Reduced brain connectivity and mental flexibility in mild traumatic brain injury.
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ABSTRACT:
SUBMITTER: Pang EW
PROVIDER: S-EPMC4748313 | biostudies-other | 2016 Feb
REPOSITORIES: biostudies-other
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Project description:ObjectivesResearch suggests that the majority of mild traumatic brain injury (mTBI) patients exhibit both cognitive and emotional dysfunction within the first weeks of injury, followed by symptom resolution 3-6 months postinjury. The neuronal correlates of said dysfunction are difficult to detect with standard clinical neuroimaging, complicating differential diagnosis and early identification of patients who may not recover. This study examined whether resting state functional magnetic resonance imaging (fMRI) provides objective markers of injury and predicts cognitive, emotional, and somatic complaints in mTBI patients semiacutely (<3 weeks postinjury) and in late recovery (3-5 month) phases.MethodsTwenty-seven semiacute mTBI patients and 26 gender, age, and education-matched controls were studied. Fifteen of 27 patients returned for a follow-up visit 3-5 months postinjury. The main dependent variables were spontaneous fluctuations (temporal correlation) in the default-mode (DMN) and fronto-parietal task-related networks as measured by fMRI.ResultsSignificant differences in self-reported cognitive, emotional, and somatic complaints were observed (all P < 0.05), despite normal clinical (T1 and T2) imaging and neuropsychological testing results. Mild TBI patients demonstrated decreased functional connectivity within the DMN and hyper-connectivity between the DMN and lateral prefrontal cortex. Measures of functional connectivity exhibited high levels of sensitivity and specificity for patient classification and predicted cognitive complaints in the semi-acute injury stage. However, no changes in functional connectivity were observed across a 4-month recovery period.ConclusionsAbnormal connectivity between the DMN and frontal cortex may provide objective biomarkers of mTBI and underlie cognitive impairment.
| S-EPMC3204375 | biostudies-literature
Project description:ObjectiveThe aims of this study were to investigate changes in regional brain volume after concussion (mild traumatic brain injury) and to examine the relationship between change in brain volume and cognitive deficits.DesignTwenty-eight patients with mild traumatic brain injury and 27 age-matched controls were included in this study. Magnetic resonance imaging (3 T) data were obtained from the participants. Structural brain volume changes were examined using tensor-based morphometry, which identifies regional structural differences in the whole brain, including cerebrospinal fluid, gray matter, and white matter. Volume contraction and expansion were compared between groups using a two-sample t test. The association between time post-injury or neurocognitive function and volumetric changes was examined using regression analysis.ResultsIndividuals with mild traumatic brain injury exhibited volume reduction in the brainstem, including the pontine reticular formation. Regional cerebral volume changes were not associated with time post-injury but were significantly associated with neurocognitive function, especially with executive card sorting test, forward digit span test, and performance on verbal learning test. The greater regional cerebral volume was associated with better cognitive performance after mild traumatic brain injury.ConclusionDecreased brainstem volume may indicate its vulnerability to traumatic injury, and cerebral volume in specific regions was positively associated with patients' cognitive function after injury.
| S-EPMC8032213 | biostudies-literature
Project description:Mild traumatic brain injury (mTBI) is the most common neurological disorder and is typically characterized by temporally limited cognitive impairment and emotional symptoms. Previous examinations of intrinsic resting state networks in mTBI have primarily focused on abnormalities in static functional connectivity, and deficits in dynamic functional connectivity have yet to be explored in this population. Resting-state data was collected on 48 semi-acute (mean = 14 days post-injury) mTBI patients and 48 matched healthy controls. A high-dimensional independent component analysis (N = 100) was utilized to parcellate intrinsic connectivity networks (ICN), with a priori hypotheses focusing on the default-mode network (DMN) and sub-cortical structures. Dynamic connectivity was characterized using a sliding window approach over 126 temporal epochs, with standard deviation serving as the primary outcome measure. Finally, distribution-corrected z-scores (DisCo-Z) were calculated to investigate changes in connectivity in a spatially invariant manner on a per-subject basis. Following appropriate correction for multiple comparisons, no significant group differences were evident on measures of static or dynamic connectivity within a priori ICN. Reduced (HC > mTBI patients) static connectivity was observed in the DMN at uncorrected (p < 0.005) thresholds. Finally, a trend (p = 0.07) for decreased dynamic connectivity in patients across all ICN was observed during spatially invariant analyses (DisCo-Z). In the semi-acute phase of recovery, mTBI was not reliably associated with abnormalities in static or dynamic functional connectivity within the DMN or sub-cortical structures.
| S-EPMC4504345 | biostudies-literature
Project description:PURPOSE:To investigate whether there is imaging evidence of hypothalamic injury in patients with mild traumatic brain injury (MTBI), which is a major public health problem due to the high prevalence and difficulty in diagnosis and treatment. MATERIALS AND METHODS:Twenty-four patients (mean age 34.2, range, 18-56 years) with symptomatic MTBI and 22 age-matched healthy controls (mean age 37.0, range 20-61 years) participated in the study. Diffusion kurtosis imaging was performed with diffusion-weighted images acquired along 30 gradient directions and three b-values (b?=?0, 1000, 2000 s/mm2 ) based on a twice-refocused spin-echo sequence with a 3T magnetic resonance imaging (MRI) scanner. Resting-state functional (f)MRI with standard echo planar imaging (EPI) were performed to localize the resting-state networks (RSN) and hypothalamic functional connectivity. RESULTS:There were significantly reduced mean kurtosis (P?=?0.0092) and radial kurtosis (P?=?0.0078) in patients as compared to controls in the hypothalamus. Furthermore, there was a significant negative correlation (r?=?-0.675, P?=?0.0007) between radial kurtosis in the hypothalamus and fatigue severity scale in patients. The MTBI group also showed disrupted hypothalamic RSNs, with significantly decreased positive connectivity in medial prefrontal cortex, inferior posterior parietal, and cingulate regions but increased connectivity in the peri-hypothalamic regions and cerebellum, together with significantly decreased negative RSNs in visual and bilateral premotor areas (cluster corrected P < 0.05). CONCLUSION:Our results show disruption of functional and structural hypothalamic connectivity in patients with MTBI, and might further the understanding of an array of clinical symptoms in MTBI such as sleep disturbance and fatigue. LEVEL OF EVIDENCE:2 J. Magn. Reson. Imaging 2017;45:1105-1112.
| S-EPMC5274605 | biostudies-literature
Project description:Mental fatigue in healthy individuals is typically observed under conditions of high cognitive demand, particularly when effort is required to perform a task for a long period of time-thus the concepts of fatigue and effort are closely related. In brain injured individuals, mental fatigue can be a persistent and debilitating symptom. Presence of fatigue after brain injury is prognostic for return to work/school and engagement in activities of daily life. As such, it should be a high priority for treatment in this population, but because there is little understanding of its behavioral and neural underpinnings, the target for such treatment is unknown. Here, the neural underpinnings of fatigue and effort are investigated in active duty military service members with mild traumatic brain injury (mTBI) and demographically-matched orthopedic controls. Participants performed a Constant Effort task for which they were to hold a pre-defined effort level constant for long durations during fMRI scanning. The task allowed for investigation of the neural systems underlying fatigue and their relationship with sense of effort. While brain activation associated with effort and fatigue did not differentiate the mTBI and controls, functional connectivity amongst active brain regions did. The mTBI group demonstrated immediate hyper-connectivity that increased with effort level but diminished quickly when there was a need to maintain effort. Controls, in contrast, demonstrated a similar pattern of hyper-connectivity, but only when maintaining effort over time. Connectivity, particularly between the left anterior insula, rostral anterior cingulate cortex, and right-sided inferior frontal regions, correlated with effort-level and state fatigue in mTBI participants. These connections also correlated with effort level in the Control group, but only the connection between the left insula and superior medial frontal gyrus correlated with fatigue, suggesting a differing pattern of connectivity. These findings align, in part, with the dopamine imbalance, and neural efficiency hypotheses that pose key roles for medial frontal connections with insular or striatal regions in motivating or optimizing performance. Sense of effort and fatigue are closely related. As people fatigue, sense of effort increases systematically. The data propose a complex link between sense of effort, fatigue, and mTBI that is centered in what may be an inefficient neural system due to brain trauma that warrants further investigation.
| S-EPMC6345685 | biostudies-literature
Project description:Mild traumatic brain injury (mTBI) may affect normal cognition and behavior by disrupting the functional connectivity networks that mediate efficient communication among brain regions. In this study, we analyzed brain connectivity profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 31 mTBI patients and 55 normal controls. We used phase-locking value estimates to compute functional connectivity graphs to quantify frequency-specific couplings between sensors at various frequency bands. Overall, normal controls showed a dense network of strong local connections and a limited number of long-range connections that accounted for approximately 20% of all connections, whereas mTBI patients showed networks characterized by weak local connections and strong long-range connections that accounted for more than 60% of all connections. Comparison of the two distinct general patterns at different frequencies using a tensor representation for the connectivity graphs and tensor subspace analysis for optimal feature extraction showed that mTBI patients could be separated from normal controls with 100% classification accuracy in the alpha band. These encouraging findings support the hypothesis that MEG-based functional connectivity patterns may be used as biomarkers that can provide more accurate diagnoses, help guide treatment, and monitor effectiveness of intervention in mTBI.
| S-EPMC4632071 | biostudies-literature
Project description:Mild traumatic brain injury (mTBI) can result in symptoms that affect a person's cognitive and social abilities. Improvements in diagnostic methodologies are necessary given that current clinical techniques have limited accuracy and are solely based on self-reports. Recently, resting state functional network connectivity (FNC) has shown potential as an important imaging modality for the development of mTBI biomarkers. The present work explores the use of dynamic functional network connectivity (dFNC) for mTBI detection. Forty eight mTBI patients (24 males) and age-gender matched healthy controls were recruited. We identified a set of dFNC states and looked at the possibility of using each state to classify subjects in mTBI patients and healthy controls. A linear support vector machine was used for classification and validated using leave-one-out cross validation. One of the dFNC states achieved a high classification performance of 92% using the area under the curve method. A series of t-test analysis revealed significant dFNC increases between cerebellum and sensorimotor networks. This significant increase was detected in the same dFNC state useful for classification. Results suggest that dFNC can be used to identify optimal dFNC states for classification excluding those that does not contain useful features.
| S-EPMC6051314 | biostudies-other
Project description:Older age is associated with worsened outcome after mild traumatic brain injury (mTBI) and a higher risk of developing persistent post-traumatic complaints. However, the effects of mTBI sequelae on brain connectivity at older age and their association with post-traumatic complaints remain understudied.We analyzed multi-echo resting-state functional magnetic resonance imaging data from 25 older adults with mTBI (mean age: 68 years, SD: 5 years) in the subacute phase (mean injury to scan interval: 38 days, SD: 9 days) and 20 age-matched controls. Severity of complaints (e.g. fatigue, dizziness) was assessed using self-reported questionnaires. Group independent component analysis was used to identify intrinsic connectivity networks (ICNs). The effects of group and severity of complaints on ICNs were assessed using spatial maps intensity (SMI) as a measure of within-network connectivity, and (static) functional network connectivity (FNC) as a measure of between-network connectivity.Patients indicated a higher total severity of complaints than controls. Regarding SMI measures, we observed hyperconnectivity in left-mid temporal gyrus (cognitive-language network) and hypoconnectivity in the right-fusiform gyrus (visual-cerebellar network) that were associated with group. Additionally, we found interaction effects for SMI between severity of complaints and group in the visual(-cerebellar) domain. Regarding FNC measures, no significant effects were found.In older adults, changes in cognitive-language and visual(-cerebellar) networks are related to mTBI. Additionally, group-dependent associations between connectivity within visual(-cerebellar) networks and severity of complaints might indicate post-injury (mal)adaptive mechanisms, which could partly explain post-traumatic complaints (such as dizziness and balance disorders) that are common in older adults during the subacute phase.
| S-EPMC9279274 | biostudies-literature
Project description:The thalamo-cortical resting state functional connectivity of seven sub-thalamic regions were examined in a prospectively recruited population of 77 acute mild TBI (mTBI) patients within the first 10 days (mean 6?±?3 days) of injury and 35 neurologically intact control subjects using the Oxford thalamic connectivity atlas. Neuropsychological assessments were conducted using the Automated Neuropsychological Assessment Metrics (ANAM). A subset of participants received a magentic resonance spectroscopy (MRS) exam to determine metabolite concentrations in the thalamus and the posterior cingulate cortex. Results show that patients performed worse than the control group on various subtests of ANAM and the weighted throughput score, suggesting reduced cognitive performance at this early stage of injury. Both voxel and region of interest based analysis of the resting state fMRI data demonstrated that acute mTBI patients have increased functional connectivity between the various sub-thalamic regions and cortical regions associated with sensory processing and the default mode network (DMN). In addition, a significant reduction in NAA/Cr was observed in the thalamus in the mTBI patients. Furthermore, an increase in Cho/Cr ratio specific to mTBI patients with self-reported sensory symptoms was observed compared to those without self-reported sensory symptoms. These results provide novel insights into the neural mechanisms of the brain state related to internal rumination and arousal, which have implications for new interventions for mTBI patients with persistent symptoms. Furthermore, an understanding of heightened sensitivity to sensory related inputs during early stages of injury may facilitate enhanced prediction of safe return to work.
| S-EPMC4577461 | biostudies-literature
Project description:Traumatic brain injury (TBI) often has long-term debilitating sequelae in cognitive and behavioral domains. Understanding how TBI impacts functional integrity of brain networks that underlie these domains is key to guiding future approaches to TBI rehabilitation. In the current study, we investigated the differences in inter-hemispheric functional connectivity (FC) of resting state networks (RSNs) between chronic mild-to-severe TBI patients and normal comparisons (NC), focusing on two externally oriented networks (i.e., the fronto-parietal network [FPN] and the executive control network [ECN]), one internally oriented network (i.e., the default mode network [DMN]), and one somato-motor network (SMN). Seed voxel correlation analysis revealed that TBI patients displayed significantly less FC between lateralized seeds and both homologous and non-homologous regions in the opposite hemisphere for externally oriented networks but not for DMN or SMN; conversely, TBI patients showed increased FC within regions of the DMN, especially precuneus and parahippocampal gyrus. Region of interest correlation analyses confirmed the presence of significantly higher inter-hemispheric FC in NC for the FPN (p?<?0.01), and ECN (p?<?0.05), but not for the DMN (p?>?0.05) or SMN (p?>?0.05). Further analysis revealed that performance on a neuropsychological test measuring organizational skills and visuo-spatial abilities administered to the TBI group, the Rey-Osterrieth Complex Figure Test, positively correlated with FC between the right FPN and homologous regions. Our findings suggest that distinct RSNs display specific patterns of aberrant FC following TBI; this represents a step forward in the search for biomarkers useful for early diagnosis and treatment of TBI-related cognitive impairment.
| S-EPMC4909322 | biostudies-literature