The classical view of sensory information mainly flowing into barrel cortex at layer IV, moving u... more The classical view of sensory information mainly flowing into barrel cortex at layer IV, moving up for complex feature processing and lateral interactions in layers II and III, then down to layers V and VI for output and corticothalamic feedback is becoming increasingly undermined by new evidence. We review the neurophysiology of sensing and processing whisker deflections, emphasizing the general processing and organisational principles present along the entire sensory pathway—from the site of physical deflection at the whiskers to the encoding of deflections in the barrel cortex. Many of these principles support the classical view. However, we also highlight the growing number of exceptions to these general principles, which complexify the system and which investigators should be mindful of when interpreting their results. We identify gaps in the literature for experimentalists and theorists to investigate, not just to better understand whisker sensation but also to better understa...
Recent Advances in Structural Integrity Analysis - Proceedings of the International Congress (APCF/SIF-2014)
Rat whiskers, and their associated neural substrate, comprise a highly evolved bio-sensory system... more Rat whiskers, and their associated neural substrate, comprise a highly evolved bio-sensory system used to perceive the world with an acuity that matches human vision or hearing. Study of the whisker sensory system is becoming an attractive research topic due to its fundamental importance as a fine sensor in neuroscience and due to the potential to develop biomimetic robotics. In this paper, a truncated conical beam model is used to study the natural frequency of a rat whisker. In addition to the proof of two generic natural frequency relationships for a truncated conical beam, our numerical results show that there exists a window where the natural frequencies of a rat whisker are very sensitive to the change of the rotational constraint at the base. This has significance for the function of the sensor since the rat follicle constraints can be manipulated by a behaving rat, thereby altering the natural frequencies of the whisker.
Halogenated BODIPY probes allow lipid imaging in brain tissue with different level of specificity... more Halogenated BODIPY probes allow lipid imaging in brain tissue with different level of specificity for the white matter that are linked to the chemical identity of the halogen substituent.
Primary sensory cortex in the auditory, somatosensory and visual systems in adult animals shows a... more Primary sensory cortex in the auditory, somatosensory and visual systems in adult animals shows a capacity for plasticity subsequent to receptor organ damage. Here I review our own work in this area, on auditory cortex contralateral to a lesioned cochlea. I review the conditions required to establish that the cortical change is plasticity and not simply the residue of prelesion responses. I demonstrate that loss of cortical surround inhibition does not, in itself, cause plasticity of auditory cortical maps, as hypothesized in other sensory systems. However, such loss of surround inhibition does lead to unmasking of new excitatory and inhibitory responses in single auditory cortical neurons and this has implications for the standard model for the structure of receptive fields of A1 neurons. I propose an alternative model for the receptive field structure.
Traumatic brain injury (TBI) can result in excitation: inhibition imbalance, as well as a range o... more Traumatic brain injury (TBI) can result in excitation: inhibition imbalance, as well as a range of chronic neurological deficits. However, how TBI affects different interneurons, and how this relates to behavioral abnormalities, remains poorly understood. This study examined the effects of a mixed diffuse‐focal model of TBI, the lateral fluid percussion injury (LFPI), on interneurons, 8 weeks post‐TBI in rats. Brains were labeled with antibodies against calbindin, parvalbumin, calretinin, neuropeptide Y, and somatostatin, and the number of interneurons were assessed in the cortex and hippocampus following LFPI. LFPI caused a reduction in the numbers of interneurons mediating both perisomatic and dendritic inhibition in the somatosensory cortex. In hippocampus, there were heterogenous changes in the number of interneurons while motor cortex, showed no obvious loss in any of the subsets of interneurons after TBI. In parallel to the investigations of changes in the number of interneurons, we also investigated the long‐term behavioral consequences of LFPI. Behaviorally, rats given an LFPI displayed transient reduction in performance in motor tasks and were significantly impaired in reversal learning in the water maze task post‐TBI. We also report here progressive neurodegeneration in cortex and hippocampus indicated by Fluoro‐Jade C in the different brain areas examined after injury. Our findings suggest differential vulnerability of inhibitory neurons to LFPI in the different brain areas examined after injury. These data will aid in evaluation of new treatments for TBI and help target specific neuronal subtypes as a function of injury time and type.
Perceptual learning, the improvement in sensory discriminations with practise, is also subject to... more Perceptual learning, the improvement in sensory discriminations with practise, is also subject to stimulus-specific interference from temporal jitter in a learning session or manipulations applied between or immediately after sessions. We demonstrate a novel form of perceptual interference where even a brief cueing exposure to a complex speech-in-noise task produces a forward interference on subsequent speech-in-noise learning. This potent interference generalizes across cueing context but specifically affects only late learning in the subsequent task, is resistant to the remediating effects of sleep and persists across an overnight delay involving sleep, and can be evoked by a single exposure 1 day before the learning. Learning in the speech-in-noise task is due to generalized improvements in discriminating and extracting signals (speech) from noise and we hypothesize that the forward interference represents interference with improvements in access to higher-level representations i...
Until the late twentieth century, it was believed that different sensory modalities were processe... more Until the late twentieth century, it was believed that different sensory modalities were processed by largely independent pathways in the primate cortex, with cross-modal integration only occurring in specialized polysensory areas. This model was challenged by the finding that the peripheral representation of the primary visual cortex (V1) receives monosynaptic connections from areas of the auditory cortex in the macaque. However, auditory projections to V1 have not been reported in other primates. We investigated the existence of direct interconnections between V1 and auditory areas in the marmoset, a New World monkey. Labelled neurons in auditory cortex were observed following 4 out of 10 retrograde tracer injections involving V1. These projections to V1 originated in the caudal subdivisions of auditory cortex (primary auditory cortex, caudal belt and parabelt areas), and targeted parts of V1 that represent parafoveal and peripheral vision. Injections near the representation of th...
The pitch of vocalizations is a key communication feature aiding recognition of individuals and s... more The pitch of vocalizations is a key communication feature aiding recognition of individuals and separating sound sources in complex acoustic environments. The neural representation of the pitch of periodic sounds is well defined. However, many natural sounds, like complex vocalizations, contain rich, aperiodic or not strictly periodic frequency content and/or include high-frequency components, but still evoke a strong sense of pitch. Indeed, such sounds are the rule, not the exception but the cortical mechanisms for encoding pitch of such sounds are unknown. We investigated how neurons in the high-frequency representation of primary auditory cortex (A1) of marmosets encoded changes in pitch of four natural vocalizations, two centred around a dominant frequency similar to the neuron's best sensitivity and two around a much lower dominant frequency. Pitch was varied over a fine range that can be used by marmosets to differentiate individuals. The responses of most high-frequency A1 neurons were sensitive to pitch changes in all four vocalizations, with a smaller proportion of the neurons showing pitch-insensitive responses. Classically defined excitatory drive, from the neuron's monaural frequency response area, predicted responses to changes in vocalization pitch in <30% of neurons suggesting most pitch tuning observed is not simple frequency-level response. Moreover, 39% of A1 neurons showed call-invariant tuning of pitch. These results suggest that distributed activity across A1 can represent the pitch of natural sounds over a fine, functionally relevant range, and exhibits pitch tuning for vocalizations within and outside the classical neural tuning area.
Many studies on the subjective perception of non-linguistic sounds have focused on only a single ... more Many studies on the subjective perception of non-linguistic sounds have focused on only a single percept, e.g. pleasantness,. In the present study, we have examined three different perception-related factors to also allow us to look at any inter-relationships between them that could be related to objective features. Objective features of the NLSs in this database were calculated and subjective perceptions were recorded from participants. These two elements - objective features and subjective perceptions - were then mapped together using various statistical and mathematical techniques. So as to ground our results in a meaningful context, we chose to map a set of objective features to human percepts which had been used in previous studies of NLS perception, but which had not yet been related back to objective features or combinations thereof.
Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relati... more Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relative head-brain movement, can result in long-lasting cognitive and motor deficits which can be particularly consequential when they occur in young people with a long life ahead. Much is known of the molecular and anatomical changes produced in TBI but much less is known of the consequences of these changes to neuronal functionality, especially in the cortex. Given that much of our interior and exterior lives are dependent on responsiveness to information from and about the world around us, we have hypothesized that a significant contributor to the cognitive and motor deficits seen after TBI could be changes in sensory processing. To explore this hypothesis, and to develop a model test system of the changes in neuronal functionality caused by TBI, we have examined neuronal encoding of simple and complex sensory input in the rat's exploratory and discriminative tactile system, the large ...
Autism Spectrum Disorder (ASD), characterized by impaired communication skills and repetitive beh... more Autism Spectrum Disorder (ASD), characterized by impaired communication skills and repetitive behaviors, can also result in differences in sensory perception. Individuals with ASD often perform normally in simple auditory tasks but poorly compared to typically developed (TD) individuals on complex auditory tasks like discriminating speech from complex background noise. A common trait of individuals with ASD is hypersensitivity to auditory stimulation. No studies to our knowledge consider whether hypersensitivity to sounds is related to differences in speech-in-noise discrimination. We provide novel evidence that individuals with high-functioning ASD show poor performance compared to TD individuals in a speech-in-noise discrimination task with an attentionally demanding background noise, but not in a purely energetic noise. Further, we demonstrate in our small sample that speech-hypersensitivity does not appear to predict performance in the speech-in-noise task. The findings support ...
Computer methods in biomechanics and biomedical engineering, 2017
Traumatic brain injury (TBI), induced by impact of an object with the head, is a major health pro... more Traumatic brain injury (TBI), induced by impact of an object with the head, is a major health problem worldwide. Rats are a well-established animal analogue for study of TBI and the weight-drop impact-acceleration (WDIA) method is a well-established model in rats for creating diffuse TBI, the most common form of TBI seen in humans. However, little is known of the biomechanics of the WDIA method and, to address this, we have developed a four-degrees-of-freedom multi-body mass-spring-damper model for the WDIA test in rats. An analytical expression of the maximum skull acceleration, one of the important head injury predictor, was derived and it shows that the maximum skull acceleration is proportional to the impact velocity but independent of the impactor mass. Furthermore, a dimensional analysis disclosed that the maximum force on the brain and maximum relative displacement between brain and skull are also linearly proportional to impact velocity. Additionally, the effects of the impa...
Neurons in the Middle Temporal area (MT) of the primate cerebral cortex respond to moving visual ... more Neurons in the Middle Temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of “neurometric” thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide anesthetized marmoset monkeys, a species which has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds, and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was...
The classical view of sensory information mainly flowing into barrel cortex at layer IV, moving u... more The classical view of sensory information mainly flowing into barrel cortex at layer IV, moving up for complex feature processing and lateral interactions in layers II and III, then down to layers V and VI for output and corticothalamic feedback is becoming increasingly undermined by new evidence. We review the neurophysiology of sensing and processing whisker deflections, emphasizing the general processing and organisational principles present along the entire sensory pathway—from the site of physical deflection at the whiskers to the encoding of deflections in the barrel cortex. Many of these principles support the classical view. However, we also highlight the growing number of exceptions to these general principles, which complexify the system and which investigators should be mindful of when interpreting their results. We identify gaps in the literature for experimentalists and theorists to investigate, not just to better understand whisker sensation but also to better understa...
Recent Advances in Structural Integrity Analysis - Proceedings of the International Congress (APCF/SIF-2014)
Rat whiskers, and their associated neural substrate, comprise a highly evolved bio-sensory system... more Rat whiskers, and their associated neural substrate, comprise a highly evolved bio-sensory system used to perceive the world with an acuity that matches human vision or hearing. Study of the whisker sensory system is becoming an attractive research topic due to its fundamental importance as a fine sensor in neuroscience and due to the potential to develop biomimetic robotics. In this paper, a truncated conical beam model is used to study the natural frequency of a rat whisker. In addition to the proof of two generic natural frequency relationships for a truncated conical beam, our numerical results show that there exists a window where the natural frequencies of a rat whisker are very sensitive to the change of the rotational constraint at the base. This has significance for the function of the sensor since the rat follicle constraints can be manipulated by a behaving rat, thereby altering the natural frequencies of the whisker.
Halogenated BODIPY probes allow lipid imaging in brain tissue with different level of specificity... more Halogenated BODIPY probes allow lipid imaging in brain tissue with different level of specificity for the white matter that are linked to the chemical identity of the halogen substituent.
Primary sensory cortex in the auditory, somatosensory and visual systems in adult animals shows a... more Primary sensory cortex in the auditory, somatosensory and visual systems in adult animals shows a capacity for plasticity subsequent to receptor organ damage. Here I review our own work in this area, on auditory cortex contralateral to a lesioned cochlea. I review the conditions required to establish that the cortical change is plasticity and not simply the residue of prelesion responses. I demonstrate that loss of cortical surround inhibition does not, in itself, cause plasticity of auditory cortical maps, as hypothesized in other sensory systems. However, such loss of surround inhibition does lead to unmasking of new excitatory and inhibitory responses in single auditory cortical neurons and this has implications for the standard model for the structure of receptive fields of A1 neurons. I propose an alternative model for the receptive field structure.
Traumatic brain injury (TBI) can result in excitation: inhibition imbalance, as well as a range o... more Traumatic brain injury (TBI) can result in excitation: inhibition imbalance, as well as a range of chronic neurological deficits. However, how TBI affects different interneurons, and how this relates to behavioral abnormalities, remains poorly understood. This study examined the effects of a mixed diffuse‐focal model of TBI, the lateral fluid percussion injury (LFPI), on interneurons, 8 weeks post‐TBI in rats. Brains were labeled with antibodies against calbindin, parvalbumin, calretinin, neuropeptide Y, and somatostatin, and the number of interneurons were assessed in the cortex and hippocampus following LFPI. LFPI caused a reduction in the numbers of interneurons mediating both perisomatic and dendritic inhibition in the somatosensory cortex. In hippocampus, there were heterogenous changes in the number of interneurons while motor cortex, showed no obvious loss in any of the subsets of interneurons after TBI. In parallel to the investigations of changes in the number of interneurons, we also investigated the long‐term behavioral consequences of LFPI. Behaviorally, rats given an LFPI displayed transient reduction in performance in motor tasks and were significantly impaired in reversal learning in the water maze task post‐TBI. We also report here progressive neurodegeneration in cortex and hippocampus indicated by Fluoro‐Jade C in the different brain areas examined after injury. Our findings suggest differential vulnerability of inhibitory neurons to LFPI in the different brain areas examined after injury. These data will aid in evaluation of new treatments for TBI and help target specific neuronal subtypes as a function of injury time and type.
Perceptual learning, the improvement in sensory discriminations with practise, is also subject to... more Perceptual learning, the improvement in sensory discriminations with practise, is also subject to stimulus-specific interference from temporal jitter in a learning session or manipulations applied between or immediately after sessions. We demonstrate a novel form of perceptual interference where even a brief cueing exposure to a complex speech-in-noise task produces a forward interference on subsequent speech-in-noise learning. This potent interference generalizes across cueing context but specifically affects only late learning in the subsequent task, is resistant to the remediating effects of sleep and persists across an overnight delay involving sleep, and can be evoked by a single exposure 1 day before the learning. Learning in the speech-in-noise task is due to generalized improvements in discriminating and extracting signals (speech) from noise and we hypothesize that the forward interference represents interference with improvements in access to higher-level representations i...
Until the late twentieth century, it was believed that different sensory modalities were processe... more Until the late twentieth century, it was believed that different sensory modalities were processed by largely independent pathways in the primate cortex, with cross-modal integration only occurring in specialized polysensory areas. This model was challenged by the finding that the peripheral representation of the primary visual cortex (V1) receives monosynaptic connections from areas of the auditory cortex in the macaque. However, auditory projections to V1 have not been reported in other primates. We investigated the existence of direct interconnections between V1 and auditory areas in the marmoset, a New World monkey. Labelled neurons in auditory cortex were observed following 4 out of 10 retrograde tracer injections involving V1. These projections to V1 originated in the caudal subdivisions of auditory cortex (primary auditory cortex, caudal belt and parabelt areas), and targeted parts of V1 that represent parafoveal and peripheral vision. Injections near the representation of th...
The pitch of vocalizations is a key communication feature aiding recognition of individuals and s... more The pitch of vocalizations is a key communication feature aiding recognition of individuals and separating sound sources in complex acoustic environments. The neural representation of the pitch of periodic sounds is well defined. However, many natural sounds, like complex vocalizations, contain rich, aperiodic or not strictly periodic frequency content and/or include high-frequency components, but still evoke a strong sense of pitch. Indeed, such sounds are the rule, not the exception but the cortical mechanisms for encoding pitch of such sounds are unknown. We investigated how neurons in the high-frequency representation of primary auditory cortex (A1) of marmosets encoded changes in pitch of four natural vocalizations, two centred around a dominant frequency similar to the neuron's best sensitivity and two around a much lower dominant frequency. Pitch was varied over a fine range that can be used by marmosets to differentiate individuals. The responses of most high-frequency A1 neurons were sensitive to pitch changes in all four vocalizations, with a smaller proportion of the neurons showing pitch-insensitive responses. Classically defined excitatory drive, from the neuron's monaural frequency response area, predicted responses to changes in vocalization pitch in <30% of neurons suggesting most pitch tuning observed is not simple frequency-level response. Moreover, 39% of A1 neurons showed call-invariant tuning of pitch. These results suggest that distributed activity across A1 can represent the pitch of natural sounds over a fine, functionally relevant range, and exhibits pitch tuning for vocalizations within and outside the classical neural tuning area.
Many studies on the subjective perception of non-linguistic sounds have focused on only a single ... more Many studies on the subjective perception of non-linguistic sounds have focused on only a single percept, e.g. pleasantness,. In the present study, we have examined three different perception-related factors to also allow us to look at any inter-relationships between them that could be related to objective features. Objective features of the NLSs in this database were calculated and subjective perceptions were recorded from participants. These two elements - objective features and subjective perceptions - were then mapped together using various statistical and mathematical techniques. So as to ground our results in a meaningful context, we chose to map a set of objective features to human percepts which had been used in previous studies of NLS perception, but which had not yet been related back to objective features or combinations thereof.
Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relati... more Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relative head-brain movement, can result in long-lasting cognitive and motor deficits which can be particularly consequential when they occur in young people with a long life ahead. Much is known of the molecular and anatomical changes produced in TBI but much less is known of the consequences of these changes to neuronal functionality, especially in the cortex. Given that much of our interior and exterior lives are dependent on responsiveness to information from and about the world around us, we have hypothesized that a significant contributor to the cognitive and motor deficits seen after TBI could be changes in sensory processing. To explore this hypothesis, and to develop a model test system of the changes in neuronal functionality caused by TBI, we have examined neuronal encoding of simple and complex sensory input in the rat's exploratory and discriminative tactile system, the large ...
Autism Spectrum Disorder (ASD), characterized by impaired communication skills and repetitive beh... more Autism Spectrum Disorder (ASD), characterized by impaired communication skills and repetitive behaviors, can also result in differences in sensory perception. Individuals with ASD often perform normally in simple auditory tasks but poorly compared to typically developed (TD) individuals on complex auditory tasks like discriminating speech from complex background noise. A common trait of individuals with ASD is hypersensitivity to auditory stimulation. No studies to our knowledge consider whether hypersensitivity to sounds is related to differences in speech-in-noise discrimination. We provide novel evidence that individuals with high-functioning ASD show poor performance compared to TD individuals in a speech-in-noise discrimination task with an attentionally demanding background noise, but not in a purely energetic noise. Further, we demonstrate in our small sample that speech-hypersensitivity does not appear to predict performance in the speech-in-noise task. The findings support ...
Computer methods in biomechanics and biomedical engineering, 2017
Traumatic brain injury (TBI), induced by impact of an object with the head, is a major health pro... more Traumatic brain injury (TBI), induced by impact of an object with the head, is a major health problem worldwide. Rats are a well-established animal analogue for study of TBI and the weight-drop impact-acceleration (WDIA) method is a well-established model in rats for creating diffuse TBI, the most common form of TBI seen in humans. However, little is known of the biomechanics of the WDIA method and, to address this, we have developed a four-degrees-of-freedom multi-body mass-spring-damper model for the WDIA test in rats. An analytical expression of the maximum skull acceleration, one of the important head injury predictor, was derived and it shows that the maximum skull acceleration is proportional to the impact velocity but independent of the impactor mass. Furthermore, a dimensional analysis disclosed that the maximum force on the brain and maximum relative displacement between brain and skull are also linearly proportional to impact velocity. Additionally, the effects of the impa...
Neurons in the Middle Temporal area (MT) of the primate cerebral cortex respond to moving visual ... more Neurons in the Middle Temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of “neurometric” thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide anesthetized marmoset monkeys, a species which has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds, and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was...
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Papers by Ramesh Rajan