The neuroscience of meditation is providing insight into meditation's beneficial effects on well-being and informing understanding of consciousness. However, further research is needed to explicate mechanisms linking brain activity and meditation. Non-invasive brain stimulation (NIBS) presents a promising approach for causally investigating neural mechanisms of meditation. Prior NIBS-meditation research has predominantly targeted frontal and parietal cortices suggesting that it might be possible to boost the behavioral and neural effects of meditation with NIBS. Moreover, NIBS has revealed distinct neural signatures in long-term meditators. Nonetheless, methodological variations in NIBS-meditation research contributes to challenges for definitive interpretation of previous results. Future NIBS studies should further investigate core substrates of meditation, including specific brain networks and oscillations, and causal neural mechanisms of advanced meditation. Overall, NIBS-meditation research holds promise for enhancing meditation-based interventions in support of well-being and resilience in both non-clinical and clinical populations, and for uncovering the brain-mind mechanisms of meditation and consciousness.

Background: Disease-modifying agents to counteract cognitive impairment in older age remain elusive. Hence, identifying modifiable factors promoting resilience, as the capacity of the brain to maintain cognition and function with aging and disease, is paramount. In Alzheimer’s disease (AD), education and occupation are typical cognitive reserve proxies. However, the importance of psychological factors is being increasingly recognized, as their operating biological mechanisms are elucidated. Purpose in life (PiL), one of the pillars of psychological well-being, has previously been found to reduce the deleterious effects of AD-related pathological changes on cognition. However, whether PiL operates as a resilience factor in middle-aged individuals and what are the underlying neural mechanisms remain unknown. Methods: Data was obtained from 624 middle-aged adults (mean age 53.71 ± 6.9; 303 women) from the Barcelona Brain Health Initiative cohort. Individuals with lower (LP; N = 146) and higher (HP; N = 100) PiL rates, according to the division of this variable into quintiles, were compared in terms of cognitive status, a measure reflecting brain burden (white matter lesions; WMLs), and resting-state functional connectivity, examining system segregation (SyS) parameters using 14 common brain circuits. Results: Neuropsychological status and WMLs burden did not differ between the PiL groups. However, in the LP group, greater WMLs entailed a negative impact on executive functions. Subjects in the HP group showed lower SyS of the dorsal default-mode network (dDMN), indicating lesser segregation of this network from other brain circuits. Specifically, HP individuals had greater inter-network connectivity between specific dDMN nodes, including the frontal cortex, the hippocampal formation, the midcingulate region, and the rest of the brain. Greater functional connectivity in some of these nodes positively correlated with cognitive performance. Conclusion: Expanding previous findings on AD pathology and advanced age, the present results suggest that higher rates of PiL may promote resilience against brain changes already observable in middle age. Furthermore, having a purposeful life implies larger functional integration of the dDMN, which may potentially reflect greater brain reserve associated to better cognitive function.

Neuroimaging investigations have revealed interindividual variations in anatomy, metabolism, activity, and connectivity of specific cortical association areas through which years of education (YoE), as a common proxy of cognitive reserve, may operate in the face of age- or pathology-associated brain changes. However, the associated molecular properties of YoE-related brain regions and the biological pathways involved remain poorly understood. In the present study we first identified brain areas that showed an association between cortical thickness and YoE among 122 cognitively healthy older human individuals (87 female). We subsequently characterized molecular properties of these regions by studying brain-wide microarray measurements of regional gene expression. In accordance with previous studies, we observed that YoE were associated with higher cortical thickness in medial prefrontal, anterior cingulate, and orbitofrontal areas. Compared with the rest of the cortex, these regions exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in ionotropic and metabotropic neurotransmission as well as activation of immune response. Our genome-wide expression profile analysis of YoE-related brain regions points to distinct molecular pathways that may underlie a higher capacity for plastic changes in response to lifetime intellectual enrichment and potentially also a higher resilience to age-related pathologic brain changes. SIGNIFICANCE STATEMENT We combined a neuroimaging-based analysis with a transcriptome-wide gene expression approach to investigate the molecular-functional properties of cortical regions associated with educational attainment, as a commonly used proxy for cognitive reserve, in older individuals. The strongest association with education was observed in specific areas of the medial prefrontal cortex, and these areas exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in neurotransmission and immune responses. These findings complement previous neuroimaging studies in the field and point to novel biological pathways that may mediate the beneficial effects of high educational attainment on adaptability to cope with, or prevent, age-related brain changes. The identified genes and pathways now warrant further exploration in mechanistic studies.

Combining non-invasive brain stimulation (NIBS) with resting-state functional magnetic resonance imaging (rs-fMRI) is a promising approach to characterize and potentially optimize the brain networks subtending cognition that changes as a function of age. However, whether multifocal NIBS approaches are able to modulate rs-fMRI brain dynamics in aged populations, and if these NIBS-induced changes are consistent with the simulated electric current distribution on the brain remains largely unknown. In the present investigation, thirty-one cognitively healthy older adults underwent two different multifocal real transcranial direct current stimulation (tDCS) conditions (C1 and C2) and a sham condition in a crossover design during a rs-fMRI acquisition. The real tDCS conditions were designed to electrically induce two distinct complex neural patterns, either targeting generalized frontoparietal cortical overactivity (C1) or a detachment between the frontal areas and the posteromedial cortex (C2). Data revealed that the two tDCS conditions modulated rs-fMRI differently. C1 increased the coactivation of multiple functional couplings as compared to sham, while a smaller number of connections increased in C1 as compared to C2. At the group level, C1-induced changes were topographically consistent with the calculated electric current density distribution. At the individual level, the extent of tDCS-induced rs-fMRI modulation in C1 was related with the magnitude of the simulated electric current density estimates. These results highlight that multifocal tDCS procedures can effectively change rs-fMRI neural functioning in advancing age, being the induced modulation consistent with the spatial distribution of the simulated electric current on the brain. Moreover, our data supports that individually tailoring NIBS-based interventions grounded on subject-specific structural data might be crucial to increase tDCS potential in future studies amongst older adults.