Cognitive control subprocess deficits and compensatory modulation mechanisms in patients with frontal lobe injury revealed by EEG markers: a basic study to guide brain stimulation

Abstract

Background: Frontal lobe injury (FLI) is related to cognitive control impairments, but the influences of FLI on the internal subprocesses of cognitive control remain unclear.

Aims: We sought to identify specific biomarkers for long-term dysfunction or compensatory modulation in different cognitive control subprocesses.

Methods: A retrospective case-control study was conducted. Event-related potentials (ERP), oscillations and functional connectivity were used to analyse electroencephalography (EEG) data from 12 patients with unilateral frontal lobe injury (UFLI), 12 patients with bilateral frontal lobe injury (BFLI) and 26 healthy controls (HCs) during a Go/NoGo task, which included several subprocesses: perceptual processing, anticipatory preparation, conflict monitoring and response decision.

Results: Compared with the HC group, N2 (the second negative peak in the averaged ERP waveform) latency, and frontal and parietal oscillations were decreased only in the BFLI group, whereas P3 (the third positive peak in the averaged ERP waveform) amplitudes and sensorimotor oscillations were decreased in both patient groups. The functional connectivity of the four subprocesses was as follows: alpha connections of posterior networks in the BFLI group were lower than in the HC and UFLI groups, and these alpha connections were negatively correlated with neuropsychological tests. Theta connections of the dorsal frontoparietal network in the bilateral hemispheres of the BFLI group were lower than in the HC and UFLI groups, and these connections in the uninjured hemisphere of the UFLI group were higher than in the HC group, which were negatively correlated with behavioural performances. Delta and theta connections of the midfrontal-related networks in the BFLI group were lower than in the HC group. Theta across-network connections in the HC group were higher than in the BFLI group but lower than in the UFLI group.

Conclusions: The enhancement of low-frequency connections reflects compensatory mechanisms. In contrast, alpha connections are the opposite, therefore revealing more abnormal neural activity and less compensatory connectivity as the severity of injury increases. The nodes of the above networks may serve as stimulating targets for early treatment to restore corresponding functions. EEG biomarkers can measure neuromodulation effects in heterogeneous patients.

Keywords: Cerebral Cortex; Cognitive Dysfunction; Executive Function; Prefrontal Cortex; Trauma and Stressor Related Disorders.

Figure 1

Flowchart of enrolment of the subjects. All of these patients were evaluated by physicians with professional clinical experience based on clinical diagnostic criteria. BFLI, bilateral frontal lobe injury; CT, computed tomography; EEG, electroencephalography; GCS, Glasgow Coma Scale; HC, healthy control; MRI, magnetic resonance imaging; TBI, traumatic brain injury; UFLI, unilateral frontal lobe injury.

Figure 2

Event-related potential results under Go and NoGo conditions. (A) Average ERP waveforms for HC, UFLI and BFLI groups under the Go condition. Black line: responses of HCs. Red line: responses of patients with UFLI. Light blue line: responses of patients with BFLI. The representative electrode locations are as follows: left parietal (P3), middle parietal (Pz) and right parietal (P4) scalp sites. (B) Topographical maps of the P3 (240–390 ms) for the HC, UFLI and BFLI groups under the Go condition. (C) Average ERP waveforms for the HC, UFLI and BFLI groups under the NoGo condition. Black line: responses of the HCs. Red line: responses of patients with UFLI. Light blue line: responses of patients with BFLI. The representative electrode locations are as follows: left frontal (F3), middle frontal (Fz) and right frontal (F4) scalp sites. (D) Topographical maps of the P3 (300–430 ms) for HC, UFLI and BFLI groups under the NoGo condition. BFLI, bilateral frontal lobe injury; ERP, event-related potential; HC, healthy control; UFLI, unilateral frontal lobe injury.

Figure 3

Event-related oscillation results under Go and NoGo conditions. (A) Time-frequency spectrograms of Go oscillatory power are plotted separately for HC (top panel), UFLI (median panel), and BFLI (bottom panel) groups at the middle frontal (Fz), middle central (Cz) and middle parietal (Pz) scalp sites. The red and black solid boxes indicate the delta (1–4 Hz) and theta (4–8 Hz) frequency bands in the same time window (150–550 ms) of interest, respectively, that are averaged for the analysis of variance (ANOVA). (B) Topographical maps of delta (left panel) and theta (right panel) power are plotted separately for HC (top panel), UFLI (median panel), and BFLI (bottom panel) groups averaged across all trials within Go blocks. (C) Time-frequency spectrograms of NoGo oscillatory power are plotted separately for HC (top panel), UFLI (median panel) and BFLI (bottom panel) groups at the middle frontal (Fz), middle central (Cz) and middle parietal (Pz) scalp sites. The red and black solid boxes indicate the delta (1–4 Hz) and theta (4–8 Hz) frequency bands in the same time window (150–550 ms) of interest, respectively, that are averaged for the ANOVA. (D) Topographical maps of delta (left panel) and theta (right panel) power are plotted separately for HC (top panel), UFLI (median panel) and BFLI (bottom panel) groups averaged across all trials within NoGo blocks. BFLI, bilateral frontal lobe injury; HC, healthy control; UFLI, unilateral frontal lobe injury.

Figure 4

Global functional connectivity under Go and NoGo conditions. (A) Average SWPLI at 0.1~100 Hz from −300 ms to 800 ms after the stimuli in the HC, UFLI and BFLI groups. (B) Time courses of the average SWPLI for delta, theta and alpha frequency bands in HC, UFLI and BFLI groups. (C) Statistical results of the whole-brain SWPLI for delta, theta and alpha frequency bands. **p<0.01, ***p<0.001. BFLI, bilateral frontal lobe injury; HC, healthy control; SWPLI, standardised weighted-phase lag index; UFLI, unilateral frontal lobe injury.

Figure 5

Topographical differentiation between groups for functional connectivity under Go and NoGo conditions. (A) Significant topographical representations between channels for delta, theta and alpha frequency bands of the HC group versus the UFLI group, the HC group versus the BFLI group, and the UFLI group versus the BFLI group under the Go condition. The red colour indicates higher values for the second group than the first group, the blue colour indicates the opposite. (B) Significant topographical representations between channels for delta and theta frequency bands of the HC group versus the UFLI group, the HC group versus the BFLI group, and the UFLI group versus the BFLI group in the NoGo condition. The red colour indicates higher values for the second group than the first group, the blue colour indicates the opposite. BFLI, bilateral frontal lobe injury; HC, healthy control; UFLI, unilateral frontal lobe injury.