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Network Mapping of Connectivity Alterations in Disorder of Consciousness: Towards Targeted Neuromodulation.

ABSTRACT: Disorder of consciousness (DoC) refers to a group of clinical conditions that may emerge after brain injury, characterized by a varying decrease in the level of consciousness that can last from days to years. An understanding of its neural correlates is crucial for the conceptualization and application of effective therapeutic interventions. Here we propose a quantitative meta-analysis of the neural substrate of DoC emerging from functional magnetic resonance (fMRI) and positron emission tomography (PET) studies. We also map the relevant networks of resulting areas to highlight similarities with Resting State Networks (RSNs) and hypothesize potential therapeutic solutions leveraging network-targeted noninvasive brain stimulation. Available literature was reviewed and analyzed through the activation likelihood estimate (ALE) statistical framework to describe resting-state or task-dependent brain activation patterns in DoC patients. Results show that task-related activity is limited to temporal regions resembling the auditory cortex, whereas resting-state fMRI data reveal a diffuse decreased activation affecting two subgroups of cortical (angular gyrus, middle frontal gyrus) and subcortical (thalamus, cingulate cortex, caudate nucleus) regions. Clustering of their cortical functional connectivity projections identify two main altered functional networks, related to decreased activity of (i) the default mode and frontoparietal networks, as well as (ii) the anterior salience and visual/auditory networks. Based on the strength and topography of their connectivity profile, biophysical modeling of potential brain stimulation solutions suggests the first network as the most feasible target for tES, tDCS neuromodulation in DoC patients.

SUBMITTER: Mencarelli L

PROVIDER: S-EPMC7141258 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Network Mapping of Connectivity Alterations in Disorder of Consciousness: Towards Targeted Neuromodulation.

Mencarelli Lucia L Biagi Maria Chiara MC Salvador Ricardo R Romanella Sara S Ruffini Giulio G Rossi Simone S Santarnecchi Emiliano E

Journal of clinical medicine 20200318 3

Disorder of consciousness (DoC) refers to a group of clinical conditions that may emerge after brain injury, characterized by a varying decrease in the level of consciousness that can last from days to years. An understanding of its neural correlates is crucial for the conceptualization and application of effective therapeutic interventions. Here we propose a quantitative meta-analysis of the neural substrate of DoC emerging from functional magnetic resonance (fMRI) and positron emission tomogra ...[more]

PMID: 32197485

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Project description:ContextRecent neuroimaging studies have associated activity in the default mode network (DMN) with self-referential and pain processing, both of which are altered in borderline personality disorder (BPD). In patients with BPD, antinociception has been linked to altered activity in brain regions involved in the cognitive and affective evaluation of pain. Findings in healthy subjects indicate that painful stimulation leads to blood oxygenation level-dependent signal decreases and changes in the functional architecture of the DMN.ObjectivesTo connect the previously separate research areas of DMN connectivity and altered pain perception in BPD and to explore DMN connectivity during pain processing in patients with BPD.DesignCase-control study.SettingUniversity hospital.ParticipantsTwenty-five women with BPD, including 23 (92%) with a history of self-harm, and 22 age-matched control subjects.InterventionsPsychophysical assessment and functional magnetic resonance imaging during painful heat vs neutral temperature stimulation.Main outcome measureConnectivity of DMN as assessed via independent component analysis and psychophysiological interaction analysis.ResultsCompared with control subjects, patients with BPD showed less integration of the left retrosplenial cortex and left superior frontal gyrus into the DMN. Higher BPD symptom severity and trait dissociation were associated with an attenuated signal decrease of the DMN in response to painful stimulation. During pain vs neutral, patients with BPD exhibited less posterior cingulate cortex seed region connectivity with the left dorsolateral prefrontal cortex.ConclusionsPatients with BPD showed significant alterations in DMN connectivity, with differences in spatial integrity and temporal characteristics. These alterations may reflect a different cognitive and affective appraisal of pain as less self-relevant and aversive as well as a deficiency in the switching between baseline and task-related processing. This deficiency may be related to everyday difficulties of patients with BPD in regulating their emotions, focusing mindfully on 1 task at a time, and efficiently shifting their attention from one task to another.

Project description:Altered brain network connectivity is a potential biomarker for obsessive-compulsive disorder (OCD). A meta-analysis of resting-state MRI studies by Gürsel et al. (2018) described altered functional connectivity in OCD patients within and between the default mode network (DMN), the salience network (SN), and the frontoparietal network (FPN), as well as evidence for aberrant fronto-striatal circuitry. Here, we tested the replicability of these meta-analytic rsfMRI findings by measuring functional connectivity during resting-state fMRI in a new sample of OCD patients (n = 24) and matched controls (n = 33). We performed seed-to-voxel analyses using 30 seed regions from the prior meta-analysis. OCD patients showed reduced functional connectivity between the SN and the DMN compared to controls, replicating previous findings. We did not observe significant group differences of functional connectivity within the DMN, SN, nor FPN. Additionally, we observed reduced connectivity between the visual network to both the DMN and SN in OCD patients, in particular reduced functional connectivity between lateral parietal seeds and the left inferior lateral occipital pole. Furthermore, the right lateral parietal seed (associated with the DMN) was more strongly correlated with a cluster in the right lateral occipital cortex and precuneus (a region partly overlapping with the Dorsal Attentional Network (DAN)) in patients. Importantly, this latter finding was positively correlated to OCD symptom severity. Overall, our study partly replicated prior meta-analytic findings, highlighting hypoconnectivity between SN and DMN as a potential biomarker for OCD. Furthermore, we identified changes between the SN and the DMN with the visual network. This suggests that abnormal connectivity between cortex regions associated with abstract functions (transmodal regions such as the DMN), and cortex regions associated with constrained neural processing (unimodal regions such as the visual cortex), may be important in OCD.

Dataset Information

Network Mapping of Connectivity Alterations in Disorder of Consciousness: Towards Targeted Neuromodulation.

Publications

Network Mapping of Connectivity Alterations in Disorder of Consciousness: Towards Targeted Neuromodulation.

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