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Keywords
Objective
Alzheimer’s disease (AD) is a growing challenge worldwide, which is why the search for early-onset predictors must be focused as soon as possible. Longitudinal studies that investigate courses of neuropsychological and other variables screen for such predictors correlated to mild cognitive impairment (MCI). However, one often neglected issue in analyses of such studies is measurement invariance (MI), which is often assumed but not tested for. This study uses the absence of MI (non-MI) and latent factor scores instead of composite variables to assess properties of cognitive domains, compensation mechanisms, and their predictability to establish a method for a more comprehensive understanding of pathological cognitive decline.
Methods
An exploratory factor analysis (EFA) and a set of increasingly restricted confirmatory factor analyses (CFAs) were conducted to find latent factors, compared them with the composite approach, and to test for longitudinal (partial-)MI in a neuropsychiatric test battery, consisting of 14 test variables. A total of 330 elderly (mean age: 73.78 ± 1.52 years at baseline) were analyzed two times (3 years apart).
Results
EFA revealed a four-factor model representing declarative memory, attention, working memory, and visual–spatial processing. Based on CFA, an accurate model was estimated across both measurement timepoints. Partial non-MI was found for parameters such as loadings, test- and latent factor intercepts as well as latent factor variances. The latent factor approach was preferable to the composite approach.
Conclusion
The overall assessment of non-MI latent factors may pose a possible target for this field of research. Hence, the non-MI of variances indicated variables that are especially suited for the prediction of pathological cognitive decline, while non-MI of intercepts indicated general aging-related decline. As a result, the sole assessment of MI may help distinguish pathological from normative aging processes and additionally may reveal compensatory neuropsychological mechanisms.
Highlights
• Transcranial ultrasound neuromodulation/stimulation (TUS) is a growing field.
• We conducted a double-blind sham-controlled within-subjects large sample TUS study.
• Right prefrontal cortex TUS inhibits midfrontal theta electroencephalography (MFT).
• TUS MFT inhibition explains greater approach versus withdrawal in a virtual T-maze.
• This distinct TUS-MFT-behavior link merits future basic and applied research.
Abstract
Recent reviews highlighted low-intensity transcranial focused ultrasound (TUS) as a promising new tool for non-invasive neuromodulation in basic and applied sciences. Our preregistered double-blind within-subjects study (N = 152) utilized TUS targeting the right prefrontal cortex, which, in earlier work, was found to positively enhance self-reported global mood, decrease negative states of self-reported emotional conflict (anxiety/worrying), and modulate related midfrontal functional magnetic resonance imaging activity in affect regulation brain networks. To further explore TUS effects on objective physiological and behavioral variables, we used a virtual T-maze task that has been established in prior studies to measure motivational conflicts regarding whether participants execute approach versus withdrawal behavior (with free-choice responses via continuous joystick movements) while allowing to record related electroencephalographic data such as midfrontal theta activity (MFT). MFT, a reliable marker of conflict representation on a neuronal level, was of particular interest to us since it has repeatedly been shown to explain related behavior, with relatively low MFT typically preceding approach-like risky behavior and relatively high MFT typically preceding withdrawal-like risk aversion. Our central hypothesis is that TUS decreases MFT in T-maze conflict situations and thereby increases approach and reduces withdrawal. Results indicate that TUS led to significant MFT decreases, which significantly explained increases in approach behavior and decreases in withdrawal behavior. This study expands TUS evidence on a physiological and behavioral level with a large sample size of human subjects, suggesting the promise of further research based on this distinct TUS-MFT-behavior link to influence conflict monitoring and its behavioral consequences. Ultimately, this can serve as a foundation for future clinical work to establish TUS interventions for emotional and motivational mental health.