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Reich, L.

Publications and source records attributed to Reich, L..

3 recordsLinked to original sources

The brain dynamics of congenitally blind people seeing faces with sound

Sensory substitution devices (SSDs) convert images to sounds to equip blind individuals with nominally visual functions, like face or letter sensitivity. Prior studies showed that image-to-sound SSDs engage cortices ordinarily specialised for visual functions. However, the brain dynamics of SSD-supported perception remains unknown. Either visual cortices are the first locus of discrimination of SSD percepts, or their activation is a byproduct of perceptual processes unfurling elsewhere, such as in auditory cortices. Resolving this uncertainty is critical for understanding the contribution of visual cortices to mechanisms subserving SSD-induced perceptions in the blind. Using electrical neuroimaging of EEG data from congenitally blind adults, we show for the first time that visual cortices are the earliest site of face and letter sensitivity when conveyed via SSDs, though with distinct temporal dynamics and spatial localizations. In the case of faces versus scrambled faces, differences first manifested at 460ms post-stimulus onset as topographic EEG modulations that were in turn localized to a network of right-hemisphere regions, including the fusiform face area (FFA) as well as lateral occipital cortices. In the case of discerning vertically versus horizontally oriented letter shapes, differences first manifested at 370ms post-stimulus onset as topographic EEG modulations that were localized to a network of left-hemisphere regions, including the occipital pole and the occipito-temporal junction extending into the angular gyrus. Notably, early-latency auditory evoked potentials did not differ based on visual properties of the soundscapes. These collective data support the proposition that responses to soundscapes are routed to brain circuits ordinarily specialized for processing visual information and that these circuits are the loci of the initial discriminant processes. By providing the temporal dynamics of SSD perception, our findings provide unique evidence for the theory that cortices are characterised by task-contingent functional organisation. HighlightsO_LISensory substitution devices (SSDs) provide the blind access to visual information C_LIO_LIBrain dynamics in visual cortices to SSD-conveyed object images are unknown C_LIO_LIEarly EEG sensitivity for faces and letters was localized to the visual cortex C_LIO_LIThe blind visual cortex takes part in early SSD processing for visual categories C_LI eTOC blurbWe characterise for the first time the brain dynamics of the blind using soundscapes for face and letter discrimination. Faces recruited the FFA at 460ms post-stimulus onset, whereas letters recruited the occipital pole, occipito-temporal junction, and angular gyrus at 370ms post-stimulus onset. Our findings of the temporal dynamics of SSD perception uniquely support the theory that cortices are characterised by task-selective sensory-independent functional organisation.

neuroscience↗

Single-cell multiomic analysis reveals the involvement of Type I interferon-responsive CD8+ T cells in amyloid beta-associated memory loss

Alzheimers disease (AD) is the leading cause of dementia worldwide, but there are limited therapeutic options and no current cure. While the involvement of microglia in AD has been highly appreciated, the role of other innate and adaptive immune cells remains largely unknown, partly due to their scarcity and heterogeneity. This study aimed to study non-microglial immune cells in wild type and AD-transgenic mouse brains across different ages. Our results uncovered the presence of a unique CD8+ T cell population that were selectively increased in aging AD mouse brains, here referred to as "disease-associated T cells (DATs)". These DATs were found to express an elevated tissue-resident memory and Type I interferon-responsive gene signature. Further analysis of aged AD mouse brains showed that these CD8+ T cells were not present in peripheral or meningeal tissues. Preventing CD8+ T cell development in AD-transgenic mice via genetic deletion of beta-2 microglobulin (B2m) led to a reduction of amyloid-{beta} plaque formation in aged mice, and improved memory in AD-transgenic mice as early as four months of age. The integration of transcriptomic and epigenomic profiles at the single-cell level revealed potential transcription factors that reshape the regulomes of CD8+ T cells. These findings highlight a critical role for DATs in the progression of AD and provide a new avenue for treatment.

immunology↗

The carnitine shuttle links mitochondrial metabolism to histone acetylation and lipogenesis

Acetyl-CoA is a central metabolite used for lipid synthesis in the cytosol and histone acetylation in the nucleus, among other pathways. The two major precursors to acetyl-CoA in the nuclear-cytoplasmic compartment are citrate and acetate, which are processed to acetyl-CoA by ATP-citrate lyase (ACLY) and acyl-CoA synthetase short-chain 2 (ACSS2), respectively. While some evidence has suggested the existence of additional routes to nuclear-cytosolic acetyl-CoA, such pathways remain poorly defined. To investigate this, we generated cancer cell lines lacking both ACLY and ACSS2. Unexpectedly, and in contrast to observations in fibroblasts, ACLY and ACSS2 double knockout (DKO) cancer cells remain viable and proliferate, maintain pools of cytosolic acetyl-CoA, and are competent to acetylate proteins in both cytosolic and nuclear compartments. Using stable isotope tracing, we show that both glucose and fatty acids feed acetyl-CoA pools and histone acetylation in DKO cells. Moreover, we provide evidence for the carnitine shuttle and carnitine acetyltransferase (CrAT) as a substantial pathway to transfer two-carbon units from mitochondria to cytosol independent of ACLY. Indeed, in the absence of ACLY, glucose can feed fatty acid synthesis in a carnitine responsive and CrAT-dependent manner. This work defines a carnitine-facilitated route to produce nuclear-cytosolic acetyl-CoA, shedding light on the intricate regulation and compartmentalization of acetyl-CoA metabolism

cell biology↗