Chandler Sours

Default Mode Network Interference in Mild Traumatic Brain Injury – A Pilot Resting State Study

In this study we investigated the functional connectivity in 23 Mild TBI (mTBI) patients with and without memory complaints using resting state fMRI in the sub-acute stage of injury as well as a group of control participants. Results indicate that mTBI patients with memory complaints performed significantly worse than patients without memory complaints on tests assessing memory from the Automated Neuropsychological Assessment Metrics (ANAM). Altered functional connectivity was observed between the three groups between the default mode network (DMN) and the nodes of the task positive network (TPN). Altered functional connectivity was also observed between both the TPN and DMN and nodes associated with the Salience Network (SN). Following mTBI there is a reduction in anti-correlated networks for both those with and without memory complaints for the DMN, but only a reduction in the anti-correlated network in mTBI patients with memory complaints for the TPN. Furthermore, an increased functional connectivity between the TPN and SN appears to be associated with reduced performance on memory assessments. Overall the results suggest that a disruption in the segregation of the DMN and the TPN at rest may be mediated through both a direct pathway of increased FC between various nodes of the TPN and DMN, and through an indirect pathway that links the TPN and DMN through nodes of the SN. This disruption between networks may cause a detrimental impact on memory functioning following mTBI, supporting the Default Mode Interference Hypothesis in the context of mTBI related memory deficits.

A longitudinal evaluation of diffusion kurtosis imaging in patients with mild traumatic brain injury

Abstract Primary objective: To investigate longitudinal diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) changes in white and grey matter in patients with mild traumatic brain injury (mTBI). Research design: A prospective case-control study. Methods and procedures: DKI data was obtained from 24 patients with mTBI along with cognitive assessments within 10 days, 1 month and 6 months post-injury and compared with age-matched control (n = 24). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusion (λr), mean kurtosis (MK) and radial kurtosis (Kr) were extracted from the thalamus, internal capsule and corpus callosum. Main outcomes and results: Results demonstrate reduced Kr and MK in the anterior internal capsule in patients with mTBI across the three visits, and reduced MK in the posterior internal capsule during the 10 day time point. Correlations were observed between the change in MK or Kr between 1–6 months and the improvements in cognition between the 1 and 6 month visits in the thalamus, internal capsule and corpus callosum. Conclusions: These data demonstrate that DKI may be sensitive in tracking pathophysiological changes associated with mTBI and may provide additional information to conventional DTI parameters in evaluating longitudinal changes following TBI.

Longitudinal and prognostic evaluation of mild traumatic brain injury: A 1H-magnetic resonance spectroscopy study.

In the majority of patients with mild traumatic brain injury (mTBI), brain tissue impairment is undetectable by computed tomography and/or structural magnetic resonance imaging. Even in confirmed cases of head injury, conventional neuroimaging methods lack sensitivity in predicting neuropsychological outcomes of patients. The objectives of this study were to (1) cross-sectionally determine deviations in the neurometabolic profile of patients with mTBI from healthy controls at different stages of mTBI using tightly controlled examination windows, and (2) determine associations between acute neurometabolic markers of mTBI and chronic neurocognitive performance. Patients were examined at the early subacute (n=43; 5.44 ± 3.15 days post-injury (DPI)), late subacute (n=33; 37.00 ± 12.26 DPI) and chronic (n=27; 195.30 ± 19.60 DPI) stages of mTBI. Twenty-one neurologically intact subjects were used as controls. Proton magnetic resonance spectroscopy imaging ((1)H-MRSI) was used to obtain metabolic measurements from different brain regions. The Automated Neuropsychological Assessment Metrics (ANAM) was used for cognitive evaluation of patients at the chronic stage of mTBI. Measurements in the thalamus and centrum semiovale (CSV) emerged as the most indicative of injury and were used to predict neurocognitive outcome. The major findings of this study are (1) decreases in Cho/Cre (choline-to-creatine ratio) measured in the thalamus (p=0.042) and CSV (p=0.017) at the late subacute stage of mTBI; (2) positive associations of early subacute Cre measurements in the CSV with chronic ANAM scores measuring performance in delayed (r=0.497, p=0.019) and immediate (r=0.391, p=0.072) code substitution. These findings show that metabolic measurements in the thalamus and CSV can potentially serve as diagnostic and prognostic markers of mTBI.

Disruptions in Resting State Functional Connectivity and Cerebral Blood Flow in Mild Traumatic Brain Injury Patients

Mild traumatic brain injury (mTBI) is often occult to conventional imaging techniques. However, there is growing evidence that mTBI patients who lack evidence of structural intracranial injury may develop post-concussive syndrome (PCS). We investigated longitudinal alterations in resting state functional connectivity (rs-FC) in brain networks in a population of 28 patients compared to 28 matched control participants. Rs-FC and cerebral blood flow (CBF) within the nodes of the Default Mode Network (DMN) and Task Positive Network (TPN) were assessed at three time points including acute, sub-acute, and chronic stages following mTBI. Participants received the Automated Neuropsychological Assessment Metrics (ANAM) to assess cognitive performance. Main findings indicate that despite normalized cognitive performance, chronic mTBI patients demonstrate increased rs-FC between the DMN and regions associated with the salience network (SN) and TPN compared to the control populations, as well as reduced strength of rs-FC within the DMN at the acute stage of injury. In addition, chronic mTBI patients demonstrate an imbalance in the ratio of CBF between nodes of the DMN and TPN. Furthermore, preliminary exploratory analysis suggests that compared to those without chronic PCS, patients with chronic PCS reveal an imbalance in the ratio of CBF between the DMN nodes and TPN nodes across multiple stages of recovery. Findings suggest that the altered network perfusion with the associated changes in rs-FC may be a possible predictor of which mTBI patients will develop chronic PCS.

Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients

The aim of this study was to investigate if discrete wavelet decomposition provides additional insight into resting-state processes through the analysis of functional connectivity within specific frequency ranges within the default mode network (DMN) that may be affected by mild traumatic brain injury (mTBI). Participants included 32 mTBI patients (15 with postconcussive syndrome [PCS+] and 17 without [PCS-]). mTBI patients received resting-state functional magnetic resonance imaging (rs-fMRI) at acute (within 10 days of injury) and chronic (6 months postinjury) time points and were compared with 31 controls (healthy control [HC]). The wavelet decomposition divides the time series into multiple frequency ranges based on four scaling factors (SF1: 0.125-0.250 Hz, SF2: 0.060-0.125 Hz, SF3: 0.030-0.060 Hz, SF4: 0.015-0.030 Hz). Within each SF, wavelet connectivity matrices for nodes of the DMN were created for each group (HC, PCS+, PCS-), and bivariate measures of strength and diversity were calculated. The results demonstrate reduced strength of connectivity in PCS+ patients compared with PCS- patients within SF1 during both the acute and chronic stages of injury, as well as recovery of connectivity within SF1 across the two time points. Furthermore, the PCS- group demonstrated greater network strength compared with controls at both time points, suggesting a potential compensatory or protective mechanism in these patients. These findings stress the importance of investigating resting-state connectivity within multiple frequency ranges; however, many of our findings are within SF1, which may overlap with frequencies associated with cardiac and respiratory activities.

Altered segregation between task-positive and task-negative regions in mild traumatic brain injury

Changes in large-scale brain networks that accompany mild traumatic brain injury (mTBI) were investigated using functional magnetic resonance imaging (fMRI) during the N-back working memory task at two cognitive loads (1-back and 2-back). Thirty mTBI patients were examined during the chronic stage of injury and compared to 28 control participants. Demographics and behavioral performance were matched across groups. Due to the diffuse nature of injury, we hypothesized that there would be an imbalance in the communication between task-positive and Default Mode Network (DMN) regions in the context of effortful task execution. Specifically, a graph-theoretic measure of modularity was used to quantify the extent to which groups of brain regions tended to segregate into task-positive and DMN sub-networks. Relative to controls, mTBI patients showed reduced segregation between the DMN and task-positive networks, but increased functional connectivity within the DMN regions during the more cognitively demanding 2-back task. Together, our findings reveal that patients exhibit alterations in the communication between and within neural networks during a cognitively demanding task. These findings reveal altered processes that persist through the chronic stage of injury, highlighting the need for longitudinal research to map the neural recovery of mTBI patients.

Cortical multisensory connectivity is present near birth in humans.

How the newborn brain adapts to its new multisensory environment has been a subject of debate. Although an early theory proposed that the brain acquires multisensory features as a result of postnatal experience, recent studies have demonstrated that the neonatal brain is already capable of processing multisensory information. For multisensory processing to be functional, it is a prerequisite that multisensory convergence among neural connections occur. However, multisensory connectivity has not been examined in human neonates nor are its location(s) or afferent sources understood. We used resting state functional MRI (fMRI) in two independent cohorts of infants to examine the functional connectivity of two cortical areas known to be multisensory in adults: the intraparietal sulcus (IPS) and the superior temporal sulcus (STS). In the neonate, the IPS was found to demonstrate significant functional connectivity with visual association and somatosensory association areas, while the STS showed significant functional connectivity with the visual association areas, primary auditory cortex, and somatosensory association areas. Our findings establish that each of these areas displays functional communication with cortical regions representing various sensory modalities. This demonstrates the presence of cortical areas with converging sensory inputs, representing that the functional architecture needed for multisensory processing is already present within the first weeks of life.

Modulation of Resting State Functional Connectivity of the Motor Network by Transcranial Pulsed Current Stimulation

The effects of transcranial pulsed current stimulation (tPCS) on resting state functional connectivity (rs-FC) within the motor network were investigated. Eleven healthy participants received one magnetic resonance imaging (MRI) session with three resting state functional MRI (rs-fMRI) scans, one before stimulation (PRE-STIM) to collect baseline measures, one during stimulation (STIM), and one after 13 min of stimulation (POST-STIM). Rs-FC measures during the STIM and POST-STIM conditions were compared to the PRE-STIM baseline. Regions of interest for the rs-FC analysis were extracted from the significantly activated clusters obtained during a finger tapping motor paradigm and included the right primary motor cortex (R M1), left primary motor cortex (L M1), supplemental motor area (SMA), and cerebellum (Cer). The main findings were reduced rs-FC between the left M1 and surrounding motor cortex, and increased rs-FC between the left M1 and left thalamus during stimulation, but increased rs-FC between the Cer and right insula after stimulations. Bivariate measures of connectivity demonstrate reduced strength of connectivity for the whole network average (p=0.044) and reduced diversity of connectivity for the network average during stimulation (p=0.024). During the POST-STIM condition, the trend of reduced diversity for the network average was statistically weaker (p=0.071). In conclusion, while many of the findings are comparable to previous reports using simultaneous transcranial direct current stimulation (tDCS) and fMRI acquisition, we also demonstrate additional changes in connectivity patterns that are induced by tPCS.

Modulation of working memory load distinguishes individuals with and without balance impairments following mild traumatic brain injury

ABSTRACT Objectives: Balance and gait deficits can persist after mild traumatic brain injury (TBI), yet an understanding of the underlying neural mechanism remains limited. The purpose of this study was to investigate differences in attention network modulation in patients with and without balance impairments 2–8 weeks following mild TBI. Methods: Using functional magnetic resonance imaging, we compared activity and functional connectivity of cognitive brain regions of the default mode, central-executive and salience networks during a 2-back working memory task in participants with mild TBI and balance impairments (n = 7, age 47 ± 15 years) or no balance impairments (n = 7, age 47 ± 15 years). Results: We first identified greater activation in the lateral occipital cortex in the balance impaired group. Second, we observed stronger connectivity of left pre-supplementary motor cortex in the balance impaired group during the working memory task, which was related to decreased activation of regions within the salience and central executive networks and greater suppression of the default mode network. Conclusions: Results suggest a link between impaired balance and modulation of cognitive resources in patients in mTBI. Findings also highlight the potential importance of moving beyond traditional balance assessments towards an integrative assessment of cognition and balance in this population.

In Vivo MRI and MRS of Cerebrovascular Function Following Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability resulting in reduced quality of life for the patients and a significant economic burden to the society. Advances in magnetic resonance imaging techniques are enabling researchers to obtain critical insights into the pathophysiology of the TBI sequelae and also aiding clinicians in predicting long term outcome of TBI patients of all severities. Advanced MRI techniques are able to detect subtle changes in structural integrity of neural tissue as well as changes in functional neural networks. Multi-parametric approaches, including diffusion tensor imaging, functional MRI, magnetic resonance spectroscopy, and arterial spin labeling to non-invasively measure brain perfusion, show promise in detecting trauma-induced biophysical, biochemical and cerebrovascular alterations respectively. Together these techniques are bound to provide us with a better understanding of the sequelae of TBI non-invasively that may lead to better management of TBI patients.