Behavior-related visual activations in the auditory cortex of nonhuman primates.

While it is well established that sensory cortical regions traditionally thought to be unimodal can be activated by stimuli from modalities other than the dominant one, functions of such foreign-modal activations are still not clear. Here we show that visual activations in early auditory cortex can be related to whether or not the monkeys engaged in audio-visual tasks, to the time when the monkeys reacted to the visual component of such tasks, and to the correctness of the monkeys' response to the auditory component of such tasks. These relationships between visual activations and behavior suggest that auditory cortex can be recruited for visually-guided behavior and that visual activations can prime auditory cortex such that it is prepared for processing future sounds. Our study thus provides evidence that foreign-modal activations in sensory cortex can contribute to a subject's ability to perform tasks on stimuli from foreign and dominant modalities.

Absence of eye position effects in the early auditory cortex of monkeys.

This study aims to investigate whether the position of the eyes affects the neuronal activity in auditory cortex in a condition in which not the active control of eye position but the execution of hand movements was required relative to stimuli. Two monkeys were trained to perform audio-visual tasks in which they had to use their hand to respond to both the visual and the auditory stimuli to earn a reward. We recorded the spiking activity and the local field potentials from the core fields of auditory cortex, along with the eye position of the monkeys while they performed the tasks. We found that both the spiking activity and the local field potentials did not significantly vary with the eye position. This was the case both during the presentation of sounds and during other periods of the tasks. Our results indicate that eye position did not affect the neuronal activity in auditory cortex during the audio-visual tasks. Our results, together with the previous finding that eye position affects the neuronal activity in auditory cortex during eye fixation tasks, suggest that the presence of eye position effects in auditory cortex depends on the specific behavior a subject has to exhibit to obtain a reward.

Auditory perception is influenced by the orientation of the trunk relative to a sound source.

The study investigated how hearing depends on the whole body, head and trunk orientation relative to a sound source. In normal hearing humans we examined auditory thresholds and their ability to recognize logatomes (bi-syllabic non-sense words) at different whole body, head and trunk rotation relative to a sound source. We found that auditory threshold was increased and logatome recognition was impaired when the body or the trunk were rotated 40° away from a sound source compared to when the body or the trunk was oriented towards the sound source. Conversely, no effects were seen when only the head was rotated. Further, an increase of thresholds and impairment of logatome recognition were also observed after unilateral vibration of dorsal neck muscles that induces, per se, long-lasting illusory trunk displacement relative to the head. Thus, our findings support the idea that processing of acoustic signals depends on where a sound is located within a reference system defined by the subject's trunk coordinates.

Comparison of Pupil Dilation Responses to Unexpected Sounds in Monkeys and Humans.

Pupil dilation in response to unexpected stimuli has been well documented in human as well as in non-human primates; however, this phenomenon has not been systematically compared between the species. This analogy is also crucial for the role of non-human primates as an animal model to investigate neural mechanisms underlying the processing of unexpected stimuli and their evoked pupil dilation response. To assess this qualitatively, we used an auditory oddball paradigm in which we presented subjects a sequence of the same sounds followed by occasional deviants while we measured their evoked pupil dilation response (PDR). We used deviants (a frequency deviant, a pink noise burst, a monkey vocalization and a whistle sound) which differed in the spectral composition and in their ability to induce arousal from the standard. Most deviants elicited a significant pupil dilation in both species with decreased peak latency and increased peak amplitude in monkeys compared to humans. A temporal Principal Component Analysis (PCA) revealed two components underlying the PDRs in both species. The early component is likely associated to the parasympathetic nervous system and the late component to the sympathetic nervous system, respectively. Taken together, the present study demonstrates a qualitative similarity between PDRs to unexpected auditory stimuli in macaque and human subjects suggesting that macaques can be a suitable model for investigating the neuronal bases of pupil dilation. However, the quantitative differences in PDRs between species need to be investigated in further comparative studies.

Electrochemistry of Graphene Nanoplatelets Printed Electrodes for Cortical Direct Current Stimulation.

Possible risks stemming from the employment of novel, micrometer-thin printed electrodes for direct current neural stimulation are discussed. To assess those risks, electrochemical methods are used, including cyclic voltammetry, square-wave voltammetry, and electrochemical impedance spectroscopy. Experiments were conducted in non-deoxidized phosphate-buffered saline to better emulate living organism conditions. Since preliminary results obtained have shown unexpected oxidation peaks in 0-0.4 V potential range, the source of those was further investigated. Hypothesized redox activity of printing paste components was disproven, supporting further development of proposed fabrication technology of stimulating electrodes. Finally, partial permeability and resulting electrochemical activity of underlying silver-based printed layers of the device were pointed as the source of potential tissue irritation or damage. Employing this information, electrodes with corrected design were investigated, yielding no undesired redox processes.

Representation of Auditory Task Components and of Their Relationships in Primate Auditory Cortex.

The current study aimed to resolve some of the inconsistencies in the literature on which mental processes affect auditory cortical activity. To this end, we studied auditory cortical firing in four monkeys with different experience while they were involved in six conditions with different arrangements of the task components sound, motor action, and water reward. Firing rates changed most strongly when a sound-only condition was compared to a condition in which sound was paired with water. Additional smaller changes occurred in more complex conditions in which the monkeys received water for motor actions before or after sounds. Our findings suggest that auditory cortex is most strongly modulated by the subjects' level of arousal, thus by a psychological concept related to motor activity triggered by reinforcers and to readiness for operant behavior. Our findings also suggest that auditory cortex is involved in associative and emotional functions, but not in agency and cognitive effort.

Associations between sounds and actions in primate prefrontal cortex.

Behavioral flexibility allows animals to cope with changing situations, for example, to execute different actions to the same stimulus to achieve specific goals in different situations. The selection of the appropriate action in a given situation hinges on the previously learned associations between stimuli, actions, and outcomes. We showed in our recent study that early auditory cortex of nonhuman primates contributes to the selection of the actions to sounds by representing the associations between sounds and actions. That is, neurons in auditory cortex respond differently to a given sound when it signals different actions that are required to obtain a reward. Here, using the same monkey and the same tasks, we investigated whether the ventrolateral part of prefrontal cortex also represents such audiomotor associations as well as whether and how these representations differ from those in auditory cortex. Mirroring auditory cortex, neuronal responses to a given sound in prefrontal cortex changed with audiomotor associations, and the neuronal responses were largest when the sound signaled a no-go response. These findings suggest that prefrontal cortex also represents audiomotor associations and thus contributes to the selection of the actions to sounds during goal-directed behavior. The neuronal activity related to audiomotor associations started later in prefrontal cortex than in auditory cortex, suggesting that the representations in prefrontal cortex may originate in auditory cortex or in earlier stages of the auditory system.

Predictive cues for auditory stream formation in humans and monkeys.

Auditory perception is improved when stimuli are predictable, and this effect is evident in a modulation of the activity of neurons in the auditory cortex as shown previously. Human listeners can better predict the presence of duration deviants embedded in stimulus streams with fixed interonset interval (isochrony) and repeated duration pattern (regularity), and neurons in the auditory cortex of macaque monkeys have stronger sustained responses in the 60-140 ms post-stimulus time window under these conditions. Subsequently, the question has arisen whether isochrony or regularity in the sensory input contributed to the enhancement of the neuronal and behavioural responses. Therefore, we varied the two factors isochrony and regularity independently and measured the ability of human subjects to detect deviants embedded in these sequences as well as measuring the responses of neurons the primary auditory cortex of macaque monkeys during presentations of the sequences. The performance of humans in detecting deviants was significantly increased by regularity. Isochrony enhanced detection only in the presence of the regularity cue. In monkeys, regularity increased the sustained component of neuronal tone responses in auditory cortex while isochrony had no consistent effect. Although both regularity and isochrony can be considered as parameters that would make a sequence of sounds more predictable, our results from the human and monkey experiments converge in that regularity has a greater influence on behavioural performance and neuronal responses.

Early Sensory Loss Alters the Dendritic Branching and Spine Density of Supragranular Pyramidal Neurons in Rodent Primary Sensory Cortices.

Multisensory integration in primary auditory (A1), visual (V1), and somatosensory cortex (S1) is substantially mediated by their direct interconnections and by thalamic inputs across the sensory modalities. We have previously shown in rodents (Mongolian gerbils) that during postnatal development, the anatomical and functional strengths of these crossmodal and also of sensory matched connections are determined by early auditory, somatosensory, and visual experience. Because supragranular layer III pyramidal neurons are major targets of corticocortical and thalamocortical connections, we investigated in this follow-up study how the loss of early sensory experience changes their dendritic morphology. Gerbils were sensory deprived early in development by either bilateral sciatic nerve transection at postnatal day (P) 5, ototoxic inner hair cell damage at P10, or eye enucleation at P10. Sholl and branch order analyses of Golgi-stained layer III pyramidal neurons at P28, which demarcates the end of the sensory critical period in this species, revealed that visual and somatosensory deprivation leads to a general increase of apical and basal dendritic branching in A1, V1, and S1. In contrast, dendritic branching, particularly of apical dendrites, decreased in all three areas following auditory deprivation. Generally, the number of spines, and consequently spine density, along the apical and basal dendrites decreased in both sensory deprived and non-deprived cortical areas. Therefore, we conclude that the loss of early sensory experience induces a refinement of corticocortical crossmodal and other cortical and thalamic connections by pruning of dendritic spines at the end of the critical period. Based on present and previous own results and on findings from the literature, we propose a scenario for multisensory development following early sensory loss.

Associations between sounds and actions in early auditory cortex of nonhuman primates.

An individual may need to take different actions to the same stimulus in different situations to achieve a given goal. The selection of the appropriate action hinges on the previously learned associations between stimuli, actions, and outcomes in the situations. Here, using a go/no-go paradigm and a symmetrical reward, we show that early auditory cortex of nonhuman primates represents such associations, in both the spiking activity and the local field potentials. Sound-evoked neuronal responses changed with sensorimotor associations shortly after sound onset, and the neuronal responses were largest when the sound signaled that a no-go response was required in a trial to obtain a reward. Our findings suggest that association processes take place in the auditory system and do not necessarily rely on association cortex. Thus, auditory cortex may contribute to a rapid selection of the appropriate motor responses to sounds during goal-directed behavior.

Neuronal correlates of auditory streaming in the auditory cortex of behaving monkeys.

This study tested the hypothesis that spiking activity in the primary auditory cortex of monkeys is related to auditory stream formation. Evidence for this hypothesis was previously obtained in animals that were passively exposed to stimuli and in which differences in the streaming percept were confounded with differences between the stimuli. In this study, monkeys performed an operant task on sequences that were composed of light flashes and tones. The tones alternated between a high and a low frequency and could be perceived either as one auditory stream or two auditory streams. The flashes promoted either a one-stream percept or a two-stream percept. Comparison of different types of sequences revealed that the neuronal responses to the alternating tones were more similar when the flashes promoted auditory stream integration, and were more dissimilar when the flashes promoted auditory stream segregation. Thus our findings show that the spiking activity in the monkey primary auditory cortex is related to auditory stream formation.

Neuronal Correlates of Auditory Streaming in Monkey Auditory Cortex for Tone Sequences without Spectral Differences.

This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman's population separation model of auditory streaming.

Metamaterial-based transmit and receive system for whole-body magnetic resonance imaging at ultra-high magnetic fields.

Magnetic resonance imaging (MRI) at ultra-high fields (UHF), such as 7 T, provides an enhanced signal-to-noise ratio and has led to unprecedented high-resolution anatomic images and brain activation maps. Although a variety of radio frequency (RF) coil architectures have been developed for imaging at UHF conditions, they usually are specialized for small volumes of interests (VoI). So far, whole-body coil resonators are not available for commercial UHF human whole-body MRI systems. The goal of the present study was the development and validation of a transmit and receive system for large VoIs that operates at a 7 T human whole-body MRI system. A Metamaterial Ring Antenna System (MRAS) consisting of several ring antennas was developed, since it allows for the imaging of extended VoIs. Furthermore, the MRAS not only requires lower intensities of the irradiated RF energy, but also provides a more confined and focused injection of excitation energy on selected body parts. The MRAS consisted of several antennas with 50 cm inner diameter, 10 cm width and 0.5 cm depth. The position of the rings was freely adjustable. Conformal resonant right-/left-handed metamaterial was used for each ring antenna with two quadrature feeding ports for RF power. The system was successfully implemented and demonstrated with both a silicone oil and a water-NaCl-isopropanol phantom as well as in vivo by acquiring whole-body images of a crab-eating macaque. The potential for future neuroimaging applications was demonstrated by the acquired high-resolution anatomic images of the macaque's head. Phantom and in vivo measurements of crab-eating macaques provided high-resolution images with large VoIs up to 40 cm in xy-direction and 45 cm in z-direction. The results of this work demonstrate the feasibility of the MRAS system for UHF MRI as proof of principle. The MRAS shows a substantial potential for MR imaging of larger volumes at 7 T UHF. This new technique may provide new diagnostic potential in spatially extended pathologies such as searching for spread-out tumor metastases or monitoring systemic inflammatory processes.

Category-specific neuronal activity in left and right auditory cortex and in medial geniculate body of monkeys.

We address the question of whether the auditory cortex of the left and right hemisphere and the auditory thalamus are differently involved in the performance of cognitive tasks. To understand these differences on the level of single neurons we compared neuronal firing in the primary and posterior auditory cortex of the two hemispheres and in the medial geniculate body in monkeys while subjects categorized pitch relationships in tone sequences. In contrast to earlier findings in imaging studies performed on humans, we found little difference between the three brain regions in terms of the category-specificity of their neuronal responses, of tonic firing related to task components, and of decision-related firing. The differences between the results in humans and monkeys may result from the type of neuronal activity considered and how it was analyzed, from the auditory cortical fields studied, or from fundamental differences between these species.

Persistent neural activity in auditory cortex is related to auditory working memory in humans and nonhuman primates.

Working memory is the cognitive capacity of short-term storage of information for goal-directed behaviors. Where and how this capacity is implemented in the brain are unresolved questions. We show that auditory cortex stores information by persistent changes of neural activity. We separated activity related to working memory from activity related to other mental processes by having humans and monkeys perform different tasks with varying working memory demands on the same sound sequences. Working memory was reflected in the spiking activity of individual neurons in auditory cortex and in the activity of neuronal populations, that is, in local field potentials and magnetic fields. Our results provide direct support for the idea that temporary storage of information recruits the same brain areas that also process the information. Because similar activity was observed in the two species, the cellular bases of some auditory working memory processes in humans can be studied in monkeys.

Neuronal activity in primate prefrontal cortex related to goal-directed behavior during auditory working memory tasks.

Prefrontal cortex (PFC) has been documented to play critical roles in goal-directed behaviors, like representing goal-relevant events and working memory (WM). However, neurophysiological evidence for such roles of PFC has been obtained mainly with visual tasks but rarely with auditory tasks. In the present study, we tested roles of PFC in auditory goal-directed behaviors by recording local field potentials in the auditory region of left ventrolateral PFC while a monkey performed auditory WM tasks. The tasks consisted of multiple events and required the monkey to change its mental states to achieve the reward. The events were auditory and visual stimuli, as well as specific actions. Mental states were engaging in the tasks and holding task-relevant information in auditory WM. We found that, although based on recordings from one hemisphere in one monkey only, PFC represented multiple events that were important for achieving reward, including auditory and visual stimuli like turning on and off an LED, as well as bar touch. The responses to auditory events depended on the tasks and on the context of the tasks. This provides support for the idea that neuronal representations in PFC are flexible and can be related to the behavioral meaning of stimuli. We also found that engaging in the tasks and holding information in auditory WM were associated with persistent changes of slow potentials, both of which are essential for auditory goal-directed behaviors. Our study, on a single hemisphere in a single monkey, reveals roles of PFC in auditory goal-directed behaviors similar to those in visual goal-directed behaviors, suggesting that functions of PFC in goal-directed behaviors are probably common across the auditory and visual modality. This article is part of a Special Issue entitled SI: Auditory working memory.

Tonic effects of the dopaminergic ventral midbrain on the auditory cortex of awake macaque monkeys.

This study shows that ongoing electrical stimulation of the dopaminergic ventral midbrain can modify neuronal activity in the auditory cortex of awake primates for several seconds. This was reflected in a decrease of the spontaneous firing and in a bidirectional modification of the power of auditory evoked potentials. We consider that both effects are due to an increase in the dopamine tone in auditory cortex induced by the electrical stimulation. Thus, the dopaminergic ventral midbrain may contribute to the tonic activity in auditory cortex that has been proposed to be involved in associating events of auditory tasks (Brosch et al. Hear Res 271:66-73, 2011) and may modulate the signal-to-noise ratio of the responses to auditory stimuli.

The Travelling-Wave Primate System: A New Solution for Magnetic Resonance Imaging of Macaque Monkeys at 7 Tesla Ultra-High Field.

INTRODUCTION: Neuroimaging of macaques at ultra-high field (UHF) is usually conducted by combining a volume coil for transmit (Tx) and a phased array coil for receive (Rx) tightly enclosing the monkey's head. Good results have been achieved using vertical or horizontal magnets with implanted or near-surface coils. An alternative and less costly approach, the travelling-wave (TW) excitation concept, may offer more flexible experimental setups on human whole-body UHF magnetic resonance imaging (MRI) systems, which are now more widely available. Goal of the study was developing and validating the TW concept for in vivo primate MRI. METHODS: The TW Primate System (TWPS) uses the radio frequency shield of the gradient system of a human whole-body 7 T MRI system as a waveguide to propagate a circularly polarized B1 field represented by the TE11 mode. This mode is excited by a specifically designed 2-port patch antenna. For receive, a customized neuroimaging monkey head receive-only coil was designed. Field simulation was used for development and evaluation. Signal-to-noise ratio (SNR) was compared with data acquired with a conventional monkey volume head coil consisting of a homogeneous transmit coil and a 12-element receive coil. RESULTS: The TWPS offered good image homogeneity in the volume-of-interest Turbo spin echo images exhibited a high contrast, allowing a clear depiction of the cerebral anatomy. As a prerequisite for functional MRI, whole brain ultrafast echo planar images were successfully acquired. CONCLUSION: The TWPS presents a promising new approach to fMRI of macaques for research groups with access to a horizontal UHF MRI system.