Journal of Neuroscience最新文献

Psychedelics profoundly alter subjective experience and brain dynamics. Brain oscillations express signatures of near-critical dynamics, relevant for healthy function. Alterations in the proximity to criticality have been suggested to underlie the experiential and neurological effects of psychedelics. Here, we investigate the effects of a psychedelic substance (DMT) on the criticality of brain oscillations, and in relation to subjective experience, in humans of either sex. We find that DMT shifts the dynamics of brain oscillations away from criticality in alpha and adjacent frequency bands. In this context, entropy is increased while complexity is reduced. We find that the criticality-shifts observed in alpha and theta bands correlate with the intensity ratings of self-dissolution, a hallmark of psychedelic experience. Finally, using a recently developed metric, the functional excitatory-inhibitory ratio, we find that the DMT-induced criticality-shift in brain oscillations is toward subcritical regimes. These findings have major implications for the neuronal understanding of the self and psychedelics, as well as for the neurological basis of altered states of consciousness.

The neural signatures of preparing overt eye movements and directing covert spatial attention overlap as they recruit the same brain areas. Yet, these neural signatures are dissociable at the single cell level: Specific cells within visuo-oculomotor areas are exclusively involved in motor preparation or covert attention. Nevertheless, it has been proposed that many cells in visuo-oculomotor areas are involved in both motor preparation and covert attention, and consequently their neural signatures should functionally overlap to a large degree. Here, we directly tested this proposal: We combined human (both sexes) EEG with sensitive decoding techniques to investigate whether the neural signatures of preparatory overt and covert attention are dissociable across large-scale neuronal populations. We found that neural decoding reliably discerned whether overt or covert attention was shifted well before saccade initiation. Further, inverted encoding modeling revealed earlier and sharper spatially selective activity in preparatory overt than in covert attention. We then asked whether preparatory overt attention achieved sharper spatial selectivity by using "more-of-the-same" covert attention or by recruiting an additional neural process. Cross-decoding results demonstrated that preparatory overt attention recruited at least one additional, frontal process. This additional spatially selective process emerged early and likely reflects motor preparation or predictive remapping. To summarize, we found that the neural signatures of overt and covert attention overlap, yet diverge rapidly, in part because overt attention employs an additional spatially selective neural process. Extending beyond a dissociation on the single-cell level, our findings demonstrate that population-level neural activity dissociates preparatory overt from covert attention.

Neuroanatomical features across spatial scales contribute to functional specialization and individual differences in behavior across species. Among species with gyrencephalic brains, gyral crown height, which measures a key aspect of the morphology of cortical folding, may represent an anatomical characteristic that importantly shapes neural function. Nevertheless, little is known about the relationship between functional selectivity and gyral crowns-especially in clinical populations. Here, we investigated this relationship and found that the size and gyral crown height of the middle, but not posterior, face-selective region on the fusiform gyrus were decreased in individuals with developmental prosopagnosia (N = 22; 68% female; aged 25-62) compared with neurotypical controls (NTs; N = 25; 60% females; aged 21-55), and this difference was related to face perception. Additional analyses replicated the relationship between gyral crowns and face-selective region size in 1,053 NTs (55% females; aged 22-36). These results inform theoretical models of face processing while also providing a novel neuroanatomical feature contributing to the cortical infrastructure supporting face processing.

Sensorimotor and cognitive abilities undergo substantial changes throughout the human lifespan, but the corresponding changes in the functional properties of cortical networks remain poorly understood. This can be studied using temporal and spatial scales of functional magnetic resonance imaging (fMRI) signals, which provide a robust description of the topological structure and temporal dynamics of neural activity. For example, timescales of resting-state fMRI signals parsimoniously predict a significant amount of the individual variability in functional connectivity networks identified in adult human brains. In the present study, we quantified and compared temporal and spatial scales in resting-state fMRI data collected from 2,352 subjects of either sex between the ages of 5 and 100 in Developmental, Young Adult, and Aging datasets from the Human Connectome Project. For most cortical regions, we found that both temporal and spatial scales decreased with age throughout the lifespan, with the visual cortex and the limbic network consistently showing the largest and smallest scales, respectively. For some prefrontal regions, however, these two scales displayed non-monotonic trajectories and peaked around the same time during adolescence and decreased throughout the rest of the lifespan. We also found that cortical myelination increased monotonically throughout the lifespan, and its rate of change was significantly correlated with the changes in both temporal and spatial scales across different cortical regions in adulthood. These findings suggest that temporal and spatial scales in fMRI signals, as well as cortical myelination, are closely coordinated during both development and aging.

Mouse superficial superior colliculus (sSC) has been found to have orientation selective maps, suggesting a fundamentally different selectivity than in primate SC. Moreover, orientation selectivity in mouse sSC appears to change with stimulus properties such as size, shape, and spatial frequency, in contradistinction to the computational principle of invariance in primates. To reconcile mouse and primate mechanisms for orientation selectivity, we constructed a computational model of mouse sSC populations with circular-symmetric, center-surround (i.e., not intrinsically orientation selective), stimulus-invariant receptive fields (RFs), classically used to describe monkey lateral geniculate nucleus (LGN) neurons. This model produced population maps similar to those found in mouse sSC, which show strong radial orientation preferences at retinotopic locations along stimulus edges. We show how this selectivity depended critically on spatial frequency tuning of the model units. The model predicted a shift from radial to anti-radial orientation preferences from the same simulated units at high stimulus spatial frequencies, also consistent with measurements from mouse sSC. We found intrinsically oriented RFs were largely unnecessary to explain the imaging data but could explain a possible small subpopulation of intrinsically orientation selective neurons. We conclude that to study orientation selectivity in mouse sSC and other systems, the problem is not the choice of stimulus. Rather than endless tweaks to find the perfect, unbiased stimulus, image-computable population modeling is the solution. Regardless of the stimulus presented, comparing how well models of intrinsically or non-intrinsically orientation selective units account for empirical data provides definitive evidence for underlying neural selectivity.

During passive listening, the brain maintains a hierarchy of predictive models to monitor the statistics of its surroundings. The automatic discovery of regular patterns has been associated with a gradual increase in sustained tonic magnetoencephalography (MEG)/electroencephalography activity, sourced in auditory, hippocampal, and frontal areas-reflecting evidence accumulation and establishment of a regularity model. Conversely, when a regular pattern is interrupted, the sustained activity drops-indicating disengagement from the model. However, how such models are established in and retrieved from memory and the conditions under which they are activated and interrupted remain underexplored. In this MEG experiment (N = 26 human participants; both sexes), we examined how neural responses related to model "establishment" and "interruption" are influenced by (1) the rate of stimulus presentation (tone presentation rate 20 vs 40 Hz) and (2) the novelty of the experienced acoustic structure (novel vs resumed regular pattern). The results show that (1) the dynamics of model interruption and establishment are independent of stimulus presentation rate, and that (2) model establishment occurred much faster when an experienced versus novel pattern was presented after pattern interruption, suggesting reactivation of the stored original model facilitated by the hippocampus. (3) Finally, sustained-response rises in response to pattern establishment and interruption were localized in auditory, hippocampal, and frontal sources, supporting top-down model information flow. These results unveil the temporal dynamics and neural network underlying the brain's construction and selection of predictive models to monitor changes in sensory statistics.

Age-related decline underlies cognitive functions such as sensorimotor control, executive functioning, memory, and language production (LP), whereas language comprehension (LC) tends to remain intact or improve across healthy adult lifespan. This preservation likely stems from structural and functional integrity within core language network (cLAN) regions. To investigate this hypothesis, we analyzed the relationships among brain's resting-state functional connectivity (FC), structural connectivity (SC), and language behavior (LC and LP) using a cross-sectional cohort of healthy adults (N = 652; M/F = 322/330; aged 18-88) from the Cambridge Centre for Ageing and Neuroscience (CamCAN) dataset. Six cognitive tasks assessing LC and LP were employed, with neuroimaging measures focused on region-specific connections within the cLAN. Using generalized additive mixed models (GAMMs), complex brain-behavior interactions were identified. Behavioral analyses revealed established age-related dichotomy, LC abilities in vocabulary and proverb comprehension improved, and in syntactic and semantic comprehension remained stable, whereas LP tasks, e.g., verbal fluency, picture priming, and tip of tongue, exhibited significant decline across the lifespan. SC exhibited decline in both intra- and interhemispheric frontotemporal and frontal lobe connections, contrasted by preserved or enhanced temporal lobe connectivity, supporting a pattern of frontal vulnerability concomitant with temporal resilience. Age-related FC patterns demonstrated overall preservation, reflecting compensatory mechanisms to sustain functional integrity despite structural degradation. GAMM analyses revealed complex relationships between brain connectivity and language performance across age. Thus, integrating knowledge of brain structure, function, and language abilities, we identified the brain network mechanisms associated with dichotomous language behavior along lifespan.

Two major glutamate decarboxylase isoforms (i.e., GAD65 and GAD67) together synthesize the majority of γ-aminobutyric acid (GABA) in our nervous system. However, the subcellular distribution of these enzymes and their relative impacts on synaptic GABA release remain unclear. To address this important question, here we monitored their synaptic trafficking in male and female mouse brains and dissociated neuronal cultures. We noticed that, unlike some major glutamate-biosynthesizing enzymes, e.g., glutaminase and glutamate dehydrogenase, which were primarily associated with perisomatic mitochondria, both GADs together were highly enriched at GABAergic presynapses. Nevertheless, when expressed separately in GAD-deficient human neurons derived from a male stem cell line, GAD65 exhibited preferential distribution at presynapses over GAD67. Despite these differences in subcellular localization, both GADs produced equivalent levels of intracellular GABA, which adequately diffused to axon terminals, and triggered robust GABAergic activities. These findings raised the question of whether the presynaptic recruitment of GADs is, after all, necessary for reliable GABAergic transmission. To examine this hypothesis, we further swapped or removed the trafficking signals from both GAD isoforms and even artificially restricted them at nonsynaptic compartments, including the cell nucleus. Despite our attempts, the chimeric and mutant GAD variants continued to produce sufficient amount of intracellular GABA for vesicular loading and presynaptic release. These results indicate that GAD65 and GAD67 are functionally redundant in GABA production, if expressed equitably in neurons, and irrespective of GADs' subcellular trafficking profile, diffusion of GABA molecules from distant sources can effectively supply and replenish the presynaptic terminals for functional activities.

The ON visual pathway is initiated by the deactivation of mGluR6, coupled to the opening of TRPM1 channels in retinal ON-bipolar cell dendrites. Here, we show that a second metabotropic glutamate receptor, mGluR5, is localized with TRPM1 and mGluR6 in the dendrites of ON-bipolar cells. To examine the function of mGluR5, we performed electroretinogram (ERG) recordings in mice of either sex and found that the amplitude of the b-wave, which is primarily a measure of ON-bipolar cell light-driven activity, is reduced in mGluR5 knock-out mice compared with wild type. In the mGluR5^-/- retina, we observed weaker mGluR6 immunofluorescence in the dendritic tips of ON-bipolar cells that could explain the smaller ERG b-wave. To observe the effect of mGluR5 without perturbing mGluR6 expression, wild-type mice were injected with MTEP, an allosteric antagonist of mGluR5. MTEP increased the amplitude of the b-wave in response to dim stimuli and caused an inflection in the intensity-response plot for flashes in the mesopic range. In the brain, postsynaptic mGluR5 regulates presynaptic glutamate release via endocanabinoid-mediated retrograde signaling. Therefore, we tested the effect of the CB1 receptor antagonist, SR1417A, on the ERG and found that the b-wave was affected as by MTEP, including an inflection in the intensity-response. We further showed that the CB1 receptor agonist, ACEA, reversed the effects of MTEP. Together, our results indicate that mGluR5 plays a role in gain-control at the photoreceptor to ON-bipolar cell synapses, likely via an endocannabinoid-mediated retrograde feedback.

The hippocampus plays a crucial role in consolidating episodic memories from diverse experiences that encompass spatial, temporal, and novel information. This study analyzed the spike patterns of hippocampal place cells in the CA3 and CA1 areas of male rats that sequentially foraged in five rooms, including familiar and novel rooms, followed by a rest period. Across the five rooms, both CA3 and CA1 place cells showed overlapping spatial representations. In a postexperience rest period, both CA3 and CA1 place cells increased baseline spike rates depending on the temporal distance from when the cells had place fields. In addition, CA3 place cells that encoded novel environments showed stronger sharp-wave ripple (SWR) reactivation. Coordinated reactivation of CA1 place cell ensembles that encoded temporally distant environments was eliminated. These results suggest that, following sequential experiences in multiple environments, increases in SWR-induced spikes of hippocampal neurons more specifically process novelty-related aspects of memory, while global increases in baseline spike rates process temporal distance-related aspects.