Functional Connectivity Of Fronto-parietal Networks Research Articles

Resting-state networks and anosognosia in Alzheimer's disease.

Recent evidence suggests that anosognosia or unawareness of cognitive impairment in Alzheimer's Disease (AD) may be explained by a disconnection between brain regions involved in accessing and monitoring information regarding self and others. It has been demonstrated that AD patients with anosognosia have reduced connectivity within the default mode network (DMN) and that anosognosia in people with prodromal AD is positively associated with bilateral anterior cingulate cortex (ACC), suggesting a possible role of this region in mechanisms of awareness in the early phase of disease. We hypothesized that anosognosia in AD is associated with an imbalance between the activity of large-scale resting-state functional magnetic resonance imaging (fMRI) networks, in particular the DMN, the salience network (SN), and the frontoparietal network (FPN). Sixty patients with MCI and AD dementia underwent fMRI and neuropsychological assessment including the Anosognosia Questionnaire Dementia (AQ-D), a measure of anosognosia based on a discrepancy score between patient's and carer's judgments. After having applied Independent Component Analysis (ICA) to resting fMRI data we performed: (i) correlations between the AQ-D score and functional connectivity in the DMN, SN, and FPN, and (ii) comparisons between aware and unaware patients of the DMN, SN, and FPN functional connectivity. We found that anosognosia was associated with (i) weak functional connectivity within the DMN, in posterior and middle cingulate cortex particularly, (ii) strong functional connectivity within the SN in ACC, and between the SN and basal ganglia, and (iii) a heterogenous effect concerning the functional connectivity of the FPN, with a weak connectivity between the FPN and PCC, and a strong connectivity between the FPN and ACC. The observed effects were controlled for differences in severity of cognitive impairment and age. Anosognosia in the AD continuum is associated with a dysregulation of the functional connectivity of three large-scale networks, namely the DMN, SN, and FPN.

Cognitive training and brain stimulation in patients with cognitive impairment: a randomized controlled trial

BackgroundRepeated sessions of training and non-invasive brain stimulation have the potential to enhance cognition in patients with cognitive impairment. We hypothesized that combining cognitive training with anodal transcranial direct current stimulation (tDCS) will lead to performance improvement in the trained task and yield transfer to non-trained tasks.MethodsIn our randomized, sham-controlled, double-blind study, 46 patients with cognitive impairment (60–80 years) were randomly assigned to one of two interventional groups. We administered a 9-session cognitive training (consisting of a letter updating and a Markov decision-making task) over 3 weeks with concurrent 1-mA anodal tDCS over the left dorsolateral prefrontal cortex (20 min in tDCS, 30 s in sham group). Primary outcome was trained task performance (letter updating task) immediately after training. Secondary outcomes included performance in tasks testing working memory (N-back task), decision-making (Wiener Matrices test) and verbal memory (verbal learning and memory test), and resting-state functional connectivity (FC). Tasks were administered at baseline, at post-assessment, and at 1- and 7-month follow-ups (FU). MRI was conducted at baseline and 7-month FU. Thirty-nine participants (85%) successfully completed the intervention. Data analyses are reported on the intention-to-treat (ITT) and the per-protocol (PP) sample.ResultsFor the primary outcome, no difference was observed in the ITT (β = 0.1, 95%-CI [− 1.2, 1.3, p = 0.93] or PP sample (β = − 0.2, 95%-CI [− 1.6, 1.2], p = 0.77). However, secondary analyses in the N-back working memory task showed that, only in the PP sample, the tDCS outperformed the sham group (PP: % correct, β = 5.0, 95%-CI [− 0.1, 10.2], p = 0.06, d-prime β = 0.2, 95%-CI [0.0, 0.4], p = 0.02; ITT: % correct, β = 3.0, 95%-CI [− 3.9, 9.9], p = 0.39, d-prime β = 0.1, 95%-CI [− 0.1, 0.3], p = 0.5). Frontoparietal network FC was increased from baseline to 7-month FU in the tDCS compared to the sham group (pFDR < 0.05). Exploratory analyses showed a correlation between individual memory improvements and higher electric field magnitudes induced by tDCS (ρtDCS = 0.59, p = 0.02). Adverse events did not differ between groups, questionnaires indicated successful blinding (incidence rate ratio, 1.1, 95%-CI [0.5, 2.2]).ConclusionsIn sum, cognitive training with concurrent brain stimulation, compared to cognitive training with sham stimulation, did not lead to superior performance enhancements in patients with cognitive impairment. However, we observed transferred working memory benefits in patients who underwent the full 3-week intervention. MRI data pointed toward a potential intervention-induced modulation of neural network dynamics. A link between individual performance gains and electric fields suggested dosage-dependent effects of brain stimulation. Together, our findings do not support the immediate benefit of the combined intervention on the trained function, but provide exploratory evidence for transfer effects on working memory in patients with cognitive impairment. Future research needs to explore whether individualized protocols for both training and stimulation parameters might further enhance treatment gains.Trial registrationThe study is registered on ClinicalTrials.gov (NCT04265378). Registered on 7 February 2020. Retrospectively registered.

Dual-functional Network Regulation Underlies the Central Executive System in Working Memory

The frontoparietal network (FPN) and cingulo-opercular network (CON) may exert top-down regulation corresponding to the central executive system (CES) in working memory (WM); however, contributions and regulatory mechanisms remain unclear. We examined network interaction mechanisms underpinning the CES by depicting CON- and FPN-mediated whole-brain information flow in WM. We used datasets from participants performing verbal and spatial working memory tasks, divided into encoding, maintenance, and probe stages. We used general linear models to obtain task-activated CON and FPN nodes to define regions of interest (ROI); an online meta-analysis defined alternative ROIs for validation. We calculated whole-brain functional connectivity (FC) maps seeded by CON and FPN nodes at each stage using beta sequence analysis. We used Granger causality analysis to obtain the connectivity maps and assess task-level information flow patterns. For verbal working memory, the CON functionally connected positively and negatively to task-dependent and task-independent networks, respectively, at all stages. FPN FC patterns were similar only in the encoding and maintenance stages. The CON elicited stronger task-level outputs. Main effects were: stable CON → FPN, CON → DMN, CON → visual areas, FPN → visual areas, and phonological areas → FPN. The CON and FPN both up-regulated task-dependent and down-regulated task-independent networks during encoding and probing. Task-level output was slightly stronger for the CON. CON → FPN, CON → DMN, visual areas → CON, and visual areas → FPN showed consistent effects. The CON and FPN might together underlie the CES’s neural basis and achieve top-down regulation through information interaction with other large-scale functional networks, and the CON may be a higher-level regulatory core in WM.

Functional reconfiguration of task-active frontoparietal control network facilitates abstract reasoning.

While the brain's functional network architecture is largely conserved between resting and task states, small but significant changes in functional connectivity support complex cognition. In this study, we used a modified Raven's Progressive Matrices Task to examine symbolic and perceptual reasoning in human participants undergoing fMRI scanning. Previously, studies have focused predominantly on discrete symbolic versions of matrix reasoning, even though the first few trials of the Raven's Advanced Progressive Matrices task consist of continuous perceptual stimuli. Our analysis examined the activation patterns and functional reconfiguration of brain networks associated with resting state and both symbolic and perceptual reasoning. We found that frontoparietal networks, including the cognitive control and dorsal attention networks, were significantly activated during abstract reasoning. We determined that these same task-active regions exhibited flexibly-reconfigured functional connectivity when transitioning from resting state to the abstract reasoning task. Conversely, we showed that a stable network core of regions in default and somatomotor networks was maintained across both resting and task states. We propose that these regionally-specific changes in the functional connectivity of frontoparietal networks puts the brain in a "task-ready" state, facilitating efficient task-based activation.

Brain functional connectivity in chronic tic disorders and Gilles de la Tourette syndrome.

The pathophysiology of chronic tic disorder (cTD) and Gilles de la Tourette syndrome (GTS) is characterized by the dysfunction of both motor and non - motor cortico - striatal - thalamo - cortical (CSTC) circuitries, which leads to tic release and comorbids. A role of fronto - parietal network (FPN) connectivity breakdown has been postulated for tic pathogenesis, given that the FPN entertain connections with limbic, paralimbic, and CSTC networks. Our study was aimed at characterizing the FPN functional connectivity in cTD and GTS in order to assess the role of its deterioration in tic severity and the degree of comorbids. We recorded scalp EEG during resting state in patients with cTD and GTS. The eLORETA current source densities were analyzed, and the lagged phase synchronization (LPS) was calculated to estimate nonlinear functional connectivity between cortical areas. We found that the FPN functional connectivity in delta band was more detrimental in more severe GTS patients. Also, the sensorimotor functional connectivity in beta2 band was stronger in more severe cTD and GTS patients. FPN functional connectivity deterioration correlated with comorbids presence and severity in patients with GTS. Our data suggest that a FPN disconnection may contribute to the motoric symptomatology and comorbid severity in GTS, whereas sensorimotor disconnection may contribute to tic severity in cTD and GTS. Although preliminary, our study points out a differently disturbed brain connectivity between patients with cTD and GTS. This may serve as diagnostic marker and potentially interesting base to develop pharmacological and noninvasive neuromodulation trials aimed at reducing tic symptomatology.

Age at onset reveals different functional connectivity abnormalities in prodromal Alzheimer's disease.

Age at symptom onset (AAO) underlies different Alzheimer's disease (AD) clinical variants: late-onset AD (LOAD) is characterized by memory deficits, while early-onset AD (EOAD) presents predominantly with non-memory symptoms. The involvement of different neural networks may explain these distinct clinical phenotypes. In this study, we tested the hypothesis of an early and selective involvement of neural networks based on AAO in AD. Twenty memory clinic patients with prodromal AD (i.e., mild cognitive impairment with an AD-like cerebrospinal fluid profile) and 30 healthy controls underwent a cognitive evaluation and a resting state functional MRI exam. Independent component analysis was performed to assess functional connectivity (FC) in the following networks: default mode, frontoparietal, limbic, visual, and sensorimotor. Patients were stratified into late-onset (pLOAD) and early-onset (pEOAD) prodromal AD according to the AAO and controls were stratified into younger and older groups accordingly. Decreased FC within the default mode and the limbic networks was observed in pLOAD, while pEOAD showed lower FC in the frontoparietal and visual networks. The sensorimotor network did not show differences between groups. A significant association was found between memory and limbic network FC in pLOAD, and between executive functions and frontoparietal network FC in pEOAD, although the latter association did not survive multiple comparison correction. Our findings indicate that aberrant connectivity in memory networks is associated with pLOAD, while networks underlying executive and visuo-spatial functions are affected in pEOAD. These findings are in line with the hypothesis that the pathophysiological mechanisms underlying EOAD and LOAD are distinct.

Effective Connectivity of the Fronto-Parietal Network during the Tangram Task in a Natural Environment

Although the neural basis underlying visuospatial reasoning has been widely explored by neuroimaging techniques, the brain activation patterns during naturalistic visuospatial reasoning such as tangram remains unclear. In this study, the directional functional connectivity of fronto-parietal networks during the tangram task was carefully inspected by using combined functional near-infrared spectroscopy (fNIRS) and conditional Granger causality analysis (GCA). Meanwhile, the causal networks during the traditional spatial reasoning task were also characterized to exhibit the differences with those during the tangram task. We discovered that the tangram task in a natural environment showed enhanced activation in the fronto-parietal regions, particularly the frontal cortex. In addition, a strong directional connectivity from the right prefrontal cortex to left angular gyrus was detected for the complex spatial reasoning condition of spatial reasoning task, whereas no effective connectivity was identified between the frontal and parietal cortices during the tangram task. Further correlation analyses showed that the behavioral performance in the spatial reasoning rather than the tangram task manifested the relationship with the connectivity between the frontal and parietal cortex. Our findings demonstrate that the tangram task measures a different aspect of the visuospatial reasoning ability which requires more trial-and-error strategies and creative thinking rather than inductive reasoning. In particular, the frontal cortex is mostly involved in tangram puzzle-solving, whereas the interaction between frontal and parietal cortices is regulated by the hands-on experience during the tangram task.

The altered right frontoparietal network functional connectivity in migraine and the modulation effect of treatment.

Aims This study aims to investigate the resting-state functional connectivity (rs-fc) of the right frontoparietal network (rFPN) between migraineurs and healthy controls (HCs) in order to determine how the rFPN rs-fc can be modulated by effective treatment. Methods One hundred patients and 46 matched HCs were recruited. Migraineurs were randomized to verum acupuncture, sham acupuncture, and waiting list groups. Resting-state functional magnetic resonance imaging data were collected before and after longitudinal treatments. Independent component analysis was applied in the data analysis. Results We found that migraineurs showed decreased rs-fc between the rFPN and bilateral precuneus compared with HCs. After treatments (real and sham), rFPN rs-fc with the precuneus was significantly reduced. This reduction was associated with headache intensity relief. In order to explore the role of the precuneus in acupuncture modulation, we performed a seed-based rs-fc analysis using the precuneus as a seed and found that the precuneus rs-fc with the bilateral rostral anterior cingulate cortex/medial prefrontal cortex, ventral striatum, and dorsolateral prefrontal cortex was significantly enhanced after treatment. Conclusion Our results suggest that migraineurs are associated with abnormal rFPN rs-fc. An effective treatment, such as acupuncture, may relieve symptoms by strengthening the cognitive adaptation/coping process. Elucidation of the adaptation/coping mechanisms may open up a new window for migraine management.

Functional neuroimaging: the adaptive mechanisms in migraine.

Migraine is a common neurological disorder characterized by a primary brain dysfunction subtended by an episodic activation and sensitization of the trigemino-vascular pain pathway. Although migraine attacks are clinically welldefined, the underlying pathophysiology of the more complex migraine scenario is largely unknown. Functional brain changes, that occur because of repeated migraine attacks, may be explained through a maladaptive feedforward allostatic cascade model. The fundamental assumption is that “the brain is a central organ of stress” [1], able to detect stressful or potentially stressful situations and react in form of behavioural and/or physiologic responses. These brain responses, mediated by the autonomic nervous system and neuroendocrine mechanisms, could be either adaptive or maladaptive. In this context, allostasis is the ability to protect the body through adaptation [2]. Contrariwise, the allostatic load and overload, resulting from repeated stress and/or allostasis [3], refers to the wear and tear on the systems that normally support adaptation. Compelling evidence suggests that the brain of migraine patients is significantly different from healthy controls. Some of these differences are related to abnormal cortical activity during painful stimulations, suggesting an “adaptive” response observed in the course of moderate or high noxious trigeminal stimulations. Conversely, other differences relate to abnormality in responses that should be adaptive but become impaired or maladaptive, such as altered brainstem processing. More recently, a decreased functional connectivity was demonstrated within the fronto-parietal network (FPN) in patients with migraine without and with aura in the absence of clinically relevant executive deficits. FPN represents the neural substrate of executive functions and FPN functional abnormalities might be a part of a complex cascade that terminates in a migraine attack. Specifically, FPN functional connectivity changes could underlie a defective executive functioning in which high-demanding conditions cannot be correctly processed and solved by patients with migraine, escalating the brain adaptive response, likely resulting in a risk factor for headache attacks. In conclusion, we believe that in migraine an internal state of dysregulation creates an allostatic load with maladaptive consequences on brain, behaviour, physiological regulation and systemic physiology that progress in a feedforward cascade. Thus, we suggest that migraine should be considered a brain disease and not simply a recurrent acute pain syndrome.

Cognitive correlates of frontoparietal network connectivity ‘at rest’ in individuals with differential risk for psychotic disorder

Altered frontoparietal network functional connectivity (FPN-fc) has been associated with neurocognitive dysfunction in individuals with (risk for) psychotic disorder. Cannabis use is associated with cognitive and FPN-fc alterations in healthy individuals, but it is not known whether cannabis exposure moderates the FPN-fc-cognition association. We studied FPN-fc in relation to psychosis risk, as well as the moderating effects of psychosis risk and cannabis use on the association between FPN-fc and (social) cognition. This was done by collecting resting-state fMRI scans and (social) cognitive test results from 63 patients with psychotic disorder, 73 unaffected siblings and 59 controls. Dorsolateral prefrontal cortex (DLPFC) seed-based correlation analyses were used to estimate FPN-fc group differences. Additionally, group×FPN-fc and cannabis×FPN-fc interactions in models of cognition were assessed with regression models. Results showed that DLPFC-fc with the left precuneus, right inferior parietal lobule, right middle temporal gyrus (MTG), inferior frontal gyrus (IFG) regions and right insula was decreased in patients compared to controls. Siblings had reduced DLPFC-fc with the right MTG, left middle frontal gyrus, right superior frontal gyrus, IFG regions, and right insula compared to controls, with an intermediate position between patients and controls for DLPFC–IFG/MTG and insula-fc. There were no significant FPN-fc×group or FPN-fc×cannabis interactions in models of cognition. Reduced DLPFC–insula-fc was associated with worse social cognition in the total sample. In conclusion, besides patient- and sibling-specific FPN-fc alterations, there was evidence for trait-related alterations. FPN-fc-cognition associations were not conditional on familial liability or cannabis use. Lower FPN-fc was associated with lower emotion processing in the total group.