Central Executive Network and Executive Function in Patients With Alzheimer's Disease and Healthy Individuals: Meta-Analysis of Structural and Functional MRI.

OBJECTIVE: The neural architecture of executive function is of interest given its utility as a transdiagnostic predictor of adaptive functioning. However, a gap exists in the meta-analytic literature assessing this relationship in neuropsychiatric populations, concordance between structural and functional architecture, and the relationship with neuropsychological assessment of executive function. Given the importance of the central executive network (CEN) in Alzheimer's disease, this population may be useful in understanding this relationship in Alzheimer's disease pathology. METHODS: A meta-analysis of studies (k=21) was conducted to elucidate the relationship between executive function and CEN for structural architecture (k=10; N=1,027) among patients with Alzheimer's disease (k=6; N=250) and healthy control subjects (HCs) (k=4; N=777) and for functional architecture (k=11; N=522) among patients with Alzheimer's disease (k=6; N=306) and HCs (k=5; N=216). Random-effects modeling was used to increase accuracy of conclusions about population means. RESULTS: Analyses revealed a positive brain-behavior relationship (pr=0.032, 95% CI=0.07, 0.54), although there was a lack of statistically significant heterogeneity between functional and structural neuroimaging (Q=9.89, p=0.971, I2=0.00%) and between the Alzheimer's and HC groups in functional (Q=8.18, p=0.612, I2=0.00%) and structural (Q=1.60, p=0.996, I2=0.00%) neuroimaging. Similarly, a lack of statistically significant heterogeneity was revealed between functional and structural neuroimaging among patients with Alzheimer's disease (Q=3.59, p=0.980, I2=0.00%) and HCs (Q=3.67, p=0.885, I2=0.00%). CONCLUSIONS: Structural and functional imaging in the CEN are predictive of executive function performance among patients with Alzheimer's disease and HCs. Regardless of how the CEN is affected, behavior is correlated to the degree to which the CEN is affected. Findings are significant in the context of methodological decisions in multimodal neuroimaging research.

Prefrontal resting-state connectivity and antidepressant response: no associations in the ELECT-TDCS trial.

Functional and structural MRI of prefrontal cortex (PFC) may provide putative biomarkers for predicting the treatment response to transcranial direct current stimulation (tDCS) in depression. A recent MRI study from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Theror Depression Study) showed that depression improvement after tDCS was associated with gray matter volumes of PFC subregions. Based thereon, we investigated whether antidepressant effects of tDCS are similarly associated with baseline resting-state functional connectivity (rsFC). A subgroup of 51 patients underwent baseline rsFC-MRI. All patients of ELECT-TDCS were randomized to three treatment arms for 10 weeks (anodal-left, cathodal-right PFC tDCS plus placebo medication; escitalopram 10 mg/day for 3 weeks and 20 mg/day thereafter plus sham tDCS; and placebo medication plus sham tDCS). RsFC was calculated for various PFC regions and analyzed in relation to the individual antidepressant response. There was no significant association between baseline PFC connectivity of essential structural regions, nor any other PFC regions (after correction for multiple comparisons) and patients' individual antidepressant response. This study did not reveal an association between antidepressants effects of tDCS and baseline rsFC, unlike the gray matter volume findings. Thus, the antidepressant effects of tDCS may be differentially related to structural and functional MRI measurements.

The goal priority network as a neural substrate of Conscientiousness.

Conscientiousness is a personality trait associated with many important life outcomes, but little is known about the mechanisms that underlie it. We investigated its neural correlates using functional connectivity analysis in fMRI, which identifies brain regions that act in synchrony. We tested the hypothesis that a broad network resembling a combination of the salience and ventral attention networks, which we provisionally label the goal priority network (GPN), is a neural correlate of Conscientiousness. Self- and peer-ratings of Conscientiousness were collected in a community sample of adults who underwent a resting-state fMRI scan (N = 218). An independent components analysis yielded five components that overlapped substantially with the GPN. We examined synchrony within and between these GPN subcomponents. Synchrony within one of the components-mainly comprising regions of anterior insula, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex-was significantly associated with Conscientiousness. Connectivity between this component and the four other GPN components was also significantly associated with Conscientiousness. Our results support the hypothesis that variation in a network that enables prioritization of multiple goals may be central to Conscientiousness.

Functional integrity in children with anoxic brain injury from drowning.

Drowning is a leading cause of accidental injury and death in young children. Anoxic brain injury (ABI) is a common consequence of drowning and can cause severe neurological morbidity in survivors. Assessment of functional status and prognostication in drowning victims can be extremely challenging, both acutely and chronically. Structural neuroimaging modalities (CT and MRI) have been of limited clinical value. Here, we tested the utility of resting-state functional MRI (rs-fMRI) for assessing brain functional integrity in this population. Eleven children with chronic, spastic quadriplegia due to drowning-induced ABI were investigated. All were comatose immediately after the injury and gradually regained consciousness, but with varying ability to communicate their cognitive state. Eleven neurotypical children matched for age and gender formed the control group. Resting-state fMRI and co-registered T1-weighted anatomical MRI were acquired at night during drug-aided sleep. Network integrity was quantified by independent components analysis (ICA), at both group- and per-subject levels. Functional-status assessments based on in-home observations were provided by families and caregivers. Motor ICNs were grossly compromised in ABI patients both group-wise and individually, concordant with their prominent motor deficits. Striking preservations of perceptual and cognitive ICNs were observed, and the degree of network preservation correlated (ρ = 0.74) with the per-subject functional status assessments. Collectively, our findings indicate that rs-fMRI has promise for assessing brain functional integrity in ABI and, potentially, in other disorders. Furthermore, our observations suggest that the severe motor deficits observed in this population can mask relatively intact perceptual and cognitive capabilities. Hum Brain Mapp 38:4813-4831, 2017. © 2017 Wiley Periodicals, Inc.

Resting-state networks predict individual differences in common and specific aspects of executive function.

The goal of the present study was to examine relationships between individual differences in resting state functional connectivity as ascertained by fMRI (rs-fcMRI) and performance on tasks of executive function (EF), broadly defined as the ability to regulate thoughts and actions. Unlike most previous research that focused on the relationship between rs-fcMRI and a single behavioral measure of EF, in the current study we examined the relationship of rs-fcMRI with individual differences in subcomponents of EF. Ninety-one adults completed a resting state fMRI scan and three separate EF tasks outside the magnet: inhibition of prepotent responses, task set shifting, and working memory updating. From these three measures, we derived estimates of common aspects of EF, as well as abilities specific to working memory updating and task shifting. Using Independent Components Analysis (ICA), we identified across the group of participants several networks of regions (Resting State Networks, RSNs) with temporally correlated time courses. We then used dual regression to explore how these RSNs covaried with individual differences in EF. Dual regression revealed that increased higher common EF was associated with connectivity of a) frontal pole with an attentional RSN, and b) Crus I and II of the cerebellum with the right frontoparietal RSN. Moreover, higher shifting-specific abilities were associated with increased connectivity of angular gyrus with a ventral attention RSN. The results of the current study suggest that the organization of the brain at rest may have important implications for individual differences in EF, and that individuals higher in EF may have expanded resting state networks as compared to individuals with lower EF.

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS).

Bidirectional effects on interhemispheric resting-state functional connectivity induced by excitatory and inhibitory repetitive transcranial magnetic stimulation.

Several recent studies using functional magnetic resonance imaging (fMRI) have shown that repetitive transcranial magnetic stimulation (rTMS) affects not only brain activity in stimulated regions but also resting-state functional connectivity (RSFC) between the stimulated region and other remote regions. However, these studies have only demonstrated an effect of either excitatory or inhibitory rTMS on RSFC, and have not clearly shown the bidirectional effects of both types of rTMS. Here, we addressed this issue by performing excitatory and inhibitory quadripulse TMS (QPS), which is considered to exert relatively large and long-lasting effects on cortical excitability. We found that excitatory rTMS (QPS with interstimulus intervals of 5 ms) decreased interhemispheric RSFC between bilateral primary motor cortices, whereas inhibitory rTMS (QPS with interstimulus intervals of 50 ms) increased interhemispheric RSFC. The magnitude of these effects on RSFC was significantly correlated with that of rTMS-induced effects on motor evoked potential from the corresponding muscle. The bidirectional effects of QPS were also observed in the stimulation over prefrontal and parietal association areas. These findings provide evidence for the robust bidirectional effects of excitatory and inhibitory rTMSs on RSFC, and raise a possibility that QPS can be a powerful tool to modulate RSFC.

Abnormal frontostriatal connectivity and serotonin function in gambling disorder: A preliminary exploratory study.

Background: The neurobiological mechanisms of gambling disorder are not yet fully characterized, limiting the development of treatments. Defects in frontostriatal connections have been shown to play a major role in substance use disorders, but data on behavioral addictions, such as gambling disorder, are scarce. The aim of this study was to 1) investigate whether gambling disorder is associated with abnormal frontostriatal connectivity and 2) characterize the key neurotransmitter systems underlying the connectivity abnormalities. Methods: Fifteen individuals with gambling disorder and 17 matched healthy controls were studied with resting-state functional connectivity MRI and three brain positron emission tomography scans, investigating dopamine (18F-FDOPA), opioid (11C-carfentanil) and serotonin (11C-MADAM) function. Frontostriatal connectivity was investigated using striatal seed-to-voxel connectivity and compared between the groups. Neurotransmitter systems underlying the identified connectivity differences were investigated using region-of-interest and voxelwise approaches. Results: Individuals with gambling disorder showed loss of functional connectivity between the right nucleus accumbens (NAcc) and a region in the right dorsolateral prefrontal cortex (DLPFC) (PFWE <0.05). Similarly, there was a significant Group x right NAcc interaction in right DLPFC 11C-MADAM binding (p = 0.03) but not in 18F-FDOPA uptake or 11C-carfentanil binding. This was confirmed in voxelwise analyses showing a widespread Group x right NAcc interaction in the prefrontal cortex 11C-MADAM binding (PFWE <0.05). Right NAcc 11C-MADAM binding potential correlated with attentional impulsivity in individuals with gambling disorder (r = -0.73, p = 0.005). Discussion: Gambling disorder is associated with right hemisphere abnormal frontostriatal connectivity and serotonergic function. These findings will contribute to understanding the neurobiological mechanism and may help identify potential treatment targets for gambling disorder.

Altered cerebellar-amygdala connectivity in violent offenders: A resting-state fMRI study.

It has repeatedly been reported, that there are differences in grey matter volume (GMV) between violent offenders and non-violent controls. However, it remains unclear, if structural brain abnormalities influence resting-state functional connectivity (RS-fc) between brain regions. Therefore, in the present investigation, 31 male high-risk violent prisoners were compared to 30 non-criminal controls with respect to RS-fc between brain areas. Seed regions for resting-state analysis were selected based on GMV differences between the two groups. Overall, inmates had more GMV in the cerebellum than controls and revealed higher RS-fc between the cerebellum and the amygdala. In contrast, controls relative to prisoners showed higher RS-fc between the cerebellum and the orbitofrontal cortex (OFC). In addition, controls showed more GMV in the dorsolateral prefrontal cortex (DLPFC). Inmates relative to controls had higher RS-fc within the DLPFC. Results are discussed with respect to cerebellar contributions to a brain network underlying moral behavior and violence. Enhanced cerebellar-amygdala connectivity in violent offenders might reflect alterations in the processing of moral emotions. Heightened functional connectivity between cerebellar hemispheres and the OFC in controls could be a correlate of enhanced emotion regulation capacities. Higher functional intra-DLPFC connectivity in violent offenders might represent an effort to regulate emotions.

Altered brain connectivity in sagittal craniosynostosis.

OBJECT: Sagittal nonsyndromic craniosynostosis (sNSC) is the most common form of NSC. The condition is associated with a high prevalence (> 50%) of deficits in executive function. The authors employed diffusion tensor imaging (DTI) and functional MRI to evaluate whether hypothesized structural and functional connectivity differences underlie the observed neurocognitive morbidity of sNSC. METHODS: Using a 3-T Siemens Trio MRI system, the authors collected DTI and resting-state functional connectivity MRI data in 8 adolescent patients (mean age 12.3 years) with sNSC that had been previously corrected via total vault cranioplasty and 8 control children (mean age 12.3 years) without craniosynostosis. Data were analyzed using the FMRIB Software Library and BioImageSuite. RESULTS: Analyses of the DTI data revealed white matter alterations approaching statistical significance in all supratentorial lobes. Statistically significant group differences (sNSC < control group) in mean diffusivity were localized to the right supramarginal gyrus. Analysis of the resting-state seed in relation to whole-brain data revealed significant increases in negative connectivity (anticorrelations) of Brodmann area 8 to the prefrontal cortex (Montreal Neurological Institute [MNI] center of mass coordinates [x, y, z]: -6, 53, 6) and anterior cingulate cortex (MNI coordinates 6, 43, 14) in the sNSC group relative to controls. Furthermore, in the sNSC patients versus controls, the Brodmann area 7, 39, and 40 seed had decreased connectivity to left angular gyrus (MNI coordinates -31, -61, 34), posterior cingulate cortex (MNI coordinates 13, -52, 18), precuneus (MNI coordinates 10, -55, 54), left and right parahippocampus (MNI coordinates -13, -52, 2 and MNI coordinates 11, -50, 2, respectively), lingual (MNI coordinates -11, -86, -10), and fusiform gyri (MNI coordinates -30, -79, -18). Intrinsic connectivity analysis also revealed altered connectivity between central nodes in the default mode network in sNSC relative to controls; the left and right posterior cingulate cortices (MNI coordinates -5, -35, 34 and MNI coordinates 6, -42, 39, respectively) were negatively correlated to right hemisphere precuneus (MNI coordinates 6, -71, 46), while the left ventromedial prefrontal cortex (MNI coordinates 6, 34, -8) was negatively correlated to right middle frontal gyrus (MNI coordinates 40, 4, 33). All group comparisons (sNSC vs controls) were conducted at a whole brain-corrected threshold of p < 0.05. CONCLUSIONS: This study demonstrates altered neocortical structural and functional connectivity in sNSC that may, in part or substantially, underlie the neuropsychological deficits commonly reported in this population. Future studies combining analysis of multimodal MRI and clinical characterization data in larger samples of participants are warranted.