Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD ...is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms.
Pain can be elicited through all mammalian sensory pathways yet cross-modal sensory integration, and its relationship to clinical pain, is largely unexplored. Centralized chronic pain conditions such ...as fibromyalgia are often associated with symptoms of multisensory hypersensitivity. In this study, female patients with fibromyalgia demonstrated cross-modal hypersensitivity to visual and pressure stimuli compared with age- and sex-matched healthy controls. Functional magnetic resonance imaging revealed that insular activity evoked by an aversive level of visual stimulation was associated with the intensity of fibromyalgia pain. Moreover, attenuation of this insular activity by the analgesic pregabalin was accompanied by concomitant reductions in clinical pain. A multivariate classification method using support vector machines (SVM) applied to visual-evoked brain activity distinguished patients with fibromyalgia from healthy controls with 82% accuracy. A separate SVM classification of treatment effects on visual-evoked activity reliably identified when patients were administered pregabalin as compared with placebo. Both SVM analyses identified significant weights within the insular cortex during aversive visual stimulation. These data suggest that abnormal integration of multisensory and pain pathways within the insula may represent a pathophysiological mechanism in some chronic pain conditions and that insular response to aversive visual stimulation may have utility as a marker for analgesic drug development.
Socioeconomic disadvantage during childhood is associated with a myriad of negative adult outcomes. One mechanism through which disadvantage undermines positive outcomes may be by disrupting the ...development of self-control. The goal of the present study was to examine pathways from three key indicators of socioeconomic disadvantage – low family income, low maternal education, and neighborhood poverty – to neural and behavioral measures of response inhibition. We utilized data from a representative cohort of 215 twins (ages 7–18 years, 70% male) oversampled for exposure to disadvantage, who participated in the Michigan Twins Neurogenetics Study (MTwiNS), a study within the Michigan State University Twin Registry (MSUTR). Our child-friendly Go/No-Go task activated the bilateral inferior frontal gyrus (IFG), and activation during this task predicted behavioral inhibition performance, extending prior work on adults to youth. Critically, we also found that neighborhood poverty, assessed via geocoding, but not family income or maternal education, was associated with IFG activation, a finding that we replicated in an independent sample of disadvantaged youth. Further, we found that neighborhood poverty predicted response inhibition performance via its effect on IFG activation. These results provide the first mechanistic evidence that disadvantaged contexts may undermine self-control via their effect on the brain. The broader neighborhood, beyond familial contexts, may be critically important for this association, suggesting that contexts beyond the home have profound effects on the developing brain and behaviors critical for future health, wealth, and wellbeing.
•The mechanisms linking socioeconomic disadvantage to poor life outcomes are unclear.•We found neighborhood poverty to be correlated with behavioral response inhibition.•Neighborhood poverty, not income or education, uniquely predicted IFG activity.•IFG activity mediated neighborhood poverty-response inhibition associations.•Where youth live may be critically important to their brain development.
Objective
There is increasing demand for prediction of chronic pain treatment outcomes using machine‐learning models, in order to improve suboptimal pain management. In this exploratory study, we ...used baseline brain functional connectivity patterns from chronic pain patients with fibromyalgia (FM) to predict whether a patient would respond differentially to either milnacipran or pregabalin, 2 drugs approved by the US Food and Drug Administration for the treatment of FM.
Methods
FM patients participated in 2 separate double‐blind, placebo‐controlled crossover studies, one evaluating milnacipran (n = 15) and one evaluating pregabalin (n = 13). Functional magnetic resonance imaging during rest was performed before treatment to measure intrinsic functional brain connectivity in several brain regions involved in pain processing. A support vector machine algorithm was used to classify FM patients as responders, defined as those with a ≥20% improvement in clinical pain, to either milnacipran or pregabalin.
Results
Connectivity patterns involving the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) individually classified pregabalin responders versus milnacipran responders with 77% accuracy. Performance of this classification improved when both PCC and DLPFC connectivity patterns were combined, resulting in a 92% classification accuracy. These results were not related to confounding factors, including head motion, scanner sequence, or hardware status. Connectivity patterns failed to differentiate drug nonresponders across the 2 studies.
Conclusion
Our findings indicate that brain functional connectivity patterns used in a machine‐learning framework differentially predict clinical response to pregabalin and milnacipran in patients with chronic pain. These findings highlight the promise of machine learning in pain prognosis and treatment prediction.
Abstract Autism spectrum disorders (ASD) are associated with disturbances of neural connectivity. Functional connectivity between neural structures is typically examined within the context of a ...cognitive task, but also exists in the absence of a task (i.e., “rest”). Connectivity during rest is particularly active in a set of structures called the default network, which includes the posterior cingulate cortex (PCC), retrosplenial cortex, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus. We previously reported that adults with ASD relative to controls show areas of stronger and weaker connectivity within the default network. The objective of the present study was to examine the default network in adolescents with ASD. Sixteen adolescents with ASD and 15 controls participated in a functional MRI study. Functional connectivity was examined between a PCC seed and other areas of the default network. Both groups showed connectivity in the default network. Relative to controls, adolescents with ASD showed widespread weaker connectivity in nine of the eleven areas of the default network. Moreover, an analysis of symptom severity indicated that poorer social skills and increases in restricted and repetitive behaviors and interests correlated with weaker connectivity, whereas poorer verbal and non-verbal communication correlated with stronger connectivity in multiple areas of the default network. These findings indicate that adolescents with ASD show weaker connectivity in the default network than previously reported in adults with ASD. The findings also show that weaker connectivity within the default network is associated with specific impairments in ASD.
Healthy aging is marked by declines in a variety of cognitive and motor abilities. A better understanding of the aging brain may aid in elucidating the neural substrates of these behavioral effects. ...Investigations of resting state functional brain connectivity have provided insights into pathology, and to some degree, healthy aging. Given the role of the cerebellum in both motor and cognitive behaviors, as well as its known volumetric declines with age, investigating cerebellar networks may shed light on the neural bases of age-related functional declines. We mapped the resting state networks of the lobules of the right hemisphere and the vermis of the cerebellum in a group of healthy older adults and compared them to those of young adults. We report disrupted cortico-cerebellar resting state network connectivity in older adults. These results remain even when controlling for cerebellar volume, signal-to-noise ratio, and signal-to-fluctuation noise ratio. Specifically, there was consistent disruption of cerebellar connectivity with both the striatum and the medial temporal lobe. Associations between connectivity strength and both sensorimotor and cognitive task performances indicate that cerebellar engagement with the default mode network and striatal pathways is associated with better performance for older adults. These results extend our understanding of the resting state networks of the aging brain to include cortico-cerebellar networks, and indicate that age differences in network connectivity strength are important for behavior.
•We investigated age differences in resting state cortico-cerebellar networks.•Older adults showed widespread decreases in cortico-cerebellar connectivity.•Cerebellar connectivity with the basal ganglia and medial temporal lobe is impacted.•Cerebellar connectivity relates to motor and cognitive behavior in older adults.
The cerebellum plays a role in a wide variety of complex behaviors. In order to better understand the role of the cerebellum in human behavior, it is important to know how this structure interacts ...with cortical and other subcortical regions of the brain. To date, several studies have investigated the cerebellum using resting-state functional connectivity magnetic resonance imaging (fcMRI; Krienen and Buckner, 2009; O'Reilly et al., 2010; Buckner et al., 2011). However, none of this work has taken an anatomically-driven lobular approach. Furthermore, though detailed maps of cerebral cortex and cerebellum networks have been proposed using different network solutions based on the cerebral cortex (Buckner et al., 2011), it remains unknown whether or not an anatomical lobular breakdown best encompasses the networks of the cerebellum. Here, we used fcMRI to create an anatomically-driven connectivity atlas of the cerebellar lobules. Timecourses were extracted from the lobules of the right hemisphere and vermis. We found distinct networks for the individual lobules with a clear division into "motor" and "non-motor" regions. We also used a self-organizing map (SOM) algorithm to parcellate the cerebellum. This allowed us to investigate redundancy and independence of the anatomically identified cerebellar networks. We found that while anatomical boundaries in the anterior cerebellum provide functional subdivisions of a larger motor grouping defined using our SOM algorithm, in the posterior cerebellum, the lobules were made up of sub-regions associated with distinct functional networks. Together, our results indicate that the lobular boundaries of the human cerebellum are not necessarily indicative of functional boundaries, though anatomical divisions can be useful. Additionally, driving the analyses from the cerebellum is key to determining the complete picture of functional connectivity within the structure.
Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ...ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults showed greater recruitment of the WM network than younger adults across all loads, with decline at the highest load. Ten days of adaptive training on a verbal WM task improved performance and led to greater brain responsiveness at higher loads for both groups. For older adults the activation peak shifted rightward towards higher loads. Finally, training increased task-related functional connectivity in older adults, both within the WM network and between this task-positive network and the task-negative/default-mode network. These results provide new evidence for functional plasticity with training in older adults and identify a potential signature of improvement at the neural level.
•Brain activity increases with working memory load before reaching an apparent ceiling.•Older adults show greater brain activity and reach ceiling faster than younger adults.•Training increases the range of brain activity across memory loads regardless of age.•Training shifts the activation peak rightward toward higher loads in older adults.•Results identify a potential signature of improvement at the neural level.
Aging is typically associated with declines in sensorimotor performance. Previous studies have linked some age-related behavioral declines to reductions in network segregation. For example, compared ...to young adults, older adults typically exhibit weaker functional connectivity within the same functional network but stronger functional connectivity between different networks. Based on previous animal studies, we hypothesized that such reductions of network segregation are linked to age-related reductions in the brain's major inhibitory transmitter, gamma aminobutyric acid (GABA). To investigate this hypothesis, we conducted graph theoretical analyses of resting state functional MRI data to measure sensorimotor network segregation in both young and old adults. We also used magnetic resonance spectroscopy to measure GABA levels in the sensorimotor cortex and collected a battery of sensorimotor behavioral measures. We report four main findings. First, relative to young adults, old adults exhibit both less segregated sensorimotor brain networks and reduced sensorimotor GABA levels. Second, less segregated networks are associated with lower GABA levels. Third, less segregated networks and lower GABA levels are associated with worse sensorimotor performance. Fourth, network segregation mediates the relationship between GABA and performance. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. More broadly, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks.
•Older age is associated with reduced segregation in the sensorimotor network and reduced GABA levels in sensorimotor cortex.•Reduced segregation in the sensorimotor network is associated with lower sensorimotor GABA levels.•Individual differences in sensorimotor GABA levels correlate with sensorimotor performance.•This relationship between sensorimotor GABA and sensorimotor behavior is mediated by sensorimotor network segregation.
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