Deficits in the interpretation of others' intentions from gaze-direction or other social attention cues are well-recognized in ASD. Here we investigated whether an EEG brain computer interface (BCI) can be used to train social cognition skills in ASD patients. We performed a single-arm feasibility clinical trial and enrolled 15 participants (mean age 22y 2m) with high-functioning ASD (mean full-scale IQ 103). Participants were submitted to a BCI training paradigm using a virtual reality interface over seven sessions spread over 4 months. The first four sessions occurred weekly, and the remainder monthly. In each session, the subject was asked to identify objects of interest based on the gaze direction of an avatar. Attentional responses were extracted from the EEG P300 component. A final follow-up assessment was performed 6-months after the last session. To analyze responses to joint attention cues participants were assessed pre and post intervention and in the follow-up, using an ecologic “Joint-attention task.” We used eye-tracking to identify the number of social attention items that a patient could accurately identify from an avatar's action cues (e.g., looking, pointing at). As secondary outcome measures we used the Autism Treatment Evaluation Checklist (ATEC) and the Vineland Adaptive Behavior Scale (VABS). Neuropsychological measures related to mood and depression were also assessed. In sum, we observed a decrease in total ATEC and rated autism symptoms (Sociability; Sensory/Cognitive Awareness; Health/Physical/Behavior); an evident improvement in Adapted Behavior Composite and in the DLS subarea from VABS; a decrease in Depression (from POMS) and in mood disturbance/depression (BDI). BCI online performance and tolerance were stable along the intervention. Average P300 amplitude and alpha power were also preserved across sessions. We have demonstrated the feasibility of BCI in this kind of intervention in ASD. Participants engage successfully and consistently in the task. Although the primary outcome (rate of automatic responses to joint attention cues) did not show changes, most secondary neuropsychological outcome measures showed improvement, yielding promise for a future efficacy trial.(clinical-trial ID: NCT02445625—clinicaltrials.gov).

How aging concomitantly modulates the structural integrity of the brain and retina in healthy individuals remains an outstanding question. Given the strong bottom-up retinocortical connectivity, it is important to study how these structures co-evolve during healthy aging in order to unravel mechanisms that may affect the physiological integrity of both structures. For the 56 participants in the study, primary visual cortex (BA17), as well as frontal, parietal and temporal regions thicknesses were measured in T1-weighted magnetic resonance imaging (MRI), and retinal macular thickness (10 neuroretinal layers) was measured by optical coherence tomography (OCT) imaging. We investigated the statistical association of these measures and their age dependence. We found an age-related decay of primary visual cortical thickness that was significantly correlated with a decrease in global and multiple layer retinal thicknesses. The atrophy of both structures might jointly account for the decline of various visual capacities that accompany the aging process. Furthermore, associations with other cortical regions suggest that retinal status may index cortical integrity in general.

Autism spectrum disorder is characterized by abnormal function in core social brain regions. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback. Following up the demonstration of neuromodulation in healthy participants, in this repeated-measure design clinical trial, 15 autism spectrum disorder patients were enrolled in a 5-session training program of real-time functional magnetic resonance imaging neurofeedback targeting facial emotion expressions processing, using the posterior superior temporal sulcus as region-of-interest. Participants were able to modulate brain activity in this region-of-interest, over multiple sessions. Moreover, we identified the relevant clinical and neural effects, as documented by whole-brain neuroimaging results and neuropsychological measures, including emotion recognition of fear, immediately after the intervention and persisting after 6 months. Neuromodulation profiles demonstrated subject-specificity for happy, sad, and neutral facial expressions, an unsurprising variable pattern in autism spectrum disorder. Modulation occurred in negative or positive directions, even for neutral faces, in line with their often-perceived ambiguity in autism spectrum disorder. Striatal regions (associated with success/failure of neuromodulation), saliency (insula/anterior cingulate cortex), and emotional control (medial prefrontal cortex) networks were recruited during neuromodulation. Recruitment of the operant learning network is consistent with participants’ engagement. Compliance, immediate intervention benefits, and their persistence after 6 months pave the way for a future Phase IIb/III, randomized controlled clinical trial, with a larger sample that will allow to conclude on clinical benefits from neurofeedback training in autism spectrum disorder (NCT02440451). Lay abstract Neurofeedback is an emerging therapeutic approach in neuropsychiatric disorders. Its potential application in autism spectrum disorder remains to be tested. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback in targeting social brain regions in autism spectrum disorder. In this clinical trial, autism spectrum disorder patients were enrolled in a program with five training sessions of neurofeedback. Participants were able to control their own brain activity in this social brain region, with positive clinical and neural effects. Larger, controlled, and blinded clinical studies will be required to confirm the benefits.

The retina may serve as putative window into neuropathology of synaptic loss in Alzheimer’s disease (AD). Here, we investigated synapse-rich layers versus layers composed by nuclei/cell bodies in an early stage of AD. In addition, we examined the associations between retinal changes and molecular and structural markers of cortical damage. We recruited 20 AD patients and 17 healthy controls (HC). Combining optical coherence tomography (OCT), magnetic resonance (MR), and positron emission tomography (PET) imaging, we measured retinal and primary visual cortex (V1) thicknesses, along with V1 amyloid β (Aβ) retention ([11C]-PiB PET tracer) and neuroinflammation ([11C]-PK11195 PET tracer). We found that V1 showed increased amyloid-binding potential, in the absence of neuroinflammation. Although thickness changes were still absent, we identified a positive association between the synapse-rich inner plexiform layer (IPL) and V1 in AD. This retinocortical interplay might reflect changes in synaptic function resulting from Aβ deposition, contributing to early visual loss.

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