Grewen K, Gao W

Abstract
Prenatal drug exposure (PDE) is known to affect fetal brain development with documented long-term consequences. Most studies of PDE effects on the brain are based on animal models. In this study, based on a large sample of 133 human neonates and leveraging a novel linear mixed-effect model designed for intersubject variability analyses, we studied the effects of six prenatally exposed drugs (i.e., nicotine, alcohol, selective serotonin reuptake inhibitor, marijuana, cocaine, and opioids) on neonatal whole-brain functional organization and compared them with five other critical nondrug variables (i.e., gestational age at birth/scan, sex, birth weight, and maternal depression). The behavioral implications were also examined. Magnitude-wise, through summing across individual drug effects, our results highlighted ~5% of whole-brain functional connections (FCs) affected by PDE, which was highly comparable with the combined effects of the five nond rug variables. Spatially, the detected PDE effects featured drug-specific patterns with a common bias in higher-order brain regions/networks. Regarding brain-behavioral relationships, the detected connections showing significant drug effects also demonstrated significant correlations with 3-month behavioral outcomes. Further mediation analyses supported a mediation role of the detected brain FCs between PDE status and cognitive/language outcomes. Our findings of widespread, and spatially biased PDE effect patterns coupled with significant behavioral implications may hopefully stimulate more human-based studies into effects of PDE on long-term developmental outcomes.

PMID: 32779835 [PubMed - as supplied by publisher]

An examination of maternal prenatal BMI and human fetal brain development.

Wed, 08/12/2020 - 21:39
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An examination of maternal prenatal BMI and human fetal brain development.

J Child Psychol Psychiatry. 2020 Aug 10;:

Authors: Norr ME, Hect JL, Lenniger CJ, Van den Heuvel M, Thomason ME

Abstract
BACKGROUND: Prenatal development is a time when the brain is acutely vulnerable to insult and alteration by environmental factors (e.g., toxins, maternal health). One important risk factor is maternal obesity (Body Mass Index > 30). Recent research indicates that high maternal BMI during pregnancy is associated with increased risk for numerous physical health, cognitive, and mental health problems in offspring across the lifespan. It is possible that heightened maternal prenatal BMI influences the developing brain even before birth.
METHODS: The present study examines this possibility at the level of macrocircuitry in the human fetal brain. Using a data-driven strategy for parcellating the brain into subnetworks, we test whether MRI functional connectivity within or between fetal neural subnetworks varies with maternal prenatal BMI in 109 fetuses between the ages of 26 and 39weeks.
RESULTS: We discovered that strength of connectivity between two subnetworks, left anterior insula/inferior frontal gyrus (aIN/IFG) and bilateral prefrontal cortex (PFC), varied with maternal BMI. At the level of individual aIN/IFG-PFC connections, we observed both increased and decreased between-network connectivity with a tendency for increased within-hemisphere connectivity and reduced cross-hemisphere connectivity in higher BMI pregnancies. Maternal BMI was not associated with global differences in network topography based on network-based statistical analyses.
CONCLUSIONS: Overall effects were localized in regions that will later support behavioral regulation and integrative processes, regions commonly associated with obesity-related deficits. By establishing onset in neural differences prior to birth, this study supports a model in which maternal BMI-related risk is associated with fetal connectome-level brain organization with implications for offspring long-term cognitive development and mental health.

PMID: 32779186 [PubMed - as supplied by publisher]

Plasticity and Spontaneous Activity Pulses in Disused Human Brain Circuits.

Wed, 08/12/2020 - 21:39
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Plasticity and Spontaneous Activity Pulses in Disused Human Brain Circuits.

Neuron. 2020 Aug 05;107(3):580-589.e6

Authors: Newbold DJ, Laumann TO, Hoyt CR, Hampton JM, Montez DF, Raut RV, Ortega M, Mitra A, Nielsen AN, Miller DB, Adeyemo B, Nguyen AL, Scheidter KM, Tanenbaum AB, Van AN, Marek S, Schlaggar BL, Carter AR, Greene DJ, Gordon EM, Raichle ME, Petersen SE, Snyder AZ, Dosenbach NUF

Abstract
To induce brain plasticity in humans, we casted the dominant upper extremity for 2 weeks and tracked changes in functional connectivity using daily 30-min scans of resting-state functional MRI (rs-fMRI). Casting caused cortical and cerebellar regions controlling the disused extremity to functionally disconnect from the rest of the somatomotor system, while internal connectivity within the disused sub-circuit was maintained. Functional disconnection was evident within 48 h, progressed throughout the cast period, and reversed after cast removal. During the cast period, large, spontaneous pulses of activity propagated through the disused somatomotor sub-circuit. The adult brain seems to rely on regular use to maintain its functional architecture. Disuse-driven spontaneous activity pulses may help preserve functionally disconnected sub-circuits.

PMID: 32778224 [PubMed - in process]

Abnormal Fractional Amplitude of Low-Frequency Fluctuation Changes in Patients with Monocular Blindness: A Functional Magnetic Resonance Imaging (MRI) Study.

Tue, 08/11/2020 - 21:38

Abnormal Fractional Amplitude of Low-Frequency Fluctuation Changes in Patients with Monocular Blindness: A Functional Magnetic Resonance Imaging (MRI) Study.

Med Sci Monit. 2020 Aug 10;26:e926224

Authors: Fang JW, Yu YJ, Tang LY, Chen SY, Zhang MY, Sun T, Wu SN, Yu K, Li B, Shao Y

Abstract
BACKGROUND We used fractional amplitude of low-frequency fluctuation (fALFF) technology to investigate spontaneous cerebral activity in patients with monocular blindness (MB) and in healthy controls (HCs). MATERIAL AND METHODS Thirty MB patient and 15 HCs were included in this study. All subjects were scanned by resting-state functional magnetic resonance imaging (rs-fMRI). The independent sample t test and chi-squared test were applied to analyze demographics of MB patients and HCs. The 2-sample t test and receiver operating characteristic (ROC) curves were applied to identify the difference in average fALFF values between MB patients and HCs. Pearson's correlation analysis was applied to explore the relationship between the average fALFF values of brain areas and clinical behavior in the MB group. RESULTS MB patients had lower fALFF values in the left anterior cingulate and higher fALFF values in the left precuneus and right and left inferior parietal lobes than in HCs. Moreover, the mean fALFF values of MB patients in the left anterior cingulate had negative correlations with the anxiety scale score (r=-0.825, P<0.001) and the depression scale score (r=-0.871, P<0.001). CONCLUSIONS Our study found that MB patients had abnormal spontaneous activities in the visual and vision-related regions. The finding of abnormal neuronal activity helps to reveal the underlying neuropathologic mechanisms of vision loss.

PMID: 32773731 [PubMed - as supplied by publisher]

Abnormal subgenual anterior cingulate circuitry is unique to women but not men with chronic pain.

Tue, 08/11/2020 - 21:38

Abnormal subgenual anterior cingulate circuitry is unique to women but not men with chronic pain.

Pain. 2020 Aug 05;:

Authors: Osborne NR, Cheng JC, Rogachov A, Kim JA, Hemington KS, Bosma RL, Inman RD, Davis KD

Abstract
The subgenual anterior cingulate cortex (sgACC) plays an important role in pain modulation. We previously demonstrated sex differences in sgACC functional connectivity (FC) in healthy individuals. Given that many chronic pain conditions show sex differences in prevalence, here we tested the hypothesis that people with chronic pain exhibit a sex-specific pattern of abnormal sgACC FC. We acquired resting state functional magnetic resonance imaging (fMRI) data from 156 (82W:74M) healthy participants and 38 (19W:19M) people with chronic low back pain resulting from ankylosing spondylitis (AS), a condition that predominantly affects men. We confirmed that there are sex differences in sgACC FC in our large cohort of healthy adults; women had greater sgACC FC with the precuneus, a key node of the default mode network, and men had greater sgACC FC with the posterior insula and the operculum. Next, we identified an interaction effect between sex and pain status (healthy/chronic pain) for sgACC FC. Within the chronic pain group, women had greater sgACC FC than men to the salience, default mode, and sensorimotor networks. Compared to healthy women, women with chronic pain also had greater sgACC FC to the precuneus and ACC and lower FC to the hippocampus and frontal regions. No differences in sgACC FC were seen in men with vs. without chronic pain. Our findings indicate that abnormal sgACC circuitry is unique to women but not men with AS-related chronic pain. These sex differences may impact the benefit of therapeutics that target the sgACC for chronic pain.

PMID: 32773597 [PubMed - as supplied by publisher]

Neural signatures of sleep recovery following melatonin treatment for pediatric concussion.

Tue, 08/11/2020 - 21:38

Neural signatures of sleep recovery following melatonin treatment for pediatric concussion.

J Neurotrauma. 2020 Aug 09;:

Authors: Iyer K, Zalesky A, Cocchi L, Barlow KM

Abstract
Evidence-based treatments for children with persistent post-concussion symptoms (PPCS) are few and limited. Common PPCS complaints such as sleep disturbance and fatigue could be ameliorated via the supplementation of melatonin, which has significant neuroprotective and anti-inflammatory properties. This study aims to identify neural signatures of melatonin treatment with changes in sleep disturbances and clinical recovery in a pediatric cohort with PPCS. We examined structural and functional neuroimaging (MRI) in 62 children with PPCS in a randomized, double-blind, placebo-controlled trial of 3mg or 10mg of melatonin (NCT01874847). The primary outcome was the total youth self-report Post-Concussion Symptom Inventory (PCSI) score after 28 days of treatment. Secondary outcomes included the change in the sleep domain PCSI score and sleep-wake behavior (assessed using wrist-worn actigraphy). Whole-brain analyses of (i) functional connectivity (FC) of resting-state fMRI, and (ii) structural grey matter (GM) volumes via voxel-based morphometry were assessed immediately before and after melatonin treatment and compared to placebo in order to identify neural effects of melatonin treatment. Increased FC of posterior default mode network (DMN) regions with visual, somatosensory and dorsal networks was detected in the melatonin groups over time. FC increases also corresponded with reduced wake periods (r=-0.27, p=0.01). Children who did not recover (n=39) demonstrated significant FC increases within anterior DMN and limbic regions compared to those that did recover (i.e. PCSI scores returned to pre-injury level n=23) over time, (p=0.026). Increases in GM volume within the posterior cingulate cortex were found to correlate with reduced wakefulness after sleep onset (r=-0.32, p=0.001) and sleep symptom improvement (r=0.29, p=0.02). Although melatonin treatment did not improve PPCS overall clinically, our study finds that melatonin treatment significantly improved subjective and objective sleep parameters with related function-structure relationships within and between brain regions interacting with the DMN.

PMID: 32772826 [PubMed - as supplied by publisher]

Interaction of Catechol-O-methyltransferase Val158 Met polymorphism and sex influences association of parietal intrinsic functional connectivity and immediate verbal memory.

Tue, 08/11/2020 - 21:38

Interaction of Catechol-O-methyltransferase Val158 Met polymorphism and sex influences association of parietal intrinsic functional connectivity and immediate verbal memory.

Brain Behav. 2020 Aug 08;:e01784

Authors: Wu S, Upadhyay N, Lu J, Jiang X, Li S, Qing Z, Wang J, Liang X, Zhang X, Zhang B

Abstract
INTRODUCTION: Sex differences modulate catechol-O-methyltransferase (COMT) genotype effect at a synaptic dopamine level, which influences brain function as well as cognitive performance. In this study, we investigated how COMT Val158 Met polymorphism and sex affect intrinsic functional connectivity and memory.
METHODS: Intrinsic functional networks were extracted using independent component analysis of resting-state functional magnetic resonance imaging data from 186 healthy young COMT-genotyped participants. The association of these functional networks and memory function was tested to investigate whether the effect of COMT × sex interaction influences the association of intrinsic functional connectivity and memory performance. Quadratic curve fit estimation was used to examine the relationship between functional connectivity and speculative dopamine level among groups.
RESULTS: COMT MM/MV carriers, relative to VV carriers, showed increased functional connectivity in left superior parietal lobule and right inferior frontal gyrus. Further, male MM/MV carriers showed significant higher mean functional connectivity in left inferior parietal lobule relative to male VV carriers and female MM/MV carriers, which was associated with worse immediate verbal recall performance. Additionally, the relationship between inferior parietal lobule functional connectivity and speculative dopamine level among groups fits the quadratic curve.
CONCLUSIONS: These findings suggest that the interaction of COMT genotype and sex might regulate synaptic dopaminergic concentrations and influence the association of intrinsic functional connectivity and immediate verbal memory in left inferior parietal lobule.

PMID: 32772512 [PubMed - as supplied by publisher]

Joint Embedding: A scalable alignment to compare individuals in a connectivity space.

Tue, 08/11/2020 - 21:38

Joint Embedding: A scalable alignment to compare individuals in a connectivity space.

Neuroimage. 2020 Aug 06;:117232

Authors: Nenning KH, Xu T, Schwartz E, Arroyo J, Woehrer A, Franco AR, Vogelstein JT, Margulies DS, Liu H, Smallwood J, Milham MP, Langs G

Abstract
A common coordinate space enabling comparison across individuals is vital to understanding human brain organization and individual differences. By leveraging dimensionality reduction algorithms, high-dimensional fMRI data can be represented in a low-dimensional space to characterize individual features. Such a representative space encodes the functional architecture of individuals and enables the observation of functional changes across time. However, determining comparable functional features across individuals in resting-state fMRI in a way that simultaneously preserves individual-specific connectivity structure can be challenging. In this work we propose scalable joint embedding to simultaneously embed multiple individual brain connectomes within a common space that allows individual representations across datasets to be aligned. Using Human Connectome Project data, we evaluated the joint embedding approach by comparing it to the previously established orthonormal alignment model. Alignment using joint embedding substantially increased the similarity of functional representations across individuals while simultaneously capturing their distinct profiles, allowing individuals to be more discriminable from each other. Additionally, we demonstrated that the common space established using resting-state fMRI provides a better overlap of task-activation across participants. Finally, in a more challenging scenario - alignment across a lifespan cohort aged from 6 to 85 - joint embedding provided a better prediction of age (r2=0.65) than the prior alignment model. It facilitated the characterization of functional trajectories across lifespan. Overall, these analyses establish that joint embedding can simultaneously capture individual neural representations in a common connectivity space aligning functional data across participants and populations and preserve individual specificity.

PMID: 32771618 [PubMed - as supplied by publisher]

Modelling Subject Variability in the Spatial and Temporal Characteristics of Functional Modes.

Tue, 08/11/2020 - 21:38

Modelling Subject Variability in the Spatial and Temporal Characteristics of Functional Modes.

Neuroimage. 2020 Aug 06;:117226

Authors: Harrison SJ, Bijsterboch JD, Segerdahl AR, Fitzgibbon SP, Farahibozorg SR, Duff EP, Smith SM, Woolrich MW

Abstract
Recent work has highlighted the scale and ubiquity of subject variability in observations from functional MRI data (fMRI). Furthermore, it is highly likely that errors in the estimation of either the spatial presentation of, or the coupling between, functional regions can confound cross-subject analyses, making accurate and unbiased representations of functional data essential for interpreting any downstream analyses. Here, we extend the framework of probabilistic functional modes (PFMs) (Harrison et al., 2015) to capture cross-subject variability not only in the mode spatial maps, but also in the functional coupling between modes and in mode amplitudes. A new implementation of the inference now also allows for the analysis of modern, large-scale data sets, and the combined inference and analysis package, PROFUMO, is available from git.fmrib.ox.ac.uk/samh/profumo. A new implementation of the inference now also allows for the analysis of modern, large-scale data sets. Using simulated data, resting-state data from 1000 subjects collected as part of the Human Connectome Project (Van Essen et al., 2013), and an analysis of 14 subjects in a variety of continuous task-states (Kieliba et al., 2019), we demonstrate how PFMs are able to capture, within a single model, a rich description of how the spatio-temporal structure of resting-state fMRI activity varies across subjects. We also compare the new PFM model to the well established independent component analysis with dual regression (ICA-DR) pipeline. This reveals that, under PFM assumptions, much more of the (behaviorally relevant) cross-subject variability in fMRI activity should be attributed to the variability in spatial maps, and that after accounting for this functional coupling between modes primarily reflects current cognitive state. This has fundamental implications for the interpretation of cross-sectional studies of functional connectivity that do not capture cross-subject variability to the same extent as PFMs.

PMID: 32771617 [PubMed - as supplied by publisher]

Open eyes and closed eyes elicit different temporal properties of brain functional networks.

Tue, 08/11/2020 - 21:38

Open eyes and closed eyes elicit different temporal properties of brain functional networks.

Neuroimage. 2020 Aug 06;:117230

Authors: Weng Y, Liu X, Hu H, Huang H, Zheng S, Chen Q, Song J, Cao B, Wang J, Wang S, Huang R

Abstract
The eyes are our windows to the brain. There are differences in brain activity between people who have their eyes closed (EC) and eyes open (EO). Previous studies focused on differences in brain functional properties between these eyes conditions based on an assumption that brain activity is a static phenomenon. However, the dynamic nature of the brain activity in different eyes conditions is still unclear. In this study, we collected resting-state fMRI data from 21 healthy subjects in the EC and EO conditions. Using a sliding time window approach and a k-means clustering algorithm, we calculated the temporal properties of dynamic functional connectivity (dFC) states in the eyes conditions. We also used graph theory to estimate the dynamic topological properties of functional networks in the two conditions. We detected two dFC states, a hyper-connected State 1 and a hypo-connected State 2. We showed the following results: (i) subjects in the EC condition stayed longer in the hyper-connected State 1 than those in the EO; (ii) subjects in the EO condition stayed longer in the hypo-connected State 2 than those in the EC; and (iii) the dFC state transformed into the other state more frequently during EC than during EO. We also found the variance of the characteristic path length was higher during EC than during EO in the hyper-connected State 1. These results indicate that brain activity may be more active and unstable during EC than during EO. Our findings may provide insights into the dynamic nature of the resting-state brain and could be a useful reference for future rs-fMRI studies.

PMID: 32771616 [PubMed - as supplied by publisher]

Resting-state functional magnetic resonance imaging with independent component analysis for presurgical seizure onset zone localization: A systematic review and meta-analysis.

Mon, 08/10/2020 - 21:36
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Resting-state functional magnetic resonance imaging with independent component analysis for presurgical seizure onset zone localization: A systematic review and meta-analysis.

Epilepsia. 2020 Aug 08;:

Authors: Chakraborty AR, Almeida NC, Prather KY, O'Neal CM, Wells AA, Chen S, Conner AK

Abstract
OBJECTIVE: One of the greatest challenges of achieving successful surgical outcomes in patients with epilepsy is the ability to properly localize the seizure onset zone (SOZ). Many techniques exist for localizing the SOZ, including intracranial electroencephalography, magnetoencephalography, and stereoelectroencephalography. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) in conjunction with independent component analysis (ICA) has been utilized for presurgical planning of SOZ resection, with varying results. In this meta-analysis, we analyze the current role of rs-fMRI in identifying the SOZ for presurgical planning for patients with drug-resistant epilepsy. Specifically, we seek to demonstrate its current effectiveness compared to other methods of SOZ localization.
METHODS: A literature review was conducted using the PubMed, MEDLINE, and Embase databases up to May of 2020. A total of 253 articles were screened, and seven studies were chosen for analysis. Each study was analyzed for SOZ localization by ground truth, SOZ localization by rs-fMRI with ICA, principal component analysis, or intrinsic connectivity contrast, and outcomes of surgery. A meta-analysis was performed to analyze how ground truth compares to rs-fMRI in SOZ localization.
RESULTS: The odds ratio comparing ground truth to rs-fMRI was 2.63 (95% confidence interval = 0.66-10.56). Average concordance of rs-fMRI SOZ localization compared with ground truth localization across studies was 71.3%.
SIGNIFICANCE: In the hunt for less invasive presurgical planning for epilepsy surgery, rs-fMRI with ICA provides a promising avenue for future standard practice. Our preliminary results show no significant difference in surgical outcomes between traditional standards of SOZ localization and rs-fMRI with ICA. We believe that rs-fMRI could be a step forward in this search. Further investigation comparing rs-fMRI to traditional methods of SOZ localization should be conducted, with the hope of moving toward relying solely on noninvasive screening methods.

PMID: 32770853 [PubMed - as supplied by publisher]

Effects of Chronic Pharmacological Treatment on Functional Brain Network Connectivity in Patients with Schizophrenia.

Mon, 08/10/2020 - 21:36
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Effects of Chronic Pharmacological Treatment on Functional Brain Network Connectivity in Patients with Schizophrenia.

Psychiatry Res. 2020 Aug 04;:113338

Authors: Lin X, Deng J, Dong G, Li S, Wu P, Sun H, Liu L, Shi J, Fan Y, Lu L, Li P

Abstract
Schizophrenia is characterized by the dysfunction of various brain networks. Previous studies suggested that pharmacological treatments for schizophrenia induce functional changes in localized brain regions. However, the effects of antipsychotic treatments on brain networks associated with symptom improvement are still elusive. The elucidation of antipsychotic-induced functional brain changes is essential for the development of biologically informed treatment strategies. Forty-five healthy controls and 44 patients with schizophrenia underwent resting-state fMRI scans at baseline. The patients underwent a second scan after 6 weeks of antipsychotic treatment. At baseline, patients exhibited a significant decrease in functional connectivity of the cingulate gyrus in the default mode network compared to healthy controls, and this decrease was negatively correlated with symptom severity. Clinical improvements were observed after 6 weeks treatment, accompanied by an increase in functional connectivity of the cingulate gyrus in the default mode network and the inferior parietal lobule in the executive control network. The changes in functional connectivity of the inferior parietal lobule were significantly correlated with symptom improvement. These longitudinal neuroimaging findings suggest that schizophrenia might be an outcome of the disruption of the optimal balance of brain networks, and reestablishing this balance through antipsychotic treatment may result in clinical symptom improvement.

PMID: 32768152 [PubMed - as supplied by publisher]

Long-lasting connectivity changes induced by intensive first-person shooter gaming.

Sun, 08/09/2020 - 21:34
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Long-lasting connectivity changes induced by intensive first-person shooter gaming.

Brain Imaging Behav. 2020 Aug 07;:

Authors: Momi D, Smeralda CL, Di Lorenzo G, Neri F, Rossi S, Rossi A, Santarnecchi E

Abstract
Action videogames have been shown to induce modifications in perceptual and cognitive systems, as well as in brain structure and function. Nevertheless, whether such changes are correlated with brain functional connectivity modifications outlasting the training period is not known. Functional magnetic resonance imaging (fMRI) was used in order to quantify acute and long-lasting connectivity changes following a sustained gaming experience on a first-person shooter (FPS) game. Thirty-five healthy participants were assigned to either a gaming or a control group prior to the acquisition of resting state fMRI data and a comprehensive cognitive assessment at baseline (T0), post-gaming (T1) and at a 3 months' follow-up (T2). Seed-based resting-state functional connectivity (rs-FC) analysis revealed a significant greater connectivity between left thalamus and left parahippocampal gyrus in the gamer group, both at T1 and at T2. Furthermore, a positive increase in the rs-FC between the cerebellum, Heschl's gyrus and the middle frontal gyrus paralleled improvements of in-gaming performance. In addition, baseline rs-FC of left supramarginal gyrus, left middle frontal gyrus and right cerebellum were associated with individual changes in videogame performance. Finally, enhancement of perceptual and attentional measures was observed at both T1 and T2, which correlated with a pattern of rs-FC changes in bilateral occipito-temporal regions belonging to the visual and attention fMRI networks. The present findings increase knowledge on functional connectivity changes induced by action videogames, pointing to a greater and long-lasting synchronization between brain regions associated with spatial orientation, visual discrimination and motor learning even after a relatively short multi-day gaming exposure.

PMID: 32767208 [PubMed - as supplied by publisher]

Abnormal degree centrality in lifelong premature ejaculation patients: an fMRI study.

Sun, 08/09/2020 - 21:34
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Abnormal degree centrality in lifelong premature ejaculation patients: an fMRI study.

Brain Imaging Behav. 2020 Aug 06;:

Authors: Gao M, Feng N, Liu X, Sun J, Hou G, Zhang L, Yin H, Guo B, Wu J, Huang M, Yuan J, Guo J, Liu P

Abstract
Lifelong premature ejaculation (PE) is one of the most prevalent male sexual dysfunctions. It is still not well known about the possible neural mechanisms of lifelong PE. This study tried to investigate the abnormal characteristics of brain functional networks of lifelong PE and to assess relationships of PE-related functional abnormalities with clinical symptoms. Functional magnetic resonance imaging (fMRI) data and clinical symptoms were collected from 45 lifelong PE patients and 37 healthy controls (HCs) since 2016, including disease and sexual life history, intravaginal ejaculatory latency time measured by stopwatch and other scales. The degree centrality (DC) approach were applied to distinguish altered brain functions between the two groups (p < 0.05, false discovery rate corrected). Correlation analysis was then performed to examine relationships between the imaging findings and clinical symptoms (p < 0.05, Bonferroni corrected). Results showed that compared with HCs, lifelong PE patients had increased DC value in the medial prefrontal cortex (mPFC), precuneus and primary somatosensory cortex (SI) as well as decreased DC value in the insula and orbitofrontal cortex. After controlling for anxiety and depression levels, the significant difference in the mPFC was not found. The DC value in the SI positively correlated with premature ejaculation diagnostic tool (PEDT) score in the patients. The present findings indicate that lifelong PE patients have altered DC in brain regions involved in sensation, motivation and inhibitory control processing. Our study may improve our understanding and provide a new sight into the further research of lifelong PE.

PMID: 32767047 [PubMed - as supplied by publisher]

Changes in Cortical Thickness Are Associated With Cognitive Ability in Postoperative School-Aged Children With Tetralogy of Fallot.

Sun, 08/09/2020 - 21:34
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Changes in Cortical Thickness Are Associated With Cognitive Ability in Postoperative School-Aged Children With Tetralogy of Fallot.

Front Neurol. 2020;11:691

Authors: Ma S, Li Y, Liu Y, Xu C, Li H, Yao Q, Wang Y, Yang Z, Zuo P, Yang M, Mo X

Abstract
In children with tetralogy of Fallot (TOF), there is a risk of brain injury even if intracardiac deformities are corrected. This population follow-up study aimed to identify the correlation between cerebral morphology changes and cognition in postoperative school-aged children with TOF. Resting-state functional magnetic resonance imaging (rs-fMRI) and the Wechsler Intelligence Scale for Children-Chinese revised edition (WISC-CR) were used to assess the difference between children with TOF and healthy children (HCs). Multiple linear regression showed that the TOF group had a lower verbal intelligence quotient (VIQ, 95.000 ± 13.433, p = 0.001) than the HC group and that VIQ had significant positive correlations with the cortical thickness of both the left precuneus (p < 0.05) and the right caudal middle frontal gyrus (p < 0.05) after adjustment for preoperative SpO2, preoperative systolic blood pressure (SBP), preoperative diastolic blood pressure (DBP) and time of aortic override (AO). Our results suggested that brain injury induced by TOF would exert lasting effects on cortical and cognitive development at least to school age. This study provides direct evidence of the relationship between cortical thickness and VIQ and of the need for strengthened verbal training in school-aged TOF patients after corrective surgery.

PMID: 32765405 [PubMed - as supplied by publisher]

Epilepsy-Related Brain Network Alterations in Patients With Temporal Lobe Glioma in the Left Hemisphere.

Sun, 08/09/2020 - 21:34
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Epilepsy-Related Brain Network Alterations in Patients With Temporal Lobe Glioma in the Left Hemisphere.

Front Neurol. 2020;11:684

Authors: Fang S, Zhou C, Fan X, Jiang T, Wang Y

Abstract
Background: Seizures are a common symptom in patients with temporal lobe gliomas and may result in brain network alterations. However, brain network changes caused by glioma-related epilepsy (GRE) remain poorly understood. Objective: In this study, we applied graph theory analysis to delineate topological networks with resting-state functional magnetic resonance images (rs-fMRI) and investigated characteristics of functional networks in patients with GRE. Methods: Thirty patients with low-grade gliomas in the left temporal lobe were enrolled and classified into GRE (n = 15) and non-GRE groups. Twenty healthy participants matched for age, sex, and education level were enrolled. All participants had rs-fMRI data. Sensorimotor, visual, default mode, auditory, and right executive control networks were used to construct connection matrices. Topological properties of those sub-networks were investigated. Results: Compared to that in the GRE group, four edges with higher functional connectivity were noted in the non-GRE group. Moreover, 21 edges with higher functional connectivity were identified in the non-GRE group compared to the healthy group. All significant alterations in functional edges belong to the visual network. Increased global efficiency and decreased shortest path lengths were noted in the non-GRE group compared to the GRE and healthy groups. Compared with that in the healthy group, nodal efficiency of three nodes was higher in the GRE and non-GRE groups and the degree centrality of six nodes was altered in the non-GRE group. Conclusion: Temporal lobe gliomas in the left hemisphere and GRE altered visual networks in an opposing manner. These findings provide a novel insight into brain network alterations induced by GRE.

PMID: 32765403 [PubMed - as supplied by publisher]

Regional Hurst Exponent Reflects Impulsivity-Related Alterations in Fronto-Hippocampal Pathways Within the Waiting Impulsivity Network.

Sun, 08/09/2020 - 21:34
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Regional Hurst Exponent Reflects Impulsivity-Related Alterations in Fronto-Hippocampal Pathways Within the Waiting Impulsivity Network.

Front Physiol. 2020;11:827

Authors: Neufang S, Akhrif A

Abstract
In general, the Hurst exponent. is used as a measure of long-term memory of time series. In previous neuroimaging studies, H has been introduced as one important parameter to define resting-state networks, reflecting upon global scale-free properties emerging from a network. H has been examined in the waiting impulsivity (WI) network in an earlier study. We found that alterations of H in the anterior cingulate cortex (H A C C ) and the nucleus accumbens (H N A c c ) were lower in high impulsive (highIMP) compared to low impulsive (lowIMP) participants. Following up on those findings, we addressed the relation between altered fractality in H A C C and H N A c c and brain activation and neural network connectivity. To do so, brain activation maps were calculated, and network connectivity was determined using the Dynamic Causal Modeling (DCM) approach. Finally, 1-H scores were determined to quantify the alterations of H. This way, the focus of the analyses was placed on the potential effects of alterations of H on neural network activation and connectivity. Correlation analyses between the alterations of H A C C /H N A c c and activation maps and DCM estimates were performed. We found that the alterations of H predominantly correlated with fronto-hippocampal pathways and correlations were significant only in highIMP subjects. For example, alterations of H A C C was associated with a decrease in neural activation in the right HC in combination with increased ACC-hippocampal connectivity. Alteration inH N A c c , in return, was related to an increase in bilateral prefrontal activation in combination with increased fronto-hippocampal connectivity. The findings, that the WI network was related to H alteration in highIMP subjects indicated that impulse control was not reduced per se but lacked consistency. Additionally, H has been used to describe long-term memory processes before, e.g., in capital markets, energy future prices, and human memory. Thus, current findings supported the relation of H toward memory processing even when further prominent cognitive functions were involved.

PMID: 32765298 [PubMed - as supplied by publisher]