Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct 17:19:1671804.
doi: 10.3389/fnhum.2025.1671804. eCollection 2025.

Aperiodic brain activity changes in patients with stroke following virtual reality-based upper limb robotic rehabilitation: a pilot Randomized Controlled Trial

Affiliations

Aperiodic brain activity changes in patients with stroke following virtual reality-based upper limb robotic rehabilitation: a pilot Randomized Controlled Trial

Maria Cristina Mauro et al. Front Hum Neurosci. .

Abstract

Introduction: Stroke-related brain changes have traditionally been studied through oscillatory electroencephalographic (EEG) activity, but recent evidence highlights the value of aperiodic components. This pilot randomized controlled trial aimed to assess stroke-related aperiodic EEG changes following virtual reality-based robotic rehabilitation using the Spectral Exponent Index (SEI).

Methods: Nineteen patients with subacute stroke were randomized to unilateral (n = 9) or bilateral (n = 10) upper limb training with a robotic exoskeleton (30 sessions). EEG was recorded at rest before (T0), after (T1), and at 1-week follow-up (T2). SEI was computed for hemispheric and sensorimotor clusters, in affected (AH) and unaffected (UH) hemispheres. Clinical evaluation was performed at T0 and T1 with validated clinical scales.

Results: At T0, the SEI in the sensorimotor cluster of the AH was significantly lower than in the UH. At T1, the SEI in the AH increased together with clinical improvements in upper limb motor function. At T2, the SEI in the AH decreased again and was lower than in the UH. No differences were found between unilateral and bilateral groups.

Discussion: Robotic rehabilitation modulated the aperiodic EEG background in the affected hemisphere of patients with stroke, particularly in sensorimotor areas. These SEI changes mirrored motor recovery, suggesting that it may represent a useful biomarker to track localized neural mechanisms of functional improvement after stroke. No differences between unilateral and bilateral training likely reflect the pilot sample size or shared cortical mechanisms of action activated by both rehabilitation approaches.

Clinical trial registration: ClinicalTrials.gov registration number: NCT05176600.

Keywords: Spectral Exponent Index (SEI); quantitative electroencephalography (QEEG); rehabilitation; robotics; virtual reality (VR).

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Arm light exoskeleton rehab station (ALEx RS).
Figure 2
Figure 2
CONSORT flow diagram of participant screening, allocation, treatment, evaluations and follow-up. Total number of participants (n) are shown at each stage.
Figure 3
Figure 3
Clinical scales before (T0) and after (T1) rehabilitation, for the unilateral (UG, green) and bilateral (BG, red) group. FMA-UE, Fugl-Meyer assessment for upper extremity; ARAT, action research arm test; WMFT, wolf motor function test; MI, Motricity Index. *p < 0.05, **p < 0.01.
Figure 4
Figure 4
Spectral Exponent Index (SEI) in the hemispheric cluster for all patients (left), for the unilateral group (center), and for the bilateral group (right). SEI values are averaged over the hemispheric cluster, i.e., all electrodes of each hemisphere (affected: red; unaffected: blue). T0: baseline timepoint; T1: end of rehabilitation; T2: follow-up.
Figure 5
Figure 5
Spectral Exponent Index (SEI) in the sensorimotor cluster for all patients (left), for the unilateral group (center), and for the bilateral group (right). *p < 0.05, **p < 0.01. The red colored asterisk refers to the significant difference between SEI in the affected sensorimotor cluster at timepoint T0 (before rehabilitation) and the one at timepoint T1 (after rehabilitation). The black colored asterisks refer instead to the comparison between affected and unaffected hemispheres at timepoints T0 and T2 (follow-up). SEI values are averaged over the sensorimotor cluster, i.e., electrodes anatomically over primary motor and somatosensory cortex, for each hemisphere (affected: red; unaffected: blue).

References

    1. Ahmadlou M., Adeli H., Adeli A. (2010). New diagnostic EEG markers of the Alzheimer's disease using visibility graph. J. Neural. Transm. 117, 1099–1109. 10.1007/s00702-010-0450-3 - DOI - PubMed
    1. Ajčević M., Furlanis G., Miladinović A., Buoite Stella A., Caruso P., Ukmar M., et al. (2021). Early EEG alterations correlate with CTP hypoperfused volumes and neurological deficit: a wireless EEG Study in hyper-acute ischemic stroke. Ann. Biomed. Eng. 49, 2150–2158. 10.1007/s10439-021-02735-w - DOI - PMC - PubMed
    1. Alashram A. R. (2024). Combined robot-assisted therapy virtual reality for upper limb rehabilitation in stroke survivors: a systematic review of randomized controlled trials. Neurol. Sci. 45, 5141–5155. 10.1007/s10072-024-07628-z - DOI - PubMed
    1. Aprile I., Germanotta M., Cruciani A., Loreti S., Pecchioli C., Cecchi F., et al. (2020). Upper limb robotic rehabilitation after stroke: a multicenter, randomized clinical trial. J. Neurol. Phys. Ther. 44, 3–14. 10.1097/NPT.0000000000000295 - DOI - PubMed
    1. Biskamp J., Isla Cainzos S., Higgen F. L., Gerloff C., Magnus T. (2022). Normalization of aperiodic electrocorticography components indicates fine motor recovery after sensory cortical stroke in mice. Stroke 53, 2945–2953. 10.1161/STROKEAHA.122.039335 - DOI - PubMed

Associated data

LinkOut - more resources