Probing Our Built-in Calculator: A Systematic Narrative Review of Noninvasive Brain Stimulation Studies on Arithmetic Operation-Related Brain Areas.

This systematic review presented a comprehensive survey of studies that applied transcranial magnetic stimulation and transcranial electrical stimulation to parietal and nonparietal areas to examine the neural basis of symbolic arithmetic processing. All findings were compiled with regard to the three assumptions of the triple-code model (TCM) of number processing. Thirty-seven eligible manuscripts were identified for review (33 with healthy participants and 4 with patients). Their results are broadly consistent with the first assumption of the TCM that intraparietal sulcus both hold a magnitude code and engage in operations requiring numerical manipulations such as subtraction. However, largely heterogeneous results conflicted with the second assumption of the TCM that the left angular gyrus subserves arithmetic fact retrieval, such as the retrieval of rote-learned multiplication results. Support is also limited for the third assumption of the TCM, namely, that the posterior superior parietal lobule engages in spatial operations on the mental number line. Furthermore, results from the stimulation of brain areas outside of those postulated by the TCM show that the bilateral supramarginal gyrus is involved in online calculation and retrieval, the left temporal cortex in retrieval, and the bilateral dorsolateral prefrontal cortex and cerebellum in online calculation of cognitively demanding arithmetic problems. The overall results indicate that multiple cortical areas subserve arithmetic skills.

Conditioning and pseudoconditioning differently change intrinsic excitability of inhibitory interneurons in the neocortex.

Many studies indicate a broad role of various classes of GABAergic interneurons in the processes related to learning. However, little is known about how the learning process affects intrinsic excitability of specific classes of interneurons in the neocortex. To determine this, we employed a simple model of conditional learning in mice where vibrissae stimulation was used as a conditioned stimulus and a tail shock as an unconditioned one. In vitro whole-cell patch-clamp recordings showed an increase in intrinsic excitability of low-threshold spiking somatostatin-expressing interneurons (SST-INs) in layer 4 (L4) of the somatosensory (barrel) cortex after the conditioning paradigm. In contrast, pseudoconditioning reduced intrinsic excitability of SST-LTS, parvalbumin-expressing interneurons (PV-INs), and vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) with accommodating pattern in L4 of the barrel cortex. In general, increased intrinsic excitability was accompanied by narrowing of action potentials (APs), whereas decreased intrinsic excitability coincided with AP broadening. Altogether, these results show that both conditioning and pseudoconditioning lead to plastic changes in intrinsic excitability of GABAergic interneurons in a cell-specific manner. In this way, changes in intrinsic excitability can be perceived as a common mechanism of learning-induced plasticity in the GABAergic system.

Neuroscience: Memory modification without catastrophe.

Adaptive behaviour is supported by changes in neuronal networks. Insight into maintaining these memories - preventing their catastrophic loss - despite further network changes occurring due to novel learning is provided in a new study.

CD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators.

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian olfactory receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.

Gaze patterns reflect the retrieval and selection of memories in a context-dependent object location retrieval task.

Selective retrieval of context-relevant memories is critical for animal survival. A behavioral index that captures its dynamic nature in real time is necessary to investigate this retrieval process. Here, we found a bias in eye gaze towards the locations previously associated with individual objects during retrieval. Participants learned two locations associated with each visual object and recalled one of them indicated by a contextual cue in the following days. Before the contextual cue presentation, participants often gazed at both locations associated with the given object on the background screen (look-at-both), and the frequency of look-at-both gaze pattern increased as learning progressed. Following the cue presentation, their gaze shifted toward the context-appropriate location. Interestingly, participants showed a higher accuracy of memory retrieval in trials where they gazed at both object-associated locations, implying functional advantage of the look-at-both gaze patterns. Our findings indicate that naturalistic eye movements reflect the dynamic process of memory retrieval and selection, highlighting the potential of eye gaze as an indicator for studying these cognitive processes.

Perturbation Variability Does Not Influence Implicit Sensorimotor Adaptation.

Implicit adaptation has been regarded as a rigid process that automatically operates in response to movement errors to keep the sensorimotor system precisely calibrated. This hypothesis has been challenged by recent evidence suggesting flexibility in this learning process. One compelling line of evidence comes from work suggesting that this form of learning is context-dependent, with the rate of learning modulated by error history. Specifically, learning was attenuated in the presence of perturbations exhibiting high variance compared to when the perturbation is fixed. However, these findings are confounded by the fact that the adaptation system corrects for errors of different magnitudes in a non-linear manner, with the adaptive response increasing in a proportional manner to small errors and saturating to large errors. Through simulations, we show that this non-linear motor correction function is sufficient to explain the effect of perturbation variance without referring to an experience-dependent change in error sensitivity. Moreover, by controlling the distribution of errors experienced during training, we provide empirical evidence showing that there is no measurable effect of perturbation variance on implicit adaptation. As such, we argue that the evidence to date remains consistent with the rigidity assumption.

Neural inhibition as implemented by an actor-critic model involves the human dorsal striatum and ventral tegmental area.

Inhibition is implicated across virtually all human experiences. As a trade-off of being very efficient, this executive function is also prone to many errors. Rodent and computational studies show that midbrain regions play crucial roles during errors by sending dopaminergic learning signals to the basal ganglia for behavioural adjustment. However, the parallels between animal and human neural anatomy and function are not determined. We scanned human adults while they performed an fMRI inhibitory task requiring trial-and-error learning. Guided by an actor-critic model, our results implicate the dorsal striatum and the ventral tegmental area as the actor and the critic, respectively. Using a multilevel and dimensional approach, we also demonstrate a link between midbrain and striatum circuit activity, inhibitory performance, and self-reported autistic and obsessive-compulsive subclinical traits.

Does intensity matter? A randomized crossover study of the role of acute exercise intensity on cognitive performance and motor speed and accuracy.

There is a well-recognized, yet nuanced, positive relationship between acute physical activity and cognitive function. However, the precise impact of exercise intensity remains ambiguous. We tested learning and memory, working memory and processing speed, and motor speed and accuracy across three distinct exercise intensities. A sample of 207 participants (100 female) between 18 and 44 years (mean age: 22.5±3.7years) completed all study procedures. Utilizing a within-subjects, cross-over design, participants completed moderate (35% VO2 Max), vigorous (70% VO2 Max), and sedentary (no exercise) conditions. Cognitive and motor assessments, including the Paced Auditory Serial Addition Test (PASAT), Rey Auditory Verbal Learning Test (RAVLT), Typing Speed Test, and Ten Key Data Entry Task, were conducted approximately 60min post-exercise. There were no significant differences in primary cognitive or motor outcome measures across the three exercise intensities, even with the study being strongly powered. There was, however, a small difference on the fastest trial of the PASAT, where vigorous-intensity exercise yielded slightly better performance compared to both sedentary and moderate-intensity exercise. This effect was no longer significant when including VO2 Max or maximum heart rate as indicators of fitness. There were no interactions on outcome variables by exercise intensity when including biological sex in the models. Thus, a single bout of acute exercise, regardless of its intensity, did not alter cognitive and motor performance when measured approximately 1h post-exercise. Findings highlight the importance of large samples and suggest that the temporal dynamics post-exercise might play a pivotal role in cognitive outcomes.

Motor learning and performance in schizophrenia and aging: two different patterns of decline.

Psychomotor slowing has consistently been observed in schizophrenia, however research on motor learning in schizophrenia is limited. Additionally, motor learning in schizophrenia has never been compared with the waning of motor learning abilities in the elderly. Therefore, in an extensive study, 30 individuals with schizophrenia, 30 healthy age-matched controls and 30 elderly participants were compared on sensorimotor learning tasks including sequence learning and adaptation (both explicit and implicit), as well as tracking and aiming. This paper presents new findings on an explicit motor sequence learning task, an explicit verbal learning task and a simple aiming task and summarizes all previously published findings of this large investigation. Individuals with schizophrenia and elderly had slower Movement Time (MT)s compared with controls in all tasks, however both groups improved over time. Elderly participants learned slower on tracking and explicit sequence learning while individuals with schizophrenia adapted slower and to a lesser extent to movement perturbations in adaptation tasks and performed less well on cognitive tests including the verbal learning task. Results suggest that motor slowing is present in schizophrenia and the elderly, however both groups show significant but different motor skill learning. Cognitive deficits seem to interfere with motor learning and performance in schizophrenia while task complexity and decreased movement precision interferes with motor learning in the elderly, reflecting different underlying patterns of decline in these conditions. In addition, evidence for motor slowing together with impaired implicit adaptation supports the influence of cerebellum and the cerebello-thalamo-cortical-cerebellar (CTCC) circuits in schizophrenia, important for further understanding the pathophysiology of the disorder.

The ventromedial prefrontal cortex in response to threat omission is associated with subsequent explicit safety memory.

In order to memorize and discriminate threatening and safe stimuli, the processing of the actual absence of threat seems crucial. Here, we measured brain activity with fMRI in response to both threat conditioned stimuli and their outcomes by combining threat learning with a subsequent memory paradigm. Participants (N = 38) repeatedly saw a variety of faces, half of which (CS+) were associated with an aversive unconditioned stimulus (US) and half of which were not (CS-). When an association was later remembered, the hippocampus had been more active (than when forgotten). However, the ventromedial prefrontal cortex predicted subsequent memory specifically during safe associations (CS- and US omission responses) and the left dorsolateral prefrontal cortex during outcomes in general (US and US omissions). In exploratory analyses of the theoretically important US omission, we found extended involvement of the medial prefrontal cortex and an enhanced functional connectivity to visual and somatosensory cortices, suggesting a possible function in sustaining sensory information for an integration with semantic memory. Activity in visual and somatosensory cortices together with the inferior frontal gyrus also predicted memory performance one week after learning. The findings imply the importance of a close interplay between prefrontal and sensory areas during the processing of safe outcomes-or 'nothing'-to establish declarative safety memory.

Investigating the Effect of Contextual Cueing with Face Stimuli on Electrophysiological Measures in Younger and Older Adults.

Extracting repeated patterns from our surroundings plays a crucial role in contextualizing information, making predictions, and guiding our behavior implicitly. Previous research showed that contextual cueing enhances visual search performance in younger adults. In this study, we investigated whether contextual cueing could also improve older adults' performance and whether age-related differences in the neural processes underlying implicit contextual learning could be detected. Twenty-four younger and 25 older participants performed a visual search task with contextual cueing. Contextual information was generated using repeated face configurations alongside random new configurations. We measured RT difference between new and repeated configurations; ERPs to uncover the neural processes underlying contextual cueing for early (N2pc), intermediate (P3b), and late (r-LRP) processes; and multiscale entropy and spectral power density analyses to examine neural dynamics. Both younger and older adults showed similar contextual cueing benefits in their visual search efficiency at the behavioral level. In addition, they showed similar patterns regarding contextual information processing: Repeated face configurations evoked decreased finer timescale entropy (1-20 msec) and higher frequency band power (13-30 Hz) compared with new configurations. However, we detected age-related differences in ERPs: Younger, but not older adults, had larger N2pc and P3b components for repeated compared with new configurations. These results suggest that contextual cueing remains intact with aging. Although attention- and target-evaluation-related ERPs differed between the age groups, the neural dynamics of contextual learning were preserved with aging, as both age groups increasingly utilized more globally grouped representations for repeated face configurations during the learning process.

Adolescents flexibly adapt action selection based on controllability inferences.

From early in life, we encounter both controllable environments, in which our actions can causally influence the reward outcomes we experience, and uncontrollable environments, in which they cannot. Environmental controllability is theoretically proposed to organize our behavior. In controllable contexts, we can learn to proactively select instrumental actions that bring about desired outcomes. In uncontrollable environments, Pavlovian learning enables hard-wired, reflexive reactions to anticipated, motivationally salient events, providing "default" behavioral responses. Previous studies characterizing the balance between Pavlovian and instrumental learning systems across development have yielded divergent findings, with some studies observing heightened expression of Pavlovian learning during adolescence and others observing a reduced influence of Pavlovian learning during this developmental stage. In this study, we aimed to investigate whether a theoretical model of controllability-dependent arbitration between learning systems might explain these seemingly divergent findings in the developmental literature, with the specific hypothesis that adolescents' action selection might be particularly sensitive to environmental controllability. To test this hypothesis, 90 participants, aged 8-27, performed a probabilistic-learning task that enables estimation of Pavlovian influence on instrumental learning, across both controllable and uncontrollable conditions. We fit participants' data with a reinforcement-learning model in which controllability inferences adaptively modulate the dominance of Pavlovian versus instrumental control. Relative to children and adults, adolescents exhibited greater flexibility in calibrating the expression of Pavlovian bias to the degree of environmental controllability. These findings suggest that sensitivity to environmental reward statistics that organize motivated behavior may be heightened during adolescence.

The hidden fitness of the male zebra finch courtship song.

Vocal learning in songbirds is thought to have evolved through sexual selection, with female preference driving males to develop large and varied song repertoires1-3. However, many songbird species learn only a single song in their lifetime4. How sexual selection drives the evolution of single-song repertoires is not known. Here, by applying dimensionality-reduction techniques to the singing behaviour of zebra finches (Taeniopygia guttata), we show that syllable spread in low-dimensional feature space explains how single songs function as honest indicators of fitness. We find that this Gestalt measure of behaviour captures the spectrotemporal distinctiveness of song syllables in zebra finches; that females strongly prefer songs that occupy more latent space; and that matching path lengths in low-dimensional space is difficult for young males. Our findings clarify how simple vocal repertoires may have evolved in songbirds and indicate divergent strategies for how sexual selection can shape vocal learning.

Migratory neurons in adult songbirds spread their wings.

Throughout the life of the adult songbird, neurons are recruited into brain regions important for song learning. Movies captured by Shvedov et al. demonstrate this dynamic process in the live animal, revealing the mechanisms of neuronal migration in the adult brain.

Fostering self-regulated learning in preschool through dynamic assessment methodologies.

Self-regulated learning is a transversal competency which plays a central role in acquiring autonomy. This investigation aimed to support approaches that foster self-regulated learning in preschool. We proposed to improve preschoolers' self-regulated learning strategies (i.e., forethought, performance, and self-reflection) through the educational intervention Pipo and Mia, the magic knights, hypothesizing different results when comparing levels of the program intervention. Participants included 115 preschoolers and their nine teachers. Teachers implemented the program to children, and engaged in professional training simultaneously. Aiming to validate the Dynamic Assessment of Self-regulation in Preschool (DASP) method socially, it was used as children's pre and post-measure, and focus groups were conducted with teachers to assess its validity. Results showed improvements in children's use of strategies, and some significant differences between intervention levels. Teachers highlighted the DASP method potentialities. The study's contributions and constraints are discussed considering implications for practice, research, theory, and policy.

CA3 Circuit Model Compressing Sequential Information in Theta Oscillation and Replay.

The hippocampus plays a critical role in the compression and retrieval of sequential information. During wakefulness, it achieves this through theta phase precession and theta sequences. Subsequently, during periods of sleep or rest, the compressed information reactivates through sharp-wave ripple events, manifesting as memory replay. However, how these sequential neuronal activities are generated and how they store information about the external environment remain unknown. We developed a hippocampal cornu ammonis 3 (CA3) computational model based on anatomical and electrophysiological evidence from the biological CA3 circuit to address these questions. The model comprises theta rhythm inhibition, place input, and CA3-CA3 plastic recurrent connection. The model can compress the sequence of the external inputs, reproduce theta phase precession and replay, learn additional sequences, and reorganize previously learned sequences. A gradual increase in synaptic inputs, controlled by interactions between theta-paced inhibition and place inputs, explained the mechanism of sequence acquisition. This model highlights the crucial role of plasticity in the CA3 recurrent connection and theta oscillational dynamics and hypothesizes how the CA3 circuit acquires, compresses, and replays sequential information.

Basolateral amygdala parvalbumin interneurons coordinate oscillations to drive reward behaviors.

The basolateral amygdala (BLA) mediates both fear and reward learning.1,2 Previous work has shown that parvalbumin (PV) interneurons in the BLA contribute to BLA oscillatory states integral to fear expression.3,4,5,6,7 However, despite it being critical to our understanding of reward behaviors, it is unknown whether BLA oscillatory states and PV interneurons similarly contribute to reward processing. Local field potentials in the BLA were collected as male and female mice consumed sucrose reward, where prominent changes in the beta band (15-30 Hz) emerged with reward experience. During consumption of one water bottle during a two-water-bottle choice test, rhythmic optogenetic stimulation of BLA PVs produced a robust bottle preference, showing that PVs can sufficiently drive reward seeking. Finally, to demonstrate that PV activity is necessary for reward value use, PVs were chemogenetically inhibited following outcome devaluation, rendering mice incapable of using updated reward representations to guide their behavior. Taken together, these experiments provide novel information about the physiological signatures of reward while highlighting BLA PV interneuron contributions to behaviors that are BLA dependent. This work builds upon established knowledge of PV involvement in fear expression and provides evidence that PV orchestration of unique BLA network states is involved in both learning types.

A cerebro-cerebellar network for learning visuomotor associations.

Consensus is rapidly building to support a role for the cerebellum beyond motor function, but its contributions to non-motor learning remain poorly understood. Here, we provide behavioral, anatomical and computational evidence to demonstrate a causal role for the primate posterior lateral cerebellum in learning new visuomotor associations. Reversible inactivation of the posterior lateral cerebellum of male monkeys impeded the learning of new visuomotor associations, but had no effect on movement parameters, or on well-practiced performance of the same task. Using retrograde transneuronal transport of rabies virus, we identified a distinct cerebro-cerebellar network linking Purkinje cells in the posterior lateral cerebellum with a region of the prefrontal cortex that is critical in learning visuomotor associations. Together, these results demonstrate a causal role for the primate posterior lateral cerebellum in non-motor, reinforcement learning.

Memory reactivation in slow wave sleep enhances relational learning in humans.

Sleep boosts the integration of memories, and can thus facilitate relational learning. This benefit may be due to memory reactivation during non-REM sleep. We set out to test this by explicitly cueing reactivation using a technique called targeted memory reactivation (TMR), in which sounds are paired with learned material in wake and then softly played during subsequent sleep, triggering reactivation of the associated memories. We specifically tested whether TMR in slow wave sleep leads to enhancements in inferential thinking in a transitive inference task. Because the Up-phase of the slow oscillation is more responsive to cues than the Down-phase, we also asked whether Up-phase stimulation is more beneficial for such integration. Our data show that TMR during the Up-Phase boosts the ability to make inferences, but only for the most distant inferential leaps. Up-phase stimulation was also associated with detectable memory reinstatement, whereas Down-phase stimulation led to below-chance performance the next morning. Detection of memory reinstatement after Up-state stimulation was negatively correlated with performance on the most difficult inferences the next morning. These findings demonstrate that cueing memory reactivation at specific time points in sleep can benefit difficult relational learning problems.

Hemispheric dominance in HVC is experience-dependent in juvenile male zebra finches.

Juvenile male zebra finches (Taeniopygia guttata) must be exposed to an adult tutor during a sensitive period to develop normal adult song. The pre-motor nucleus HVC (acronym used as a proper name), plays a critical role in song learning and production (cf. Broca's area in humans). In the human brain, left-side hemispheric dominance in some language regions is positively correlated with proficiency in linguistic skills. However, it is unclear whether this pattern depends upon language learning, develops with normal maturation of the brain, or is the result of pre-existing functional asymmetries. In juvenile zebra finches, even though both left and right HVC contribute to song production, baseline molecular activity in HVC is left-dominant. To test if HVC exhibits hemispheric dominance prior to song learning, we raised juvenile males in isolation from adult song and measured neuronal activity in the left and right HVC upon first exposure to an auditory stimulus. Activity in the HVC was measured using the immediate early gene (IEG) zenk (acronym for zif-268, egr-1, NGFI-a, and krox-24) as a marker for neuronal activity. We found that neuronal activity in the HVC of juvenile male zebra finches is not lateralized when raised in the absence of adult song, while normally-reared juvenile birds are left-dominant. These findings show that there is no pre-existing asymmetry in the HVC prior to song exposure, suggesting that lateralization of the song system depends on learning through early exposure to adult song and subsequent song-imitation practice.