Gray matter volume in women with the BRCA mutation with and without ovarian removal: evidence for increased risk of late-life Alzheimer's disease or dementia.

OBJECTIVE: Ovarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimer's disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counseled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM showing women without the BRCAm had cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and bilateral salpingo-oophorectomy (BSO) noted changes in cognition. METHODS: The present, cross-sectional study examined whole-brain differences in gray matter (GM) volume using high-resolution, quantitative magnetic resonance imaging in women with BRCAm and intact ovaries (BRCA-preBSO [study cohort with BRCA mutation prior to oophorectomy]; n = 9) and after surgery with (BSO + estradiol-based therapy [ERT]; n = 10) and without (BSO; n = 10) postsurgical estradiol hormone therapy compared with age-matched women (age-matched controls; n = 10) with their ovaries. RESULTS: The BRCA-preBSO and BSO groups showed significantly lower GM volume in the left medial temporal and frontal lobe structures. BSO + ERT exhibited few areas of lower GM volume compared with age-matched controls. Novel to this study, we also observed that all three BRCAm groups exhibited significantly higher GM volume compared with age-matched controls, suggesting continued plasticity. CONCLUSIONS: The present study provides evidence, through lower GM volume, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, postsurgical ERT seems to ameliorate GM losses.

Combining exercise with cognitive training and vitamin D3 to improve functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI). Results from the SYNERGIC trial.

Changes in functional brain connectivity (FBC) may indicate how lifestyle modifications can prevent the progression to dementia; FBC identifies areas that are spatially separate but temporally synchronized in their activation and is altered in those with mild cognitive impairment (MCI), a prodromal state between healthy cognitive aging and dementia. Participants with MCI were randomly assigned to one of five study arms. Three times per week for 20-weeks, participants performed 30-min of (control) cognitive training, followed by 60-min of (control) physical exercise. Additionally, a vitamin D3 (10,000 IU/pill) or a placebo capsule was ingested three times per week for 20-weeks. Using the CONN toolbox, we measured FBC change (Post-Pre) across four statistical models that collapsed for and/or included some or all study arms. We conducted Pearson correlations between FBC change and changes in physical and cognitive functioning. Our sample included 120 participants (mean age: 73.89 ± 6.50). Compared to the pure control, physical exercise (model one; p-False Discovery Rate (FDR) < 0.01 & < 0.05) with cognitive training (model two; p-FDR = < 0.001), and all three interventions combined (model four; p-FDR = < 0.01) demonstrated an increase in FBC between regions of the Default-Mode Network (i.e., hippocampus and angular gyrus). After controlling for false discovery rate, there were no significant correlations between change in connectivity and change in cognitive or physical function. Physical exercise alone appears to be as efficacious as combined interventional strategies in altering FBC, but implications for behavioral outcomes remain unclear.

Frailty and functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI): baseline results from the SYNERGIC Trial.

Functional brain connectivity (FBC), or areas that are anatomically separate but temporally synchronized in their activation, represent a sensitive biomarker for monitoring dementia progression. It is unclear whether frailty is associated with FBC in those at higher risk of progression to dementia (e.g., mild cognitive impairment -MCI-) and if sex plays a role. We used baseline data from the SYNERGIC trial, including participants with MCI that received brain MRI. In this cross-sectional analyses (n = 100), we measured frailty using a deficit accumulation frailty index. Using the CONN toolbox, we assessed FBC of networks and regions of interest across the entire connectome. We used Pearson's correlation to investigate the relationship between FBC and frailty index in the full sample and by sex. We also divided the full sample and each sex into tertiles based upon their frailty index score and then assessed between-tertile differences in FBC. The full sample (cluster: size = 291 p-FDR < 0.05) and males (cluster: size = 993 and 451 p-FDR < 0.01) demonstrated that increasing (stronger) connectivity between the right hippocampus and clusters in the temporal gyrus was positively correlated with increasing (worse) frailty. Males also demonstrated between-tertile differences in right hippocampus connectivity to clusters in the lateral occipital cortex (cluster: size = 289 p-FDR < 0.05). Regardless of frailty status, females demonstrated stronger within-network connectivity of the Default-Mode (p = 0.024). Our results suggest that increasing (worse) frailty was associated with increasing (stronger) connectivity between regions not typically linked, which may reflect a compensation tactic by the plastic brain. Furthermore, the relationship between the two variables appears to differ by sex. Our results may help elucidate why specific individuals progress to a dementia syndrome. NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676.

What Executive Function Network is that? An Image-Based Meta-Analysis of Network Labels.

The current state of label conventions used to describe brain networks related to executive functions is highly inconsistent, leading to confusion among researchers regarding network labels. Visually similar networks are referred to by different labels, yet these same labels are used to distinguish networks within studies. We performed a literature review of fMRI studies and identified nine frequently-used labels that are used to describe topographically or functionally similar neural networks: central executive network (CEN), cognitive control network (CCN), dorsal attention network (DAN), executive control network (ECN), executive network (EN), frontoparietal network (FPN), working memory network (WMN), task positive network (TPN), and ventral attention network (VAN). Our aim was to meta-analytically determine consistency of network topography within and across these labels. We hypothesized finding considerable overlap in the spatial topography among the neural networks associated with these labels. An image-based meta-analysis was performed on 158 group-level statistical maps (SPMs) received from authors of 69 papers listed on PubMed. Our results indicated that there was very little consistency in the SPMs labeled with a given network name. We identified four clusters of SPMs representing four spatially distinct executive function networks. We provide recommendations regarding label nomenclature and propose that authors looking to assign labels to executive function networks adopt this template set for labeling networks.

Corrigendum: Altered Brain Microstate Dynamics in Adolescents With Narcolepsy.

[This corrects the article DOI: 10.3389/fnhum.2016.00369.].

Elucidating the putative link between prefrontal neurotransmission, functional connectivity, and affective symptoms in irritable bowel syndrome.

Altered neural mechanisms are well-acknowledged in irritable bowel syndrome (IBS), a disorder of brain-gut-communication highly comorbid with anxiety and depression. As a key hub in corticolimbic inhibition, medial prefrontal cortex (mPFC) may be involved in disturbed emotion regulation in IBS. However, aberrant mPFC excitatory and inhibitory neurotransmission potentially contributing to psychological symptoms in IBS remains unknown. Using quantitative magnetic resonance spectroscopy (qMRS), we compared mPFC glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA+) concentrations in 64 women with IBS and 32 age-matched healthy women (HCs) and investigated their association with anxiety and depression in correlational and subgroup analyses. Applying functional magnetic resonance imaging (fMRI), we explored whether altered neurotransmission was paralleled by aberrant mPFC resting-state functional connectivity (FC). IBS patients did not differ from HCs with respect to mPFC GABA+ or Glx levels. Anxiety was positively associated with mPFC GABA+ concentrations in IBS, whereas Glx was unrelated to psychological or gastrointestinal symptoms. Subgroup comparisons of patients with high or low anxiety symptom severity and HCs revealed increased GABA+ in patients with high symptom severity, and lower mPFC FC with adjacent anterior cingulate cortex (ACC), a crucial region of emotion modulation. Our findings provide novel evidence that altered prefrontal inhibitory neurotransmission may be linked to anxiety in IBS.

A study of neural activity and functional connectivity within the olfactory brain network in Parkinson's disease.

Olfactory dysfunction is an early manifestation of Parkinson's disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort.

Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstrate altered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However, alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changes remain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthy controls [HC]) with respect to aINS glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA+) concentrations and addressed possible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonance spectroscopy of bilateral aINS to assess Glx and GABA+ concentrations. Questionnaire data from all participants and prospective symptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related and psychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P < 0.05, right aINS P < 0.001), whereas no group differences were detected for GABA+ concentrations. Lower right-lateralized Glx concentrations in patients were substantially predicted by longer pain duration, while less frequent use of adaptive pain-coping predicted lower Glx in left aINS. Our findings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results also indicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and of the left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.

Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome.

Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

Olfactory fMRI: Implications of Stimulation Length and Repetition Time.

Studying olfaction with functional magnetic resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA), and by plotting the event-related time course of brain activation in the 4 olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all 4 olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

Evidence for cognitive resource imbalance in adolescents with narcolepsy.

The study investigated brain activity changes during performance of a verbal working memory task in a population of adolescents with narcolepsy. Seventeen narcolepsy patients and twenty healthy controls performed a verbal working memory task during simultaneous fMRI and EEG acquisition. All subjects also underwent MRS to measure GABA and Glutamate concentrations in the medial prefrontal cortex. Activation levels in the default mode network and left middle frontal gyrus were examined to investigate whether narcolepsy is characterized by an imbalance in cognitive resources. Significantly increased deactivation within the default mode network during task performance was observed for the narcolepsy patients for both the encoding and recognition phases of the task. No evidence for task performance deficits or reduced activation within the left middle frontal gyrus was noted for the narcolepsy patients. Correlation analyses between the spectroscopy and fMRI data indicated that deactivation of the anterior aspect of the default mode in narcolepsy patients correlated more with increased concentrations of Glutamate and decreased concentrations of GABA. In contrast, deactivation in the default mode was correlated with increased concentrations of GABA and decreased concentrations of Glutamate in controls. The results suggested that narcolepsy is not characterized by a deficit in working memory but rather an imbalance of cognitive resources in favor of monitoring and maintaining attention over actual task performance. This points towards dysregulation within the sustained attention system being the origin behind self-reported cognitive difficulties in narcolepsy.

Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome.

Increased perception of visceral stimuli is a key feature of Irritable Bowel Syndrome (IBS). While altered resting-state functional connectivity (rsFC) has been also reported in IBS, the relationship between visceral hypersensitivity and aberrant rsFC is unknown. We therefore assessed rsFC within the salience, sensorimotor and default mode networks in patients with and without visceral hypersensitivity and in healthy controls (HCs). An exploratory resting-state functional magnetic resonance imaging study was performed in 41 women with IBS and 20 HCs. Group independent component analysis was used to derive intrinsic brain networks. Rectal thresholds were determined and patients were subdivided into groups with increased (hypersensitive IBS, N = 21) or normal (normosensitive IBS, N = 20) visceral sensitivity. Between-group comparisons of rsFC were carried-out using region-of-interest analyses and peak rsFC values were extracted for correlational analyses. Relative to normosensitive IBS, hypersensitive patients showed increased positive rsFC of pregenual anterior cingulate cortex and thalamus within the salience network and of posterior insula within the sensorimotor network. When compared to both hypersensitive IBS and HCs, normosensitive IBS showed decreased positive rsFC of amygdala and decreased negative rsFC in dorsal anterior insula within the DMN. DMN and sensorimotor network rsFC were associated with rectal perception thresholds, and rsFC in posterior insula was correlated with reported symptom severity in IBS. Our exploratory findings suggest that visceral sensitivity in IBS is related to changes in FC within resting-state networks associated with interoception, salience and sensory processing. These alterations may play an important role in hypervigilance and hyperalgesia in IBS.

Increased fMRI Sensitivity at Equal Data Burden Using Averaged Shifted Echo Acquisition.

There is growing evidence as to the benefits of collecting BOLD fMRI data with increased sampling rates. However, many of the newly developed acquisition techniques developed to collect BOLD data with ultra-short TRs require hardware, software, and non-standard analytic pipelines that may not be accessible to all researchers. We propose to incorporate the method of shifted echo into a standard multi-slice, gradient echo EPI sequence to achieve a higher sampling rate with a TR of <1 s with acceptable spatial resolution. We further propose to incorporate temporal averaging of consecutively acquired EPI volumes to both ameliorate the reduced temporal signal-to-noise inherent in ultra-fast EPI sequences and reduce the data burden. BOLD data were collected from 11 healthy subjects performing a simple, event-related visual-motor task with four different EPI sequences: (1) reference EPI sequence with TR = 1440 ms, (2) shifted echo EPI sequence with TR = 700 ms, (3) shifted echo EPI sequence with every two consecutively acquired EPI volumes averaged and effective TR = 1400 ms, and (4) shifted echo EPI sequence with every four consecutively acquired EPI volumes averaged and effective TR = 2800 ms. Both the temporally averaged sequences exhibited increased temporal signal-to-noise over the shifted echo EPI sequence. The shifted echo sequence with every two EPI volumes averaged also had significantly increased BOLD signal change compared with the other three sequences, while the shifted echo sequence with every four EPI volumes averaged had significantly decreased BOLD signal change compared with the other three sequences. The results indicated that incorporating the method of shifted echo into a standard multi-slice EPI sequence is a viable method for achieving increased sampling rate for collecting event-related BOLD data. Further, consecutively averaging every two consecutively acquired EPI volumes significantly increased the measured BOLD signal change and the subsequently calculated activation map statistics.

Altered Brain Microstate Dynamics in Adolescents with Narcolepsy.

Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13-20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional MRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics.

Relationship between white matter microstructure abnormalities and ADHD symptomatology in adolescents.

The present study sought to evaluate whether white matter microstructure abnormalities observed in a cohort of adolescents with attention-deficit/hyperactivity disorder (ADHD) have specific relationships with either or both Hyperactivity/Impulsivity and Inattentive ADHD symptom domains that would support a dimensional view of ADHD as adopted in the DSM-V. Diffusion tensor imaging (DTI) data were acquired on 22 adolescents diagnosed with ADHD. Multiple regression analyses were performed to determine whether scalar DTI measures in 13 tracts-of-interest demonstrated meaningful associations with Hyperactivity/Impulsivity or Inattentive symptom severity. Fractional anisotropy and radial diffusivity measures of white matter integrity exhibited significant linear relationships with Hyperactivity/Impulsivity and Inattentive symptom severity. However, only radial diffusivity in the right superior longitudinal fasciculus was specifically linked to Inattentive symptom severity and not Hyperactivity/Impulsivity symptom severity. Our results provide preliminary evidence that symptom domains in ADHD are linked to neuroanatomical substrates and confirm the value in examining ADHD from a dimensional perspective.

Hoarding disorder and obsessive-compulsive disorder show different patterns of neural activity during response inhibition.

Although hoarding disorder (HD) has been historically conceptualized as a subtype or dimension of obsessive-compulsive disorder (OCD), preliminary evidence suggests that these two disorders have distinct neural underpinnings. The aim of the present study was to compare the hemodynamic responses of HD patients, OCD patients, and healthy controls (HC) during response inhibition on a high-conflict Go/NoGo task that has previously proved sensitive to OCD. Participants comprised 24 HD patients, 24 OCD patients, and 24 HCs who completed a Go/NoGo task during functional magnetic resonance imaging (fMRI). Although behavioral data showed no difference among the groups in Go/NoGo task performance, significant differences in hemodynamic activity were noted. During correct rejects (successful response inhibition), HD patients showed greater right precentral gyrus activation, whereas OCD patients exhibited greater right orbitofrontal activation, as assessed using a region of interest approach. During errors of commission (response inhibition failures), OCD patients, but not HD patients, were characterized by excessive activity in left and right orbitofrontal gyrus. The present results lend further support to the biological distinction between HD and OCD, and they are consistent with previous research suggesting frontal hypoactivity in HD patients during hoarding-unrelated tasks.

The role of top-down control in different phases of a sensorimotor timing task: a DCM study of adults and adolescents.

The ability to precisely coordinate motor control to regularly-paced sensory stimuli requires an ability often called 'mental timekeeping', a distinct form of cognitive function. A consistent feature among conceptual models of the internal clock mechanism is an element of 'top-down' cognitive control. Although lesion and fMRI studies have provided indirect evidence supporting the role of the prefrontal cortex in exerting top-down influence over lower-level sensory and motor regions, little direct evidence exists. We investigated changes in Dynamic Causal Modeling (DCM)-measured top-down control of sensorimotor timing during different phases of a unimanual, auditory-paced finger-tapping task in a cohort of healthy adults and adolescents. The brain regions examined were organized into a network of excitatory connections between bilateral dorso- and ventrolateral prefrontal cortices and motor and auditory cortices. This baseline connectivity changed depending on whether participants listened passively to the pacing cue, synchronized their regular interval finger tapping with the cue, or continued tapping in absence of the cue. Subjects who performed better at maintaining the prescribed tapping pace in the absence of the auditory cue relied more on top-down control of the motor and sensory regions, while those with less accurate performance relied more on sensory driven, bottom-up control of the motor cortex. No significant maturational effects were observed in either the behavioral or DCM path weight data. Both right and left prefrontal cortex were found to exert control over timing behavioral accuracy, but there were distinctly lateralized roles with respect to optimal performance.

fMRI task parameters influence hemodynamic activity in regions implicated in mental set switching.

Mental set switching is a complex executive function that is required when the focus of attention must be altered in order to adapt to a frequently-changing environment. While there is generally acceptance that switching is subserved by a fronto-parietal network, there is a considerable lack of consistency across studies as to other brain regions involved in executing mental set switches. This functional magnetic resonance imaging study sought to determine whether paradigmatic design aspects such as stimulus complexity, motor response complexity, and stimulus ordering could account for the differences in reporting of brain regions associated with mental set switching across previous studies. Several brain regions, including the striatum and anterior cingulate, previously associated with mental set switching were found to be related more to resolving intra-stimulus interference conferred by increased stimulus complexity and increased motor response complexity than to executing the mental set switch. In considering stimulus ordering, defined as the number of non-switch trials preceding a switch trial, brain activity was not observed in the fronto-parietal regions typically associated with switching but rather in regions in the anterior prefrontal cortex, sensorimotor cortex, and secondary visual cortices. Our results indicate that these important paradigm design aspects that are theoretically unrelated to set switching per se should be balanced and controlled for in future experiments, so as not to obscure clear identification of brain regions truly engaged in mental set switching.

Overcoming residual interference in mental set switching: neural correlates and developmental trajectory.

Mental set switching is a key facet of executive control measured behaviorally through reaction time or accuracy (i.e., 'switch costs') when shifting among task types. One of several experimentally dissociable influences on switch costs is 'task set inertia', conceptualized as the residual interference conferred when a previous stimulus-response tendency interferes with subsequent stimulus processing on a new task. Task set inertia is thought to represent the passive decay of the previous stimulus-response set from working memory, and its effects decrease with increased interstimulus interval. Closely spaced trials confer high task set inertia, while sparsely spaced trials confer low task set inertia. This functional magnetic resonance imaging (fMRI) study characterized, for the first time, two opposing brain systems engaged to resolve task set inertia: 1) a frontoparietal 'cortical control' network for overcoming high task set inertia interference and 2) a subcortical-motor network more active during trials with low task set inertia. These networks were distinct from brain regions showing general switching effects (i.e., switch>non-switch) and from other previously characterized interference effects. Moreover, there were ongoing maturational effects throughout adolescence for the brain regions engaged to overcome high task set inertia not seen for generalized switching effects. These novel findings represent a new avenue of exploration of cognitive set switching neural function.

Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury.

Several reports show that traumatic brain injury (TBI) results in abnormalities in the coordinated activation among brain regions. Because most previous studies examined moderate/severe TBI, the extensiveness of functional connectivity abnormalities and their relationship to postconcussive complaints or white matter microstructural damage are unclear in mild TBI. This study characterized widespread injury effects on multiple integrated neural networks typically observed during a task-unconstrained "resting state" in mild TBI patients. Whole brain functional connectivity for twelve separate networks was identified using independent component analysis (ICA) of fMRI data collected from thirty mild TBI patients mostly free of macroscopic intracerebral injury and thirty demographically-matched healthy control participants. Voxelwise group comparisons found abnormal mild TBI functional connectivity in every brain network identified by ICA, including visual processing, motor, limbic, and numerous circuits believed to underlie executive cognition. Abnormalities not only included functional connectivity deficits, but also enhancements possibly reflecting compensatory neural processes. Postconcussive symptom severity was linked to abnormal regional connectivity within nearly every brain network identified, particularly anterior cingulate. A recently developed multivariate technique that identifies links between whole brain profiles of functional and anatomical connectivity identified several novel mild TBI abnormalities, and represents a potentially important new tool in the study of the complex neurobiological sequelae of TBI.