Depression is a multifaceted illness with large interindividual variability in clinical response to treatment. In the era of digital medicine and precision therapeutics, new personalized treatment approaches are warranted for depression. Here, we use a combination of longitudinal ecological momentary assessments of depression, neurocognitive sampling synchronized with electroencephalography, and lifestyle data from wearables to generate individualized predictions of depressed mood over a 1-month time period. This study, thus, develops a systematic pipeline for N-of-1 personalized modeling of depression using multiple modalities of data. In the models, we integrate seven types of supervised machine learning (ML) approaches for each individual, including ensemble learning and regression-based methods. All models were verified using fourfold nested cross-validation. The best-fit as benchmarked by the lowest mean absolute percentage error, was obtained by a different type of ML model for each individual, demonstrating that there is no one-size-fits-all strategy. The voting regressor, which is a composite strategy across ML models, was best performing on-average across subjects. However, the individually selected best-fit models still showed significantly less error than the voting regressor performance across subjects. For each individual’s best-fit personalized model, we further extracted top-feature predictors using Shapley statistics. Shapley values revealed distinct feature determinants of depression over time for each person ranging from co-morbid anxiety, to physical exercise, diet, momentary stress and breathing performance, sleep times, and neurocognition. In future, these personalized features can serve as targets for a personalized ML-guided, multimodal treatment strategy for depression.

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Loneliness and wisdom have opposing impacts on health and well-being, yet their neuro-cognitive bases have never been simultaneously investigated. In this study of 147 healthy human subjects sampled across the adult lifespan, we simultaneously studied the cognitive and neural correlates of loneliness and wisdom in the context of an emotion bias task. Aligned with the social threat framework of loneliness, we found that loneliness was associated with reduced speed of processing when angry emotional stimuli were presented to bias cognition. In contrast, we found that wisdom was associated with greater speed of processing when happy emotions biased cognition. Source models of electroencephalographic data showed that loneliness was specifically associated with enhanced angry stimulus-driven theta activity in the left transverse temporal region of interest, which is located in the area of the temporoparietal junction (TPJ), while wisdom was specifically related to increased TPJ theta activity during happy stimulus processing. Additionally, enhanced attentiveness to threatening stimuli for lonelier individuals was observed as greater beta activity in left superior parietal cortex, while wisdom significantly related to enhanced happy stimulus-evoked alpha activity in the left insula. Our results demonstrate emotion-context driven modulations in cognitive neural circuits by loneliness versus wisdom.

18A fundamental set of cognitive abilities enable humans to efficiently process goal-relevant 19 information, suppress irrelevant distractions, maintain information in working memory, and act flexibly 20 in different behavioral contexts. Yet, studies of human cognition and their underlying neural mechanisms 21 usually evaluate these cognitive constructs in silos, instead of comprehensively in-tandem within the 22 same individual. Here, we developed a scalable, mobile platform that we refer to "BrainE" (short for 23Brain Engagement), to rapidly assay several essential aspects of cognition simultaneous with wireless 24 electroencephalography (EEG) recordings. Using BrainE, we rapidly assessed five aspects of cognition 25including (1) selective attention, (2) response inhibition, (3) working memory, (4) flanker interference 26 and (5) emotion interference processing, in 102 healthy young adults. We evaluated stimulus encoding 27 in all tasks using the EEG neural recordings, and isolated the cortical sources of the spectrotemporal EEG 28 dynamics. Additionally, we used BrainE in a two-visit study in a subset of 25 young adults to investigate 29 the reliability of the neuro-cognitive data as well as its plasticity to transcranial magnetic stimulation 30 (TMS). We found that stimulus encoding on multiple cognitive tasks could be rapidly assessed, 31identifying common as well as distinct task processes in both sensory and cognitive control brain regions. 32Event related synchronization (ERS) in the theta (3-7 Hz) and alpha (8-12 Hz) frequencies as well as 33 event related desynchronization (ERD) in the beta frequencies (13-30 Hz) were distinctly observed in 34 each task. The observed ERS/ERD effects were overall anticorrelated. The two-visit study confirmed 35 high test-retest reliability for both cognitive and neural data, and neural responses showed specific TMS 36 protocol driven modulation. This first study with the BrainE platform showcases its utility in studying 37 neuro-cognitive dynamics in a rapid and scalable fashion. 38 2 39

Choice selection strategies and decision-making are typically investigated using multiple-choice gambling paradigms that require participants to maximize expected value of rewards. However, research shows that performance in such paradigms suffers from individual biases towards the frequency of gains such that users often choose smaller frequent gains over larger rarely occurring gains, also referred to as melioration. To understand the basis of this subjective tradeoff, we used a simple 2-choice reward task paradigm in 186 healthy human adult subjects sampled across the adult lifespan. Cortical source reconstruction of simultaneously recorded electroencephalography suggested distinct neural correlates for maximizing reward magnitude versus frequency. We found that activations in the parahippocampal and entorhinal areas, which are typically linked to memory function, specifically correlated with maximization of reward magnitude. In contrast, maximization of reward frequency was correlated with activations in the lateral orbitofrontal cortices and operculum, typical areas involved in reward processing. These findings reveal distinct neural processes serving reward frequency versus magnitude maximization that can have clinical translational utility to optimize decision-making.