Frontoparietal Functional Connectivity Research Articles

Cerebrovascular disease influences functional and structural network connectivity in patients with amnestic mild cognitive impairment and Alzheimer\u2019s disease

BackgroundPatients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach.MethodsWe examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains.ResultsWe demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition.ConclusionsWe demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment.

Abnormal fronto‐parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition.

Frontoparietal Structural Connectivity in Childhood Predicts Development of Functional Connectivity and Reasoning Ability: A Large-Scale Longitudinal Investigation.

Prior research points to a positive concurrent relationship between reasoning ability and both frontoparietal structural connectivity (SC) as measured by diffusion tensor imaging (Tamnes et al., 2010) and frontoparietal functional connectivity (FC) as measured by fMRI (Cocchi et al., 2014). Further, recent research demonstrates a link between reasoning ability and FC of two brain regions in particular: rostrolateral prefrontal cortex (RLPFC) and the inferior parietal lobe (IPL) (Wendelken et al., 2016). Here, we sought to investigate the concurrent and dynamic, lead-lag relationships among frontoparietal SC, FC, and reasoning ability in humans. To this end, we combined three longitudinal developmental datasets with behavioral and neuroimaging data from 523 male and female participants between 6 and 22 years of age. Cross-sectionally, reasoning ability was most strongly related to FC between RLPFC and IPL in adolescents and adults, but to frontoparietal SC in children. Longitudinal analysis revealed that RLPFC-IPL SC, but not FC, was a positive predictor of future changes in reasoning ability. Moreover, we found that RLPFC-IPL SC at one time point positively predicted future changes in RLPFC-IPL FC, whereas, in contrast, FC did not predict future changes in SC. Our results demonstrate the importance of strong white matter connectivity between RLPFC and IPL during middle childhood for the subsequent development of both robust FC and good reasoning ability.SIGNIFICANCE STATEMENT The human capacity for reasoning develops substantially during childhood and has a profound impact on achievement in school and in cognitively challenging careers. Reasoning ability depends on communication between lateral prefrontal and parietal cortices. Therefore, to understand how this capacity develops, we examined the dynamic relationships over time among white matter tracts connecting frontoparietal cortices (i.e., structural connectivity, SC), coordinated frontoparietal activation (functional connectivity, FC), and reasoning ability in a large longitudinal sample of subjects 6-22 years of age. We found that greater frontoparietal SC in childhood predicts future increases in both FC and reasoning ability, demonstrating the importance of white matter development during childhood for subsequent brain and cognitive functioning.

ECoG spectrum changes at different xenon-isoflurane anaesthesia depths.

The purpose of this study is to assess the frontal and parietal ECoG spectrum (gamma range) changes during isoflurane and combined xenon-isoflurane anaesthesia in rats. Experiments were carried out on four adult male Sprague-Dawley rats (250-300 g). The anaesthesia was induced with isoflurane and maintained with isoflurane and a xenon-isoflurane mixture. The rats were maintained at two different anaesthetic depths: light (isoflurane anaesthesia) and deep (isoflurane and xenon-isoflurane anaesthesia). The frontal and the parietal cortical activity was assessed by computing the median frequency, spectral edge frequency and functional connectivity between these two areas during light and deep anaesthesia. We noticed a decrease in cortical connectivity under deep isoflurane anaesthesia and an increase in connectivity under deep xenon-isoflurane anaesthesia. Moreover, during xenon-isoflurane anaesthesia, a trend of regularity of electro-cortical activity was present compared with isoflurane anaesthesia. Xenon-isoflurane deep anaesthesia demonstrated a series of specific ECoG features regarding frontoparietal functional connectivity (gamma range connectivity increase) and regularity of the electrocortical activity compared with isoflurane anaesthesia.

Theta-band functional connectivity in the dorsal fronto-parietal network predicts goal-directed attention

Functional imaging studies have identified a dorsal fronto-parietal network whose activity reflects shifts of attention in space and is sensitive to the behavioural relevance of stimuli. In patients with severe deficits of spatial attention this network is often structurally preserved. Here, we show that resting-state EEG functional connectivity in the dorsal fronto-parietal network predicts impaired goal-directed processing in stroke patients with spatial attention deficits. Eleven right-hemisphere damaged patients with different degrees of contralesional spatial deficits and sixteen age-matched healthy controls performed a visuo-spatial task which required them to react to a central target while ignoring task-relevant distracters presented left or right of fixation. Unlike controls, performance of patients was not modulated by the goal-relevance of peripheral distracters. Compared to controls patients showed a significant decrease in theta-band connectivity between the right dorsolateral prefrontal cortex and the right superior parietal region. Moreover, in both groups we observed a significant correlation between fronto-parietal connectivity and the behavioural effect of distracter relevance. These findings indicate that fronto-parietal functional connectivity is impaired in patients with spatial attention deficits and predicts effects of goal-relevant information on target processing.

Functional anatomy of cortical areas characterized by Von Economo neurons

Von Economo’s neurons (VENs) are large, bipolar or corkscrew-shaped neurons located in layers III and V of the frontoinsular and the anterior cingulate cortices. VENs are reported to be altered in pathologies such as frontotemporal dementia and autism, in which the individual’s self control is seriously compromised. We have recently reviewed the evolutionary appearance of VENs and we are currently studying their distribution in different neurodegenerative diseases. To investigate the role of VENs in the active human brain, we have explored the functional connectivity of brain areas containing VENs by analyzing resting state functional connectivity (rsFC) in 20 healthy volunteers. Our results show that cortical areas containing VENs form a network of frontoparietal functional connectivity. With the use of fuzzy clustering techniques, we find that this network comprises four sub-networks: the first network cluster resembles a “saliency detection” attentional network, which includes superior frontal cortex (Brodmann’s Area, BA 10), inferior parietal lobe, anterior insula, and dorsal anterior cingulate cortex; the second cluster, part of a “sensory-motor network”, comprises the superior temporal, precentral and postcentral areas; the third cluster consists of frontal ventromedial and ventrodorsal areas constituted by parts of the “anterior default mode network”; and the fourth cluster encompasses dorsal anterior cingulate cortex, dorsomedial prefrontal, and superior frontal (BA 10) areas, resembling the anterior part of the “dorsal attentional network”. Thus, the network that emerges from analyzing functional connectivity among areas that are known to contain VENs is primarily involved in functions of saliency detection and self-regulation. In addition, parts of this network constitute sub-networks that partially overlap with the default mode, the sensory-motor and the dorsal attentional networks.This work was supported by grants from PROGETTO TRASLAZIONALE, Department of Neuroscience, University of Torino.

Editorial: General anesthesia: from theory to experiments.

Editorial: General anesthesia: from theory to experiments.

Aberrant Executive and Frontoparietal Functional Connectivity in Very Preterm Infants With Diffuse White Matter Abnormalities

BackgroundDiffuse white matter abnormalities are identified in up to 80% of very preterm infants on magnetic resonance imaging at 40 weeks' postmenstrual age. Several studies have observed an association between diffuse white matter abnormalities and cognitive deficits. We hypothesized that very preterm infants (gestational age ≤32 weeks) with diffuse white matter abnormalities will exhibit reduced executive control and frontoparietal functional connectivity compared with infants without diffuse white matter abnormalities measured using resting state functional magnetic resonance imaging at term-equivalent age. MethodsWe quantified diffuse white matter abnormality volume objectively using an automated segmentation approach and defined diffuse white matter abnormality severity as no-mild (volume ≤50th percentile; N = 13) and moderate-severe (N = 14). Resting state networks of interests were identified using probabilistic independent component analysis. Within network functional connectivity was calculated between the different pair of nodes in a given network using partial correlation coefficients. ResultsWe studied 27 very preterm infants born at a mean (standard deviation) gestational age of 26.9 (2.0) weeks and imaged at 39.6 (1.4) weeks' postmenstrual age. Within-network connectivity was significantly reduced in the moderate-severe diffuse white matter abnormalities group than in the no-mild diffuse white matter abnormalities group for the executive control (P < 0.001) and frontoparietal (P = 0.02) networks. As expected, connectivity in three control resting state networks was similar: visual (P = 0.17), motor (P = 0.89), and somatosensory (P = 0.69) networks. ConclusionsVery preterm infants with moderate or severe diffuse white matter abnormalities exhibited reduced functional connectivity in important cognitive and attention networks. This aberrant connectivity may be the early life antecedent to the cognitive deficits reported at 2 years of age or later in such infants.

Regional amyloid burden and intrinsic connectivity networks in cognitively normal elderly subjects.

Although previous studies demonstrated decreased functional connectivity in the default mode network in the cognitively normal older adults with amyloid burden, effects of amyloid burden in the other large-scale intrinsic connectivity networks are not yet clear. The aim of this study was to investigate the distinctive association pattern of amyloid-β deposition on the three large-scale intrinsic connectivity networks (the default mode network, salience network and central executive network) in older adults with normal cognition. Fifty-six older adults with normal cognition underwent functional magnetic resonance imaging and were dichotomized using 11C-labelled Pittsburgh compound B positron emission tomography imaging into subjects with (PiB+; n=27) and without (PiB-; n=29) detectable amyloid burden. We found that the functional connectivities of (i) the default mode network were greater; (ii) the salience network were not different; and (iii) the central executive network were lower in the Pittsburgh compound B positive group, compared with the Pittsburgh compound B negative group. Anterior cingulate cortex Pittsburgh compound B retention was negatively correlated with the functional connectivities of the posterior default mode network, and positively correlated with fronto-parietal functional connectivity (within the central executive network) in the Pittsburgh compound B positive group. The anti-correlation strength between the default mode network and the central executive network was negatively correlated with the anterior cingulate cortex Pittsburgh compound B levels. Additionally, significant group × episodic memory interactions with functional connectivities in the posterior default mode network, and the frontal default mode network were observed. Our results of aberrant default mode network functional connectivity and distinctive correlation patterns between the Pittsburgh compound B retention in the anterior cingulate cortex and functional connectivities in the default mode network and central executive network in the Pittsburgh compound B positive group might reflect a detrimental effect of amyloid retention on functional changes in the course of Alzheimer's disease progression.

Functional anatomy of cortical areas characterized by Von Economo neurons

Von Economo's neurons (VENs) are large, bipolar or corkscrew-shaped neurons located in layers III and V of the frontoinsular and the anterior cingulate cortices. VENs are reported to be altered in pathologies such as frontotemporal dementia and autism, in which the individual's self control is seriously compromised. To investigate the role of VENs in the active human brain, we have explored the functional connectivity of brain areas containing VENs by analyzing resting state functional connectivity (rsFC) in 20 healthy volunteers. Our results show that cortical areas containing VENs form a network of frontoparietal functional connectivity. With the use of fuzzy clustering techniques, we find that this network comprises four sub-networks: the first network cluster resembles a "saliency detection" attentional network, which includes superior frontal cortex (Brodmann's Area, BA 10), inferior parietal lobe, anterior insula, and dorsal anterior cingulate cortex; the second cluster, part of a "sensory-motor network", comprises the superior temporal, precentral and postcentral areas; the third cluster consists of frontal ventromedial and ventrodorsal areas constituted by parts of the "anterior default mode network"; and the fourth cluster encompasses dorsal anterior cingulate cortex, dorsomedial prefrontal, and superior frontal (BA 10) areas, resembling the anterior part of the "dorsal attentional network". Thus, the network that emerges from analyzing functional connectivity among areas that are known to contain VENs is primarily involved in functions of saliency detection and self-regulation. In addition, parts of this network constitute sub-networks that partially overlap with the default mode, the sensory-motor and the dorsal attentional networks.

Frontoparietal Connectivity and Hierarchical Structure of the Brain’s Functional Network during Sleep

Frontal and parietal regions are associated with some of the most complex cognitive functions, and several frontoparietal resting-state networks can be observed in wakefulness. We used functional magnetic resonance imaging data acquired in polysomnographically validated wakefulness, light sleep, and slow-wave sleep to examine the hierarchical structure of a low-frequency functional brain network, and to examine whether frontoparietal connectivity would disintegrate in sleep. Whole-brain analyses with hierarchical cluster analysis on predefined atlases were performed, as well as regression of inferior parietal lobules (IPL) seeds against all voxels in the brain, and an evaluation of the integrity of voxel time-courses in subcortical regions-of-interest. We observed that frontoparietal functional connectivity disintegrated in sleep stage 1 and was absent in deeper sleep stages. Slow-wave sleep was characterized by strong hierarchical clustering of local submodules. Frontoparietal connectivity between IPL and superior medial and right frontal gyrus was lower in sleep stages than in wakefulness. Moreover, thalamus voxels showed maintained integrity in sleep stage 1, making intrathalamic desynchronization an unlikely source of reduced thalamocortical connectivity in this sleep stage. Our data suggest a transition from a globally integrated functional brain network in wakefulness to a disintegrated network consisting of local submodules in slow-wave sleep, in which frontoparietal inter-modular nodes may play a role, possibly in combination with the thalamus.

Frontoparietal connectivity in substance-naïve youth with and without a family history of alcoholism

Frontoparietal connections underlie key executive cognitive functions. Abnormalities in the frontoparietal network have been observed in chronic alcoholics and associated with alcohol-related cognitive deficits. It remains unclear whether neurobiological differences in frontoparietal circuitry exist in substance-naïve youth who are at-risk for alcohol use disorders. This study used functional connectivity magnetic resonance imaging and diffusion tensor imaging to examine frontoparietal connectivity and underlying white matter microstructure in 20 substance-naïve youth with a family history of alcohol dependence and 20 well-matched controls without familial substance use disorders. Youth with a family history of alcohol dependence showed significantly less functional connectivity between posterior parietal and dorsolateral prefrontal seed regions ( ps < .05), as compared to family history negative controls; however, they did not show differences in white matter architecture within tracts subserving frontoparietal circuitry ( ps > .34). Substance-naïve youth with a family history of alcohol dependence show less frontoparietal functional connectivity in the absence of white matter microstructural abnormalities as compared to youth with no familial risk. This may suggest a potential neurobiological marker for the development of substance use disorders.

Long-term effects of motor training on resting-state networks and underlying brain structure

Acquired motor skills are coded in fronto-parietal brain networks, but how these networks evolve through motor training is unclear. On the one hand, increased functional connectivity has been shown immediately after a training session; on the other hand, training-induced structural changes are visible only after several weeks. Based on known associations between functional and structural network development during human ontogeny, we hypothesised that learning a challenging motor task leads to long-lasting changes in functional resting-state networks and the corresponding cortical and sub-cortical brain structures. Using longitudinal functional and structural MRI at multiple time points, we demonstrate increased fronto-parietal network connectivity one week after two brief motor training sessions in a dynamic balancing task, although subjects were engaged in their regular daily activities during the week. Repeated training sessions over six consecutive weeks progressively modulate these changes in accordance with individual performance improvements. Multimodal correlation analyses showed an association between structural grey matter alterations and functional connectivity changes in prefrontal and supplementary-motor areas. These coincident changes were most prominent in the first three weeks of training. In contrast, changes in fronto-parietal functional connectivity and the underlying white matter fibre structure developed gradually during the six weeks. Our results demonstrate a tight correlation between training-induced functional and structural brain plasticity on the systems level and suggest a functional relevance of intrinsic brain activity for morphological adaptation in the human brain.