Deafness induces complete crossmodal plasticity in a belt region of dorsal auditory cortex.

Many neural areas, where patterned activity is lost following deafness, have the capacity to become activated by the remaining sensory systems. This crossmodal plasticity can be measured at perceptual/behavioural as well as physiological levels. The dorsal zone (DZ) of auditory cortex of deaf cats is involved in supranormal visual motion detection, but its physiological level of crossmodal reorganisation is not well understood. The present study of early-deaf DZ (and hearing controls) used multiple single-channel recording methods to examine neuronal responses to visual, auditory, somatosensory and combined stimulation. In early-deaf DZ, no auditory activation was observed, but 100% of the neurons were responsive to visual cues of which 21% were also influenced by somatosensory stimulation. Visual and somatosensory responses were not anatomically organised as they are in hearing cats, and fewer multisensory neurons were present in the deaf condition. These crossmodal physiological results closely correspond with and support the perceptual/behavioural enhancements that occur following hearing loss.

Development of multisensory processing in ferret parietal cortex.

It is well known that the nervous system adjusts itself to its environment during development. Although a great deal of effort has been directed towards understanding the developmental processes of the individual sensory systems (e.g., vision, hearing, etc.), only one major study has examined the maturation of multisensory processing in cortical neurons. Therefore, the present investigation sought to evaluate multisensory development in a different cortical region and species. Using multiple single-unit recordings in anaesthetised ferrets (n = 18) of different ages (from postnatal day 80 to 300), we studied the responses of neurons from the rostral posterior parietal (PPr) area to presentations of visual, tactile and combined visual-tactile stimulation. The results showed that multisensory neurons were infrequent at the youngest ages (pre-pubertal) and progressively increased through the later ages. Significant response changes that result from multisensory stimulation (defined as multisensory integration [MSI]) were observed in post-pubertal adolescent animals, and the magnitude of these integrated responses also increased across this age group. Furthermore, non-significant multisensory response changes were progressively increased in adolescent animals. Collectively, at the population level, MSI was observed to shift from primarily suppressive levels in infants to increasingly higher levels in later stages. These data indicate that, like the unisensory systems from which it is derived, multisensory processing shows developmental changes whose specific time course may be regionally and species-dependent.

Effects of developmental alcohol exposure on cortical multisensory integration.

Fetal alcohol spectrum disorder (FASD) is one of the most common causes of mental disabilities in the world with a prevalence of 1%-6% of all births. Sensory processing deficits and cognitive problems are a major feature in this condition. Because developmental alcohol exposure can impair neuronal plasticity, and neuronal plasticity is crucial for the establishment of neuronal circuits in sensory areas, we predicted that exposure to alcohol during the third trimester equivalent of human gestation would disrupt the development of multisensory integration (MSI) in the rostral portion of the posterior parietal cortex (PPr), an integrative visual-tactile area. We conducted in vivo electrophysiology in 17 ferrets from four groups (saline/alcohol; infancy/adolescence). A total of 1157 neurons were recorded after visual, tactile and combined visual-tactile stimulation. A multisensory (MS) enhancement or suppression is characterized by a significantly increased or decreased number of elicited spikes after combined visual-tactile stimulation compared to the strongest unimodal (visual or tactile) response. At the neuronal level, those in infant animals were more prone to show MS suppression whereas adolescents were more prone to show MS enhancement. Although alcohol-treated animals showed similar developmental changes between infancy and adolescence, they always 'lagged behind' controls showing more MS suppression and less enhancement. Our findings suggest that alcohol exposure during the last months of human gestation would stunt the development of MSI, which could underlie sensory problems seen in FASD.

Multisensory responses in a belt region of the dorsal auditory cortical pathway.

A basic function of the cerebral cortex is to receive and integrate information from different sensory modalities into a comprehensive percept of the environment. Neurons that demonstrate multisensory convergence occur across the necortex but are especially prevalent in higher order association areas. However, a recent study of a cat higher order auditory area, the dorsal zone (DZ) of auditory cortex, did not observe any multisensory features. Therefore, the goal of the present investigation was to address this conflict using recording and testing methodologies that are established for exposing and studying multisensory neuronal processing. Among the 482 neurons studied, we found that 76.6% were influenced by non-auditory stimuli. Of these neurons, 99% were affected by visual stimulation, but only 11% by somatosensory. Furthermore, a large proportion of the multisensory neurons showed integrated responses to multisensory stimulation, constituted a majority of the excitatory and inhibitory neurons encountered (as identified by the duration of their waveshape) and exhibited a distinct spatial distribution within DZ. These findings demonstrate that the DZ of auditory cortex robustly exhibits multisensory properties and that the proportions of multisensory neurons encountered are consistent with those identified in other higher order cortices.

Early hearing loss induces plasticity within extra-striate visual cortex.

Supranormal perceptual performance has been observed within the intact senses of early-deaf or blind humans and animals. For cortical areas deprived of their normal sensory input, numerous studies have shown that the lesioned modality is replaced by that of the intact sensory modalities through a process termed crossmodal plasticity. In contrast, little is known about the effects of loss of a particular sensory modality on the cortical representations of the remaining, intact sensory modalities. In the present study, an area of extrastriate visual cortex from early-deaf adult cats was examined for features of dendritic plasticity known to occur after early-deafness. Using light-microscopy of Golgi-stained pyramidal neurons from the posterolateral lateral suprasylvian (PLLS) cortex, dendritic spine density significantly increased (~19%), while spine head size was slightly but significantly decreased (~9%) following early hearing loss. Curiously, these changes were not localized to regions of the visual PLLS known to receive auditory inputs, but instead showed a broad pattern more reflective of the distribution of the area's visual features. Whereas hearing loss results in crossmodal plasticity in auditory cortices, the same peripheral lesion can also induce intramodal plasticity within representations of the intact sensory systems that may also contribute to supranormal performance.

Synaptic Basis for Cross-modal Plasticity: Enhanced Supragranular Dendritic Spine Density in Anterior Ectosylvian Auditory Cortex of the Early Deaf Cat.

In the cat, the auditory field of the anterior ectosylvian sulcus (FAES) is sensitive to auditory cues and its deactivation leads to orienting deficits toward acoustic, but not visual, stimuli. However, in early deaf cats, FAES activity shifts to the visual modality and its deactivation blocks orienting toward visual stimuli. Thus, as in other auditory cortices, hearing loss leads to cross-modal plasticity in the FAES. However, the synaptic basis for cross-modal plasticity is unknown. Therefore, the present study examined the effect of early deafness on the density, distribution, and size of dendritic spines in the FAES. Young cats were ototoxically deafened and raised until adulthood when they (and hearing controls) were euthanized, the cortex stained using Golgi-Cox, and FAES neurons examined using light microscopy. FAES dendritic spine density averaged 0.85 spines/µm in hearing animals, but was significantly higher (0.95 spines/µm) in the early deaf. Size distributions and increased spine density were evident specifically on apical dendrites of supragranular neurons. In separate tracer experiments, cross-modal cortical projections were shown to terminate predominantly within the supragranular layers of the FAES. This distributional correspondence between projection terminals and dendritic spine changes indicates that cross-modal plasticity is synaptically based within the supragranular layers of the early deaf FAES.

Single-unit analysis of somatosensory processing in the core auditory cortex of hearing ferrets.

The recent findings in several species that the primary auditory cortex processes non-auditory information have largely overlooked the possibility of somatosensory effects. Therefore, the present investigation examined the core auditory cortices (anterior auditory field and primary auditory cortex) for tactile responsivity. Multiple single-unit recordings from anesthetised ferret cortex yielded histologically verified neurons (n = 311) tested with electronically controlled auditory, visual and tactile stimuli, and their combinations. Of the auditory neurons tested, a small proportion (17%) was influenced by visual cues, but a somewhat larger number (23%) was affected by tactile stimulation. Tactile effects rarely occurred alone and spiking responses were observed in bimodal auditory-tactile neurons. However, the broadest tactile effect that was observed, which occurred in all neuron types, was that of suppression of the response to a concurrent auditory cue. The presence of tactile effects in the core auditory cortices was supported by a substantial anatomical projection from the rostral suprasylvian sulcal somatosensory area. Collectively, these results demonstrate that crossmodal effects in the auditory cortex are not exclusively visual and that somatosensation plays a significant role in modulation of acoustic processing, and indicate that crossmodal plasticity following deafness may unmask these existing non-auditory functions.

Crossmodal reorganization in the early deaf switches sensory, but not behavioral roles of auditory cortex.

It is well known that early disruption of sensory input from one modality can induce crossmodal reorganization of a deprived cortical area, resulting in compensatory abilities in the remaining senses. Compensatory effects, however, occur in selected cortical regions and it is not known whether such compensatory phenomena have any relation to the original function of the reorganized area. In the cortex of hearing cats, the auditory field of the anterior ectosylvian sulcus (FAES) is largely responsive to acoustic stimulation and its unilateral deactivation results in profound contralateral acoustic orienting deficits. Given these functional and behavioral roles, the FAES was studied in early-deafened cats to examine its crossmodal sensory properties as well as to assess the behavioral role of that reorganization. Recordings in the FAES of early-deafened adults revealed robust responses to visual stimulation as well as receptive fields that collectively represented the contralateral visual field. A second group of early-deafened cats was trained to localize visual targets in a perimetry array. In these animals, cooling loops were surgically placed on the FAES to reversibly deactivate the region, which resulted in substantial contralateral visual orienting deficits. These results demonstrate that crossmodal plasticity can substitute one sensory modality for another while maintaining the functional repertoire of the reorganized region.

Multisensory and unisensory neurons in ferret parietal cortex exhibit distinct functional properties.

Despite the fact that unisensory and multisensory neurons are comingled in every neural structure in which they have been identified, no systematic comparison of their response features has been conducted. Towards that goal, the present study was designed to examine and compare measures of response magnitude, latency, duration and spontaneous activity in unisensory and bimodal neurons from the ferret parietal cortex. Using multichannel single-unit recording, bimodal neurons were observed to demonstrate significantly higher response levels and spontaneous discharge rates than did their unisensory counterparts. These results suggest that, rather than merely reflect different connectional arrangements, unisensory and multisensory neurons are likely to differ at the cellular level. Thus, it can no longer be assumed that the different populations of bimodal and unisensory neurons within a neural region respond similarly to a given external stimulus.

A comparison of multisensory features of two auditory cortical areas: primary (A1) and higher-order dorsal zone (DZ).

From myriads of ongoing stimuli, the brain creates a fused percept of the environment. This process, which culminates in perceptual binding, is presumed to occur through the operations of multisensory neurons that occur throughout the brain. However, because different brain areas receive different inputs and have different cytoarchitechtonics, it would be expected that local multisensory features would also vary across regions. The present study investigated that hypothesis using multiple single-unit recordings from anesthetized cats in response to controlled, electronically-generated separate and combined auditory, visual, and somatosensory stimulation. These results were used to compare the multisensory features of neurons in cat primary auditory cortex (A1) with those identified in the nearby higher-order auditory region, the Dorsal Zone (DZ). Both regions exhibited the same forms of multisensory neurons, albeit in different proportions. Multisensory neurons exhibiting excitatory or inhibitory properties occurred in similar proportions in both areas. Also, multisensory neurons in both areas expressed similar levels of multisensory integration. Because responses to auditory cues alone were so similar to those that included non-auditory stimuli, it is proposed that this effect represents a mechanism by which multisensory neurons subserve the process of perceptual binding.

OpNotes and Clinical Exercises: Activities to Enhance the Clinical Context of the Preclerkship Anatomy Dissection Laboratory.

PROBLEM: Despite numerous pedagogical approaches and technologies now available for medical gross anatomy, students can find it difficult to translate what occurs in a dissection laboratory into the context of clinical practice. APPROACH: Using complementary and collaborative approaches at 2 different medical schools, Virginia Commonwealth University (VCU) and University of Maryland (UM), we designed and implemented a series of clinical activities in the preclerkship medical gross anatomy laboratory that directly link dissected structures to clinical procedures. These activities specifically direct students to perform simulated clinically related procedures on anatomic donors during laboratory dissection sessions. The activities are called OpNotes at VCU and Clinical Exercises at UM. Each activity in the VCU OpNotes requires about 15 minutes of group activity at the end of a scheduled laboratory and involves faculty to grade the student responses submitted via a web-based-assessment form. Each exercise in UM Clinical Exercises also requires about 15 minutes of group activity during the schedule laboratory but does not involve faculty to complete grading. OUTCOMES: Cumulatively, the activities in OpNotes and Clinical Exercises both brought clinical context directly to anatomical dissections. These activities began in 2012 at UM and 2020 at VCU, allowing a multiyear and multi-institute development and testing of this innovative approach. Student participation was high, and perception of its effectiveness was almost uniformly positive. NEXT STEPS: Future iterations of the program will work to assess the efficacy of the program as well as to streamline the scoring and delivery of the formative components. Collectively, we propose that the concept of executing clinic-like procedures on donors in anatomy courses is an effective means of enhancing learning in the anatomy laboratory while concurrently underscoring the relevance of basic anatomy to future clinical practice.

Dendritic spine density in multisensory versus primary sensory cortex.

In sensory areas, neuronal dendritic spines receive sensory-specific inputs whose net activity drives neuronal spiking responses to effective external stimuli. Previous studies indicate that neurons in primary sensory cortical areas, which largely receive inputs from a single sensory modality, exhibit an average of 0.5-1.4 dendritic spines/µm, depending on species. In higher-order, associational cortices, inputs converge from multiple sensory sources onto individual, multisensory neurons. This raises the question: when inputs from two different modalities converge onto individual neurons, how are the dendritic spines apportioned to subserve the generation of robust spiking responses to each modality? As inputs arrive from two different sensory sources, it might be expected that neurons in multisensory areas exhibit approximately double the spine density of neurons in areas that receive just one sensory input. The present study examined this possibility in Golgi-stained neurons from ferret primary auditory (A1) and somatosensory (S1) cortices, as well as from regions in which inputs from two different sensory modalities converge: the lateral rostral suprasylvian sulcus (LRSS) and the rostral posterior parietal (PPr) areas. Dendritic spine density (spines/µm) was measured for pyramidal neurons in layers 2-3 and layers 5-6 for each cortical area from three animals using light microscopy. Primary sensory regions A1 and S1 showed remarkably similar average spine densities (A1 = 1.27 spines/µm ± 0.3 s.d.; S1 = 1.14 spines/µm ± 0.3), but average spine densities from the multisensory areas were lower (LRSS = 0.98 ± 0.3; PPr = 1.04 ± 0.3). Thus, for a given cortical area, dendritic spine density appears to be determined by factors other than the levels of sensory modality convergence.

Adult deafness induces somatosensory conversion of ferret auditory cortex.

In response to early or developmental lesions, responsiveness of sensory cortex can be converted from the deprived modality to that of the remaining sensory systems. However, little is known about capacity of the adult cortex for cross-modal reorganization. The present study examined the auditory cortices of animals deafened as adults, and observed an extensive somatosensory conversion within as little as 16 days after deafening. These results demonstrate that cortical cross-modal reorganization can occur after the period of sensory system maturation.

Early hearing-impairment results in crossmodal reorganization of ferret core auditory cortex.

Numerous investigations of cortical crossmodal plasticity, most often in congenital or early-deaf subjects, have indicated that secondary auditory cortical areas reorganize to exhibit visual responsiveness while the core auditory regions are largely spared. However, a recent study of adult-deafened ferrets demonstrated that core auditory cortex was reorganized by the somatosensory modality. Because adult animals have matured beyond their critical period of sensory development and plasticity, it was not known if adult-deafening and early-deafening would generate the same crossmodal results. The present study used young, ototoxically-lesioned ferrets (n = 3) that, after maturation (avg. = 173 days old), showed significant hearing deficits (avg. threshold = 72 dB SPL). Recordings from single-units (n = 132) in core auditory cortex showed that 72% were activated by somatosensory stimulation (compared to 1% in hearing controls). In addition, tracer injection into early hearing-impaired core auditory cortex labeled essentially the same auditory cortical and thalamic projection sources as seen for injections in the hearing controls, indicating that the functional reorganization was not the result of new or latent projections to the cortex. These data, along with similar observations from adult-deafened and adult hearing-impaired animals, support the recently proposed brainstem theory for crossmodal plasticity induced by hearing loss.

An examination of somatosensory area SIII in ferret cortex.

A somatotopically organized region on the suprasylvian gyrus of the ferret was examined using multiunit recordings and anatomical tracer injections. This area, which contains a representation of the face, was bordered by the primary somatosensory area (SI), anteriorly, and by the visually responsive rostral posterior parietal cortex (PPr), posteriorly. Anatomical tracers revealed connections to this region from cortical areas MI, SI, MRSS, PPr, and the thalamic posterior nucleus. These results are consistent with previous work in ferrets as well as with the location, physiology, and connectivity of area SIII in cats. Given its associations, functional properties, location, and homology, it is proposed that this region represents the third cortical somatosensory area (SIII) in ferrets.

A simple vector-like law for perceptual information combination is also followed by a class of cortical multisensory bimodal neurons.

An interdisciplinary approach to sensory information combination shows a correspondence between perceptual and neural measures of nonlinear multisensory integration. In psychophysics, sensory information combinations are often characterized by the Minkowski formula, but the neural substrates of many psychophysical multisensory interactions are unknown. We show that audiovisual interactions - for both psychophysical detection threshold data and cortical bimodal neurons - obey similar vector-like Minkowski models, suggesting that cortical bimodal neurons could underlie multisensory perceptual sensitivity. An alternative Bayesian model is not a good predictor of cortical bimodal response. In contrast to cortex, audiovisual data from superior colliculus resembles the 'City-Block' combination rule used in perceptual similarity metrics. Previous work found a simple power law amplification rule is followed for perceptual appearance measures and by cortical subthreshold multisensory neurons. The two most studied neural cell classes in cortical multisensory interactions may provide neural substrates for two important perceptual modes: appearance-based and performance-based perception.

Crashing from cadaver to computer: Covid-driven crisis-mode pedagogy spawns active online substitute for teaching gross anatomy.

In early 2020, the Covid-19 crisis forced medical institutions worldwide to convert quickly to online platforms for content delivery. Although many components of medical education were adaptable to that format, anatomical dissection laboratory lost substantial content in that conversion, including features of active student participation, three-dimensional spatial relationships of structures, and the perception of texture, variation, and scale. The present study aimed to develop and assess online anatomy laboratory sessions that sought to preserve benefits of the dissection experience for first-year medical students. The online teaching package was based on a novel form of active videography that emulates eye movement patterns that occur during processes of visual identification, scene analysis, and learning. Using this video-image library of dissected materials, content was presented through asynchronous narrated laboratory demonstrations and synchronous/active video conference sessions and included a novel, video-based assessment tool. Data were obtained using summative assessments and a final course evaluation. Test scores for the online practical examination were significantly improved over those for previous in-person dissection-based examinations, as evidenced by several measures of performance (Mean: 2015-2019: 82.5%; 2020: 94.9%; P = 0.003). Concurrently, didactic test scores were slightly, but not significantly, improved (Mean: 2015-2019: 88.0%; 2020: 89.9%). Student evaluations of online sessions and overall course were highly positive. Results indicated that this innovative online teaching package can provide an effective alternative when in-person dissection laboratory is unavailable. Although this approach consumed considerable faculty time for video editing, further development will include video conference breakout rooms to emulate dissection small-group teamwork.

Neuroanatomical identification of crossmodal auditory inputs to interneurons in somatosensory cortex.

Multisensory convergence is the first, requisite step in the process that generates neural responses to events involving more than one sensory modality. Although anatomical studies have documented the merging of afferents from different sensory modalities within a given area, they do not provide insight into the architecture of connectivity at the neuronal level that underlies multisensory processing. In fact, few anatomical studies of multisensory convergence at the neuronal level have been conducted. The present study used a combination of tract-tracing, immunocytochemistry, and confocal microscopic techniques to examine the connections related to crossmodal auditory cortical inputs to somatosensory area SIV. Axons labeled from auditory cortex were found in contact with immunolabeled interneurons in SIV, some of which also colocalized vesicular glutamate transporter 1, indicating the presence of an active, glutamatergic synapse. No specific subtype of inhibitory interneuron appeared to be targeted by the crossmodal contacts. These results provide insight into the structural basis for multisensory processing at the neuronal level and offer anatomical evidence for the direct involvement of inhibitory interneurons in multisensory processing.

What is a multisensory cortex? A laminar, connectional, and functional study of a ferret temporal cortical multisensory area.

Now that examples of multisensory neurons have been observed across the neocortex, this has led to some confusion about the features that actually designate a region as "multisensory." While the documentation of multisensory effects within many different cortical areas is clear, often little information is available about their proportions or net functional effects. To assess the compositional and functional features that contribute to the multisensory nature of a region, the present investigation used multichannel neuronal recording and tract tracing methods to examine the ferret temporal region: the lateral rostral suprasylvian sulcal area. Here, auditory-tactile multisensory neurons were predominant and constituted the majority of neurons across all cortical layers whose responses dominated the net spiking activity of the area. These results were then compared with a literature review of cortical multisensory data and were found to closely resemble multisensory features of other, higher-order sensory areas. Collectively, these observations argue that multisensory processing presents itself in hierarchical and area-specific ways, from regions that exhibit few multisensory features to those whose composition and processes are dominated by multisensory activity. It seems logical that the former exhibit some multisensory features (among many others), while the latter are legitimately designated as "multisensory."

Dystrophic muscle distribution in late-stage muscular dystrophy.

There is scant information about the comprehensive distribution of dystrophic muscles in muscular dystrophy. Despite different clinical presentations of muscular dystrophy, a recent multi-center study concluded that phenotypic distribution of dystrophic muscles is independent of clinical phenotype and suggested that there is a common pattern of involved muscles. To evaluate this possibility, the present case report used cadaveric dissection to determine the whole-body distribution of fat-infiltrated, dystrophic muscles from a 72-year-old white male cadaver with adult-onset, late-stage muscular dystrophy. Severely dystrophic muscles occupied the pectoral, gluteal and pelvic regions, as well as the arm, thigh and posterior leg. In contrast, muscles of the head, neck, hands and feet largely appeared unaffected. Histopathology and a CT-scan supported these observations. This pattern of dystrophic muscles generally conformed with that described in the multi-center study, and provides prognostic insight for patients and the physicians treating them.