Brain Oscillatory Modes as a Proxy of Stroke Recovery

Abstract

BackgroundStroke is the leading cause of long-term disability, making the search for successful rehabilitation treatment one of the most important public health issues. A better understanding of the neural mechanisms underlying impairment and recovery is critical for optimizing treatments. Objective: We studied the longitudinal changes in brain oscillatory modes, linked to GABAergic system activity, and determined their importance for residual upper-limb motor functions and recovery.MethodsTranscranial Magnetic Stimulation (TMS) was combined with scalp Electroencephalography (EEG) to analyze TMS-induced brain oscillations in a cohort of 66 stroke patients in the acute (N = 60), early (N = 48), and late subacute stages (N = 37).ResultsA data-driven parallel factor analysis (PARAFAC) approach to tensor decomposition extracted brain oscillatory modes, which significantly evolved longitudinally across stroke stages (permutation tests, p_Bonf < 0.05). Notably, the observed decrease of the α-mode, known to be linked with GABAergic system activity, was mainly driven by the recovering patients and was supportive of stroke recovery at the group level (Bayesian Kendall correlation, moderate to strong statistical evidence).ConclusionsOverall, longitudinal evaluation of brain modes provides novel insights into functional reorganization of brain networks after a stroke. Notably, we propose that the observed α-mode decrease could correspond to a beneficial disinhibition toward the late subacute stage that fosters plasticity and facilitates recovery. These results confirm the relevance of future individual and direct monitoring of post-stroke modulations in inhibitory system activity, with the ultimate goal of designing electrophysiological biomarkers and refining therapies based on personalized neuromodulation.

Keywords: GABAergic disinhibition; TMS-EEG; motor recovery; stroke; α oscillations.

Figure 1.

Protocol design and main data processing pipeline. (A). Protocol design including 3 TMS-EEG sessions (referred to as the acute, early subacute, and late subacute stages, respectively). (B). Signal processing pipeline for computing induced oscillation maps. For each patient and channel, the evoked activity was removed from the clean signal prior to the time-frequency (TF) transform. Each TF map was z transformed before averaging across trials. (C). Tensor decomposition using the PARAFAC approach. Induced oscillation maps were compiled into a tensor, with the patient and stroke stages as the 4th and 5th dimensions, respectively, and decomposed using the PARAFAC algorithm. This decomposition led to several components, or modes, whose weights are represented in the space (topography), frequency, time, patient, and stroke-stage dimensions, from left to right.

Figure 2.

Upper-limb motor impairment evolution. From left to right: FM-UE-total score distributions significantly increased across stroke stages for the whole cohort (N = 66), the recovering group (N = 40), and for the subsets of recovering patients (N = 17) and patients that fulfilled the criterion of minimum clinically important difference (MCID+, N = 12) included in the full longitudinal analysis (see text).

Figure 3.

Brain oscillatory modes in acute stroke patients and their modulation toward subacute stages. (A) PARAFAC decomposition of the 4D tensor of the TMS-induced oscillations in acute stroke patients. Modes are sorted by row according to their main frequency peak, from low frequencies (1/f spectral trend, blue) and α (8 Hz, red) to β (15 Hz, green) frequency bands (top to bottom). Each column depicts the relative weights (from 0 to maximum) of each mode in the space, frequency, time, and patient dimensions (from left to right). The mode frequency peak is highlighted in color on the y-axis. Data were flipped for patients whose lesion was located on the right hemisphere so that the ipsilesional side was the left side. (B) PARAFAC decomposition of the longitudinal 5D tensor in all patients. The modes are represented identically, except for the addition of a fifth dimension representing the stroke stage (right). The asterisk and colored lines indicate significant effects of the pairwise comparisons of the stroke stages within the 1/f (blue lines) and α (red lines) modes for the acute (A) versus late subacute (LSA) stages and the early subacute (ESA) versus late subacute (LSA) stages (permutation test, p_Bonf < 0.05, see Statistical analysis).

Figure 4.

Evolution of brain oscillatory modes from acute to subacute stages. (A) PARAFAC decomposition of the 5D tensor in all patients. The modes are sorted by peak frequency, from 1/f (blue) and α (red) to β (green) bands. Each column depicts the relative weights (from 0 to maximum) of each mode in the space, frequency, time, patient, and stroke-stage dimensions (from left to right), limited here to A and ESA. (B and C). The results of the same decomposition, run separately on the A and LSA stages (B) and on the ESA and LSA stages (C). The asterisk and colored lines indicate significant effects of the pairwise comparisons of the stroke stages (permutation test, p_Bonf < .05, see Statistical analysis).

Figure 5.

Links among brain oscillatory modes, motor impairment and motor recovery. (A). PARAFAC decomposition of the 5D tensor in stable (left) and recovering (right) patients. (B) Association between the α-band mode and (a) motor impairment in the acute stage, and (b-c) motor recovery toward the early (b) and late (c) subacute stages. The Kendall rank correlation coefficient (τ) and Bayesian factors (BF₁₀) are indicated for each comparison, and all data are plotted according to their rank.

Figure 6.

Time course of GABAergic inhibition and its relationship with recovery. The changes in early TMS-evoked reactivity (as demonstrated in Harquel et al,) and in late TMS-induced α waves, both most likely correlates of a decrease in GABAergic activity at different spatial scales, represent recovery-facilitating functional disinhibition after the detrimental hyper-inhibitory period in the hyper-acute stage after the stroke. Based on the present findings, this disinhibition occurs in 2 phases: first locally within the ipsilesional motor cortex in the acute to subacute stage, and then more broadly toward the late subacute stage. Such disinhibition fosters structural and functional plasticity that support motor recovery.^,,