Cerebellar disruption impairs working memory during evidence accumulation.
Ontology highlight
ABSTRACT:
SUBMITTER: Deverett B
PROVIDER: S-EPMC6635393 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Cerebellar disruption impairs working memory during evidence accumulation.
Deverett Ben B Kislin Mikhail M Tank David W DW Wang Samuel S-H SS
Nature communications 20190716 1
To select actions based on sensory evidence, animals must create and manipulate representations of stimulus information in memory. Here we report that during accumulation of somatosensory evidence, optogenetic manipulation of cerebellar Purkinje cells reduces the accuracy of subsequent memory-guided decisions and causes mice to downweight prior information. Behavioral deficits are consistent with the addition of noise and leak to the evidence accumulation process. We conclude that the cerebellum ...[more]
Similar Datasets
Project description:It has been proposed that evidence accumulation determines not only the speed and accuracy of simple perceptual decisions but also influences performance on tasks assessing higher-order cognitive abilities, such as working memory (WM). Accordingly, estimates of evidence accumulation based on diffusion decision modeling of perceptual decision-making tasks have been found to correlate with WM performance. Here we use diffusion decision modeling in combination with latent factor modeling to test the stronger prediction that practice-induced changes in evidence accumulation correlate with changes in WM performance. Analyses are based on data from the COGITO Study, in which 101 young adults practiced a battery of cognitive tasks, including three simple two-choice reaction time tasks and three WM tasks, in 100 day-to-day training sessions distributed over 6 months. In initial analyses, drift rates were found to correlate across the three choice tasks, such that latent factors of evidence accumulation could be established. These latent factors of evidence accumulation were positively correlated with latent factors of practiced and unpracticed WM tasks, both before and after practice. As predicted, individual differences in changes of evidence accumulation correlated positively with changes in WM performance. Our findings support the proposition that decision making and WM both rely on the active maintenance of task-relevant internal representations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
| S-EPMC10030378 | biostudies-literature
Project description:Verbal working memory is one of the most studied non-motor functions with robust cerebellar involvement. While the superior cerebellum (lobule VI) has been associated with articulatory control, the inferior cerebellum (lobule VIIIa) has been linked to phonological storage. The present study was aimed to elucidate the differential roles of these regions by investigating whether the cerebellum might contribute to verbal working memory via predictions based on sequence learning/detection. 19 healthy adult subjects completed an fMRI-based Sternberg task which included repeating and novel letter sequences that were phonologically similar or dissimilar. It was hypothesized that learning a repeating sequence of study letters would reduce phonological storage demand and associated right inferior cerebellar activations and that this effect would be modulated by phonological similarity of the study letters. Specifically, while increased phonological storage demand due to high phonological similarity was expected to be reflected in increased right inferior cerebellar activations for similar relative to dissimilar study letters, the reduction in activation for repeating relative to novel sequences was expected to be more profound for phonologically similar than for dissimilar study letters, especially at higher memory load. Results confirmed the typical effects of cognitive load (5 vs. 2 study letters) and phonological similarity in several cerebellar and neocortical brain regions as well as in behavioral data (accuracy and response time). Importantly, activations in superior and inferior cerebellar regions were differentially modulated as a function of similarity and sequence novelty, indicating that particularly lobule VIIIa may contribute to verbal working memory by generating predictions of letter sequences that reduce the likelihood of phonological loop failure before stored items need to be retrieved. The present study is consistent with other investigations that support prediction, which can be based on sequence learning or detection, as an overarching cerebellar function.
| S-EPMC6373538 | biostudies-literature
Project description:Memory consolidation has been proposed as a function of sleep. However, sleep is a complex phenomenon characterized by several features including duration, intensity, and continuity. Sleep continuity is disrupted in different neurological and psychiatric conditions, many of which are accompanied by memory deficits. This finding has raised the question of whether the continuity of sleep is important for memory consolidation. However, current techniques used in sleep research cannot manipulate a single sleep feature while maintaining the others constant. Here, we introduce the use of optogenetics to investigate the role of sleep continuity in memory consolidation. We optogenetically targeted hypocretin/orexin neurons, which play a key role in arousal processes. We used optogenetics to activate these neurons at different intervals in behaving mice and were able to fragment sleep without affecting its overall amount or intensity. Fragmenting sleep after the learning phase of the novel object recognition (NOR) task significantly decreased the performance of mice on the subsequent day, but memory was unaffected if the average duration of sleep episodes was maintained at 62-73% of normal. These findings demonstrate the use of optogenetic activation of arousal-related nuclei as a way to systematically manipulate a specific feature of sleep. We conclude that regardless of the total amount of sleep or sleep intensity, a minimal unit of uninterrupted sleep is crucial for memory consolidation.
| S-EPMC3156195 | biostudies-literature
Project description:A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between cognitive performance and cerebellar integrity in a specific degeneration of the cerebellar cortex: Spinocerebellar Ataxia type 6 (SCA6). The results demonstrate a critical relationship between verbal working memory and grey matter density in superior (bilateral lobules VI and crus I of lobule VII) and inferior (bilateral lobules VIIIa and VIIIb, and right lobule IX) parts of the cerebellum. We demonstrate that distinct cerebellar regions subserve different components of the prevalent psychological model for verbal working memory based on a phonological loop. The work confirms the involvement of the cerebellum in verbal working memory and defines specific subsystems for this within the cerebellum.
| S-EPMC4040406 | biostudies-literature
Project description:Transfer of learning refers to successful application of previously acquired knowledge or skills to novel settings. Although working memory (WM) is thought to play a role in transfer learning, direct evidence of the effect of limitations in WM on transfer learning is lacking. To investigate, we used an acquired equivalence paradigm that included tests of association and transfer learning. The effects of imposing an acute WM limitation on young adults was tested (within-subjects design: N = 27 adults; Mage = 24 years) by conducting learning transfer tests concurrent with a secondary task that required carrying a spatial WM load when performing the learned/transfer trial (Load condition) to acutely limit WM resources or no WM load (No-Load condition; WM was unloaded prior to performing the learned/transfer trial). Analyses showed that although success on the transfer trials was high in the No-Load condition, performance dropped to chance in the Load condition. Performance on tests of learned associations remained high in both conditions. These results indicate that transfer of learning depends on access to WM resources and suggest that even healthy young individuals may be affected in their ability to cross-utilize knowledge when cognitive resources become scarce, such as when engaging in two tasks simultaneously (e.g., using satellite navigation while driving).
| S-EPMC10457230 | biostudies-literature
Project description:The generation of myelin-forming oligodendrocytes persists throughout life and is regulated by neural activity. Here we tested whether experience-driven changes in oligodendrogenesis are important for memory consolidation. We found that water maze learning promotes oligodendrogenesis and de novo myelination in the cortex and associated white matter tracts. Preventing these learning-induced increases in oligodendrogenesis without affecting existing oligodendrocytes impaired memory consolidation of water maze, as well as contextual fear, memories. These results suggest that de novo myelination tunes activated circuits, promoting coordinated activity that is important for memory consolidation. Consistent with this, contextual fear learning increased the coupling of hippocampal sharp wave ripples and cortical spindles, and these learning-induced increases in ripple-spindle coupling were blocked when oligodendrogenesis was suppressed. Our results identify a non-neuronal form of plasticity that remodels hippocampal-cortical networks following learning and is required for memory consolidation.
| S-EPMC7579726 | biostudies-literature
Project description:Substantial portions of the cerebellum appear to support non-motor functions; however, previous investigations of cerebellar involvement in cognition have revealed only a coarse degree of specificity. Although somatotopic maps have been observed within cerebellum, similar precision within cortico-cerebellar networks supporting non-motor functions has not previously been reported. Here, we find that human cerebellar lobule VIIb/VIIIa differentially codes key aspects of visuospatial cognition. Ipsilateral visuospatial representations were observed during both a visual working memory and an attentionally demanding visual receptive field-mapping fMRI task paradigm. Moreover, within lobule VIIb/VIIIa, we observed a functional dissociation between spatial coding and visual working memory processing. Visuospatial representations were found in the dorsomedial portion of lobule VIIb/VIIIa, and load-dependent visual working memory processing was shifted ventrolaterally. A similar functional gradient for spatial versus load processing was found in posterior parietal cortex. This cerebral cortical organization was well predicted by functional connectivity with spatial and load regions of cerebellar lobule VIIb/VIIIa. Collectively, our findings indicate that recruitment by visuospatial attentional functions within cerebellar lobule VIIb/VIIIa is highly specific. Furthermore, the topographic arrangement of these functions is mirrored in frontal and parietal cortex. These findings motivate a closer examination of cortico-cerebellar functional specialization across a broad range of cognitive domains.
| S-EPMC6257946 | biostudies-literature
Project description:Learning and memory are assumed to be supported by mechanisms that involve cholinergic transmission and hippocampal theta. Using G protein-coupled receptor-activation-based acetylcholine sensor (GRABACh3.0) with a fiber-photometric fluorescence readout in mice, we found that cholinergic signaling in the hippocampus increased in parallel with theta/gamma power during walking and REM sleep, while ACh3.0 signal reached a minimum during hippocampal sharp-wave ripples (SPW-R). Unexpectedly, memory performance was impaired in a hippocampus-dependent spontaneous alternation task by selective optogenetic stimulation of medial septal cholinergic neurons when the stimulation was applied in the delay area but not in the central (choice) arm of the maze. Parallel with the decreased performance, optogenetic stimulation decreased the incidence of SPW-Rs. These findings suggest that septo-hippocampal interactions play a task-phase-dependent dual role in the maintenance of memory performance, including not only theta mechanisms but also SPW-Rs.
| S-EPMC8054002 | biostudies-literature
Project description:To make successful evidence-based decisions, the brain must rapidly and accurately transform sensory inputs into specific goal-directed behaviors. Most experimental work on this subject has focused on forebrain mechanisms. Using a novel evidence-accumulation task for mice, we performed recording and perturbation studies of crus I of the lateral posterior cerebellum, which communicates bidirectionally with numerous forebrain regions. Cerebellar inactivation led to a reduction in the fraction of correct trials. Using two-photon fluorescence imaging of calcium, we found that Purkinje cell somatic activity contained choice/evidence-related information. Decision errors were represented by dendritic calcium spikes, which in other contexts are known to drive cerebellar plasticity. We propose that cerebellar circuitry may contribute to computations that support accurate performance in this perceptual decision-making task.
| S-EPMC6105309 | biostudies-literature
Project description:Although children with heavy prenatal alcohol exposure may exhibit the distinctive facial dysmorphology seen in full or partial fetal alcohol syndrome (FAS/PFAS), many lack that dysmorphology. This study examined the functional organization of working memory in the brain in three groups of children-those meeting diagnostic criteria for FAS or PFAS, heavily exposed (HE) nonsyndromal children, and healthy controls. A verbal n-back task (1-back and 0-back) was administered to 47 children (17 with FAS/PFAS, 13 HE, and 17 controls) during fMRI. Intra-group one-sample t-tests were used to identify activity regions of interest central to verbal working memory including the dorsal prefrontal cortex (dPFC), inferior frontal gyrus, caudate/putamen, parietal cortex, and cerebellar Crus I/lobule VI and lobule VIIB-IX. Whereas groups did not differ in task sensitivity, fMRI analyses suggested different patterns of sub-network recruitment across groups. Controls primarily recruited left inferior frontal gyrus (Broca's area). By contrast, HE primarily recruited an extensive set of fronto-striatal regions, including left dPFC and left caudate, and the FAS/PFAS group relied primarily on two cerebellar subregions and parietal cortex. This study is, to our knowledge, the first to demonstrate differential recruitment of critical brain regions that subserve basic function in children with different fetal alcohol spectrum disorders compared to controls. The distinct activation patterns seen in the two exposed groups may be related to substantial differences in alcohol dose/occasion to which these groups were exposed in utero.
| S-EPMC6870023 | biostudies-literature