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PubMed2004

P2Y-mediated Ca2+ response is spatiotemporally graded and synchronized in sensory neurons: a two-photon photolysis study.

ATP is thought to be an initiator and modulator of noxious pain sensation. We employed two-photon photolysis to apply ATP locally and transiently, thus mimicking ATP release upon cell damage or exocytosis. Using this technique, an increase in intracellular Ca2+ concentration ([Ca2+]i) was induced via P2Y receptors in individual sensory neurons, or in a neurite region. The ATP-induced [Ca2+]i rise was attenuated by applications of either a phospholipase C inhibitor, or inhibitors for IP3 or ryanodine receptors. These results indicate that intracellular Ca2+ stores play a major role in contributing to the increase in [Ca2+]i. Spatiotemporal analysis revealed that local and transient applications of ATP increased [Ca2+]i by release from intracellular stores, but in a unique, graded, and synchronized manner. 1) As the duration of local ATP application was prolonged, the latency decreased and the magnitude of the [Ca2+]i rise increased; 2) The time course of the rising phase of the [Ca2+]i response to ATP was essentially the same over the cell body, once [Ca2+]i had started to rise. It is anticipated that sensory responses may be modulated variably, depending on the spatiotemporal characteristics of the ATP-related [Ca2+]i profile.

Adenosine Triphosphate↗
PubMed2003

Animal models of bone metastasis.

BACKGROUND: Animal models are important tools to investigate the pathogenesis and develop treatment strategies for bone metastases in humans. However, there are few spontaneous models of bone metastasis despite the fact that rodents (rats and mice) and other animals (dogs and cats) often spontaneously develop cancer. Therefore, most experimental models of bone metastasis in rodents require injection or implantation of neoplastic cells into orthotopic locations, bones, or the left ventricle of the heart. METHODS: The current study reviews the natural incidence and clinical manifestation of bone metastases of mammary and prostate carcinoma in animals, as well as the experimental models developed in mice using animal and human-derived neoplasms. RESULTS: Rats, mice, dogs, and cats often develop spontaneous mammary carcinoma, but bone metastases are rare. Intact and neutered dogs develop prostate carcinoma that is usually androgen independent and may be associated with regional bone invasion or distant bone metastasis. Normal dog prostate tissue induces new bone formation in vivo and can serve as a model of osteoblastic metastasis without concurrent bone destruction. Experimental models of osteolytic, osteoblastic, and mixed osteolytic/osteoblastic bone metastases include syngeneic rodent neoplasms or human xenografts implanted at orthotopic sites (e.g., breast or prostate glands) in immunodeficient mice, injection of cancer cells into the left ventricle of the heart, or direct injection into bones. New transgenic mouse models of cancer have a low incidence of spontaneous bone metastasis, but cell lines derived from these tumors can be selected in vivo for increased incidence of bone metastasis. It is essential to validate and correctly interpret the lesions in models of bone metastasis to accurately correlate the data from animal models to human disease. Animal models have provided support for the "seed and soil" hypothesis of bone metastasis. However, the roles of vascular patterns in the metaphyses of long bones and rapid bone turnover in young animals in the pathogenesis of metastasis in experimental models are uncertain. Improvements in the imaging of experimental animals in vivo using fluorescent markers or light emitted from luciferase have led to increased sensitivity of detection and more accurate quantification of bone metastases. For example, imaging of human prostate carcinoma PC-3M cells transfected with luciferase, following injection into the left ventricle, has demonstrated that there is rapid localization of tumor cells to bones and other organs, such as the kidneys and lungs. CONCLUSIONS: Animal models of metastasis have supported drug development and have been useful for identification of metastasis suppressor and promoter genes as novel targets for the development of novel therapies. Further refinement of these models will involve spatiotemporal analysis of the metastatic process by imaging and use of image data to stage disease and guide tissue sampling for gene expression profiling via gene array technology. In the future, integrated analyses of these models will be needed to understand the complexities of this important disease process.

Animals↗
PubMed2025

Unveiling the Dynamics of SARS-CoV-2 Gamma and Delta Waves in Paraná, Brazil - Delta Displacing a Persistent Gamma Through Alternative Routes of Dispersal.

The Gamma and Delta variants of concern (VOCs) of SARS-CoV-2 drove the second and third wave in Brazil and significantly intensified the number of cases and deaths. In this study, we investigate the timeline and origins of the Gamma and Delta variants using a spatiotemporal analysis based on 1508 genomes collected between March and September 2021 from health administrative regions in Paraná state, Brazil. Our findings indicate that community transmission of Gamma-P.1 began in late 2020, with substantial contributions from the Northeast and North regions. In contrast, our analysis of the Delta-AY.101 genomes underscored the crucial role of Paraná in national-level transmission dynamics beginning in late March 2021. At a local level, the movement estimates inferred from the monophyletic clades showed that the Curitiba health region was the primary source for Gamma-P.1, with a substantial contribution from Londrina. This health-region also emerged as an important hub for Delta-AY.101. Our phylogeographical GLM analysis demonstrates that air travel fluxes and population size at the origin of locations were the strongest predictors of shaping SARS-CoV-2 dispersal dynamics within Paraná. In addition, viral load analysis suggests that Gamma-P.1 and Delta-AY.101 may have maintained a similarly high transmissibility potential throughout the evaluated months, providing insights into the prolonged co-circulation dynamics. Our study underscores the relevance of understanding SARS-CoV-2 introductions and regional circulation contributions at the country level to enhance public health preparedness and strengthen local surveillance programs.

Brazil↗
PubMed1993

The establishment of murine Hox-1 expression domains during patterning of the limb.

Region-specific expression patterns have been described recently for several candidate, developmental regulatory genes in the vertebrate limb. We have identified and mapped homeobox containing genes of the 5' part of the murine Hox-1 cluster by chromosomal walking. The expression of Hox-1.8, Hox-1.9, Hox-1.10, and a paralog of the Hox-4 cluster (Hox-4.5) were analyzed during stages when the developing limb pattern was being laid down. Each of these Hox genes was expressed in a restricted domain along the proximodistal axis of the limb at stage E 12.5. Only minor asymmetries were seen along the other two axes. A detailed spatiotemporal analysis of Hox expression, including three-dimensional reconstructions, revealed that the expression domains became progressively established between stages E 9.5 and E 12.5. Expression started from a small posterior and distal region and expanded toward the anterior part of the limb for 2 days. Depending on the gene and developmental stage, expression expands either along the ventral or the dorsal periphery. The establishment of the patterns was correlated to the growth process in the limb. Hox-1.8 and Hox-1.9 were also expressed in part of the somatopleure adjacent to the forelimb. The displacement of this domain toward the tip of the limb during development suggests that Hox-1.8 and Hox-1.9 were expressed in muscle precursor cells which migrate into the limb. The importance of these findings for the proposed models of limb pattern formation is discussed.

Amino Acid Sequence↗
PubMed2002

Somatosensory evoked magnetic fields following passive movement compared with tactile stimulation of the index finger.

Cortical processing of passive finger movement was assessed magnetoencephalographically in 12 healthy volunteers and compared with somatosensory evoked magnetic fields (SEF) following tactile stimulation. A new device comprising a clamp-like digit holder facilitated bilateral guidance of the briskly elevated index finger. Both passive movement and tactile stimulation induced activation of the contralateral primary somatosensory (SI) cortex, indicated by six SEF deflections with inter-individually rather consistent peak latencies of 20-230 ms following proprioceptive and 20-300 ms following tactile stimulation. SEF responses to the two stimulus modalities clearly differed with regard to peak latencies, amplitudes and orientations of equivalent current dipoles (ECDs). The strength and orientation of proprioception-related ECDs suggested sequential activation of SI generators, with possible involvement of areas 3a and/or 2 at around 20 ms, area 4 at approximate peak latencies of 65 and 100 ms and area 3b between 150 to 230 ms. Passive movement elicited additional activation of cortical regions outside SI, including the bilateral perisylvian regions and the contralateral cingulate gyrus at latencies of 40-470 and 150-500 ms respectively. The study provides new results with respect to the spatiotemporal analysis of proprioception-related cortical processing and may contribute to a better understanding of the modality-specific organization of the human somatosensory cortex.

Adult↗
PubMed1991

The functional anatomy of middle latency auditory evoked potentials.

The neural origins of middle latency auditory evoked potentials (MAEP) were studied in rat cortex. MAEP were mapped from the cortical surface with a high spatial resolution electrode array. Spatiotemporal analysis, based on multivariate statistical methods, was then used to relate putative neural generators of the MAEP complex to established cytoarchitectural anatomy. These data indicate that the MAEP waveform reflects systematic asynchronous activation of both primary and secondary auditory cortex during the processing of simple click stimuli.

Acoustic Stimulation↗
PubMed1995

The spatiotemporal organization of auditory, visual, and auditory-visual evoked potentials in rat cortex.

Four placements of an 8 x 8 channel microelectrode array were used to map auditory, visual, and combined auditory-visual evoked potentials (AEP, VEP, AVEP) from a total of 256 electrode sites over a 7 x 7 mm2 area including most of somatosensory, auditory, and visual cortex in the right hemisphere of the rat. The unimodal AEP and VEP consisted of an archetypal response sequence representing a systematic spatial and temporal activation of primary and secondary sensory cortex. Spatiotemporal analysis of these waveforms indicated that they could be decomposed into a small number of spatial and temporal components; components that are related to patterns of specific and non-specific thalamocortical projections connecting the auditory and visual nuclei of the thalamus with primary and secondary auditory and visual cortex. These data suggest that the AEP and VEP complex are the cortical reflection of asynchronous activation of parallel thalamocortical projection systems. The areal distribution of the AEP and VEP also overlapped, primarily in secondary auditory and visual cortex, indicating that these regions contain populations of cells responding to either modality. Polymodal auditory-visual stimulation resulted in unique activation of two isolated populations of neurons positioned in secondary auditory and secondary visual cortex which were revealed by difference waveforms, computed by subtracting the sum of the AEP and VEP from the AVEP complex. Retrograde labeling of the polymodal zones indicated that they receive parallel thalamocortical projections primarily from non-specific auditory and visual thalamic nuclei including the medial and dorsal divisions of the medial geniculate nucleus (MGm and MGd), the suprageniculate nucleus (SGN), and the lateral posterior nucleus (LP). The polymodal zone in visual cortex also receives specific projections from the dorsal division of the lateral geniculate nucleus (LGd). These data conform to a general model of thalamocortical organization in which specific thalamic nuclei with a high degree of modality specificity make restricted projections to primary sensory cortex and parts of secondary sensory cortex, and association thalamic nuclei with a high degree of sensory convergence make more divergent cortical projections. Primary and secondary sensory cortex, as well as distinct zones of polysensory cortex appear to be activated in tandem via parallel thalamocortical projections. Thus, the cerebral cortex must have simultaneous access to both unimodal and polymodal sensory information.

Animals↗
PubMed1989

Neuromagnetic field modeling of multiple brain regions producing interictal spikes in human epilepsy.

A method of spatiotemporal analysis, using multiple current dipoles to represent activity in multiple brain regions, was applied to the interpretation of extracranial neuromagnetic fields generated by epileptic spikes in patients with focal seizure disorders. This method permitted the identification and approximate localization of cellular currents within single and multiple brain regions engaged over the entire duration of the human epileptic spike complex. These results suggest that spatially and temporally overlapping electrical currents in human epileptic cortex may be investigated non-invasively in the magnetoencephalogram if appropriate physical models are applied.

Brain↗
PubMed1990

Bioregulatory mechanisms at the level of cell organelle interactions: microspectrofluorometric in situ studies.

The spatiotemporal analysis of bioregulatory mechanisms at the level of intracellular multienzyme complexes and organelle interactions is made possible by the availability of endogenous and exogenous fluorescence probes, the development of microspectrofluorometers allowing one- and two-dimensional scans of intracellular fluorescence reactions, and the use of micromanipulatory techniques enabling the rapid alteration of metabolic states. Absorbed photons are not only a tool for quantitative evaluation of metabolic processes, they can also trigger alterations of cell membranes and functions as mediated by photosensitizer drugs. In the hierarchy of intracellular organization different levels of complexity are accessible to study, such as the regulation of multienzyme complexes and the interaction of organelle complexes. Typical applications of these methods are the investigation of drug effects (e.g., on melanoma cells), metabolic and structural alterations (e.g., in cystic fibrosis and Gaucher fibroblasts), organelle interactions in cells treated with toxic agents. The implications are relevant to biotechnology for better control of metabolite production and processing, design and testing of new drugs, understanding of drug resistance and better targeting of drugs or probes to selected intracellular sites. In addition, such in vitro methods can contribute to the provision of an alternative to "whole animal experiments" as already achieved in human and mouse fibroblasts, hepatocytes, hepatoma, Swiss 3T3 cells and other cells in culture, especially with regards to an analysis of the action of xenobiotics and drugs in cell physiology and pathology, fluorescence recovery after photobleaching, study of cytoskeleton dynamics and multiparameter probing of organelle activity during in vitro wound repair.

Animals↗
PubMed2004

Prefrontal-cingulate activation during executive control: which comes first?

The Stroop test requires executive control functions, in particular inhibition of a learned routine (in this case, word reading). The spatiotemporal analysis of brain activation during Stroop task execution was performed in 16 healthy subjects using high-density event-related potentials (ERPs) and dipole source modeling (BESA software). Scalp ERP analysis revealed the neurophysiological substrate of the interference effect: first, a greater negativity in the incongruent as compared to the congruent and neutral conditions was found between 350 and 450 ms poststimulus over left frontocentral scalp regions. Source analysis of the difference wave (incongruent-congruent) indicated that a generator localized in left prefrontal cortex (PFC) contributed to this effect. Second, immediately after the first effect, a greater positivity in the incongruent as compared to the congruent and neutral conditions developed between 450 and 550 ms poststimulus over midline frontocentral scalp regions. A generator of this effect was located in right anterior cingulate cortex (ACC). ACC activation seems to follow the activation of PFC with some overlap between the two components. Possible interpretation of this finding is that PFC signals ACC when executive control is required and ACC implements the control.

Adult↗
PubMed2004

Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man.

The SOD1 mutant mouse is the most widely used model of human amyotrophic lateral sclerosis (ALS). To determine where and when the pathological changes of motor neuron disease begins, we performed a comprehensive spatiotemporal analysis of disease progression in SOD1(G93A) mice. Quantitative pathological analysis was performed in the same mice at multiple ages at neuromuscular junctions (NMJ), ventral roots, and spinal cord. In addition, a patient with sporadic ALS who died unexpectedly was examined at autopsy. Mice became clinically weak at 80 days and died at 131 +/- 5 days. At 47 days, 40% of end-plates were denervated whereas there was no evidence of ventral root or cell body loss. At 80 days, 60% of ventral root axons were lost but there was no loss of motor neurons. Motor neuron loss was well underway by 100 days. Microglial and astrocytic activation around motor neurons was not identified until after the onset of distal axon degeneration. Autopsy of the ALS patient demonstrated denervation and reinnervation changes in muscle but normal appearing motor neurons. We conclude that in this widely studied animal model of human ALS, and in this single human case, motor neuron pathology begins at the distal axon and proceeds in a "dying back" pattern.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Spatiotemporal pH dynamics following insertion of neural microelectrode arrays.

Insertion trauma is a critical issue when assessing intracortical electrophysiological and neurochemical recordings. Previous reports document a wide variety of insertion techniques with speeds ranging from 10 microm/s to 10 m/s. We hypothesize that insertion speed has an effect on tissue trauma induced by implantation of a neural probe. In order to monitor the neural interface during and after probe insertion, we have developed a silicon-substrate array with hydrous iridium oxide microelectrodes for potentiometric recording of extracellular pH (pH(e)), a measure of brain homeostasis. Microelectrode sites were sensitive to pH in the super-Nernstian range (-85.9 mV/pH unit) and selective over other analytes including ascorbic acid, Na(+), K(+), Ca(2+), and Mg(2+). Following insertion, arrays recorded either triphasic or biphasic pH(e) responses, with a greater degree of prolonged acidosis for insertions at 50 microm/s than at 0.5 mm/s or 1.0 mm/s (p<0.05). Spatiotemporal analysis of the recordings also revealed micro-scale variability in the pH(e) response along the array, even when using the same insertion technique. Implants with more intense acidosis were often associated histologically with blood along the probe tract. The potentiometric microsensor array has implications not only as a useful tool to measure extracellular pH, but also as a feedback tool for delivery of pharmacological agents to treat surgical brain trauma.

Acidosis↗
PubMed2005

Characterizing the topography of membrane receptors and signaling molecules from spatial patterns obtained using nanometer-scale electron-dense probes and electron microscopy.

The flow of information through a cell requires the constant remodeling of cell signaling networks. Thus, spatially and temporally resolved microscopy of signaling components is needed to understand the behavior of normal cells as well as to uncover abnormal behavior leading to human disease. Nanoprobe labeling and transmission electron microscopy of cytoplasmic face-up sheets of cell membrane have been developed as a high-resolution approach to map the interactions of proteins and lipid during cell signaling. Membrane sheets are labeled with 3-15 nm electron-dense probes for receptors, signaling proteins and lipids and micrographs record the distributions of the probes relative to each other and to surface features. Here, we establish computational methods to extract spatial coordinates of probes from micrographs, to analyze and statistically validate the clustering and co-clustering of these probes and to integrate results between experiments in order to establish the relative spatial distributions of single and multiple probes. Our analyses, and the resulting programs for automating data collection and for carrying out statistical and clustering analyses provide toolboxes specialized for the spatiotemporal analysis and modeling of signal transduction pathways.

Animals↗
PubMed2006

The neural basis of conditional reasoning: an event-related potential study.

The spatiotemporal analysis of brain activation during the execution of conditional reasoning tasks (the four inference forms: Modus Ponens (MP), Modus Tollens (MT), affirming the consequent (AC), and denying the antecedent (DA)) and one baseline task (BS) was performed in 12 normal young adult participants using high-density event-related brain potentials (ERPs). Results showed that the early components elicited by the five task types were not significantly different. Reasoning tasks elicited a more negative EPR deflection (N600) than did the BS task in the time window of 500-700 ms after onset of the minor premise. Dipole source analysis of the difference wave (MP-BS) suggested that a generator localized in the left anterior cingulate cortex (BA 24) was involved in the activation and the application of the inference rules. ERP components of the five tasks were similar in the subsequent time period between 700 and 1700 ms. Following that period, a greater negativity in the reasoning tasks, in comparison to the BS task, developed between 1700 and 2000 ms poststimulus over the left fronto-central scalp regions. A generator of this effect was located in the right anterior cingulate cortex (BA 24) and was possibly related to cognitive control. The results indicate that the cingulate cortex was activated by conditional reasoning tasks with purely abstract materials and support the view that human reasoning is not a unified phenomenon but is content-sensitive.

Adolescent↗
PubMed2006

El Niño effects on influenza mortality risks in the state of California.

Recent El Niño events have emphasized the need to develop modelling techniques to assess climate-related health events. Experts agree that climate changes affect the spread of infectious diseases and that the geographic range of infectious diseases may expand as a result of these changes. Nevertheless, the world health modelling community cannot yet predict, with reasonable accuracy, when or where exactly these effects will occur or how large the threat of these diseases will be to particular populations. This study compared the spatiotemporal patterns of influenza mortality risk in the state of California during El Niño vs normal weather periods. By applying a stochastic methodology to county-specific mortality data, various sources of uncertainty were accounted for, and informative influenza mortality maps and profiles were generated. This methodology enabled the detection of significant effects of climate change on the influenza risk distributions. Geographical maps of risk variation during El Niño differed from those during normal weather, the corresponding covariances exhibited distinct space-time dependence features, and the temporal mean mortality profiles were considerably higher during normal weather than during El Niño. These rather unexpected results of spatiotemporal analysis are worth further investigation that seeks substantive and biologically plausible explanations. The findings of this study can offer a methodological framework to evaluate public health management strategies.

Aged↗
PubMed2002

Acrylamide neuropathy. II. Spatiotemporal characteristics of nerve cell damage in brainstem and spinal cord.

Previous studies of acrylamide (ACR) neuropathy in rat PNS [Toxicol. Appl. Pharmacol. 151 (1998) 211] and cerebellum [Neurotoxicology, 2002a] have suggested that axon degeneration was not a primary effect and was, therefore, of unclear neurotoxicological significance. To continue morphological examination of ACR neurotoxicity in CNS, a cupric silver stain method was used to define spatiotemporal characteristics of nerve cell body, dendrite, axon and terminal degeneration in brainstem and spinal cord. Rats were exposed to ACR at a dose-rate of either 50 mg/kg per day (i.p.) or 21 mg/kg per day (p.o.), and at selected times brains and spinal cord were removed and processed for silver staining. Results show that intoxication at the higher ACR dose-rate produced a nearly pure terminalopathy in brainstem and spinal cord regions, ie. widespread nerve terminal degeneration and swelling were present in the absence of significant argyrophilic changes in neuronal cell bodies, dendrites or axons. Exposure to the lower ACR dose-rate caused initial nerve terminal argyrophilia in selected brainstem and spinal cord regions. As intoxication continued, axon degeneration developed in white matter of these CNS areas. At both dose-rates, argyrophilic changes in brainstem nerve terminals developed prior to the onset of significant gait abnormalities. In contrast, during exposure to the lower ACR dose-rate the appearance of axon degeneration in either brainstem or spinal cord was relatively delayed with respect to changes in gait. Thus, regardless of dose-rate, ACR intoxication produced early, progressive nerve terminal degeneration. Axon degeneration occurred primarily during exposure to the lower ACR dose-rate and developed after the appearance of terminal degeneration and neurotoxicity. Spatiotemporal analysis suggested that degeneration began at the nerve terminal and then moved as a function of time in a somal direction along the corresponding axon. These data suggest that nerve terminals are a primary site of ACR action and that expression of axonopathy is restricted to subchronic dosing-rates.

Acrylamide↗
PubMed2003

Acrylamide neuropathy. II. Spatiotemporal characteristics of nerve cell damage in brainstem and spinal cord.

Previous studies of acrylamide (ACR) neuropathy in rat PNS [Toxicol. Appl. Pharmacol. 151 (1998) 211] and cerebellum [NeuroToxicology 23 (2002) 397] have suggested that axon degeneration was not a primary effect and was, therefore, of unclear neurotoxicological significance. To continue morphological examination of ACR neurotoxicity in CNS, a cupric silver stain method was used to define spatiotemporal characteristics of nerve cell body, dendrite, axon and terminal degeneration in brainstem and spinal cord. Rats were exposed to ACR at a dose-rate of either 50 mg/kg per day (i.p.) or 21 mg/kg per day (p.o.), and at selected times brains and spinal cord were removed and processed for silver staining. Results show that intoxication at the higher ACR dose-rate produced a nearly pure terminalopathy in brainstem and spinal cord regions, i.e. widespread nerve terminal degeneration and swelling were present in the absence of significant argyrophilic changes in neuronal cell bodies, dendrites or axons. Exposure to the lower ACR dose-rate caused initial nerve terminal argyrophilia in selected brainstem and spinal cord regions. As intoxication continued, axon degeneration developed in white matter of these CNS areas. At both dose-rates, argyrophilic changes in brainstem nerve terminals developed prior to the onset of significant gait abnormalities. In contrast, during exposure to the lower ACR dose-rate the appearance of axon degeneration in either brainstem or spinal cord was relatively delayed with respect to changes in gait. Thus, regardless of dose-rate, ACR intoxication produced early, progressive nerve terminal degeneration. Axon degeneration occurred primarily during exposure to the lower ACR dose-rate and developed after the appearance of terminal degeneration and neurotoxicity. Spatiotemporal analysis suggested that degeneration began at the nerve terminal and then moved as a function of time in a somal direction along the corresponding axon. These data suggest that nerve terminals are a primary site of ACR action and that expression of axonopathy is restricted to subchronic dosing-rates.

Acrylamide↗
PubMed2000

Multisensory auditory-somatosensory interactions in early cortical processing revealed by high-density electrical mapping.

We investigated the time-course and scalp topography of multisensory interactions between simultaneous auditory and somatosensory stimulation in humans. Event-related potentials (ERPs) were recorded from 64 scalp electrodes while subjects were presented with auditory-alone stimulation (1000-Hz tones), somatosensory-alone stimulation (median nerve electrical pulses), and simultaneous auditory-somatosensory (AS) combined stimulation. Interaction effects were assessed by comparing the responses to combined stimulation with the algebraic sum of responses to the constituent auditory and somatosensory stimuli when they were presented alone. Spatiotemporal analysis of ERPs and scalp current density (SCD) topographies revealed AS interaction over the central/postcentral scalp which onset at approximately 50 ms post-stimulus presentation. Both the topography and timing of these interactions are consistent with multisensory integration early in the cortical processing hierarchy, in brain regions traditionally held to be unisensory.

Acoustic Stimulation↗