Showing papers in "Brain Imaging and Behavior in 2016"

Application of advanced machine learning methods on resting-state fMRI network for identification of mild cognitive impairment and Alzheimer’s disease

Abstract: The study of brain networks by resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for identifying patients with dementia from healthy controls (HC). Using graph theory, different aspects of the brain network can be efficiently characterized by calculating measures of integration and segregation. In this study, we combined a graph theoretical approach with advanced machine learning methods to study the brain network in 89 patients with mild cognitive impairment (MCI), 34 patients with Alzheimer’s disease (AD), and 45 age-matched HC. The rs-fMRI connectivity matrix was constructed using a brain parcellation based on a 264 putative functional areas. Using the optimal features extracted from the graph measures, we were able to accurately classify three groups (i.e., HC, MCI, and AD) with accuracy of 88.4 %. We also investigated performance of our proposed method for a binary classification of a group (e.g., MCI) from two other groups (e.g., HC and AD). The classification accuracies for identifying HC from AD and MCI, AD from HC and MCI, and MCI from HC and AD, were 87.3, 97.5, and 72.0 %, respectively. In addition, results based on the parcellation of 264 regions were compared to that of the automated anatomical labeling atlas (AAL), consisted of 90 regions. The accuracy of classification of three groups using AAL was degraded to 83.2 %. Our results show that combining the graph measures with the machine learning approach, on the basis of the rs-fMRI connectivity analysis, may assist in diagnosis of AD and MCI.

Gender and creativity: an overview of psychological and neuroscientific literature

Abstract: The topic of gender differences in creativity is one that generates substantial scientific and public interest, but also courts considerable controversy. Owing to the heterogeneous nature of the findings associated with this line of research, the general picture often appears puzzling or obscure. This article presents a selective overview of psychological and neuroscientific literature that has a relevant bearing on the theme of gender and creativity. Topics that are explored include the definition and methods of assessing creativity, a summary of behavioral investigations on gender in relation to creativity, postulations that have been put forward to understand gender differences in creative achievement, gender-based differences in the structure and function of the brain, gender-related differences in behavioral performance on tasks of normative cognition, and neuroscientific studies of gender and creativity. The article ends with a detailed discussion of the idea that differences between men and women in creative cognition are best explained with reference to the gender-dependent adopted strategies or cognitive style when faced with generative tasks.

Sparse temporally dynamic resting-state functional connectivity networks for early MCI identification.

Abstract: In conventional resting-state functional MRI (R-fMRI) analysis, functional connectivity is assumed to be temporally stationary, overlooking neural activities or interactions that may happen within the scan duration. Dynamic changes of neural interactions can be reflected by variations of topology and correlation strength in temporally correlated functional connectivity networks. These connectivity networks may potentially capture subtle yet short neural connectivity disruptions induced by disease pathologies. Accordingly, we are motivated to utilize disrupted temporal network properties for improving control-patient classification performance. Specifically, a sliding window approach is firstly employed to generate a sequence of overlapping R-fMRI sub-series. Based on these sub-series, sliding window correlations, which characterize the neural interactions between brain regions, are then computed to construct a series of temporal networks. Individual estimation of these temporal networks using conventional network construction approaches fails to take into consideration intrinsic temporal smoothness among successive overlapping R-fMRI sub-series. To preserve temporal smoothness of R-fMRI sub-series, we suggest to jointly estimate the temporal networks by maximizing a penalized log likelihood using a fused sparse learning algorithm. This sparse learning algorithm encourages temporally correlated networks to have similar network topology and correlation strengths. We design a disease identification framework based on the estimated temporal networks, and group level network property differences and classification results demonstrate the importance of including temporally dynamic R-fMRI scan information to improve diagnosis accuracy of mild cognitive impairment patients.

Default mode network dissociation in depressive and anxiety states

Abstract: The resting state brain networks, particularly the Default Mode Network (DMN), have been found to be altered in several psychopathological conditions such as depression and anxiety. In this study we hypothesized that cortical areas of the DMN, particularly the anterior regions - medial prefrontal cortex and anterior cingulate cortex - would show an increased functional connectivity associated with both anxiety and depression. Twenty-four healthy participants were assessed using Hamilton Depression and Anxiety Rating Scales and completed a resting-state functional magnetic resonance imaging scan. Multiple regression was performed in order to identify which areas of the DMN were associated with anxiety and depression scores. We found that the functional connectivity of the anterior portions of DMN, involved in self-referential and emotional processes, was positively correlated with anxiety and depression scores, whereas posterior areas of the DMN, involved in episodic memory and perceptual processing were negatively correlated with anxiety and depression scores. The dissociation between anterior and posterior cortical midline regions, raises the possibility of a functional specialization within the DMN in terms of self-referential tasks and contributes to the understanding of the cognitive and affective alterations in depressive and anxiety states.

Cortical thinning in former professional soccer players.

Abstract: Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3 T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process.

Mapping anhedonia-specific dysfunction in a transdiagnostic approach: an ALE meta-analysis

Abstract: Anhedonia is a prominent symptom in neuropsychiatric disorders, most markedly in major depressive disorder (MDD) and schizophrenia (SZ). Emerging evidence indicates an overlap in the neural substrates of anhedonia between MDD and SZ, which supported a transdiagnostic approach. Therefore, we used activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging studies in MDD and SZ to examine the neural bases of three subdomains of anhedonia: consummatory anhedonia, anticipatory anhedonia and emotional processing. ALE analysis focused specifically on MDD or SZ was used later to dissociate specific anhedonia-related neurobiological impairments from potential disease general impairments. ALE results revealed that consummatory anhedonia was associated with decreased activation in ventral basal ganglia areas, while anticipatory anhedonia was associated with more substrates in frontal-striatal networks except the ventral striatum, which included the dorsal anterior cingulate, middle frontal gyrus and medial frontal gyrus. MDD and SZ patients showed similar neurobiological impairments in anticipatory and consummatory anhedonia, but differences in the emotional experience task, which may also involve affective/mood general processing. These results support that anhedonia is characterized by alterations in reward processing and relies on frontal-striatal brain circuitry. The transdiagnostic approach is a promising way to reveal the overall neurobiological framework that contributes to anhedonia and could help to improve targeted treatment strategies.

Canonical feature selection for joint regression and multi-class identification in Alzheimer’s disease diagnosis

Abstract: Fusing information from different imaging modalities is crucial for more accurate identification of the brain state because imaging data of different modalities can provide complementary perspectives on the complex nature of brain disorders. However, most existing fusion methods often extract features independently from each modality, and then simply concatenate them into a long vector for classification, without appropriate consideration of the correlation among modalities. In this paper, we propose a novel method to transform the original features from different modalities to a common space, where the transformed features become comparable and easy to find their relation, by canonical correlation analysis. We then perform the sparse multi-task learning for discriminative feature selection by using the canonical features as regressors and penalizing a loss function with a canonical regularizer. In our experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset, we use Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) images to jointly predict clinical scores of Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) and also identify multi-class disease status for Alzheimer’s disease diagnosis. The experimental results showed that the proposed canonical feature selection method helped enhance the performance of both clinical score prediction and disease status identification, outperforming the state-of-the-art methods.

Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD).

Abstract: Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region.

Music supported therapy promotes motor plasticity in individuals with chronic stroke.

Abstract: Novel rehabilitation interventions have improved motor recovery by induction of neural plasticity in individuals with stroke. Of these, Music-supported therapy (MST) is based on music training designed to restore motor deficits. Music training requires multimodal processing, involving the integration and co-operation of visual, motor, auditory, affective and cognitive systems. The main objective of this study was to assess, in a group of 20 individuals suffering from chronic stroke, the motor, cognitive, emotional and neuroplastic effects of MST. Using functional magnetic resonance imaging (fMRI) we observed a clear restitution of both activity and connectivity among auditory-motor regions of the affected hemisphere. Importantly, no differences were observed in this functional network in a healthy control group, ruling out possible confounds such as repeated imaging testing. Moreover, this increase in activity and connectivity between auditory and motor regions was accompanied by a functional improvement of the paretic hand. The present results confirm MST as a viable intervention to improve motor function in chronic stroke individuals.

Striatum morphometry is associated with cognitive control deficits and symptom severity in internet gaming disorder

Abstract: Internet gaming disorder (IGD), identified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Section III as a condition warranting more clinical research, may be associated with impaired cognitive control. Previous IGD-related studies had revealed structural abnormalities in the prefrontal cortex, an important part of prefrontal-striatal circuits, which play critical roles in cognitive control. However, little is known about the relationship between the striatal nuclei (caudate, putamen, and nucleus accumbens) volumes and cognitive control deficit in individuals with IGD. Twenty-seven adolescents with IGD and 30 age-, gender- and education-matched healthy controls participated in this study. The volume differences of the striatum were assessed by measuring subcortical volume in FreeSurfer. Meanwhile, the Stroop task was used to detect cognitive control deficits. Correlation analysis was used to investigate the relationship between striatal volumes and performance in the Stroop task as well as severity in IGD. Relative to controls, the IGD committed more incongruent condition response errors during the Stroop task and showed increased volumes of dorsal striatum (caudate) and ventral striatum (nucleus accumbens). In addition, caudate volume was correlated with Stroop task performance and nucleus accumbens (NAc) volume was associated with the internet addiction test (IAT) score in the IGD group. The increased volumes of the right caudate and NAc and their association with behavioral characteristics (i.e., cognitive control and severity) in IGD were detected in the present study. Our findings suggest that the striatum may be implicated in the underlying pathophysiology of IGD.

Label-aligned multi-task feature learning for multimodal classification of Alzheimer's disease and mild cognitive impairment.

Abstract: Multimodal classification methods using different modalities of imaging and non-imaging data have recently shown great advantages over traditional single-modality-based ones for diagnosis and prognosis of Alzheimer's disease (AD), as well as its prodromal stage, i.e., mild cognitive impairment (MCI). However, to the best of our knowledge, most existing methods focus on mining the relationship across multiple modalities of the same subjects, while ignoring the potentially useful relationship across different subjects. Accordingly, in this paper, we propose a novel learning method for multimodal classification of AD/MCI, by fully exploring the relationships across both modalities and subjects. Specifically, our proposed method includes two subsequent components, i.e., label-aligned multi-task feature selection and multimodal classification. In the first step, the feature selection learning from multiple modalities are treated as different learning tasks and a group sparsity regularizer is imposed to jointly select a subset of relevant features. Furthermore, to utilize the discriminative information among labeled subjects, a new label-aligned regularization term is added into the objective function of standard multi-task feature selection, where label-alignment means that all multi-modality subjects with the same class labels should be closer in the new feature-reduced space. In the second step, a multi-kernel support vector machine (SVM) is adopted to fuse the selected features from multi-modality data for final classification. To validate our method, we perform experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using baseline MRI and FDG-PET imaging data. The experimental results demonstrate that our proposed method achieves better classification performance compared with several state-of-the-art methods for multimodal classification of AD/MCI.

Static and dynamic posterior cingulate cortex nodal topology of default mode network predicts attention task performance

Abstract: Characterization of the default mode network (DMN) as a complex network of functionally interacting dynamic systems has received great interest for the study of DMN neural mechanisms. In particular, understanding the relationship of intrinsic resting-state DMN brain network with cognitive behaviors is an important issue in healthy cognition and mental disorders. However, it is still unclear how DMN functional connectivity links to cognitive behaviors during resting-state. In this study, we hypothesize that static and dynamic DMN nodal topology is associated with upcoming cognitive task performance. We used graph theory analysis in order to understand better the relationship between the DMN functional connectivity and cognitive behavior during resting-state and task performance. Nodal degree of the DMN was calculated as a metric of network topology. We found that the static and dynamic posterior cingulate cortex (PCC) nodal degree within the DMN was associated with task performance (Reaction Time). Our results show that the core node PCC nodal degree within the DMN was significantly correlated with reaction time, which suggests that the PCC plays a key role in supporting cognitive function.

Alterations in default-mode network connectivity may be influenced by cerebrovascular changes within 1 week of sports related concussion in college varsity athletes: a pilot study

Abstract: The goal of this pilot study is to use complementary MRI strategies to quantify and relate cerebrovascular reactivity, resting cerebral blood flow and functional connectivity alterations in the first week following sports concussion in college varsity athletes. Seven college athletes (3F/4M, age = 19.7 ± 1.2 years) were imaged 3-6 days following a diagnosed sports related concussion and compared to eleven healthy controls with no history of concussion (5M/6F, 18-23 years, 7 athletes). Cerebrovascular reactivity and functional connectivity were measured using functional MRI during a hypercapnia challenge and via resting-state regional partial correlations, respectively. Resting cerebral blood flow was quantified using arterial spin labeling MRI methods. Group comparisons were made within and between 18 regions of interest. Cerebrovascular reactivity was increased after concussion when averaged across all regions of interest (p = 0.04), and within some default-mode network regions, the anterior cingulate and the right thalamus (p < 0.05) independently. The FC was increased in the concussed athletes within the default-mode network including the left and right hippocampus, precuneus and ventromedial prefrontal cortex (p < 0.01), with measures being linearly related to cerebrovascular reactivity in the hippocampus in the concussed athletes. Significant resting cerebral blood flow changes were not detected between the two groups. This study provides evidence for increased cerebrovascular reactivity and functional connectivity in the medial regions of the default-mode network within days of a single sports related concussion in college athletes. Our findings emphasize the utility of complementary cerebrovascular measures in the interpretation of alterations in functional connectivity following concussion.

Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder.

Abstract: Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level.

Characterizing and differentiating task-based and resting state fMRI signals via two-stage sparse representations

Abstract: A relatively underexplored question in fMRI is whether there are intrinsic differences in terms of signal composition patterns that can effectively characterize and differentiate task-based or resting state fMRI (tfMRI or rsfMRI) signals. In this paper, we propose a novel two-stage sparse representation framework to examine the fundamental difference between tfMRI and rsfMRI signals. Specifically, in the first stage, the whole-brain tfMRI or rsfMRI signals of each subject were composed into a big data matrix, which was then factorized into a subject-specific dictionary matrix and a weight coefficient matrix for sparse representation. In the second stage, all of the dictionary matrices from both tfMRI/rsfMRI data across multiple subjects were composed into another big data-matrix, which was further sparsely represented by a cross-subjects common dictionary and a weight matrix. This framework has been applied on the recently publicly released Human Connectome Project (HCP) fMRI data and experimental results revealed that there are distinctive and descriptive atoms in the cross-subjects common dictionary that can effectively characterize and differentiate tfMRI and rsfMRI signals, achieving 100% classification accuracy. Moreover, our methods and results can be meaningfully interpreted, e.g., the well-known default mode network (DMN) activities can be recovered from the very noisy and heterogeneous aggregated big-data of tfMRI and rsfMRI signals across all subjects in HCP Q1 release.

Different neural modifications underpin PTSD after different traumatic events: an fMRI meta-analytic study

Abstract: Post-traumatic stress disorder (PTSD) is an anxiety condition that can develop after exposure to trauma such as physical or sexual assault, injury, combat-related trauma, natural disaster or death. Although an increasing number of neurobiological studies carried out over the past 20 years have allowed clarifying the neural substrate of PTSD, the neural modifications underpinning PTSD are still unclear. Here we used activation likelihood estimation meta-analysis (ALE) to determine whether PTSD has a consistent neural substrate. We also explored the possibility that different traumatic events produce different alterations in the PTSD neural network. In neuroimaging studies of PTSD, we found evidence of a consistent neural network including the bilateral insula and cingulate cortex as well as the parietal, frontal and limbic areas. We also found that specific networks of brain areas underpin PTSD after different traumatic events and that these networks may be related to specific aspects of the traumatic events. We discuss our results in light of the functional segregation of the brain areas involved in PTSD.

Hippocampal volume and cingulum bundle fractional anisotropy are independently associated with verbal memory in older adults.

Abstract: The objective of this study was to investigate the relationship of medial temporal lobe and posterior cingulate cortex (PCC) volumetrics as well as fractional anisotropy of the cingulum angular bundle (CAB) and the cingulum cingulate gyrus (CCG) bundle to performance on measures of verbal memory in non-demented older adults. The participants were 100 non-demented adults over the age of 70 years from the Einstein Aging Study. Volumetric data were estimated from T1-weighted images. The entire cingulum was reconstructed using diffusion tensor MRI and probabilistic tractography. Association between verbal episodic memory and MRI measures including volume of hippocampus (HIP), entorhinal cortex (ERC), PCC and fractional anisotropy of CAB and CCG bundle were modeled using linear regression. Relationships between atrophy of these structures and regional cingulum fractional anisotropy were also explored. Decreased HIP volume on the left and decreased fractional anisotropy of left CAB were associated with lower memory performance. Volume changes in ERC, PCC and CCG disruption were not associated with memory performance. In regression models, left HIP volume and left CAB-FA were each independently associated with episodic memory. The results suggest that microstructural changes in the left CAB and decreased left HIP volume independently influence episodic memory performance in older adults without dementia. The importance of these findings in age and illness-related memory decline require additional exploration.

Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women

Abstract: Anxiety disorders are characterized by hyperactivity in both the amygdala and the anterior insula. Interventions that normalize activity in these areas may therefore be effective in treating anxiety disorders. Recently, there has been significant interest in the potential use of oxytocin (OT), as well as vasopressin (AVP) antagonists, as treatments for anxiety disorders. In this double-blind, placebo-controlled, pharmaco- fMRI study, 153 men and 151 women were randomized to treatment with either 24 IU intranasal OT, 20 IU intranasal AVP, or placebo and imaged with fMRI as they played the iterated Prisoner’s Dilemma game with same-sex human and computer partners. In men, OT attenuated the fMRI response to unreciprocated cooperation (CD), a negative social interaction, within the amygdala and anterior insula. This effect was specific to interactions with human partners. In contrast, among women, OT unexpectedly attenuated the amygdala and anterior insula response to unreciprocated cooperation from computer but not human partners. Among women, AVP did not significantly modulate the response to unreciprocated cooperation in either the amygdala or the anterior insula. However, among men, AVP attenuated the BOLD response to CD outcomes with human partners across a relatively large cluster including the amygdala and the anterior insula, which was contrary to expectations. Our results suggest that OT may decrease the stress of negative social interactions among men, whereas these effects were not found in women interacting with human partners. These findings support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders.

Moderate and late preterm infants exhibit widespread brain white matter microstructure alterations at term-equivalent age relative to term-born controls

Abstract: Despite the many studies documenting cerebral white matter microstructural alterations associated with very preterm birth (<32 weeks’ gestation), there is a dearth of similar research in moderate and late preterm infants (born 32–36 weeks’ gestation), who experience higher rates of neurodevelopmental delays than infants born at term (≥37 weeks’ gestation). We therefore aimed to determine whether whole brain white matter microstructure differs between moderate and late preterm infants and term-born controls at term-equivalent age, as well as to identify potential perinatal risk factors for white matter microstructural alterations in moderate and late preterm infants. Whole brain white matter microstructure was studied in 193 moderate and late preterm infants and 83 controls at term-equivalent age by performing Tract-Based Spatial Statistics analysis of diffusion tensor imaging data. Moderate and late preterm infants had lower fractional anisotropy and higher mean, axial and radial diffusivities compared with controls in nearly 70 % of the brain’s major white matter fiber tracts. In the moderate and late preterm group, being born small for gestational age and male sex were associated with lower fractional anisotropy, largely within the optic radiation, corpus callosum and corona radiata. In conclusion, moderate and late preterm infants exhibit widespread brain white matter microstructural alterations compared with controls at term-equivalent age, in patterns consistent with delayed or disrupted white matter microstructural development. These findings may underpin some of the neurodevelopmental delays observed in moderate and late preterm children.

Intrinsic brain abnormalities in irritable bowel syndrome and effect of anxiety and depression

Abstract: This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated intrinsic brain abnormalities in irritable bowel syndrome (IBS) and effect of anxiety and depression. Thirty IBS patients and 31 matched healthy controls underwent rs-fMRI scanning. Regional brain activity was evaluated by measuring the amplitude of low-frequency fluctuation (ALFF) and compared between IBS patients and healthy controls with a two-sample t-test. Areas with abnormal ALFF were further used as seeds in subsequent inter-regional functional connectivity (FC) analysis. Statistical analyses were also performed by including anxiety and depression as covariates to evaluate their effect. Compared to healthy controls, IBS patients showed decreased ALFF in several core default mode network regions (medial prefrontal cortex [MPFC], posterior cingulate cortex [PCC], bilateral inferior parietal cortices [IPC]), and in middle frontal cortex, right orbital part of the superior frontal gyrus (ORBsup), dorsal anterior cingulate cortex (dACC), and ventral anterior cingulated cortex (vACC), while they showed increased ALFF in bilateral posterior insula and cuneus. In addition, IBS patients revealed decreased inter-regional positive FC between MPFC and right ORBsup, between vACC and PCC, as well as decreased negative FC between MPFC and left posterior insula, while they showed increased negative FC between MPFC and cuneus. The inclusion of anxiety and depression as covariates abolished ALFF differences in dACC and vACC, but none of the FC differences. In conclusion: IBS patients had disturbed intrinsic brain function. High levels of anxiety and depression in IBS patients could account for their decreased intrinsic brain activity in regions (the ACC) involved in affective processing.

A preliminary study of the effects of working memory training on brain function.

Abstract: Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (Cogmed™) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts.

Action observation and imitation in autism spectrum disorders: an ALE meta-analysis of fMRI studies.

Abstract: Previous studies have shown that the mirror neuron system (MNS) plays an important role in action understanding. However, whether and how the MNS activity is different in individuals with autism spectrum disorders (ASD) and typically developed (TD) individuals are still unclear. The current study used activation likelihood estimation to conduct a meta-analysis of functional magnetic resonance imaging studies that investigated action observation and imitation in ASD and TD individuals. Thirteen studies were selected, and the contrasts focused on the brain effects in ASD and TD participants and the differences between the two groups. The results showed that compared with TD individuals, ASD individuals exhibited stronger effects in the anterior inferior parietal lobule, a part of the putative human MNS. In addition, the ASD group demonstrated altered effects in the occipital cortex, dorsolateral prefrontal cortex, cingulate cortex, and insula. These results suggest that ASD individuals demonstrate dysfunction of the MNS during action observation and imitation. Furthermore, brain regions involved in visual processing, executive function, and social cognitive function might also show dysfunction during action task performance.

Exposure to childhood trauma is associated with altered n-back activation and performance in healthy adults: implications for a commonly used working memory task

Abstract: Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79% ± 19 vs. 92% ± 9, p = 0.049); accuracy and response time otherwise did not differ between groups. During the 0-back, ELS participants demonstrated increased activation in the superior temporal gyrus/insula, left inferior parietal lobule (IPL) (both corrected p < 0.001), and middle temporal and parahippocampal gyrus (MTG/PHG)(corrected p < 0.010). During the 2-back, ELS was associated with greater activation in the IPL, MTG/PHG and inferior frontal gyrus (corrected p < 0.001), with a trend towards precuneus activation (p = 0.080). These findings support previous research showing that ELS is associated with impaired neurobehavioral performance and changes in brain activation, suggesting recruitment of additional cognitive resources during WM in ELS. Based on these findings, ELS screening in future WM imaging studies appears warranted.

Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes

Abstract: The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic ‘reward’ circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 μg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes.

An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer's disease.

Abstract: Cortical and subcortical nuclei degenerate in the dementias, but less is known about changes in the white matter tracts that connect them. To better understand white matter changes in behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer's disease (EOAD), we used a novel approach to extract full 3D profiles of fiber bundles from diffusion-weighted MRI (DWI) and map white matter abnormalities onto detailed models of each pathway. The result is a spatially complex picture of tract-by-tract microstructural changes. Our atlas of tracts for each disease consists of 21 anatomically clustered and recognizable white matter tracts generated from whole-brain tractography in 20 patients with bvFTD, 23 with age-matched EOAD, and 33 healthy elderly controls. To analyze the landscape of white matter abnormalities, we used a point-wise tract correspondence method along the 3D profiles of the tracts and quantified the pathway disruptions using common diffusion metrics - fractional anisotropy, mean, radial, and axial diffusivity. We tested the hypothesis that bvFTD and EOAD are associated with preferential degeneration in specific neural networks. We mapped axonal tract damage that was best detected with mean and radial diffusivity metrics, supporting our network hypothesis, highly statistically significant and more sensitive than widely studied fractional anisotropy reductions. From white matter diffusivity, we identified abnormalities in bvFTD in all 21 tracts of interest but especially in the bilateral uncinate fasciculus, frontal callosum, anterior thalamic radiations, cingulum bundles and left superior longitudinal fasciculus. This network of white matter alterations extends beyond the most commonly studied tracts, showing greater white matter abnormalities in bvFTD versus controls and EOAD patients. In EOAD, network alterations involved more posterior white matter - the parietal sector of the corpus callosum and parahipoccampal cingulum bilaterally. Widespread but distinctive white matter alterations are a key feature of the pathophysiology of these two forms of dementia.

Male brain ages faster: the age and gender dependence of subcortical volumes.

Abstract: Effects of gender on grey matter (GM) volume differences in subcortical structures of the human brain have consistently been reported. Recent research evidence suggests that both gender and brain size influences volume distribution in subcortical areas independently. The goal of this study was to determine the effects of the interplay between brain size, gender and age contributing to volume differences of subcortical GM in the human brain. High-resolution T1-weighted images were acquired from 53 healthy males and 50 age-matched healthy females. Total GM volume was determined using voxel-based morphometry. We used model-based subcortical segmentation analysis to measure the volume of subcortical nuclei. Main effects of gender, brain volume and aging on subcortical structures were examined using multivariate analysis of variance. No significant difference was found in total brain volume between the two genders after correcting for total intracranial volume. Our analysis revealed significantly larger hippocampus volume for females. Additionally, GM volumes of the caudate nucleus, putamen and thalamus displayed a significant age-related decrease in males as compared to females. In contrast to this only the thalamic volume loss proved significant for females. Strikingly, GM volume decreases faster in males than in females emphasizing the interplay between aging and gender on subcortical structures. These findings might have important implications for the interpretation of the effects of unalterable factors (i.e. gender and age) in cross-sectional structural MRI studies. Furthermore, the volume distribution and changes of subcortical structures have been consistently related to several neuropsychiatric disorders (e.g. Parkinson's disease, attention deficit hyperactivity disorder, etc.). Understanding these changes might yield further insight in the course and prognosis of these disorders.

Abnormal asymmetry in frontostriatal white matter in children with attention deficit hyperactivity disorder

Abstract: A growing body of work utilizing structural and functional brain imaging and neurocognitive measures of executive and attentional function indicates anomalous asymmetry in ADHD. This study examined the white-matter volume and diffusion properties of frontostriatal tracts, as a function of hemisphere, in ADHD and healthy controls. Forty-three young males (21 ADHD–Combined Type and 22 controls) aged 10–18 years underwent structural and diffusion weighted MRI. Tractography applying constrained spherical deconvolution (CSD) was used to construct frontostriatal tracts between each of caudate and putamen and each of dorsolateral prefrontal, ventrolateral prefrontal and orbitofrontal cortices (DLPFC, VLPFC and OFC) in each hemisphere, to examine both volumetric and diffusion microstructure properties. Young people with ADHD did not show the right hemisphere lateralization of volume in the Caudate-VLPFC and Caudate-DLPFC tracts that was evident in controls, however the ADHD group displayed a pronounced lateralization to the left for fractional anisotropy in the Putamen-VLPFC tracts. The degree of volume asymmetry did not correlate with symptom severity; however fractional anisotropy (FA) values that were more strongly lateralized to the left in the Putamen-VLPFC white matter were associated with greater symptom severity. ADHD was associated with anomalous hemispheric asymmetries in both tract volume and underlying white-matter microstructure in major fibre tracts of the frontostriatal system. Our observations of both weaker lateralization to the right in terms of tract volume and stronger lateralization to the left in terms of FA values for the ADHD group, suggests that previous inconsistencies in the literature may reflect the influence of such asymmetries.

The association between alterations of eye movement control and cerebral intrinsic functional connectivity in Parkinson's disease

Abstract: Patients with Parkinson's disease (PD) present with eye movement disturbances that accompany the cardinal motor symptoms. Previous studies have consistently found evidence that large-scale functional networks are critically involved in eye movement control. We challenged the hypothesis that altered eye movement control in patients with PD is closely related to alterations of whole-brain functional connectivity in association with the neurodegenerative process. Saccadic and pursuit eye movements by video-oculography and 'resting-state' functional MRI (3 Tesla) were recorded from 53 subjects, i.e. 31 patients with PD and 22 matched healthy controls. Video-oculographically, a broad spectrum of eye movement impairments was demonstrated in PD patients vs. controls, including interrupted smooth pursuit, hypometric saccades, and a high distractibility in anti-saccades. Significant correlations between altered oculomotor parameters and functional connectivity measures were observed, i.e. the worse the oculomotor performance was, the more the regional functional connectivity in cortical, limbic, thalamic, cerebellar, and brainstem areas was decreased. Remarkably, decreased connectivity between major nodes of the default mode network was tightly correlated with the prevalence of saccadic intrusions as a measure for distractability. In conclusion, dysfunctional eye movement control in PD seems to be primarily associated with (cortical) executive deficits, rather than being related to the ponto-cerebellar circuits or the oculomotor brainstem nuclei. Worsened eye movement performance together with the potential pathophysiological substrate of decreased intrinsic functional connectivity in predominantly oculomotor-associated cerebral functional networks may constitute a behavioral marker in PD.

Olfactory bulb volume predicts therapeutic outcome in major depression disorder

Abstract: The volume of the olfactory bulb (OB) is strongly reduced in patients with major depressive disorder (MDD) and this group exhibits markedly decreased olfactory function It has been suggested that olfactory input is important for maintaining balance in limbic neurocircuits The aim of our study was to investigate whether reduced OB volume is associated with response to therapy in MDD Twenty-four inpatients (all women, age 21-49 years, mean 38 ± 10 years SD) with MDD and 36 healthy controls (all women, age 20-52 years, mean 36 ± 10 years SD) underwent structural MRI OB volume was compared between responders (N = 13) and non-responders (N = 11) to psychotherapy Retest of OB volume was performed about 6 months after the end of therapy in nine of the patients Therapy responders exhibited no significant difference in OB volume compared to healthy controls However, average OB volume of non-responders was 23 % smaller compared to responders (p = 0011) Furthermore, OB volume was correlated with the change of depression severity (r = 46, p = 024) Volume of the OB did not change in the course of therapy OB volume may be a biological vulnerability factor for the occurrence and/or maintenance of depression, at least in women

Increased interhemispheric resting-state functional connectivity after sleep deprivation: a resting-state fMRI study

Abstract: Several functional imaging studies have investigated the regional effects of sleep deprivation (SD) on impaired brain function; however, potential changes in the functional interactions between the cerebral hemispheres after SD are not well understood. In this study, we used a recently validated approach, voxel-mirrored homotopic connectivity (VMHC), to directly examine the changes in interhemispheric homotopic resting-state functional connectivity (RSFC) after SD. Resting-state functional MRI (fMRI) was performed in 28 participants both after rest wakefulness (RW) and a total night of SD. An interhemispheric RSFC map was obtained by calculating the Pearson correlation (Fisher Z transformed) between each pair of homotopic voxel time series for each subject in each condition. The between-condition differences in interhemispheric RSFC were then examined at global and voxelwise levels separately. Significantly increased global VMHC was found after sleep deprivation; specifically, a significant increase in VMHC was found in specific brain regions, including the thalamus, paracentral lobule, supplementary motor area, postcentral gyrus and lingual gyrus. No regions showed significantly reduced VMHC after sleep deprivation. Further analysis indicates that these findings did not depend on the various sizes of smoothing kernels that were adopted in the preprocessing steps and that the differences in these regions were still significant with or without global signal regression. Our data suggest that the increased VMHC might reflect the compensatory involvement of bilateral brain areas, especially the bilateral thalamus, to prevent cognitive performance deterioration when sleep pressure is elevated after sleep deprivation. Our findings provide preliminary evidence of interhemispheric correlation changes after SD and contribute to a better understanding of the neural mechanisms of SD.