Chronic Mild Traumatic Brain Injury: Aberrant Static and Dynamic Connectomic Features Identified Through Machine Learning Model Fusion

Abstract

Traumatic Brain Injury (TBI) is a frequently occurring condition and approximately 90% of TBI cases are classified as mild (mTBI). However, conventional MRI has limited diagnostic and prognostic value, thus warranting the utilization of additional imaging modalities and analysis procedures. The functional connectomic approach using resting-state functional MRI (rs-fMRI) has shown great potential and promising diagnostic capabilities across multiple clinical scenarios, including mTBI. Additionally, there is increasing recognition of a fundamental role of brain dynamics in healthy and pathological cognition. Here, we undertake an in-depth investigation of mTBI-related connectomic disturbances and their emotional and cognitive correlates. We leveraged machine learning and graph theory to combine static and dynamic functional connectivity (FC) with regional entropy values, achieving classification accuracy up to 75% (77, 74 and 76% precision, sensitivity and specificity, respectively). As compared to healthy controls, the mTBI group displayed hypoconnectivity in the temporal poles, which correlated positively with semantic (r = 0.43, p < 0.008) and phonemic verbal fluency (r = 0.46, p < 0.004), while hypoconnectivity in the right dorsal posterior cingulate correlated positively with depression symptom severity (r = 0.54, p < 0.0006). These results highlight the importance of residual FC in these regions for preserved cognitive and emotional function in mTBI. Conversely, hyperconnectivity was observed in the right precentral and supramarginal gyri, which correlated negatively with semantic verbal fluency (r=-0.47, p < 0.003), indicating a potential ineffective compensatory mechanism. These novel results are promising toward understanding the pathophysiology of mTBI and explaining some of its most lingering emotional and cognitive symptoms.

Altered hippocampal connectivity dynamics predicts memory performance in neuropsychiatric lupus: a resting-state fMRI study using cross-recurrence quantification analysis

“…In contrast to SPL, the left angular gyrus did not display significant cortical atrophy in the present study or aberrant perfusion dynamics in either group of patients with SLE. 11 Interestingly, hyperconnectivity of the left angular gyrus has been documented in at least one other condition (cerebral small vessel disease), 45 characterised by widespread cerebral perfusion disturbances, whereas a similar finding has been recently reported in another inferior parietal region (the supramarginal gyrus 46 ). However, hyperconnectivity of either region with the rest of the brain was negatively associated with cognitive performance in both the present study and another previous study of our group.…”

“…However, hyperconnectivity of either region with the rest of the brain was negatively associated with cognitive performance in both the present study and another previous study of our group. 46 It is thus difficult to rely on previous findings of task-related activations in these regions or on associations between resting-state FC and cognitive performance in healthy participants to help interpret the present findings in a pathological condition. Therefore, we can only surmise as to why left angular hyperconnectivity did not appear to be beneficial to verbal episodic memory capacity based on the fact that this region is considered as one of the major connecting hubs of the resting-state networks 47 and part of the DMN, 48 and as such it consistently shows deactivation during task performance in healthy participants.…”

Functional connectivity-hemodynamic (un)coupling changes in chronic mild brain injury are associated with mental health and neurocognitive indices: a resting state fMRI study

“…The voxel BOLD time series consisted of 150 dynamic volumes, while the voxel size was 3 × 3 × 3 mm (3 mm isotropic). Initial fMRI data preparation steps are in line with previous work of our team on data from the same MRI system [ 28 , 42 – 44 , 56 , 57 ] (see supplementary material ).…”

“…Hypoconnectivity was displayed in the temporal poles, which correlated positively with semantic and phonemic verbal fluency, while hypoconnectivity in the right dorsal posterior cingulate cortex (PCC) correlated positively with depression severity. Conversely, hyperconnectivity was observed in the right precentral and supramarginal gyri, which correlated negatively with semantic verbal fluency, indicating a potentially ineffective compensatory mechanism [ 28 ].…”