Showing papers in "Brain Imaging and Behavior in 2020"

The superior longitudinal fascicle: reconsidering the fronto-parietal neural network based on anatomy and function.

Abstract: Due primarily to the extensive disposition of fibers and secondarily to the methodological preferences of researchers, the superior longitudinal fasciculus (SLF) subdivisions have multiple names, complicating SLF research. Here, we collected and reassessed existing knowledge regarding the SLF, which we used to propose a four-term classification of the SLF based mainly on function: dorsal SLF, ventral SLF, posterior SLF, and arcuate fasciculus (AF); these correspond to the traditional SLF II, SLF III or anterior AF, temporoparietal segment of the SLF or posterior AF, and AF or AF long segment, respectively. Each segment has a distinct functional role. The dorsal SLF is involved in visuospatial attention and motor control, while the ventral SLF is associated with language-related networks, auditory comprehension, and articulatory processing in the left hemisphere. The posterior SLF is involved in language-related processing, including auditory comprehension, reading, and lexical access, while the AF is associated with language-related activities, such as phonological processing; the right AF plays a role in social cognition and visuospatial attention. This simple proposed classification permits a better understanding of the SLF and may comprise a convenient classification for use in research and clinical practice relating to brain function.

Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy

Abstract: Previous neuroimaging studies have detected markers of neuroinflammation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring brain metabolites linked to inflammation, but has only been applied to discrete regions of interest in ME/CFS. We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain. Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients. Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). Choline (CHO), myo-inositol (MI), lactate (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over creatine (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups. Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate (p < 0.001). Metabolite ratios in seven regions were correlated with fatigue (p < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p < 0.05), which was not attributable to increased body temperature or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p < 0.05). We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.

Altered functional connectivity patterns of insular subregions in major depressive disorder after electroconvulsive therapy.

Abstract: Although electroconvulsive therapy (ECT) is an efficient treatment for major depressive disorder (MDD), however, it also brings memory impairment. The insula is a critical brain structure for coordinating affective, cognitive memory, saliency processing, and attention switching suggesting functional activity of insula maybe an important indicator to delineate the treatment and side effects of ECT. Here, Resting-state functional connectivity analyses of insular subregions were performed to reveal the changes of connectivity in 23 MDD patients before and after ECT and 25 healthy control (HC) and identified significantly increased functional connectivity of the right ventral anterior insular subregion with bilateral caudate, angular gyrus, and dorsolateral prefrontal cortex after ECT. Granger causality analyses identified significantly increased effective connectivity from dorsolateral prefrontal cortex to right angular gyrus in MDD patients after ECT. Furthermore, increased effective connectivity from dorsolateral prefrontal cortex to right angular gyrus exhibited significantly positive correlation with changed Hamilton Rating Scale for Depression scores. These results showed that ECT can normalize abnormal functional connectivity and effective connectivity in MDD. Our findings also indicated that the right ventral anterior insula and effective connectivity from dorsolateral prefrontal cortex to right angular gyrus are biomarkers of antidepressant effects during ECT of MDD.

Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity.

Abstract: Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging.

Morphological changes in subregions of hippocampus and amygdala in major depressive disorder patients

Abstract: Despite many neuroimaging studies in the past years, the neuroanatomical substrates of major depressive disorder (MDD) subcortical structures are still not well understood. Since hippocampus and amygdala are the two vital subcortical structures that most susceptible to MDD, finding the evidence of morphological changes in their subregions may bring some new insights for MDD research. Combining structural magnetic resonance imaging (MRI) with novel morphometry analysis methods, we recruited 25 MDD patients and 28 healthy controls (HC), and investigated their volume and morphological differences in hippocampus and amygdala. Relative to volumetric method, our methods detected more significant global morphological atrophies (p<0.05). More precisely, subiculum and cornu ammonis (CA) 1 subregions of bilateral hippocampus, lateral (LA) and basolateral ventromedial (BLVM) of left amygdala and LA, BLVM, central (CE), amygdalostriatal transition area (ASTR), anterior cortical (ACO) and anterior amygdaloid area (AAA) of right amygdala were demonstrated prone to atrophy. Correlation analyses between each subject's surface eigenvalues and Hamilton Depression Scale (HAMD) were then performed. Correlation results showed that atrophy areas in hippocampus and amygdala have slight tendencies of expanding into other subregions with the development of MDD. Finally, we performed group morphometric analysis and drew the atrophy and expansion areas between MDD-Medicated group (only 19 medicated subjects in MDD group were included) and HC group, found some preliminary evidence about subregional morphological resilience of hippocampus and amygdala. These findings revealed new pathophysiologic patterns in the subregions of hippocampus and amygdala, which can help with subsequent smaller-scale MDD research.

Shared and specific functional connectivity alterations in unmedicated bipolar and major depressive disorders based on the triple-network model

Abstract: Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) in clinical practice, especially during depressive episodes. A unifying triple-network model, involving the default mode network (DMN), central executive network (CEN) and salience network (SN), has been proposed to explain the neural physiopathology of psychiatric and neurological disorders. Although several studies revealed shared and specific alterations between BD and MDD in key regions of DMN, CEN, and SN, and a few studies used different measures to detect detailed alterations in the triple networks in BD and MDD, their shared and specific patterns of altered functional connectivity (FC) in the triple networks has remained unclear. In this study, we acquired resting-state fMRI (R-fMRI) data from 38 unmedicated BD and 35 unmedicated MDD patients during depressive episodes along with 47 healthy controls. We first determined the spatially independent components of the DMN, SN, and CEN by using independent component analysis (ICA); then we estimated the inter-ROI and inter-network FC for each group. By comparing the differences between the three groups, we obtained the following results: (1) both the BD and MDD patients showed shared weaker intra-network FC in the left mPFC and right precuneus within the DMN as well as weaker inter-ROI FC between the left AI and right AI compared with the healthy controls; (2) the BD had weaker while the MDD had stronger intra-network FC in the right dlPFC within the rCEN as well as stronger inter-ROI FC between the right dlPFC and right ANG compared with the healthy controls; (3) the BD showed specific, stronger inter-ROI FC between the left PPC and right AI as well as stronger inter-network FC between the lCEN and SN compared with either the MDD or the control group. Our findings provide new information for understanding the neural physiopathology and clinical symptoms of depressed BD and MDD patients.

Frequency-dependent changes in fractional amplitude of low-frequency oscillations in Alzheimer’s disease: a resting-state fMRI study

Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative disease in elderly individuals. We conducted this study to examine whether alterations in the fractional amplitudes of low-frequency fluctuations (fALFF) in the AD spectrum were frequency-dependent and symptom-relevant. A total of 43 patients with subjective cognitive decline (SCD), 52 with amnestic mild cognitive impairment (aMCI), 44 with Alzheimer’s dementia (d-AD) and 55 well-matched controls participated in resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitudes were measured using fALFF within the slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz) bands. Repeated-measures analysis of variance was performed on fALFF within two bands and correlated with neuropsychological test scores. The significant main effects of frequency and group on fALFF differed widely across brain regions. There were more varied areas in the slow-5 band than the slow-4 band. The fALFF associated with primary disease effects was mainly distributed in the parietal lobe. Obvious frequency band and group interaction effects were observed in the left angular gyrus, left calcarine fissure and surrounding cortex, left superior cerebellum, left cuneus and right lingual gyrus. Neuropsychological tests scores were significantly correlated with the fALFF magnitude of the left cuneus and right lingual in the slow-5 band. Our results suggested that the AD continuum had abnormal amplitudes in intrinsic brain activity, and these abnormalities were frequency-dependent and mainly associated with the slow-5 band rather than the slow-4 band. This may guide the frequency choice of future rs-fMRI studies and provide new insights into the neuropathophysiology of AD.

Multimodal data revealed different neurobiological correlates of intelligence between males and females.

Abstract: Intelligence is a socially and scientifically interesting topic because of its prominence in human behavior, yet there is little clarity on how the neuroimaging and neurobiological correlates of intelligence differ between males and females, with most investigations limited to using either mass-univariate techniques or a single neuroimaging modality. Here we employed connectome-based predictive modeling (CPM) to predict the intelligence quotient (IQ) scores for 166 males and 160 females separately, using resting-state functional connectivity, grey matter cortical thickness or both. The identified multimodal, IQ-predictive imaging features were then compared between genders. CPM showed high out-of-sample prediction accuracy (r > 0.34), and integrating both functional and structural features further improved prediction accuracy by capturing complementary information (r = 0.45). Male IQ demonstrated higher correlations with cortical thickness in the left inferior parietal lobule, and with functional connectivity in left parahippocampus and default mode network, regions previously implicated in spatial cognition and logical thinking. In contrast, female IQ was more correlated with cortical thickness in the right inferior parietal lobule, and with functional connectivity in putamen and cerebellar networks, regions previously implicated in verbal learning and item memory. Results suggest that the intelligence generation of males and females may rely on opposite cerebral lateralized key brain regions and distinct functional networks consistent with their respective superiority in cognitive domains. Promisingly, understanding the neural basis of gender differences underlying intelligence may potentially lead to optimized personal cognitive developmental programs and facilitate advancements in unbiased educational test design.

Patterns of white matter hyperintensities associated with cognition in middle-aged cognitively healthy individuals.

Abstract: White matter hyperintensities (WMH) are commonly detected in the brain of elderly individuals and have been associated with a negative impact on multiple cognitive domains. We aim to investigate the impact of global and regional distribution of WMH on episodic memory and executive function in middle-aged cognitively unimpaired participants [N = 561 (45–75 years)] enriched for Alzheimer’s disease risk factors. WMH were automatically segmented from FLAIR, T1 and FSE MR images. WMH load was calculated both globally and regionally. At each cerebral lobe, regional WMH load was measured at four equidistant layers extending from the lateral ventricles to juxtacortical areas. Cognition was measured by The Memory Binding Test (MBT) and WAIS-IV subtests. Global composite z-scores were calculated for the two cognitive domains. Association between global and regional WMH measurements were sought against cognitive measures, both in global composite scores and in individual subtests. We adjusted cognition and WMH burden for the main sociodemographic (age, sex and education) and genetic factors (APOE-e4). Memory and executive function were significantly associated with global WMH load. Regionally, lower executive performance was mainly associated with higher deep WMH load in frontal areas and, to a lower degree, in occipital, parietal and temporal regions. Lower episodic memory performance was correlated with higher WMH burden in deep frontal and occipital areas. Our novel methodological approach of regional analysis allowed us to reveal the association between cognition and WMH in strategic brain locations. Our results suggest that, even a small WMH load can impact cognition in cognitively unimpaired middle-aged subjects.

Gender differences in cortical morphological networks.

Abstract: Cortical morphological networks (CMN), where each network models the relationship in morphology between different cortical brain regions quantified using a specific measurement (e.g., cortical thickness), have not been investigated with respect to gender differences in the human brain. Cortical processes are expected to involve complex interactions between different brain regions, univariate methods thus might overlook informative gender markers. Hence, by leveraging machine learning techniques with the potential to highlight multivariate interacting effects, we found that the most discriminative CMN connections between males and females were derived from the left hemisphere using the mean sulcal depth as measurement. However, for both left and right hemispheres, the first most discriminative morphological connection revealed across all cortical attributes involved (entorhinal cortex ↔ caudal anterior cingulate cortex) and (entorhinal cortex ↔ transverse temporal cortex) respectively, which gives us new insights into behavioral gender differences from an omics perspective and might explain why males and females learn differently.

A magnetic resonance spectroscopy investigation in symptomatic former NFL players.

Abstract: The long-term neurologic consequences of exposure to repetitive head impacts (RHI) are not well understood. This study used magnetic resonance spectroscopy (MRS) to examine later-life neurochemistry and its association with RHI and clinical function in former National Football League (NFL) players. The sample included 77 symptomatic former NFL players and 23 asymptomatic individuals without a head trauma history. Participants completed cognitive, behavior, and mood measures. N-acetyl aspartate, glutamate/glutamine, choline, myo-inositol, creatine, and glutathione were measured in the posterior (PCG) and anterior (ACG) cingulate gyrus, and parietal white matter (PWM). A cumulative head impact index (CHII) estimated RHI. In former NFL players, a higher CHII correlated with lower PWM creatine (r = −0.23, p = 0.02). Multivariate mixed-effect models examined neurochemical differences between the former NFL players and asymptomatic individuals without a history of head trauma. PWM N-acetyl aspartate was lower among the former NFL players (mean diff. = 1.02, p = 0.03). Between-group analyses are preliminary as groups were recruited based on symptomatic status. The ACG was the only region associated with clinical function, including positive correlations between glutamate (r = 0.32, p = 0.004), glutathione (r = 0.29, p = 0.02), and myo-inositol (r = 0.26, p = 0.01) with behavioral/mood symptoms. Other positive correlations between ACG neurochemistry and clinical function emerged (i.e., behavioral/mood symptoms, cognition), but the positive directionality was unexpected. All analyses controlled for age, body mass index, and education (for analyses examining clinical function). In this sample of symptomatic former NFL players, there was a direct effect between RHI and reduced cellular energy metabolism (i.e., lower creatine). MRS neurochemicals associated with neuroinflammation also correlated with behavioral/mood symptoms.

Supervised machine learning for diagnostic classification from large-scale neuroimaging datasets

Abstract: There are growing concerns about the generalizability of machine learning classifiers in neuroimaging. In order to evaluate this aspect across relatively large heterogeneous populations, we investigated four disorders: Autism spectrum disorder (N = 988), Attention deficit hyperactivity disorder (N = 930), Post-traumatic stress disorder (N = 87) and Alzheimer’s disease (N = 132). We applied 18 different machine learning classifiers (based on diverse principles) wherein the training/validation and the hold-out test data belonged to samples with the same diagnosis but differing in either the age range or the acquisition site. Our results indicate that overfitting can be a huge problem in heterogeneous datasets, especially with fewer samples, leading to inflated measures of accuracy that fail to generalize well to the general clinical population. Further, different classifiers tended to perform well on different datasets. In order to address this, we propose a consensus-classifier by combining the predictive power of all 18 classifiers. The consensus-classifier was less sensitive to unmatched training/validation and holdout test data. Finally, we combined feature importance scores obtained from all classifiers to infer the discriminative ability of connectivity features. The functional connectivity patterns thus identified were robust to the classification algorithm used, age and acquisition site differences, and had diagnostic predictive ability in addition to univariate statistically significant group differences between the groups. A MATLAB toolbox called Machine Learning in NeuroImaging (MALINI), which implements all the 18 different classifiers along with the consensus classifier is available from Lanka et al. (2019) The toolbox can also be found at the following URL: https://github.com/pradlanka/malini .

Hippocampal viscoelasticity and episodic memory performance in healthy older adults examined with magnetic resonance elastography.

Abstract: Episodic memory is particularly sensitive to normative aging; however, studies investigating the structure-function relationships that support episodic memory have primarily been limited to gross volumetric measures of brain tissue health. Magnetic resonance elastography (MRE) is an emerging non-invasive, high-resolution imaging technique that uniquely quantifies brain viscoelasticity, and as such, provides a more specific measure of neural microstructural integrity. Recently, a significant double dissociation between orbitofrontal cortex-fluid intelligence and hippocampal-relational memory structure-function relationships was observed in young adults, highlighting the potential of sensitive MRE measures for studying brain health and its relation to cognitive function. However, the structure-function relationship observed by MRE has not yet been explored in healthy older adults. In this study, we examined the relationship between hippocampal (HC) viscoelasticity and episodic memory in cognitively healthy adults aged 66–73 years (N = 11), as measured with the verbal-paired associates (VPA) subtest from the Wechsler Memory Scale (WMS-R). Given the particular dependence of verbal memory tasks on the left HC, unilateral HC MRE measurements were considered for the first time. A significant negative correlation was found between left HC damping ratio, ξ and VPA recall score (rs = −0.77, p = 0.009), which is consistent with previous findings of a relationship between HC ξ and memory performance in young adults. Conversely, correlations between right HC ξ with VPA recall score were not significant. These results highlight the utility of MRE to study cognitive decline and brain aging and suggest its possible use as a sensitive imaging biomarker for memory-related impairments.

Functional brain changes associated with cognitive training in healthy older adults: A preliminary ALE meta-analysis.

Abstract: Accumulating evidence suggests that cognitive training (CT) programs may provide healthy older adults (OAs) with cognitive benefits that are accompanied by alterations in neural activity. The current review offers the first quantitative synthesis of the available literature on the neural effects of CT in healthy aging. It was hypothesized that OAs would evidence increased and decreased neural activations across various challenging CTs, and that these effects would be observed as significantly altered clusters within regions of the frontoparietal network (FPN). Online databases and reference lists were searched to identify peer-reviewed publications that reported assessment of neural changes associated with CT programs in healthy OAs. Among the 2097 candidate studies identified, 14 studies with a total of 238 participants met inclusionary criteria. GingerALE software was used to quantify neural effects in a whole-brain analysis. The activation likelihood estimation technique revealed significant increases in activation following CT in the left hemisphere middle frontal gyrus, precentral gyrus, and posterior parietal cortex, extending to the superior occipital gyrus. Two clusters of diminished neural activity following CT were identified within the right hemisphere middle frontal gyrus and supramarginal gyrus, extending to the superior temporal gyrus. These results provide preliminary evidence of common neural effects of different CT interventions within regions of the FPN. Findings may inform future investigations of neuroplasticity across the lifespan, including clinical applications of CT, such as assessing treatment outcomes.

Neuroanatomical correlates of apathy and disinhibition in behavioural variant frontotemporal dementia

Abstract: Neuroanatomical correlates of apathy and disinhibition, behavioral abnormalities in behavioral variant Frontotemporal dementia (bvFTD) remain unclear. In this study 45 participants (25 bvFTD patients and 20 controls) provided data on clinical, neuropsychological, behavioral (on Frontal Systems Behavior (FrSBe) Scale), cortical volume (on voxel-based morphometry (VBM)) and tract based spatial fractional anisotropy ((FA) on magnetic resonance imaging (MRI), allowing examination of the neural correlates of apathy and disinhibition. The patients with bvFTD had predominant grey matter loss and corresponding white matter fractional anisotropy reduction in the frontal and temporal lobe compared to the controls. Grey matter loss in frontal, temporal and limbic structures correlated with apathy and degeneration in temporal limbic brain areas correlated with disinhibition. FA changes in inferior fronto-occipital fasciculus and forceps minor correlated with apathy and fibre integrity changes in the superior longitudinal fasciculus correlated with disinhibition. The current study suggests that apathy and disinhibition arises due to changes in the frontal, temporal and limbic brain areas in bvFTD.

Differential associations of engagement in physical activity and estimated cardiorespiratory fitness with brain volume in middle-aged to older adults.

Abstract: Previous work has confirmed the benefits of aerobic exercise for brain aging, however mechanisms underlying these effects remain unclear. Two measures of exercise, time spent in moderate-to-vigorous physical activity (MVPA) and cardiorespiratory fitness (CRF), may reflect different pathways linking activity to brain health. Using data from the UK Biobank, the largest sample combining neuroimaging and objectively measured MVPA available to date (n = 7148, nmale = 3062, nfemale = 4086; age = 62.14 ± 7.40 years), we found that, when adjusted for covariates including MVPA, CRF was positively associated with overall gray matter volume (FDR p = 1.28E-05). In contrast, when adjusted for covariates including CRF, MVPA was positively associated with left and right hippocampal (FDR pleft = 0.01; FDR pright = 0.02) volumes, but not overall gray matter volume. Both CRF and MVPA were inversely associated with white matter hyperintensity lesion loads (FDR pCRF = 0.002; pMVPA = 0.02). Our results suggest separable effects of engagement in exercise behaviors (MVPA) and the physiological effects of exercise (CRF) on structural brain volumes, which may have implications for differential pathways linking exercise and brain benefits.

Language reorganization after resection of low-grade gliomas: an fMRI task based connectivity study

Abstract: Few studies addressed the evolution of brain activity before and after brain tumor resection. Using a fMRI naming task, we evaluated possible underlying plasticity phenomena. Thirty-two patients with left low-grade gliomas (16 women; age = 38.6 ± 8.31 years) and 19 healthy controls (7 women; age = 42.4 ± 12.1) were included in the study. An overt picture-naming task (DO80) was performed pre and post (3 months) surgery, as well as within the MRI in a covert manner. Exams included an injected 3DT1, a T2FLAIR, a DTI and a GE-EPI (task) sequence. Activations maps were compared with picture naming score, FA and MD maps were estimated, a VLSM analysis was performed on tumor masks, and disconnectome maps were reconstructed. Pre-surgery, the left parahippocampal gyrus (LPH) was inversely associated with task performance. Increased pre-post surgery left lingual gyrus (LLG) activity was found related to decreased picture naming performance. The evolution of left lingual gyrus (LLG) activity was negatively associated with the evolution of picture naming performance. In controls, the LPH was functionally connected to the right precentral gyrus (RPCG) and slightly to the LLG. This was not clearly retrieved in the patient group. Preoperatively, the LLG was connected to the left planum temporale and to the right lingual gyrus. The same result was found for controls. Postoperatively, the LLG was only connected to the RPCG. No association was found between evolution of FA/MD and evolution of picture naming performance. There is not one unique pattern of pre- and postoperative plasticity concerning picture-naming performance in DLGG patients.

Coupling of cerebral blood flow and functional connectivity is decreased in healthy aging

Abstract: Aging leads to cerebral perfusion and functional connectivity changes that have been assessed using various neuroimaging techniques. In addition, a link between these two parameters has been demonstrated in healthy young adults. In this work, we employed arterial spin labeling (ASL) fMRI to measure global and voxel-wise differences in cerebral blood flow (CBF) and intrinsic connectivity contrast (ICC) in the resting state in a group of cognitively normal elderly subjects and a group of cognitively normal young subjects, in order to assess the effects of aging on CBF-ICC coupling, which had not been previously evaluated. Our results showed age-related global and regional CBF decreases in prefrontal mesial areas, lateral frontal regions, insular cortex, lateral parietal areas, precuneus and occipital regions. Subcortically, perfusion was reduced in the medial thalamus and caudate nucleus. ICC was also found reduced with age in prefrontal cortical areas and insular cortex, affecting key nodes of the default mode and salience networks. Areas of ICC and CBF decrease partially overlapped, however, the CBF reduction was more extensive and encompassed more areas. This dissociation was accompanied by a decrease in CBF-ICC coupling. These results suggest that aging leads to a disruption in the relationship between CBF and intrinsic functional connectivity that could be due to neurovascular dysregulation.

Detecting microstructural white matter abnormalities of frontal pathways in children with ADHD using advanced diffusion models

Abstract: Studies using diffusion tensor imaging (DTI) have documented alterations in the attention and executive system in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). While abnormalities in the frontal lobe have also been reported, the associated white matter fiber bundles have not been investigated comprehensively due to the complexity in tracing them through fiber crossings. Furthermore, most studies have used a non-specific DTI model to understand white matter abnormalities. We present results from a first study that uses a multi-shell diffusion MRI (dMRI) data set coupled with an advanced multi-fiber tractography algorithm to probe microstructural measures related to axonal/cellular density and volume of fronto-striato-thalamic pathways in children with ADHD (N = 30) and healthy controls (N = 28). Head motion was firstly examined as a priority in order to assure that no group difference existed. We investigated 45 different white matter fiber bundles in the brain. After correcting for multiple comparisons, we found lower axonal/cellular packing density and volume in ADHD children in 8 of the 45 fiber bundles, primarily in the right hemisphere as follows: 1) Superior longitudinal fasciculus-II (SLF-II) (right), 2) Thalamus to precentral gyrus (right), 3) Thalamus to superior-frontal gyrus (right), 4) Caudate to medial orbitofrontal gyrus (right), 5) Caudate to precentral gyrus (right), 6) Thalamus to paracentral gyrus (left), 7) Caudate to caudal middlefrontal gyrus (left), and 8) Cingulum (bilateral). Our results demonstrate reduced axonal/cellular density and volume in certain frontal lobe white matter fiber tracts, which sub-serve the attention function and executive control systems. Further, our work shows specific microstructural abnormalities in the striato-thalamo-cortical connections, which have not been previously reported in children with ADHD.

Differential insular cortex sub-regional atrophy in neurodegenerative diseases: a systematic review and meta-analysis.

Abstract: The insular cortex is proposed to function as a central brain hub characterized by wide-spread connections and diverse functional roles. As a result, its centrality in the brain confers high metabolic demands predisposing it to dysfunction in disease. However, the functional profile and vulnerability to degeneration varies across the insular sub-regions. The aim of this systematic review and meta-analysis is to summarize and quantitatively analyze the relationship between insular cortex sub-regional atrophy, studied by voxel based morphometry, with cognitive and neuropsychiatric deficits in frontotemporal dementia (FTD), Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). We systematically searched through Pubmed and Embase and identified 519 studies that fit our criteria. A total of 41 studies (n = 2261 subjects) fulfilled the inclusion criteria for the meta-analysis. The peak insular coordinates were pooled and analyzed using Anatomic Likelihood Estimation. Our results showed greater left anterior insular cortex atrophy in FTD whereas the right anterior dorsal insular cortex showed larger clusters of atrophy in AD and PD/DLB. Yet contrast analyses did not reveal significant differences between disease groups. Functional analysis showed that left anterior insular cortex atrophy is associated with speech, emotion, and affective-cognitive deficits, and right dorsal atrophy with perception and cognitive deficits. In conclusion, insular sub-regional atrophy, particularly the anterior dorsal region, may contribute to cognitive and neuropsychiatric deficits in neurodegeneration. Our results support anterior insular cortex vulnerability and convey the differential involvement of the insular sub-regions in functional deficits in neurodegenerative diseases.

Aerobic exercise increases hippocampal subfield volumes in younger adults and prevents volume decline in the elderly

Abstract: Exercise improves both physical and mental health and increases neurogenesis in the dendate gyrus (DG) of the hippocampus. The aim of this study was to examine whether exercising, as compared to no change in regular physical activity, would impact on hippocampal volume, and in particular the core hippocampal structures, DG and cornu ammonis (CA) subfields, and whether any changes would be moderated by age. Thirty nine previously sedentary healthy participants were randomized to either a standardized progressive aerobic exercise program or to “no change” for 16 weeks. Mental health including profile of mood states (POMS), was assessed before and every 4 weeks during the program. Magnetic resonance imaging to examine hippocampal subfields was carried out before and after the program. Aerobic exercise resulted in a significant improvement of the POMS item ‘vigour’ compared to those in the control group. Overall left hippocampal and left CA4-DG volumes increased significantly in the exercise group while no significant changes were seen in the control group. Older adults in the control group demonstrated significant reductions in CA4-DG subfields over the study, whereas older adults in the exercise group did not show volume decline. These findings reinforce the literature that exercise has a beneficial effect on mental health and can prevent age-related volume decline. Exercise to Improve Resilience, https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4 , NCT02541136, Rec Ref 2011/45/13.

Graph-based network analysis of resting-state fMRI: test-retest reliability of binarized and weighted networks

Abstract: In the past decade, resting-state functional magnetic resonance imaging (rs-fMRI) and graph-based measures have been widely used to quantitatively characterize the architectures of brain functional networks in healthy individuals and in patients with abnormalities related to psychopathic and neurological disorders. To accurately evaluate the topological organization of brain functional networks, the definition of the nodes and edges for the construction of functional networks is critical. Furthermore, both types of brain functional networks (binarized networks and weighted networks) are widely used to analyze topological organization. However, how to best select the network type is still debated. Consequently, we investigated the test-retest reliability of brain functional networks with binarized and weighted edges using two independent datasets and four strategies for defining nodes. We revealed fair to good reliability for a majority of network topological attributes and overall higher reliabilities for weighted networks than for binarized networks. For regional nodal efficiency, weighted networks also showed higher reliability across nodes. Thus, our findings imply that weighted networks contain more information, leading to more stable results. In addition, we found that the reliability of brain functional networks was influenced by the node definition strategy and that more precise of nodal definition were associated with higher reliability. The time effect of reliability was restricted, as no differences between long-term and short-term reliability were observed. In conclusion, our results suggest that weighted networks have better reliability because they reflect more topological information, implying broader applications of weighted networks related to normal and disordered function of the human brain.

Impaired functional connectivity of limbic system in migraine without aura

Abstract: Aberrant functional connectivity of brain networks has been demonstrated in migraine sufferers. Functional magnetic resonance imaging (fMRI) may illustrate altered connectivity in patients suffering from migraine without aura (MwoA). Here, we applied a seed-based approach based on limbic regions to investigate disrupted functional connectivity between spontaneous migraine attacks. Resting-state fMRI data were obtained from 28 migraine patients without aura and 23 well-matched healthy controls (HC). The functional connectivity of the limbic system was characterized using a seed-based whole-brain correlation method. The resulting functional connectivity measurements were assessed for correlations with other clinical features. Neuropsychological data revealed significantly increased connectivity between the limbic system (bilateral amygdala and right hippocampus) and left middle occipital gyrus (MOG), and a positive correlation was revealed between disease duration and connective intensity of the left amygdala and the ipsilateral MOG. There was decreased functional connectivity between the right amygdala and contralateral orbitofrontal cortex (OFC). In addition, resting-state fMRI showed that, compared to HC, patients without aura had significant functional connectivity consolidation between the bilateral hippocampus and cerebellum, and a negative correlation was detected between scores on the headache impact test (HIT) and connectivity intensity of the right hippocampus and bilateral cerebellum. There was decreased functional connectivity between the left hippocampus and three brain areas, encompassing the bilateral inferior parietal gyri (IPG) and contralateral supplementary motor area (SMA). There were no structural differences between the two groups. Our data suggest that migraine patients have disrupted limbic functional connectivity to pain-related regions of the modulatory and encoding cortices, which are associated with specific clinical characteristics. Disturbances of resting-state functional connectivity may play a key role in neuropathological features, perception and affection of migraine. The current study provides further insights into the complex scenario of migraine mechanisms.

Regional growth trajectories of cortical myelination in adolescents and young adults: longitudinal validation and functional correlates

Abstract: Adolescence is a time of continued cognitive and emotional evolution occurring with continuing brain development involving synaptic pruning and cortical myelination. The hypothesis of this study is that heavy myelination occurs in cortical regions with relatively direct, predetermined circuitry supporting unimodal sensory or motor functions and shows a steep developmental slope during adolescence (12–21 years) until young adulthood (22–35 years) when further myelination decelerates. By contrast, light myelination occurs in regions with highly plastic circuitry supporting complex functions and follows a delayed developmental trajectory. In support of this hypothesis, cortical myelin content was estimated and harmonized across publicly available datasets provided by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) and the Human Connectome Project (HCP). The cross-sectional analysis of 226 no-to-low alcohol drinking NCANDA adolescents revealed relatively steeper age-dependent trajectories of myelin growth in unimodal primary motor cortex and flatter age-dependent trajectories in multimodal mid/posterior cingulate cortices. This pattern of continued myelination showed smaller gains when the same analyses were performed on 686 young adults of the HCP cohort free of neuropsychiatric diagnoses. Critically, a predicted correlation between a motor task and myelin content in motor or cingulate cortices was found in the NCANDA adolescents, supporting the functional relevance of this imaging neurometric. Furthermore, the regional trajectory slopes were confirmed by performing longitudinally consistent analysis of cortical myelin. In conclusion, coordination of myelin content and circuit complexity continues to develop throughout adolescence, contributes to performance maturation, and may represent active cortical development climaxing in young adulthood.

Predicting full-scale and verbal intelligence scores from functional Connectomic data in individuals with autism Spectrum disorder.

Abstract: Decoding how intelligence is engrained in the human brain construct is vital in the understanding of particular neurological disorders. While the majority of existing studies focus on characterizing intelligence in neurotypical (NT) brains, investigating how neural correlates of intelligence scores are altered by atypical neurodevelopmental disorders, such as Autism Spectrum Disorders (ASD), is almost absent. To help fill this gap, we use a connectome-based predictive model (CPM) to predict intelligence scores from functional connectome data, derived from resting-state functional magnetic resonance imaging (rsfMRI). The utilized model learns how to select the most significant positive and negative brain connections, independently, to predict the target intelligence scores in NT and ASD populations, respectively. In the first step, using leave-one-out cross-validation we train a linear regressor robust to outliers to identify functional brain connections that best predict the target intelligence score (p − value < 0.01). Next, for each training subject, positive (respectively negative) connections are summed to produce single-subject positive (respectively negative) summary values. These are then paired with the target training scores to train two linear regressors: (a) a positive model which maps each positive summary value to the subject score, and (b) a negative model which maps each negative summary value to the target score. In the testing stage, by selecting the same connections for the left-out testing subject, we compute their positive and negative summary values, which are then fed to the trained negative and positive models for predicting the target score. This framework was applied to NT and ASD populations independently to identify significant functional connections coding for full-scale and verbal intelligence quotients in the brain.

Voxel-wise meta-analysis of task-related brain activation abnormalities in major depressive disorder with suicide behavior

Abstract: Previous task-fMRI studies have reported the abnormal brain activations in major depressive disorders (MDD) with suicidal behavior. However, there is no consensus of opinion on task-fMRI imaging findings of the suicidal brain. We performed a meta-analysis to integrate the results of reported studies to find the consistent task-related alteration pattern of brain activations in MDD patients with suicidal behavior, aiming to investigate brain functional alterations in association with a vulnerability to suicidal behavior. Using the SDM (Seed-based d Mapping) method, we conducted a meta-analysis of the task-fMRI studies to compare the brain activations between major depressive disorder (MDD) patients with a history of suicidal behavior (suicide attempter, ATT) and the MDD patients without suicidal behavior (non-attempters, NAT) during tasks. Our systematic search identified 7 task-fMRI studies comprising 366 individuals, i.e., 150 ATT and 216 NAT. We found that brain activation in ATT increased in the left insula, while decreased in the bilateral fusiform gyrus compared to NAT during the fMRI tasks. We found the brain activation changes in the insula and fusiform gyrus in MDD patients with a history of suicide attempt during fMRI tasks. The brain activation changes in these regions were associated with the dysfunction of emotion regulation, processing negative information and self-awareness which may increase the vulnerability of suicidal behavior in MDD patients.

Altered amygdala resting-state functional connectivity following acupuncture stimulation at BaiHui (GV20) in first-episode drug-Naïve major depressive disorder

Abstract: Amygdala is an important locus of dysfunction implicated in major depressive disorder(MDD). Aberrant amygdala networks(AN) had been reported in resting-state functional magnetic resonance imaging (rs-fMRI) study. The safety and efficacy of acupuncture treatment for MDD have been verified in previous clinical studies. This study is aimed to investigate whether acupuncture at GV20 could modulate the abnormal AN of patients with the first-episode, drug-naive MDD by using rs-fMRI combined with functional connectivity (FC) method. Thirty MDD patient underwent 6-min rs-fMRI scans respectively before and after 20-min electro-acupuncture stimulate(EAS) at GV20. Twenty-nine healthy subjects underwent only a 6-min rs-fMRI scan. Based on the amygdala as the seed region, FC method was adopted to examine abnormal AN in patients by comparing with healthy subjects and to evaluate the influence of EAS on intrinsic connectivity within the AN in patients with MDD. Compared to healthy subjects, MDD patients had aberrant intrinsic AN which mainly showed increased FC between amygdala and hippocampus, precuneus, precentral gyrus and angular gyrus, as well as decreased FC between amygdala and orbital frontal cortex(OFC). Moreover, our results indicated that EAS at GV20 induced increased/decreased FC between amygdala and certain regions in MDD patients. In addition, the intrinsic amygdala FC within other certain brain regions in MDD patients were regulated by EAS at GV20. The abnormal AN of MDD patients could be modulated by EAS at GV20. Our findings may further provide the potential imaging evidence to support the modulatory mechanisms of acupuncture on MDD.

Accumulation of high magnitude acceleration events predicts cerebrovascular reactivity changes in female high school soccer athletes.

Abstract: Mitigating the effects of repetitive exposure to head trauma has become a major concern for the general population, given the growing body of evidence that even asymptomatic exposure to head accelerations is linked with increased risk for negative life outcomes and that risk increases as exposure is prolonged over many years. Among women's sports, soccer currently exhibits the highest growth in participation and reports the largest number of mild traumatic brain injuries annually, making female soccer athletes a relevant population in assessing the effects of repetitive exposure to head trauma. Cerebrovascular biomarkers may be useful in assessing the effects of repetitive head trauma, as these are thought to contribute directly to neurocognitive symptoms associated with mild traumatic brain injury. Here we use fMRI paired with a hypercapnic breath hold task along with monitoring of head acceleration events, to assess the relationship between cerebrovascular brain changes and exposure to repetitive head trauma over a season of play in female high school soccer athletes. We identified longitudinal changes in cerebrovascular reactivity that were significantly associated with prolonged accumulation to high magnitude (> 75th percentile) head acceleration events. Findings argue for active monitoring of athletes during periods of exposure to head acceleration events, illustrate the importance of collecting baseline (i.e., pre-exposure) measurements, and suggest modeling as a means of guiding policy to mitigate the effects of repetitive head trauma.

Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level

Abstract: Cognitive deficits are a major complaint in breast cancer patients, even before chemotherapy. Comprehension of the cerebral mechanisms related to cognitive impairment in breast cancer patients remains difficult due to the scarcity of studies investigating both cognitive and anatomical imaging changes. Furthermore, only some of the patients experienced cognitive decline following chemotherapy, yet few studies have identified risk factors for cognitive deficits in these patients. It has been shown that education level could impact cognitive abilities during the recovery phase following chemotherapy. Our main aim was to longitudinally evaluate cognitive and anatomical changes associated with cancer and chemotherapy in breast cancer patients. Our secondary aim was to assess the impact of education level on cognitive performances and gray matter (GM) atrophy in these patients. Twenty patients were included before chemotherapy (T1), 1 month (T2) and 1 year (T3) after chemotherapy. Twenty-seven controls without a history of cancer were assessed at T1 and T3 only. Cluster groups based on education level were defined for both groups and were further compared. Comparison between patients and controls revealed deficits in patients on verbal episodic memory retrieval at T1 and T3 and on executive functions at T3. After chemotherapy, breast cancer patients had GM atrophy that persisted or recovered 1 year after chemotherapy depending on the cortical areas. Increase in GM volumes from T1 to T3 were also found in both groups. At T2, patients with a higher level of education compared to lower level exhibited higher episodic memory retrieval and state anxiety scores, both correlating with cerebellar volume. This higher level of education group exhibited hippocampal atrophy. Our results suggest that, before chemotherapy, cancer-related processes impact cognitive functioning and that this impact seems exacerbated by the effect of chemotherapy on certain brain regions. Increase in GM volumes after chemotherapy were unexpected and warrant further investigations. Higher education level was associated, 1 month after the end of chemotherapy, with greater anxiety and hippocampal atrophy despite a lack of cognitive deficits. These results suggest, for the first time, the occurrence of compensation mechanisms that may be linked to cognitive reserve in relationship to state anxiety. This identification of factors, which may compensate cognitive impairment following chemotherapy, is critical for patient care and quality of life.

Differences in functional brain network connectivity during stories presented in audio, illustrated, and animated format in preschool-age children.

Abstract: The American Academy of Pediatrics (AAP) recommends that parents begin reading to their children soon after birth, and limits on screen-based media. Benefits of traditional book-sharing are well documented in children, while cited deleterious effects of animated content on narrative processing are controversial. The influence of story format on underlying functional brain networks has not previously been studied. Thirty-three healthy children were recruited for this study via advertisement at an academic medical center, which involved functional magnetic resonance imaging (fMRI) at a single visit. Twenty-seven of them completed fMRI (82%; 15 boys, 12 girls; mean 58 ± 8 months old). The fMRI protocol involved the presentation of 3 similar, unrhymed stories by the same author lasting 5 min each in audio, illustrated, and animated format during separate runs, followed by a test of factual recall. Within- and between-network functional connectivity (FC) was compared across formats involving five functional networks, which were defined via literature review and refined via a data-driven parcellation method: visual perception, visual imagery, language, Default Mode (DMN), and cerebellar association. For illustration relative to audio, FC was decreased within the language network and increased between visual, DMN, and cerebellar networks, suggesting decreased strain on the language network afforded by pictures and visual imagery. Between-network connectivity was decreased for all networks for animation relative to the other formats, particularly illustration, suggesting a bias towards visual perception at the expense of network integration. These findings suggest substantial differences in functional brain network connectivity for animated and more traditional story formats in preschool-age children, reinforcing the appeal of illustrated storybooks at this age to provide efficient scaffolding for language, and suggesting novel neurobiological correlates of how functional networks may contribute to this process.