bioRxiv Subject Collection: Neuroscience's Journal
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Friday, November 1st, 2024
| Time |
Event |
| 8:30a |
From single words to sentence production: Shared cortical representations but distinct temporal dynamics
Sentence production is the uniquely human ability to transform complex thoughts into strings of words. Despite the importance of this process, language production research has primarily focused on single words. It remains an untested assumption that insights from this literature generalize to more naturalistic utterances like sentences. Here, we investigate this using high-resolution neurosurgical recordings (ECoG) and an overt production experiment where patients produce six words in isolation (picture naming) and in sentences (scene description). We used machine learning models to identify the unique brain activity pattern for each word during picture naming, and used these patterns to decode which words patients were processing while they produced sentences. In sensorimotor cortex, this procedure predicted each noun in the order it was said in the sentence, confirming that words share cortical representations across tasks. However, in inferior and middle frontal gyri (IFG and MFG), the order in which words were processed depended on the syntactic structure of the sentence. This dynamic interplay between sentence structure and word processing reveals that sentence production is not simply a sequence of single word production tasks. We argue that it is time for the field to leverage the extensive literature on word production for studying more naturalistic linguistic constructs like sentences. | | 8:30a |
Touch to text: Spatiotemporal evolution of braille letter representations in blind readers
Visual deprivation does not silence the visual cortex, which is responsive to auditory, tactile, and other nonvisual tasks in blind persons. However, the underlying functional dynamics of the neural networks mediating such crossmodal responses remain unclear. Here, using braille reading as a model framework to investigate these networks, we presented sighted (N=13) and blind (N=12) readers with individual visual print and tactile braille alphabetic letters, respectively, during MEG recording. Using time-resolved multivariate pattern analysis and representational similarity analysis, we traced the alphabetic letter processing cascade in both groups of participants. We found that letter representations unfolded more slowly in blind than in sighted brains, with decoding peak latencies ~200 ms later in braille readers. Focusing on the blind group, we found that the format of neural letter representations transformed within the first 500 ms after stimulus onset from a low-level structure consistent with peripheral nerve afferent coding to high-level format reflecting pairwise letter embeddings in a text corpus. The spatiotemporal dynamics of the transformation suggest that the processing cascade proceeds from a starting point in somatosensory cortex to early visual cortex and then to inferotemporal cortex. Together our results give insight into the neural mechanisms underlying braille reading in blind persons and the dynamics of functional reorganization in sensory deprivation. | | 8:30a |
Practice beyond performance stabilization increases the use of online adjustments to unpredictable perturbations in an interceptive task
In recent decades, research has focused on motor adjustments in interception tasks within predictable environments. However, emerging studies suggest that continued practice beyond performance stabilization enhances the ability to adapt to unpredictable events. The objective of this study was to investigate the effects of practicing until performance stabilization versus extended practice through superstabilization on the ability to adjust to unpredictable perturbations in intercepting a moving target. We hypothesized superstabilization would better facilitate motor adjustments in response to unpredictable perturbations. Forty participants engaged in an interception task until they achieved either performance stabilization or superstabilization. Subsequently, both stabilization and superstabilization groups were tested in an unpredictable environment, where, in certain trials, the target's velocity unexpectedly changed after the onset of the movement. The findings revealed that the superstabilization group made more adjustments in response to these perturbations than the stabilization group, attributed to their developed capacity to use online feedback as a control mechanism more efficiently. In contrast, the practice until performance stabilization did not foster this adaptive mechanism. These results support the notion that learning is a dynamic process that extends beyond the point of performance stabilization, emphasizing the benefits of continued practice for mastering complex motor tasks in variable contexts. | | 8:30a |
Consistent hierarchies of single-neuron timescales in mice, macaques and humans
The intrinsic timescales of single neurons are thought to be hierarchically organized across the cortex. This conclusion, however, is primarily based on analyses of neural responses from macaques. Whether hierarchical variation in timescales is a general brain organizing principle across mammals remains unclear. Here we took a cross-species approach and estimated neuronal timescales of thousands of single neurons recorded across multiple areas in mice, monkeys, and humans using a task-agnostic method. We identify largely consistent hierarchies of timescales in frontal and limbic regions across species: hippocampus had the shortest timescale whereas anterior cingulate cortex had the longest. Within this scheme, variability across species was found, most notably in amygdala and orbitofrontal cortex. We show that variation in timescales is not simply related to differences in spiking statistics nor the result of cytoarchitectonic features such as cortical granularity. Thus, hierarchically organized timescales are a consistent organizing principle across species and appear to be related to a combination of intrinsic and extrinsic factors. | | 9:47a |
Thalamic integration of basal ganglia and cerebellar circuits during motor learning
The ability to control movement and learn new motor skills is one of the fundamental functions of the brain. The basal ganglia (BG) and the cerebellum (CB) are two key brain regions involved in controlling movement, and neuronal plasticity within these two regions is crucial for acquiring new motor skills. However, how these regions interact to produce a cohesive unified motor output remains elusive. Here, we discovered that a subset of neurons in the motor thalamus receive converging synaptic inputs from both BG and CB. By performing multi-site fiber photometry in mice learning motor tasks, we found that motor thalamus neurons integrate BG and CB signals and show distinct movement-related activity. Lastly, we found a critical role of these thalamic neurons and their BG and CB inputs in motor learning and control. These results identify the thalamic convergence of BG and CB and its crucial role in integrating movement signals. | | 9:47a |
The adolescent frontal cortex shows stronger population-level encoding of information than the adult during a putative sensitive period
Adolescence is considered to be a sensitive period for brain development, but it is not clear how the neocortex functions differently at this stage. We hypothesized that if there is a sensitive period in the dorsomedial prefrontal cortex (dmPFC) during adolescence, then we might find this area shows stronger encoding of task-related information at adolescent ages than at adult ages. To enable optical access to task-related layer 2/3 neural activity in the developing mouse, we imaged mice under a 2-photon microscope while they learned an auditory go/no-go task. We found adolescent mice (postnatal day P30-45) learned the task to criterion faster than adult mice (P60-75). When we compared neural activity in expert mice with comparable performance between the two age groups, we found that a similar fraction of single cells encoded task variables in the two groups. However, task information could be better decoded from the adolescent dmPFC population activity than the adult, even when we controlled for differences in head-fixed running. Adolescents also showed greater noise correlation than adults, and shuffling to remove this noise correlation suggested noise correlation contributed to gain of function in adolescent compared to adult brain. We suggest a working model for an adolescent sensitive period in the frontal association cortex in which greater capacity for distributed encoding of information in the adolescent dmPFC underlies increased sensitivity to experiences that occur at this stage of life. | | 10:17a |
Dentate Gyrus Norepinephrine Ramping Facilitates Aversive Contextual Processing
Dysregulation in aversive contextual processing is believed to affect several forms of psychopathology, including post-traumatic stress disorder (PTSD). The dentate gyrus (DG) is an important brain region in contextual discrimination and disambiguation of new experiences from prior memories. The DG also receives dense projections from the locus coeruleus (LC), the primary source of norepinephrine (NE) in the mammalian brain, which is active during stressful events. However, how noradrenergic dynamics impact DG-dependent function during contextual discrimination and pattern separation remains unclear. Here, we report that aversive contextual processing in mice is linked to linear elevations in tonic norepinephrine release dynamics within the DG and report that this engagement of prolonged norepinephrine release is sufficient to produce contextual disambiguation, even in the absence of a salient aversive stimulus. These findings suggest that spatiotemporal ramping characteristics of LC-NE release in the DG during stress likely serve an important role in driving contextual processing. | | 10:17a |
Novel environment exposure drives temporally defined and region-specific chromatin accessibility and gene expression changes in the hippocampus
Curiosity-driven interactions with novel cues in our environment represent a common behavioral trait across the animal kingdom. Exposure to a novel environment (NE) reshapes the brain by promoting structural and functional changes in multiple brain areas, including the hippocampus. This experience-dependent circuit reorganization is thought to be driven in part by changes in gene expression. While NE exposure has been shown to rapidly induce the expression of FOS and other immediate-early gene transcription factors (IEG TFs), the downstream IEG-driven genes (e.g. late response genes) that serve to mediate NE-dependent circuit remodeling, as well as the DNA regulatory elements that drive the expression of these genes, remain largely unexplored. We employed a combination of hippocampal single-nucleus multiomics and bulk RNA sequencing of the DG, CA3, and CA1 regions to characterize over time the NE-driven gene expression and chromatin accessibility changes downstream of IEG induction. We observe strong hippocampal region-specificity in excitatory neuron late-response gene programs as well as diversity in the inhibitory neuron and non-neuronal gene responses. In addition, compared to a short exposure, prolonged exposure to NE caused more robust induction of late-response genes, suggesting that sustained environmental stimulation is more effective at triggering the long-lasting molecular changes that support memory formation. Notably, chromatin-level analyses revealed thousands of cell-type-specific changes in chromatin accessibility in response to NE exposure. Coordinated analysis of both chromatin accessibility and gene expression within individual cells revealed the Fos binding site referred to as the AP-1 motif as a major predictor of neuronal cell-type-specific late-response gene expression. Together, these data provide a rich resource of hippocampal chromatin accessibility and gene expression changes in response to novel experience, a physiological stimulus that affects learning and memory. | | 12:16p |
Subregional activity in the dentate gyrus is amplified during elevated cognitive demands
Neural activity in the dentate gyrus (DG) is required for the detection and discrimination of novelty, context and patterns, amongst other cognitive processes. Prior work has demonstrated that there are differences in the activation of granule neurons in the supra and infrapyramidal blades of the DG during a range of hippocampal dependent tasks. Here we used an automated touch screen pattern separation task combined to temporally controlled tagging of active neurons to determine how performance in a cognitively demanding task affected patterns of neural activity in the DG. We found an increase in the blade-biased activity of suprapyramidal mature granule cells (mGCs) during the performance of a high cognitive demand segment of the task, with a further characteristic distribution of active neurons along the apex to blade, and hilar to molecular layer axes. Chemogenetic inhibition of adult-born granule cells (abDGCs) beyond a critical window of their maturation significantly impaired performance of mice when cognitive demand was high, but not when it was low. abDGC inhibition also elevated the total activity of mGCs and disturbed the patterned distribution of active mGCs even in mice that eventually succeeded in the task. Conversely chemogenetic inhibition of mGCs reduced success in the high cognitive demand portion of this task and decreased the global number of active GCs without affecting the patterned distribution of active cells. These findings demonstrate how a high cognitive demand pattern separation task preferentially activates mGCs in subregions of the DG and are consistent with an inhibitory role for abDGCs on the dentate circuit which in part governs the spatially organized patterns of activity of mGCs. |
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