Quantifying myelin density in the feline auditory cortex.

The cerebral cortex comprises many distinct regions that differ in structure, function, and patterns of connectivity. Current approaches to parcellating these regions often take advantage of functional neuroimaging approaches that can identify regions involved in a particular process with reasonable spatial resolution. However, neuroanatomical biomarkers are also very useful in identifying distinct cortical regions either in addition to, or in place of functional measures. For example, differences in myelin density are thought to relate to functional differences between regions, are sensitive to individual patterns of experience, and have been shown to vary across functional hierarchies in a predictable manner. Accordingly, the current study provides quantitative stereological estimates of myelin density for each of the 13 regions that make up the feline auditory cortex. We demonstrate that significant differences can be observed between auditory cortical regions, with the highest myelin density observed in the regions that comprise the auditory core (i.e., the primary auditory cortex and anterior auditory field). Moreover, our myeloarchitectonic map suggests that myelin density varies in a hierarchical fashion that conforms to the traditional model of spatial organization in auditory cortex. Taken together, these results establish myelin as a useful biomarker for parcellating auditory cortical regions, and provide detailed estimates against which other, less invasive methods of quantifying cortical myelination may be compared.

Eight Weeks of Daily Cannabidiol Supplementation Improves Sleep Quality and Immune Cell Cytotoxicity.

BACKGROUND: The endocannabinoid system is active in nervous and immune cells and involves the expression of two cannabinoid receptor genes (CB1 and CB2), along with endogenous endocannabinoid ligands, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), and their synthetic enzymes. Cannabidiol (CBD) is a non-intoxicating exogenous cannabinoid agonist derived from plants that, at high doses, has received FDA approval as an anticonvulsant for epileptic seizures, and at low doses is marketed as a food-grade supplement for improved mental health, sleep quality, and immunological function. At present, the predominance of published CBD clinical research has focused on ameliorative or disease-specific intervention, with few trials investigating CBD effects in healthy populations. METHODS: This clinical study aimed to investigate the effects of 8 weeks of 50 mg oral CBD on mental health, sleep quantity and quality, and immune cell function in healthy, college-aged individuals. Twenty-eight participants (average age 25.9 ± 6.1 y) were randomized to receive either daily oral capsules of 50 mg of CBD (CB, n = 14) or a calorie-matched placebo (CN, n = 14). Participants completed pre- and post-intervention assessments, including anthropometric measurements, mental health surveys, sleep analysis, and immunological function assessments. RESULTS: After completing the 8-week intervention, there were no significant changes in body weight and BMI (CN: 1.09 ± 0.89%: CB: 1.41 ± 1.07%), or body fat percentage (CN: 9.01 ± 7.51%: CB: 8.57 ± 7.81%), respectively (values are % change pre to post, p > 0.05). There were also no significant differences between CB and CN groups with respect to mental health measures, sleep quantity, or circulating immunophenotype as a result of the intervention. However, the CB group experienced significant improvements in sleep quality measured objectively using a sleep questionnaire (p = 0.0023) and enhanced Natural Killer (NK) immune cell function assessed in situ (p = 0.0125). CONCLUSIONS: Eight weeks of daily 50 mg CBD may improve sleep quality, and NK immunosurveillance in healthy, younger adults.

Sign language experience has little effect on face and biomotion perception in bimodal bilinguals.

Sensory and language experience can affect brain organization and domain-general abilities. For example, D/deaf individuals show superior visual perception compared to hearing controls in several domains, including the perception of faces and peripheral motion. While these enhancements may result from sensory loss and subsequent neural plasticity, they may also reflect experience using a visual-manual language, like American Sign Language (ASL), where signers must process moving hand signs and facial cues simultaneously. In an effort to disentangle these concurrent sensory experiences, we examined how learning sign language influences visual abilities by comparing bimodal bilinguals (i.e., sign language users with typical hearing) and hearing non-signers. Bimodal bilinguals and hearing non-signers completed online psychophysical measures of face matching and biological motion discrimination. No significant group differences were observed across these two tasks, suggesting that sign language experience is insufficient to induce perceptual advantages in typical-hearing adults. However, ASL proficiency (but not years of experience or age of acquisition) was found to predict performance on the motion perception task among bimodal bilinguals. Overall, the results presented here highlight a need for more nuanced study of how linguistic environments, sensory experience, and cognitive functions impact broad perceptual processes and underlying neural correlates.

Effects of Oral Cannabidiol on Health and Fitness in Healthy Adults: An 8-Week Randomized Trial.

BACKGROUND: There is a lack of research on the effects of cannabidiol (CBD) on health-related fitness, physical activity, cognitive health, psychological wellbeing, and concentrations of C-reactive protein (CRP) in healthy individuals. CBD has potential anti-inflammatory and neuroprotective effects. METHODS: This study aimed to investigate the effects of 8 weeks of CBD on the above-mentioned measures in healthy individuals. Forty-eight participants were randomized into two groups receiving either oral capsules of 50 mg of CBD or a calorie-matched placebo daily. Participants completed pre- and post-intervention assessments, including blood draws, body composition, fitness, physical activity, and self-reported surveys. RESULTS: There were no significant differences between groups regarding body composition, aerobic fitness, muscular strength, physical activity, cognitive health, psychological wellbeing, and resting CRP concentrations. However, the placebo group experienced a decline in mean peak power and relative peak power compared to the CBD group. CONCLUSIONS: The results suggest that 8 weeks of CBD supplementation may prevent declines in anaerobic fitness over time. However, long-term CBD supplementation may not be beneficial for altering measures of health-related fitness, mental health, and inflammation in healthy individuals.

The gradient in gray matter thickness across auditory cortex and differential cortical thickness changes following perinatal deafness.

In the absence of hearing during development, the brain adapts and repurposes what was destined to become auditory cortex. As cortical thickness is commonly used as a proxy to identify cortical regions that have undergone plastic changes, the purpose of this investigation was to compare cortical thickness patterns between hearing and deaf cats. In this study, normal hearing (n = 29) and deaf (n = 26) cats were scanned to examine cortical thickness in hearing controls, as well as differential changes in thickness as a consequence of deafness. In hearing cats, a gradient in cortical thickness was identified across auditory cortex in which it is thinner in more dorsal regions and thicker in more ventral regions. Compared with hearing controls, differential thickening and thinning was observed in specific regions of deaf auditory cortex. More dorsal regions were found to be bilaterally thicker in the deaf group, while more ventral regions in the left hemisphere were thinner. The location and nature of these changes creates a gradient along the dorsoventral axis, wherein dorsal auditory cortical fields are thicker, whereas more ventral fields are thinner in deaf animals compared with hearing controls.

Emotional distraction and facilitation across sense and time.

Emotional stimuli can disrupt or enhance task performance according to factors that are presently poorly understood. One potentially important determinant is the sensory modality involved. In unimodal visual paradigms (visual task-irrelevant stimuli during a visual task) emotional stimuli frequently produce distraction effects; however, the effects across modalities appear more complex and may also depend on factors related to stimulus timing. It is entirely unclear how task-irrelevant visual stimuli impact auditory task performance in cross-modal paradigms. This project explored task performance as a function of sensory modality, emotional valence, and stimulus timing. In Study 1, participants (N = 50) completed a visual stimulus detection task in the presence of task-irrelevant negative and neutral images and sounds. Accuracy was disrupted in the presence of visual but not auditory emotional stimuli, particularly when the target and task-irrelevant stimulus appeared simultaneously. In Study 2, participants (N = 38) completed an equivalent auditory stimulus detection task. In sharp contrast to the effects observed with visual targets, response times and accuracy were enhanced in the presence of auditory emotional stimuli at the first timepoint but disrupted at later timepoints. However, there was no effect of task-irrelevant visual stimuli on auditory task performance. These findings demonstrate the importance of both sensory modality and timing in determining how emotional stimuli affect task performance and lay the groundwork for future studies examining the interaction between emotional and attentional processes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The relationship between multisensory associative learning and multisensory integration.

Integrating sensory information from multiple modalities leads to more precise and efficient perception and behaviour. The process of determining which sensory information should be perceptually bound is reliant on both low-level stimulus features, as well as multisensory associations learned throughout development based on the statistics of our environment. Here, we explored the relationship between multisensory associative learning and multisensory integration using encephalography (EEG) and behavioural measures. Sixty-one participants completed a three-phase study. First, participants were exposed to novel audiovisual shape-tone pairings with frequent and infrequent stimulus pairings and completed a target detection task. EEG recordings of the mismatch negativity (MMN) and P3 were calculated as neural indices of multisensory associative learning. Next, the same learned stimulus pairs were presented in audiovisual as well as unisensory auditory and visual modalities while both early (<100 ms) and late neural indices of multisensory integration were recorded. Finally, participants completed an analogous behavioural speeded-response task, with behavioural indices of multisensory gain calculated using the Race Model. Significant relationships were found in fronto-central and occipital areas between neural measures of associative learning and both early and late indices of multisensory integration in frontal and centro-parietal areas, respectively. Participants who showed stronger indices of associative learning also exhibited stronger indices of multisensory integration of the stimuli they learned to associate. Furthermore, a significant relationship was found between neural index of early multisensory integration and behavioural indices of multisensory gain. These results provide insight into the neural underpinnings of how higher-order processes such as associative learning guide multisensory integration.

Relationship between Speed of Response Inhibition and Ability to Suppress a Step in Midlife and Older Adults.

In young adults, performance on a test of response inhibition was recently found to be correlated with performance on a reactive balance test where automated stepping responses must occasionally be inhibited. The present study aimed to determine whether this relationship holds true in older adults, wherein response inhibition is typically deficient and the control of postural equilibrium presents a greater challenge. Ten participants (50+ years of age) completed a seated cognitive test (stop signal task) followed by a reactive balance test. Reactive balance was assessed using a modified lean-and-release system where participants were required to step to regain balance following perturbation, or suppress a step if an obstacle was present. The stop signal task is a standardized cognitive test that provides a measure of the speed of response inhibition called the Stop Signal Reaction Time (SSRT). Muscle responses in the legs were compared between conditions where a step was allowed or blocked to quantify response inhibition of the step. The SSRT was significantly related to leg muscle suppression during balance recovery in the stance leg. Thus, participants that were better at inhibiting their responses in the stop signal task were also better at inhibiting an unwanted leg response in favor of grasping a supportive handle. The relationship between a seated cognitive test using finger responses and leg muscle suppression when a step was blocked indicates a context-independent, generalized capacity for response inhibition. This suggests that a simple cognitive test such as the stop signal task could be used clinically to predict an individual's capacity for adapting balance reactions and fall risk. The present results provide support for future studies, with larger samples, to verify this relationship between stop signal reaction time and leg response during balance recovery.

Hearing loss and brain plasticity: the hyperactivity phenomenon.

Many aging adults experience some form of hearing problems that may arise from auditory peripheral damage. However, it has been increasingly acknowledged that hearing loss is not only a dysfunction of the auditory periphery but also results from changes within the entire auditory system, from periphery to cortex. Damage to the auditory periphery is associated with an increase in neural activity at various stages throughout the auditory pathway. Here, we review neurophysiological evidence of hyperactivity, auditory perceptual difficulties that may result from hyperactivity, and outline open conceptual and methodological questions related to the study of hyperactivity. We suggest that hyperactivity alters all aspects of hearing-including spectral, temporal, spatial hearing-and, in turn, impairs speech comprehension when background sound is present. By focusing on the perceptual consequences of hyperactivity and the potential challenges of investigating hyperactivity in humans, we hope to bring animal and human electrophysiologists closer together to better understand hearing problems in older adulthood.

Assessment of anesthesia on physiological stability and BOLD signal reliability during visual or acoustic stimulation in the cat.

BACKGROUND: Neuroimaging methods including fMRI provide powerful tools to observe whole-brain functional networks. This is particularly powerful in animal models, allowing these networks to be probed using complementary methods. However, most animals must be anesthetized for neuroimaging, giving rise to complications resulting from anesthetic effects on the animal's physiological and neurological functions. For example, an established protocol for feline neuroimaging involves co-administration of ketamine and isoflurane - the latter of which is known to suppress cortical function. NEW METHOD: Here, we compare this established protocol to alfaxalone, a single-agent anesthetic for functional neuroimaging. We first compare the two in a controlled environment to assess relative safety and to measure physiological stability over an extended time window. We then compare patterns of auditory and visually-evoked activity measured at 7  T to assess mean signal strength and between-subjects signal variability. RESULTS IN COMPARISON WITH EXISTING METHODS: We show that alfaxalone results in more stable respiratory rates over the 120 min testing period, with evidence of smaller between-measurements variability within this time window, when compared to ketamine plus isoflurane. Moreover, we demonstrate that both agents evoke similar mean BOLD signals across animals, but that alfaxalone elicits more consistent BOLD activity in response to sound stimuli across all ROIs observed. CONCLUSIONS: Alfaxalone is observed to be more physiologically stable, evoking a more consistent BOLD signal across animals than the co-administration of ketamine and isoflurane. Thus, an alfaxalone-based protocol may represent a better approach for neuroimaging in animal models requiring anesthesia.

What and How the Deaf Brain Sees.

Over the past decade, there has been an unprecedented level of interest and progress into understanding visual processing in the brain of the deaf. Specifically, when the brain is deprived of input from one sensory modality (such as hearing), it often compensates with supranormal performance in one or more of the intact sensory systems (such as vision). Recent psychophysical, functional imaging, and reversible deactivation studies have converged to define the specific visual abilities that are enhanced in the deaf, as well as the cortical loci that undergo crossmodal plasticity in the deaf and are responsible for mediating these superior visual functions. Examination of these investigations reveals that central visual functions, such as object and facial discrimination, and peripheral visual functions, such as motion detection, visual localization, visuomotor synchronization, and Vernier acuity (measured in the periphery), are specifically enhanced in the deaf, compared with hearing participants. Furthermore, the cortical loci identified to mediate these functions reside in deaf auditory cortex: BA 41, BA 42, and BA 22, in addition to the rostral area, planum temporale, Te3, and temporal voice area in humans; primary auditory cortex, anterior auditory field, dorsal zone of auditory cortex, auditory field of the anterior ectosylvian sulcus, and posterior auditory field in cats; and primary auditory cortex and anterior auditory field in both ferrets and mice. Overall, the findings from these studies show that crossmodal reorganization in auditory cortex of the deaf is responsible for the superior visual abilities of the deaf.

Motor preparation for compensatory reach-to-grasp responses when viewing a wall-mounted safety handle.

The present study explored how motor cortical activity was influenced by visual perception of complex environments that either afforded or obstructed arm and leg reactions in young, healthy adults. Most importantly, we focused on compensatory balance reactions where the arms were required to regain stability following unexpected postural perturbation. Our first question was if motor cortical activity from the hand area automatically corresponds to the visual environment. Affordance-based priming of the motor system was assessed using single-pulse Transcranial Magnetic Stimulation (TMS) to determine if visual access to a wall-mounted support handle influenced corticospinal excitability. We evaluated if hand actions were automatically facilitated and/or suppressed by viewing an available handle within graspable range. Our second question was if the requirement for rapid movement to recover balance played a role in modulating any affordance effect in the hands. The goal was to disentangle motor demands related to postural threat from the impact of observation alone. For balance trials, a custom-built, lean and release apparatus was used to impose temporally unpredictable postural perturbations. In all balance trials, perturbations were of sufficient magnitude to evoke a compensatory change-in-support response; therefore, any recovery action needed to carefully take into account the affordances and constraints of the perceived environment to prevent a fall. Consistent with our first hypothesis, activity in an intrinsic hand muscle was increased when participants passively viewed a wall-mounted safety handle, in both seated and standing contexts. Contrary to our second hypothesis, this visual priming was absent when perturbations were imposed and the handle was needed to regain balance. Our results reveal that motor set is influenced by simply viewing objects that afford a grasp. We suggest that such preparation may provide an advantage when generating balance recovery actions that require quickly grasping a supportive handle. This priming effect likely competes with other task-dependent influences that regulate cortical motor output. Future studies should expand from limitations inherent with single-pulse TMS alone, to determine if vision of our surrounding world influences motor set in other contexts (e.g., intensified postural threat) and investigate if this priming corresponds to overt behavior.

Modified Origins of Cortical Projections to the Superior Colliculus in the Deaf: Dispersion of Auditory Efferents.

Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (N = 5, 3 female) with perinatal-onset deafness. The superior colliculus was exposed to a retrograde pathway tracer, and subsequently labeled cells throughout the cerebrum were identified and quantified. Overall, the percentage of cortical projections arising from auditory cortex was substantially increased, not decreased, in early-deaf cats compared with intact animals. Furthermore, the distribution of labeled cortical neurons was no longer localized to a particular cortical subregion of auditory cortex but dispersed across auditory cortical regions. Collectively, these results demonstrate that, although patterns of cortical afferents are stable following perinatal deafness, the patterns of cortical efferents to the superior colliculus are highly mutable.SIGNIFICANCE STATEMENT When a sense is lost, the remaining senses are functionally enhanced through compensatory crossmodal plasticity. In deafness, brain regions that normally process sound contribute to enhanced visual and somatosensory perception. We demonstrate that hearing loss alters connectivity between sensory cortex and the superior colliculus, a midbrain region that integrates sensory representations to guide orientation behavior. Contrasting expectation, the proportion of projections from auditory cortex increased in deaf animals compared with normal hearing, with a broad distribution across auditory fields. This is the first description of changes in cortical efferents following sensory loss and provides support for models predicting an inability to form a coherent, multisensory percept of the environment following periods of abnormal development.

Cortical and thalamic connectivity to the second auditory cortex of the cat is resilient to the onset of deafness.

It has been well established that following sensory loss, cortical areas that would normally be involved in perceiving stimuli in the absent modality are recruited to subserve the remaining senses. Despite this compensatory functional reorganization, there is little evidence to date for any substantial change in the patterns of anatomical connectivity between sensory cortices. However, while many auditory areas are contracted in the deaf, the second auditory cortex (A2) of the cat undergoes a volumetric expansion following hearing loss, suggesting this cortical area may demonstrate a region-specific pattern of structural reorganization. To address this hypothesis, and to complement existing literature on connectivity within auditory cortex, we injected a retrograde neuronal tracer across the breadth and cortical thickness of A2 to provide the first comprehensive quantification of projections from cortical and thalamic auditory and non-auditory regions to the second auditory cortex, and to determine how these patterns are affected by the onset of deafness. Neural projections arising from auditory, visual, somatomotor, and limbic cortices, as well as thalamic nuclei, were compared across normal hearing, early-deaf, and late-deaf animals. The results demonstrate that, despite previously identified changes in A2 volume, the pattern of projections into this cortical region are unaffected by the onset of hearing loss. These results fail to support the idea that crossmodal plasticity reflects changes in the pattern of projections between cortical regions and provides evidence that the pattern of connectivity that supports normal hearing is retained in the deaf brain.

Effects of neonatal deafness on resting-state functional network connectivity.

Normal brain development depends on early sensory experience. Behavioral consequences of brain maturation in the absence of sensory input early in life are well documented. For example, experiments with mature, neonatally deaf human or animal subjects have revealed improved peripheral visual motion detection and spatial localization abilities. Such supranormal behavioral abilities in the nondeprived sensory modality are evidence of compensatory plasticity occurring in deprived brain regions at some point or throughout development. Sensory deprived brain regions may simply become unused neural real-estate resulting in a loss of function. Compensatory plasticity and loss of function are likely reflected in the differences in correlations between brain networks in deaf compared with hearing subjects. To address this, we used resting-state functional magnetic resonance imaging (fMRI) in lightly anesthetized hearing and neonatally deafened cats. Group independent component analysis (ICA) was used to identify 20 spatially distinct brain networks across all animals including auditory, visual, somatosensory, cingulate, insular, cerebellar, and subcortical networks. The resulting group ICA components were back-reconstructed to individual animal brains. The maximum correlations between the time-courses associated with each spatial component were computed using functional network connectivity (FNC). While no significant differences in the delay to peak correlations were identified between hearing and deaf cats, we observed 10 (of 190) significant differences in the amplitudes of between-network correlations. Six of the significant differences involved auditory-related networks and four involved visual, cingulate, or somatosensory networks. The results are discussed in context of known behavioral, electrophysiological, and anatomical differences following neonatal deafness. Furthermore, these results identify novel targets for future investigations at the neuronal level.

Catlas: An magnetic resonance imaging-based three-dimensional cortical atlas and tissue probability maps for the domestic cat (Felis catus).

Brain atlases play an important role in effectively communicating results from neuroimaging studies in a standardized coordinate system. Furthermore, brain atlases extend analysis of functional magnetic resonance imaging (MRI) data by delineating regions of interest over which to evaluate the extent of functional activation as well as measures of inter-regional connectivity. Here, we introduce a three-dimensional atlas of the cat cerebral cortex based on established cytoarchitectonic and electrophysiological findings. In total, 71 cerebral areas were mapped onto the gray matter (GM) of an averaged T1-weighted structural MRI acquired at 7 T from eight adult domestic cats. In addition, a nonlinear registration procedure was used to generate a common template brain as well as GM, white matter, and cerebral spinal fluid tissue probability maps to facilitate tissue segmentation as part of the standard preprocessing pipeline for MRI data analysis. The atlas and associated files can also be used for planning stereotaxic surgery and for didactic purposes.

Origins of thalamic and cortical projections to the posterior auditory field in congenitally deaf cats.

Crossmodal plasticity takes place following sensory loss, such that areas that normally process the missing modality are reorganized to provide compensatory function in the remaining sensory systems. For example, congenitally deaf cats outperform normal hearing animals on localization of visual stimuli presented in the periphery, and this advantage has been shown to be mediated by the posterior auditory field (PAF). In order to determine the nature of the anatomical differences that underlie this phenomenon, we injected a retrograde tracer into PAF of congenitally deaf animals and quantified the thalamic and cortical projections to this field. The pattern of projections from areas throughout the brain was determined to be qualitatively similar to that previously demonstrated in normal hearing animals, but with twice as many projections arising from non-auditory cortical areas. In addition, small ectopic projections were observed from a number of fields in visual cortex, including areas 19, 20a, 20b, and 21b, and area 7 of parietal cortex. These areas did not show projections to PAF in cats deafened ototoxically near the onset of hearing, and provide a possible mechanism for crossmodal reorganization of PAF. These, along with the possible contributions of other mechanisms, are considered.

Sensory Development: Brief Visual Deprivation Alters Audiovisual Interactions.

Two recent studies have independently demonstrated that short periods of visual deprivation early in human development can have long-term functional consequences on sensory perception and on the balance between auditory and visual attention.