Resting-state Functional Connectivity Magnetic Resonance Imaging Research Articles

Neuroimaging in Frontotemporal Lobar Degeneration: Research and Clinical Utility.

Frontotemporal lobar dementia (FTLD) is a clinically and pathologically complex disease. Advances in neuroimaging techniques have provided a specialized set of tools to investigate underlying pathophysiology and identify clinical biomarkers that aid in diagnosis, prognostication, monitoring, and identification of appropriate endpoints in clinical trials. In this chapter, we review data discussing the utility of neuroimaging biomarkers in sporadic FTLD, with an emphasis on current and future clinical applications. Among those modalities readily utilized in clinical settings, T1-weighted structural magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) are best supported in differential diagnosis and as targets for clinical trial endpoints. However, a number of nonclinical neuroimaging modalities, including diffusion tensor imaging and resting-state functional connectivity MRI, show promise as biomarkers to predict progression and as clinical trial endpoints. Other neuroimaging modalities, including amyloid PET, Tau PET, and arterial spin labeling MRI, are also discussed, though more work is required to establish their utility in FTLD in clinical settings.

Correction of respiratory artifacts in MRI head motion estimates

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison ‘single-shot’ datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with functional MRI quality reductions. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects from motion estimates. Subsequently, we demonstrate that utilizing a band-stop filter improves post-processing fMRI data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package.

Cortico-thalamic dysconnection in early-stage schizophrenia: a functional connectivity magnetic resonance imaging study.

Studies have indicated thalamus-related network dysfunction in schizophrenia and psychotic disorders. However, whether thalamus-related functional connectivity (FC) contributes to the psychopathology and cognitive deficits of early-stage schizophrenia requires further investigation. A total of 34 patients with early-stage schizophrenia (illness duration = 1.62 ± 1.16 years; age = 26.00 ± 6.34years) and 34 age- and sex-matched healthy controls were enrolled in our study and underwent comprehensive assessments of the clinical symptoms of schizophrenia, working memory tasks, and resting-state FC magnetic resonance imaging. The patients with early-stage schizophrenia had increased FC of the thalamus with the bilateral postcentral and temporal gyri, inferior occipital cortex, and temporal pole and decreased FC of the thalamus with the vestibulocerebellum and frontal pole compared with the controls. Furthermore, increased FC between the thalamus and temporal pole was positively correlated with positive scores of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and negatively correlated with performance on working memory tasks in early-stage schizophrenia. Increased FC of the thalamus with the inferior occipital cortex was positively associated with negative PANSS scores and negatively correlated with Personal and Social Performance Scale scores in early-stage schizophrenia. Our results supported the vital role of thalamus-related network dysfunction in the psychopathology and cognitive deficits of early-stage schizophrenia.

Differences in interregional brain connectivity in children with unilateral hearing loss.

To identify functional network architecture differences in the brains of children with unilateral hearing loss (UHL) using resting-state functional-connectivity magnetic resonance imaging (rs-fcMRI). Prospective observational study. Children (7 to 17 years of age) with severe to profound hearing loss in one ear, along with their normal hearing (NH) siblings, were recruited and imaged using rs-fcMRI. Eleven children had right UHL; nine had left UHL; and 13 had normal hearing. Forty-one brain regions of interest culled from established brain networks such as the default mode (DMN); cingulo-opercular (CON); and frontoparietal networks (FPN); as well as regions for language, phonological, and visual processing, were analyzed using regionwise correlations and conjunction analysis to determine differences in functional connectivity between the UHL and normal hearing children. When compared to the NH group, children with UHL showed increased connectivity patterns between multiple networks, such as between the CON and visual processing centers. However, there were decreased, as well as aberrant connectivity patterns with the coactivation of the DMN and FPN, a relationship that usually is negatively correlated. Children with UHL demonstrate multiple functional connectivity differences between brain networks involved with executive function, cognition, and language comprehension that may represent adaptive as well as maladaptive changes. These findings suggest that possible interventions or habilitation, beyond amplification, might be able to affect some children's requirement for additional help at school. 3b. Laryngoscope, 127:2636-2645, 2017.

Effects of mindfulness based stress reduction therapy on subjective bother and neural connectivity in chronic tinnitus.

To evaluate the impact of a Mindfulness Based Stress Reduction (MBSR) program in patients with chronic bothersome tinnitus on the (1) severity of symptoms of tinnitus and (2) functional connectivity in neural attention networks. Open-label interventional pilot study. Outpatient academic medical center. A total of 13 adult participants with a median age of 55 years, suffering from bothersome tinnitus. An 8-week MBSR program was conducted by a trained MBSR instructor. The primary outcome measure was the difference in patient-reported tinnitus symptoms using the Tinnitus Handicap Index (THI) and Tinnitus Functional Index (TFI) between pre-intervention, post-MBSR, and 4-week post-MBSR assessments. Secondary outcomes included change in measurements of depression, anxiety, mindfulness, and cognitive abilities. Functional connectivity magnetic resonance imaging (MRI) was performed at pre- and post-MBSR intervention time points to serve as a neuroimaging biomarker of critical cortical networks. Scores on the THI and TFI showed statistically significant and clinically meaningful improvement over the course of the study with a median ΔTHI of -16 and median ΔTFI of -14.8 between baseline and 4-week follow-up scores. Except for depression, there was no significant change in any of the secondary outcome measures. Analysis of the resting state functional connectivity MRI (rs-fcMRI) data showed increased connectivity in the post-MBSR group in attention networks but not the default network. Participation in an MBSR program is associated with decreased severity in tinnitus symptoms and depression and connectivity changes in neural attention networks. MBSR is a promising treatment option for chronic bothersome tinnitus that is both noninvasive and inexpensive.

Functional connectivity constrains the category-related organization of human ventral occipitotemporal cortex.

One of the most robust and oft-replicated findings in cognitive neuroscience is that several spatially distinct, functionally dissociable ventral occipitotemporal cortex (VOTC) regions respond preferentially to different categories of concrete entities. However, the determinants of this category-related organization remain to be fully determined. One recent proposal is that privileged connectivity of these VOTC regions with other regions that store and/or process category-relevant properties may be a major contributing factor. To test this hypothesis, we used a multicategory functional magnetic resonance imaging (MRI) localizer to individually define category-related brain regions of interest (ROIs) in a large group of subjects (n = 33). We then used these ROIs in resting-state functional connectivity MRI analyses to explore spontaneous functional connectivity among these regions. We demonstrate that during rest, distinct category-preferential VOTC regions show differentially stronger functional connectivity with other regions that have congruent category-preference, as defined by the functional localizer. Importantly, a "tool"-preferential region in the left medial fusiform gyrus showed differentially stronger functional connectivity with other left lateralized cortical regions associated with perceiving and knowing about common tools-posterior middle temporal gyrus (involved in perception of nonbiological motion), lateral parietal cortex (critical for reaching, grasping, manipulating), and ventral premotor cortex (involved in storing/executing motor programs)-relative to other category-related regions in VOTC of both the right and left hemisphere. Our findings support the claim that privileged connectivity with other cortical regions that store and/or process category-relevant properties constrains the category-related organization of VOTC.

Functional Imaging of the Developing Brain at the Bedside Using Diffuse Optical Tomography.

While histological studies and conventional magnetic resonance imaging (MRI) investigations have elucidated the trajectory of structural changes in the developing brain, less is known regarding early functional cerebral development. Recent investigations have demonstrated that resting-state functional connectivity MRI (fcMRI) can identify networks of functional cerebral connections in infants. However, technical and logistical challenges frequently limit the ability to perform MRI scans early or repeatedly in neonates, particularly in those at greatest risk for adverse neurodevelopmental outcomes. High-density diffuse optical tomography (HD-DOT), a portable imaging modality, potentially enables early continuous and quantitative monitoring of brain function in infants. We introduce an HD-DOT imaging system that combines advancements in cap design, ergonomics, and data analysis methods to allow bedside mapping of functional brain development in infants. In a cohort of healthy, full-term neonates scanned within the first days of life, HD-DOT results demonstrate strong congruence with those obtained using co-registered, subject-matched fcMRI and reflect patterns of typical brain development. These findings represent a transformative advance in functional neuroimaging in infants, and introduce HD-DOT as a powerful and practical method for quantitative mapping of early functional brain development in normal and high-risk neonates.

Resting-state functional connectivity MRI reveals active processes central to cognition.

Analysis of spontaneously correlated low-frequency activity fluctuations across the brain using functional magnetic resonance imaging (MRI)-commonly referred to as resting-state functional connectivity (RSFC) MRI-was initially seen as a useful tool for mapping functional-anatomic networks in the living human brain, characterizing brain changes and differences in clinical populations, and studying comparative anatomy across species. However, little was known about the potential relevance of RSFC to cognitive processes. Indeed, there has been considerable controversy and debate as to the utility of studying the resting-state in cognitive neuroscience. However, recent work has shown that RSFC, rather than merely reflecting passive or epiphenomenal activity within underlying functional-anatomic networks, reveals important dynamic processes that play an active role in cognition. RSFC has been associated with individual differences in a number of behavioral and cognitive domains, including perception, language, learning and memory, and the organization of conceptual knowledge. In this article, we review and integrate the latest research demonstrating that RSFC is functionally relevant to human behavior and higher-level cognition, and propose a hypothesis regarding its mechanism of action on functional network dynamics and cognition. We conclude that RSFC MRI will be an invaluable tool for future discovery of the fundamental neurocognitive interactions that underlie cognition. WIREs Cogn Sci 2014, 5:233-245. doi: 10.1002/wcs.1275 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.

Biomarkers and Brain Connectivity

The investigation of Alzheimer disease (AD) with neuroimaging has often focused on 2 different brain regions. Researchers using positron emission tomographic (PET) imaging of glucose metabolism with fludeoxyglucose F 18 described hypometabolism in the lateral temporoparietal cortex and especially the medial parietal cortex encompassing the precuneus and posterior cingulate.1 Investigations using magnetic resonance imaging showed that patients with AD had substantial atrophy in the medial temporal lobes (MTLs), specifically the hippocampus and entorhinal cortex. Considerable work has extended these findings to individuals who may be in early stages of AD as reflected by mild cognitive impairment. Although subsequently it has become clear that involvement of these anatomical areas is not modality specific (that is, medial temporal hypometabolism and medial parietal atrophy are both reported in AD), the pathological relationship of degeneration in these 2 brain regions has been difficult to understand. Imagingbiomarkershave linked these regional changes to pathology, but this has raised more questions. Amyloid PET imaginghasmade it clear that theprecuneusandposterior cingulate are the site of relatively early deposition of β-amyloid (Aβ), thecentralprotein in the AD plaque. About a third of cognitively normal older people have brainAβdeposition, andwhen present, it almost invariably occurs in this region. However, the MTL, at least in early stages, is relatively devoid of Aβ, as seen at postmortem examination and with amyloid PET imaging. Postmortem studies, however, have linked theMTL strongly to the other key pathology of AD, the neurofibrillary tangle,2 reflectingpathological formsof the tau protein. This further establishes a major mystery of AD: how areamyloidpathology in themedial parietal cortexand taupathology in the MTL related? These 2 structures are linked through their participation inaneural systemknownas thedefaultmodenetwork (DMN). Thisnetworkhasbeenstudied invivousing resting-state functional connectivitymagnetic resonance imaging. By examiningthespontaneoussynchronyof thefunctionalmagnetic resonance imaging signal, functional network connections are detectedat rest thatparallel brainnetworks that areactiveduring specific types of cognitive tasks. The DMN is a tasknegative network that is deactivatedduring externally driven cognition but becomes active during introspective processes such as future planning and memory recall. It is also of particular interest because it becomes disconnected in patients withADand in cognitively normal older peoplewhohave evidence of brain Aβ on amyloid PET imaging. Thus, probing the functional connectivity of the DMN can provide insight into relationships between2major nodesof this network, theMTL andmedial parietal cortex. Wang et al3 examined changes in the DMN in 207 cognitively normal older people who had cerebrospinal fluid obtained for themeasurement of Aβ42 andphosphorylated tau. Lower levels of CSFAβ42 arewidely reported to parallel brain deposition of Aβ seenwith PET. Thus, it is not surprising that lower CSF Aβ42 in this study was associated with disconnection of the DMN since previous PET studies revealed similar findings. Within this network, however, Aβ42 affected connectivitybetween theposterior cingulate cortex (PCC) and the MTLmore thanconnectionsbetween thePCCandothernodes of the network. Biomarkers of tau are largely thought to indicate a stage later in the pathological progression of AD than Aβbecause theyare regardedas indicativeofAβ-initiatedneurodegeneration. In this study,phosphorylated taualso showed a relationshipwith connectivity such that higher levels of CSF phosphorylated tau were associated with PCC and MTL disconnection. In thesedata, the findings foreachbiomarkerwere present while controlling for the other, and the effects were not explained by age or atrophy of the relevant brain regions. Thiswork thusextendspreviousdataby showingnetworkdisconnection in asymptomatic individuals in a particularly important pathway and showing that this effect is seen for biomarkers reflecting both amyloid and neurodegenerative processes. It also provides hints about how these 2 pathological processes and anatomical regions might be related. Fromaclinical perspective, the results suggest that a relatively simple magnetic resonance imaging measure might be a reasonablebiomarker for earlyAD.Thecaveats, however, are substantial. Forexample, technical factors inassessing restingstate networks are crucial: small amounts of headmotion can produce artifacts that are difficult to detect, there are multiple approaches todata analysis, and reliability over timeand across centers has not been extensively established. Furthermore, validating this approach as a biomarker requires much stronger links todiseasephenotypes that include theprogression to AD dementia. Nevertheless, the appeal of this technique is that it can be performed on available clinical instruments, requires no particular cognitive task, and can be obtained in a fewminutes. Targeting 2brain regions for analysis—the PCC and the MTL—could be a simple and widely applicabledata-analytic approach to trackearlydisease if thedifficult technical issues, predictive value, sensitivity, and specificity can be worked out. Regardless of the clinical utility, the data presented by Wang et al3 show that changes in 2 different biomarkers reflectingdifferent aspects ofADpathological progressionaffect Related article page 1242 Opinion

Exploring Functional Connectivity Networks with Multichannel Brain Array Coils

The use of multichannel array head coils in functional and structural magnetic resonance imaging (MRI) provides increased signal-to-noise ratio (SNR), higher sensitivity, and parallel imaging capabilities. However, their benefits remain to be systematically explored in the context of resting-state functional connectivity MRI (fcMRI). In this study, we compare signal detectability within and between commercially available multichannel brain coils, a 32-Channel (32Ch), and a 12-Channel (12Ch) at 3T, in a high-resolution regime to accurately map resting-state networks. We investigate whether the 32Ch coil can extract and map fcMRI more efficiently and robustly than the 12Ch coil using seed-based and graph-theory-based analyses. Our findings demonstrate that although the 12Ch coil can be used to reveal resting-state connectivity maps, the 32Ch coil provides increased detailed functional connectivity maps (using seed-based analysis) as well as increased global and local efficiency, and cost (using graph-theory-based analysis), in a number of widely reported resting-state networks. The exploration of subcortical networks, which are scarcely reported due to limitations in spatial-resolution and coil sensitivity, also proved beneficial with the 32Ch coil. Further, comparisons regarding the data acquisition time required to successfully map these networks indicated that scan time can be significantly reduced by 50% when a coil with increased number of channels (i.e., 32Ch) is used. Switching to multichannel arrays in resting-state fcMRI could, therefore, provide both detailed functional connectivity maps and acquisition time reductions, which could further benefit imaging special subject populations, such as patients or pediatrics who have less tolerance in lengthy imaging sessions.

Antidepressants Normalize the Default Mode Network in Patients With Dysthymia

The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain's DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown. To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity. After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011. University research institute. Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex. We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain's DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity. Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain's DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity. The baseline imaging findings are consistent with those found in patients with major depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression.

Distinct neural signatures detected for ADHD subtypes after controlling for micro-movements in resting state functional connectivity MRI data

In recent years, there has been growing enthusiasm that functional magnetic resonance imaging (MRI) could achieve clinical utility for a broad range of neuropsychiatric disorders. However, several barriers remain. For example, the acquisition of large-scale datasets capable of clarifying the marked heterogeneity that exists in psychiatric illnesses will need to be realized. In addition, there continues to be a need for the development of image processing and analysis methods capable of separating signal from artifact. As a prototypical hyperkinetic disorder, and movement-related artifact being a significant confound in functional imaging studies, ADHD offers a unique challenge. As part of the ADHD-200 Global Competition and this special edition of Frontiers, the ADHD-200 Consortium demonstrates the utility of an aggregate dataset pooled across five institutions in addressing these challenges. The work aimed to (1) examine the impact of emerging techniques for controlling for “micro-movements,” and (2) provide novel insights into the neural correlates of ADHD subtypes. Using support vector machine (SVM)-based multivariate pattern analysis (MVPA) we show that functional connectivity patterns in individuals are capable of differentiating the two most prominent ADHD subtypes. The application of graph-theory revealed that the Combined (ADHD-C) and Inattentive (ADHD-I) subtypes demonstrated some overlapping (particularly sensorimotor systems), but unique patterns of atypical connectivity. For ADHD-C, atypical connectivity was prominent in midline default network components, as well as insular cortex; in contrast, the ADHD-I group exhibited atypical patterns within the dlPFC regions and cerebellum. Systematic motion-related artifact was noted, and highlighted the need for stringent motion correction. Findings reported were robust to the specific motion correction strategy employed. These data suggest that resting-state functional connectivity MRI (rs-fcMRI) data can be used to characterize individual patients with ADHD and to identify neural distinctions underlying the clinical heterogeneity of ADHD.

Functional Relevance of Micromodules in the Human Association Cortex Delineated with High-Resolution fMRI

Recent advancement of resting-state functional connectivity magnetic resonance imaging (MRI) has provided a method for drawing boundaries of brain areas. However, it remains to be elucidated how the parcellated areas in the association cortex relate to the spatial extent of the brain activation which ought to reflect a functional unit in the neural network supporting that particular function. To address this issue, in the present study, we first mapped boundaries and 2 adjacent activations in the human inferior frontal cortex, and then examined the spatial relationship between the boundaries and the 2 activations. The boundaries mapped with high-resolution functional magnetic resonance imaging revealed a collection of micromodules, the size of which was approximately only 12 mm on average, much smaller than the Brodmann areas. Each of the 2 activations associated with 2 functions, response inhibition and feedback processing, was smaller in size than the micromodules. By comparing the spatial patterns between the boundaries and the 2 activations, it was revealed that the brain activations were less likely to be located on the boundaries. These results suggest the functional relevance of the areas in the association cortex delineated by the boundary mapping method based on resting-state functional connectivity MRI.

Hemispheric Asymmetry of Visual Scene Processing in the Human Brain: Evidence from Repetition Priming and Intrinsic Activity

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.

Recovery of hippocampal network connectivity correlates with cognitive improvement in mild alzheimer's disease patients treated with donepezil assessed by resting‐state fMRI

To identify the neural correlates of cognitive improvement in mild Alzheimer's disease (AD) subjects following 12 weeks of donepezil treatment. Resting-state functional connectivity magnetic resonance imaging (R-fMRI) was used to measure the hippocampal functional connectivity (HFC) in 14 mild AD and 18 age-matched normal (CN) subjects. AD subjects were scanned at baseline and after donepezil treatment. CN subjects were scanned only at baseline as a reference to identify regions correlated or anticorrelated to the hippocampus. Before each scan, participants underwent cognitive, behavioral, and functional assessments. After donepezil treatment, neural correlates of cognitive improvement measured by Mini-Mental State Examination scores were identified in the left parahippocampus, dorsolateral prefrontal cortex (DLPFC), and inferior frontal gyrus. Improvement in AD Assessment Scale-cognitive subscale scores correlated with the HFC changes in the left DLPFC and middle frontal gyrus. Stronger recovery in the network connectivity was associated with cognitive improvement. R-fMRI may provide novel insights into the brain's responses to AD treatment in clinical pharmacological trials, and also may predict clinical response.

The search for neuroimaging biomarkers of Alzheimer's disease with advanced MRI techniques

The aim of this review is to examine the recent literature on using advanced magnetic resonance imaging (MRI) techniques for finding neuroimaging biomarkers that are sensitive to the detection of risks for Alzheimer's disease (AD). Since structural MRI techniques, such as brain structural volumetry and voxel-based morphometry (VBM), have been widely used for AD studies and extensively reviewed, we will only briefly touch on the topics of volumetry and morphometry. The focus of the current review is about the more recent developments in the search for AD neuroimaging biomarkers with functional MRI (fMRI), resting-state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), arterial spin-labeling (ASL), and magnetic resonance spectroscopy (MRS).