Electrophysiology publications

Objective . Spontaneous activity in the abdominal ganglion of Aplysia can be used as a convenient bioelectricity source in tests of novel MRI-based functional imaging methods, such as functional Magnetic Resonance Electrical Impedance Tomography (fMREIT). In these tests, it is necessary to find a consistent treatment that modulates neural activity, so that these results can be compared with control data. Effects of MREIT imaging currents combined with treatment were also of interest. Approach . Potassium chloride (KCl) was employed as a rhythm modulator. In a series of experiments, effects of adding different volumes of KCl solution were tested and compared with experiments on control groups that had artificial sea water administered. In all cases, neuronal activity was measured with micro electrode arrays. Main results . It was possible to reversibly stop spontaneous activity in ganglia by increasing the extracellular potassium chloride concentration to 89 mM. There was no effect on experimental outcomes when current was administered to the sample chamber between recordings. Significance . KCl can be used as a reversible neural modulator for testing neural detection methods.

Evidence for intrinsic functional connectivity (FC) within the human brain is largely from neuroimaging studies of hemodynamic activity. Data are lacking from anatomically precise electrophysiological recordings in the most widely studied nodes of human brain networks. Here we used a combination of fMRI and electrocorticography (ECoG) in five human neurosurgical patients with electrodes in the canonical “default” (medial prefrontal and posteromedial cortex), “dorsal attention” (frontal eye fields and superior parietal lobule), and “frontoparietal control” (inferior parietal lobule and dorsolateral prefrontal cortex) networks. In this unique cohort, simultaneous intracranial recordings within these networks were anatomically matched across different individuals. Within each network and for each individual, we found a positive, and reproducible, spatial correlation for FC measures obtained from resting-state fMRI and separately recorded ECoG in the same brains. This relationship was reliably identified for electrophysiological FC based on slow (<1 Hz) fluctuations of high-frequency broadband (70–170 Hz) power, both during wakeful rest and sleep. A similar FC organization was often recovered when using lower-frequency (1–70 Hz) power, but anatomical specificity and consistency were greatest for the high-frequency broadband range. An interfrequency comparison of fluctuations in FC revealed that high and low-frequency ranges often temporally diverged from one another, suggesting that multiple neurophysiological sources may underlie variations in FC. Together, our work offers a generalizable electrophysiological basis for intrinsic FC and its dynamics across individuals, brain networks, and behavioral states. SIGNIFICANCE STATEMENT The study of human brain networks during wakeful “rest”, largely with fMRI, is now a major focus in both cognitive and clinical neuroscience. However, little is known about the neurophysiology of these networks and their dynamics. We studied neural activity during wakeful rest and sleep within neurosurgical patients with directly implanted electrodes. We found that network activity patterns showed striking similarities between fMRI and direct recordings in the same brains. With improved resolution of direct recordings, we also found that networks were best characterized with specific activity frequencies and that different frequencies show different profiles of within-network activity over time. Our work clarifies how networks spontaneously organize themselves across individuals, brain networks, and behavioral states.

Objective . Implantable neural electrode devices are important tools for neuroscience research and have an increasing range of clinical applications. However, the intricacies of the biological response after implantation, and their ultimate impact on recording performance, remain challenging to elucidate. Establishing a relationship between the neurobiology and chronic recording performance is confounded by technical challenges related to traditional electrophysiological, material, and histological limitations. This can greatly impact the interpretations of results pertaining to device performance and tissue health surrounding the implant. Approach . In this work, electrophysiological activity and immunohistological analysis are compared after controlling for motion artifacts, quiescent neuronal activity, and material failure of devices in order to better understand the relationship between histology and electrophysiological outcomes. Main results . Even after carefully accounting for these factors, the presence of viable neurons and lack of glial scarring does not convey single unit recording performance. Significance . To better understand the biological factors influencing neural activity, detailed cellular and molecular tissue responses were examined. Decreases in neural activity and blood oxygenation in the tissue surrounding the implant, shift in expression levels of vesicular transporter proteins and ion channels, axon and myelin injury, and interrupted blood flow in nearby capillaries can impact neural activity around implanted neural interfaces. Combined, these tissue changes highlight the need for more comprehensive, basic science research to elucidate the relationship between biology and chronic electrophysiology performance in order to advance neural technologies.

The posterior auricular muscle (PAM) reflex to sounds has been used clinically to determine hearing threshold as an alternative to other audiological diagnostic measures such as the auditory brainstem response. We have shown that the PAM response is also sensitive to interaural timing differences in normally hearing adults. PAM responses were evoked by both ipsilateral/ contralateral monaural stimulation and by binaural stimulation. Introducing sound delays ipsilaterally or contralaterally decreased the PAM response amplitude and increased its latency. The PAM response in this study shows a qualitatively similar pattern to that seen by the binaural interaction component (BIC) of the auditory brainstem potential to binaural clicks described in previous studies, in that both: have their shortest latency and maximal amplitudes centred around zero interaural timing differences, have response latencies increase with increasing interaural delays up to 1.2 ms and have response amplitudes decrease with increasing interaural delays of up to 1.2 ms. Our data show that the PAM response may be useful in measuring binaural integration in humans non-invasively for diagnostic or research studies.

Parsing simultaneous speech requires listeners use pitch-guided segregation which can be affected by the signal-to-noise ratio (SNR) in the auditory scene. The interaction of these two cues may occur at multiple levels within the cortex. The aims of the current study were to assess the correspondence between oscillatory brain rhythms and determine how listeners exploit pitch and SNR cues to successfully segregate concurrent speech. We recorded electrical brain activity while participants heard double-vowel stimuli whose fundamental frequencies (F0s) differed by zero or four semitones (STs) presented in either clean or noise-degraded (+5 dB SNR) conditions. We found that behavioral identification was more accurate for vowel mixtures with larger pitch separations but F0 benefit interacted with noise. Time-frequency analysis decomposed the EEG into different spectrotemporal frequency bands. Low-frequency (θ, β) responses were elevated when speech did not contain pitch cues (0ST > 4ST) or was noisy, suggesting a correlate of increased listening effort and/or memory demands. Contrastively, γ power increments were observed for changes in both pitch (0ST > 4ST) and SNR (clean > noise), suggesting high-frequency bands carry information related to acoustic features and the quality of speech representations. Brain-behavior associations corroborated these effects; modulations in low-frequency rhythms predicted the speed of listeners' perceptual decisions with higher bands predicting identification accuracy. Results are consistent with the notion that neural oscillations reflect both automatic (pre-perceptual) and controlled (post-perceptual) mechanisms of speech processing that are largely divisible into high- and low-frequency bands of human brain rhythms.

Intracortical microelectrode arrays, especially the Utah array, remain the most common choice for obtaining high dimensional recordings of spiking neural activity for brain computer interface and basic neuroscience research. Despite the widespread use and established design, mechanical, material and biological challenges persist that contribute to a steady decline in recording performance (as evidenced by both diminished signal amplitude and recorded cell population over time) or outright array failure. Device implantation injury causes acute cell death and activation of inflammatory microglia and astrocytes that leads to a chronic neurodegeneration and inflammatory glial aggregation around the electrode shanks and often times fibrous tissue growth above the pia along the bed of the array within the meninges. This multifaceted deleterious cascade can result in substantial variability in performance even under the same experimental conditions. We track both impedance signatures and electrophysiological performance of 4 × 4 floating microelectrode Utah arrays implanted in the primary monocular visual cortex (V1m) of Long-Evans rats over a 12-week period. We employ a repeatable visual stimulation method to compare signal-to-noise ratio as well as single- and multi-unit yield from weekly recordings. To explain signal variability with biological response, we compare arrays categorized as either Type 1, partial fibrous encapsulation, or Type 2, complete fibrous encapsulation and demonstrate performance and impedance signatures unique to encapsulation type. We additionally assess benefits of a biomolecule coating intended to minimize distance to recordable units and observe a temporary improvement on multi-unit recording yield and single-unit amplitude.

This study is the physiological complement to previous behavioral work that demonstrated that rhesus monkeys are able to allocate attention about the surrounding space based on brief, broadband auditory cues. Single-unit recordings were taken from the intermediate layers of the superior colliculus (iSC) while the subjects oriented to visual and auditory targets in the context of a cuing task with their heads unrestrained. The results show a correlation between behavioral manifestations of attention allocation, attention capture and inhibition of return, and modulation of target-evoked responses in single iSC neurons. NEW & NOTEWORTHY These results show for the first time a neural correlate of attention capture and inhibition of return in response to auditory stimuli in the superior colliculus of the head-unrestrained monkey.

Natural environments elicit both phase-locked and non-phase-locked neural responses to the stimulus in the brain. The interpretation of the BOLD signal to date has been based on an association of the non-phase-locked power of high-frequency local field potentials (LFPs), or the related spiking activity in single neurons or groups of neurons. Previous studies have not examined the prediction of the BOLD signal by phase-locked responses. We examined the relationship between the BOLD response and LFPs in the same nine human subjects from multiple corresponding points in the auditory cortex, using amplitude modulated pure tone stimuli of a duration to allow an analysis of phase locking of the sustained time period without contamination from the onset response. The results demonstrate that both phase locking at the modulation frequency and its harmonics, and the oscillatory power in gamma/high-gamma bands are required to predict the BOLD response. Biophysical models of BOLD signal generation in auditory cortex therefore require revision and the incorporation of both phase locking to rhythmic sensory stimuli and power changes in the ensemble neural activity.

Extracellular field potentials (EFP) are widely used to evaluate in vivo neural activity, but identification of multiple sources and their relative contributions is often ambiguous, making the interpretation of the EFP difficult. We have therefore analyzed a model EFP from a simple brainstem circuit with separable pre- and postsynaptic components to determine whether we could isolate its sources. Our previous papers had shown that the barn owl neurophonic largely originates with spikes from input axons and synapses that terminate on the neurons in the nucleus laminaris (NL) (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274–2290, 2010; Kuokkanen PT, Ashida G, Carr CE, Wagner H, Kempter R. J Neurophysiol 110: 117–130, 2013; McColgan T, Liu J, Kuokkanen PT, Carr CE, Wagner H, Kempter R. eLife 6: e26106, 2017). To determine how much the postsynaptic NL neurons contributed to the neurophonic, we recorded EFP responses in NL in vivo. Power spectral analyses showed that a small spectral component of the evoked response, between 200 and 700 Hz, could be attributed to the NL neurons’ spikes, while nucleus magnocellularis (NM) spikes dominate the EFP at frequencies ≳1 kHz. Thus, spikes of NL neurons and NM axons contribute to the EFP in NL in distinct frequency bands. We conclude that if the spectral components of source types are different and if their activities can be selectively modulated, the identification of EFP sources is possible. NEW & NOTEWORTHY Extracellular field potentials (EFPs) generate clinically important signals, but their sources are incompletely understood. As a model, we have analyzed the auditory neurophonic in the barn owl’s nucleus laminaris. There the EFP originates predominantly from spiking in the afferent axons, with spectral power ≳1 kHz, while postsynaptic laminaris neurons contribute little. In conclusion, the identification of EFP sources is possible if they have different spectral components and if their activities can be modulated selectively.

Maternal behaviors are essential for the survival of the young. Previous studies implicated the medial preoptic area (MPOA) as an important region for maternal behaviors, but details of the maternal circuit remain incompletely understood. Here we identify estrogen receptor alpha (Esr1)-expressing cells in the MPOA as key mediators of pup approach and retrieval. Reversible inactivation of MPOAEsr1+ cells impairs those behaviors, whereas optogenetic activation induces immediate pup retrieval. In vivo recordings demonstrate preferential activation of MPOAEsr1+ cells during maternal behaviors and changes in MPOA cell responses across reproductive states. Furthermore, channelrhodopsin-assisted circuit mapping reveals a strong inhibitory projection from MPOAEsr1+ cells to ventral tegmental area (VTA) non-dopaminergic cells. Pathway-specific manipulations reveal that this projection is essential for driving pup approach and retrieval and that VTA dopaminergic cells are reliably activated during those behaviors. Altogether, this study provides new insight into the neural circuit that generates maternal behaviors.

How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL-PFC interactions underlie working memory for everyday experiences.

Objective . Current steering techniques have shown promise in retinal prostheses as a way to increase the number of distinct percepts elicitable without increasing the number of implanted electrodes. Previously, it has been shown that ‘virtual’ electrodes can be created between simultaneously stimulated electrode pairs, producing unique cortical response patterns. This study investigated whether virtual electrodes could be created using 2D current steering, and whether these virtual electrodes can produce cortical responses with predictable spatial characteristics. Approach . Normally-sighted eyes of seven adult anaesthetised cats were implanted with a 42-channel electrode array in the suprachoroidal space and multi-unit neural activity was recorded from the visual cortex. Stimuli were delivered to individual physical electrodes, or electrodes grouped into triangular, rectangular, and hexagonal arrangements. Varying proportions of charge were applied to each electrode in a group to ‘steer’ current and create virtual electrodes. The centroids of cortical responses to stimulation of virtual electrodes were compared to those evoked by stimulation of single physical electrodes. Main results . Responses to stimulation of groups of up to six electrodes with equal ratios of charge on each electrode resulted in cortical activation patterns that were similar to those elicited by the central physical electrode (centroids: RM ANOVA on ranks, p > 0.05; neural spread: one-way ANOVA on Ranks, p > 0.05). We were also able to steer the centroid of activation towards the direction of any of the electrodes of the group by applying a greater charge to that electrode, but the movement in the centroid was not found to be significant. Significance . The results suggest that current steering is possible in two dimensions between up to at least six electrodes, indicating it may be possible to increase the number of percepts in patients without increasing the number of physical electrodes. Being able to reproduce spatial characteristics of responses to individual physical electrodes suggests that this technique could also be used to compensate for faulty electrodes.

Objective: The goal for this research was to identify molecular mechanisms that explain animal-to-animal variability in chronic intracortical recordings. Approach: Microwire electrodes were implanted into Sprague Dawley rats at an acute (1 week) and a chronic (14 weeks) time point. Weekly recordings were conducted, and action potentials were evoked in the barrel cortex by deflecting the rat's whiskers. At 1 and 14 weeks, tissue was collected, and mRNA was extracted. mRNA expression was compared between 1 and 14 weeks using a high throughput multiplexed qRT-PCR. Pearson correlation coefficients were calculated between mRNA expression and signal-to-noise ratios at 14 weeks. Main results: At 14 weeks, a positive correlation between signal-to-noise ratio (SNR) and NeuN and GFAP mRNA expression was observed, indicating a relationship between recording strength and neuronal population, as well as reactive astrocyte activity. The inflammatory state around the electrode interface was evaluated using M1-like and M2-like markers. Expression for both M1-like and M2-like mRNA markers remained steady from 1 to 14 weeks. Anti-inflammatory markers, CD206 and CD163, however, demonstrated a significant positive correlation with SNR quality at 14 weeks. VE-cadherin, a marker for adherens junctions, and PDGFR-β, a marker for pericytes, both partial representatives of blood-brain barrier health, had a positive correlation with SNR at 14 weeks. Endothelial adhesion markers revealed a significant increase in expression at 14 weeks, while CD45, a pan-leukocyte marker, significantly decreased at 14 weeks. No significant correlation was found for either the endothelial adhesion or pan-leukocyte markers. Significance: A positive correlation between anti-inflammatory and blood-brain barrier health mRNA markers with electrophysiological efficacy of implanted intracortical electrodes has been demonstrated. These data reveal potential mechanisms for further evaluation to determine potential target mechanisms to improve consistency of intracortical electrodes recordings and reduce animal-to-animal/implant-to-implant variability.

Healthy aging is associated with marked effects on sleep, including its daily amount and architecture, as well as the specific EEG oscillations. Neither the neurophysiological underpinnings nor the biological significance of these changes are understood, and crucially the question remains whether aging is associated with reduced sleep need or a diminished capacity to generate sufficient sleep. Here we tested the hypothesis that aging may affect local cortical networks, disrupting the capacity to generate and sustain sleep oscillations, and with it the local homeostatic response to sleep loss. We performed chronic recordings of cortical neural activity and local field potentials from the motor cortex in young and older male C57BL/6J mice, during spontaneous waking and sleep, as well as during sleep after sleep deprivation. In older animals, we observed an increase in the incidence of non-rapid eye movement sleep local field potential slow waves and their associated neuronal silent (OFF) periods, whereas the overall pattern of state-dependent cortical neuronal firing was generally similar between ages. Furthermore, we observed that the response to sleep deprivation at the level of local cortical network activity was not affected by aging. Our data thus suggest that the local cortical neural dynamics and local sleep homeostatic mechanisms, at least in the motor cortex, are not impaired during healthy senescence in mice. This indicates that powerful protective or compensatory mechanisms may exist to maintain neuronal function stable across the life span, counteracting global changes in sleep amount and architecture. SIGNIFICANCE STATEMENT The biological significance of age-dependent changes in sleep is unknown but may reflect either a diminished sleep need or a reduced capacity to generate deep sleep stages. As aging has been linked to profound disruptions in cortical sleep oscillations and because sleep need is reflected in specific patterns of cortical activity, we performed chronic electrophysiological recordings of cortical neural activity during waking, sleep, and after sleep deprivation from young and older mice. We found that all main hallmarks of cortical activity during spontaneous sleep and recovery sleep after sleep deprivation were largely intact in older mice, suggesting that the well-described age-related changes in global sleep are unlikely to arise from a disruption of local network dynamics within the neocortex.

Synaptic plasticity in the lamellar CA3 to CA1 circuitry has been extensively studied while interlamellar CA1 to CA1 connections have not yet received much attention. One of our earlier studies demonstrated that axons of CA1 pyramidal neurons project to neighboring CA1 neurons, implicating information transfer along a longitudinal interlamellar network. Still, it remains unclear whether long-term synaptic plasticity is present within this longitudinal CA1 network. Here, we investigate long-term synaptic plasticity between CA1 pyramidal cells, using in vitro and in vivo extracellular recordings and 3D holography glutamate uncaging. We found that the CA1-CA1 network exhibits NMDA receptor-dependent long-term potentiation (LTP) without direction or layer selectivity. By contrast, we find no significant long-term depression (LTD) under various LTD induction protocols. These results implicate unique synaptic properties in the longitudinal projection suggesting that the interlamellar CA1 network could be a promising structure for hippocampus-related information processing and brain diseases.

Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher-processing centers. Efferent activation inhibits OHC active amplification within the mammalian cochlea, through the activation of a calcium-permeable α9α10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels. Correct operation of this feedback requires careful matching of acoustic input with the strength of cochlear inhibition (Galambos, 1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by the rate of MOC activity and short-term facilitation at the MOC–OHC synapse (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in mice of either sex) that a mutation in the α9α10 nAChR with increased duration of channel gating (Taranda et al., 2009) greatly elongates hair cell-evoked IPSCs and Ca 2+ signals. Interestingly, MOC–OHC synapses of L9 ′ T mice presented reduced quantum content and increased presynaptic facilitation. These phenotypic changes lead to enhanced and sustained synaptic responses and OHC hyperpolarization upon high-frequency stimulation of MOC terminals. At the cochlear physiology level these changes were matched by a longer time course of efferent MOC suppression. This indicates that the properties of the MOC–OHC synapse directly determine the efficacy of the MOC feedback to the cochlea being a main player in the “gain control” of the auditory periphery. SIGNIFICANCE STATEMENT Plasticity can involve reciprocal signaling across chemical synapses. An opportunity to study this phenomenon occurs in the mammalian cochlea whose sensitivity is regulated by efferent olivocochlear neurons. These release acetylcholine to inhibit sensory hair cells. A point mutation in the hair cell's acetylcholine receptor that leads to increased gating of the receptor greatly elongates IPSCs. Interestingly, efferent terminals from mutant mice present a reduced resting release probability. However, upon high-frequency stimulation transmitter release facilitates strongly to produce stronger and far longer-lasting inhibition of cochlear function. Thus, central neuronal feedback on cochlear hair cells provides an opportunity to define plasticity mechanisms in cholinergic synapses other than the highly studied neuromuscular junction.

Significance Listeners with hearing loss have trouble communicating in many social settings. In such situations, listeners with normal hearing suppress the neural representation of competing sounds, a process known as auditory selective attention. We compared hearing-impaired (HI) and normal-hearing (NH) listeners on a spatial selective attention task while measuring neural responses using electroencephalography. Compared with NH listeners, HI listeners have poorer sensitivity to spatial cues, perform more poorly on the selective attention task, and show weaker neural suppression of competing sounds. Moreover, these different measures are correlated both for HI and for NH listeners. These results suggest that poor spatial acuity produces problems with selective attention. These findings have implications both for basic science and for development of next-generation hearing aids.

Unlike cisplatin, which forms bifunctional DNA adducts, monofunctional platinum(II) complexes bind only one strand of DNA and might target cancer without causing auditory side-effects associated with cisplatin treatment. We synthesized the monofunctional triamine-ligated platinum(II) complexes, Pt(diethylenetriamine)Cl, [Pt(dien)Cl]+, and Pt(N,N-diethyldiethylenetriamine)Cl, [Pt(Et2dien)Cl]+, and the monofunctional heterocyclic-ligated platinum(II) complexes, pyriplatin and phenanthriplatin, and compared their 5'-GMP binding rates, cellular compartmental distribution and cellular viability effects. A zebrafish inner ear model was used to determine if the monofunctional complexes and cisplatin caused hearing threshold shifts and reduced auditory hair cell density. The four monofunctional complexes had varied relative GMP binding rates, but similar cytosolic and nuclear compartmental uptake in three cancer cell lines (A549, Caco2, HTB16) and a control cell line (IMR90). Phenanthriplatin had the strongest effect against cellular viability, comparable to cisplatin, followed by [Pt(Et2dien)Cl]+, pyriplatin and [Pt(dien)Cl]+. Phenanthriplatin also produced the highest hearing threshold shifts followed by [Pt(dien)Cl]+, [Pt(Et2dien)Cl]+, cisplatin and pyriplatin. Hair cell counts taken from four regions of the zebrafish saccule showed that cisplatin significantly reduced hair cell density in three regions and phenanthriplatin in only one region, with the other complexes having no significant effect. Utricular hair cell density was not reduced by any of the compounds. Our results suggest that placing greater steric hindrance cis to one side of the platinum coordinating center in monofunctional complexes promotes efficient targeting of the nuclear compartment and guanosine residues, and may be responsible for reducing cancer cell viability. Also, the monofunctional compounds caused hearing threshold shifts with minimal effect on hair cell density, which suggests that they may affect different pathways than cisplatin.

Neuromodulators such as noradrenaline appear to play a crucial role in learning and memory. The goal of this study was to determine the role of norepinephrine in representation of odorant identity and value by olfactory bulb oscillations in an olfactory learning task. We wanted to determine whether the different bandwidths of olfactory bulb oscillations encode information involved in associating the odor with the value, and whether norepinephrine is involved in modulating this association. To this end mice expressing halorhodopsin under the dopamine-beta-hydrolase (DBH) promoter received an optetrode implant targeted to the olfactory bulb. Mice learned to differentiate odorants in a go-no-go task. A receiver operating characteristic (ROC) analysis showed that there was development of a broadband differential rewarded vs. unrewarded odorant-induced change in the power of local field potential oscillations as the mice became proficient in discriminating between two odorants. In addition, the change in power reflected the value of the odorant rather than the identity. Furthermore, optogenetic silencing of local noradrenergic axons in the olfactory bulb altered the differential oscillatory power response to the odorants for the theta, beta, and gamma bandwidths.

Natural sound is composed of various frequencies. Although the core region of the primate auditory cortex has functionally defined sound frequency preference maps, how the map is organized in the auditory areas of the belt and parabelt regions is not well known. In this study, we investigated the functional organizations of the core, belt, and parabelt regions encompassed by the lateral sulcus and the superior temporal sulcus in the common marmoset ( Callithrix jacchus ). Using optical intrinsic signal imaging, we obtained evoked responses to band-pass noise stimuli in a range of sound frequencies (0.5–16 kHz) in anesthetized adult animals and visualized the preferred sound frequency map on the cortical surface. We characterized the functionally defined organization using histologically defined brain areas in the same animals. We found tonotopic representation of a set of sound frequencies (low to high) within the primary (A1), rostral (R), and rostrotemporal (RT) areas of the core region. In the belt region, the tonotopic representation existed only in the mediolateral (ML) area. This representation was symmetric with that found in A1 along the border between areas A1 and ML. The functional structure was not very clear in the anterolateral (AL) area. Low frequencies were mainly preferred in the rostrotemplatal (RTL) area, while high frequencies were preferred in the caudolateral (CL) area. There was a portion of the parabelt region that strongly responded to higher sound frequencies (>5.8 kHz) along the border between the rostral parabelt (RPB) and caudal parabelt (CPB) regions.