Participants were recruited near McGill University, Canada. Participants were community-dwelling, healthy older adults aged 65 years and above. The data reported reflect the intent-to-treat population (N=92) from the INHANCE randomized clinical trial (see published protocol for details [13]). The study enrolled participants from July 2021 to December 2023, with the final follow-up in June 2024.

Participants were community-dwelling, healthy older adults. Inclusion criteria included individuals aged 65 years or older, proficient in English or French, capable of fulfilling study requirements, and cognitively intact with a Montreal Cognitive Assessment total score of ≥23, a cut-off that optimizes diagnostic sensitivity and specificity [24]. Exclusion criteria included neurocognitive disorders, suicidal ideation, major depression indicated by a total score of >10 on the Geriatric Depression Scale–Short Form, prior experience using BrainHQ within the past 5 years, concurrent clinical trial participation, pregnancy, substance abuse, or medical conditions hindering study engagement. Full details are provided in the protocol [13].

The Freeze Frame assessment is a cognitive task designed to measure speeded inhibitory control using a reverse go/no-go paradigm [25-27]. Participants are shown a target image at the beginning of each block, followed by a rapid sequence of images consisting of both targets and foils, presented with unequal probabilities under constrained viewing durations. The interstimulus interval varied randomly between 500 and 1500 milliseconds. Participants were instructed to withhold their response when a target appeared while executing a speeded motor response to all foil stimuli. See Figure 1 for a visual representation of the task structure.

The adaptive dimension of the assessment was target frequency, with lower target frequencies increasing task difficulty. There are 7 possible target frequency levels: 40%, 35%, 30%, 25%, 20%, 15%, and 10%. All participants began the assessment at a target frequency of 30%. Adaptation occurred over 5 epochs, with each epoch consisting of 30 trials. Performance-based adjustments to target frequency were made based on the abilities of each participant. If the participant correctly withheld responses to at least 80% of targets and correctly responded to at least 80% of foils, the task progressed to a more difficult level (ie, a lower target frequency). If these accuracy thresholds were not met, the task became easier by increasing the target frequency on the subsequent epoch.

The raw threshold score was recorded as an integer ranging from 1 to 7, where 1 corresponded to the easiest condition (40% target frequency) and 7 represented the most challenging condition (10% target frequency). While threshold scores were used in the raw data output, these thresholds were converted to mean accuracy, as discussed in the protocol [13].

The study was developed in accordance with the Declaration of Helsinki guidelines and was approved by the Western Institutional Review Board (IRB00000533) and Research Ethics Board of McGill University Health Centre (2020‐6474). All participants provided written informed consent.

Study data were recorded into a secure, web-based electronic case report form at the study site through the Longitudinal Online Research and Imaging System (LORIS). This system meets relevant privacy and security standards for electronic trial data entry and storage, as well as the Health Insurance Portability and Accountability Act and Personal Information Protection and Electronic Documents Act standards for confidentiality and privacy [28]. Following consent, each participant was assigned a standardized Participant Identification Number composed of digits to identify the study and digits to identify the participant. All electronic case report form data entries were deidentified, using the Participant Identification Number and not the participant’s name.

Participants received CAD $40 (approximately US $30) for completing the baseline visit, which included the measures described below. Payment followed the completion of the visit. Additional details are provided in the protocol [13].

The study was registered on November 4, 2019, before participant enrollment under the name “Improving Neurological Health in Aging Via Neuroplasticity-based Computerized Exercise (INHANCE)” with identification number NCT04149457.

Blinded staff conducted assessment administration and scoring. Following informed consent, participants completed a structured clinical interview, the Freeze Frame assessment, and a validated neuropsychological assessment of executive function (NIH EXAMINER). The structured clinical interview (20 minutes, in person) collected key demographic (eg, age, gender, education). The Freeze Frame assessment (8 minutes, in person) evaluated inhibitory control. NIH EXAMINER (20 minutes, in person) assessed executive function [8], and performance was measured using the executive composite score [10], which is automatically generated by the assessment program and converted to a z score per the registered protocol [13].

Participants (N=92) had a mean age of 71.90 (SD 4.86; range: 65‐83) years and a mean education level of 16.45 (SD 3.40, range: 9‐27) years. Of the 92 participants, 61 (66%) identified as female and 31 (34%) identified as male. The baseline NIH EXAMINER executive composite mean was 0.43 (SD 0.57; range: −1.50 to 1.52; see Table 1). A complete characterization of the intent-to-treat population has been published previously [29].

The distribution of Freeze Frame assessment scores is displayed in Figure 2A. Mean accuracy was 92.01% (SD 4.70%), with a skew of −0.99 and a kurtosis of 0.37. With respect to extreme scores, the highest recorded mean accuracy was 98%, achieved by 3 (3.75%) participants with no participant obtaining a perfect score. The lowest recorded mean accuracy was 77.33%, observed in 1 (1.25%) participant. Participants required an average of 4.27 (SD 0.16) minutes to complete the assessment.

Performance on the Freeze Frame assessment showed a small but statistically significant negative association with age (ρ=−0.22, P=.046), and a significant effect of gender with women performing better than men (P=.01). In contrast, the association between Freeze Frame performance and years of education was nonsignificant (ρ=−0.09, P=.44; see Figure 2B–D).

With respect to executive function, Freeze Frame performance was positively correlated with the NIH EXAMINER executive composite score (r=0.26; P=.02; see Figure 2E). Linear regression showed that Freeze Frame scores were significantly associated with the NIH EXAMINER executive composite score (F_1,78=5.693; P=.02) and modestly accounted for 6.8% of the variance (R²=0.068).

A total of 12 participants (13% of the sample) did not have mean accuracy scores that could be calculated from threshold scores due to administrative errors. Missing data were not imputed for baseline data of predefined exploratory outcomes data, and Freeze Frame associations reflect participants from the intent-to-treat population with complete data at baseline. There were no statistical differences between those with versus without Freeze Frame mean accuracy scores across demographic variables or NIH EXAMINER scores.

Freeze Frame assesses inhibitory control and, in this study, captured modest variance in overall executive function, with better Freeze Frame performance associated with better NIH EXAMINER performance. Older participants exhibited lower accuracy on the task compared to participants who were relatively younger. Educational background did not influence task performance. Extreme scores were minimal, suggesting that the assessment did not have notable ceiling or floor effects. The duration of the assessment was brief, at 4 minutes, and the SD suggests that completion times were stable and did not introduce significant variability due to differences in participant pacing. These results provide preliminary evidence that Freeze Frame may serve as a useful indicator of executive function and that healthy older adults are generally able to complete the assessment within a feasible administration time.

Performance on most cognitive assessments declines with age, largely due to the complex interplay of structural, functional, and neurochemical changes that occur in the aging brain [30]. While considerable individual differences exist, age-related reductions in cortical thickness, functional connectivity, and neuromodulatory control generally result in measurable decreases in cognitive function over one’s lifespan, such as slower information processing and diminished executive functioning [7]. In contrast, assessments associated with crystallized intelligence, such as general content knowledge, vocabulary, and spelling, often remain stable or improve with age [31]. In this study, performance on the Freeze Frame assessment was found to decrease modestly with age, with relatively younger participants outperforming older participants. This pattern is consistent with the intended design of Freeze Frame to evaluate cognitive networks that are vulnerable to age-related decline [25-27,32,33].

In this study, women demonstrated significantly better performance than men on the Freeze Frame assessment, which is consistent with previous evaluations of Freeze Frame [34] as well as other validated assessments of executive function [35]. This finding aligns with prior research suggesting that women often exhibit better response inhibition and cognitive control, particularly in tasks requiring rapid decision-making using go/no-go paradigms [36]. These differences may be due to strategy differences [37] or may be influenced by sociocultural factors, including differences in early-life experiences and cognitive engagement. Neurobiological factors, including structural and functional variations in prefrontal networks, which play a critical role in executive function abilities, may also contribute to these observed performance disparities [38]. The findings underscore the importance of considering sex-based differences in cognitive assessments and highlight the need for further research to explore underlying mechanisms driving such differences and their implications for cognitive aging and disease vulnerability.

The relatively small proportion of variance in NIH EXAMINER scores explained by Freeze Frame (6.8%) suggests that the assessment captures limited aspects of the broader executive function construct. The modest shared variance highlights that most individual differences in executive function remain unexplained by Freeze Frame alone. This is not unexpected given that the NIH EXAMINER executive composite score integrates performance across multiple domains of executive function, whereas Freeze Frame is narrowly focused on a speeded version of inhibitory control. Freeze Frame may nevertheless serve as a useful, fully remote, and self-administered proxy within research or clinical screening contexts that rely on rapid evaluation. The findings reported further highlight the value of incorporating additional tasks using the same remote assessment methodology (such as those capturing other aspects of executive function like working memory) to develop a comprehensive evaluation of overall functioning.

The generalizability of the study findings is constrained by the limited demographic diversity of the participant sample, which may not fully represent racial and ethnic minority groups [29]. As a result, the applicability of these findings to more diverse and lower-education populations remains uncertain, beyond preliminary evidence from a prior study involving a sample with greater racial and educational diversity [34], and warrants further investigation. Additionally, the age range of participants (65-83 years) was restricted due to the study’s inclusion criteria, potentially limiting the ability to detect associations across a broader age spectrum. Another methodological limitation pertains to the Freeze Frame assessment specifically, where 13% of threshold scores could not be converted to mean accuracy, which reduced the analytic sample to 80 and likely diminished the statistical power of the analyses and may have attenuated the magnitude of observed effects.

The INHANCE study is distinguished by several methodological strengths, including a rigorous study design, the implementation of stringent inclusion criteria, and adherence to a prespecified statistical analysis plan. A key advantage of this study is the use of a computerized assessment platform, which enhances standardization, reliability, and efficiency in data collection. Furthermore, the digital nature of the assessment allows for broad scalability, making it accessible to individuals across diverse geographic and socioeconomic backgrounds who have access to an internet-enabled device. This broad accessibility supports the potential for large-scale implementation in both research and clinical settings pending further validation studies.

Findings from this study highlight the preliminary sensitivity of Freeze Frame to evaluate higher-order cognitive abilities. Freeze Frame may serve as a scalable behavioral proxy for detecting executive function deficits in aging populations. Future research should investigate whether lower performance on this task is an early indicator of heightened risk for cognitive decline. Additionally, further studies are needed to determine the utility of Freeze Frame in clinical populations known to exhibit executive dysfunction, such as individuals with attention deficit disorder, traumatic brain injury, or mild cognitive impairment. Examining the predictive validity of Freeze Frame in relation to real-world functional decline will be critical in establishing its clinical applicability as a screening tool.