Josef P. Rauschecker - US grants

DESCRIPTION: Multiple cortical maps and their functional specialization have been demonstrated extensively in the visual system of primates. Much less is known about multiple representations in the auditory cortex. This is surprising because a thorough knowledge of nonprimary auditory cortex is undoubtedly necessary for the ultimate understanding of the neural basis of speech perception and of a variety of central speech and hearing disorders. The goal of my research is to identify the role different areas in the auditory cortex of the rhesus monkey play in auditory perception, in auditory scene analysis, and in the neural decoding of complex sounds, particularly those relevant for acoustic communication. Analogies to feature extraction and figure-ground discrimination in the visual system will be drawn as closely as possible. Neurons in higher cortical areas are known to be selective for more complex stimuli. The first specific aim of this proposal is, therefore, to analyze, using complex sounds, the nature of stimulus preferences in single neurons of non primary auditory cortex in the rhesus monkey and the mechanisms for generating these preferences (Hypothesis 1: Neurons in non primary auditory cortex respond to progressively more complex sounds within a hierarchy of cortical areas). The use of behaviorally relevant, species-specific vocalizations and their component elements will receive particular attention for the analysis of single neurons in the superior temporal gyrus (STG). The response will be compared to those in primary auditory cortex. The second aim is then to investigate the organization of stimulus preferences into computational maps across the cortical surface in the STG, particularly the lateral belt areas (Hypothesis 2: Stimulus preferences within a certain parameter domain is organized in an orderly fashion parallel to the cortical surface). Thirdly, the connections between different cortical areas and their input from the thalamus will be identified using anatomical tracers injected into physiologically identified regions (Hypothesis 3: regions with similar stimulus preferences are connected to regions with the same preference, whereby a convergence from wider input regions takes place in hierarchically higher areas). The laminar organization of input/output connections in the cortex will receive particular attention through careful track reconstructions. This research will advance our understanding of the functional organization and specialization of the cerebral cortex in higher mammals and its role in sensory perception. In particular, it will aid our understanding of non primary auditory cortex and of the neural mechanisms underlying the processing of complex sounds. It will rejuvenate work on the neurobiology of acoustic communication in primates and thus provide an important link between the neuroethological work in more specialized species and functional brain imaging work in humans on auditory speech perception. Ultimately, it will aid the understanding of major dysfunctions of hearing, such as sensory and phonological aphasia and will enable us to design more appropriate auditory prostheses based upon processing principles in the central auditory system.

Speech perception is one of our most important abilities - something that we have an innate ability
for but nevertheless spend many years acquiring as children- and that is of the utmost
importance for us in social interactions. It is also one of the abilities more commonly affected by strokes as well as by hearing loss. Speech perception is characterized by considerable flexibility and robustness - we can understand speakers in noisy environments, and we can cope with
variations in the speaker's gender, accent, or mood, all of which affect the nature of the speech signal we need to decode. A better understanding of the neural basis of speech perception, thus, impacts on clinical issues such as recovery from aphasic stroke, as well as on educational neuroscience, inasmuch as the studies will have relevance for second language learning and the development of multilingual children. With support from the National Science Foundation, Dr. Josef Rauschecker seeks answers to understand the neural basis of speech perception. His studies will help to transfer knowledge gained from animal models of auditory perception toward the understanding of higher cognitive processes of speech and language perception in humans. The notions of hierarchical networks, processing streams, and higher-order computational maps have been used successfully in animal research on complex visual and auditory perception. Dr. Rauschecker will perform analogous investigations directly in humans using noninvasive,
high-resolution functional magnetic resonance imaging (fMRI) to determine activation of auditory cortices by speech and speech-like sounds. Using high-field fMRI the studies will not only determine the location of cortical areas activated by natural and synthetic speech sounds, as opposed to other sounds with similar complexity, but also for the first time reveal detailed
organizational principles of higher-order acoustic-phonetic feature maps within human auditory and language cortex. The studies will provide a wealth of new information in the under-researched field of higher auditory pathways in humans, as well as insight into general organizational principles of
functional architecture in cortical processing.

The broader impacts of this project include opportunities for hands-on research experience by undergraduate and graduate students in Cognitive Neuroscience. This direct immersion into ongoing research will lead to tighter integration of teaching and research. The funded project will
enhance the infrastructure for research at Georgetown University and contribute to two formal training programs offered at GU. The project will strive to increase further the number of minority students at all levels. It will broadly disseminate results through publications and public databases
to scientific as well as lay audiences, thus, enhancing scientific understanding by the public.

[unreadable] DESCRIPTION (provided by applicant): Vision has long served as a model system in health and disease for the analysis of perceptual and cognitive systems at the level of the cerebral cortex. Great progress has also been made in recent years regarding an understanding of higher cortical areas involved in auditory cognition. However, knowledge about auditory processing streams still lags far behind that in vision. We propose to use single-and multi-unit electrophysiology to study cortical areas along the superior temporal gyrus (STG) and sulcus (STS) in a nonhuman primate, the rhesus macaque, whose cortical organization is similar to that of humans. Our analysis is based on the hypothesis that at least 2 specialized processing streams exist both in the visual and auditory system, an antero-ventral stream for the identification of objects, and a postero-dorsal stream for the analysis of space. Thus we predict that anterior superior temporal areas (AST) rostral and lateral to primary auditory cortex (A1) show enhanced selectivity for auditory objects regardless of spatial location (Specific Aim 1), whereas posterior superior temporal areas (PST) caudal to A1 show enhanced selectivity for location in space regardless of auditory object type (Specific Aim 2). We will focus on the processing of species-specific communication calls and will test whether neurons in the superior temporal (ST) cortex can form invariances for pitch and caller identity. In a third Specific Aim, we will use anatomical tracers, injected into physiologically characterized regions, to uncover the input connections to AST and PST from auditory, visual, and multisensory areas. Our studies, using alert monkeys trained in a behavioral task, will contribute to the understanding of unified principles of perception and cognition across sensory systems. They will further our understanding of deficits in human cognition from stroke or Alzheimer's disease, which result in visual and auditory agnosia as well as loss of spatial orientation. The studies are also relevant for disorders such as dyslexia and autism, which include problems in reading comprehension or a person's ability for social communication. Auditory processing deficits are a common symptom in both, and clarification of the neural mechanisms for auditory cortical communication is a major prerequisite for finding a cure. Finally, understanding temporal cortex with its massive connections to frontal cortex will yield important clues about higher mental disorders, such as schizophrenia, which are often characterized by auditory hallucinations. [unreadable] [unreadable] [unreadable]

Rauschecker 0730255

PIRE: International Research Program in Cognitive and Computational Neuroscience

In this Partnership for International Research and Education award, Georgetown University and Howard University will develop a multi-lateral international neuroscience collaboration involving several German and French institutions. The U.S. researchers and students involved will work with teams at the Technical University of Munich led by Arthur Konnerth, at the Ludwig-Maximilians-University in Munich led by Benedikt Grothe, at the Max Planck Institute for Biological Cybernetics in Tubingen led by Nikos Logothetis, at the Eberhard-Karls-University in Tubingen led by Peter Thier, at the Laboratory for Molecular and Cellular Neurobiology in Gif-sur-Yvette led by Gabriella Ugolini, and at the Brain and Cognition Research Center in Toulouse led by Simon Thorpe. They will form a focused, integrated, and complementary collaboration to lead neuroscience research and education on the international stage. Research topics include the neuronal functions of the cerebral cortex associated with auditory object processing, motion processing and contextual motor behavior, and the interaction of stimulus processing and category processing to produce object recognition.

This award will help to train the next generation of globally engaged scientists and engineers, as approximately twenty undergraduate students, fourteen graduate students, and five postdoctoral researchers will be funded to conduct research abroad with the German and French partners over the five-year course of the award. In addition, this award will allow Georgetown and Howard Universities to pursue their plans of developing a joint doctoral program with the Technical University of Munich and will leverage funds already received by the Technical University of Munich from the German Research Foundation, which encourage U.S. / German collaboration by allowing German doctoral students to conduct research at Georgetown via the International Research Training Group program. This award will enhance an already-existing neuroscience collaboration between Howard University and Georgetown University and will broaden participation by taking advantage of Howard University's ability to recruit under-represented minority students. The project overall is designed to broaden students' perspectives through an active international collaboration and participation in jointly organized international summer academies. The award includes funding for an outside evaluator to determine how well the project reaches its goals.

This award receives support from NSF's Office of International Science and Engineering and Division of Behavioral and Cognitive Sciences.

Object recognition is a crucial cognitive task for all sensory modalities. A particular challenge in object recognition is that physically dissimilar stimuli can have the same label (e.g., the same word spoken by different people, or the same face viewed under different lighting conditions), while physically similar stimuli may be labeled differently (e.g., hearing "b" or "p" based on small differences on when the vocal folds start vibrating). In audition, various animal species, but especially humans, have developed an elaborate system for communication based on the discrimination of fine acoustic differences between complex sounds. Speech perception is probably the most remarkable achievement in this domain and one that may influence the overall architecture of auditory cortex. The underlying neural mechanisms are poorly understood, however. With support from the National Science Foundation, Maximilian Riesenhuber and Josef P. Rauschecker of Georgetown University will address this issue by integrating behavioral results with functional magnetic resonance imaging (fMRI) measures of brain activity. The team will apply the insights gained in understanding the neural bases of visual object recognition to auditory object recognition. One study will investigate the neural mechanisms underlying the categorization and discrimination of speech sounds as well as the transformation of bottom-up acoustic information into categorical phonetic information along the cortical auditory hierarchy. The second study will investigate neuronal plasticity in auditory object recognition by training humans on an auditory categorization task involving modified monkey communication calls. By using novel yet natural auditory communication sounds, the investigators will be able to study the interaction of acoustic information and category labeling during learning and during recognition. The findings will be relevant for the understanding of higher-level auditory processing but also for a general understanding of the interactions between sensory and task-specific information in the brain as well as the commonalities and differences in the mechanisms supporting recognition of speech and non-speech sounds in the brain.

Understanding the general principles of sensory processing in the brain, and in particular identifying the underlying neural mechanisms across sensory modalities, has implications for education (e.g., second language learning) and in engineering (e.g., the development of neurally-inspired speech recognition systems). The research project will also help train the next generation of scientists, at the graduate and undergraduate level, with a particular focus on underrepresented minorities. At the graduate level, the project directly involves graduate students from Georgetown University's Interdisciplinary PhD Program in Neuroscience, both at the thesis level and for introductory lab rotations. The project will further impact undergraduate education at Georgetown and beyond, with the opportunity for undergraduates to participate in the project as part of their cognitive science curriculum, or during summer internships. The summer outreach program for undergraduate students has a strong focus on minority recruitment through a partnership with Howard University in Washington, DC.

DESCRIPTION (provided by applicant): Tinnitus, a mostly whistling, buzzing, or hissing phantom sound perceived in the absence of a corresponding external stimulus, is perceived by about 15% of the adult population, and about 75% of all patients with hearing loss. It can cause severe suffering, and to date, no reliable cure has been found. The causes of tinnitus are still poorly understood. The fact that it persists after section of the auditory nerve indicates that its origin lies within the central auditory system. Based on previous research on tinnitus and somatosensory phantom perception in humans and animals, our hypotheses about tinnitus generation are as follows. Damage to the auditory periphery (e.g. as a consequence of loud-noise exposure or aging), which does not even have to manifest itself in a measurable hearing loss, causes some central auditory neurons to lose their input. It is known from research on somatosensory phantom sensations that brain areas that have lost their input due to peripheral damages start responding to stimuli that are normally processed in adjacent areas. We assume that, just like the area of somatosensory cortex that previously processed sensory input from a now amputated hand, starts responding to touches on the face (which are normally processed in an adjacent area of somatosensory cortex), the areas of auditory cortex affected by hearing loss start responding to hearing-loss edge frequencies. This assumption is corroborated by the fact that psychophysical experiments on patients with hearing loss have shown that sensitivity for edge frequencies increases. The resulting imbalance in neuronal activity is mistakenly interpreted as a sound signal - the tinnitus. As not all patients with hearing loss perceive tinnitus, we assume that activity in extra-auditory structures can regulate neuronal auditory activity and prevent tinnitus perception. A likely candidate for such a structure is the paralimbic nucleus accumbens. This part of the ventral striatum has excitatory connections to the reticular thalamic nucleus (RTN), which in turn can inhibit the medial geniculate nucleus (MGN), the thalamic relay between the inferior colliculus and the auditory cortex assumed to be involved with the direction of attention. In tinnitus patients, NAc gray-matter volume is significantly reduced compared to healthy controls. It seems plausible to assume that the volume- reduced NAc of tinnitus patients cannot exert the inhibition necessary to block the excessive activation that ultimately gives rise to the tinnitus percept. It speaks in favor of the assumption of a connection between tinnitus and the NAc that both tinnitus and activity in the subcallosal area (including the NAc) are modulated by stress, arousal, and sleep deprivation. The aims of the proposed research are 1) to provide direct evidence for reorganization of tonotopic maps in central auditory structures by means of high-resolution functional MRI, both in tinnitus patients and in patients matched for hearing loss who do not perceive tinnitus, and 2) to investigate the role of the NAc in tinnitus by a. comparing NAc volume in tinnitus patients and patients matched for hearing loss who do not perceive tinnitus, using high-resolution structural MRI and voxel-based morphometry, and b. comparing, by means of high-resolution functional MRI, activation in central auditory structures and the NAc of patients with intermittent tinnitus in periods during which they do perceive tinnitus and periods during which they do not. Our predictions are that we will find reorganization of tonotopic maps in all patients with hearing loss, but reduced NAc volume and activity only in patients who do (at the time of measurement) perceive tinnitus. These results would guide tinnitus research into a new direction and open up a new point of intervention by emphasizing the modulatory role of extra-auditory structures responsible for the direction of attention.

DESCRIPTION (provided by applicant): Visual deprivation is one of the most extreme conditions leading brain regions to adopt new functions in response to environmental constraints, that is, to compensate for the loss of a sensory modality. Studies in visually deprived animals and in blind humans have long demonstrated the cross-modal recruitment of the visual cortex to process non-visual information. Yet, little is known about the functional parcellation of the reorganized occipital cortex and its precise role in the processing of non-visual information and in higher cognitive functions. The main aims of the present project are (1) to determine the sensory organization of the occipital cortex in blind subjects, (2) to identify the source of non-visual input to occipital cortex in the blind, and (3) to determine the functional role of the occipital cortex of blind subjects in the processing of non-visual stimuli, particularly when using a sensory substitution device. Using functional Magnetic Resonance Imaging (fMRI), we will examine brain activity related to tactile and auditory stimulation while subjects try to either identify or localize stimuli. This will allow us to determine whether domain specificity exists within the reorganized occipital cortex for sensory modality and/or for identification and localization. Using Diffusion Tensor Imaging (DTI) and Voxel-Based Morphometry (VBM), two relatively novel structural MRI techniques, we will investigate the structural basis of cerebral adaptive changes in blind subjects. VBM will allow us to examine if grey-matter cell density and volume in the blind occipital cortex are the same as those in the occipital cortex of sighted persons;DTI will examine the strength of white-matter fiber tracts projecting to and from occipital cortex in both subject groups, thus determining relative changes in the source of non-visual input in the blind. To test to what extent blindness is accompanied by enhanced non-visual abilities and to determine the functional role of occipital cortex in the blind, we will supplement brain imaging with extended psychophysical evaluations. We will examine the co-variance of behavioral performance with activation of brain regions by tactile or auditory stimulation, and in particular with occipital activation elicited by perception through a visual- to-auditory sensory substitution device. We predict that brain areas that are normally not recruited by sounds can be activated during the use of the sensory substitution device according to the stimuli perceived and/or the task performed and commensurate with proficiency of use. PUBLIC HEALTH RELEVANCE A better understanding of the physiological mechanisms underlying brain and cognitive plasticity in blindness will help to develop more adequate rehabilitation strategies and assistive devices for the blind, such as visual prostheses or sensory substitution devices. In a wider perspective, this will provide us with valuable information regarding brain plasticity in general and how the brain modifies its own organization in response to environmental constraints. This could further inspire the development of neuropsychological and rehabilitation methods for patients with brain injuries.

DESCRIPTION (provided by applicant): In recent years, great progress has been made in understanding cortical areas involved in auditory perception and cognition. Work from our laboratory as well as many others has demonstrated the existence of functionally specialized processing streams in both humans and nonhuman animals (see Rauschecker, 2012, for review). A ventral what-stream was shown to be involved in the identification of complex sounds; a dorsal where- stream was defined as specialized in processing space and motion. Work in the previous funding period has concentrated on understanding processing principles in the ventral stream and has produced numerous results (see Progress Report). Work in the upcoming funding cycle will focus on the dorsal stream. In particular, we propose to study auditory areas within posterior superior temporal cortex (pST) and auditory-related areas in parietal and premotor cortex of awake rhesus monkeys. Building on prior results, we predict that areas of the dorsal stream in pST and parietal cortex are particularly selective for spatial location. In addition, a new, expanded role for dorsal-stream function in audio-motor control and integration has been proposed (Rauschecker, 2011). We will test this hypothesis by training monkeys to produce sound sequences on a special-built behavioral apparatus (monkey piano). These sequences as well as untrained control sequences will then be used as auditory stimuli in functional magnetic resonance imaging (fMRI) studies and single-/multi- unit recordings from the same monkeys. The study is divided into three specific aims: Aim 1 will investigate tuning for spatial and temporal properties in areas of the caudal belt and parabelt (CB/CPB) using fMRI and single-/multi-unit recording. Specialization for motion-in-space will be tested by presenting stimuli mimicking looming objects. Aims 2 and 3 will study the newly proposed role of the dorsal stream in audio-motor control and integration: Aim 2 will utilize fMRI in combination with behavioral training; Aim 3 will use parallel recording from multiple sites with multi-electrode arrays (MEAs). By testing how features relevant to spatial and audio- motor functions are represented relative to each other in dorsal-stream areas, we will determine whether these functions are accomplished relatively independently in two branches of the stream, or whether they are combined into one integrated audio-spatio-motor processing pathway. Our studies, using alert monkeys trained in a behavioral task, will contribute to the understanding of unified principles of cortical function across sensory systems. They will further our understanding of deficits in human perception and cognition from stroke or Alzheimer's disease, which result in visual and auditory agnosia as well as loss of spatial orientation. The studies are also relevant for disorders such as dyslexia and autism, which include problems in language comprehension or ability for social communication. Finally, understanding temporal and parietal networks with their massive connections to frontal cortex will yield important clues about higher neurological and mental dysfunctions, such as attention-deficit disorder and schizophrenia.

DESCRIPTION (provided by applicant): Visual deprivation and blindness famously cause certain brain regions to reorganize in response to environmental constraints and in order to compensate for the loss of a sensory modality. Studies in visually deprived animals and blind humans have long demonstrated the cross-modal recruitment of the visual cortex to process nonvisual information. Yet, little is known about the functional specialization of the reorganized visual cortex (VC), its precise role in the processing of nonvisual information, or the source and routing of its nonvisual inputs. The main aims of the present project are, therefore, to (1) determine the functional organization of the occipital cortex in blind volunteers using a sensory substitution device, (2) to examine whether nonvisual information is processed hierarchically in the VC of the blind, and (3) identify the structural basis of adaptive changes and the source of nonvisual input to VC in the blind. Results from three years of funding by this grant have demonstrated that spatial and nonspatial processing streams do indeed exist for auditory and tactile processing (Renier et al., 2009). Furthermore, spatial auditory and tactile processing in the VC of the early blind occur in the same dorsal-stream regions as visual spatial processing in sighted subjects (Renier et al., 2010). These findings have led us to hypothesize that functionally specialized modules are preserved in the cortex of the early blind. We will pursue this hypothesis further by testing paradigms within the ventral stream. Thus, using functional magnetic resonance imaging, we will examine brain activity in blind subjects while they identify (via the auditory modality) houses, faces and 2-D geometrical shapes coded into sound patterns. These experiments will allow us to determine whether the parahippocampal place area (PPA), the fusiform face area (FFA), and the lateral occipital complex (LOC) retain their designated functional roles in early blindness, while switching their input modality. We will also examine the organization of VC by testing whether nonvisual information is processed in a hierarchical manner, in the same way that normal sensory information is processed in its intact sensory system. Using complexity-varied pitch information, we will determine if early-to-late visual regions of the blind respond to sound in the direction of simple-to-complex levels of pitch processing. Finally, using diffusion tensor imaging (DTI) and analysis of functional connectivity, we will investigate the structural basis of adaptive changes in the cerebral cortex and white matter of blind subjects. Using DTI, we will examine the strength of white-matter fiber tracts projecting to and from VC in both subject groups, thus determining relative changes in the connections between VC and other cortical areas. We will also test how visual and other sensory areas interact during auditory and tactile information processing in blind and sighted volunteers, and whether this interaction depends on the strength of anatomical pathways connecting these areas. Combining the two different methodological approaches will provide us an excellent opportunity to identify the source of nonvisual inputs to VC in the early blind.

? DESCRIPTION (provided by applicant): Two cortical pathways originate from primary core areas of auditory cortex: a ventral pathway subserving identification of sounds, and a dorsal pathway, which was originally defined - similar to the visual system - as a processing stream for space and motion. We have recently proposed that this dorsal pathway should be redefined in a wider sense as a processing stream for sensorimotor integration and control (Rauschecker, 2011). This broader function explicitly includes spatial processing but also extends to the processing of temporal sequences, including spoken speech and musical melodies in humans. In this project, we will test the expanded model of the auditory dorsal stream by training rhesus monkeys to produce fixed sound sequences on a newly designed behavioral apparatus (monkey piano). By pressing a lever the monkey will produce a musical tone of a specific pitch; by pressing several levers in succession, the monkey will produce a melody. After a monkey has learned to reliably play the same melody, we will perform functional magnetic resonance imaging (fMRI) of auditory-responsive brain regions in the awake monkey while it listens to the learned self-generated sequence. Control stimuli include melodies the monkey has been passively exposed to by listening to another monkey play for the same amount of time, and novel melodies that the monkey never heard before. Preliminary data suggest that areas activated by the self-generated melody include a region in inferior parietal cortex as well as one focus each in dorsal and ventral premotor cortex. The locations of activated regions will guide subsequent electrophysiological recording with linear microelectrode arrays (LMAs). Each recording site will be tested with the same sequences. Next we will record neuronal responses in premotor cortex to passive listening of the sound sequences and compare them to neuronal activity obtained when the monkey actively produces the sequence with and without sound. Finally, we will add video of a monkey playing the sound sequence on the monkey piano and study multisensory interactions along the dorsal stream using fMRI and LMAs. In particular, responses in caudal auditory belt and parabelt will be compared with those in inferior parietal and premotor cortex in simultaneous recordings. Our studies, using alert monkeys trained in a behavioral task, will contribute to the understanding of unified principles of perception and cognition across sensory systems and their interactions with the motor system. Investigating the auditory dorsal stream in a nonhuman primate will provide valuable information about the evolution of speech and music in humans. Our studies are highly relevant for higher-order processing disorders of audition and speech, such as dysarthria, apraxia of speech, aphasia and specific language disorders which involve inadequate coordination between sensory and motor systems. The results will also improve our understanding of disorders of sensory-motor integration, such as ataxia, which may be caused by stroke or neurodegenerative disease, thus, leading to better therapies and rehabilitation strategies.

This award provides a substantial upgrade to Georgetown University's 3 Tesla Siemens MRI scanner, which supports the innovative neuroimaging research conducted by 37 researchers from 8 different institutions in the region including (Georgetown University, Catholic University, Children's National Medical Center, Gallaudet University, George Washington University, American University, National Rehabilitation Hospital, and the Veterans Administration). This upgrade will increase the quality of the images acquired and allow the researchers using this scanner to make use of the latest developments in MRI pulse sequences notably those developed for the Human Connectome Project, which will provide better temporal resolution for studies of brain function, better spatial resolution including greater precision with regards to subtle differences in axonal connectivity, and better estimation of metabolite concentration via magnetic resonance spectroscopy (MRS). These improvements will support not only the various researchers but also provide educational opportunities for high school, undergraduate, and graduate students from across the greater Washington, DC metro region that encompasses a diverse ethnic and socioeconomic population.

Researchers from 8 different institutions in the greater Washington, DC metro region conduct a wide variety of neuroimaging research using the Siemens Magnetom Tim 3T MRI scanner at Georgetown University. One area of research focuses on neurodevelopment with studies examining reward processing, executive function, autism, reading and math difficulties, and spatial and creative relational reasoning. Another area of research uses this scanner to better understand basic neurological processes related to visual attention, spatial/object-based selection, somatosensory learning and cross-modal integration, sensory cortical organization, and cross-modal plasticity in blind individuals. The Siemens Prisma upgrade significantly increases the capabilities of this facility by providing two new radio frequency head coils, a 32- and 64-channel, that greatly increase the signal-to-noise ratio (SNR) as well as allow for greater scanning parallelization. With the boost in SNR afforded by this upgrade, investigators will have greater flexibility in their functional MRI paradigms with higher spatial and temporal resolution. In addition, the ability to use the Human Connectome Project pulse sequences will greatly improve the power to detect subtle neuroanatomic differences using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).

Project Summary/Abstract Two cortical pathways originate from early core and belt areas of auditory cortex: a ventral pathway subserving identification of sounds, and a dorsal pathway that was originally defined ? similar to the visual system ? as a processing stream for space and motion. It has been proposed that the auditory dorsal pathway should be reframed in a wider sense as a processing stream for sensorimotor integration and control (Rauschecker, 2011). This broader function explicitly includes spatial processing but also extends to the processing of auditory-motor sequences, including spoken speech and musical melodies in humans. In this long-term project, we will test the expanded model of the auditory dorsal stream by training rhesus monkeys to produce sound sequences on a new behavioral apparatus (?monkey piano?) developed in our laboratory (Archakov et al., 2020). By pressing a lever, the monkey produces a tone of a specific pitch; by pressing several levers in succession, the monkey produces a melody. After an animal has learned to reliably play the same sequence, auditory-responsive brain regions are identified through whole-brain functional magnetic resonance imaging (fMRI) while the animal is alert and listens to the learned self-produced sequence. Control stimuli include melodies the monkey has been passively exposed to, and novel melodies that the monkey has never heard before. Results from the previous funding cycle show that listening to the self-produced melody activates not only auditory areas but also motor regions of the brain, thus demonstrating the existence of internal models linking perception and action. The locations of activated regions will now guide electrophysiological recording with linear microelectrode arrays (LMAs). We will record neuronal responses in auditory and motor regions of cortex to passive listening of the sound sequences and compare them to neuronal activity obtained when the monkey actively produces the sequence with and without sound. Finally, we will add video of a monkey playing the sound sequence on the monkey piano and study multisensory interactions along the dorsal stream using fMRI and LMAs. In particular, responses in caudal auditory belt and parabelt will be compared with those in premotor cortex and posterior parietal cortex in simultaneous recordings. Our studies, using alert monkeys trained in a behavioral task, will contribute to the understanding of unified principles of perception and cognition across sensory systems and their interactions with the motor system in the form of internal models. Investigating the auditory dorsal stream in a nonhuman primate will provide essential information on the origin of human communication, including speech and music. Our studies are relevant for higher?level processing disorders of speech and its production, such as apraxia of speech, non-fluent aphasia, and specific language disorders that involve inadequate coordination between sensory and motor systems. The results will also improve our understanding of sensorimotor disorders, such as ataxia, which may be caused by stroke or neurodegenerative disease, thus leading to better therapies and rehabilitation strategies.