Exploring functional neural alterations in patients with persistent post-concussive symptoms: preliminary results from a multimodal study

Concussion represents a public health concern given its incidence and the significant proportion of patients developing persistent post-concussive symptoms (PPCS). While electrophysiology and neuroimaging studies show promise in identifying brain function changes, the pathophysiology of PPCS remains unclear. This study aims to bridge this gap by integrating behavioral assessments with complementary functional magnetic resonance imaging (fMRI) and high-density electroencephalography (HD-EEG) data in patients with PPCS. By leveraging both modalities’ strength, we hope to achieve a more comprehensive understanding of the neural dynamics underlying PPCS. We plan to include 80 patients diagnosed with a concussion based on medical evaluation and with PPCS as signified by a Rivermead Post-Concussion Symptoms Questionnaire (RPQ) score of 16 or higher. Our outcome measures included 3T fMRI and 128-channel HD-EEG recordings in patients with PPCS, alongside behavioral assessments encompassing Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Beck Depression Inventory (BDI). The fMRI analyses focused on thalamocortical connectivity, while HD-EEG focused on whole-brain power spectrum and peak frequency analyses. Additionally, RPQ scores were correlated with fMRI findings, with age and sex as covariates. Data from the patient group were compared to an age-matched control cohort who underwent identical examinations. In our preliminary sample, thirty-four patients (9 males, mean age: 39y.±11.4) with PPCS (RPQ: 40.4±12.5) were recruited between 1 to 12 months post-injury (median: 91 days [59–186]). Twenty-five controls (15 males, mean age: 38.7y.±12.8) were also included. Behavioral assessments revealed that, on average, patients scored at or above the clinical thresholds on the BDI (mean ± SD: 17.3±8.7; threshold = 10), PSQI (11.4±3.9; threshold =5), and ESS (median [IQR]: 9 [5.5-14]; threshold = 9). These scores were all significantly higher than those of the control group (p < 0.001), which had RPQ (0 [0–2]), BDI (2 [0–4]), ESS (6.5±3.5), and PSQI (4.1±2.3). fMRI results indicated increased connectivity in patients between the left thalamus and precentral gyrus (p-FDR=0.023), as well as between the left ventral anterior nucleus and the lateral occipital cortex (p-FDR<0.001), precentral gyrus (p-FDR<0.001), lingual gyrus (p-FDR=0.006), cuneal cortex (p-FDR=0.027), and postcentral gyrus (p-FDR=0.03). Additionally, RPQ scores showed moderate positive correlations between the right ventral anterior thalamic nucleus and both the intracalcarine cortex (p-FDR=0.007) and lateral occipital cortex (p-FDR=0.032). EEG power spectral analysis suggests a shift towards lower frequencies for patients, who more often showed a main alpha peak closer to the theta range, although this difference was not significant. In contrast, higher frequencies (i.e., beta), were more prominent in controls compared to patients (p=0.015). These results confirm previously published behavioral patterns of patients with PPCS and further highlight the potential role of thalamocortical dysfunction in PPCS while underscoring the utility of integrating fMRI and HD-EEG in understanding its pathophysiology.