Fast Feedback Responses to Categorical Sensorimotor Errors That Do Not Indicate Error Magnitude Are Optimized Based on Short- and Long-Term Memory.

Mutations in the synaptic gene SHANK3 lead to a neurodevelopmental disorder known as Phelan-McDermid syndrome (PMS). PMS is a relatively common monogenic and highly penetrant cause of autism spectrum disorder (ASD) and intellectual disability (ID), and frequently presents with attention deficits. The underlying neurobiology of PMS is not fully known and pharmacological treatments for core symptoms do not exist. Here, we report the production and characterization of a Shank3-deficient rat model of PMS, with a genetic alteration similar to a human SHANK3 mutation. We show that Shank3-deficient rats exhibit impaired long-term social recognition memory and attention, and reduced synaptic plasticity in the hippocampal-medial prefrontal cortex pathway. These deficits were attenuated with oxytocin treatment. The effect of oxytocin on reversing non-social attention deficits is a particularly novel finding, and the results implicate an oxytocinergic contribution in this genetically defined subtype of ASD and ID, suggesting an individualized therapeutic approach for PMS.DOI: http://dx.doi.org/10.7554/eLife.18904.001

A common problem in motor control concerns how to generate patterns of muscle activity when there are redundant solutions to attain a behavioral goal. Optimal feedback control is a theory that has guided many behavioral studies exploring how the motor system incorporates task redundancy. This theory predicts that kinematic errors that deviate the limb should not be corrected if one can still attain the behavioral goal. Studies in humans demonstrate that the motor system can flexibly integrate visual and proprioceptive feedback of the limb with goal redundancy within 90 ms and 70 ms, respectively. Here, we show monkeys (Macaca mulatta) demonstrate similar abilities to exploit goal redundancy. We trained four male monkeys to reach for a goal that was either a narrow square or a wide, spatially redundant rectangle. Monkeys exhibited greater trial-by-trial variability when reaching to the wide goal consistent with exploiting goal redundancy. On random trials we jumped the visual feedback of the hand and found monkeys corrected for the jump when reaching to the narrow goal and largely ignored the jump when reaching for the wide goal. In a separate set of experiments, we applied mechanical loads to the arm of the monkey and found similar corrective responses based on goal shape. Muscle activity reflecting these different corrective responses were detected for the visual and mechanical perturbations starting at ∼90 and ∼70 ms, respectively. Thus, rapid motor responses in macaques can exploit goal redundancy similar to humans, creating a paradigm to study the neural basis of goal-directed motor action and motor redundancy.SIGNIFICANCE STATEMENT Moving in the world requires selecting from an infinite set of possible motor commands. Theories predict that motor commands are selected that exploit redundancies. Corrective responses in humans to either visual or proprioceptive disturbances of the limb can rapidly exploit redundant trajectories to a goal in <100 ms after a disturbance. However, uncovering the neural correlates generating these rapid motor corrections has been hampered by the absence of an animal model. We developed a behavioral paradigm in monkeys that incorporates redundancy in the form of the shape of the goal. Critically, monkeys exhibit corrective responses and timings similar to humans performing the same task. Our paradigm provides a model for investigating the neural correlates of sophisticated rapid motor corrections.

A first salt shock event alters transcriptional and physiological responses to a second event, being possible to identify 26 genes associated with long-term memory. Soil salinity significantly affects rice cultivation, resulting in large losses in growth and productivity. Studies report that a disturbing event can prepare the plant for a subsequent event through memory acquisition, involving physiological and molecular processes. Therefore, genes that provide altered responses in subsequent events define a category known as "memory genes". In this work, the RNA-sequencing (RNA-Seq) technique was used to analyse the transcriptional profile of rice plants subjected to different salt shock events and to characterise genes associated with long-term memory. Plants subjected to recurrent salt shock showed differences in stomatal conductance, chlorophyll index, electrolyte leakage, and the number of differentially expressed genes (DEGs), and they had lower Na+/K+ ratios than plants that experienced only one stress event. Additionally, the mammalian target of rapamycin (mTOR) pathways, and carbohydrate and amino acid-associated pathways were altered under all conditions. Memory genes can be classified according to their responses during the first event (+ or -) and the second shock event (+ or -), being possible to observe a larger number of transcripts for groups [+ /-] and [-/ +], genes characterised as "revised response." This is the first long-term transcriptional memory study in rice plants under salt shock, providing new insights into the process of plant memory acquisition.

The number of TKAs performed in the United States is expected to increase substantially in the next two decades [6]. Additionally, surgeons are performing TKAs in younger and more active patients. While many articles discuss the importance of radiographic alignment, soft-tissue balancing is essential to a successful TKA. There remains great controversy in how surgeons obtain correct alignment and soft-tissue tensioning. Some surgeons utilize a measured resection technique, while other surgeons favor a gap-balancing technique. As such, I have invited two internationally known orthopaedic surgeons to discuss these two approaches, both of which seek to achieve the same general goal — a well-aligned and well-balanced TKA. Bryan D. Springer MD is an attending joint replacement surgeon at the OrthoCarolina Hip and Knee Center in Charlotte, NC, USA, and a member of The Knee Society. Dr. Springer is the recipient of numerous Knee Society Awards, and has extensive experience with the gap-balancing technique. Sebastien Parratte MD, PhD is an attending joint replacement surgeon and assistant professor of orthopedic surgery at the University Hospital of Marseille in Marseille, France. Dr. Parratte likewise has received numerous Knee Society and Hip Society Awards, and has considerable experience with the measured resection technique. Matthew P. Abdel MD:What do you each see as the advantages of the gap-balancing or measured resection techniques, in terms of achieving ligament balance? Bryan D. Springer MD: Instability following TKA remains one of the most common modes of early failure. The gap-balancing technique is based on the progressive release of ligaments to create equal and symmetric flexion and extension gaps. It is imperative that one understands what structures affect extension, flexion, and both in order to create proper balance. One of the fundamental differences between the gap-balancing technique and measured resection technique lies in setting the rotation of the femoral component to achieve a symmetric flexion gap. Measured resection relies on arbitrary bony landmarks (surgical transepicondylar axis, posterior condylar axis, and anteroposterior (AP) axis of the femur) in order to set rotation. While bony landmarks may occasionally provide accurate rotation of the femoral component, one major disadvantage is the surgeon’s inability to accurately and reproducibly find them intraoperatively. Research has suggested there is wide variability in femoral component rotation when using bony landmarks, which leads to asymmetry of the flexion space and condylar lift off (Fig. 1) in flexion [3]. Open in a separate window Fig. 1 This schematic depicts condylar lift off that occurs when there is asymmetry of the flexion space. Published courtesy of Bryan D. Springer MD.

Goal-directed action control comes into play when selecting between competing action alternatives. Response capture reflects the susceptibility of the motor system to incitement by task-irrelevant action impulses; the subsequent selective suppression of incorrect action impulses aims to counteract response capture and facilitate the desired response. The goal of this experiment was to clarify physiological mechanisms of response capture and suppression of action impulses during conflict at the level of the motor system. We administered single-pulse TMS at various intervals preceding speeded choice responses. The correct response side was designated by stimulus color, whereas stimulus location (which could match or conflict with response side) was to be ignored. TMS pulses triggered motor evoked potential and silent period, providing sensitive indices of cortico-spinal excitation and inhibition. Motor evoked potential data showed the typical progressive increase in cortico-spinal motor excitability leading up to the imminent (correct) response, which started earlier on nonconflict than on conflict trials. On conflict trials, the irrelevant stimulus location captured the incorrect response, as expressed by an early and transient rise in excitability. Silent period data showed that, already early during the response process, inhibition of the incorrect response was stronger for conflict than for nonconflict trials. Furthermore, inhibition decreased over time for nonconflict trials facilitating the imminent correct response while maintaining higher levels of inhibition on conflict trials. In conclusion, dynamic patterns of cortico-spinal excitability provide unique physiological evidence for the expression and selective suppression of action impulses captured by competing action alternatives.

ABSTRACTObjectives: This cross-sectional experiment examined the influence of aging on cross-cultural differences in memory errors. Previous research revealed that Americans committed more categorical memory errors than Turks; we tested whether the cognitive constraints associated with aging impacted the pattern of memory errors across cultures. Furthermore, older adults are vulnerable to memory errors for semantically-related information, and we assessed whether this tendency occurs across cultures.Methods: Younger and older adults from the US and Turkey studied word pairs, with some pairs sharing a categorical relationship and some unrelated. Participants then completed a cued recall test, generating the word that was paired with the first. These responses were scored for correct responses or different types of errors, including categorical and semantic.Results: The tendency for Americans to commit more categorical memory errors emerged for both younger and older adults. In addition, older adults across cultures committed more memory errors, and these were for semantically-related information (including both categorical and other types of semantic errors).Conclusion: Heightened vulnerability to memory errors with age extends across cultural groups, and Americans’ proneness to commit categorical memory errors occurs across ages. The findings indicate some robustness in the ways that age and culture influence memory errors.

The basal ganglia, especially the circuits originating from the putamen, are essential for controlling normal body movements. Notably, the putamen receives inputs not only from motor cortical areas but also from multiple sensory cortices. However, how these sensory signals are processed in the putamen remains unclear. We recorded the activity of tentative medium spiny neurons in the caudal part of the putamen when the monkey viewed many fractal objects. We found many neurons that responded to these objects, mostly in the ventral region. We called this region "putamen tail" (PUTt), as it is dorsally adjacent to "caudate tail" (CDt). Although PUTt and CDt are mostly separated by a thin layer of white matter, their neurons shared several features. Almost all of them had receptive fields in the contralateral hemifield. Moreover, their responses were object selective (i.e., variable across objects). The object selectivity was higher in the ventral region (i.e., CDt > PUTt). Some neurons above PUTt, which we called the caudal-dorsal putamen (cdPUT), also responded to objects, but less selectively than PUTt. Next, we examined whether these visual neurons changed their responses based on the reward outcome. We found that many neurons encoded the values of many objects based on long-term memory, but not based on short-term memory. Such stable value responses were stronger in PUTt and CDt than in cdPUT. These results suggest that PUTt, together with CDt, controls saccade/attention among objects with different historical values, and may control other motor actions as well.SIGNIFICANCE STATEMENT Although the putamen receives inputs not only from motor cortical areas but also from sensory cortical areas, how these sensory signals are processed remains unclear. Here we found that neurons in the caudal-ventral part of the putamen (putamen tail) process visual information including spatial and object features. These neurons discriminate many objects, first by their visual features and later by their reward values as well. Importantly, the value discrimination was based on long-term memory, but not on short-term memory. These results suggest that the putamen tail controls saccade/attention among objects with different historical values and might control other motor actions as well.

Are specific distributed coactivations in the brain during memory retrieval a signature of retrieval outcome? Here we show that this is indeed the case. Widespread brain networks were reported to be involved in the retrieval of long-term episodic memories. Although functional coactivation among particular regions occurs during episodic memory retrieval, it is unknown to what extent it contributes to the accuracy and confidence of recollection. In this study we set out to explore this question. Participants saw a narrative documentary movie. A week later they underwent an fMRI scan during which they either accepted or rejected factual or fictitious verbal statements concerning the movie. Correct vs. incorrect responses to factual statements were more common and were provided with higher confidence than those made to fictitious statements. Whereas activity in the retrieval network correlated mostly with confidence, coactivations primarily correlated with memory accuracy. Specifically, coactivations of left medial temporal lobe regions with temporal and parietal cortices were greater during correct responses to factual statements, but did not differ between responses to fictitious statements. We propose that network coactivations play a role in recovering memory traces that are relevant to online retrieval cues, culminating in distinct retrieval outcomes.

The experience of childbirth is an important life experience for women. However, in-depth knowledge about long-term experiences is limited. The aim of the study was to describe women's experiences two to 20 years after birth. This study is a part of a meta-synthesis project about childbearing in the Nordic countries. Methodologically, the study was a secondary analysis performed on original data from three selected qualitative studies by the authors, in three Nordic countries, Finland, Iceland and Sweden, and in two different forms of care, birth centre care and standard maternity care. There were 29 participants, both primipara and multiparous women. The result from this study shows that women, in a long-term perspective describe childbirth as an encounter with different participants and the most important is with the midwife. The midwife is also important in connection to the atmosphere experienced during birth. The childbirth experience has a potential to strengthen self-confidence and trust in others or, on the contrary, it can mean failure or distrust. Impersonal encounters linger feelings of being abandoned and alone. This dimension is in particular demonstrated in the description of the woman who had given birth at standard maternity care. The conclusion of this study is that childbirth experience has a potential to strengthen self-confidence and trust in others or on the contrary failure or distrust. Maternity care should be organized in a way that emphasis this aspects of care.

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

When the human motor system adapts to novel dynamics of the arm during reaching, hand trajectories tends to converge toward a roughly straight line. This straight line is thought to be the desired trajectory of the system. Trial-to-trial changes in performance are well described by a first order state-space model: errors in a given trial affect performance on the subsequent trial as a function of the distance in state space between the two trials. This function describes the generalization patterns that govern adaptation. Whereas the desired trajectory and the generalization function have been quantified for short-term adaptation, little is known about their behavior with long-term training. We report that when subjects are trained to reach in novel force fields over multiple days, the state-space model suggests that the desired trajectory undergoes systematic changes. In a constant field, the desired trajectory becomes curved. The direction of change of the desired trajectory is affected by the training protocol, such that occasional unperturbed trials (catch trials) caused subject to increasingly under-compensate for the perturbations whereas a lack of such trials caused subjects to increasingly overcompensate for the perturbations. We suggest that the desired trajectory is not constant, but is a result of an optimization that considers the success rate. In this optimization process, subjects weigh more heavily the importance of certain trials: either those that are infrequent or those that cause large errors.

Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw.

Which brain regions participate in musical processing remains controversial. During singing and listening a familiar song, it is necessary to retrieve information from the long-term memory. However, the precise mechanism involved in musical processing is unclear. Amusia is impaired perception, understanding, or production of music not attributable to disease of the peripheral auditory pathways or motor system. We report a case of a 36-year-old right-handed man who lost the ability to discriminate or reproduce rhythms after a right temporoparietal lobe infarction. We diagnosed him as an amusic patient using the online version of Montreal Battery of Evaluation of Amusia (MBEA). This case report suggests that amusia could appear after right temporoparietal lobe infarction. Further research is needed to elucidate the dynamic musical processing mechanism and its associated neural structures.

Complementary roles of cortical oscillations in automatic and controlled processing during rapid serial tasks

Antipsychotic medications are associated with significant weight gain, type 2 diabetes mellitus, dyslipidemia, and increased cardiovascular risk. Suggested mechanisms of weight gain from antipsychotic medication include antagonism of histamine and serotonin receptors, and effects on the hypothalamic-pituitary-adrenal axis. The objective of this study was to determine if mifepristone, a glucocorticoid receptor antagonist, could prevent olanzapine-induced weight gain. This was a randomized, double-blind trial. Fifty-seven lean, healthy men (body mass index 18-25 kg/m(2)) aged 19-38 years were randomized to olanzapine (7.5 mg) (n=22), olanzapine (7.5 mg) plus mifepristone (600 mg) (n=24), or mifepristone (600 mg) (n=11) daily for 2 weeks in an institutional setting. Subjects were provided food ad libitum to accentuate weight gain. Body weight was measured daily. The mean change in baseline weight was +3.2+/-0.9 kg in subjects receiving olanzapine versus +2.0+/-1.2 kg in those receiving olanzapine plus mifepristone (P<0.0001). Subjects receiving mifepristone alone had a similar degree of weight gain compared to those receiving olanzapine plus mifepristone. The olanzapine group had significant increases in waist circumference when compared with the olanzapine plus mifepristone group (3.7+/-1.3 cm vs. 2.2+/-1.9 cm, respectively; P=0.006). Fasting insulin and triglycerides increased more in the olanzapine group, although differences were not statistically significant. Mifepristone was effective in attenuating the increase in weight associated with olanzapine treatment over a 2-week period. Longer-term studies are required to examine the durability and full magnitude of this response.