Functional characterization of the fronto-parietal reaching and grasping network: reversible deactivation of M1 and areas 2, 5, and 7b in awake behaving monkeys.

In the present investigation, we examined the role of different cortical fields in the fronto-parietal reaching and grasping network in awake, behaving macaque monkeys. This network is greatly expanded in primates compared to other mammals and coevolved with glabrous hands with opposable thumbs and the extraordinary dexterous behaviors employed by a number of primates, including humans. To examine this, we reversibly deactivated the primary motor area (M1), anterior parietal area 2, and posterior parietal areas 5L and 7b individually while monkeys were performing two types of reaching and grasping tasks. Reversible deactivation was accomplished with small microfluidic thermal regulators abutting specifically targeted cortical areas. Placement of these devices in the different cortical fields was confirmed post hoc in histologically processed tissue. Our results indicate that the different areas examined form a complex network of motor control that is overlapping. However, several consistent themes emerged that suggest the independent roles that motor cortex, area 2, area 7b, and area 5L play in the motor planning and execution of reaching and grasping movements. Area 5L is involved in the early stages and area 7b the later stages of a reaching and grasping movement, motor cortex is involved in all aspects of the execution of the movement, and area 2 provides proprioceptive feedback throughout the movement. We discuss our results in the context of previous studies that explored the fronto-parietal network, the overlapping (but also independent) functions of different nodes of this network, and the rapid compensatory plasticity of this network.NEW & NOTEWORTHY This is the first study to directly compare the results of cooling different portions of the fronto-parietal reaching and grasping network (motor cortex, anterior and posterior parietal cortex) in the same animals and the first to employ a complex, bimanual reaching and grasping task that is ethologically relevant. Whereas cooling area 7b or area 5L evoked deficits at distinct task phases, cooling M1 evoked a general set of deficits and cooling area 2 evoked proprioceptive deficits.

Reversal of Age-Related Changes in Cortical Sound-Azimuth Selectivity with Training.

The compromised abilities to understand speech and localize sounds are two hallmark deficits in aged individuals. Earlier studies have shown that age-related deficits in cortical neural timing, which is clearly associated with speech perception, can be partially reversed with auditory training. However, whether training can reverse aged-related cortical changes in the domain of spatial processing has never been studied. In this study, we examined cortical spatial processing in ~21-month-old rats that were trained on a sound-azimuth discrimination task. We found that animals that experienced 1 month of training displayed sharper cortical sound-azimuth tuning when compared to the age-matched untrained controls. This training-induced remodeling in spatial tuning was paralleled by increases of cortical parvalbumin-labeled inhibitory interneurons. However, no measurable changes in cortical spatial processing were recorded in age-matched animals that were passively exposed to training sounds with no task demands. These results that demonstrate the effects of training on cortical spatial domain processing in the rodent model further support the notion that age-related changes in central neural process are, due to their plastic nature, reversible. Moreover, the results offer the encouraging possibility that behavioral training might be used to attenuate declines in auditory perception, which are commonly observed in older individuals.

Age-related changes in sound onset and offset intensity coding in auditory cortical fields A1 and CL of rhesus macaques.

Inhibition plays a key role in shaping sensory processing in the central auditory system and has been implicated in sculpting receptive field properties such as sound intensity coding and also in shaping temporal patterns of neuronal firing such as onset- or offset-evoked responses. There is substantial evidence supporting a decrease in inhibition throughout the ascending auditory pathway in geriatric animals. We therefore examined intensity coding of onset (ON) and offset (OFF) responses in auditory cortex of aged and young monkeys. A large proportion of cells in the primary auditory cortex (A1) and the caudolateral field (CL) displayed nonmonotonic rate-level functions for OFF responses in addition to nonmonotonic coding of ON responses. Aging differentially affected ON and OFF responses; the magnitude of effects was generally greater for ON responses. In addition to higher firing rates, neurons in old monkeys exhibited a significant increase in the proportion of monotonic rate-level functions and had higher best intensities than those in young monkeys. OFF responses in young monkeys displayed a range of intensity coding relationships with ON responses of the same cells, ranging from highly similar to highly dissimilar. Dissimilarity in ON/OFF coding was greater in CL and was reduced with aging, which was largely explained by a preferential decrease in the percentage of cells with nonmonotonic coding of ON and OFF responses. The changes we observed are consistent with previously demonstrated alterations in inhibition in the ascending auditory pathway of primates and could be involved in age-related deficits in the temporal processing of sounds.NEW & NOTEWORTHY Aging has a major impact on intensity coding of neurons in auditory cortex of rhesus macaques. Neural responses to sound onset and offset were affected to different extents, and their rate-level functions became more mutually similar, which could be accounted for by the loss of nonmonotonic intensity coding in geriatric monkeys. These findings were consistent with weakened inhibition in the central auditory system and could contribute to auditory processing deficits in elderly subjects.

Age-Related Changes in Temporal Processing of Rapidly-Presented Sound Sequences in the Macaque Auditory Cortex.

The mammalian auditory cortex is necessary to resolve temporal features in rapidly-changing sound streams. This capability is crucial for speech comprehension in humans and declines with normal aging. Nonhuman primate studies have revealed detrimental effects of normal aging on the auditory nervous system, and yet the underlying influence on temporal processing remains less well-defined. Therefore, we recorded from the core and lateral belt areas of auditory cortex when awake young and old monkeys listened to tone-pip and noise-burst sound sequences. Elevated spontaneous and stimulus-driven activity were the hallmark characteristics in old monkeys. These old neurons showed isomorphic-like discharge patterns to stimulus envelopes, though their phase-locking was less precise. Functional preference in temporal coding between the core and belt existed in the young monkeys but was mostly absent in the old monkeys, in which old belt neurons showed core-like response profiles. Finally, the analysis of population activity patterns indicated that the aged auditory cortex demonstrated a homogenous, distributed coding strategy, compared to the selective, sparse coding strategy observed in the young monkeys. Degraded temporal fidelity and highly-responsive, broadly-tuned cortical responses could underlie how aged humans have difficulties to resolve and track dynamic sounds leading to speech processing deficits.

Spectral and spatial tuning of onset and offset response functions in auditory cortical fields A1 and CL of rhesus macaques.

The mammalian auditory cortex is necessary for spectral and spatial processing of acoustic stimuli. Most physiological studies of single neurons in the auditory cortex have focused on the onset and sustained portions of evoked responses, but there have been far fewer studies on the relationship between onset and offset responses. In the current study, we compared spectral and spatial tuning of onset and offset responses of neurons in primary auditory cortex (A1) and the caudolateral (CL) belt area of awake macaque monkeys. Several different metrics were used to determine the relationship between onset and offset response profiles in both frequency and space domains. In the frequency domain, a substantial proportion of neurons in A1 and CL displayed highly dissimilar best stimuli for onset- and offset-evoked responses, although even for these neurons, there was usually a large overlap in the range of frequencies that elicited onset, and offset responses and distributions of tuning overlap metrics were mostly unimodal. In the spatial domain, the vast majority of neurons displayed very similar best locations for onset- and offset-evoked responses, along with unimodal distributions of all tuning overlap metrics considered. Finally, for both spectral and spatial tuning, a slightly larger fraction of neurons in A1 displayed nonoverlapping onset and offset response profiles, relative to CL, which supports hierarchical differences in the processing of sounds in the two areas. However, these differences are small compared with differences in proportions of simple cells (low overlap) and complex cells (high overlap) in primary and secondary visual areas.NEW & NOTEWORTHY In the current study, we examine the relationship between the tuning of neural responses evoked by the onset and offset of acoustic stimuli in the primary auditory cortex, as well as a higher-order auditory area-the caudolateral belt field-in awake rhesus macaques. In these areas, the relationship between onset and offset response profiles in frequency and space domains formed a continuum, ranging from highly overlapping to highly nonoverlapping.

Improved methods for acrylic-free implants in nonhuman primates for neuroscience research.

Traditionally, head fixation devices and recording cylinders have been implanted in nonhuman primates (NHP) using dental acrylic despite several shortcomings associated with acrylic. The use of more biocompatible materials such as titanium and PEEK is becoming more prevalent in NHP research. We describe a cost-effective set of procedures that maximizes the integration of headposts and recording cylinders with the animal's tissues while reducing surgery time. Nine rhesus monkeys were implanted with titanium headposts, and one of these was also implanted with a recording chamber. In each case, a three-dimensional printed replica of the skull was created based on computerized tomography scans. The titanium feet of the headposts were shaped, and the skull thickness was measured preoperatively, reducing surgery time by up to 70%. The recording cylinder was manufactured to conform tightly to the skull, which was fastened to the skull with four screws and remained watertight for 8.5 mo. We quantified the amount of regression of the skin edge at the headpost. We found a large degree of variability in the timing and extent of skin regression that could not be explained by any single recorded factor. However, there was not a single case of bone exposure; although skin retracted from the titanium, skin also remained adhered to the skull adjacent to those regions. The headposts remained fully functional and free of complications for the experimental life of each animal, several of which are still participating in experiments more than 4 yr after implant.NEW & NOTEWORTHY Cranial implants are often necessary for performing neurophysiology research with nonhuman primates. We present methods for using three-dimensional printed monkey skulls to form and fabricate acrylic-free implants preoperatively to decrease surgery times and the risk of complications and increase the functional life of the implant. We focused on reducing costs, creating a feasible timeline, and ensuring compatibility with existing laboratory systems. We discuss the importance of using more biocompatible materials and enhancing osseointegration.

Effects of aging on the response of single neurons to amplitude-modulated noise in primary auditory cortex of rhesus macaque.

Temporal envelope processing is critical for speech comprehension, which is known to be affected by normal aging. Whereas the macaque is an excellent animal model for human cerebral cortical function, few studies have investigated neural processing in the auditory cortex of aged, nonhuman primates. Therefore, we investigated age-related changes in the spiking activity of neurons in primary auditory cortex (A1) of two aged macaque monkeys using amplitude-modulated (AM) noise and compared these responses with data from a similar study in young monkeys (Yin P, Johnson JS, O'Connor KN, Sutter ML. J Neurophysiol 105: 582-600, 2011). For each neuron, we calculated firing rate (rate code) and phase-locking using phase-projected vector strength (temporal code). We made several key findings where neurons in old monkeys differed from those in young monkeys. Old monkeys had higher spontaneous and driven firing rates, fewer neurons that synchronized with the AM stimulus, and fewer neurons that had differential responses to AM stimuli with both a rate and temporal code. Finally, whereas rate and temporal tuning functions were positively correlated in young monkeys, this relationship was lost in older monkeys at both the population and single neuron levels. These results are consistent with considerable evidence from rodents and primates of an age-related decrease in inhibition throughout the auditory pathway. Furthermore, this dual coding in A1 is thought to underlie the capacity to encode multiple features of an acoustic stimulus. The apparent loss of ability to encode AM with both rate and temporal codes may have consequences for stream segregation and effective speech comprehension in complex listening environments.

Age-related changes of auditory brainstem responses in nonhuman primates.

Nonhuman primates, compared with humans and rodents, have historically been far less used for studies of age-related hearing loss, primarily because of their long life span and high cost of maintenance. Strong similarities in genetics, anatomy, and neurophysiology of the auditory nervous system between humans and monkeys, however, could provide fruitful opportunities to enhance our understanding of hearing loss. The present study used a common, noninvasive technique for testing hearing sensitivity in humans, the auditory brainstem response (ABR), to assess the hearing of 48 rhesus macaques from 6 to 35 yr of age to clicks and tone stimuli between 0.5 and 16.0 kHz. Old monkeys, particularly those above 21.5 yr of age, had missing ABR waveforms at high frequencies. Regression analyses revealed that ABR threshold increased as a function of age at peaks II and IV simultaneously. In the suprathreshold hearing condition (70 dB peak sound pressure level), ABR-based audiograms similarly varied as a function of age such that old monkeys had smaller peak amplitudes and delayed latencies at low, middle, and high frequencies. Peripheral hearing differences remained a major influence associated with age-related changes in audiometric functions of old monkeys at a comparable sensation level across animals. The present findings suggest that hearing loss occurs in old monkeys across a wide range of frequencies and that these deficits increase in severity with age. Parallel to prior studies in monkeys, we found weak effects of sex on hearing, and future investigations are necessary to clarify its role in age-related hearing loss.

Reversible deactivation of higher-order posterior parietal areas. II. Alterations in response properties of neurons in areas 1 and 2.

The role that posterior parietal (PPC) and motor cortices play in modulating neural responses in somatosensory areas 1 and 2 was examined with reversible deactivation by transient cooling. Multiunit recordings from neurons in areas 1 and 2 were collected from six anesthetized adult monkeys (Macaca mulatta) before, during, and after reversible deactivation of areas 5L or 7b or motor cortex (M1/PM), while select locations on the hand and forelimb were stimulated. Response changes were quantified as increases and decreases to stimulus-driven activity relative to baseline and analyzed during three recording epochs: during deactivation ("cool") and at two time points after deactivation ("rewarm 1," "rewarm 2"). Although the type of response change observed was variable, for neurons at the recording sites tested >90% exhibited a significant change in response during cooling of 7b while cooling area 5L or M1/PM produced a change in 75% and 64% of sites, respectively. These results suggest that regions in the PPC, and to a lesser extent motor cortex, shape the response characteristics of neurons in areas 1 and 2 and that this kind of feedback modulation is necessary for normal somatosensory processing. Furthermore, this modulation appears to happen on a minute-by-minute basis and may serve as the substrate for phenomena such as somatosensory attention.

Reversible deactivation of higher-order posterior parietal areas. I. Alterations of receptive field characteristics in early stages of neocortical processing.

Somatosensory processing in the anesthetized macaque monkey was examined by reversibly deactivating posterior parietal areas 5L and 7b and motor/premotor cortex (M1/PM) with microfluidic thermal regulators developed by our laboratories. We examined changes in receptive field size and configuration for neurons in areas 1 and 2 that occurred during and after cooling deactivation. Together the deactivated fields and areas 1 and 2 form part of a network for reaching and grasping in human and nonhuman primates. Cooling area 7b had a dramatic effect on receptive field size for neurons in areas 1 and 2, while cooling area 5 had moderate effects and cooling M1/PM had little effect. Specifically, cooling discrete locations in 7b resulted in expansions of the receptive fields for neurons in areas 1 and 2 that were greater in magnitude and occurred in a higher proportion of sites than similar changes evoked by cooling the other fields. At some sites, the neural receptive field returned to the precooling configuration within 5-22 min of rewarming, but at other sites changes in receptive fields persisted. These results indicate that there are profound top-down influences on sensory processing of early cortical areas in the somatosensory cortex.

Fabrication of an inexpensive, implantable cooling device for reversible brain deactivation in animals ranging from rodents to primates.

We have developed a compact and lightweight microfluidic cooling device to reversibly deactivate one or more areas of the neocortex to examine its functional macrocircuitry as well as behavioral and cortical plasticity. The device, which we term the "cooling chip," consists of thin silicone tubing (through which chilled ethanol is circulated) embedded in mechanically compliant polydimethylsiloxane (PDMS). PDMS is tailored to compact device dimensions (as small as 21 mm(3)) that precisely accommodate the geometry of the targeted cortical area. The biocompatible design makes it suitable for both acute preparations and chronic implantation for long-term behavioral studies. The cooling chip accommodates an in-cortex microthermocouple measuring local cortical temperature. A microelectrode may be used to record simultaneous neural responses at the same location. Cortex temperature is controlled by computer regulation of the coolant flow, which can achieve a localized cortical temperature drop from 37 to 20°C in less than 3 min and maintain target temperature to within ±0.3°C indefinitely. Here we describe cooling chip fabrication and performance in mediating cessation of neural signaling in acute preparations of rodents, ferrets, and primates.

Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity.

The auditory cortex is critical for perceiving a sound's location. However, there is no topographic representation of acoustic space, and individual auditory cortical neurons are often broadly tuned to stimulus location. It thus remains unclear how acoustic space is represented in the mammalian cerebral cortex and how it could contribute to sound localization. This report tests whether the firing rates of populations of neurons in different auditory cortical fields in the macaque monkey carry sufficient information to account for horizontal sound localization ability. We applied an optimal neural decoding technique, based on maximum likelihood estimation, to populations of neurons from 6 different cortical fields encompassing core and belt areas. We found that the firing rate of neurons in the caudolateral area contain enough information to account for sound localization ability, but neurons in other tested core and belt cortical areas do not. These results provide a detailed and plausible population model of how acoustic space could be represented in the primate cerebral cortex and support a dual stream processing model of auditory cortical processing.

Hierarchical and serial processing in the spatial auditory cortical pathway is degraded by natural aging.

The compromised abilities to localize sounds and to understand speech are two hallmark deficits in aged individuals. The auditory cortex is necessary for these processes, yet we know little about how normal aging affects these early cortical fields. In this study, we recorded the spatial tuning of single neurons in primary (auditory cortex, A1) and secondary (caudolateral field, CL) auditory cortical areas in young and aged alert rhesus macaques. We found that the neurons of aged animals had greater spontaneous and driven activity, and broader spatial tuning compared with those of younger animals. Importantly, spatial tuning was not sharpened between A1 and CL in aged monkeys as it is in younger monkeys. This implies that a major effect of normal aging is a degradation of the hierarchical processing between serially connected cortical areas, which could be a key contributing mechanism of the general cognitive decline that is commonly observed in normal aging.

Representation of con-specific vocalizations in the core and belt areas of the auditory cortex in the alert macaque monkey.

Auditory cortical processing in primates has been proposed to be divided into two parallel processing streams, a caudal spatial stream and a rostral nonspatial stream. Previous single neuron studies have indicated that neurons in the rostral lateral belt respond selectively to vocalization stimuli, whereas imaging studies have indicated that selective vocalization processing first occurs in higher order cortical areas. To test the dual stream hypothesis and to find evidence to account for the difference between the electrophysiological and imaging results, we recorded the responses of single neurons in core and belt auditory cortical fields to both forward and reversed vocalizations. We found that there was little difference in the overall firing rate of neurons across different cortical areas or between forward and reversed vocalizations. However, more information was carried in the overall firing rate for forward vocalizations compared with reversed vocalizations in all areas except the rostral field of the core (area R). These results are consistent with the imaging results and are inconsistent with early rostral cortical areas being involved in selectively processing vocalization stimuli based on a firing rate code. They further suggest that a more complex processing scheme is in play in these early auditory cortical areas.

The relationship between magnetic and electrophysiological responses to complex tactile stimuli.

BACKGROUND: Magnetoencephalography (MEG) has become an increasingly popular technique for non-invasively characterizing neuromagnetic field changes in the brain at a high temporal resolution. To examine the reliability of the MEG signal, we compared magnetic and electrophysiological responses to complex natural stimuli from the same animals. We examined changes in neuromagnetic fields, local field potentials (LFP) and multi-unit activity (MUA) in macaque monkey primary somatosensory cortex that were induced by varying the rate of mechanical stimulation. Stimuli were applied to the fingertips with three inter-stimulus intervals (ISIs): 0.33s, 1s and 2s. RESULTS: Signal intensity was inversely related to the rate of stimulation, but to different degrees for each measurement method. The decrease in response at higher stimulation rates was significantly greater for MUA than LFP and MEG data, while no significant difference was observed between LFP and MEG recordings. Furthermore, response latency was the shortest for MUA and the longest for MEG data. CONCLUSION: The MEG signal is an accurate representation of electrophysiological responses to complex natural stimuli. Further, the intensity and latency of the MEG signal were better correlated with the LFP than MUA data suggesting that the MEG signal reflects primarily synaptic currents rather than spiking activity. These differences in latency could be attributed to differences in the extent of spatial summation and/or differential laminar sensitivity.

Visually induced plasticity of auditory spatial perception in macaques.

When experiencing spatially disparate visual and auditory stimuli, a common percept is that the sound originates from the location of the visual stimulus, an illusion known as the ventriloquism effect. This illusion can persist for tens of minutes, a phenomenon termed the ventriloquism aftereffect. The underlying neuronal mechanisms of this rapidly induced plasticity remain unclear; indeed, it remains untested whether similar multimodal interactions occur in other species. We therefore tested whether macaque monkeys experience the ventriloquism aftereffect similar to the way humans do. The ability of two monkeys to determine which side of the midline a sound was presented from was tested before and after a period of 20-60 min in which the monkeys experienced either spatially identical or spatially disparate auditory and visual stimuli. In agreement with human studies, the monkeys did experience a shift in their auditory spatial perception in the direction of the spatially disparate visual stimulus, and the aftereffect did not transfer across sounds that differed in frequency by two octaves. These results show that macaque monkeys experience the ventriloquism aftereffect similar to the way humans do in all tested respects, indicating that these multimodal interactions are a basic phenomenon of the central nervous system.

Sex and Electrode Configuration in Transcranial Electrical Stimulation.

Transcranial electrical stimulation (tES) can be an effective non-invasive neuromodulation procedure. Unfortunately, the considerable variation in reported treatment outcomes, both within and between studies, has made the procedure unreliable for many applications. To determine if individual differences in cranium morphology and tissue conductivity can account for some of this variation, the electrical density at two cortical locations (temporal and frontal) directly under scalp electrodes was modeled using a validated MRI modeling procedure in 23 subjects (12 males and 11 females). Three different electrode configurations (non-cephalic, bi-cranial, and ring) commonly used in tES were modeled at three current intensities (0.5, 1.0, and 2.0 mA). The aims were to assess the effects of configuration and current intensity on relative current received at a cortical brain target directly under the stimulating electrode and to characterize individual variation. The different electrode configurations resulted in up to a ninefold difference in mean current densities delivered to the brains. The ring configuration delivered the least current and the non-cephalic the most. Female subjects showed much less current to the brain than male subjects. Individual differences in the current received and differences in electrode configurations may account for significant variability in current delivered and, thus, potentially a significant portion of reported variation in clinical outcomes at two commonly targeted regions of the brain.

Impact of diet-derived signaling molecules on human cognition: exploring the food-brain axis.

The processes that define mammalian physiology evolved millions of years ago in response to ancient signaling molecules, most of which were acquired by ingestion and digestion. In this way, evolution inextricably linked diet to all major physiological systems including the nervous system. The importance of diet in neurological development is well documented, although the mechanisms by which diet-derived signaling molecules (DSMs) affect cognition are poorly understood. Studies on the positive impact of nutritive and non-nutritive bioactive molecules on brain function are encouraging but lack the statistical power needed to demonstrate strong positive associations. Establishing associations between DSMs and cognitive functions like mood, memory and learning are made even more difficult by the lack of robust phenotypic markers that can be used to accurately and reproducibly measure the effects of DSMs. Lastly, it is now apparent that processes like neurogenesis and neuroplasticity are embedded within layers of interlocked signaling pathways and gene regulatory networks. Within these interdependent pathways and networks, the various transducers of DSMs are used combinatorially to produce those emergent adaptive gene expression responses needed for stimulus-induced neurogenesis and neuroplasticity. Taken together, it appears that cognition is encoded genomically and modified by epigenetics and epitranscriptomics to produce complex transcriptional programs that are exquisitely sensitive to signaling molecules from the environment. Models for how DSMs mediate the interplay between the environment and various neuronal processes are discussed in the context of the food-brain axis.

Cortical connections of the second somatosensory area and the parietal ventral area in macaque monkeys.

To gain insight into how cortical fields process somatic inputs and ultimately contribute to complex abilities such as tactile object perception, we examined the pattern of connections of two areas in the lateral sulcus of macaque monkeys: the second somatosensory area (S2), and the parietal ventral area (PV). Neuroanatomical tracers were injected into electrophysiologically and/or architectonically defined locations, and labeled cell bodies were identified in cortex ipsilateral and contralateral to the injection site. Transported tracer was related to architectonically defined boundaries so that the full complement of connections of S2 and PV could be appreciated. Our results indicate that S2 is densely interconnected with the primary somatosensory area (3b), PV, and area 7b of the ipsilateral hemisphere, and with S2, 7b, and 3b in the opposite hemisphere. PV is interconnected with areas 3b and 7b, with the parietal rostroventral area, premotor cortex, posterior parietal cortex, and with the medial auditory belt areas. Contralateral connections were restricted to PV in the opposite hemisphere. These data indicate that S2 and PV have unique and overlapping patterns of connections, and that they comprise part of a network that processes both cutaneous and proprioceptive inputs necessary for tactile discrimination and recognition. Although more data are needed, these patterns of interconnections of cortical fields and thalamic nuclei suggest that the somatosensory system may not be segregated into two separate streams of information processing, as has been hypothesized for the visual system. Rather, some fields may be involved in a variety of functions that require motor and sensory integration.

Effects of intensity and location on sound location discrimination in macaque monkeys.

Sound localization performance is degraded at low stimulus intensities in humans, and while the sound localization ability of humans and macaque monkeys appears similar, the effects of intensity have yet to be described in the macaque. We therefore defined the ability of four macaque monkeys to localize broadband noise stimuli at four different absolute intensities and six different starting locations in azimuth. Results indicate that performance was poorest at the lowest intensity tested (25 dB SPL), intermediate at 35 dB SPL, and equivalent at 55 and 75 dB SPL. Localization performance was best at 0 degree (directly in front of the animal) and was systematically degraded at more peripheral locations (+/-30 degrees and 90 degrees) and worst at a location directly behind the animal. Reaction times showed the same trends, with reaction times increasing with decreasing stimulus intensity, even under conditions where the monkey discriminated the location change with the same performance. These results indicate that sound level as well as position profoundly influences sound localization ability.