Kristina M. Visscher

Experience is thought to modify neural connections to adapt the network to be more optimal for the environment. Given the brain's complexity, multiple network changes could each move the system toward optimality. Standard approaches examine each connection independently; these studies have often shown considerable interindividual variability and modest effects (Marek et al., 2022). Here, we take a different strategy, determining how a whole-brain connection pattern differs from the typical pattern, that is, how idiosyncratic the pattern is. We examined how the idiosyncrasy of whole-brain connection patterns varies with frequency of the use of that part of cortex for attention-demanding tasks, focusing on central versus peripheral vision in healthy individuals (who use central vision more frequently for attention-demanding tasks). We found that the whole-brain pattern of functional connections to the cortical representations of central vision is idiosyncratic, whereas patterns of connections to representations of peripheral vision were very similar person to person in healthy vision controls (14 females, 9 males). In a second set of analyses, we examined the brains of people with central vision loss (11 females, 10 males) who use a portion of peripheral vision [the preferred retinal locus (PRL)] more frequently for attention-demanding tasks in their daily lives. The cortical representation of the PRL exhibits more idiosyncratic connections, compared with a control brain region or compared with the same brain region in matched healthy vision controls. These results are consistent with the hypothesis that increased attentive use of a brain area results in idiosyncratic patterns of whole-brain connections.

Science communication plays an essential role in bridging the gap between researchers and the general public. Now, more than ever, it is essential for neuroscientists to interact with their communities to increase understanding of basic neuroscience concepts and enhance trust in academic scientists as members of the community. However, it can be difficult, as scientists, to develop and maintain effective lines of communication with the public. To address this, at the University of Alabama at Birmingham, we have been organizing public outreach events aimed to educate the public about various aspects of neuroscience. The goal of this article is to share our strategy for expanding our successful once-per-year “Brain Awareness Week” event to a year-round “Neuroscience for All” program and to provide practical materials and a dedicated, interactive GitHub-based platform for discussion of personal experiences and extensions and improvements to materials. We hope that the resources and examples we outline will facilitate other institutions to easily expand existing programs or create new ones from scratch and that our online forum will facilitate broader discussion and improvement of neuroscience outreach initiatives across institutions.

The cognitively-intact oldest-old (85 +) may be the most-resilient members of their birth cohort; due to survivorship effects (e.g., depletion of susceptibles), risk factors associated with brain aging biomarkers in younger samples may not generalize to the cognitively-intact oldest-old. We evaluated associations between established aging-related risk factors and brain-predicted age difference (brainPAD) in a cross-sectional cognitively-intact oldest-old sample. Additionally, we evaluated brainPAD-cognition associations to characterize brain maintenance vs. cognitive reserve in our sample. Oldest-old adults (N = 206; 85–99 years; Montreal Cognitive Assessment > 22 or neurologist evaluation) underwent T1-weighted MRI; brainPAD was generated with brainageR, such that more-positive brainPAD reflected more-advanced brain aging. Sex, education, alcohol and smoking history, exercise history, BMI, cardiovascular and metabolic disease history, and anticholinergic medication burden were self-reported. Global cognitive z-score and coefficient of variation were derived from the UDS 3.0 cognitive battery; crystallized-fluid discrepancy was derived from the NIH Toolbox Cognitive Battery. Mean brainPAD was -7.99 (SD: 5.37; range: -24.50, 6.03). Women showed more-delayed brain aging than men (B = -2.9, 95% CI = -4.6, -1.1, p = 0.002). No other exposures were significantly associated with brainPAD. BrainPAD was not associated with any cognitive variable. These findings suggest that cognitively-intact oldest-old adults may be atypically-resistant to risk factors associated with aging in younger samples, consistent with survivorship effects in aging. Furthermore, brainPAD may have limited explanatory value for cognitive performance in cognitively-intact oldest-old adults, potentially due to high cognitive reserve. Overall, our findings highlight the impact of survivorship effects on brain aging research. Graphical Abstract

Experience is thought to modify neural connections to adapt the network to be more optimal for the environment. Given the brain’s complexity, multiple network changes could each move the system toward optimality. Standard methods ignore this multiplicity and examine each connection independently; these studies have often shown considerable inter-individual variability and modest effects (1). Here, we take a different strategy, determining how a whole-brain connection pattern differs from the typical pattern, that is, how ‘idiosyncratic’ the pattern is. We examined how the idiosyncrasy of whole brain connection patterns varies with frequency of the use of that part of cortex for attention-demanding tasks, focusing on central versus peripheral vision in healthy individuals (where individuals use central vision more frequently for attention-demanding tasks). We found that the whole-brain pattern of functional connections to the cortical representations of central vision is idiosyncratic, whereas patterns of connections to representations of peripheral vision were very similar person-to-person. In a second set of analyses, we examined the brains of people with central vision loss who use a portion of peripheral vision (called the preferred retinal locus) more frequently for attention-demanding tasks in their daily lives. The cortical representation of the preferred retinal locus exhibits more idiosyncratic connections, compared to a control brain region, or compared to the same brain region in matched control participants with healthy vision. These results are consistent with the hypothesis that increased attentive use of a brain area results in idiosyncratic patterns of whole brain connections. Significance Statement: We found that increased attentive use of a brain region results in more idiosyncratic patterns of connections of that region to the rest of the brain. Our findings support the view that V1 retains the capacity for plasticity well beyond the critical period and that these adaptations are idiosyncratic to the individual’s experiences. This approach suggests that tailoring personalized rehabilitation plans for individuals with retinal diseases may be more effective than a ‘one size fits all’ approach. More generally, it offers a promising framework for investigating brain plasticity in both typical and clinical populations, especially in the context of sensory loss and compensatory adaptation.

Patients with central vision loss due to macular degeneration (MD) must rely on their peripheral vision for tasks normally performed by the fovea. Many patients develop a preferred retinal locus (PRL), an eccentric retinal location used as a substitute for the damaged fovea in tasks such as face recognition, navigation, and reading. However, the mechanisms underlying PRL development remain elusive, and no single hypothesis fully explains its characteristics. Investigations into PRL development are hindered by oculomotor assessments, which often focus on fixation ability while neglecting other eye movement characteristics and potentially conflating different behaviors over time. In previous work, we introduced a series of oculomotor metrics in cases of simulated central vision loss, demonstrating that complex profiles of eye movement behavior can be extracted from a simple visual task. Here we present longitudinal data from 10 patients with MD as evidence of the feasibility of using these metrics to characterize different profiles of eye movements following central vision loss. Consistent with findings in healthy individuals using artificial scotoma, the metrics reveal substantial individual differences in behavior, both at baseline and after visual training. Overall, patients exhibit significantly higher saccadic re-referencing than controls, despite larger inter-individual differences. These metrics provide a detailed evaluation of oculomotor behavior in patients with central vision loss and offer a valuable tool for assessing progress in training protocols.

The cognitively-intact oldest-old (85+) may be the most-resilient members of their birth cohort; due to survivorship effects (e.g., depletion of susceptibles), risk factors associated with brain aging biomarkers in younger samples may not generalize to the oldest-old. We evaluated associations between established aging-related risk factors and brain-predicted age difference (brainPAD) in a cross-sectional cognitively-intact oldest-old sample. Additionally, we evaluated brainPAD-cognition associations to characterize brain maintenance vs. cognitive reserve in our sample. Oldest-old adults (N = 206; 85-99 years; MoCA > 22 or neurologist evaluation) underwent T1-weighted MRI; brainPAD was generated with brainageR, such that more-positive brainPAD reflected relatively advanced brain aging. Sex, educational attainment, alcohol and smoking history, exercise history, BMI, cardiovascular and metabolic disease history, and anticholinergic medication burden were self-reported. Global cognitive z-score and coefficient of variation were derived from the NACC UDS 3.0 cognitive battery; crystallized-fluid discrepancy was derived from the NIH Toolbox Cognitive Battery. Mean brainPAD was -7.99 (SD: 5.37; range: -24.50, 6.03). Women showed more-delayed brain aging than men (B = -2.35, 95% CI = - 4.28, -0.41, p = 0.018). No other exposures were associated with brainPAD. BrainPAD was not associated with any cognitive variable. These findings suggest that cognitively-intact oldest-old adults may be atypically-resistant to risk factors associated with aging in younger samples, consistent with survivorship effects in aging. Furthermore, brainPAD may have limited explanatory value for cognitive performance in cognitively-intact oldest-old adults, potentially due to high cognitive reserve. Overall, our findings highlight the impact of survivorship effects on brain aging research. Highlights Brain-predicted age difference was assessed in cognitively-intact oldest-old (≥85) Mean brain-predicted age corresponded to an 8-year delay in brain aging Brain age in oldest-old was not associated with self-reported health history Brain age was not associated with cognitive performance

The brain is organized into systems and networks of interacting components. The functional connections among these components give insight into the brain’s organization and may underlie some cognitive effects of aging. Examining the relationship between individual differences in brain organization and cognitive function in older adults who have reached oldest-old ages with healthy cognition can help us understand how these networks support healthy cognitive aging. We investigated functional network segregation in 146 cognitively healthy participants aged 85+ in the McKnight Brain Aging Registry (MBAR). We found that the segregation of the association system and the individual networks within the association system (the fronto-parietal network , cingulo-opercular network, and default mode network), has strong associations with overall cognition and processing speed. We also provide a healthy oldest-old (85+) cortical parcellation that can be used in future work in this age group. This study shows that network segregation of the oldest-old brain is closely linked to cognitive performance. This work adds to the growing body of knowledge about differentiation in the aged brain by demonstrating that cognitive ability is associated with differentiated functional networks in very old individuals representing successful cognitive aging.

Human behavior can be remarkably shaped by experience, such as the removal of sensory input. Many studies of conditions such as stroke, limb amputation, and vision loss have examined how removal of input changes brain function. However, an important question yet to be answered is: when input is lost, does the brain change its connectivity to preferentially use some remaining inputs over others? In individuals with healthy vision, the central portion of the retina is preferentially used for everyday visual tasks, due to its ability to discriminate fine details. When central vision is lost in conditions like macular degeneration, peripheral vision must be relied upon for those everyday tasks, with some portions receiving “preferential” usage over others. Using resting‐state fMRI collected during total darkness, we examined how deprivation and preferential usage influence the intrinsic functional connectivity of sensory cortex by studying individuals with selective vision loss due to late stages of macular degeneration. Specifically, we examined functional connectivity between category‐selective visual areas and the cortical representation of three areas of the retina: the lesioned area, a preferentially used region of the intact retina, and a non‐preferentially used region. We found that cortical regions representing spared portions of the peripheral retina, regardless of whether they are preferentially used, exhibit plasticity of intrinsic functional connectivity in macular degeneration. Cortical representations of spared peripheral retinal locations showed stronger connectivity to MT, a region involved in processing motion. These results suggest that the long‐term loss of central vision can produce widespread effects throughout spared representations in early visual cortex, regardless of whether those representations are preferentially used. These findings support the idea that connections to visual cortex maintain the capacity for change well after critical periods of visual development.

Executive control of movement enables inhibiting impulsive responses critical for successful navigation of the environment. Circuits mediating stop commands involve prefrontal and basal ganglia structures with fMRI evidence demonstrating increased activity during response inhibition in the dorsolateral prefrontal cortex (dlPFC)—often ascribed to maintaining task attentional demands. Using direct intraoperative cortical recordings in male and female human subjects, we investigated oscillatory dynamics along the rostral-caudal axis of dlPFC during a modified Go/No-go task, probing components of both proactive and reactive motor control. We assessed whether cognitive control is topographically organized along this axis and observed that low-frequency power increased prominently in mid-rostral dlPFC when inhibiting and delaying responses. These findings provide evidence for a key role for mid-rostral dlPFC low-frequency oscillations in sculpting motor control.

Human behavior can be remarkably shaped by experience, such as the removal of sensory input. Many studies of conditions such as stroke, limb amputation, and vision loss have examined how the removal of input changes brain function. However, an important question has yet to be answered: when input is lost, does the brain change its connectivity to preferentially use some remaining inputs over others? In individuals with healthy vision, the central portion of the retina is preferentially used for everyday visual tasks, due to its ability to discriminate fine details. However, when central vision is lost in conditions like macular degeneration, peripheral vision must be relied upon for those everyday tasks, with certain portions receiving “preferential” usage over others. Using resting-state fMRI collected during total darkness, we examined how deprivation and preferential usage influence the intrinsic functional connectivity of sensory cortex by studying individuals with selective vision loss due to late stages of macular degeneration. We found that cortical regions representing spared portions of the peripheral retina, regardless of whether they are preferentially used, exhibit plasticity of intrinsic functional connectivity in macular degeneration. Cortical representations of spared peripheral retinal locations showed stronger connectivity to MT, a region involved in processing motion. These results suggest that long-term loss of central vision can produce widespread effects throughout spared representations in early visual cortex, regardless of whether those representations are preferentially used. These findings support the idea that connections to visual cortex maintain the capacity for change well after critical periods of visual development. Highlights Portions of early visual cortex representing central vs. peripheral vision exhibit different patterns of connectivity to category-selective visual regions. When central vision is lost, cortical representations of peripheral vision display stronger functional connections to MT than central representations. When central vision is lost, connectivity to regions selective for tasks that involve central vision (FFA and PHA) are not significantly altered. These effects do not depend on which locations of peripheral vision are used more.