Excitation/Inhibition balance relates to cognitive function and gene expression in temporal lobe epilepsy: a high density EEG assessment with aperiodic exponent

Abstract

Patients with epilepsy are characterized by a dysregulation of excitation/inhibition balance (E/I). The assessment of E/I may inform clinicians during the diagnosis and therapy management, even though it is rarely performed. An accessible measure of the E/I of the brain represents a clinically relevant feature. Here, we exploited the exponent of the aperiodic component of the power spectrum of the electroencephalography (EEG) signal, as a non-invasive and cost-effective proxy of the E/I balance. We recorded resting-state activity with high-density EEG from 67 patients with temporal lobe epilepsy and 35 controls. We extracted the exponent of the aperiodic fit of the power spectrum from source-reconstructed EEG and tested differences between patients with epilepsy and controls. Spearman's correlation was performed between the exponent and clinical variables (age of onset, epilepsy duration and neuropsychology) and cortical expression of epilepsy-related genes derived from the Allen Human Brain Atlas. Patients with temporal lobe epilepsy showed a significantly larger exponent, corresponding to inhibition-directed E/I balance, in bilateral frontal and temporal regions. Lower E/I in the left entorhinal and bilateral dorsolateral prefrontal cortices corresponded to a lower performance of short-term verbal memory. Limited to patients with temporal lobe epilepsy, we detected a significant correlation between the exponent and the cortical expression of GABRA1, GRIN2A, GABRD, GABRG2, KCNA2 and PDYN genes. EEG aperiodic exponent maps the E/I balance non-invasively in patients with epilepsy and reveals a close relationship between altered E/I patterns, cognition and genetics.

Keywords: aperiodic exponent; excitation/inhibition balance; genetic expression; memory functioning; temporal lobe epilepsy.

Graphical Abstract

Figure 1

Analytical pipeline. The present figure displays the analytical steps performed. Panel A follows the steps for extracting aperiodic exponents from resting-state EEG recordings. Panel B graphically explains the statistical comparison performed. Panel C represents the correlational analysis between clinical variables, neuropsychological assessment, gene expression and aperiodic exponent.

Figure 2

Statistical difference across groups of the nodal aperiodic exponent. Panel A displays the statistical difference of the aperiodic exponent comparing all patients with temporal lobe epilepsy (All patients; N = 67), left temporal lobe epilepsy (left-TLE; N = 30), right temporal lobe epilepsy (right-TLE; N = 17) and BTLE (N = 20) versus HC (N = 35). Panel B shows the PSD and the fit of the aperiodic component (fit) and the corresponding exponent values (exp) of the regions with the maximum t-value in each of the comparisons performed for patients with epilepsy (orange line) and HC (blue line). Specifically, we reported lingual left (lingual L), middle temporal left (middle temporal L), temporal pole left (temporal pole L) and frontal pole left (frontal pole L), derived from the Desikan–Killiany atlas. The statistical test used was permutation two-tail t-test. Cortical maps are thresholded at P < 0.05 after FDR correction.

Figure 3

Exponent correlation with clinical and transcriptomics variables. Panel A shows the spatial distribution on the cortex of the node-wise correlation (Spearman’s rho) between the region aperiodic exponent and the number of ASMs and the short-term verbal memory functioning measured by the Imm-Recall of the RAVLT. Panel B displays the exponent-gene expression correlation both for patients with TLE patients (upper line) and the control group (controls; lower line). In the correlation plots, each dot represents the related gene expression level in the x-axis and the relative aperiodic exponent level in the y-axis of all the ROIs of the atlas. The shaded area around the correlation line represents the 95% confidence interval. The brain plots in black and white illustrate the node-wise cortical expression of the corresponding gene.