Hippocampal-occipital connectivity reflects autobiographical memory deficits in aphantasia.

Aphantasia refers to reduced or absent visual imagery. While most of us can readily recall decade-old personal experiences (autobiographical memories, AM) with vivid mental images, there is a dearth of information about whether the loss of visual imagery in aphantasics affects their AM retrieval. The hippocampus is thought to be a crucial hub in a brain-wide network underlying AM. One important question is whether this network, especially the connectivity of the hippocampus, is altered in aphantasia. In the current study, we tested 14 congenital aphantasics and 16 demographically matched controls in an AM fMRI task to investigate how key brain regions (i.e. hippocampus and visual-perceptual cortices) interact with each other during AM re-experiencing. All participants were interviewed regarding their autobiographical memory to examine their episodic and semantic recall of specific events. Aphantasics reported more difficulties in recalling AM, were less confident about their memories, and described less internal and emotional details than controls. Neurally, aphantasics displayed decreased hippocampal and increased visual-perceptual cortex activation during AM retrieval compared to controls. In addition, controls showed strong negative functional connectivity between the hippocampus and the visual cortex during AM and resting-state functional connectivity between these two brain structures predicted better visualization skills. Our results indicate that visual mental imagery plays an important role in detail-rich vivid AM, and that this type of cognitive function is supported by the functional connection between the hippocampus and the visual-perceptual cortex.

Neuronal activation patterns during self-referential pain imagination.

In clinical assessments and pain therapy, patients are asked to imagine themselves in pain. However, the underlying neuronal processes remain poorly understood. Prior research has focused on empathy for pain or reported small sample sizes. Thus, the present study aimed to promote the neurobiological understanding of self-referential pain imagination. We hypothesised to find activation contrasts (pain vs. no pain) across pain-related areas and expected two of the most prominent predictors of chronic pain, pain sensitivity (PS) and locus of control (LoC), to be moderators. In an fMRI study, N = 82 participants completed a pain imagination task, in which they were asked to imagine themselves in painful and non-painful situations presented in the form of pictures and texts. After each trial, they were instructed to give painfulness ratings. As a laboratory measure of PS, electrical pain thresholds were assessed. A questionnaire was completed to measure LoC. Across presentation modes we found activity contrasts in previously pain-related regions, such as the prefrontal, supplementary motor, primary motor, somatosensory and posterior parietal cortices, and the cerebellum. We found positive associations of PS and external LoC with painfulness ratings, and a negative correlation between PS and internal LoC. Despite our hypotheses, neither PS nor internal LoC were significant predictors of the BOLD-signal contrasts. Though future studies are needed to draw further conclusions, our results provide preliminary evidence of a potential neuronal imagination-perception overlap in pain.

Understanding societal challenges: a NeurotechEU perspective.

Futuristic universities like The NeurotechEU and the technological innovations they provide will shape and serve society, but will also require support from society. Positive attitudes about neuro-technologies will increase their reach within society and may also impact policy-making, including funding decisions. However, the acceptability rates, especially of invasive neuro-technologies, are quite low and the majority of people are more worried than enthusiastic about them. The question therefore arises as to what neuro-technological advances should entail. In a rare effort to reach out to the public, we propose to conduct a trans-national survey with the goal to better understand the challenges of our NeurotechEU nations. We aim to compare and contrast our nations specifically with respect to their perspectives on neuro-technological advances, i.e., their needs for, interests in, access to, knowledge of and trust in neuro-technologies, and whether these should be regulated. To this end, we have developed the first version of a new tool-the Understanding Societal Challenges Questionnaire (USCQ)-which assesses all six of these dimensions (needs, interest, access, knowledge, trust, and policy-making) and is designed for administration across EU/AC countries. In addition to trans-national comparisons, we will also examine the links of our nations' perspectives on neuro-technological advances to demographic and personality variables, for example, education and socio-economic status, size of the residential area, the Big Five personality traits, religiosity, political standings, and more. We expect that this research will provide a deeper understanding of the challenges that our nations are facing as well as the similarities and differences between them, and will also help uncover the variables that predict positive and negative attitudes toward neuro-technological advances. By integrating this knowledge into the scientific process, The NeurotechEU may be able to develop neuro-technologies that people really care about, are ethical and regulated, and actually understood by the user.

Do patients prefer a human doctor, artificial intelligence, or a blend, and is this preference dependent on medical discipline? Empirical evidence and implications for medical practice.

Today the doctor-patient relationship typically takes place in a face-to-face setting. However, with the advent of artificial intelligence (AI) systems, two further interaction scenarios are possible: an AI system supports the doctor's decision regarding diagnosis and/or treatment while interacting with the patient, or an AI system could even substitute the doctor and hence a patient interacts with a chatbot (i.e., a machine) alone. Against this background, we report on an online experiment in which we analyzed data from N = 1,183 people. The data was collected in German-speaking countries (Germany, Austria, Switzerland). The participants were asked to imagine they had been suffering from medical conditions of unknown origin for some time and that they were therefore visiting a health center to seek advice from a doctor. We developed descriptions of patient-doctor interactions (referred to as vignettes), thereby manipulating the patient's interaction partner: (i) human doctor, (ii) human doctor with an AI system, and (iii) an AI system only (i.e., chatbot). Furthermore, we manipulated medical discipline: (i) cardiology, (ii) orthopedics, (iii) dermatology, and (iv) psychiatry. Based on this 3 × 4 experimental within-subjects design, our results indicate that people prefer a human doctor, followed by a human doctor with an AI system, and an AI system alone came in last place. Specifically, based on these 12 hypothetical interaction situations, we found a significant main effect of a patient's interaction partner on trust, distrust, perceived privacy invasion, information disclosure, treatment adherence, and satisfaction. Moreover, perceptions of trust, distrust, and privacy invasion predicted information disclosure, treatment adherence, and satisfaction as a function of interaction partner and medical discipline. We found that the situation in psychiatry is different from the other three disciplines. Specifically, the six outcome variables differed strongly between psychiatry and the three other disciplines in the "human doctor with an AI system" condition, while this effect was not that strong in the other conditions (human doctor, chatbot). These findings have important implications for the use of AI in medical care and in the interaction between patients and their doctors.

Sex differences in trajectories of cortical development in autistic children from 2-13 years of age.

Previous studies have reported alterations in cortical thickness in autism. However, few have included enough autistic females to determine if there are sex specific differences in cortical structure in autism. This longitudinal study aimed to investigate autistic sex differences in cortical thickness and trajectory of cortical thinning across childhood. Participants included 290 autistic (88 females) and 139 nonautistic (60 females) individuals assessed at up to 4 timepoints spanning ~2-13 years of age (918 total MRI timepoints). Estimates of cortical thickness in early and late childhood as well as the trajectory of cortical thinning were modeled using spatiotemporal linear mixed effects models of age-by-sex-by-diagnosis. Additionally, the spatial correspondence between cortical maps of sex-by-diagnosis differences and neurotypical sex differences were evaluated. Relative to their nonautistic peers, autistic females had more extensive cortical differences than autistic males. These differences involved multiple functional networks, and were mainly characterized by thicker cortex at ~3 years of age and faster cortical thinning in autistic females. Cortical regions in which autistic alterations were different between the sexes significantly overlapped with regions that differed by sex in neurotypical development. Autistic females and males demonstrated some shared differences in cortical thickness and rate of cortical thinning across childhood relative to their nonautistic peers, however these areas were relatively small compared to the widespread differences observed across the sexes. These results support evidence of sex-specific neurobiology in autism and suggest that processes that regulate sex differentiation in the neurotypical brain contribute to sex differences in the etiology of autism.

Spirituality and anxiety in pastoral care workers and physicians in the first wave of the COVID-19 pandemic.

Background: The COVID-19 pandemic had serious impact on the well-being of health care workers and highlighted the need for resources to help hospital staff to cope with psychologically negative consequences. The purpose of this study was to investigate the potentially protective effect of spirituality, as measured by the construct of transpersonal trust, against anxiety in physicians and in hospital pastoral care workers. In addition, transpersonal trust was compared to the effects of other potential resources, namely sense of coherence, optimism, and resilience. We also explored the relationship between transpersonal trust and anxiety and how it was moderated by sense of coherence and expected a significant effect. Method: The sample included N = 405 participants (n = 151 pastoral care workers and n = 254 physicians) who completed an online survey during the first wave of the COVID-19 pandemic between 20th April and 05th July, 2020, that comprised established questionnaires assessing anxiety, transpersonal trust, sense of coherence, and resilience. Results: There was no statistically significant negative relationship between transpersonal trust and anxiety in either profession or broken down by occupational group. Multiple regression analysis revealed that sense of coherence inversely predicted generalized anxiety, while transpersonal trust, resilience, and optimism did not. As hypothesized, the association between transpersonal trust and anxiety was moderated by sense of coherence. However, we could not confirm our hypothesis of a protective effect of transpersonal trust against anxiety. Conclusion: Our results point to the significant role of sense of coherence as a protective factor against anxiety and highlight the complexity of the relationship among spirituality, transpersonal trust, and anxiety.

Cerebellar Volumetry in Ataxias: Relation to Ataxia Severity and Duration.

Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C). Our cross-sectional data set comprised mutation carriers of SCA1 (N=12), SCA3 (N=62), SCA6 (N=14), as well as MSA-C patients (N=16). Cerebellar volumes were obtained from T1-weighted magnetic resonance images. To compare the different atrophy patterns, we performed a z-transformation and plotted the intercept of each patient group's model at the mean of 7 years of ataxia duration as well as at the mean ataxia severity of 14 points in the SARA sum score. In addition, we plotted the extrapolation at ataxia duration of 0 years as well as 0 points in the SARA sum score. Patients with MSA-C demonstrated the most pronounced volume loss, particularly in the cerebellar white matter, at the late time intercept. Patients with SCA6 showed a pronounced volume loss in cerebellar grey matter with increasing ataxia severity compared to all other patient groups. MSA-C, SCA1 and SCA3 showed a prominent atrophy of the cerebellar white matter. Our results (i) confirmed SCA6 being considered as a pure cerebellar grey matter disease, (ii) emphasise the involvement of cerebellar white matter in the neuropathology of SCA1, SCA3 and MSA-C, and (iii) reflect the rapid clinical progression in MSA-C.

No verbal overshadowing in aphantasia: The role of visual imagery for the verbal overshadowing effect.

The verbal overshadowing effect refers to the phenomenon that the verbal description of a past complex stimulus impairs its subsequent recognition. Theoretical explanations range from interference between different mental representations to the activation of different processing orientations or a provoked shift in the recognition criterion. In our study, 61 participants with aphantasia (= lack of mental imagery) and 70 controls participated in a verbal overshadowing paradigm. The verbal overshadowing effect did not occur in people with aphantasia, although the effect was replicated in controls. We speculate that this is either due to the lack of visual representations in people with aphantasia that verbal descriptions could interfere with, or to the absence of a shift in processing orientation during verbalisation. To rule out criterion-based explanations, further research is needed to distinguish between discriminability and response bias in people with aphantasia. Finally, data indicated that the verbal overshadowing effect may even be reversed in individuals with aphantasia, partly due to a lower memory performance in the no verbalisation condition. Effects of further variables are discussed, such as mental strategies, memory confidence, and difficulty, quantity and quality of verbalisation.

Linking enlarged choroid plexus with plasma analyte and structural phenotypes in clinical high risk for psychosis: A multisite neuroimaging study.

BACKGROUND: Choroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes. METHODS: Clinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. RESULTS: Compared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1ß (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]. CONCLUSIONS: CHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR.

The role of dopamine in visual imagery-An experimental pharmacological study.

Mental imagery enables people to simulate experiences in their minds without the presence of an external stimulus. The underlying biochemical mechanisms are poorly understood but there is vague evidence that dopamine may play a significant role. A better understanding at the biochemical level could help to unravel the mechanisms of mental imagery and related phenomena such as aphantasia (= lack of voluntary mental imagery), but also opens up possibilities for interventions to enhance or restore mental imagery. To test the hypothesis that acute dopamine depletion leads to a decrease in the strength of mental imagery, N = 22 male participants will be administered an amino acid mixture containing branched-chain amino acids (BCAAs) and tryptophan (TRP) to transiently reduce dopamine synthesis and further N = 22 male participants will receive a placebo. Plasma prolactin (PRL) levels are determined as a peripheral marker of brain dopamine function. The strength of mental imagery will be measured before and after ingestion of the BCAA/TRP mixture using the method of mental imagery priming. Additional exploratory analyses will use genetic data to investigate possible effects of variations on dopaminergic gene loci (e.g., DAT1) on dopamine levels and strength of mental imagery. The results show […].

Where's Wanda? The influence of visual imagery vividness on visual search speed measured by means of hidden object pictures.

Previous research demonstrated effects of visual imagery on search speed in visual search paradigms. However, these effects were rather small, questioning their ecological validity. Thus, our present study aimed to generalize these effects to more naturalistic material (i.e., a paradigm that allows for top-down strategies in highly complex visual search displays that include overlapping stimuli while simultaneously avoiding possibly confounding search instructions). One hundred and four participants with aphantasia (= absence of voluntary mental imagery) and 104 gender and age-matched controls were asked to find hidden objects in several hidden object pictures with search times recorded. Results showed that people with aphantasia were significantly slower than controls, even when controlling for age and general processing speed. Thus, effects of visual imagery might be strong enough to influence the perception of our real-life surroundings, probably because of the involvement of visual imagery in several top-down strategies.

Cerebellar volumetry in ataxias: Relation to ataxia severity and duration.

Background: Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C). Methods: Our cross-sectional data set comprised mutation carriers of SCA1 (N=12), SCA3 (N=62), SCA6 (N=14), as well as MSA-C patients (N=16). Cerebellar volumes were obtained from T1-weighted magnetic resonance images. To compare the different atrophy patterns, we performed a z-transformation and plotted the intercept of each patient group's model at the mean of 7 years of ataxia duration as well as at the mean ataxia severity of 14 points in the SARA sum score. In addition, we plotted the extrapolation at ataxia duration of 0 years as well as 0 points in the SARA sum score. Results: Patients with MSA-C demonstrated the most pronounced volume loss, particularly in the cerebellar white matter, at the late time intercept. Patients with SCA6 showed a pronounced volume loss in cerebellar grey matter with increasing ataxia severity compared to all other patient groups. MSA-C, SCA1 and SCA3 showed a prominent atrophy of the cerebellar white matter. Conclusion: Our results (i) confirmed SCA6 being considered as a pure cerebellar gray matter disease, (ii) emphasise the involvement of cerebellar white matter in the neurophatology of SCA1, SCA3 and MSA-C, and (iii) reflect the rapid clinical progression in MSA-C.

No increased prevalence of prosopagnosia in aphantasia: Visual recognition deficits are small and not restricted to faces.

Aphantasia and prosopagnosia are both rare conditions with impairments in visual cognition. While prosopagnosia refers to a face recognition deficit, aphantasics exhibit a lack of mental imagery. Current object recognition theories propose an interplay of perception and mental representations, making an association between recognition performance and visual imagery plausible. While the literature assumes a link between aphantasia and prosopagnosia, other impairments in aphantasia have been shown to be rather global. Therefore, we assumed that aphantasics do not solely exhibit impairments in face recognition but rather in general visual recognition performance, probably moderated by stimulus complexity. To test this hypothesis, 65 aphantasics were compared to 55 controls in a face recognition task, the Cambridge Face Memory Test, and a corresponding object recognition task, the Cambridge Car Memory Test. In both tasks, aphantasics performed worse than controls, indicating mild recognition deficits without face-specificity. Additional correlations between imagery vividness and performance in both tasks were found, suggesting that visual imagery influences visual recognition not only in imagery extremes. Stimulus complexity produced the expected moderation effect but only for the whole imagery-spectrum and only with face stimuli. Overall, the results imply that aphantasia is linked to a general but mild deficit in visual recognition.

A novel geometry-based analysis of hippocampal morphometry in mesial temporal lobe epilepsy.

Hippocampal volumetry is an essential tool in researching and diagnosing mesial temporal lobe epilepsy (mTLE). However, it has a limited ability to detect subtle alterations in hippocampal morphometry. Here, we establish and apply a novel geometry-based tool that enables point-wise morphometric analysis based on an intrinsic coordinate system of the hippocampus. We hypothesized that this point-wise analysis uncovers structural alterations not measurable by volumetry, but associated with histological underpinnings and the neuropsychological profile of mTLE. We conducted a retrospective study in 204 individuals with mTLE and 57 age- and gender-matched healthy subjects. FreeSurfer-based segmentations of hippocampal subfields in 3T-MRI were subjected to a geometry-based analysis that resulted in a coordinate system of the hippocampal mid-surface and allowed for point-wise measurements of hippocampal thickness and other features. Using point-wise analysis, we found significantly lower thickness and higher FLAIR signal intensity in the entire affected hippocampus of individuals with hippocampal sclerosis (HS-mTLE). In the contralateral hippocampus of HS-mTLE and the affected hippocampus of MRI-negative mTLE, we observed significantly lower thickness in the presubiculum. Impaired verbal memory was associated with lower thickness in the left presubiculum. In HS-mTLE histological subtype 3, we observed higher curvature than in subtypes 1 and 2 (all p < .05). These findings could not be observed using conventional volumetry (Bonferroni-corrected p < .05). We show that point-wise measures of hippocampal morphometry can uncover structural alterations not measurable by volumetry while also reflecting histological underpinnings and verbal memory. This substantiates the prospect of their clinical application.

An automated, geometry-based method for hippocampal shape and thickness analysis.

The hippocampus is one of the most studied neuroanatomical structures due to its involvement in attention, learning, and memory as well as its atrophy in ageing, neurological, and psychiatric diseases. Hippocampal shape changes, however, are complex and cannot be fully characterized by a single summary metric such as hippocampal volume as determined from MR images. In this work, we propose an automated, geometry-based approach for the unfolding, point-wise correspondence, and local analysis of hippocampal shape features such as thickness and curvature. Starting from an automated segmentation of hippocampal subfields, we create a 3D tetrahedral mesh model as well as a 3D intrinsic coordinate system of the hippocampal body. From this coordinate system, we derive local curvature and thickness estimates as well as a 2D sheet for hippocampal unfolding. We evaluate the performance of our algorithm with a series of experiments to quantify neurodegenerative changes in Mild Cognitive Impairment and Alzheimer's disease dementia. We find that hippocampal thickness estimates detect known differences between clinical groups and can determine the location of these effects on the hippocampal sheet. Further, thickness estimates improve classification of clinical groups and cognitively unimpaired controls when added as an additional predictor. Comparable results are obtained with different datasets and segmentation algorithms. Taken together, we replicate canonical findings on hippocampal volume/shape changes in dementia, extend them by gaining insight into their spatial localization on the hippocampal sheet, and provide additional, complementary information beyond traditional measures. We provide a new set of sensitive processing and analysis tools for the analysis of hippocampal geometry that allows comparisons across studies without relying on image registration or requiring manual intervention.

Quantifying MR head motion in the Rhineland Study - A robust method for population cohorts.

Head motion during MR acquisition reduces image quality and has been shown to bias neuromorphometric analysis. The quantification of head motion, therefore, has both neuroscientific as well as clinical applications, for example, to control for motion in statistical analyses of brain morphology, or as a variable of interest in neurological studies. The accuracy of markerless optical head tracking, however, is largely unexplored. Furthermore, no quantitative analysis of head motion in a general, mostly healthy population cohort exists thus far. In this work, we present a robust registration method for the alignment of depth camera data that sensitively estimates even small head movements of compliant participants. Our method outperforms the vendor-supplied method in three validation experiments: 1. similarity to fMRI motion traces as a low-frequency reference, 2. recovery of the independently acquired breathing signal as a high-frequency reference, and 3. correlation with image-based quality metrics in structural T1-weighted MRI. In addition to the core algorithm, we establish an analysis pipeline that computes average motion scores per time interval or per sequence for inclusion in downstream analyses. We apply the pipeline in the Rhineland Study, a large population cohort study, where we replicate age and body mass index (BMI) as motion correlates and show that head motion significantly increases over the duration of the scan session. We observe weak, yet significant interactions between this within-session increase and age, BMI, and sex. High correlations between fMRI and camera-based motion scores of proceeding sequences further suggest that fMRI motion estimates can be used as a surrogate score in the absence of better measures to control for motion in statistical analyses.

Insights into the molecular genetic basis of individual differences in metacognition.

There is a striking lack of studies on the molecular genetic basis of metacognition, i.e., the higher-order ability to monitor mental processes. Here, an initial step toward resolving this issue was undertaken by investigating functional polymorphisms from three genes of the dopaminergic or serotonergic systems (DRD4, COMT, and 5-HTTLPR) in relation to behaviorally assessed metacognition in six paradigms across three cognitive domains. We report evidence for a task-dependent higher average confidence level (metacognitive bias) in carriers of at least one S or LG-allele in the 5-HTTLPR genotype and integrate these findings within a differential susceptibility framework.

Imaginal extinction without imagery: Dissociating the effects of visual imagery and propositional thought by contrasting participants with aphantasia, simulated aphantasia, and controls.

Imaginal exposure is a standard procedure of cognitive behavioral therapy for the treatment of anxiety and panic disorders. It is often used when in vivo exposure is not possible, too stressful for patients, or would be too expensive. Peter Lang's Bio-Informational Theory implies that imaginal exposure is effective because of the perceptual proximity of mental imagery to real events, whereas empirical findings suggest that propositional thought of fear stimuli (i.e., thinking about the stimuli without seeing them in the mind's eye) could be sufficient in therapeutical contexts. Exposure to propositional thought, instead of vivid mental imagery, would be more tolerable for patients since vivid imagery is associated with high emotional distress. To investigate whether mental imagery or propositional thought is crucial for the success of imaginal exposure, participants with the rare state of aphantasia (= absence of sensory mental imagery but with intact propositional thought) and two control groups were subjected to a fear conditioning paradigm followed by imaginal exposure and a reinstatement procedure. During imaginal exposure, control group 1 (N = 30) stared at a bright screen to disrupt visual imagery by incoming luminance (= simulated aphantasia), whereas control group 2 (N = 30) and participants with actual aphantasia (N = 30) kept their eyes closed. The results show […].

Visual impairment and retinal and brain neurodegeneration: A population-based study.

Visual impairment and retinal neurodegeneration are intrinsically connected and both have been associated with cognitive impairment and brain atrophy, but the underlying mechanisms remain unclear. To investigate whether transneuronal degeneration is implicated, we systematically assessed the relation between visual function and retinal, visual pathway, hippocampal and brain degeneration. We analyzed baseline data from 3316 eligible Rhineland Study participants with visual acuity (VA), optical coherence tomography (OCT), and magnetic resonance imaging (MRI) data available. Regional volumes, cortical volume, and fractional anisotropy (FA) were derived from T1-weighted and diffusion-weighted 3 T MRI scans. Statistical analyses were performed using multivariable linear regression and structural equation modeling. VA and ganglion cell layer (GCL) thinning were both associated with global brain atrophy (SD effect size [95% CI] -0.090 [-0.118 to -0.062] and 0.066 [0.053-0.080], respectively), and hippocampal atrophy (-0.029 [-0.055 to -0.003] and 0.114 [0.087-0.141], respectively). The effect of VA on whole brain and hippocampal volume was partly mediated by retinal neurodegeneration. Similarly, the effect of retinal neurodegeneration on brain and hippocampal atrophy was mediated through intermediate visual tracts, accounting for 5.2%-23.9% of the effect. Visual impairment and retinal neurodegeneration were robustly associated with worse brain atrophy, FA, and hippocampal atrophy, partly mediated through disintegration of intermediate visual tracts. Our findings support the use of OCT-derived retinal measures as markers of neurodegeneration, and indicate that both general and transneuronal neurodegeneration along the visual pathway, partly reflecting visual impairment, account for the association between retinal neurodegeneration and brain atrophy.