Jeffrey M. Yau

Temporal frequency channels are linked across audition and touch

Temporal frequency is a fundamental sensory dimension in audition and touch. In audition, analysis of temporal frequency is necessary for speech and music perception; in touch, the spectral analysis of vibratory signals has been implicated in texture perception and in sensing the environment through tools. Environmental oscillations impinging upon the ear are generally thought to be processed independently of oscillations impinging upon the skin. Here, we show that frequency channels are perceptually linked across audition and touch. In a series of psychophysical experiments, we demonstrate that auditory stimuli interfere with tactile frequency perception in a systematic manner. Specifically, performance on a tactile-frequency-discrimination task is impaired when an auditory distractor is presented with the tactile stimuli, but only if the frequencies of the auditory and tactile stimuli are similar. The frequency-dependent interference effect is observed whether the distractors are pure tones or band-pass noise, so an auditory percept of pitch is not required for the effect to be produced. Importantly, distractors that strongly impair frequency discrimination do not interfere with judgments of tactile intensity. This surprisingly specific crosstalk between different modalities reflects the importance of supramodal representations of fundamental sensory dimensions.

Short-Term Human Prostate Primary Xenografts An in Vivo Model of Human Prostate Cancer Vasculature and Angiogenesis

Transgenic spontaneously occurring and transplantable xenograft models of adenocarcinoma of the prostate (CaP) are established tools for the study of CaP progression and metastasis. However, no animal model of CaP has been characterized that recapitulates the response of the human prostate vascular compartment to the evolving tumor microenvironment during CaP progression. We report that primary xenografts of human CaP and of noninvolved areas of the human prostate peripheral zone transplanted to athymic nude mice provide a unique model of human angiogenesis occurring in an intact human prostate tissue microenvironment. Angiogenesis in human kidney primary xenografts established from human renal cell carcinoma and noninvolved kidney tissue, a highly vascular organ and cancer, was compared with angiogenesis in xenografts from the relatively less vascularized prostate. Immunohistochemical identification of the human versus mouse host origin of the endothelial cells and of human endothelial cell proliferation in the human prostate and human kidney xenografts demonstrated that: (a) the majority of the vessels in primary xenografts of benign and malignant tissue of both organs were lined with human endothelial cells through the 30-day study period; (b) the mean vessel density was increased in both the CaP and benign prostate xenografts relative to the initial tissue, whereas there was no significant difference in mean vessel density in the renal cell carcinoma and benign kidney xenografts compared with the initial tissue; and (c) the number of vessels with proliferating endothelial cells in primary xenografts of CaP and benign prostate increased compared with their respective initial tissue specimens, whereas the number of vessels with proliferating endothelial cells decreased in the benign kidney xenografts. Short-term primary human prostate xenografts, therefore, represent a valuable in vivo model for the study of human angiogenesis within a human tissue microenvironment and for comparison of angiogenesis in CaP versus benign prostate.

Curvature Processing Dynamics in Macaque Area V4

We have previously analyzed shape processing dynamics in macaque monkey posterior inferotemporal cortex (PIT). We described how early PIT responses to individual contour fragments evolve into tuning for multifragment shape configurations. Here, we analyzed curvature processing dynamics in area V4, which provides feedforward inputs to PIT. We contrasted 2 hypotheses: 1) that V4 curvature tuning evolves from tuning for simpler elements, analogous to PIT shape synthesis and 2) that V4 curvature tuning emerges immediately, based on purely feedforward mechanisms. Our results clearly supported the first hypothesis. Early V4 responses carried information about individual contour orientations. Tuning for multiorientation (curved) contours developed gradually over ∼50 ms. Together, the current and previous results suggest a partial sequence for shape synthesis in ventral pathway cortex. We propose that early orientation signals are synthesized into curved contour fragment representations in V4 and that these signals are transmitted to PIT, where they are then synthesized into multifragment shape representations. The observed dynamics might additionally or alternatively reflect influences from earlier (V1, V2) and later (central and anterior IT) processing stages in the ventral pathway. In either case, the dynamics of contour information in V4 and PIT appear to reflect a sequential hierarchical process of shape synthesis.

Analogous intermediate shape coding in vision and touch.

We recognize, understand, and interact with objects through both vision and touch. Conceivably, these two sensory systems encode object shape in similar ways, which could facilitate cross-modal communication. To test this idea, we studied single neurons in macaque monkey intermediate visual (area V4) and somatosensory (area SII) cortex, using matched shape stimuli. We found similar patterns of shape sensitivity characterized by tuning for curvature direction. These parallel tuning patterns imply analogous shape coding mechanisms in intermediate visual and somatosensory cortex.

ANDROGEN DEPRIVATION INDUCES RAPID INVOLUTION AND RECOVERY OF HUMAN PROSTATE VASCULATURE

The response of the prostate tissue microenvironment to androgen deprivation (AD) represents a critical component in the treatment of benign prostatic hyperplasia and prostate cancer (CaP). Primary xenografts of human benign and CaP tissue transplanted to immunocompromized SCID mice were used to characterize the response of the prostate vasculature during the initial 14 days of AD. Microvessel density and vascular lumen diameter in the prostate xenografts decreased rapidly after AD, reached a nadir on days 2-4, and recovered between days 4 and 14. The number of apoptotic endothelial cells peaked on day 2 after AD and decreased to precastration levels over days 4-7. Leakage of vascular contents in the interstitial space was apparent between days 1 and 3 after AD; however, the vascular permeability barrier reestablished between days 7 and 14. Expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor-2, and basic fibroblast growth factor protein increased in endothelial cells between days 2 and 4 after AD, which preceded vascular recovery and appeared to be a direct and specific response of the endothelial cells to AD. Lack of comparable upregulation of these genes in primary cultures of human prostate endothelial cells in response to AD suggests a role for paracrine signaling mediated through stromal or epithelial cells. VEGF-A expression by prostate endothelial cells appears to represent a key facilitator of the vascular rebound in human prostate tissue induced by removal of circulating testicular androgens.

Representation of tactile curvature in macaque somatosensory area 2

Tactile shape information is elaborated in a cortical hierarchy spanning primary (SI) and secondary somatosensory cortex (SII). Indeed, SI neurons in areas 3b and 1 encode simple contour features such as small oriented bars and edges, whereas higher order SII neurons represent large curved contour features such as angles and arcs. However, neural coding of these contour features has not been systematically characterized in area 2, the most caudal SI subdivision in the postcentral gyrus. In the present study, we analyzed area 2 neural responses to embossed oriented bars and curved contour fragments to establish whether curvature representations are generated in the postcentral gyrus. We found that many area 2 neurons (26 of 112) exhibit clear curvature tuning, preferring contours pointing in a particular direction. Fewer area 2 neurons (15 of 112) show preferences for oriented bars. Because area 2 response patterns closely resembled SII patterns, we also compared area 2 and SII response time courses to characterize the temporal dynamics of curvature synthesis in the somatosensory system. We found that curvature representations develop and peak concurrently in area 2 and SII. These results reveal that transitions from orientation tuning to curvature selectivity in the somatosensory cortical hierarchy occur within SI rather than between SI and SII.

Textural timbre: The perception of surface microtexture depends in part on multimodal spectral cues.

During haptic exploration of surfaces, complex mechanical oscillations – of surface displacement and air pressure – are generated, which are then transduced by receptors in the skin and in the inner ear. Tactile and auditory signals thus convey redundant information about texture, partially carried in the spectral content of these signals. It is no surprise, then, that the representation of temporal frequency is linked in the auditory and somatosensory systems. An emergent hypothesis is that there exists a supramodal representation of temporal frequency, and by extension texture.

Separate mechanisms for audio-tactile pitch and loudness interactions.

A major goal in perceptual neuroscience is to understand how signals from different sensory modalities are combined to produce stable and coherent representations. We previously investigated interactions between audition and touch, motivated by the fact that both modalities are sensitive to environmental oscillations. In our earlier study, we characterized the effect of auditory distractors on tactile frequency and intensity perception. Here, we describe the converse experiments examining the effect of tactile distractors on auditory processing. Because the two studies employ the same psychophysical paradigm, we combined their results for a comprehensive view of how auditory and tactile signals interact and how these interactions depend on the perceptual task. Together, our results show that temporal frequency representations are perceptually linked regardless of the attended modality. In contrast, audio-tactile loudness interactions depend on the attended modality: Tactile distractors influence judgments of auditory intensity, but judgments of tactile intensity are impervious to auditory distraction. Lastly, we show that audio-tactile loudness interactions depend critically on stimulus timing, while pitch interactions do not. These results reveal that auditory and tactile inputs are combined differently depending on the perceptual task. That distinct rules govern the integration of auditory and tactile signals in pitch and loudness perception implies that the two are mediated by separate neural mechanisms. These findings underscore the complexity and specificity of multisensory interactions.

Feeling form: the neural basis of haptic shape perception.

The tactile perception of the shape of objects critically guides our ability to interact with them. In this review, we describe how shape information is processed as it ascends the somatosensory neuraxis of primates. At the somatosensory periphery, spatial form is represented in the spatial patterns of activation evoked across populations of mechanoreceptive afferents. In the cerebral cortex, neurons respond selectively to particular spatial features, like orientation and curvature. While feature selectivity of neurons in the earlier processing stages can be understood in terms of linear receptive field models, higher order somatosensory neurons exhibit nonlinear response properties that result in tuning for more complex geometrical features. In fact, tactile shape processing bears remarkable analogies to its visual counterpart and the two may rely on shared neural circuitry. Furthermore, one of the unique aspects of primate somatosensation is that it contains a deformable sensory sheet. Because the relative positions of cutaneous mechanoreceptors depend on the conformation of the hand, the haptic perception of three-dimensional objects requires the integration of cutaneous and proprioceptive signals, an integration that is observed throughout somatosensory cortex.

Dissecting neural circuits for multisensory integration and crossmodal processing.

We rely on rich and complex sensory information to perceive and understand our environment. Our multisensory experience of the world depends on the brains remarkable ability to combine signals across sensory systems. Behavioural, neurophysiological and neuroimaging experiments have established principles of multisensory integration and candidate neural mechanisms. Here we review how targeted manipulation of neural activity using invasive and non-invasive neuromodulation techniques have advanced our understanding of multisensory processing. Neuromodulation studies have provided detailed characterizations of brain networks causally involved in multisensory integration. Despite substantial progress, important questions regarding multisensory networks remain unanswered. Critically, experimental approaches will need to be combined with theory in order to understand how distributed activity across multisensory networks collectively supports perception.