Neural Consequences Research Articles

Warm hands, warm hearts: An investigation of physical warmth as a prepared safety stimulus.

Recent work has demonstrated that social support figures seem to be particularly robust inhibitors of the Pavlovian fear response. Specifically, social support figures appear to act as prepared safety stimuli, stimuli that have played an important role in mammalian survival and are thus less easily associated with threat and more able to inhibit the fear response. Given some of the shared behavioral and neural consequences of both social support and physical warmth, as well as the importance of physical warmth for mammalian survival, we conducted a series of examinations designed to examine whether physical warmth is also a prepared safety stimulus. In two studies conducted in human adults, we examined whether a physically warm stimulus was less readily associated with threat (compared to soft or neutral stimuli; Study 1) and was able to inhibit the fear response elicited by other threatening cues (compared to neutral stimuli; Study 2). Results showed that physical warmth resisted association with threat (Study 1) and not only inhibited the fear response but also led to lasting inhibition even after the warm stimulus was removed (Study 2). Together, these studies indicate that physical warmth, like social support, meets the requirements of being a prepared safety stimulus, and they pave the way for future work to clarify the properties that enable cues in this category to naturally inhibit fear responding. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Considering hearing loss as a modifiable risk factor for dementia

ABSTRACT Introduction Accumulating evidence links hearing loss to impaired cognitive performance and increased risk for dementia. Hearing loss can lead to deafferentation-induced atrophy of frontotemporal brain regions and dysregulation of cognitive control networks from increased listening effort. Hearing loss is also associated with reduced social engagement, loneliness, and depression, which are independently associated with poor cognitive function. Areas Covered We summarize the evidence and postulated mechanisms linking hearing loss to dementia in older adults and synthesize the available literature demonstrating beneficial effects of hearing remediation on brain structure and function. Expert Opinion : Further research is needed to evaluate whether treatment of hearing loss may reduce risk of cognitive decline and improve neural consequences of hearing loss. Studies may investigate the pathologic mechanisms linking these late-life disorders and identify individuals vulnerable to dementia, and future clinical trials may evaluate whether hearing treatment may reduce the risk for dementia.

Music, Math, and Working Memory: Magnetoencephalography Mapping of Brain Activation in Musicians.

Musical transposing is highly demanding of working memory, as it involves mentally converting notes from one musical key (i.e., pitch scale) to another key for singing or instrumental performance. Because musical transposing involves mental adjustment of notes up or down by a specific amount, it may share cognitive elements with arithmetical operations of addition and subtraction. We compared brain activity during high and low working memory load conditions of musical transposing versus math calculations in classically trained musicians. Magnetoencephalography (MEG) was sensitive to differences of task and working memory load. Frontal-occipital connections were highly active during transposing, but not during math calculations. Right motor and premotor regions were highly active in the more difficult condition of the transposing task. Multiple frontal lobe regions were highly active across tasks, including the left medial frontal area during both transposing and calculation tasks but the right medial frontal area only during calculations. In the more difficult calculation condition, right temporal regions were highly active. In coherence analyses and neural synchrony analyses, several similarities were seen across calculation tasks; however, latency analyses were sensitive to differences in task complexity across the calculation tasks due to the high temporal resolution of MEG. MEG can be used to examine musical cognition and the neural consequences of music training. Further systematic study of brain activity during high versus low memory load conditions of music and other cognitive tasks is needed to illuminate the neural bases of enhanced working memory ability in musicians as compared to non-musicians.

P243. The Cognitive and Neural Impact of Uncontrollable Stress on Reward-Learning

Uncontrollable stress leads to learned helplessness, a risk-factor for depression. By manipulating controllability in the laboratory, we aimed to identify the cognitive and neural consequences of perceived lack of control on reward-learning.

Chronic early-life stress increases cognitive impulsivity and D2 immunoreactivity in the nucleus accumbens of adult rats.

Chronic early life stress (ECS) induced by limited bedding and nesting (LBN) material in rodents is a naturalistic stress model that mimics many of the behavioral and neural consequences of child abuse and neglect; however, the effect of ECS on adult impulsivity has never been studied. The aim of our work was to determine the effects of ECS on cognitive impulsivity and its relation to D2 immunoreactivity in the nucleus accumbens (NAc) and prefrontal cortex (PFC) of adult male rats. Sprague-Dawley rats were exposed to LBN from postnatal day 2 to 9. We evaluated dams' maternal behavior and offspring corticosterone levels. The rats' impulsive cognitive behavior was evaluated by a delay-discounting task (transitional bridge) on P70, and we evaluated D2 receptors by immunostaining. Our results indicated that ECS affected maternal behavior in the dams and increased pups' corticosterone levels at P9, but not in adults. ECS rats showed lower frequencies of choosing the delayed reinforcer and shorter latencies to cross on the delay-discounting task. In addition, ECS rats showed increased D2 immunoreactivity in the NAc when compared with controls. Our data suggest that ECS can cause impulsive behaviors in adult rats characterized by less convenient choices, likely related to an increase in D2 receptors in the NAc. These findings could contribute to our understanding of the effects of child abuse and neglect on impulsive behavior.

Hearing Instability in Children with Congenital Cytomegalovirus: Evidence and Neural Consequences.

Sensorineural hearing loss (SNHL) is a common sequela of congenital cytomegalovirus (cCMV), potentially exacerbating neurocognitive delay. The objectives of this study were to assess: (1) age at which SNHL in children with cCMV; (2) stimulability of the auditory system in children with cCMV following cochlear implantation (CI); and (3) whether features of magnetic resonance imaging (MRI) potentially are predictive of hearing outcomes. In this retrospective study of a prospectively acquired cohort, 123 children with cCMV who were referred for hearing loss at a single tertiary referral hospital over 20 years were compared with an unmatched comparative group of 90 children with GJB2-related deafness. Outcome measures were results of newborn hearing screening (NHS), behavioral audiograms, and, in a subgroup of cochlear implant (CI) users, responses from the auditory nerve and brainstem evoked by CI at initial activation, as well as lesional volume of FLAIR-hyperintense signal alterations on MRI. All but 3 of 123 children with cCMV had confirmed and persistent SNHL. At birth, 113 children with cCMV underwent NHS, 31 (27%) passed in both ears and 23 (20%) passed in one ear (no NHS data in 10 children). At the first audiologic assessment, 32 of 123 (26%) had normal hearing bilaterally; 35 of 123 (28%) had unilateral SNHL; and 57 of 123 (46%) had bilateral SNHL. More than half (67 of 123, 54%) experienced hearing deterioration in at least one ear. Survival analyses suggested that 60% of children who developed SNHL did so by 2.5 years and 80% by 5 years. In the children who passed NHS in one or both ears, 50% developed hearing loss by 3.5 years in the ear, which passed unilaterally (n=23 ears), and 50% by 5 years in bilateral passes (n=62 ears). Hearing loss was significant enough in all but one child with isolated high-frequency loss for rehabilitation to be indicated. Hearing thresholds in individual ears were in the CI range in 83% (102 of 123), although duration of deafness was sufficient to preclude implantation at our center in 13 children with unilateral SNHL. Hearing aids were indicated in 16% (20 of 123). Responses from the auditory nerve and brainstem to initial CI stimulation were similar in children with cCMV-related SNHL compared with GJB2-related SNHL. Characteristic white matter changes on MRI were seen in all children with cCMV-related SNHL (n=91), but the lesion volume in each cortical hemisphere did not predict degree of SNHL. cCMV-related SNHL is often not detected by NHS but occurs with high prevalence in early childhood. Electrophysiological measures suggest equivalent stimulability of the auditory nerve and brainstem with CI in children with cCMV and GJB2-related SNHL. Hyperintense white matter lesions on FLAIR MRI are consistently present in children with cCMV-related SNHL but cannot be used to predict its time course or degree. Combined, the data show early and rapid deterioration of hearing in children with cCMV-related SNHL with potential for good CI outcomes if SNHL is identified and managed without delay. Findings support universal newborn screening for cCMV followed by careful audiological monitoring. 3 Laryngoscope, 132:S1-S24, 2022.

A blow to the head impairs the autoregulation of brain blood flow Neural consequences

A blow to the head impairs the autoregulation of brain blood flow Neural consequences

Potential Neural Consequences for Snakes Under Captive Management

Are snakes not thought to be intelligent because they’re really dumb, or are we making it impossible for them to reach their brainpower potential by forcing them to live in depressing, boring, stressful environments? Very little research exists about how environment affects snakes’ brains directly. This article looks at the neurological benefits of enrichment in other species and makes the case to extend what we know about them to snakes.

Women with abuse-related posttraumatic stress disorder sleep more fitfully but just as long as healthy controls: an actigraphic study.

Subjective reports of sleep impairments are common in individuals with posttraumatic stress disorder (PTSD), but objective assessments of sleep have yielded mixed results. We investigated sleep via actigraphy and e-diary on 6 consecutive nights in a group of 117 women with PTSD after childhood abuse (CA; PTSD group), a group of 31 mentally healthy women with a history of CA (healthy trauma controls, HTC group) and a group of 36 nontraumatized mentally healthy women (healthy controls, HC group). The PTSD group reported lower sleep quality, more nights with nightmares, and shorter sleep duration than both HTC and HC. Actigraphic measures showed more and longer sleep interruptions in the PTSD group compared to HTC and HC, but no difference in sleep duration. While the PTSD group underestimated their sleep duration, both HTC and HC overestimated their sleep duration. HTC did not differ from HC regarding sleep impairments. Sleep in women with PTSD after CA seems to be more fragmented but not shorter compared to sleep patterns of mentally healthy control subjects. The results suggest a stronger effect of PTSD psychopathology on sleep compared to the effect of trauma per se. Treating Psychosocial and Neural Consequences of Childhood Interpersonal Violence in Adults (RELEASE), https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00000000, German Clinical Trials registration number: DRKS00005578.

Neural prediction errors depend on how an expectation was formed

When a visual event is unexpected, because it violates a train of repeated events, it excites a greater positive electrical potential at sensors positioned above occipital-parietal human brain regions (the P300). Such events can also seem to have an increased duration relative to repeated (implicitly expected) events. However, recent behavioural evidence suggests that when events are unexpected because they violate a declared prediction–a guess–there is an opposite impact on duration perception. The neural consequences of incorrect declared predictions have not been examined. We replicated the finding whereby repetition violating events elicit a larger P300 response. However, we found that events that violated a declared prediction entrained an opposite pattern of response–a smaller P300. These data suggest that the neural consequences of a violated prediction are not uniform but depend on how the prediction was formed.

Sustained microglial activation in the area postrema of collagen-induced arthritis mice

BackgroundCentral nervous system (CNS)-mediated symptoms, such as fatigue, depression, and hyperalgesia, are common complications among patients with rheumatoid arthritis (RA). However, it remains unclear how the peripheral pathology of RA spreads to the brain. Accumulated evidence showing an association between serum cytokine levels and aberrant CNS function suggests that humoral factors participate in this mechanism. In contrast to the well-known early responses of microglia (CNS-resident immune cells) in the area postrema [AP; a brain region lacking a blood–brain barrier (BBB)] to experimental inflammation, microglial alterations in the AP during chronic inflammation like RA remain unclear. Therefore, to determine whether microglia in the AP can react to persistent autoimmune-arthritis conditions, we analyzed these cells in a mouse model of collagen-induced arthritis (CIA).MethodsMicroglial number and morphology were analyzed in the AP of CIA and control mice (administered Freund’s adjuvant or saline). Immunostaining for ionized calcium-binding adaptor molecule-1 was performed at various disease phases: “pre-onset” [post-immunization day (PID) 21], “establishment” (PID 35), and “chronic” (PID 56 and 84). Quantitative analyses of microglial number and morphology were performed, with principal component analysis used to classify microglia. Interleukin-1β (IL-1β) mRNA expression was analyzed by multiple fluorescent in situ hybridization and real-time polymerase chain reaction. Behavioral changes were assessed by sucrose preference test.ResultsMicroglia in the AP significantly increased in density and exhibited changes in morphology during the establishment and chronic phases, but not the pre-onset phase. Non-subjective clustering classification of cell morphology (CIA, 1,256 cells; saline, 852 cells) showed that the proportion of highly activated microglia increased in the CIA group during establishment and chronic phases. Moreover, the density of IL-1β-positive microglia, a hallmark of functional activation, was increased in the AP. Sucrose preferences in CIA mice negatively correlated with IL-1β expression in brain regions containing the AP.ConclusionsOur findings demonstrate that microglia in the AP can sustain their activated state during persistent autoimmune arthritis, which suggests that chronic inflammation, such as RA, may affect microglia in brain regions lacking a BBB and have various neural consequences.

Putative neural consequences of captivity for elephants and cetaceans.

The present review assesses the potential neural impact of impoverished, captive environments on large-brained mammals, with a focus on elephants and cetaceans. These species share several characteristics, including being large, wide-ranging, long-lived, cognitively sophisticated, highly social, and large-brained mammals. Although the impact of the captive environment on physical and behavioral health has been well-documented, relatively little attention has been paid to the brain itself. Here, we explore the potential neural consequences of living in captive environments, with a focus on three levels: (1) The effects of environmental impoverishment/enrichment on the brain, emphasizing the negative neural consequences of the captive/impoverished environment; (2) the neural consequences of stress on the brain, with an emphasis on corticolimbic structures; and (3) the neural underpinnings of stereotypies, often observed in captive animals, underscoring dysregulation of the basal ganglia and associated circuitry. To this end, we provide a substantive hypothesis about the negative impact of captivity on the brains of large mammals (e.g., cetaceans and elephants) and how these neural consequences are related to documented evidence for compromised physical and psychological well-being.

Brain Activation Induced by Myopic and Hyperopic Defocus From Spectacles.

Purpose: To assess neural changes in perceptual effects induced by myopic defocus and hyperopic defocus stimuli in ametropic and emmetropic subjects using functional magnetic resonance imaging (fMRI).Methods: This study included 41 subjects with a mean age of 26.0 ± 2.9 years. The mean spherical equivalence refraction was −0.54 ± 0.51D in the emmetropic group and −3.57 ± 2.27D in the ametropic group. The subjects were instructed to view through full refractive correction, with values of +2.00D to induce myopic defocus state and −2.00D to induce hyperopic defocus state. This was carried over in three random sessions. Arterial spin labeling (ASL) perfusion was measured using fMRI to obtain quantified regional cerebral blood flow (rCBF). Behavioral tests including distant visual acuity (VA) and contrast sensitivity (CS), were measured every 5 min for 30 min.Results: Myopic defocus induced significantly greater rCBF increase in four cerebral regions compared with full correction: right precentral gyrus, right superior temporal gyrus, left inferior parietal lobule, and left middle temporal gyrus (P < 0.001). The differences were less significant in low myopes than emmetropes. In the hyperopic defocus session, the increased responses of rCBF were only observed in the right and left precentral gyrus. Myopic defocused VA and CS improved significantly within 5 min and reached a plateau shortly after.Conclusion: This study revealed that myopic defocus stimuli can significantly increase blood perfusion in visual attention-related cerebral regions, which suggests a potential direction for future investigation on the relationship between retinal defocus and its neural consequences.

Mental fatigue correlates with depression of task-related network and augmented DMN activity but spares the reward circuit

Long-lasting and demanding cognitive activity typically leads to mental fatigue (MF). Indirect evidence suggests that MF may be caused by altered motivational processes. Here, we hypothesized that if MF consists in an alteration of motivational states, brain functional changes induced by MF could specifically affect the brain motivation circuit. In order to test this hypothesis, we devised a functional neuroimaging protocol to detect altered brain activity in reward-related brain regions in relation to cognitively induced mental fatigue.Twenty-five healthy participants underwent a FATIGUE and a CONTROL session on different days. In the FATIGUE session, MF was induced by performing a demanding cognitive task (adapted Stroop task) during 90 min, whereas in the CONTROL session, participants were asked to read magazines for the same period of time. We measured the neural consequences of the MF induction during a working memory task (Missing Number task) while modulating extrinsic motivation with block-wise variations in monetary reward. We also tracked participants’ momentary fatigue, anxiety state and intrinsic motivation prior to and following the MF inducement and measurement.Accuracy on the Missing Number Task was lower in the FATIGUE than in the CONTROL condition. Furthermore, subjective MF, but not its behavioral manifestations, was associated with hypoactivity of the task-evoked neural responses. Importantly, activity in regions modulated by reward showed no differences between FATIGUE and CONTROL sessions. In parallel, subjective MF correlated with increased on-task activity and resting-state functional connectivity in the default mode network.These results indicate that subjective mental fatigue is not associated with altered activity in the brain motivation circuit but rather with hypoactivity in task-specific brain regions as well as relative increases of activity and connectivity in the default mode network during and after the task.

Symbols Are Special: An fMRI Adaptation Study of Symbolic, Nonsymbolic, and Non-Numerical Magnitude Processing in the Human Brain.

How are different formats of magnitudes represented in the human brain? We used functional magnetic resonance imaging adaptation to isolate representations of symbols, quantities, and physical size in 45 adults. Results indicate that the neural correlates supporting the passive processing of number symbols are largely dissociable from those supporting quantities and physical size, anatomically and representationally. Anatomically, passive processing of quantities and size correlate with activation in the right intraparietal sulcus, whereas symbolic number processing, compared with quantity processing, correlates with activation in the left inferior parietal lobule. Representationally, neural patterns of activation supporting symbols are dissimilar from neural activation patterns supporting quantity and size in the bilateral parietal lobes. These findings challenge the longstanding notion that the culturally acquired ability to conceptualize symbolic numbers is represented using entirely the same brain systems that support the evolutionarily ancient system used to process quantities. Moreover, these data reveal that regions that support numerical magnitude processing are also important for the processing of non-numerical magnitudes. This discovery compels future investigations of the neural consequences of acquiring knowledge of symbolic numbers.

First Encounters: Effects of the Microbiota on Neonatal Brain Development.

The microbiota plays important roles in host metabolism and immunity, and its disruption affects adult brain physiology and behavior. Although such findings have been attributed to altered neurodevelopment, few studies have actually examined microbiota effects on the developing brain. This review focuses on developmental effects of the earliest exposure to microbes. At birth, the mammalian fetus enters a world teeming with microbes which colonize all body sites in contact with the environment. Bacteria reach the gut within a few hours of birth and cause a measurable response in the intestinal epithelium. In adults, the gut microbiota signals to the brain via the vagus nerve, bacterial metabolites, hormones, and immune signaling, and work in perinatal rodents is beginning to elucidate which of these signaling pathways herald the very first encounter with gut microbes in the neonate. Neural effects of the microbiota during the first few days of life include changes in neuronal cell death, microglia, and brain cytokine levels. In addition to these effects of direct exposure of the newborn to microbes, accumulating evidence points to a role for the maternal microbiota in affecting brain development via bacterial molecules and metabolites while the offspring is still in utero. Hence, perturbations to microbial exposure perinatally, such as through C-section delivery or antibiotic treatment, alter microbiota colonization and may have long-term neural consequences. The perinatal period is critical for brain development and a close look at microbiota effects during this time promises to reveal the earliest, most primary effects of the microbiota on neurodevelopment.

ENIGMA-Sleep: Challenges, opportunities, and the road map.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.

Infantile Iron Deficiency Affects Brain Development in Monkeys Even After Treatment of Anemia.

A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia (IDA) has been found to undermine both normal brain growth and neurobehavioral development. Even moderate ID may affect neural maturation because when iron is limited, it is prioritized first to red blood cells over the brain. A primate model was used to investigate the neural effects of a transient ID and if deficits would persist after iron treatment. The large size and postnatal growth of the monkey brain makes the findings relevant to the metabolic and iron needs of human infants, and initiating treatment upon diagnosis of anemia reflects clinical practice. Specifically, this analysis determined whether brain maturation would still be compromised at 1 year of age if an anemic infant was treated promptly once diagnosed. The hematology and iron status of 41 infant rhesus monkeys was screened at 2-month intervals. Fifteen became ID; 12 met clinical criteria for anemia and were administered iron dextran and B vitamins for 1–2 months. MRI scans were acquired at 1 year. The volumetric and diffusion tensor imaging (DTI) measures from the ID infants were compared with monkeys who remained continuously iron sufficient (IS). A prior history of ID was associated with smaller total brain volumes, driven primarily by significantly less total gray matter (GM) and smaller GM volumes in several cortical regions. At the macrostructual level, the effect on white matter volumes (WM) was not as overt. However, DTI analyses of WM microstructure indicated two later-maturating anterior tracts were negatively affected. The findings reaffirm the importance of iron for normal brain development. Given that brain differences were still evident even after iron treatment and following recovery of iron-dependent hematological indices, the results highlight the importance of early detection and preemptive supplementation to limit the neural consequences of ID.

Transcranial Direct Current Stimulation Enhances Episodic Memory in Healthy Older Adults by Modulating Retrieval-Specific Activation.

Memory decline has become an issue of major importance in the aging society. Anodal transcranial direct current stimulation (atDCS) is a viable tool to counteract age-associated episodic memory deterioration. However, the underlying neural mechanisms are unclear. In this single-blind, sham-controlled study, we combined atDCS and functional magnetic resonance imaging to assess the behavioral and neural consequences of multiple-session atDCS in older adults. Forty-nine healthy older adults received either 10 sessions of anodal or sham stimulation over the left dorsolateral prefrontal cortex. Before and after stimulation, participants performed a source memory task in the MRI scanner. Compared to sham stimulation, atDCS significantly improved item memory performance. Additionally, atDCS significantly increased regional brain activity around the stimulation area in the prefrontal cortex and extended to the bilateral anterior cingulate cortex. Neural changes in the prefrontal cortex correlated with memory gains. Our findings therefore indicate that multiple-session offline atDCS may improve memory in older adults by inducing neural alterations.

Bayesian decision-making under stress-preserved weighting of prior and likelihood information

A rich body of empirical work has addressed the question of how stress changes the way we memorize, learn, and make high-level decisions in complex scenarios. There is evidence that stress also changes the way we perceive the world, indicating influences on decision-making at lower levels. Surprisingly, as of yet, little research has been conducted in this domain. A few studies suggest that under stress, humans tend to eschew existing knowledge, and instead focus on novel input or information from bottom-up. Decision-making in the perceptual domain has been modeled with Bayesian frameworks. Here, existing knowledge about structures and statistics of our environment is referred to as prior, whereas sensory data are termed likelihood. In this study, we directly assessed whether stress, as induced by the socially evaluated cold pressure task (SECPT), would modulate low-level decisions, specifically the weight given to sensory information, and how people reacted to changes in prior and sensory uncertainty. We found that while the stress-inducing procedure successfully elicited subjective stress ratings aswell as stress relevant physiological paramters, it did not change participants’ average reliance on sensory information. Furthermore, it did not affect participants’ sensitivity to changes in prior and sensory uncertainty, with both groups able to detect it and modulate their behavior accordingly, in a way predicted by Bayesian statistics. Our results suggest that, contrary to our predictions, stress may not directly affect lower-level sensory-motor decisions. We discuss the findings in context of time scales of the stress reaction, linked to different neural and functional consequences.