The effect of loss incentives on prospective memory in healthy older adults: study protocol of a randomized controlled trial using ultra-high field fMRI.

BACKGROUND: Prospective memory is important for our health and independence but declines with age. Hence, interventions to enhance prospective memory, for example by providing an incentive, may promote healthy ageing. The neuroanatomical correlates of prospective memory and the processing of incentive-related prospective memory changes in older adults are not fully understood. In an fMRI study, we will therefore test whether incentives improve prospective memory in older adults and how prospective memory is processed in the brain in general, and when incentives are provided. Since goals and interests change across adulthood, avoiding losses is becoming more important for older adults than achieving gains. We therefore posit that loss-related incentives will enhance prospective memory, which will be subserved by increased prefrontal and midbrain activity. METHODS: We will include n = 60 healthy older adults (60-75 years of age) in a randomized, single-blind, and parallel-group study. We will acquire 7T fMRI data in an incentive group and a control group (n = 30 each, stratified by education, age, and sex). Before and after fMRI, all participants will complete questionnaires and cognitive tests to assess possible confounders (e.g., income, personality traits, sensitivity to reward or punishment). DISCUSSION: The results of this study will clarify whether loss-related incentives can enhance prospective memory and how any enhancement is processed in the brain. In addition, we will determine how prospective memory is processed in the brain in general. The results of our study will be an important step towards a better understanding of how prospective memory changes when we get older and for developing interventions to counteract cognitive decline.

Investigating Compensatory Brain Activity in Older Adults with Subjective Cognitive Decline.

BACKGROUND: Preclinical Alzheimer's disease (AD) is one possible cause of subjective cognitive decline (SCD). Normal task performance despite ongoing neurodegeneration is typically considered as neuronal compensation, which is reflected by greater neuronal activity. Compensatory brain activity has been observed in frontal as well as parietal regions in SCD, but data are scarce, especially outside the memory domain. OBJECTIVE: To investigate potential compensatory activity in SCD. Such compensatory activity is particularly expected in participants where blood-based biomarkers indicated amyloid positivity as this implies preclinical AD. METHODS: 52 participants with SCD (mean age: 71.00±5.70) underwent structural and functional neuroimaging (fMRI), targeting episodic memory and spatial abilities, and a neuropsychological assessment. The estimation of amyloid positivity was based on plasma amyloid-ß and phosphorylated tau (pTau181) measures. RESULTS: Our fMRI analyses of the spatial abilities task did not indicate compensation, with only three voxels exceeding an uncorrected threshold at p < 0.001. This finding was not replicated in a subset of 23 biomarker positive individuals. CONCLUSION: Our results do not provide conclusive evidence for compensatory brain activity in SCD. It is possible that neuronal compensation does not manifest at such an early stage as SCD. Alternatively, it is possible that our sample size was too small or that compensatory activity may be too heterogeneous to be detected by group-level statistics. Interventions based on the individual fMRI signal should therefore be explored.

Targeting hippocampal hyperactivity with real-time fMRI neurofeedback: protocol of a single-blind randomized controlled trial in mild cognitive impairment.

BACKGROUND: Several fMRI studies found hyperactivity in the hippocampus during pattern separation tasks in patients with Mild Cognitive Impairment (MCI; a prodromal stage of Alzheimer's disease). This was associated with memory deficits, subsequent cognitive decline, and faster clinical progression. A reduction of hippocampal hyperactivity with an antiepileptic drug improved memory performance. Pharmacological interventions, however, entail the risk of side effects. An alternative approach may be real-time fMRI neurofeedback, during which individuals learn to control region-specific brain activity. In the current project we aim to test the potential of neurofeedback to reduce hippocampal hyperactivity and thereby improve memory performance. METHODS: In a single-blind parallel-group study, we will randomize n = 84 individuals (n = 42 patients with MCI, n = 42 healthy elderly volunteers) to one of two groups receiving feedback from either the hippocampus or a functionally independent region. Percent signal change of the hemodynamic response within the respective target region will be displayed to the participant with a thermometer icon. We hypothesize that only feedback from the hippocampus will decrease hippocampal hyperactivity during pattern separation and thereby improve memory performance. DISCUSSION: Results of this study will reveal whether real-time fMRI neurofeedback is able to reduce hippocampal hyperactivity and thereby improve memory performance. In addition, the results of this study may identify predictors of successful neurofeedback as well as the most successful regulation strategies. TRIAL REGISTRATION: The study has been registered with clinicaltrials.gov on the 16th of July 2019 (trial identifier: NCT04020744 ).

The Modulation of Cognitive Performance with Transcranial Alternating Current Stimulation: A Systematic Review of Frequency-Specific Effects.

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that allows the manipulation of intrinsic brain oscillations. Numerous studies have applied tACS in the laboratory to enhance cognitive performance. With this systematic review, we aim to provide an overview of frequency-specific tACS effects on a range of cognitive functions in healthy adults. This may help to transfer stimulation protocols to real-world applications. We conducted a systematic literature search on PubMed and Cochrane databases and considered tACS studies in healthy adults (age > 18 years) that focused on cognitive performance. The search yielded n = 109 studies, of which n = 57 met the inclusion criteria. The results indicate that theta-tACS was beneficial for several cognitive functions, including working memory, executive functions, and declarative memory. Gamma-tACS enhanced performance in both auditory and visual perception but it did not change performance in tasks of executive functions. For attention, the results were less consistent but point to an improvement in performance with alpha- or gamma-tACS. We discuss these findings and point to important considerations that would precede a transfer to real-world applications.

Transcranial Electric Current Stimulation During Associative Memory Encoding: Comparing tACS and tDCS Effects in Healthy Aging.

Associative memory is one of the first cognitive functions negatively affected by healthy and pathological aging processes. Non-invasive brain stimulation (NIBS) techniques are easily administrable tools to support memory. However, the optimal stimulation parameters inducing a reliable positive effect on older adult's memory performance remain mostly unclear. In our randomized, double-blind, cross-over study, 28 healthy older adults (16 females; 71.18 + 6.42 years of age) received anodal transcranial direct (tDCS), alternating current in the theta range (tACS), and sham stimulation over the left ventrolateral prefrontal cortex (VLPFC) each once during encoding. We tested associative memory performance with cued recall and recognition tasks after a retention period and again on the following day. Overall, neither tDCS nor tACS showed effects on associative memory performance. Further analysis revealed a significant difference for performance on the cued recall task under tACS compared to sham when accounting for age. Our results suggest that tACS might be more effective to improve associative memory performance than tDCS in higher aged samples.