Spatially Regularized Machine Learning for Task and Resting-state fMRI.
J Neurosci Methods. 2015 Oct 12;
Authors: Song X, Panych LP, Chen NK
BACKGROUND: Reliable mapping of brain function across sessions and/or subjects in task- and resting-state has been a critical challenge for quantitative fMRI studies although it has been intensively addressed in the past decades.
NEW METHOD: A spatially regularized support vector machine (SVM) technique was developed for the reliable brain mapping in task- and resting-state. Unlike most existing SVM-based brain mapping techniques, which implement supervised classifications of specific brain functional states or disorders, the proposed method performs a semi-supervised classification for the general brain function mapping where spatial correlation of fMRI is integrated into the SVM learning. The method can adapt to intra- and inter-subject variations induced by fMRI nonstationarity, and identify a true boundary between active and inactive voxels, or between functionally connected and unconnected voxels in a feature space.
RESULTS: The method was evaluated using synthetic and experimental data at the individual and group level. Multiple features were evaluated in terms of their contributions to the spatially regularized SVM learning. Reliable mapping results in both task- and resting-state were obtained from individual subjects and at the group level.
COMPARISON WITH EXISTING METHODS: A comparison study was performed with independent component analysis, general linear model, and correlation analysis methods. Experimental results indicate that the proposed method can provide a better or comparable mapping performance at the individual and group level.
CONCLUSIONS: The proposed method can provide accurate and reliable mapping of brain function in task- and resting-state, and is applicable to a variety of quantitative fMRI studies.
PMID: 26470627 [PubMed - as supplied by publisher]
Dysfunctional Default Mode Network in Methadone Treated Patients Who Have a Higher Heroin Relapse Risk.
Sci Rep. 2015;5:15181
Authors: Li W, Li Q, Wang D, Xiao W, Liu K, Shi L, Zhu J, Li Y, Yan X, Chen J, Ye J, Li Z, Wang Y, Wang W
The purpose of this study was to identify whether heroin relapse is associated with changes in the functional connectivity of the default mode network (DMN) during methadone maintenance treatment (MMT). Resting-state functional magnetic resonance imaging (fMRI) data of chronic heroin relapsers (HR) (12 males, 1 female, age: 36.1 ± 6.9 years) and abstainers (HA) (11males, 2 female; age: 42.1 ± 8.1 years) were investigated with an independent component analysis to address the functional connectivity of their DMN. Group comparison was then performed between the relapsers and abstainers. Our study found that the left inferior temporal gyrus and the right superior occipital gyrus associated with DMN showed decreased functional connectivity in HR when compared with HA, while the left precuneus and the right middle cingulum had increased functional connectivity. Mean intensity signal, extracted from left inferior temporal gyrus of HR patients, showed a significant negative correlation corresponding to the degree of heroin relapse. These findings suggest that altered functional connectivity of DMN may contribute to the potential neurobiological mechanism(s) of heroin relapse and have a predictive value concerning heroin relapse under MMT.
PMID: 26469876 [PubMed - as supplied by publisher]
Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study.
PLoS One. 2015;10(10):e0137977
Authors: Quattrocchi CC, de Pandis MF, Piervincenzi C, Galli M, Melgari JM, Salomone G, Sale P, Mallio CA, Carducci F, Stocchi F
OBJECTIVE: The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease.
METHODS: Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition.
RESULTS: Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79).
CONCLUSIONS: Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest.
TRIAL REGISTRATION: Clinical Trials.gov NCT01815281.
PMID: 26469868 [PubMed - as supplied by publisher]
Investigating the Temporal Patterns within and between Intrinsic Connectivity Networks under Eyes-Open and Eyes-Closed Resting States: A Dynamical Functional Connectivity Study Based on Phase Synchronization.
PLoS One. 2015;10(10):e0140300
Authors: Wang XH, Li L, Xu T, Ding Z
The brain active patterns were organized differently under resting states of eyes open (EO) and eyes closed (EC). The altered voxel-wise and regional-wise resting state active patterns under EO/EC were found by static analysis. More importantly, dynamical spontaneous functional connectivity has been observed in the resting brain. To the best of our knowledge, the dynamical mechanisms of intrinsic connectivity networks (ICNs) under EO/EC remain largely unexplored. The goals of this paper were twofold: 1) investigating the dynamical intra-ICN and inter-ICN temporal patterns during resting state; 2) analyzing the altered dynamical temporal patterns of ICNs under EO/EC. To this end, a cohort of healthy subjects with scan conditions of EO/EC were recruited from 1000 Functional Connectomes Project. Through Hilbert transform, time-varying phase synchronization (PS) was applied to evaluate the inter-ICN synchrony. Meanwhile, time-varying amplitude was analyzed as dynamical intra-ICN temporal patterns. The results found six micro-states of inter-ICN synchrony. The medial visual network (MVN) showed decreased intra-ICN amplitude during EC relative to EO. The sensory-motor network (SMN) and auditory network (AN) exhibited enhanced intra-ICN amplitude during EC relative to EO. Altered inter-ICN PS was found between certain ICNs. Particularly, the SMN and AN exhibited enhanced PS to other ICNs during EC relative to EO. In addition, the intra-ICN amplitude might influence the inter-ICN synchrony. Moreover, default mode network (DMN) might play an important role in information processing during EO/EC. Together, the dynamical temporal patterns within and between ICNs were altered during different scan conditions of EO/EC. Overall, the dynamical intra-ICN and inter-ICN temporal patterns could benefit resting state fMRI-related research, and could be potential biomarkers for human functional connectome.
PMID: 26469182 [PubMed - as supplied by publisher]
Subclinical depression severity is associated with distinct patterns of functional connectivity for subregions of anterior cingulate cortex.
J Psychiatr Res. 2015 Oct 9;71:103-111
Authors: Philippi CL, Motzkin JC, Pujara MS, Koenigs M
Depression is a prevalent psychiatric condition characterized by sad mood and anhedonia. Neuroscientific research has consistently identified abnormalities in a network of brain regions in major depression, including subregions of the anterior cingulate cortex (ACC). However, few studies have investigated whether the same neural correlates of depression symptom severity are apparent in subclinical or healthy subjects. In the current study, we used resting-state fMRI to examine functional connectivity for subregions of the ACC in N = 28 participants with subclinical levels of depression. In regression analyses, we examined relationships between depression severity and functional connectivity for pregenual ACC (pgACC), anterior subgenual ACC (sgACC), and posterior sgACC seed regions. Additionally, we examined relationships between ACC subregion connectivity and trait levels of positive and negative affect. We found distinct associations between depression severity and functional connectivity of ACC subregions. Higher depression severity was associated with reduced pgACC-striatum connectivity and reduced anterior sgACC-anterior insula connectivity. Consistent with resting-state findings in major depression, higher depression severity was also related to greater anterior sgACC-posterior cingulate connectivity and greater posterior sgACC-dorsolateral prefrontal connectivity. Lastly, there were distinct correlations between connectivity for anterior versus posterior ACC subregions and positive and negative affective traits. These findings provide novel support linking subclinical depression to the same neural substrates associated with major depression. More broadly, these results contribute to an emerging literature on dimensional approaches to psychiatric illness.
PMID: 26468907 [PubMed - as supplied by publisher]
State and Trait Components of Functional Connectivity: Individual Differences Vary with Mental State.
J Neurosci. 2015 Oct 14;35(41):13949-61
Authors: Geerligs L, Rubinov M, Cam-Can, Henson RN
UNLABELLED: Resting-state functional connectivity, as measured by functional magnetic resonance imaging (fMRI), is often treated as a trait, used, for example, to draw inferences about individual differences in cognitive function, or differences between healthy or diseased populations. However, functional connectivity can also depend on the individual's mental state. In the present study, we examined the relative contribution of state and trait components in shaping an individual's functional architecture. We used fMRI data from a large, population-based human sample (N = 587, age 18-88 years), as part of the Cambridge Centre for Aging and Neuroscience (Cam-CAN), which were collected in three mental states: resting, performing a sensorimotor task, and watching a movie. Whereas previous studies have shown commonalities across mental states in the average functional connectivity across individuals, we focused on the effects of states on the pattern of individual differences in functional connectivity. We found that state effects were as important as trait effects in shaping individual functional connectivity patterns, each explaining an approximately equal amount of variance. This was true when we looked at aging, as one specific dimension of individual differences, as well as when we looked at generic aspects of individual variation. These results show that individual differences in functional connectivity consist of state-dependent aspects, as well as more stable, trait-like characteristics. Studying individual differences in functional connectivity across a wider range of mental states will therefore provide a more complete picture of the mechanisms underlying factors such as cognitive ability, aging, and disease.
SIGNIFICANCE STATEMENT: The brain's functional architecture is remarkably similar across different individuals and across different mental states, which is why many studies use functional connectivity as a trait measure. Despite these trait-like aspects, functional connectivity varies over time and with changes in cognitive state. We measured connectivity in three different states to quantify the size of the trait-like component of functional connectivity, compared with the state-dependent component. Our results show that studying individual differences within one state (such as resting) uncovers only part of the relevant individual differences in brain function, and that the study of functional connectivity under multiple mental states is essential to disentangle connectivity differences that are transient versus those that represent more stable, trait-like characteristics of an individual.
PMID: 26468196 [PubMed - in process]
Essential tremor is associated with disruption of functional connectivity in the ventral intermediate Nucleus-Motor Cortex-Cerebellum circuit.
Hum Brain Mapp. 2015 Oct 15;
Authors: Fang W, Chen H, Wang H, Zhang H, Puneet M, Liu M, Lv F, Luo T, Cheng O, Wang X, Lu X
The clinical benefits of targeting the ventral intermediate nucleus (VIM) for the treatment of tremors in essential tremor (ET) patients suggest that the VIM is a key hub in the network of tremor generation and propagation and that the VIM can be considered as a seed region to study the tremor network. However, little is known about the central tremor network in ET patients. Twenty-six ET patients and 26 matched healthy controls (HCs) were included in this study. After considering structural and head-motion factors and establishing the accuracy of our seed region, a VIM seed-based functional connectivity (FC) analysis of resting-state functional magnetic resonance imaging (RS-fMRI) data was performed to characterize the VIM FC network in ET patients. We found that ET patients and HCs shared a similar VIM FC network that was generally consistent with the VIM anatomical connectivity network inferred from normal nonhuman primates and healthy humans. Compared with HCs, ET patients displayed VIM-related FC changes, primarily within the VIM-motor cortex (MC)-cerebellum (CBLM) circuit, which included decreased FC in the CBLM and increased FC in the MC. Importantly, tremor severity correlated with these FC changes. These findings provide the first evidence that the pathological tremors observed in ET patients might be based on a physiologically pre-existing VIM - MC - CBLM network and that disruption of FC in this physiological network is associated with ET. Further, these findings demonstrate a potential approach for elucidating the neural network mechanisms underlying this disease. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
PMID: 26467643 [PubMed - as supplied by publisher]
Individual Variability of the System-Level Organization of the Human Brain.
Cereb Cortex. 2015 Oct 13;
Authors: Gordon EM, Laumann TO, Adeyemo B, Petersen SE
Recent functional magnetic resonance imaging-based resting-state functional connectivity analyses of group average data have characterized large-scale systems that represent a high level in the organizational hierarchy of the human brain. These systems are likely to vary spatially across individuals, even after anatomical alignment, but the characteristics of this variance are unknown. Here, we characterized large-scale brain systems across two independent datasets of young adults. In these individuals, we were able to identify brain systems that were similar to those described in the group average, and we observed that individuals had consistent topological arrangement of the system features present in the group average. However, the size of system features varied across individuals in systematic ways, such that expansion of one feature of a given system predicted expansion of other parts of the system. Individual-specific systems also contained unique topological features not present in group average systems; some of these features were consistent across a minority of individuals. These effects were observed even after controlling for data quality and for the accuracy of anatomical registration. The variability characterized here has important implications for cognitive neuroscience investigations, which often assume the functional equivalence of aligned brain regions across individuals.
PMID: 26464473 [PubMed - as supplied by publisher]
BOLD signal effects of transcranial Alternating Current Stimulation (tACS) in the alpha range: A concurrent tACS-fMRI study.
Neuroimage. 2015 Oct 9;
Authors: Vosskuhl J, Huster RJ, Herrmann CS
Many studies have proven transcranial alternating current stimulation (tACS) to manipulate brain activity. Until now it is not known, however, how these manipulations in brain activity are represented in brain metabolism or how spatially specific these changes are. Alpha-tACS has been shown to enhance the amplitude of the individual alpha frequency (IAF) and a negative correlation between alpha amplitude and occipital BOLD signal was reported in numerous EEG/fMRI experiments. Thus, alpha-tACS was chosen to test the effects of tACS on the BOLD signal. A reduction thereof was expected during alpha-tACS which shows the spatial extend of tACS effects beyond modeling studies. Three groups of subjects were measured in an MRI scanner, receiving tACS at either their IAF (N=11), 1 Hz (control; N=12) or sham (i.e. no stimulation - a second control; N=11) while responding to a visual vigilance task. Stimulation was administered in an interleaved pattern of tACS-on runs and tACS-free baseline periods. The BOLD signal was analyzed in response to tACS-onset during resting state and in response to seldom target stimuli. Alpha-tACS at 1.0 mA reduced the task-related BOLD response to visual targets in the occipital cortex as compared to tACS-free baseline periods. The deactivation was strongest in an area where the BOLD signal was shown to correlate negatively with alpha amplitude. A direct effect of tACS on resting state BOLD signal levels could not be shown. Our findings suggest that tACS-related changes in BOLD activity occur only as a modulation of an existing BOLD response.
PMID: 26458516 [PubMed - as supplied by publisher]
Data-driven and Predefined ROI-based Quantification of Long-term Resting-state fMRI Reproducibility.
Brain Connect. 2015 Oct 11;
Authors: Song X, Lawrence PP, Chen NK
Resting-state functional magnetic resonance imaging (fMRI) is a promising tool for neuroscience and clinical studies. However, there exist significant variations in strength and spatial extent of resting-state functional connectivity over repeated sessions in a single or multiple subjects with identical experimental conditions. Reproducibility studies have been conducted for resting-state fMRI where the reproducibility was usually evaluated in predefined regions-of-interest (ROI). It was possible that reproducibility measures strongly depended on the ROI definition. In this work, this issue was investigated by comparing data-driven and predefined ROI-based quantification of reproducibility. In the data-driven analysis, the reproducibility was quantified using functionally connected voxels detected by a support vector machine (SVM)-based technique. In the predefined ROI-based analysis, all voxels in the predefined ROIs were included when estimating the reproducibility. Experimental results show that 1) a moderate to substantial within-subject reproducibility and a reasonable between-subject reproducibility can be obtained using functionally connected voxels identified by the SVM-based technique; 2) in the predefined ROI-based analysis, an increase in ROI size does not always result in higher reproducibility measures; 3) ROI pairs with high connectivity strength have a higher chance to exhibit high reproducibility; 4) ROI pairs with high reproducibility do not necessarily have high connectivity strength; 5) the reproducibility measured from the identified functionally connected voxels is generally higher than that measured from all voxels in predefined ROIs with typical sizes. The findings 2) and 5) suggest that conventional ROI-based analyses would under-estimate the resting-state fMRI reproducibility.
PMID: 26456172 [PubMed - as supplied by publisher]
The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.
Drug Alcohol Depend. 2015 Sep 26;
Authors: Froeliger B, McConnell PA, Stankeviciute N, McClure EA, Kalivas PW, Gray KM
BACKGROUND: Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period.
METHODS: The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning.
RESULTS: As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]).
CONCLUSIONS: Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.
PMID: 26454838 [PubMed - as supplied by publisher]
Altered executive control network resting-state connectivity in social anxiety disorder.
World J Biol Psychiatry. 2015 Oct 9;:1-11
Authors: Geiger MJ, Domschke K, Ipser J, Hattingh C, Baldwin DS, Lochner C, Stein DJ
OBJECTIVES: Research into the neural basis of social anxiety disorder (SAD) suggests alterations in prefrontal networks, which may in turn disrupt regulation of the limbic system. Better understanding of the disturbed interface between these networks may improve current pathogenic models of this disorder.
METHODS: Applying group independent component analysis (ICA) to recordings of fMRI resting-state, connectivity in the executive control network was studied in 18 patients with SAD and 15 age- and sex-matched healthy controls.
RESULTS: Results revealed a dissociation within the left executive control network, with SAD patients showing decreased connectivity of the orbitofrontal gyrus and increased connectivity of the middle frontal gyrus compared to healthy controls. In a subsequent seed-based functional connectivity analysis, patients with SAD displayed increased connectivity between the left orbitofrontal gyrus and the left amygdala.
CONCLUSIONS: Findings suggest that hypo-connectivity in the executive control network and hyper-connectivity between the orbitofrontal cortex and the amygdala may reflect a disturbance in the balance between top-down and bottom-up control processes, potentially contributing to the development of SAD.
PMID: 26452782 [PubMed - as supplied by publisher]
Specific Correlation between the Hegu Point (LI4) and the Orofacial Part: Evidence from an fMRI Study.
Evid Based Complement Alternat Med. 2015;2015:585493
Authors: Kong SP, Tan QW, Liu Y, Jing XH, Zhu B, Huo YJ, Nie BB, Yang DH
Acupoint specificity is a foundational concept in acupuncture theory. It is closely related to the function of the acupoint. In this study, we sought to probe the central mechanisms of the specific correlation between LI4 and orofacial part in Bell's palsy patients. In total, 36 patients with left Bell's palsy were divided into three groups in random order, and each group received transcutaneous electrical acupoint stimulation (TEAS) at only one of three acupoints (LI4, ST6, and a sham point). A single-block fMRI design paradigm was applied to separately detect neural activity related to different stages of TEAS (prestimulation resting state, stimulation, and poststimulation resting state). Functional magnetic resonance imaging data were acquired during TEAS. There were extensive neuronal activities in the LI4 and ST6 groups and significant differences between stimulation at real and sham points. Brain regions were activated more by real acupoint TEAS than by sham point TEAS. Brain regions that were activated with LI4 and ST6 were broadly overlapping and adjacent. Our results provide supplementary neuroimaging evidence for the existence of acupoint specificity. These results may confirm the central mechanisms of the specific correlation between the Hegu point and the orofacial part.
PMID: 26446439 [PubMed]
Altered resting perfusion and functional connectivity of default mode network in youth with autism spectrum disorder.
Brain Behav. 2015 Sep;5(9):e00358
Authors: Jann K, Hernandez LM, Beck-Pancer D, McCarron R, Smith RX, Dapretto M, Wang DJ
BACKGROUND: Neuroimaging studies can shed light on the neurobiological underpinnings of autism spectrum disorders (ASD). Studies of the resting brain have shown both altered baseline metabolism from PET/SPECT and altered functional connectivity (FC) of intrinsic brain networks based on resting-state fMRI. To date, however, no study has investigated these two physiological parameters of resting brain function jointly, or explored the relationship between these measures and ASD symptom severity.
METHODS: Here, we used pseudo-continuous arterial spin labeling with 3D background-suppressed GRASE to assess resting cerebral blood flow (CBF) and FC in 17 youth with ASD and 22 matched typically developing (TD) children.
RESULTS: A pattern of altered resting perfusion was found in ASD versus TD children including frontotemporal hyperperfusion and hypoperfusion in the dorsal anterior cingulate cortex. We found increased local FC in the anterior module of the default mode network (DMN) accompanied by decreased CBF in the same area. In our cohort, both alterations were associated with greater social impairments as assessed with the Social Responsiveness Scale (SRS-total T scores). While FC was correlated with CBF in TD children, this association between FC and baseline perfusion was disrupted in children with ASD. Furthermore, there was reduced long-range FC between anterior and posterior modules of the DMN in children with ASD.
CONCLUSION: Taken together, the findings of this study - the first to jointly assess resting CBF and FC in ASD - highlight new avenues for identifying novel imaging markers of ASD symptomatology.
PMID: 26445698 [PubMed - in process]
Altered connectivity of the dorsal and ventral visual regions in dyslexic children: a resting-state fMRI study.
Front Hum Neurosci. 2015;9:495
Authors: Zhou W, Xia Z, Bi Y, Shu H
While there is emerging evidence from behavioral studies that visual attention skills are impaired in dyslexia, the corresponding neural mechanism (i.e., deficits in the dorsal visual region) needs further investigation. We used resting-state fMRI to explore the functional connectivity (FC) patterns of the left intraparietal sulcus (IPS) and the visual word form area (VWFA) in dyslexic children (N = 21, age mean = 12) and age-matched controls (N = 26, age mean = 12). The results showed that the left IPS and the VWFA were functionally connected to each other in both groups and that both were functionally connected to left middle frontal gyrus (MFG). Importantly, we observed significant group differences in FC between the left IPS and the left MFG and between the VWFA and the left MFG. In addition, the strengths of the identified FCs were significantly correlated with the score of fluent reading, which required obvious eye movement and visual attention processing, but not with the lexical decision score. We conclude that dyslexics have deficits in the network composed of the prefrontal, dorsal visual and ventral visual regions and may have a lack of modulation from the left MFG to the dorsal and ventral visual regions.
PMID: 26441595 [PubMed - as supplied by publisher]
Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer's disease.
Front Hum Neurosci. 2015;9:474
Authors: Hafkemeijer A, Möller C, Dopper EG, Jiskoot LC, Schouten TM, van Swieten JC, van der Flier WM, Vrenken H, Pijnenburg YA, Barkhof F, Scheltens P, van der Grond J, Rombouts SA
Introduction: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. Early differentiation between both types of dementia may be challenging due to heterogeneity and overlap of symptoms. Here, we apply resting state functional magnetic resonance imaging (fMRI) to study functional brain connectivity differences between AD and bvFTD. Methods: We used resting state fMRI data of 31 AD patients, 25 bvFTD patients, and 29 controls from two centers specialized in dementia. We studied functional connectivity throughout the entire brain, applying two different analysis techniques, studying network-to-region and region-to-region connectivity. A general linear model approach was used to study group differences, while controlling for physiological noise, age, gender, study center, and regional gray matter volume. Results: Given gray matter differences, we observed decreased network-to-region connectivity in bvFTD between (a) lateral visual cortical network and lateral occipital and cuneal cortex, and (b) auditory system network and angular gyrus. In AD, we found decreased network-to-region connectivity between the dorsal visual stream network and lateral occipital and parietal opercular cortex. Region-to-region connectivity was decreased in bvFTD between superior temporal gyrus and cuneal, supracalcarine, intracalcarine cortex, and lingual gyrus. Conclusion: We showed that the pathophysiology of functional brain connectivity is different between AD and bvFTD. Our findings support the hypothesis that resting state fMRI shows disease-specific functional connectivity differences and is useful to elucidate the pathophysiology of AD and bvFTD. However, the group differences in functional connectivity are less abundant than has been shown in previous studies.
PMID: 26441584 [PubMed - as supplied by publisher]
BASCO: a toolbox for task-related functional connectivity.
Front Syst Neurosci. 2015;9:126
Authors: Göttlich M, Beyer F, Krämer UM
BASCO (BetA Series COrrelation) is a user-friendly MATLAB toolbox with a graphical user interface (GUI) which allows investigating functional connectivity in event-related functional magnetic resonance imaging (fMRI) data. Connectivity analyses extend and compliment univariate activation analyses since the actual interaction between brain regions involved in a task can be explored. BASCO supports seed-based functional connectivity as well as brain network analyses. Although there are a multitude of advanced toolboxes for investigating resting-state functional connectivity, BASCO is the first toolbox for evaluating task-related whole-brain functional connectivity employing a large number of network nodes. Thus, BASCO allows investigating task-specific rather than resting-state networks. Here, we summarize the main features of the toolbox and describe the methods and algorithms.
PMID: 26441558 [PubMed - as supplied by publisher]
Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain.
Front Neuroanat. 2015;9:119
Authors: Takaya S, Kuperberg GR, Liu H, Greve DN, Makris N, Stufflebeam SM
The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that the left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. The unique feature of the left AF is discussed in the context of the human capacity for language.
PMID: 26441551 [PubMed - as supplied by publisher]
An empirical Bayes normalization method for connectivity metrics in resting state fMRI.
Front Neurosci. 2015;9:316
Authors: Chen S, Kang J, Wang G
Functional connectivity analysis using resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a powerful technique for investigating functional brain networks. The functional connectivity is often quantified by statistical metrics (e.g., Pearson correlation coefficient), which may be affected by many image acquisition and preprocessing steps such as the head motion correction and the global signal regression. The appropriate quantification of the connectivity metrics is essential for meaningful and reproducible scientific findings. We propose a novel empirical Bayes method to normalize the functional brain connectivity metrics on a posterior probability scale. Moreover, the normalization function maps the original connectivity metrics to values between zero and one, which is well-suited for the graph theory based network analysis and avoids the information loss due to the (negative value) hard thresholding step. We apply the normalization method to a simulation study and the simulation results show that our normalization method effectively improves the robustness and reliability of the quantification of brain functional connectivity and provides more powerful group difference (biomarkers) detection. We illustrate our method on an analysis of a rs-fMRI dataset from the Autism Brain Imaging Data Exchange (ABIDE) study.
PMID: 26441493 [PubMed - as supplied by publisher]
Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rTMS.
Neuropsychopharmacology. 2015 Oct 6;
Authors: Dunlop K, Woodside B, Olmsted M, Colton P, Giacobbe P, Downar J
Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of non-response to conventional treatments. OCD pathophysiology is believed to involve abnormalities in cortico-striatal-thalamic-cortical circuits through regions such as dorsomedial prefrontal cortex (dmPFC), and ventral striatum. These regions may constitute therapeutic targets for neuromodulation treatments, such as repetitive transcranial magnetic stimulation (rTMS). However, the neurobiological predictors and correlates of successful rTMS treatment for OCD are unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) to identify neural predictors and correlates of response to 20-30 sessions of bilateral 10 Hz dmPFC-rTMS in 20 treatment-resistant OCD patients, with 40 healthy controls as baseline comparators. A region of interest in the dmPFC was used to generate whole-brain functional connectivity maps pre- and post-treatment. 10 of 20 patients met response criteria (⩾50% improvement on Yale-Brown Obsessive-Compulsive Scale, YBOCS); response to dmPFC-rTMS was sharply bimodal. dmPFC-rTMS responders had higher dmPFC-ventral striatal connectivity at baseline. The degree of reduction in this connectivity, from pre- to post-treatment, correlated to the degree of YBOCS symptomatic improvement. Baseline clinical and psychometric data did not predict treatment response. In summary, reductions in fronto-striatal hyperconnectivity were associated with treatment response to dmPFC-rTMS in OCD. This finding is consistent with previous fMRI studies of deep brain stimulation in OCD, but opposite to previous reports on mechanisms of dmPFC-rTMS in major depression. fMRI could prove useful in predicting response to dmPFC-rTMS in OCD.Neuropsychopharmacology accepted article preview online, 06 October 2015. doi:10.1038/npp.2015.292.
PMID: 26440813 [PubMed - as supplied by publisher]