Methodology and preliminary data on feasibility of a neurofeedback protocol to improve visual attention to letters in mild Alzheimer's disease

Abstract

Background: Brain-computer interface (BCI) systems are controlled by users through neurophysiological input for a variety of applications, including communication, environmental control, and motor rehabilitation. Although individuals with severe speech and physical impairment are the primary users of this technology, BCIs have emerged as a potential tool for broader populations, including delivering cognitive training/interventions with neurofeedback (NFB).

Methods: This paper describes the development and preliminary testing of a protocol for use of a BCI system with NFB as an intervention for people with mild Alzheimer's disease (AD). The intervention focused on training visual attention and language skills, as AD is often associated with functional impairments in both. This funded pilot study called for enrolling five participants with mild AD in a six-week BCI EEG-based NFB intervention that followed a four-to-seven-week baseline phase. While two participants completed the study, the remaining three participants could not complete the intervention phase because of COVID-19 restrictions.

Results: Preliminary pilot results suggested: (1) participants with mild AD were able to participate in a study with multiple assessments per week and complete all outcome measures, (2) most outcome measures were reliable during the baseline phase, and (3) all participants with mild AD learned to operate a BCI spelling system with training.

Conclusions: Although preliminary results demonstrate practical feasibility to deliver NFB intervention using a BCI to adults with AD, completion of the protocol in its entirety with more participants is needed to further assess whether implementing NFB-based cognitive intervention is justified by functional treatment outcomes.

Trial registration: This study was registered with ClinicalTrials.gov (NCT03790774).

Keywords: Alzheimer disease; Attention; Brain-computer interfaces; Cognitive remediation.

Conflict of interest statement

All authors received a salary for their work from their respective institutions.

© 2022 The Authors. Published by Elsevier Inc.

Figures

Fig. 1

Study Activities This infographic depicts the assessments conducted at each visit type and the frequency of their measure across phrases of the study. The dashed lines in the baseline phase represent the variability in number of baseline visits that varied between 4 and 7 visits based on stability of baseline performance from week-to-week.

Fig. 2

Schematic of the RSVP task and the neurofeedback to the participant. Following presentation of the target letter there is a sequence of 10 letters presented following a red cross-hair fixation cross. Neurofeedback is based on individualized alpha Power Spectral Density (PSD) percentiles at a pre-specified occipitoparietal electrode. Colored boxes range from upper 15th percentile alpha power in red, 15th - 30th percentile, 30th - 45th, 45th to 70th, and the least alpha power in green from the 70th - 100th percentiles. The current feedback the participant sees is highlighted with the white edges around one colored rectangle. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

EEG frequency data from 5 of 8 participants who made errors during pilot task Spectra are from site Oz, averaged across 2.5 s epochs during sequences where participants either made or did not make recognition errors. Besides the increased alpha power during error trials, note the steady-state visual evoked potential aligned with presentation rate of 4 Hz, which did not change based on error status. The three participants not included in this average because they did not make errors had even lower levels of alpha than the “correct” condition illustrated in the figure.

Fig. 4

Outcome Measures for Completers In general, the WJTA IV Sentence Reading Fluency, Letter Cancellation with curved foils, and AUC (Fig. 2) were the most reliable. Note examples of outcome measures in for which there was: no change in the intervention (Letter Span Backward) (d and i); a sustained learning effect continuing through the baseline and then through the intervention periods (Sentence Reading Fluency) (j); a learning effect only during the baseline (Letter cancellation with straight foils) (b and g); an apparent improvement from the intervention (Letter Cancellation with curved foils) (a), and a decrease in performance in treatment phase (Letter Span forward) (c).

Fig. 5

Examples of Electrophysiological Data for 3 participants (A) 5-s of representative EEG data taken from week #1 of intervention. The presented windows each include one full sequence of 10 letters (1 target; 9 non-targets) during the RSVP neurofeedback calibration task. Parieto-occipital alpha is clearly visible at sites P4 and Pz prior to fixation. Participant #1 demonstrates neck EMG contamination at posterior sites Oz, PO7, and PO8. (B) Demonstrative ERP averages of target and non-target responses at Pz, derived from week #1 of intervention (3 sessions; neurofeedback calibration). Participant #1 shows EMG contamination, but a large N2/P3 response. Participant #2 exhibits alpha signal but also a small yet clear ERP response to the target. Participant #4 demonstrates no visible target-related response.