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Objective High-frequency spinal cord stimulation (HF-SCS) is a potential method to provide natural and effective inspiratory muscle pacing in patients with ventilator-dependent spinal cord injuries. Experimental data have demonstrated that HF-SCS elicits physiological activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways. However, the activation thresholds, extent of activation, and optimal electrode configurations (i.e., lead separation, contact spacing, and contact length) to activate these neural elements remain unknown. Therefore, the goal of this study was to use a computational modeling approach to investigate the direct effects of HF-SCS on the spinal cord and to optimize electrode design and stimulation parameters. Materials and methods We developed a computer model of HF-SCS that consisted of two main components: 1) finite element models of the electric field generated during HF-SCS, and 2) multicompartment cable models of axons and motoneurons within the spinal cord. We systematically evaluated the neural recruitment during HF-SCS for several unique electrode designs and stimulation configurations to optimize activation of these neural elements. We then evaluated our predictions by testing two of these lead designs with in vivo canine experiments. Results Our model results suggested that within physiological stimulation amplitudes, HF-SCS activates both axons in the ventrolateral funiculi (VLF) and inspiratory intercostal motoneurons. We used our model to predict a lead design to maximize HF-SCS activation of these neural targets. We evaluated this lead design via in vivo experiments, and our computational model predictions demonstrated excellent agreement with our experimental testing. Conclusions Our computational modeling and experimental results support the potential advantages of a lead design with longer contacts and larger edge-to-edge contact spacing to maximize inspiratory muscle activation during HF-SCS at the T2 spinal level. While these results need to be further validated in future studies, we believe that the results of this study will help improve the efficacy of HF-SCS technologies for inspiratory muscle pacing.

Spinal cord stimulation (SCS) is a popular neurostimulation therapy for severe chronic pain. To improve stimulation efficacy, multiple modes are now used clinically, including conventional, burst, and 10-kHz SCS. Clinical observations have produced speculation that these modes target different neural elements and/or work via distinct mechanisms of action. However, in humans, these hypotheses cannot be conclusively answered via experimental methods. Therefore, we utilized computational modeling to assess the response of primary afferents, interneurons, and projection neurons to conventional, burst, and 10-kHz SCS. We found that local cell thresholds were always higher than afferent thresholds, arguing against direct recruitment of these local cells. Furthermore, although we observed relative threshold differences between conventional, burst, and 10-kHz SCS, the recruitment order was the same. Finally, contrary to previous reports, axon collateralization produced complex changes in activation thresholds of primary afferents. These results motivate future work to contextualize clinical observations across SCS paradigms. PERSPECTIVE: This article presents the first computational modeling study to investigate neural recruitment during conventional, burst, and 10-kilohertz spinal cord stimulation for chronic pain within a single modeling framework. The results provide insight into these treatments' unknown mechanisms of action and offer context to interpreting clinical observations.

The aims of the study were: 1. To analyse the discriminative power of neuromuscular components for classifying the pre and post muscle fatigued states. 2. To examine whether the modification of neural recruitment strategies become more/less heterogeneous due to fatigue. 3. To research the effect of Erector Spinae (ES) muscle activity collectively with Rectus Abdominis (RA) and External Oblique (EO) muscle activity to identify the reduced spine stability during fatiguing Plank. Material and methods. Twelve boys (age – 12-14 years, height 148.75 ± 10 cm, body mass 38.9 ± 7.9 kg) participated in the study. Multivariate Discriminant Analysis (DA) and Principal Component Analysis (PCA) were applied to identify the changes in the pattern of the electromyographic signals during muscle fatigue. In DA the Wilks’ lambda, p-value, canonical correlation, classification percentage and structure matrix were used. To evaluate the component validity the standard limit for Kaiser-Meyer-Olkin (KMO) was set at ≥0.529 and the p-value of Bartlett’s test was ≤0.001. The eigenvalues ≥1 were used to determine the number of Principal Components (PCs). The satisfactory percentage of non-redundant residuals were set at ≤50% with standard value >0.05. The absolute value of average communality (x̄ h2) and component loadings were set at ≥0.6, ≥0.4 respectively. Results. Standardized canonical discriminant analysis showed that pre and post fatigued conditions were significantly different (p = 0.000, Wilks’ lambda = 0.297, χ2 = 24.914, df=3). The structure matrix showed that the parameter that correlated highly with the discriminant function was ES ARV (0.514). The results showed that the classification accuracy was 95.8% between fatigued conditions. In PCA the KMO values were reduced [0.547Pre fatigue vs. 0.264Post fatigue]; the value of Bartlett’s sphericity test was in pre χ2 = 90.72 (p = 0.000) and post fatigue χ2 = 85.32 (p = 0.000); The Promax criterion with Kaiser Normalization was applied because the component rotation was non-orthogonal [Component Correlation Matrix (rCCM) = 0.520 Pre fatigue >0.3Absolute

Semantic composition, the ability to combine single words to form complex meanings, is a core feature of human language. Despite growing interest in the basis of semantic composition, the neural correlates and the interaction of regions within this network remain a matter of debate. We designed a well-controlled two-word fMRI paradigm in which phrases only differed along the semantic dimension while keeping syntactic information alike. Healthy participants listened to meaningful (“fresh apple”), anomalous (“awake apple”) and pseudoword phrases (“awake gufel”) while performing an implicit and an explicit semantic task. We identified neural signatures for distinct processes during basic semantic composition. When lexical information is kept constant across conditions and the evaluation of phrasal plausibility is examined (meaningful vs. anomalous phrases), a small set of mostly left-hemispheric semantic regions, including the anterior part of the left angular gyrus, is found active. Conversely, when the load of lexical information—independently of phrasal plausibility—is varied (meaningful or anomalous vs. pseudoword phrases), conceptual combination involves a wide-spread left-hemispheric network comprising executive semantic control regions and general conceptual representation regions. Within this network, the functional coupling between the left anterior inferior frontal gyrus, the bilateral pre-supplementary motor area and the posterior angular gyrus specifically increases for meaningful phrases relative to pseudoword phrases. Stronger effects in the explicit task further suggest task-dependent neural recruitment. Overall, we provide a separation between distinct nodes of the semantic network, whose functional contributions depend on the type of compositional process under analysis. Supplementary Information The online version contains supplementary material available at 10.1007/s00429-020-02196-2.

Visual perspective, recalling events from one's own eyes or one of several possible observer viewpoints, is a fundamental aspect of AM. Yet, exactly how visual perspective influences the functional mechanisms supporting retrieval is unclear. Here we used a multivariate analysis to characterize the spatiotemporal dynamics of networks supporting AM retrieval from multiple typical and atypical visual perspectives. Both own eyes and observer perspectives engaged an AM retrieval network (i.e., hippocampus, anterior and posterior midline, and lateral frontal and posterior cortices) that peaked during later retrieval periods, but was recruited less strongly for observer perspectives. Functional connectivity analyses with an anterior hippocampal seed revealed that visual perspective also affected the strength and timing of neural recruitment. There was stronger hippocampal connectivity with a posterior medial network during the initial retrieval of AMs from atypical observer perspectives and stronger within-MTL and ventromedial prefrontal cortex connectivity during later retrieval periods from own eyes perspectives, suggesting that visual perspective is an important factor in understanding how neocortical systems guide memory retrieval. Our findings demonstrate that adopting own eyes and observer perspectives during AM retrieval is correlated with distinct patterns of hippocampal-neocortical interactions associated with differential recruitment of the AM retrieval network during later retrieval periods, thereby supporting the central role of visual perspective in reconstructing the personal past.

Advances in technology and improvement of efficacy for many neuromodulation applications have been achieved without understanding the relationship between the stimulation parameters and the neural activity which is generated in the nervous system. It is the neural activity that ultimately drives the therapeutic benefit and the advent of evoked compound action potential recording allows this activity to be directly measured and quantified. Closed-loop control adjusts the stimulation parameters to maintain a predetermined level of neural recruitment and has been shown to provide improved pain relief in individuals with spinal cord stimulators. However, no mechanism that relates more consistent neural recruitment to patient outcomes has been proposed. The authors propose a hypothesis that may explain the difference in efficacy between open- and closed-loop operational modes by considering the relationship between measured neural recruitment with hypothetical dose and side effect response curves. This provides a rational basis for directing clinical research and improving therapeutic systems.

We examined the effect of acute intermittent hypoxia (IH) on sympathetic neural firing patterns and the role of the carotid chemoreceptors. We hypothesized exposure to acute IH would increase muscle sympathetic nerve activity (MSNA) via an increase in action potential (AP) discharge rates and within-burst firing. We further hypothesized any change in discharge patterns would be attenuated during acute chemoreceptor deactivation (hyperoxia). MSNA (microneurography) was assessed in 17 healthy adults (11 male/6 female; 31 ± 1 yr) during normoxic rest before and after 30 min of experimental IH. Prior to and following IH, participants were exposed to 2 min of 100% oxygen (hyperoxia). AP patterns were studied from the filtered raw MSNA signal using wavelet-based methodology. Compared with baseline, multiunit MSNA burst incidence ( P < 0.01), AP incidence ( P = 0.01), and AP content per burst ( P = 0.01) were increased following IH. There was an increase in the probability of a particular AP cluster firing once ( P < 0.01) and more than once ( P = 0.03) per burst following IH. There was no effect of hyperoxia on multiunit MSNA at baseline or following IH ( P > 0.05); however, hyperoxia following IH attenuated the probability of particular AP clusters firing more than once per burst ( P < 0.01). Acute IH increases MSNA by increasing AP discharge rates and within-burst firing. A portion of the increase in within-burst firing following IH can be attributed to the carotid chemoreceptors. These data advance the mechanistic understanding of sympathetic activation following acute IH in humans.

Emotion and self-referential information can both enhance memory, but whether they do so via common mechanisms across the adult lifespan remains underexplored. To address this gap, the current study directly compared, within the same fMRI paradigm, the encoding of emotionally salient and self-referential information in older adults and younger adults. Behavioral results replicated the typical patterns of better memory for emotional than neutral information and for self-referential than non-self-referential materials; these memory enhancements were present for younger and older adults. In neural activity, young and older adults showed similar modulation by emotion, but there were substantial age differences in the way self-referential processing affected neural recruitment. Contrary to our hypothesis, we found little evidence for overlap in the neural mechanisms engaged for emotional and self-referential processing. These results reveal that—just as in cognitive domains—older adults can show similar performance to younger adults in socioemotional domains even though the two age groups engage distinct neural mechanisms. These findings demonstrate the need for future research delving into the neural mechanisms supporting older adults’ memory benefits for socioemotional material.

Purpose One limitation of research that assesses the effectiveness of physical activity interventions for people with dementia is that most do not describe the intervention in sufficient detail to ascertain a theoretical basis or mechanism of action that determines the effective components. This paper aims to identify studies which evaluate the mechanisms of action of physical activity interventions for people with dementia, to further inform effective intervention development. Design/methodology/approach Papers were screened for evidence of evaluation of specific forms of physical activity, using pre-defined inclusion criteria. Analysis was conducted to ascertain if mechanisms of action were corroborated by data within and between studies. Findings The authors identified 26 studies with a measured mechanism of action; these related to the effects of physical activity on either neurological structure or endocrinal markers, including hormones. Physical activity had potential to reduce hippocampal atrophy, increase neural recruitment, activate the noradrenergic system and improve anti-inflammatory responses. While individual studies were hampered by small sample sizes, the body of evidence indicated that physical activity may have potential to delay cognitive decline. Practical implications Mechanisms of action in relation to dementia and physical activity are likely to be multifaceted, and physical activity may be protective against progression in the early stages of cognitive decline. Physical activity may be of greatest benefit if incorporated into on-going lifestyle, rather than engaged in for short periods, and combined with social interaction. Originality/value This paper is unique in its focus on the mechanisms of action of physical activity interventions for people with dementia.

Age-related changes have been identified in neural and motor level. A prominent change is reduced asymmetry in cortical activation as well as motor performance. Cortical activation models have been established based on cognitive research utilizing neuroimaging techniques to explain age-related effects on neural recruitment and reduced brain asymmetry. Recently, researchers in motor behaviour attempted to apply the models to explain motor pattern changes in aging and proposed compensation as the mechanism of the reduced motor asymmetry in older adults. Age-related alterations in movement patterns and brain activations seem to be correlated. However, based on the literature search result, no direct evidence substantiates the connection between reduced brain asymmetry and motor asymmetry in older adults. Therefore, a theoretical gap was identified. The theoretical gap exists because either neuroimaging studies have not considered motor asymmetry or motor asymmetry studies have not integrated neuroimaging techniques into study designs. Answering the research question can be valuable to both research and clinical practice. With the mechanisms of brain activation patterns during motor tasks in an aging population being better understood, protocols developed upon the new understandings can be applied to current motor interventions and better maintain the longevity of motor function of older adults.

Purpose Reorganization of language networks in aphasia takes advantage of the facts that (a) the brain is an organ of plasticity, with neuronal changes occurring throughout the life span, including following brain damage; (b) plasticity is highly experience dependent; and (c) as with any learning system, language reorganization involves a synergistic interplay between organism-intrinsic (i.e., cognitive and brain) and organism-extrinsic (i.e., environmental) variables. A major goal for clinical treatment of aphasia is to be able to prescribe treatment and predict its outcome based on the neurocognitive deficit profiles of individual patients. This review article summarizes the results of research examining the neurocognitive effects of psycholinguistically based treatment (i.e., Treatment of Underlying Forms; Thompson & Shapiro, 2005 ) for sentence processing impairments in individuals with chronic agrammatic aphasia resulting from stroke and primary progressive aphasia and addresses both behavioral and brain variables related to successful treatment outcomes. The influences of lesion volume and location, perfusion (blood flow), and resting-state neural activity on language recovery are also discussed as related to recovery of agrammatism and other language impairments. Based on these and other data, principles for promoting neuroplasticity of language networks are presented. Conclusions Sentence processing treatment results in improved comprehension and production of complex syntactic structures in chronic agrammatism and generalization to less complex, linguistically related structures in chronic agrammatism. Patients also show treatment-induced shifts toward normal-like online sentence processing routines (based on eye movement data) and changes in neural recruitment patterns (based on functional neuroimaging), with posttreatment activation of regions overlapping with those within sentence processing and dorsal attention networks engaged by neurotypical adults performing the same task. These findings provide compelling evidence that treatment focused on principles of neuroplasticity promotes neurocognitive recovery in chronic agrammatic aphasia. Presentation Video https://doi.org/10.23641/asha.10257587

We present the hypothesis that exercise-induced hyperemia, perhaps through vascular shear stress, represents an important factor responsible for the effects of physical activity (PA) on vascular insulin sensitivity. Specifically, we postulate PA involving the greatest amount of skeletal muscle mass and the greatest central neural recruitment maximizes perfusion and consequently enhances vascular insulin sensitivity in the skeletal muscle and brain.

The current study evaluated the hypothesis that six months of exercise-based cardiac rehabilitation (CR) would improve sympathetic neural recruitment in patients with ischemic heart disease (IHD). Microneurography was used to evaluate action potential (AP) discharge patterns within bursts of muscle sympathetic nerve activity (MSNA), in eleven patients with IHD (1 female; 61±9 years) pre- (Pre-CR) and post- six months of aerobic and resistance training-based CR (Post-CR). Measures were made at baseline and during maximal voluntary end-inspiratory (EI-APN) and end-expiratory apneas (EE-APN). Data were analyzed during 1-minute of baseline and the second half of apneas. At baseline, overall sympathetic activity was less Post-CR (all P0.05) but increases in both within-burst AP firing frequency (∆Pre-CR: 2±3 AP spikes/burst vs. ∆Post-CR: 4±3 AP spikes/burst; P=0.02) and AP cluster recruitment (∆Pre-CR: -1±2 vs. ∆Post-CR: 2±2; P

Aging is accompanied by frontal lobe and non-dominant hemisphere recruitment that supports executive functioning, such as inhibitory control, which is crucial to all cognitive functions. However, the spatio-temporal sequence of processing underlying successful inhibition and how it changes with age is understudied. Thus, we capitalized on the temporal precision of event-related potentials (ERPs) to assess the functional lateralization of N200 (conflict monitoring) and P300 (inhibitory performance evaluation) in young and healthy older adults during comparably performed successful stop-signal inhibition. We additionally used temporal principal components analysis (PCA) to further interrogate the continuous spatio-temporal dynamics underlying N200 and P300 activation for each group. Young adults demonstrated left hemisphere-dominant N200, while older adults demonstrated overall larger amplitudes and right hemisphere dominance. N200 activation was explained by a single PCA factor in both age groups, but with a more anterior scalp distribution in older adults. The P300 amplitudes were larger in the right hemisphere in young, but bilateral in old, with old larger than young in the left hemisphere. P300 was also explained by a single factor in young adults but by two factors in older adults, including distinct parieto-occipital and anterior activation. These findings highlight the differential functional asymmetries of conflict monitoring (N200) and inhibitory evaluation and adaptation (P300) processes and further illuminate unique age-related spatio-temporal recruitment patterns. Older adults demonstrated lateralized recruitment during conflict processing and bilateral recruitment during evaluation and adaptation, with anterior recruitment common to both processes. These fine-grained analyses are critically important for more precise understanding of age-related compensatory activation.

Humans learn about their environments by observing others, including what to fear and what to trust. Observational fear learning may be especially important early in life when children turn to their parents to gather information about their world. Yet, the vast majority of empirical research on fear learning in youth has thus far focused on firsthand classical conditioning, which may fail to capture one of the primary means by which fears are acquired during development. To address this gap in the literature, the present study examined observational fear learning in youth (n=33; age range: 6-17years) as they watched videos of their parent and an "unfamiliar parent" (i.e., another participant's parent) undergo fear conditioning. Youth demonstrated stronger fear learning when observing their parent compared to an unfamiliar parent, as indicated by changes in their self-reported liking of the stimuli to which their parents were conditioned (CS+, a geometric shape paired with an aversive noise; CS-, a geometric shape never paired with an aversive noise) and amygdala responses. Parent trait anxiety was associated with youth learning better (i.e., reporting a stronger preference for the CS- relative to CS+), and exhibiting stronger medial prefrontal-amygdala connectivity. Neuroimaging data were additionally acquired from a subset of parents during firsthand conditioning, and parental amygdala and mPFC activation were associated with youth's neural recruitment. Together, these results suggest that youth preferentially learn fears via observation of their parents, and this learning is associated with emotional traits and neural recruitment in parents.

Objective One of the challenges in treating patients with drug-resistant epilepsy is that the mechanisms of seizures are unknown. Most current interventions are based on the assumption that epileptic activity recruits neurons and progresses by synaptic transmission. However, several experimental studies have shown that neural activity in rodent hippocampi can propagate independently of synaptic transmission. Recent studies suggest these waves are self-propagating by electric field (ephaptic) coupling. In this study, we tested the hypothesis that neural recruitment during seizures can occur by electric field coupling. Methods 4-Aminopyridine was used in both in vivo and in vitro preparation to trigger seizures or epileptiform activity. A transection was made in the in vivo hippocampus and in vitro hippocampal and cortical slices to study whether the induced seizure activity can recruit neurons across the gap. A computational model was built to test whether ephaptic coupling alone can account for neural recruitment across the transection. The model prediction was further validated by in vitro experiments. Results Experimental results show that electric fields generated by seizure-like activity in the hippocampus both in vitro and in vivo can recruit neurons locally and through a transection of the tissue. The computational model suggests that the neural recruitment across the transection is mediated by electric field coupling. With in vitro experiments, we show that a dielectric material can block the recruitment of epileptiform activity across a transection, and that the electric fields measured within the gap are similar to those predicted by model simulations. Furthermore, this nonsynaptic neural recruitment is also observed in cortical slices, suggesting that this effect is robust in brain tissue. Significance These results indicate that ephaptic coupling, a nonsynaptic mechanism, can underlie neural recruitment by a small electric field generated by seizure activity and could explain the low success rate of surgical transections in epilepsy patients.

Background: Despite advances in understanding Alzheimer’s disease (AD), prediction of AD prior to symptom onset remains severely limited, even when primary risk factors such as the apolipoprotein E (APOE) ɛ4 allele are known. Objective: Although executive dysfunction is highly prevalent and is a primary contributor to loss of independence in those with AD, few studies have examined neural differences underlying executive functioning as indicators of risk for AD prior to symptom onset, when intervention might be effective. Methods: This study examined event-related potential (ERP) differences during inhibitory control in 44 cognitively intact older adults (20 ɛ4+, 24 ɛ4-), relative to 41 young adults. All participants completed go/no-go and stop-signal tasks. Results: Overall, both older adult groups exhibited slower reaction times and longer ERP latencies compared to young adults. Older adults also had generally smaller N200 and P300 amplitudes, except at frontal electrodes and for N200 stop-signal amplitudes, which were larger in older adults. Considered with intact task accuracy, these findings suggest age-related neural compensation. Although ɛ4 did not distinguish elders during go or no-go tasks, this study uniquely showed that the more demanding stop-signal task was sensitive to ɛ4 differences, despite comparable task and neuropsychological performance with non-carriers. Specifically, ɛ4+ elders had slower frontal N200 latency and larger N200 amplitude, which was most robust at frontal sites, compared with ɛ4-. Conclusion: N200 during a stop-signal task is sensitive to AD risk, prior to any evidence of cognitive dysfunction, suggesting that stop-signal ERPs may be an important protocol addition to neuropsychological testing.

Background Escalation of commitment is a common bias in human decision making. The present study examined (1) differences in neural recruitment for escalation and de-escalation decisions of prior investments, and (2) how the activations of these brain networks are affected by two factors that can arguably modulate escalation decisions: (i) self-responsibility, and (ii) framing of the success probabilities. Results Imaging data were obtained from functional magnetic resonance imaging (fMRI) applied to 29 participants. A whole-brain analysis was conducted to compare brain activations between conditions. ROI analysis, then, was used to examine if these significant activations were modulated by two contextual factors. Finally, mediation analysis was applied to explore how the contextual factors affect escalation decisions through brain activations. The findings showed that (1) escalation decisions are faster than de-escalation decisions, (2) the corresponding network of brain regions recruited for escalation (anterior cingulate cortex, insula and precuneus) decisions differs from this recruited for de-escalation decisions (inferior and superior frontal gyri), (3) the switch from escalation to de-escalation is primarily frontal gyri dependent, and (4) activation in the anterior cingulate cortex, insula and precuneus were further increased in escalation decisions, when the outcome probabilities of the follow-up investment were positively framed; and activation in the inferior and superior frontal gyri in de-escalation decisions were increased when the outcome probabilities were negatively framed. Conclusions Escalation and de-escalation decisions recruit different brain regions. Framing of possible outcomes as negative leads to escalation decisions through recruitment of the inferior frontal gyrus. Responsibility for decisions affects escalation decisions through recruitment of the superior (inferior) gyrus, when the decision is framed positively (negatively).

Age-related elevations in sympathetic nerve activity contribute to numerous deleterious consequences for cardiovascular health, particularly in postmenopausal women (PMW). Aging adversely affects aspects of sympathetic nervous system (SNS) coding to control blood pressure at rest and during physiological stress. Although PMW exhibit greater neural activity at rest, the underlying sympathetic discharge patterns, particularly during sympathoexcitation, remain unknown. This study aimed to test the hypothesis that PMW display aberrant neural coding strategies during physiological stress compared to young women (YW). Efferent muscle sympathetic nerve activity (microneurography) was measured at baseline and during the final minute of both 30% isometric handgrip (HG) and post-exercise ischemia (PEI) in five healthy YW (22 ± 2 y, 20 ± 4 kg/m 2 , mean blood pressure: 82 ± 7 mmHg) and five healthy PMW (60 ± 5 y, 23 ± 3 kg/m 2 , 87 ± 8 mmHg). Sympathetic action potential (AP) discharge patterns were examined using wavelet-based methodology. At baseline, PMW exhibited elevated integrated burst frequency (PMW 30 ± 10 vs YW 9 ± 3 bursts/min; p < 0.01) and increased AP firing (PMW 240 ± 117 vs YW 90 ± 64 APs/min, p = 0.04). Both groups had similar increases in integrated burst frequency during HG and PEI (p < 0.01 vs baseline). AP firing was elevated to a similar extent in both groups during HG (PMW Δ76 ± 60; YW Δ129 ± 146 APs/min; p < 0.01 vs baseline) and PEI (PMW Δ72 ± 51; YW Δ93 ± 64 APs/min; p < 0.01 vs baseline), with no change in the mean AP content per burst (p = 0.86). PMW had reduced recruitment of latent and larger AP subpopulations that were previously silent at baseline (group-by-condition interaction: p < 0.01), as evidenced by an increase in total AP clusters (binned according to peak-to-peak amplitude) during HG and PEI in YW (HG: Δ2 ± 1; PEI: Δ2 ± 2; both p ≤ 0.03 vs baseline) but not PMW (HG: Δ0 ± 1; PEI: Δ0 ± 1; both p ≥ 0.75 vs baseline). These preliminary data suggest that PMW display elevated resting sympathetic AP firing and aberrant reflex AP recruitment, such that the ability of the SNS to recruit subpopulations of previously silent axons during a sympathetic stressor is reduced in PWM compared to YW. These findings extend our knowledge of age-related neural coding strategies in women.

BACKGROUND AND METHODS: Clinical neuropsychology lacks tests of basic visuoperceptual and spatial skills that have well-controlled administration and sophisticated measurement methods. Items from the Visual Assessment Battery (VAB), a simultaneous match-to-sample task, assessed visual discrimination in 40 healthy adults aged 51–91 during fMRI. The tasks were designed to isolate discrimination of either location, shape, or velocity, and they each had three levels of difficulty. RESULTS: The Location task uniquely activated the dorsal visual processing stream, the Shape task the ventral stream, and the Velocity task an area encompassing V5. Greater age was associated with greater neural recruitment, particularly in frontal areas. Behaviorally, greater age was associated with prolonged response times, but not reduced accuracy. Increased difficulty was associated with slower responses and reduced accuracy, regardless of age. CONCLUSIONS: Results validated the specialization of brain regions for spatial, perceptual, and movement discriminations and the use of the VAB to assess functioning localized to these regions. Visual discrimination ability does not change dramatically with age, but like many cognitive processes, performance slows. Anterior neural recruitment during visual discrimination increases with age.

Retrieving autobiographical memories induces a natural tendency to mentally simulate alternate versions of past events, either by reconstructing the perceptual details of the originally experienced perspective or the conceptual information of what actually occurred. Here we examined whether the episodic system recruited during imaginative experiences functionally dissociates depending on the nature of this reconstruction. Using fMRI, we evaluated differential patterns of neural activity and hippocampal connectivity when twenty-nine participants naturally recalled past negative events, shifted visual perspective, or imagined better or worse outcomes than what actually occurred. We found that counterfactual thoughts were distinguished by neural recruitment in dorsomedial prefrontal cortex, whereas shifts in visual perspective were uniquely supported by the precuneus. Additionally, connectivity with the anterior hippocampus changed depending upon the mental simulation that was performed - with enhanced hippocampal connectivity with medial prefrontal cortex for counterfactual simulations and precuneus for shifted visual perspectives. Together, our findings provide a novel assessment of differences between these common methods of mental simulation and a more detailed account for the neural network underlying episodic retrieval and reconstruction.

BackgroundDisruptions in neural circuits underlying emotion regulation (ER) may be a mechanism linking child maltreatment with psychopathology. We examined the associations of maltreatment with neural responses during passive viewing of negative emotional stimuli and attempts to modulate emotional responses. We investigated whether the influence of maltreatment on neural activation during ER differed across development and whether alterations in brain function mediated the association between maltreatment and a latent general psychopathology (‘p’) factor.MethodsYouth aged 8–16 years with (n = 79) and without (n = 72) exposure to maltreatment completed an ER task assessing neural responses during passive viewing of negative and neutral images and effortful attempts to regulate emotional responses to negative stimuli. P-factor scores were defined by a bi-factor model encompassing internalizing and externalizing psychopathology.ResultsMaltreated youth had greater activation in left amygdala and salience processing regions and reduced activation in multiple regions involved in cognitive control (bilateral superior frontal gyrus, middle frontal gyrus, and dorsal anterior cingulate cortex) when viewing negative v. neutral images than youth without maltreatment exposure. Reduced neural recruitment in cognitive control regions mediated the association of maltreatment with p-factor in whole-brain analysis. Maltreated youth exhibited increasing recruitment with age in ventrolateral prefrontal cortex during reappraisal while control participants exhibited decreasing recruitment with age. Findings were similar after adjusting for co-occurring neglect.ConclusionsChild maltreatment influences the development of regions associated with salience processing and cognitive control during ER in ways that contribute to psychopathology.

The potential effects of bilingualism on executive control (EC) have been heavily debated. One possible source of discrepancy in the evidence may be that bilingualism tends to be treated as a monolithic category distinct from monolingualism. We address this possibility by examining the effects of different bilingual language experiences on brain activity related to EC performance. Participants were scanned (fMRI) while they performed a Flanker task. Behavioral data showed robust Flanker effects, not modulated by language experiences across participants. However, differences in duration of bilingual experience and extent of active language use predicted activation in distinct brain regions indicating differences in neural recruitment across conditions. This approach highlights the need to consider specific bilingual language experiences in assessing neurocognitive effects. It further underscores the utility and complementarity of neuroimaging evidence in this general line of research, contributing to a deeper understanding of the variability reported in the literature.

This study tested the hypothesis that older hypertensive women display augmented pressor responses and aberrant sympathetic neural discharge patterning in response to orthostatic stress versus older hypertensive men. We evaluated, in older hypertensive and normotensive men and women (n=12 each group), blood pressure, heart rate, cardiac index (acetylene rebreathing), total peripheral resistance, and muscle sympathetic nerve activity (microneurography) at baseline (supine; 3 minutes) and during graded head-up tilt (30° for 5 minutes and 60° for 20 minutes). Sympathetic action potential discharge patterns were studied using wavelet-based methodology. In the upright posture, systolic and diastolic blood pressure responses were greater in hypertensive women versus hypertensive men and normotensive women ( P P P P

Purpose To better understand the relationship between exposure to concussive and subconcussive head impacts, white matter integrity, and functional task-related neural activity in former U.S. football athletes. Materials and Methods Between 2011 and 2013, 61 cognitively unimpaired former collegiate and professional football players (age range, 52-65 years) provided informed consent to participate in this cross-sectional study. Participants were stratified across three crossed factors: career duration, concussion history, and primary playing position. Fractional anisotropy (FA) and blood oxygen level-dependent (BOLD) percent signal change (PSC) were measured with diffusion-weighted and task-related functional magnetic resonance imaging, respectively. Analyses of variance of FA and BOLD PSC were used to determine main or interaction effects of the three factors. Results A significant interaction between career duration and concussion history was observed; former college players with more than three concussions had lower FA in a broadly distributed area of white matter compared with those with zero to one concussion (t29 = 2.774; adjusted P = .037), and the opposite was observed for former professional players (t29 = 3.883; adjusted P = .001). A separate interaction between concussion history and position was observed: Nonspeed players with more than three concussions had lower FA in frontal white matter compared with those with zero to one concussion (t25 = 3.861; adjusted P = .002). Analysis of working memory-task BOLD PSC revealed a similar interaction between concussion history and position (all adjusted P.004). Overall, former players with lower FA tended to have lower BOLD PSC across three levels of a working memory task. Conclusion Career duration and primary playing position seem to modify the effects of concussion history on white matter structure and neural recruitment. The differences in brain structure and function were observed in the absence of clinical impairment, which suggested that multimodal imaging may provide early markers of onset of traumatic neurodegenerative disease.

Associative learning underlies the formation of new episodic memories. Associative memory improves across development, and this age-related improvement is supported by the development of the hippocampus and pFC. Recent work, however, additionally suggests a role for visual association cortex in the formation of associative memories. This study investigated the role of category-preferential visual processing regions in associative memory across development using a paired associate learning task in a sample of 56 youths (age 6–19 years). Participants were asked to bind an emotional face with an object while undergoing fMRI scanning. Outside the scanner, participants completed a memory test. We first investigated age-related changes in neural recruitment and found linear age-related increases in activation in lateral occipital cortex and fusiform gyrus, which are involved in visual processing of objects and faces, respectively. Furthermore, greater activation in these visual processing regions was associated with better subsequent memory for pairs over and above the effect of age and of hippocampal and pFC activation on performance. Recruitment of these visual processing regions mediated the association between age and memory performance, over and above the effects of hippocampal activation. Taken together, these findings extend the existing literature to suggest that greater recruitment of category-preferential visual processing regions during encoding of associative memories is a neural mechanism explaining improved memory across development.

Although autobiographical memory and episodic simulations recruit similar core brain regions, episodic simulations engage additional neural recruitment in the frontoparietal control network due to greater demands on constructive processes. However, previous functional neuroimaging studies showing differences in remembering and episodic simulation have focused on veridical retrieval of past experiences, and thus have not fully considered how retrieving the past in different ways from how it was originally experienced may also place similar demands on constructive processes. Here we examined how alternative versions of the past are constructed when adopting different egocentric perspectives during autobiographical memory retrieval compared to simulating hypothetical events from the personal past that could have occurred, or episodic counterfactual thinking. Participants were asked to generate titles for specific autobiographical memories from the last five years, and then, during functional magnetic resonance (fMRI) scanning, were asked to repeatedly retrieve autobiographical memories or imagine counterfactual events cued by the titles. We used an fMRI adaptation paradigm in order to isolate neural regions that were sensitive to adopting alternative egocentric perspectives and counterfactual simulations of the personal past. The fMRI results revealed that voxels within left posterior inferior parietal and ventrolateral frontal cortices were sensitive to novel visual perspectives and counterfactual simulations. Our findings suggest that the neural regions supporting remembering become more similar to those underlying episodic simulation when we adopt alternative egocentric perspectives of the veridical past.

A longstanding question in cognitive neuroscience and in the bilingualism literature is how early language experience influences brain development and cognitive outcomes, and whether these effects are global or specific to language-related processes. The current investigation examined the effect of the timing of language learning on the performance and neural correlates of phonological and non-verbal working memory, subcomponents of executive function. Three groups of bilinguals, who varied in terms of the timing of second language learning (i.e., simultaneous bilinguals learned their two languages from birth; early and late bilinguals who learned their second language before or after 5 years of age, respectively), performed phonological and non-verbal working memory tasks in the magnetic resonance imaging scanner. Results showed that there were no group differences in performance on either of the tasks, or in the neural correlates of performance of the non-verbal task. However, critically, we showed that despite similar behavioural performance, the groups differed in the patterns of neural recruitment during performance of the phonological working memory task. The pattern of group differences was non-linear, demonstrating similar neural recruitment for simultaneous and late bilinguals that differed from early bilinguals. Findings from the current study suggest a dynamic mapping between the brain and cognition, contributing to our current understanding of the effect of the timing of language learning on cognitive processes and demonstrating a specific effect on language-related executive function.

Childhood adversity is associated with increased risk for psychopathology. Neurodevelopmental pathways underlying this risk remain poorly understood. A recent conceptual model posits that childhood adversity can be deconstructed into at least two underlying dimensions, deprivation and threat, that are associated with distinct neurocognitive consequences. This model argues that deprivation (i.e., a lack of cognitive stimulation and learning opportunities) is associated with poor executive function (EF), whereas threat is not. We examine this hypothesis in two studies measuring EF at multiple levels: performance on EF tasks, neural recruitment during EF, and problems with EF in daily life. In Study 1, deprivation (low parental education and child neglect) was associated with greater parent-reported problems with EF in adolescents (N= 169; 13–17 years) after adjustment for levels of threat (community violence and abuse), which were unrelated to EF. In Study 2, low parental education was associated with poor working memory (WM) performance and inefficient neural recruitment in the parietal and prefrontal cortex during high WM load among adolescents (N= 51, 13–20 years) after adjusting for abuse, which was unrelated to WM task performance and neural recruitment during WM. These findings constitute strong preliminary evidence for a novel model of the neurodevelopmental consequences of childhood adversity.

Objectives Although research has identified age-by-emotion interactions in memory performance and in neural recruitment during retrieval, it remains unclear which retrieval processes are affected. The temporal resolution of event-related potentials (ERPs) provides a way to examine different component processes that operate during retrieval. Methods In the present study, younger and older adults encoded neutral and emotional images paired with neutral titles. ERPs were assessed during a recognition memory task in which participants viewed neutral titles and indicated whether each had been presented during encoding. Results An age-related posterior-to-anterior shift began in a time window typically associated with recollection-related processes (500–800 ms) while an age-by-emotion interaction occurred only during a later measurement window (800–1,200 ms). Discussion These findings suggest an effect of age on mechanisms supporting retrieval of episodic content, prior to post-retrieval processing. The potential relations to different types of detail retrieval are discussed. Further, the later age-by-emotion interactions suggest that age influences the effect of emotion on post-retrieval processes, specifically.

A single bout of resistance training induces residual fatigue, which may impair performance during subsequent endurance training if inadequate recovery is allowed. From a concurrent training standpoint, such carry-over effects of fatigue from a resistance training session may impair the quality of a subsequent endurance training session for several hours to days with inadequate recovery. The proposed mechanisms of this phenomenon include: (1) impaired neural recruitment patterns; (2) reduced movement efficiency due to alteration in kinematics during endurance exercise and increased energy expenditure; (3) increased muscle soreness; and (4) reduced muscle glycogen. If endurance training quality is consistently compromised during the course of a specific concurrent training program, optimal endurance development may be limited. Whilst the link between acute responses of training and subsequent training adaptation has not been fully established, there is some evidence suggesting that cumulative effects of fatigue may contribute to limiting optimal endurance development. Thus, the current review will (1) explore cross-sectional studies that have reported impaired endurance performance following a single, or multiple bouts, of resistance training; (2) identify the potential impact of fatigue on chronic endurance development; (3) describe the implications of fatigue on the quality of endurance training sessions during concurrent training, and (4) explain the mechanisms contributing to resistance training-induced attenuation on endurance performance from neurological, biomechanical and metabolic standpoints. Increasing the awareness of resistance training-induced fatigue may encourage coaches to consider modulating concurrent training variables (e.g., order of training mode, between-mode recovery period, training intensity, etc.) to limit the carry-over effects of fatigue from resistance to endurance training sessions.

Strength training with blood flow restriction, or KAATSU training, has been shown to be as effective as conventional strength training to promote muscular strength and hypertrophy. Several mechanisms have been suggested as hypotheses to explain the adaptations arising from this training method. Among these is metabolic stress, which exerts important physiological effects and may influence the training adaptations in question. In addition, hypoxia produced by the technique may change the neural recruitment pattern. Growth hormone (GH) concentrations increase as a result of practicing this method, which can trigger an increase in plasmatic and, perhaps, muscular insulin-like growth factor-1 (IGF-1) concentrations. The increase in concentrations of these factors can play a leading role in responses to KAATSU training. Among the effects of the GH/IGF-1 axis in muscle cells is the increase in the signalling pathway activity of the mammalian target of rapamycin (mTOR), which has been associated with increased protein synthesis. On the other hand, the decrease in the activity of the myostatin pathway, which has an antagonistic effect to mTOR, has been demonstrated after training with occlusion. Other factors, such as increases in the expression of heat shock proteins, may play an important role in adaptations to exercise. Nitric oxide synthase could increase nitric oxide concentration, which in turn has an effect on satellite cells and blood flow. However, despite the results obtained, the transfer to other situations (e.g. speed sports) is not yet clear.

Over the last several decades, neuroimaging research has identified age-related neural changes that occur during cognitive tasks. These changes are used to help researchers identify functional changes that contribute to age-related impairments in cognitive performance. One commonly reported example of such a change is an age-related decrease in the recruitment of posterior sensory regions coupled with an increased recruitment of prefrontal regions across multiple cognitive tasks. This shift is often described as a compensatory recruitment of prefrontal regions due to age-related sensory-processing deficits in posterior regions. However, age is not only associated with spatial shifts in recruitment, but also with temporal shifts, in which younger and older adults recruit the same neural region at different points in a task trial. The current study examines the possible contribution of temporal modifications in the often-reported posterior–anterior shift. Participants, ages 19–85, took part in a memory retrieval task with a protracted retrieval trial consisting of an initial memory search phase and a subsequent detail elaboration phase. Age-related neural patterns during search replicated prior reports of age-related decreases in posterior recruitment and increases in prefrontal recruitment. However, during the later elaboration phase, the same posterior regions were associated with age-related increases in activation. Further, ROI and functional connectivity results suggest that these posterior regions function similarly during search and elaboration. These results suggest that the often-reported posterior–anterior shift may not reflect the inability of older adults to engage in sensory processing, but rather a change in when they recruit this processing.SIGNIFICANCE STATEMENTThe current study provides evidence that the often-reported posterior–anterior shift in aging may not reflect a global sensory-processing deficit, as has often been reported, but rather a temporal modification in this processing in which older adults engage the same neural regions during a detail elaboration phase that younger adults engage during memory search. In other words, older adults may ultimately be able to engage the same processes as younger adults during some cognitive tasks when given the time to do so. Future research should examine the generalizability of this effect and the importance of encouraging older adults to engage in these processes through task instruction or questions.

Background Effective interventions are needed to improve brain function in mild cognitive impairment (MCI), an early stage of Alzheimer's disease (AD). The posterior cingulate cortex (PCC)/precuneus is a hub of the default mode network (DMN) and is preferentially vulnerable to disruption of functional connectivity in MCI and AD. Objective We investigated whether 12 weeks of aerobic exercise could enhance functional connectivity of the PCC/precuneus in MCI and healthy elders. Methods Sixteen MCI and 16 healthy elders (age range = 60-88) engaged in a supervised 12-week walking exercise intervention. Functional MRI was acquired at rest; the PCC/precuneus was used as a seed for correlated brain activity maps. Results A linear mixed effects model revealed a significant interaction in the right parietal lobe: the MCI group showed increased connectivity while the healthy elders showed decreased connectivity. In addition, both groups showed increased connectivity with the left postcentral gyrus. Comparing pre to post intervention changes within each group, the MCI group showed increased connectivity in 10 regions spanning frontal, parietal, temporal and insular lobes, and the cerebellum. Healthy elders did not demonstrate any significant connectivity changes. Conclusion The observed results show increased functional connectivity of the PCC/precuneus in individuals with MCI after 12 weeks of moderate intensity walking exercise training. The protective effects of exercise training on cognition may be realized through the enhancement of neural recruitment mechanisms, which may possibly increase cognitive reserve. Whether these effects of exercise training may delay further cognitive decline in patients diagnosed with MCI remains to be demonstrated.

Cognitive decline and symptoms of attention deficits, executive dysfunction, and memory impairments describe dementia in the elderly. This review focuses on particular frequency oscillations that occur within the affected brain regions which could be used to classify some idiopathic dementias as specific diseases and could contribute additional information to the clinical data in evaluating age changes that are of benefit for a treatment of cognitive alterations. The main question, whether the changes of event-related potentials (ERPs) and frequency band responses (ERBRs) for sensory stimuli are related to plasticity in neural recruitment during stabilization of sensory/cognitive mechanisms accompanying aging or are underlying pathological changes, remains unknown. We review the effect of aging on low (δ, θ, α) and high (β1, β2, γ1, γ2) ERBRs in an auditory discrimination sensorimotor tasks (low–frequency – right hand movement, high–frequency tone – left movement) at frontal, central, parietal and occipital cortical locations at short latency (post–stimulus interval 0–250 ms; putative sensory processing period) and long latency (250–600 ms; putative cognitive period). High tone stimulation and movement requirements lead to a delay of ERP components in elderly subjects and their amplitudes diminish with increasing age. The amplitudes of β2, γ, and low-frequency activity are more pronounced with progressive age, but the β1 component is less affected by age during the sensory processing. The age difference with respect to scalp distribution is tone-independent for δ/θ, but not for α-activity. Age- and tone-dependent α-changes are focused on frontal and sensorimotor areas. The low- and high-frequency amplitudes during the cognitive processing diminish with increasing age, except for the frontal β2 and γ high tone responses, while the β1 activity is more widespread than in the shorter latency period. This age difference increases in fronto–parietal direction more expressed after high tone stimulation. The age influences more the cognitive processes than the sensory ones.

With increasing popularity of internet streaming portals, the question why people develop excessive binge-watching behavior has become a focus of scientific research. The possible negative consequences of this behavior and its proximity to behavioral addictions are discussed. Since deficits of response inhibition and performance monitoring have been associated with substance use and addictive behaviors, we examined the hypothesis whether frequent binge watching is characterized by alterations in these processes. The current study examined response inhibition in a go/nogo task and performance monitoring in a flanker task using electroencephalography. Participants reported frequent binge-watching episodes (HBW, n = 35) or no binge-watching behavior (NBW, n = 33) during the past four weeks. Compared to the NBW group, HBW showed larger P3a and P3b during response inhibition and larger error-related negativity (ERN) for errors in the flanker task. Group differences in behavioral measures were not observed. The neurocognitive profile associated with frequent binge watching differs from externalizing disorders, such as substance use disorders and addictive behaviors, which are more likely to be associated with diminished amplitudes during response inhibition and performance monitoring. Current findings of increased activity in performance monitoring and inhibition tend to be associated with internalizing disorders. Therefore, symptoms such as anxiety and worry may play a role in the development of binge-watching behavior.

Objective Intracortical microelectrode implants can generate a tissue response hallmarked by glial scarring and neuron cell death within 100–150 μm of the biomaterial device. Many have proposed that any performance decline in intracortical microstimulation (ICMS) due to this foreign body tissue response could be offset by increasing the stimulation amplitude. The mechanisms of this approach are unclear, however, as there has not been consensus on how increasing amplitude affects the spatial and temporal recruitment patterns of ICMS. Approach We clarify these unknowns using in vivo two-photon imaging of mice transgenically expressing the calcium sensor GCaMP6s in Thy1 neurons or virally expressing the glutamate sensor iGluSnFr in neurons. Calcium and neurotransmitter activity are tracked in the neuronal somas and neuropil during long-train stimulation in Layer II/III of somatosensory cortex. Main results Neural calcium activity and glutamate release are dense and strongest within 20–40 μm around the electrode, falling off with distance from the electrode. Neuronal calcium increases with higher amplitude stimulations. During prolonged stimulation trains, a sub-population of somas fail to maintain calcium activity. Interestingly, neuropil calcium activity is 3-fold less correlated to somatic calcium activity for cells that drop-out during the long stimulation train compared to cells that sustain activity throughout the train. Glutamate release is apparent only within 20 μm of the electrode and is sustained for at least 10s after cessation of the 15 and 20 μA stimulation train, but not lower amplitudes. Significance These results demonstrate that increasing amplitude can increase the radius and intensity of neural recruitment, but it also alters the temporal response of some neurons. Further, dense glutamate release is highest within the first 20 μm of the electrode site even at high amplitudes, suggesting that there may be spatial limitations to the amplitude parameter space. The glutamate elevation outlasts stimulation, suggesting that high-amplitude stimulation may affect neurotransmitter re-uptake. This ultimately suggests that increasing the amplitude of ICMS device stimulation may fundamentally alter the temporal neural response, which could have implications for using amplitude to improve the ICMS effect or “offset” the effects of glial scarring.

We sought to examine the effect of varying chemoreflex stress on sympathetic neural recruitment strategies during end-expiratory apnea. We hypothesized that increases in the firing frequency and probability of low-threshold axons at the asphyxic “break point” would be exaggerated during hypoxia and attenuated during hyperoxia. Multiunit muscle sympathetic nervous system activity (MSNA) (peroneal nerve microneurography) was measured in 10 healthy male subjects (31 ± 2 yr, 25 ± 1 kg/m2). Individuals completed maximal voluntary end-expiratory apnea under normoxic, hypoxic (inspired O2 fraction: 0.17 ± 0.01), and hyperoxic (inspired O2 fraction: 0.92 ± 0.03) conditions. Action potential (AP) patterns were examined from the filtered raw signal with wavelet-based methodology. Multiunit MSNA was increased ( P ≤ 0.05) during normoxic apnea, because of an increase in the frequency and incidence of AP spikes (243 ± 75 to 519 ± 134 APs/min, P = 0.048; 412 ± 133 to 733 ± 185 APs/100 heartbeats, P = 0.02). Multiunit MSNA increased from baseline ( P < 0.01) during hypoxic apnea, which was due to an increase in the frequency and incidence of APs (192 ± 59 to 952 ± 266 APs/min, P < 0.01; 326 ± 89 to 1,212 ± 327 APs/100 heartbeats, P < 0.01). Hypoxic apnea also resulted in an increase in the probability of a particular AP cluster firing more than once per burst ( P < 0.01). Hyperoxia attenuated any increase in MSNA with apnea, such that no changes in multiunit MSNA or frequency or incidence of AP spikes were observed ( P > 0.05). We conclude that increases in frequency and incidence of APs during apnea are potentiated during hypoxia and suppressed when individuals are hyperoxic, highlighting the important impact of chemoreflex stress in AP discharge patterns. The results may have implications for neural control of the circulation in recreational activities and/or clinical conditions prone to apnea. NEW & NOTEWORTHY Our results demonstrate that, compared with normoxic end-expiratory apnea, hypoxic apnea increases the frequency and incidence of action potential spikes as well as the probability of multiple firing. We further show that this response is suppressed when individuals are hyperoxic. These data highlight the potentially important role of chemoreflex stress in neural firing and recruitment and may have implications for neural control of the circulation in recreational and/or clinical conditions prone to apnea.

Detecting threat cues in the environment is an important aspect of social functioning. This is particularly true for adolescents as social threats become more salient and they navigate increasingly complex relationships outside of the family. Sleep relates to socioemotional processing throughout development, but the neurobiological relevance of sleep for threat perceptions in adolescence remains unknown. In the present study, 46 human adolescents (aged 14-18 years; 26 female) made judgments while undergoing a brain scan about whether unfamiliar, affectively neutral, computer-generated faces were threatening. Prior to the scan, several indices of sleep were assessed nightly for two-weeks using actigraphy. Sleep duration and poor sleep quality (defined as less efficiency, more awakenings, longer awakenings), factors influenced by biological and psychosocial changes during adolescence, elicited distinct neural activation patterns. Sleep duration was positively associated with activation in visual and face processing regions (occipital cortex, occipital fusiform gyrus), and this activation was linked to increased threat detection during the threat perception task. Sleep quality was negatively related to dorsolateral prefrontal cortex activation, which moderated the relation between reaction time and exposure to faces. Findings suggest reduced threat perception for adolescents with shorter sleep durations and more impulsive responding (as evinced by less consistent RT) for adolescents experiencing worse quality sleep. This study identifies an association between sleep and neural functioning relevant for socioemotional decision making during adolescence, a time when these systems undergo significant development.

Monitoring auditory brainstem responses (ABRs) is a common method of assessing auditory processing in non-model species. Although ABRs are widely used to compare auditory abilities across taxa, the extent to which different features of acoustic stimuli affect the ABR is largely unknown in most non-mammalian species. The authors investigated the effects of varying presentation rate and onset time to determine how different features of acoustic stimuli influence the ABR in Northern saw-whet owls (Aegolius acadicus), a species known for their unique auditory adaptations and hunting abilities. At presentation rates ranging from 21.1 to 51.1 s−1, there were no differences in the size or synchrony of ABRs, suggesting that stimuli can be presented at a relatively rapid rate to maximize the number of observations recorded for analysis. While increasing onset time was associated with a decrement in response size and synchrony, tonebursts with 1 ms onset times produced overgeneralized neural responses as a result of spectral splatter. This suggests that 2 to 3 ms onset times may balance the trade-off between response synchrony and frequency specificity when comparing relative neural recruitment across frequencies. These findings highlight the importance of considering stimulus parameters when interpreting ABR data.Monitoring auditory brainstem responses (ABRs) is a common method of assessing auditory processing in non-model species. Although ABRs are widely used to compare auditory abilities across taxa, the extent to which different features of acoustic stimuli affect the ABR is largely unknown in most non-mammalian species. The authors investigated the effects of varying presentation rate and onset time to determine how different features of acoustic stimuli influence the ABR in Northern saw-whet owls (Aegolius acadicus), a species known for their unique auditory adaptations and hunting abilities. At presentation rates ranging from 21.1 to 51.1 s−1, there were no differences in the size or synchrony of ABRs, suggesting that stimuli can be presented at a relatively rapid rate to maximize the number of observations recorded for analysis. While increasing onset time was associated with a decrement in response size and synchrony, tonebursts with 1 ms onset times produced overgeneralized neural responses as a result o...

This paper presents a novel method for fast and optimal determination of recruitment (input–output, IO) curve parameters in neural stimulation. A sequential parameter estimation (SPE) method was developed based on the Fisher information matrix (FIM), with a stopping rule based on successively satisfying a specified estimation tolerance. Simulated motor responses evoked by transcranial magnetic stimulation (TMS) were used as a test bed. Performance of FIM-SPE was characterized in 10 177 simulation runs for various IO parameter values corresponding to different virtual subjects, and compared with uniform sampling. Unlike uniform sampling, FIM-SPE identifies and samples the areas of the IO curve that contain maximum information about the curve parameters. For the most relaxed stopping rule, the median number of samples required for convergence was only 17 for FIM-SPE versus 294 for uniform sampling. For the highest reliability stopping rule, more than 92% of the FIM-SPE runs converged, with a median of 88 samples, whereas all uniform sampling runs reached 1000 samples without converging. Compared to uniform sampling, FIM-SPE reduced estimation errors up to 2-fold and required 10 times fewer stimuli. FIM-SPE could improve the speed and accuracy of determination of IO curves for neural stimulation. A software implementation of the algorithm is provided online.