Forum of resting-state fMRI

Functional MRI in the investigation of blast-related traumatic brain injury.

Front Neurol. 2013;4:16

Authors: Graner J, Oakes TR, French LM, Riedy G

Abstract
This review focuses on the application of functional magnetic resonance imaging (fMRI) to the investigation of blast-related traumatic brain injury (bTBI). Relatively little is known about the exact mechanisms of neurophysiological injury and pathological and functional sequelae of bTBI. Furthermore, in mild bTBI, standard anatomical imaging techniques (MRI and computed tomography) generally fail to show focal lesions and most of the symptoms present as subjective clinical functional deficits. Therefore, an objective test of brain functionality has great potential to aid in patient diagnosis and provide a sensitive measurement to monitor disease progression and treatment. The goal of this review is to highlight the relevant body of blast-related TBI literature and present suggestions and considerations in the development of fMRI studies for the investigation of bTBI. The review begins with a summary of recent bTBI publications followed by discussions of various elements of blast-related injury. Brief reviews of some fMRI techniques that focus on mental processes commonly disrupted by bTBI, including working memory, selective attention, and emotional processing, are presented in addition to a short review of resting state fMRI. Potential strengths and weaknesses of these approaches as regards bTBI are discussed. Finally, this review presents considerations that must be made when designing fMRI studies for bTBI populations, given the heterogeneous nature of bTBI and its high rate of comorbidity with other physical and psychological injuries.

PMID: 23460082 [PubMed - in process]

Caffeine-Induced Global Reductions in Resting-State BOLD Connectivity Reflect Widespread Decreases in MEG Connectivity.

Front Hum Neurosci. 2013;7:63

Authors: Tal O, Diwakar M, Wong CW, Olafsson V, Lee R, Huang MX, Liu TT

Abstract
In resting-state functional magnetic resonance imaging (fMRI), the temporal correlation between spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal from different brain regions is used to assess functional connectivity. However, because the BOLD signal is an indirect measure of neuronal activity, its complex hemodynamic nature can complicate the interpretation of differences in connectivity that are observed across conditions or subjects. For example, prior studies have shown that caffeine leads to widespread reductions in BOLD connectivity but were not able to determine if neural or vascular factors were primarily responsible for the observed decrease. In this study, we used source-localized magnetoencephalography (MEG) in conjunction with fMRI to further examine the origins of the caffeine-induced changes in BOLD connectivity. We observed widespread and significant ( < 0.01) reductions in both MEG and fMRI connectivity measures, suggesting that decreases in the connectivity of resting-state neuro-electric power fluctuations were primarily responsible for the observed BOLD connectivity changes. The MEG connectivity decreases were most pronounced in the beta band. By demonstrating the similarity in MEG and fMRI based connectivity changes, these results provide evidence for the neural basis of resting-state fMRI networks and further support the potential of MEG as a tool to characterize resting-state connectivity.

PMID: 23459778 [PubMed - in process]

Electroconvulsive therapy response in major depressive disorder: a pilot functional network connectivity resting state FMRI investigation.

Front Psychiatry. 2013;4:10

Authors: Abbott CC, Lemke NT, Gopal S, Thoma RJ, Bustillo J, Calhoun VD, Turner JA

Abstract
Major depressive disorder (MDD) is associated with increased functional connectivity in specific neural networks. Electroconvulsive therapy (ECT), the gold-standard treatment for acute, treatment-resistant MDD, but temporal dependencies between networks associated with ECT response have yet to be investigated. In the present longitudinal, case-control investigation, we used independent component analysis to identify distinct networks of brain regions with temporally coherent hemodynamic signal change and functional network connectivity (FNC) to assess component time course correlations across these networks. MDD subjects completed imaging and clinical assessments immediately prior to the ECT series and a minimum of 5 days after the last ECT treatment. We focused our analysis on four networks affected in MDD: the subcallosal cingulate gyrus, default mode, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex (DMPFC). In an older sample of ECT subjects ( = 12) with MDD, remission associated with the ECT series reverses the relationship from negative to positive between the posterior default mode (p_DM) and two other networks: the DMPFC and left dorsal lateral prefrontal cortex (l_DLPFC). Relative to demographically healthy subjects ( = 12), the FNC between the p_DM areas and the DMPFC normalizes with ECT response. The FNC changes following treatment did not correlate with symptom improvement; however, a direct comparison between ECT remitters and non-remitters showed the pattern of increased FNC between the p_DM and l_DLPFC following ECT to be specific to those who responded to the treatment. The differences between ECT remitters and non-remitters suggest that this increased FNC between p_DM areas and the left dorsolateral prefrontal cortex is a neural correlate and potential biomarker of recovery from a depressed episode.

PMID: 23459749 [PubMed - in process]

Diffuse Disconnectivity in tBi: a resting state fMri anD Dti stuDy.

Transl Neurosci. 2012 Mar 1;3(1):9-14

Authors: Tang CY, Eaves E, Dams-O'Connor K, Ho L, Leung E, Wong E, Carpenter D, Ng J, Gordon W, Pasinetti G

Abstract
Diffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.

PMID: 23459252 [PubMed - as supplied by publisher]

Intrinsic functional connectivity of amygdala-based networks in adolescent generalized anxiety disorder.

J Am Acad Child Adolesc Psychiatry. 2013 Mar;52(3):290-299.e2

Authors: Roy AK, Fudge JL, Kelly C, Perry JS, Daniele T, Carlisi C, Benson B, Xavier Castellanos F, Milham MP, Pine DS, Ernst M

Abstract
OBJECTIVE: Generalized anxiety disorder (GAD) typically begins during adolescence and can persist into adulthood. The pathophysiological mechanisms underlying this disorder remain unclear. Recent evidence from resting state functional magnetic resonance imaging (R-fMRI) studies in adults suggests disruptions in amygdala-based circuitry; the present study examines this issue in adolescents with GAD.
METHOD: Resting state fMRI scans were obtained from 15 adolescents with GAD and 20 adolescents without anxiety who were group matched on age, sex, scanner, and intelligence. Functional connectivity of the centromedial, basolateral, and superficial amygdala subdivisions was compared between groups. We also assessed the relationship between amygdala network dysfunction and anxiety severity.
RESULTS: Adolescents with GAD exhibited disruptions in amygdala-based intrinsic functional connectivity networks that included regions in medial prefrontal cortex, insula, and cerebellum. Positive correlations between anxiety severity scores and amygdala functional connectivity with insula and superior temporal gyrus were also observed within the GAD group. There was some evidence of greater overlap (less differentiation of connectivity patterns) of the right basolateral and centromedial amygdala networks in the adolescents with, relative to those without, GAD.
CONCLUSIONS: These findings suggest that adolescents with GAD manifest alterations in amygdala circuits involved in emotion processing, similar to findings in adults. In addition, disruptions were observed in amygdala-based networks involved in fear processing and the coding of interoceptive states.

PMID: 23452685 [PubMed - in process]

Functional and structural neural network characterization of serotonin transporter knockout rats.

PLoS One. 2013;8(2):e57780

Authors: van der Marel K, Homberg JR, Otte WM, Dijkhuizen RM

Abstract
Brain serotonin homeostasis is crucially maintained by the serotonin transporter (5-HTT), and its down-regulation has been linked to increased vulnerability for anxiety- and depression-related behavior. Studies in 5-HTT knockout (5-HTT) rodents have associated inherited reduced functional expression of 5-HTT with increased sensitivity to adverse as well as rewarding environmental stimuli, and in particular cocaine hyperresponsivity. 5-HTT down-regulation may affect normal neuronal wiring of implicated corticolimbic cerebral structures. To further our understanding of its contribution to potential alterations in basal functional and structural properties of neural network configurations, we applied resting-state functional MRI (fMRI), pharmacological MRI of cocaine-induced activation, and diffusion tensor imaging (DTI) in 5-HTT rats and wild-type controls (5-HTT). We found that baseline functional connectivity values and cocaine-induced neural activity within the corticolimbic network was not significantly altered in 5-HTT versus 5-HTT rats. Similarly, DTI revealed mostly intact white matter structural integrity, except for a reduced fractional anisotropy in the genu of the corpus callosum of 5-HTT rats. At the macroscopic level, analyses of complex graphs constructed from either functional connectivity values or structural DTI-based tractography results revealed that key properties of brain network organization were essentially similar between 5-HTT and 5-HTT rats. The individual tests for differences between 5-HTT and 5-HTT rats were capable of detecting significant effects ranging from 5.8% (fractional anisotropy) to 26.1% (pharmacological MRI) and 29.3% (functional connectivity). Tentatively, lower fractional anisotropy in the genu of the corpus callosum could indicate a reduced capacity for information integration across hemispheres in 5-HTT rats. Overall, the comparison of 5-HTT and wild-type rats suggests mostly limited effects of 5-HTT genotype on MRI-based measures of brain morphology and function.

PMID: 23451267 [PubMed - in process]

Functional Networks in Parallel with Cortical Development Associate with Executive Functions in Children.

Cereb Cortex. 2013 Feb 28;

Authors: Zhong J, Rifkin-Graboi A, Ta AT, Yap KL, Chuang KH, Meaney MJ, Qiu A

Abstract
Children begin performing similarly to adults on tasks requiring executive functions in late childhood, a transition that is probably due to neuroanatomical fine-tuning processes, including myelination and synaptic pruning. In parallel to such structural changes in neuroanatomical organization, development of functional organization may also be associated with cognitive behaviors in children. We examined 6- to 10-year-old children's cortical thickness, functional organization, and cognitive performance. We used structural magnetic resonance imaging (MRI) to identify areas with cortical thinning, resting-state fMRI to identify functional organization in parallel to cortical development, and working memory/response inhibition tasks to assess executive functioning. We found that neuroanatomical changes in the form of cortical thinning spread over bilateral frontal, parietal, and occipital regions. These regions were engaged in 3 functional networks: sensorimotor and auditory, executive control, and default mode network. Furthermore, we found that working memory and response inhibition only associated with regional functional connectivity, but not topological organization (i.e., local and global efficiency of information transfer) of these functional networks. Interestingly, functional connections associated with "bottom-up" as opposed to "top-down" processing were more clearly related to children's performance on working memory and response inhibition, implying an important role for brain systems involved in late childhood.

PMID: 23448875 [PubMed - as supplied by publisher]

Functional connectivity patterns of medial and lateral macaque frontal eye fields reveal distinct visuomotor networks.

J Neurophysiol. 2013 Feb 27;

Authors: Babapoor-Farrokhran S, Hutchison RM, Gati JS, Menon RS, Everling S

Abstract
It has been previously shown that small and large amplitude saccades have different functions during vision in natural environments. Large saccades are associated with reaching movements towards objects, whereas small saccades facilitate the identification of more detailed object features necessary for successful grasping and manual manipulation. To determine whether these represent dichotomous processing streams, we used resting-state fMRI to examine the functional connectivity patterns of the medial and lateral FEF regions that encode large and small amplitude saccades, respectively. We found that the spontaneous BOLD signals of the medial FEF were functionally correlated with areas known to be involved in reaching movements and executive control processes, whereas lateral FEF was functionally correlated with cortical areas involved in object processing and in grasping, fixation, and manipulation of objects. The results provide strong evidence for two distinct visuomotor network systems in the primate brain that likely reflect the alternating phases of vision for action in natural environments.

PMID: 23446697 [PubMed - as supplied by publisher]

Resting-state functional connectivity of ventral parietal regions associated with attention reorienting and episodic recollection.

Front Hum Neurosci. 2013;7:38

Authors: Daselaar SM, Huijbers W, Eklund K, Moscovitch M, Cabeza R

Abstract
In functional neuroimaging studies, ventral parietal cortex (VPC) is recruited by very different cognitive tasks. Explaining the contributions of VPC to these tasks has become a topic of intense study and lively debate. Perception studies frequently find VPC activations during tasks involving attention-reorienting, and memory studies frequently find them during tasks involving episodic recollection. According to the Attention to Memory (AtoM) model, both phenomena can be explained by the same VPC function: bottom-up attention. Yet, a recent functional MRI (fMRI) meta-analysis suggested that attention-reorienting activations are more frequent in anterior VPC, whereas recollection activations are more frequent in posterior VPC. Also, there is evidence that anterior and posterior VPC regions have different functional connectivity patterns. To investigate these issues, we conducted a resting-state functional connectivity analysis using as seeds the center-of-mass of attention-reorienting and recollection activations in the meta-analysis, which were located in the supramarginal gyrus (SMG, around the temporo-parietal junction-TPJ) and in the angular gyrus (AG), respectively. The SMG seed showed stronger connectivity with ventrolateral prefrontal cortex (VLPFC) and occipito-temporal cortex, whereas the AG seed showed stronger connectivity with the hippocampus and default network regions. To investigate whether these connectivity differences were graded or sharp, VLPFC and hippocampal connectivity was measured in VPC regions traversing through the SMG and AG seeds. The results showed a graded pattern: VLPFC connectivity gradually decreases from SMG to AG, whereas hippocampal connectivity gradually increases from SMG to AG. Importantly, both gradients showed an abrupt break when extended beyond VPC borders. This finding suggests that functional differences between SMG and AG are more subtle than previously thought. These connectivity differences can be explained by differences in the input and output to anterior and posterior VPC regions, without the need of postulating markedly different functions. These results are as consistent with integrative accounts of VPC function, such as the AtoM model, as they are with models that ascribe completely different functions to VPC regions.

PMID: 23440005 [PubMed - in process]

Resting-state activity in the left executive control network is associated with behavioral approach and is increased in substance dependence.

Drug Alcohol Depend. 2013 Feb 18;

Authors: Krmpotich TD, Tregellas JR, Thompson LL, Banich MT, Klenk AM, Tanabe JL

Abstract
BACKGROUND: Individuals with drug addictions report increased willingness to approach rewards. Approach behaviors are thought to involve executive control processes and are more strongly represented in the left compared to right prefrontal cortex. A direct link between approach tendencies and left hemisphere activity has not been shown in the resting brain. We hypothesized that compared to controls, substance dependent individuals (SDI) would have greater left hemisphere activity in the left executive control network (ECN) at rest. METHODS: Twenty-five SDI and 25 controls completed a Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) questionnaire and underwent a resting-state fMRI scan. Group independent component analysis was performed. We used template matching to identify the left and right ECN separately and compared the corresponding components across groups. Across group, BAS scores were correlated with signal fluctuations in the left ECN and BIS scores with right ECN. RESULTS: BAS scores were higher in SDI compared to controls (p<.003) and correlated with signal fluctuation in the left ECN. SDI showed significantly more activity than controls in the left prefrontal cortex of the left ECN. Conversely, SDI showed less activity than controls in the right prefrontal cortex of the right ECN. CONCLUSIONS: Results from this study suggest that approach tendencies are related to the left ECN, even during rest. Higher resting-state signal in the left ECN may play a role in heightened approach tendencies that contribute to drug-seeking behavior.

PMID: 23428318 [PubMed - as supplied by publisher]

Network analysis of auditory hallucinations in nonpsychotic individuals.

Hum Brain Mapp. 2013 Feb 21;

Authors: Lutterveld RV, Diederen KM, Otte WM, Sommer IE

Abstract
Background: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia and can severely disrupt behavior and decrease quality of life. Identification of areas with high functional connectivity (so-called hub regions) that are associated with the predisposition to hallucinate may provide potential targets for neuromodulation in the treatment of AVH. Methods: Resting-state fMRI scans during which no hallucinations had occurred were acquired from 29 nonpsychotic individuals with AVH and 29 matched controls. These nonpsychotic individuals with AVH provide the opportunity to study AVH without several confounds associated with schizophrenia, such as antipsychotic medication use and other symptoms related to the illness. Hub regions were identified by assessing weighted connectivity strength and betweenness centrality across groups using a permutation analysis. Results: Nonpsychotic individuals with AVH exhibited increased functioning as hub regions in the temporal cortices and the posterior cingulate/precuneus, which is an important area in the default mode network (DMN), compared to the nonhallucinating controls. In addition, the right inferior temporal gyrus, left paracentral lobule and right amygdala were less important as a hub region in the AVH group. Conclusions: These results suggest that the predisposition to hallucinate may be related to aberrant functioning of the DMN and the auditory cortices. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.

PMID: 23426796 [PubMed - as supplied by publisher]

Largely Typical Patterns of Resting-State Functional Connectivity in High-Functioning Adults with Autism.

Cereb Cortex. 2013 Feb 20;

Authors: Tyszka JM, Kennedy DP, Paul LK, Adolphs R

Abstract
A leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, yet the majority of studies report effects that are either very weak, inconsistent across studies, or explain results incompletely. Here we apply multiple analytical approaches to resting-state BOLD-fMRI data at the whole-brain level. Neurotypical and high-functioning adults with autism displayed very similar patterns and strengths of resting-state connectivity. We found only limited evidence in autism for abnormal resting-state connectivity at the regional level and no evidence for altered connectivity at the whole-brain level. Regional abnormalities in functional connectivity in autism spectrum disorder were primarily in the frontal and temporal cortices. Within these regions, functional connectivity with other brain regions was almost exclusively lower in the autism group. Further examination showed that even small amounts of head motion during scanning have large effects on functional connectivity measures and must be controlled carefully. Consequently, we suggest caution in the interpretation of apparent positive findings until all possible confounding effects can be ruled out. Additionally, we do not rule out the possibility that abnormal connectivity in autism is evident at the microstructural synaptic level, which may not be reflected sensitively in hemodynamic changes measured with BOLD-fMRI.

PMID: 23425893 [PubMed - as supplied by publisher]

Functional network endophenotypes unravel the effects of apolipoprotein e epsilon 4 in middle-aged adults.

PLoS One. 2013;8(2):e55902

Authors: Goveas JS, Xie C, Chen G, Li W, Ward BD, Franczak MB, Jones JL, Antuono PG, Li SJ

Abstract
Apolipoprotein E-ε4 (APOE-ε4) accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN), executive control (ECN) and salience (SN) networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc) in these networks. Resting-state functional connectivity MRI (R-fMRI) was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.

PMID: 23424640 [PubMed - in process]

Donepezil Treatment Stabilizes Functional Connectivity During Resting State and Brain Activity During Memory Encoding in Alzheimer's Disease.

J Clin Psychopharmacol. 2013 Feb 14;

Authors: Solé-Padullés C, Bartrés-Faz D, Lladó A, Bosch B, Peña-Gómez C, Castellví M, Rami L, Bargalló N, Sánchez-Valle R, Molinuevo JL

Abstract
ABSTRACT: Previous studies with functional magnetic resonance imaging (fMRI) demonstrated a differential brain activity and connectivity after treatment with donepezil in Alzheimer disease (AD) when compared to healthy elders. Importantly however, there are no available studies where the placebo or control group included comparable AD patients relative to the treated groups. Fifteen patients recently diagnosed of AD were randomized to treatment (n = 8) or to control group (n = 7); the former receiving daily treatment of donepezil during 3 months. At baseline and follow-up, both groups underwent resting-state as well as task-fMRI examinations, this latter assessing encoding of visual scenes. The treated group showed higher connectivity in areas of the default mode network, namely the right parahippocampal gyrus at follow-up resting-fMRI as compared to the control group. On the other hand, for the task-fMRI, the untreated AD group presented progressive increased activation in the left middle temporal gyrus and bilateral precuneus at the 3-month examination compared to baseline, whereas the treated group exhibited stable patterns of brain activity. Donepezil treatment is associated with stabilization of connectivity of medial temporal regions during resting state and of brain efficiency during a cognitive demand, on the whole reducing progressive dysfunctional reorganizations observed during the natural course of the disease.

PMID: 23422370 [PubMed - as supplied by publisher]

A blind deconvolution approach to recover effective connectivity brain networks from resting state fMRI data.

Med Image Anal. 2013 Jan 29;

Authors: Wu GR, Liao W, Stramaglia S, Ding JR, Chen H, Marinazzo D

Abstract
A great improvement to the insight on brain function that we can get from fMRI data can come from effective connectivity analysis, in which the flow of information between even remote brain regions is inferred by the parameters of a predictive dynamical model. As opposed to biologically inspired models, some techniques as Granger causality (GC) are purely data-driven and rely on statistical prediction and temporal precedence. While powerful and widely applicable, this approach could suffer from two main limitations when applied to BOLD fMRI data: confounding effect of hemodynamic response function (HRF) and conditioning to a large number of variables in presence of short time series. For task-related fMRI, neural population dynamics can be captured by modeling signal dynamics with explicit exogenous inputs; for resting-state fMRI on the other hand, the absence of explicit inputs makes this task more difficult, unless relying on some specific prior physiological hypothesis. In order to overcome these issues and to allow a more general approach, here we present a simple and novel blind-deconvolution technique for BOLD-fMRI signal. In a recent study it has been proposed that relevant information in resting-state fMRI can be obtained by inspecting the discrete events resulting in relatively large amplitude BOLD signal peaks. Following this idea, we consider resting fMRI as 'spontaneous event-related', we individuate point processes corresponding to signal fluctuations with a given signature, extract a region-specific HRF and use it in deconvolution, after following an alignment procedure. Coming to the second limitation, a fully multivariate conditioning with short and noisy data leads to computational problems due to overfitting. Furthermore, conceptual issues arise in presence of redundancy. We thus apply partial conditioning to a limited subset of variables in the framework of information theory, as recently proposed. Mixing these two improvements we compare the differences between BOLD and deconvolved BOLD level effective networks and draw some conclusions.

PMID: 23422254 [PubMed - as supplied by publisher]

Abnormal function of the posterior cingulate cortex in heroin addicted users during resting-state and drug-cue stimulation task.

Chin Med J (Engl). 2013 Feb;126(4):734-9

Authors: Li Q, Yang WC, Wang YR, Huang YF, Li W, Zhu J, Zhang Y, Zhao LY, Qin W, Yuan K, von Deneen KM, Wang W, Tian J

Abstract
BACKGROUND: Previous animal and neuroimaging studies have demonstrated that brain function in heroin addicted users is impaired. However, the posterior cingulate cortex (PCC) has not received much attention. The purpose of this study was to investigate whether chronic heroin use is associated with craving-related changes in the functional connectivity of the PCC of heroin addicted users.
METHODS: Fourteen male adult chronic heroin users and fifteen age and gender-matched healthy subjects participated in the present study. The participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and a cue-induced craving task fMRI scan. The activated PCC was identified in the cue-induced craving task by means of a group contrast test. Functional connectivity was analyzed based on resting-state fMRI data in order to determine the correlation between brain regions. The relationship between the connectivity of specific regions and heroin dependence was investigated.
RESULTS: The activation of PCC, bilateral anterior cingulate cortex, caudate, putamen, precuneus, and thalamus was significant in the heroin group compared to the healthy group in the cue-induced craving task. The detectable functional connectivity of the heroin users was stronger between the PCC and bilateral insula, bilateral dorsal striatum, right inferior parietal lobule (IPL) and right supramarginal gyrus (P < 0.001) compared to that of the healthy subjects in the resting-state data analysis. The strength of the functional connectivity, both for the PCC-insula (r = 0.60, P < 0.05) and for PCC-striatum (r = 0.58, P < 0.05), was positively correlated with the duration of heroin use.
CONCLUSION: The altered functional connectivity patterns in the PCC-insula and PCC-striatum areas may be regarded as biomarkers of brain damage severity in chronic heroin users.

PMID: 23422198 [PubMed - in process]

Functional connectivity-based parcellation of amygdala using self-organized mapping : A data driven approach.

Hum Brain Mapp. 2013 Feb 18;

Authors: Mishra A, Rogers BP, Chen LM, Gore JC

Abstract
The overall goal of this work is to demonstrate how resting state functional magnetic resonance imaging (fMRI) signals may be used to objectively parcellate functionally heterogeneous subregions of the human amygdala into structures characterized by similar patterns of functional connectivity. We hypothesize that similarity of functional connectivity of subregions with other parts of the brain can be a potential basis to segment and cluster voxels using data driven approaches. In this work, self-organizing map (SOM) was implemented to cluster the connectivity maps associated with each voxel of the human amygdala, thereby defining distinct subregions. The functional separation was optimized by evaluating the overall differences in functional connectivity between the subregions at group level. Analysis of 25 resting state fMRI data sets suggests that SOM can successfully identify functionally independent nuclei based on differences in their inter subregional functional connectivity, evaluated statistically at various confidence levels. Although amygdala contains several nuclei whose distinct roles are implicated in various functions, our objective approach discerns at least two functionally distinct volumes comparable to previous parcellation results obtained using probabilistic tractography and cytoarchitectonic analysis. Association of these nuclei with various known functions and a quantitative evaluation of their differences in overall functional connectivity with lateral orbital frontal cortex and temporal pole confirms the functional diversity of amygdala. The data driven approach adopted here may be used as a powerful indicator of structure-function relationships in the amygdala and other functionally heterogeneous structures as well. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.

PMID: 23418140 [PubMed - as supplied by publisher]

An independent components and functional connectivity analysis of resting state fMRI data points to neural network dysregulation in adult ADHD.

Hum Brain Mapp. 2013 Feb 18;

Authors: Hoekzema E, Carmona S, Ramos-Quiroga JA, Richarte Fernández V, Bosch R, Soliva JC, Rovira M, Bulbena A, Tobeña A, Casas M, Vilarroya O

Abstract
Spontaneous fluctuations can be measured in the brain that reflect dissociable functional networks oscillating at synchronized frequencies, such as the default mode network (DMN). In contrast to its diametrically opposed task-positive counterpart, the DMN predominantly signals during a state of rest, and inappropriate regulation of this network has been associated with inattention, a core characteristic of attention-deficit/hyperactivity disorder (ADHD). To examine whether abnormalities can be identified in the DMN component of patients with ADHD, we applied an independent components analysis to resting state functional magnetic resonance imaging data acquired from 22 male medication-naïve adults with ADHD and 23 neurotypical individuals. We observed a stronger coherence of the left dorsolateral prefrontal cortex (dlPFC) with the DMN component in patients with ADHD which correlated with measures of selective attention. The increased left dlPFC-DMN coherence also surfaced in a whole-brain replication analysis involving an independent sample of 9 medication-naïve adult patients and 9 controls. In addition, a post hoc seed-to-voxel functional connectivity analysis using the dlPFC as a seed region to further examine this region's suggested connectivity differences uncovered a higher temporal coherence with various other neural networks and confirmed a reduced anticorrelation with the DMN. These results point to a more diffuse connectivity between functional networks in patients with ADHD. Moreover, our findings suggest that state-inappropriate neural activity in ADHD is not confined to DMN intrusion during attention-demanding contexts, but also surfaces as an insufficient suppression of dlPFC signaling in relation to DMN activity during rest. Together with previous findings, these results point to a general dysfunction in the orthogonality of functional networks. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.

PMID: 23417778 [PubMed - as supplied by publisher]

Functional reorganization associated with outcome in hand function after stroke revealed by regional homogeneity.

Neuroradiology. 2013 Feb 16;

Authors: Yin D, Luo Y, Song F, Xu D, Peterson BS, Sun L, Men W, Yan X, Fan M

Abstract
INTRODUCTION: Previous studies of task-based functional neuroimaging have shown that various patterns of functional reorganization underlie motor recovery following stroke. However, the mechanisms underlying functional reorganization that contribute to outcome differences in hand function after stroke have not been completely characterized. We, for the first time, investigate subgroups of stroke patients with different outcomes in hand function using a resting-state fMRI approach. METHODS: We selected 24 patients with subcortical stroke and divided them into two subgroups: completely paralyzed hands (CPH, 12 patients) and partially paralyzed hands (PPH, 12 patients). Twenty-four healthy controls (HCs) matched for age and handedness were also recruited. We used regional homogeneity (ReHo) method to map regional spontaneous activity across the whole brain and performed a two-sample t test between each pair of the three diagnostic groups. RESULTS: Compared to HCs, we found increased ReHo in the ipsilesional hemisphere in PPH and, conversely, increased ReHo in the contralesional hemisphere in CPH. Moreover, we detected decreased ReHo in the ipsilesional primary sensorimotor cortex and superior temporal gyrus, in addition to increased ReHo in the contralesional premotor cortex and ipsilesional medial frontal gyrus in CPH compared to PPH. Additionally, the ReHo index of these regions significantly correlated with the Fugl-Meyer assessment scores (hand + wrist) across all stroke patients. CONCLUSIONS: Our study offers a new insight into relationships between functional reorganization and outcomes in hand function after subcortical stroke, and the ReHo method can provide an effective tool for evaluating the efficiency of rehabilitative therapies following stroke.

PMID: 23417103 [PubMed - as supplied by publisher]

Cortical signatures of dyslexia and remediation: an intrinsic functional connectivity approach.

PLoS One. 2013;8(2):e55454

Authors: Koyama MS, Di Martino A, Kelly C, Jutagir DR, Sunshine J, Schwartz SJ, Castellanos FX, Milham MP

Abstract
This observational, cross-sectional study investigates cortical signatures of developmental dyslexia, particularly from the perspective of behavioral remediation. We employed resting-state fMRI, and compared intrinsic functional connectivity (iFC) patterns of known reading regions (seeds) among three dyslexia groups characterized by (a) no remediation (current reading and spelling deficits), (b) partial remediation (only reading deficit remediated), and (c) full remediation (both reading and spelling deficits remediated), and a group of age- and IQ-matched typically developing children (TDC) (total N = 44, age range = 7-15 years). We observed significant group differences in iFC of two seeds located in the left posterior reading network - left intraparietal sulcus (L.IPS) and left fusiform gyrus (L.FFG). Specifically, iFC between L.IPS and left middle frontal gyrus was significantly weaker in all dyslexia groups, irrespective of remediation status/literacy competence, suggesting that persistent dysfunction in the fronto-parietal attention network characterizes dyslexia. Additionally, relative to both TDC and the no remediation group, the remediation groups exhibited stronger iFC between L.FFG and right middle occipital gyrus (R.MOG). The full remediation group also exhibited stronger negative iFC between the same L.FFG seed and right medial prefrontal cortex (R.MPFC), a core region of the default network These results suggest that behavioral remediation may be associated with compensatory changes anchored in L.FFG, which reflect atypically stronger coupling between posterior visual regions (L.FFG-R.MOG) and greater functional segregation between task-positive and task-negative regions (L.FFG-R.MPFC). These findings were bolstered by significant relationships between the strength of the identified functional connections and literacy scores. We conclude that examining iFC can reveal cortical signatures of dyslexia with particular promise for monitoring neural changes associated with behavioral remediation.

PMID: 23408984 [PubMed - in process]