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.

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.

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.

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.

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.

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.

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.

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.

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.

Cadaver Rounds: A Comprehensive Exercise That Integrates Clinical Context Into Medical Gross Anatomy.

PROBLEM: The purpose of medical schools is to train students to care for patients; however, the temporal and conceptual gap between course work and patient care may induce students to undervalue preclinical course work, thereby decreasing learning and retention. Bringing clinical context into preclinical courses reduces this problem, and many preclinical programs incorporate "cameo" appearances of clinical material. In contrast, the authors describe a comprehensive program at Virginia Commonwealth University School of Medicine that uses the cadaver as the students' first patient to embed clinical context within preclinical anatomy. APPROACH: As the students' first patient, cadavers undergo modified physical exams, whole-body computed tomography scans, and pathology sample analysis. Students log daily dissection observations onto a "patient chart." Group findings are integrated, on a self-directed basis, into a final grand rounds-style presentation ("Cadaver Rounds") requiring students to synthesize longitudinally collected observations into a plausible clinical condition likely experienced by the cadaver-patient when alive. The entire exercise uses few additional contact hours (about six) and runs concurrently with the existing medical curriculum. OUTCOMES: According to course surveys used to assess students' perceptions of the relevance and effectiveness of Cadaver Rounds (2015-2017), the students' experience was highly positive. Participation by faculty and clinicians has been enthusiastic. NEXT STEPS: The authors hope both to identify additional authentic clinical tasks to import into the dissection lab and to partner with other programs to adopt and evaluate this clinically centered approach to anatomy.

Do the Different Sensory Areas Within the Cat Anterior Ectosylvian Sulcal Cortex Collectively Represent a Network Multisensory Hub?

Current theory supports that the numerous functional areas of the cerebral cortex are organized and function as a network. Using connectional databases and computational approaches, the cerebral network has been demonstrated to exhibit a hierarchical structure composed of areas, clusters and, ultimately, hubs. Hubs are highly connected, higher-order regions that also facilitate communication between different sensory modalities. One region computationally identified network hub is the visual area of the Anterior Ectosylvian Sulcal cortex (AESc) of the cat. The Anterior Ectosylvian Visual area (AEV) is but one component of the AESc that also includes the auditory (Field of the Anterior Ectosylvian Sulcus - FAES) and somatosensory (Fourth somatosensory representation - SIV). To better understand the nature of cortical network hubs, the present report reviews the biological features of the AESc. Within the AESc, each area has extensive external cortical connections as well as among one another. Each of these core representations is separated by a transition zone characterized by bimodal neurons that share sensory properties of both adjoining core areas. Finally, core and transition zones are underlain by a continuous sheet of layer 5 neurons that project to common output structures. Altogether, these shared properties suggest that the collective AESc region represents a multiple sensory/multisensory cortical network hub. Ultimately, such an interconnected, composite structure adds complexity and biological detail to the understanding of cortical network hubs and their function in cortical processing.

Synaptic distribution and plasticity in primary auditory cortex (A1) exhibits laminar and cell-specific changes in the deaf.

The processing sequence through primary auditory cortex (A1) is impaired by deafness as evidenced by reduced neuronal activation in A1 of cochlear-implanted deaf cats. Such a loss of neuronal excitation should be manifest as changes in excitatory synaptic number and/or size, for which the post-synaptic correlate is the dendritic spine. Therefore, the present study sought evidence for this functional disruption using Golgi-Cox/light microscopic techniques that examined spine-bearing neurons and their dendritic spine features across all laminae in A1 of early-deaf (ototoxic lesion <1 month; raised into adulthood >16 months) and hearing cats. Surprisingly, in the early-deaf significant increases in spine density and size were observed in the supragranular layers, while significant reductions in spine density were observed for spiny non-pyramidal, but not pyramidal, neurons in the granular layer. No changes in dendritic spine density consistent with loss of excitatory inputs were seen for infragranular neurons. These results indicate that long-term early-deafness induces plastic changes in the excitatory circuitry of A1 that are laminar and cell-specific. An additional finding was that, unlike the expected abundance of stellate neurons that characterize the granular layer of other primary sensory cortices, pyramidal neurons predominate within layer 4 of A1. Collectively, these observations are important for understanding how neuronal connectional configurations contribute to region-specific processing capabilities in normal brains as well as those with altered sensory experiences.

Species-dependent role of crossmodal connectivity among the primary sensory cortices.

When a major sense is lost, crossmodal plasticity substitutes functional processing from the remaining, intact senses. Recent studies of deafness-induced crossmodal plasticity in different subregions of auditory cortex indicate that the phenomenon is largely based on the "unmasking" of existing inputs. However, there is not yet a consensus on the sources or effects of crossmodal inputs to primary sensory cortical areas. In the present review, a rigorous re-examination of the experimental literature indicates that connections between different primary sensory cortices consistently occur in rodents, while primary-to-primary projections are absent/inconsistent in non-rodents such as cats and monkeys. These observations suggest that crossmodal plasticity that involves primary sensory areas are likely to exhibit species-specific distinctions.

Cortical multisensory connectivity is present near birth in humans.

How the newborn brain adapts to its new multisensory environment has been a subject of debate. Although an early theory proposed that the brain acquires multisensory features as a result of postnatal experience, recent studies have demonstrated that the neonatal brain is already capable of processing multisensory information. For multisensory processing to be functional, it is a prerequisite that multisensory convergence among neural connections occur. However, multisensory connectivity has not been examined in human neonates nor are its location(s) or afferent sources understood. We used resting state functional MRI (fMRI) in two independent cohorts of infants to examine the functional connectivity of two cortical areas known to be multisensory in adults: the intraparietal sulcus (IPS) and the superior temporal sulcus (STS). In the neonate, the IPS was found to demonstrate significant functional connectivity with visual association and somatosensory association areas, while the STS showed significant functional connectivity with the visual association areas, primary auditory cortex, and somatosensory association areas. Our findings establish that each of these areas displays functional communication with cortical regions representing various sensory modalities. This demonstrates the presence of cortical areas with converging sensory inputs, representing that the functional architecture needed for multisensory processing is already present within the first weeks of life.

Cortical and thalamic connectivity of the auditory anterior ectosylvian cortex of early-deaf cats: Implications for neural mechanisms of crossmodal plasticity.

Early hearing loss leads to crossmodal plasticity in regions of the cerebrum that are dominated by acoustical processing in hearing subjects. Until recently, little has been known of the connectional basis of this phenomenon. One region whose crossmodal properties are well-established is the auditory field of the anterior ectosylvian sulcus (FAES) in the cat, where neurons are normally responsive to acoustic stimulation and its deactivation leads to the behavioral loss of accurate orienting toward auditory stimuli. However, in early-deaf cats, visual responsiveness predominates in the FAES and its deactivation blocks accurate orienting behavior toward visual stimuli. For such crossmodal reorganization to occur, it has been presumed that novel inputs or increased projections from non-auditory cortical areas must be generated, or that existing non-auditory connections were 'unmasked.' These possibilities were tested using tracer injections into the FAES of adult cats deafened early in life (and hearing controls), followed by light microscopy to localize retrogradely labeled neurons. Surprisingly, the distribution of cortical and thalamic afferents to the FAES was very similar among early-deaf and hearing animals. No new visual projection sources were identified and visual cortical connections to the FAES were comparable in projection proportions. These results support an alternate theory for the connectional basis for cross-modal plasticity that involves enhanced local branching of existing projection terminals that originate in non-auditory as well as auditory cortices.

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.