Memory reactivation during sleep reinforces various types of learning. Basic motor skills likely benefit from sleep. There is insufficient evidence, however, on whether memory reactivation during sleep contributes to learning how to execute a novel action. Here, we investigated motor learning in a myoelectric feedback task. Human male and female participants learned to control myoelectric activity in specific arm muscles to move a computer cursor to each of 16 locations. Each location was associated with a unique sound. Half of the sounds were played during slow-wave sleep to reactivate corresponding memories of muscle control. After sleep, movements cued during sleep were performed more quickly and efficiently than uncued movements. These results demonstrated that memory reactivation during sleep contributes to learning of action execution. We conclude that sleep supports learning novel actions, which also maps onto the learning required in certain neurorehabilitation procedures. SIGNIFICANCE STATEMENT P...

Post-encoding coordinated reactivation of memory traces distributed throughout interconnected brain regions is thought to be critical for consolidation of memories. However, little is known about the role of neural circuit pathways during post-learning periods for consolidation of memories. To investigate this question, we optogenetically silenced the inputs from both auditory cortex and thalamus in the lateral amygdala (LA) for 15 min immediately following auditory fear conditioning (FC) and examined its effect on fear memory formation in mice of both sexes. Optogenetic inhibition of both inputs disrupted long-term fear memory formation tested 24 h after FC. This effect was specific such that the same inhibition did not affect short-term memory and context-dependent memory. Moreover, long-term memory was intact if the inputs were inhibited at much later time points after FC (3 h or 1 d after FC), indicating that optical inhibition for 15 min itself does not produce any nonspecific deleterious effect on fe...

Many daily choices are based on one's own knowledge. However, when predicting other people's behavior, we need to consider the differences between our knowledge and other people's presumed knowledge. Social agents need a mechanism to use privileged information for their own behavior but exclude it from predictions of others. Using fMRI, we investigated the neural implementation of such social and personal predictions in healthy human volunteers of both sexes by manipulating privileged and shared information. The medial frontal cortex appeared to have an important role in flexibly making decisions using privileged information for oneself or predicting others' behavior. Specifically, we show that ventromedial PFC tracked the state of the world independent of the type of decision (personal, social), whereas dorsomedial regions adjusted their frame of reference to the use of privileged or shared information. Sampling privileged evidence not available to another person also relied on specific interactions betwe...

Age-related hearing loss (presbycusis) is a chronic health condition that affects one-third of the world population. One hallmark of presbycusis is a difficulty hearing in noisy environments. Presbycusis can be separated into two components: alterations of peripheral mechanotransduction of sound in the cochlea and central alterations of auditory processing areas of the brain. Although the effects of the aging cochlea in hearing loss have been well studied, the role of the aging brain in hearing loss is less well understood. Therefore, to examine how age-related central processing changes affect hearing in noisy environments, we used a mouse model (Thy1-GCaMP6s X CBA) that has excellent peripheral hearing in old age. We used in vivo two-photon Ca2+ imaging to measure the responses of neuronal populations in auditory cortex (ACtx) of adult (2–6 months, nine male, six female, 4180 neurons) and aging mice (15–17 months, six male, three female, 1055 neurons) while listening to tones in noisy backgrounds. We fou...

Ankyrin scaffolding proteins are critical for membrane domain organization and protein stabilization in many different cell types including neurons. In the cerebellum, Ankyrin-R (AnkR) is highly enriched in Purkinje neurons, granule cells, and in the cerebellar nuclei. Using male and female mice with a floxed allele for Ank1 in combination with Nestin-Cre and Pcp2-Cre mice, we found that ablation of AnkR from Purkinje neurons caused ataxia, regional and progressive neurodegeneration, and altered cerebellar output. We show that AnkR interacts with the cytoskeletal protein β3 spectrin, and the potassium channel Kv3.3. Loss of AnkR reduced somatic membrane levels of β3 spectrin and Kv3.3 in Purkinje neurons. Thus, AnkR links Kv3.3 channels to the β3 spectrin-based cytoskeleton. Our results may help explain why mutations in β3 spectrin and Kv3.3 both cause spinocerebellar ataxia. SIGNIFICANCE STATEMENT Ankyrin scaffolding proteins localize and stabilize ion channels in the membrane by linking them to the sp...

Semantic processing is an amodal process with modality-specific information integrated in supramodal ‘convergence zones’ or ‘semantic hub’ with executive mechanisms that tailor semantic representation in a task-appropriate way. One unsolved question is how frontal control region dynamically interacts with temporal representation region in semantic integration. The present study addressed this issue by using inhibitory double-pulse transcranial magnetic stimulation (TMS) over the left inferior frontal gyrus (IFG) or left posterior middle temporal gyrus (pMTG) in one of eight 40-ms time windows (TWs) (3 TWs before and 5 TWs after the identification point of speech), when human participants (12 females, 14 males) were presented with semantically congruent or incongruent gesture-speech pairs but merely identified the gender of speech. We found a TW-selective disruption of gesture-speech integration, indexed by the semantic congruency effect (i.e., a cost of reaction time due to semantic conflict), when stimula...

Children with and without dyslexia differ in their behavioural responses to visual information, particularly when required to pool dynamic signals over space and time. Importantly, multiple processes contribute to behavioural responses. Here we investigated which processing stages are affected in children with dyslexia when performing visual motion processing tasks, by combining two methods that are sensitive to the dynamic processes leading to responses. We used a diffusion model which decomposes response time and accuracy into distinct cognitive constructs, and high-density EEG. 50 children with dyslexia (24 male) and 50 typically developing children (28 male) aged 6 to 14 years judged the direction of motion as quickly and accurately as possible in two global motion tasks (motion coherence and direction integration), which varied in their requirements for noise exclusion. Following our pre-registered analyses, we fitted hierarchical Bayesian diffusion models to the data, blinded to group membership. Unb...

Much animal learning is slow, with cumulative changes in behavior driven by reward prediction errors. When the abstract structure of a problem is known, however, both animals and formal learning models can rapidly attach new items to their roles within this structure, sometimes in a single trial. Frontal cortex is likely to play a key role in this process. To examine information seeking and use in a known problem structure, we trained monkeys in an explore/exploit task, requiring the animal first to test objects for their association with reward, then, once rewarded objects were found, to re-select them on further trials for further rewards. Many cells in the frontal cortex showed an explore/exploit preference aligned with the one-shot learning in the monkeys’ behavior: the population switched from an explore state to an exploit state after a single trial of learning, but partially maintained the explore state if an error indicated that learning had failed. Binary switch from explore to exploit was not exp...

Little research has been done about the neural substrate of the sub-lexical level of Chinese word recognition. In particular, it is unclear how radicals participate in Chinese word processing. We compared two measures of radical combinability: position-general radical combinability (GRC) and position-specific radical combinability (SRC) depending on whether the position of the radical is taken into account. We selected characters with embedded target radicals that had different GRC and SRC measures. These measures were used as predictors in a parametric modulation analysis and a multivariate representational similarity analysis (RSA). Human participants with native Mandarin speakers (17 males and 24 females) were asked to read words in search of animal words. Results showed that SRC is a better predictor than GRC in decoding the neural patterns. Whole-brain analysis indicated that SRC is encoded bilaterally in the inferior frontal gyrus (IFG, pars opercularis and pars triangularis), the middle frontal gyru...