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Goal-directed actions require transforming sensory information into motor plans defined across multiple parameters and reference frames. Substantial evidence supports the encoding of target direction in gaze- and body-centered coordinates within parietal and premotor regions. However, how the brain encodes the equally critical parameter of target distance remains less understood. Here, using Bayesian pattern component modeling of fMRI data during a delayed reach-to-target task, we dissociated the neural encoding of both target direction and the relative distances between target, gaze, and hand at early and late stages of motor planning. This approach revealed independent representations of direction and distance along the human dorsomedial reach pathway. During early planning, most premotor and superior parietal areas encoded a target's distance in single or multiple reference frames and encoded its direction. In contrast, distance encoding was magnified in gaze- and body-centric reference frames during late planning. These results emphasize a flexible and efficient human central nervous system that achieves goals by remapping sensory information related to multiple parameters, such as distance and direction, in the same brain areas., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Caceres et al.)

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic and cardiac-sympathetic signals. Participants were reward sensitive but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Background: Deficits in Multisensory Integration (MSI) in ASD have been reported repeatedly and have been suggested to be caused by altered long-range connectivity. Here we investigate behavioral and ERP correlates of MSI in ASD using ecologically valid videos of emotional expressions., Methods: In the present study, we set out to investigate the electrophysiological correlates of audiovisual MSI in young autistic and neurotypical adolescents. We employed dynamic stimuli of high ecological validity (500 ms clips produced by actors) that depicted fear or disgust in unimodal (visual and auditory), and bimodal (audiovisual) conditions., Results: We report robust MSI effects at both the behavioral and electrophysiological levels and pronounced differences between autistic and neurotypical participants. Specifically, neurotypical controls showed robust behavioral MSI for both emotions as seen through a significant speed-up of bimodal response time (RT), confirmed by Miller's Race Model Inequality (RMI), with greater MSI effects for fear than disgust. Adolescents with ASD, by contrast, showed behavioral MSI only for fear. At the electrophysiological level, the bimodal condition as compared to the unimodal conditions reduced the amplitudes of the visual P100 and auditory P200 and increased the amplitude of the visual N170 regardless of group. Furthermore, a cluster-based analysis across all electrodes revealed that adolescents with ASD showed an overall delayed and spatially constrained MSI effect compared to controls., Conclusion: Given that the variables we measured reflect attention, our findings suggest that MSI can be modulated by the differential effects on attention that fear and disgust produce. We also argue that the MSI deficits seen in autistic individuals can be compensated for at later processing stages by (a) the attention-orienting effects of fear, at the behavioral level, and (b) at the electrophysiological level via increased attentional effort ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Stefanou, Dundon, Bestelmeyer, Biscaldi, Smyrnis and Klein.)

Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T 1 -weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA; 17β-estradiol: β 1  = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: β 1  = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (β 1  = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (D iso ) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (β 1  = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; β 1  = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

People who are blind demonstrate remarkable abilities within the spared senses and compensatory enhancement of cognitive skills, underscored by substantial plastic reorganization in relevant neural areas. However, little is known about whether people with blindness form top-down models of the world on short timescales more efficiently to guide goal-oriented behavior. This electroencephalography study investigates this hypothesis at the neurophysiological level, focusing on contingent negative variation (CNV) as a marker of anticipatory and preparatory processes prior to expected events. In sum, 20 participants with blindness and 27 sighted participants completed a classic CNV task and a memory CNV task, both containing tactile stimuli to exploit the expertise of the former group. Although the reaction times in the classic CNV task did not differ between groups, participants who are blind reached higher performance rates in the memory task. This superior performance co-occurred with a distinct neurophysiological profile, relative to controls: greater late CNV amplitudes over central areas, suggesting enhanced stimulus expectancy and motor preparation prior to key events. Controls, in contrast, recruited more frontal sites, consistent with inefficient sensory-aligned control. We conclude that in more demanding cognitive contexts exploiting the spared senses, people with blindness efficiently generate task-relevant internal models to facilitate behavior., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Heuristics can inform human decision making in complex environments through a reduction of computational requirements (accuracy-resource trade-off) and a robustness to overparameterisation (less-is-more). However, tasks capturing the efficiency of heuristics typically ignore action proficiency in determining rewards. The requisite movement parameterisation in sensorimotor control questions whether heuristics preserve efficiency when actions are nontrivial. We developed a novel action selection-execution task requiring joint optimisation of action selection and spatio-temporal skillful execution. State-appropriate choices could be determined by a simple spatial heuristic, or by more complex planning. Computational models of action selection parsimoniously distinguished human participants who adopted the heuristic from those using a more complex planning strategy. Broader comparative analyses then revealed that participants using the heuristic showed combined decisional (selection) and skill (execution) advantages, consistent with a less-is-more framework. In addition, the skill advantage of the heuristic group was predominantly in the core spatial features that also shaped their decision policy, evidence that the dimensions of information guiding action selection might be yoked to salient features in skill learning., (© 2023. The Author(s).)

Working memory (WM) impairments are well recognized in schizophrenia patients (PSZ) and contribute to poor psycho-social outcomes in this population. Distinct neural networks underlay the ability to encode and recall visual and spatial information raising the possibility that profile of visual working memory performance may help pinpoint dysfunctional neural correlates in schizophrenia. This study assessed the resolution and associative aspects of visual working memory deficits in schizophrenia and whether these deficits arise during encoding or maintenance processes. A total of 60 participants (30 PSZ and 30 healthy controls) matched in age, gender and education assessed on a modified object in place (OiPT), a delayed non-match-to-sample (DNMST) and a delayed spatial estimation (DSET) task. Patients demonstrated lower accuracy than controls in binding visual features of the same object and recognizing novel objects as well as lower precision recalling the location of a memorized target. Moreover, response choice set size affected recognition accuracy more in PSZ than controls. However, delay duration affected spatial recall precisions, binding, and recognition accuracy equally in the two groups. Our results suggest that visual working memory (vWM) impairments in schizophrenia predominantly reflect spatial and non-spatial binding deficits, with largely preserved discrete feature information. Moreover, these impairments likely arise more during encoding than during maintenance. These binding deficits may reflect impaired effective neural functional connectivity observed in schizophrenia., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Humans show remarkable habituation to aversive events as reflected by changes of both subjective report and objective measures of stress. Although much experimental human research focuses on the effects of stress, relatively little is known about the cascade of physiological and neural responses that contribute to stress habituation. The cold pressor test (CPT) is a common method for inducing acute stress in human participants in the laboratory; however, there are gaps in our understanding of the global state changes resulting from this stress-induction technique and how these responses change over multiple exposures. Here, we measure the stress response to repeated CPT exposures using an extensive suite of physiologic measures and state-of-the-art analysis techniques. In two separate sessions on different days, participants underwent five 90 s CPT exposures of both feet and five warm water control exposures, while electrocardiography (ECG), impedance cardiography, continuous blood pressure, pupillometry, scalp electroencephalography (EEG), salivary cortisol and self-reported pain assessments were recorded. A diverse array of adaptive responses are reported that vary in their temporal dynamics within each exposure as well as habituation across repeated exposures. During cold-water exposure there was a cascade of changes across several cardiovascular measures (elevated heart rate (HR), cardiac output (CO) and Mean Arterial Pressure (MAP) and reduced left ventricular ejection time (LVET), stroke volume (SV) and high-frequency heart rate variability (HF)). Increased pupil dilation was observed, as was increased power in low-frequency bands (delta and theta) across frontal EEG electrode sites. Several cardiovascular measures also habituated over repeated cold-water exposures (HR, MAP, CO, SV, LVET) as did pupil dilation and alpha frequency activity across the scalp. Anticipation of cold water induced stress effects in the time-period immediately prior to exposure, indexed by increased pupil size and cortical disinhibition in the alpha and beta frequency bands across central scalp sites. These results provide comprehensive insight into the evolution of a diverse array of stress responses to an acute noxious stressor, and how these responses adaptively contribute to stress habituation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bullock, MacLean, Santander, Boone, Babenko, Dundon, Stuber, Jimmons, Raymer, Okafor, Miller, Giesbrecht and Grafton.)

It is becoming increasingly clear that limb loss induces wider spread reorganization of representations of the body that are nonadjacent to the affected cortical territory. Data from upper extremity amputees reveal intrusion of the representation of the ipsilateral intact limb into the former hand territory. Here we test for the first time whether this reorganization of the intact limb into the deprived cortex is specific to the neurological organization of the upper limbs or reflects large scale adaptation that is triggered by any unilateral amputation. BOLD activity was measured as human subjects with upper limb and lower limb traumatic amputation and their controls moved the toes on each foot, open and closed each hand and pursed their lips. Subjects with amputation were asked to imagine moving the missing limb while remaining still. Bayesian pattern component modeling of fMRI data showed that intact ipsilateral movements and contralateral movements of the hand and foot were distinctly represented in the deprived sensorimotor cortex years after upper limb amputation. In contrast, there was evidence reminiscent of contralateral specificity for hand and foot movements following lower limb amputation, like that seen in controls. We propose the cortical reorganization of the intact limb to be a function of use-dependent plasticity that is more specific to the consequence of upper limb loss of forcing an asymmetric reliance on the intact hand and arm. The contribution of this reorganization to phantom pain or a heightened risk of overuse and resultant maladaptive plasticity needs investigating before targeting such reorganization in intervention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The model-free algorithms of "reinforcement learning" (RL) have gained clout across disciplines, but so too have model-based alternatives. The present study emphasizes other dimensions of this model space in consideration of associative or discriminative generalization across states and actions. This "generalized reinforcement learning" (GRL) model, a frugal extension of RL, parsimoniously retains the single reward-prediction error (RPE), but the scope of learning goes beyond the experienced state and action. Instead, the generalized RPE is efficiently relayed for bidirectional counterfactual updating of value estimates for other representations. Aided by structural information but as an implicit rather than explicit cognitive map, GRL provided the most precise account of human behavior and individual differences in a reversal-learning task with hierarchical structure that encouraged inverse generalization across both states and actions. Reflecting inference that could be true, false (i.e., overgeneralization), or absent (i.e., undergeneralization), state generalization distinguished those who learned well more so than action generalization. With high-resolution high-field fMRI targeting the dopaminergic midbrain, the GRL model's RPE signals (alongside value and decision signals) were localized within not only the striatum but also the substantia nigra and the ventral tegmental area, including specific effects of generalization that also extend to the hippocampus. Factoring in generalization as a multidimensional process in value-based learning, these findings shed light on complexities that, while challenging classic RL, can still be resolved within the bounds of its core computations., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The current study used a high frequency TMS protocol known as continuous theta burst stimulation (cTBS) to test a model of hand choice that relies on competing interactions between the hemispheres of the posterior parietal cortex. Based on the assumption that cTBS reduces cortical excitability, the model predicts a significant decrease in the likelihood of selecting the hand contralateral to stimulation. An established behavioural paradigm was used to estimate hand choice in each individual, and these measures were compared across three stimulation conditions: cTBS to the left posterior parietal cortex, cTBS to the right posterior parietal cortex, or sham cTBS. Our results provide no supporting evidence for the interhemispheric competition model. We find no effects of cTBS on hand choice, independent of whether the left or right posterior parietal cortex was stimulated. Our results are nonetheless of value as a point of comparison against prior brain stimulation findings that, in contrast, provide evidence for a causal role for the posterior parietal cortex in hand choice., Competing Interests: The authors have declared that no competing interests exist.

Somatosensory short-term memory is essential for object recognition, sensorimotor learning, and, especially, Braille reading for people who are blind. This study examined how visual sensory deprivation and a compensatory focus on somatosensory information influences memory processes in this domain. We measured slow cortical negativity developing during short-term tactile memory maintenance (tactile contralateral delay activity, tCDA) in frontal and somatosensory areas while a sample of 24 sighted participants and 22 participants who are blind completed a tactile change-detection task where varying loads of Braille pin patterns served as stimuli. Auditory cues, appearing at varying latencies between sample arrays, could be used to reduce memory demands during maintenance. Participants who are blind (trained Braille readers) outperformed sighted participants behaviorally. In addition, while task-related frontal activation featured in both groups, participants who are blind uniquely showed higher tCDA amplitudes specifically over somatosensory areas. The site specificity of this component's functional relevance in short-term memory maintenance was further supported by somatosensory tCDA amplitudes first correlating across the whole sample with behavioral performance, and secondly showing sensitivity to varying memory load. The results substantiate sensory recruitment models and provide new insights into the effects of visual sensory deprivation on tactile processing. Between-group differences in the interplay between frontal and somatosensory areas during somatosensory maintenance also suggest that efficient maintenance of complex tactile stimuli in short-term memory is primarily facilitated by lateralized activity in somatosensory cortex., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Disorders of the medial temporal lobe (MTL) adversely affect visual working memory (vWM) performance, including feature binding. It is unclear whether these impairments generalize across visual dimensions or are specifically spatial. To address this issue, we compared performance in two tasks of 13 epilepsy patients, who had undergone a temporal lobectomy, and 15 healthy controls. In the vWM task, participants recalled the color of one of two polygons, previously displayed side by side. At recall, a location or shape probe identified the target. In the perceptual task, participants estimated the centroid of three visible disks. Patients recalled the target color less accurately than healthy controls because they frequently swapped the nontarget with the target color. Moreover, healthy controls and right temporal lobectomy patients made more swap errors following shape than space probes. Left temporal lobectomy patients, showed the opposite pattern of errors instead. Patients and controls performed similarly in the perceptual task. We conclude that left MTL damage impairs spatial binding in vWM, and that this impairment does not reflect a perceptual or attentional deficit., (Copyright © 2022 Alenazi et al.)

Anxiety is characterized by low confidence in daily decisions, coupled with high levels of phenomenological stress. Ventromedial prefrontal cortex (vmPFC) plays an integral role in maladaptive anxious behaviors via decreased sensitivity to threatening vs. non-threatening stimuli (fear generalization). vmPFC is also a key node in approach-avoidance decision making requiring two-dimensional integration of rewards and costs. More recently, vmPFC has been implicated as a key cortical input to the sympathetic branch of the autonomic nervous system. However, little is known about the role of this brain region in mediating rapid stress responses elicited by changes in confidence during decision making. We used an approach-avoidance task to examine the relationship between sympathetically mediated cardiac stress responses, vmPFC activity and choice behavior over long and short time-scales. To do this, we collected concurrent fMRI, EKG and impedance cardiography recordings of sympathetic drive while participants made approach-avoidance decisions about monetary rewards paired with painful electric shock stimuli. We observe first that increased sympathetic drive (shorter pre-ejection period) in states lasting minutes are associated with choices involving reduced decision ambivalence. Thus, on this slow time scale, sympathetic drive serves as a proxy for "mobilization" whereby participants are more likely to show consistent value-action mapping. In parallel, imaging analyses reveal that on shorter time scales (estimated with a trial-to-trial GLM), increased vmPFC activity, particularly during low-ambivalence decisions, is associated with decreased sympathetic state. Our findings support a role of sympathetic drive in resolving decision ambivalence across long time horizons and suggest a potential role of vmPFC in modulating this response on a moment-to-moment basis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dundon, Shapiro, Babenko, Okafor and Grafton.)

Sensory processing deficits and altered long-range connectivity putatively underlie Multisensory Integration (MSI) deficits in Autism Spectrum Disorder (ASD). The present study set out to investigate non-social MSI stimuli and their electrophysiological correlates in young neurotypical adolescents and adolescents with ASD. We report robust MSI effects at behavioural and electrophysiological levels. Both groups demonstrated normal behavioural MSI. However, at the neurophysiological level, the ASD group showed less MSI-related reduction of the visual P100 latency, greater MSI-related slowing of the auditory P200 and an overall temporally delayed and spatially constrained onset of MSI. Given the task design and patient sample, and the age of our participants, we argue that electro-cortical indices of MSI deficits in ASD: (a) can be detected in early-adolescent ASD, (b) occur at early stages of perceptual processing, (c) can possibly be compensated by later attentional processes, (d) thus leading to normal MSI at the behavioural level.

Studies investigating the functional organization of the medial temporal lobe (MTL) suggest that parahippocampal cortex (PHC) generates representations of spatial and contextual information used by the hippocampus in the formation of episodic memories. However, evidence from animal studies also implicates PHC in spatial binding of visual information held in short term, working memory. Here we examined a 46-year-old man (P.J.), after he had recovered from bilateral medial occipitotemporal cortex strokes resulting in ischemic lesions of PHC and hippocampal atrophy, and a group of age-matched healthy controls. When recalling the color of 1 of 2 objects, P.J. misidentified the target when cued by its location, but not shape. When recalling the position of 1 of 3 objects, he frequently misidentified the target, which was cued by its color. Increasing the duration of the memory delay had no impact on the proportion of binding errors, but did significantly worsen recall precision in both P.J. and controls. We conclude that PHC may play a crucial role in spatial binding during encoding of visual information in working memory.

Neuropsychological training methods of visual rehabilitation for homonymous vision loss caused by postchiasmatic damage fall into two fundamental paradigms: "compensation" and "restoration". Existing methods can be classified into three groups: Visual Scanning Training (VST), Audio-Visual Scanning Training (AViST) and Vision Restoration Training (VRT). VST and AViST aim at compensating vision loss by training eye scanning movements, whereas VRT aims at improving lost vision by activating residual visual functions by training light detection and discrimination of visual stimuli. This review discusses the rationale underlying these paradigms and summarizes the available evidence with respect to treatment efficacy. The issues raised in our review should help guide clinical care and stimulate new ideas for future research uncovering the underlying neural correlates of the different treatment paradigms. We propose that both local "within-system" interactions (i.e., relying on plasticity within peri-lesional spared tissue) and changes in more global "between-system" networks (i.e., recruiting alternative visual pathways) contribute to both vision restoration and compensatory rehabilitation, which ultimately have implications for the rehabilitation of cognitive functions.