Publications using TDT

We used acoustic clicks to study the impulse response of the neurophonic potential in the barn owl's nucleus laminaris. Clicks evoked a complex oscillatory neural response with a component that reflected the best frequency measured with tonal stimuli. The envelope of this component was obtained from the analytic signal created using the Hilbert transform. The time courses of the envelope and carrier waveforms were characterized by fitting them with filters. The envelope was better fitted with a Gaussian than with the envelope of a gamma-tone function. The carrier was better fitted with a frequency glide than with a constant instantaneous frequency. The change of the instantaneous frequency with time was better fitted with a linear fit than with a saturating nonlinearity. Frequency glides had not been observed in the bird's auditory system before. The glides were similar to those observed in the mammalian auditory nerve. Response amplitude, group delay, frequency, and phase depended in a systematic way on click level. In most cases, response amplitude decreased linearly as stimulus level decreased, while group delay, phase, and frequency increased linearly as level decreased. Thus the impulse response of the neurophonic potential in the nucleus laminaris of barn owls reflects many characteristics also observed in responses of the basilar membrane and auditory nerve in mammals.

For analyses of complex sounds, many neurons integrate information across different spectral elements via suppressive effects that are distant from the neurons' excitatory tuning. In the mustached bat, suppression evoked by sounds within the first sonar harmonic (23–30 kHz) or in the subsonar band (<23 kHz) alters responsiveness to the higher best frequencies of many neurons. This study examined features and mechanisms associated with low-frequency (LF) suppression among neurons of the lateral lemniscal nuclei (NLL). We obtained extracellular recordings from neurons in the intermediate and ventral nuclei of the lateral lemniscus, observing different forms of LF suppression related to the two above-cited frequency bands. To understand the mechanisms underlying this suppression in NLL neurons, we examined the roles of glycinergic and GABAergic input through local microiontophoretic application of strychnine, an antagonist to glycine receptors (GlyRs), or bicuculline, an antagonist to γ-aminobutyric acid type A receptors (GABA A Rs). With blockade of GABA A Rs, neurons showed an increase in firing rate to best frequency (BF) and/or LF tones but retained LF suppression of BF sounds. For neurons that displayed LF suppression tuned to 23–30 kHz, the suppression was eliminated or nearly eliminated by GlyR blockade. In contrast, GABA A R blockade did not eliminate nor had any consistent effect on suppression tuned to these frequencies. We conclude that LF suppression tuned in the 23- to 30-kHz range results from neuronal inhibition within the NLL via glycinergic inputs. For neurons displaying suppression tuned <23 kHz, neither GlyR nor GABAR blockade altered LF suppression. We conclude that such suppression originates at a lower auditory level, perhaps a result of cochlear mechanisms. These findings demonstrate that neuronal interactions within NLL create a particular form of LF suppression that contributes to the analysis of complex acoustic signals.

Experience-dependent plasticity in the central sensory systems depends on activation of both the sensory and neuromodulatory systems. Sensitization or nonspecific augmentation of central auditory neurons elicited by pseudo-conditioning with unpaired conditioning tonal (CS) and unconditioned electric leg (US) stimuli is quite different from tone-specific plasticity, called best frequency (BF) shifts, of the neurons elicited by auditory fear conditioning with paired CS and US. Therefore the neural circuits eliciting the nonspecific augmentation must be different from that eliciting the BF shifts. We first examined plastic changes in the response properties of collicular neurons of the big brown bat elicited by pseudo-conditioning and found that it elicited prominent nonspecific augmentation—an auditory response increase, a frequency-tuning broadening, and a threshold decreas—and that, in addition, it elicited a small short-lasting BF shift only when the CS frequency was 5 kHz lower than the BF of a recorded neuron. We examined the role of acetylcholine and the auditory and somatosensory cortices in these collicular changes. The development of the nonspecific augmentation was affected little by a muscarinic acetylcholine receptor antagonist applied to the inferior colliculus and by a GABA A receptor agonist applied to the auditory or somatosensory cortex. However, these drugs abolished the small short-lasting BF shift as they abolished the large long-lasting cortical and short-lasting collicular BF shifts elicited by the conditioning. These results indicate that, different from the BF shift, the nonspecific augmentation of the inferior colliculus depends on neither the cholinergic neuromodulator nor the auditory and somatosensory cortices.

In the normal guinea pig, contralateral sound inhibits more than a third of ventral cochlear nucleus (VCN) neurons but excites <4% of these neurons. However, unilateral conductive hearing loss (CHL) and cochlear ablation (CA) result in a major enhancement of contralateral excitation. The response properties of the contralateral excitation produced by CHL and CA are similar, suggesting similar pathways are involved for both types of hearing loss. Here we used the neurotoxin melittin to test the hypothesis that this “compensatory” contralateral excitation is mediated either by direct glutamatergic CN-commissural projections or by cholinergic neurons of the olivocochlear bundle (OCB) that send collaterals to the VCN. Unit responses were recorded from the left VCN of anesthetized, unilaterally deafened guinea pigs (CHL via ossicular disruption, or CA via mechanical destruction). Neural responses were obtained with 16-channel electrodes to enable simultaneous data collection from a large number of single- and multiunits in response to ipsi- and contralateral tone burst and noise stimuli. Lesions of each pathway had differential effects on the contralateral excitation. We conclude that contralateral excitation has a fast and a slow component. The fast excitation is likely mediated by glutamatergic neurons located in medial regions of VCN that send their commissural axons to the other CN via the dorsal/intermediate acoustic striae. The slow component is likely mediated by the OCB collateral projections to the CN. Commissural neurons that leave the CN via the trapezoid body are an additional source of fast, contralateral excitation.

Frequency tuning of auditory cortical neurons is typically determined by integrating spikes over the entire duration of a tone stimulus. However, this approach may mask functionally significant variations in tuning over the time course of the response. To explore this possibility, frequency response functions (FRFs) based on population multiunit activity evoked by pure tones of 175 or 200 ms duration were examined within four time windows relative to stimulus onset corresponding to "on" (10-30 ms), "early sustained" (30-100 ms), "late sustained" (100-175 ms), and "off" (185-235 or 210-260 ms) portions of responses in primary auditory cortex (A1) of 5 awake macaques. FRFs of "on" and "early sustained" responses displayed a good concordance, with best frequencies (BFs) differing, on average, by less than 0.25 octaves. In contrast, FRFs of "on" and "late sustained" responses differed considerably, with a mean difference in BF of 0.68 octaves. At many sites, tuning of "off" responses was inversely related to that of "on" responses, with "off" FRFs displaying a trough at the BF of "on" responses. Inversely correlated "on" and "off" FRFs were more common at sites with a higher "on" BF, thus suggesting functional differences between sites with low and high "on" BF. These results indicate that frequency tuning of population responses in A1 may vary considerably over the course of the response to a tone, thus revealing a temporal dimension to the representation of sound spectrum in A1.

The purpose of this study was to determine the effect of signal level and signal-to-noise ratio (SNR) on the latency and amplitude of evoked cortical activity to further our understanding of how the human central auditory system encodes signals in noise. Cortical auditory evoked potentials (CAEPs) were recorded from 15 young normal-hearing adults in response to a 1000 Hz tone presented at two tone levels in quiet and while continuous background noise levels were varied in five equivalent SNR steps. These 12 conditions were used to determine the effects of signal level and SNR level on CAEP components P1, N1, P2, and N2. Based on prior signal-in-noise experiments conducted in animals, we hypothesized that SNR, would be a key contributor to human CAEP characteristics. As hypothesized, amplitude increased and latency decreased with increasing SNR; in addition, there was no main effect of tone level across the two signal levels tested (60 and 75 dB SPL). Morphology of the P1-N1-P2 complex was driven primarily by SNR, highlighting the importance of noise when recording CAEPs. Results are discussed in terms of the current interest in recording CAEPs in hearing aid users.

Changes in oscillatory brain activity have been related to perceptual and cognitive processes such as selective attention and memory matching. Here we examined brain oscillations, measured with electroencephalography (EEG), during a semantic speech processing task that required both lexically mediated memory matching and selective attention. Participants listened to nouns spoken in male and female voices, and detected an animate target (p=20%) in a train of inanimate standards or vice versa. For a control task, subjects listened to the same words and detected a target male voice in standards of a female voice or vice versa. The standard trials of the semantic task showed enhanced upper beta (25-30 Hz) and gamma band (GBA, 30-60 Hz) activity compared to the voice task. Upper beta and GBA enhancement was accompanied by a suppression of alpha (8-12 Hz) and lower to mid beta (13-20 Hz) activity mainly localized to posterior electrodes. Enhancement of phase-locked theta activity peaking near 275 ms also occurred over the midline electrodes. Theta, upper beta, and gamma band enhancement may reflect lexically mediated template matching in auditory memory, whereas the alpha and beta suppression likely indicate increased attentional processes and memory demands.

The medial prefrontal cortex is involved in working memory and executive control. However, the collective spatiotemporal organization of the cellular network has not been possible to explain during different brain states. We show that pyramidal cells in the prelimbic cortex fire synchronized to hippocampal theta and local spindle oscillations in anesthetized rats. To identify which types of interneurons contribute to the synchronized activity, we recorded and juxtacellularly labeled parvalbumin- and calbindin-expressing (PV+/CB+) basket cells and CB-expressing, PV-negative (CB+/PV−) dendrite-targeting interneurons during both network oscillations. All CB+/PV− dendrite-targeting cells strongly decreased their firing rate during hippocampal theta oscillations. Most PV+/CB+ basket cells fired at the peak of dorsal CA1 theta cycles, similar to prefrontal pyramidal cells. We show that pyramidal cells in the ventral hippocampus also fire around the peak of dorsal CA1 theta cycles, in contrast to previously reported dorsal hippocampal pyramidal cells. Therefore, prefrontal neurons might be driven by monosynaptic connections from the ventral hippocampus during theta oscillations. During prefrontal spindle oscillations, the majority of pyramidal cells and PV+/CB+ basket cells fired preferentially at the trough and early ascending phase, but CB+/PV− dendrite-targeting cells fired uniformly at all phases. We conclude that PV+/CB+ basket cells contribute to rhythmic responses of prefrontal pyramidal cells in relation to hippocampal and thalamic inputs and CB+/PV− dendrite-targeting cells modulate the excitability of dendrites and spines regardless of these field rhythms. Distinct classes of GABAergic interneuron in the prefrontal cortex contribute differentially to the synchronization of pyramidal cells during network oscillations.

Sensory systems often encode stimulus information into the temporal pattern of action potential activity. However, little is known about how the information contained within these patterns is extracted by postsynaptic neurons. Similar to temporal coding by sensory neurons, social information in mormyrid fish is encoded into the temporal patterning of an electric organ discharge. In the current study, sensitivity to temporal patterns of electrosensory stimuli was found to arise within the midbrain posterior exterolateral nucleus (ELp). Whole-cell patch recordings from ELp neurons in vivo revealed three patterns of interpulse interval (IPI) tuning: low-pass neurons tuned to long intervals, high-pass neurons tuned to short intervals, and bandpass neurons tuned to intermediate intervals. Many neurons within each class also responded preferentially to either increasing or decreasing IPIs. Playback of electric signaling patterns recorded from freely behaving fish revealed that the IPI and direction tuning of ELp neurons resulted in selective responses to particular social communication displays characterized by distinct IPI patterns. The postsynaptic potential responses of many neurons indicated a combination of excitatory and inhibitory synaptic input, and the IPI tuning of ELp neurons was directly related to rate-dependent changes in the direction and amplitude of postsynaptic potentials. These results suggest that differences in the dynamics of short-term synaptic plasticity in excitatory and inhibitory pathways may tune central sensory neurons to particular temporal patterns of presynaptic activity. This may represent a general mechanism for the processing of behaviorally relevant stimulus information encoded into temporal patterns of activity by sensory neurons.

A common visual pathway in all amniotes is the tectofugal pathway connecting the optic tectum with the forebrain. The tectofugal pathway has been suggested to be involved in tasks such as orienting and attention, tasks that may benefit from integrating information across senses. Nevertheless, previous research has characterized the tectofugal pathway as strictly visual. Here we recorded from two stations along the tectofugal pathway of the barn owl: the thalamic nucleus rotundus (nRt) and the forebrain entopallium (E). We report that neurons in E and nRt respond to auditory stimuli as well as to visual stimuli. Visual tuning to the horizontal position of the stimulus and auditory tuning to the corresponding spatial cue (interaural time difference) were generally broad, covering a large portion of the contralateral space. Responses to spatiotemporally coinciding multisensory stimuli were mostly enhanced above the responses to the single modality stimuli, whereas spatially misaligned stimuli were not. Results from inactivation experiments suggest that the auditory responses in E are of tectal origin. These findings support the notion that the tectofugal pathway is involved in multisensory processing. In addition, the findings suggest that the ascending auditory information to the forebrain is not as bottlenecked through the auditory thalamus as previously thought.

In songbirds, as in mammals, basal ganglia-forebrain circuits are necessary for the learning and production of complex motor behaviors; however, the precise role of these circuits remains unknown. It has recently been shown that a basal ganglia-forebrain circuit in the songbird, which projects directly to vocal–motor circuitry, has a premotor function driving exploration necessary for vocal learning. It has also been hypothesized that this circuit, known as the anterior forebrain pathway (AFP), may generate an instructive signal that improves performance in the motor pathway. Here, we show that the output of the AFP directly implements a motor correction that reduces vocal errors. We use disruptive auditory feedback, contingent on song pitch, to induce learned changes in song structure over the course of hours and find that reversible inactivation of the output of the AFP produces an immediate regression of these learned changes. Thus, the AFP is involved in generating an error-reducing bias, which could increase the efficiency of vocal exploration and instruct synaptic changes in the motor pathway. We also find that learned changes in the song generated by the AFP are incorporated into the motor pathway within 1 day. Our observations support a view that basal ganglia-related circuits directly implement behavioral adaptations that minimize errors and subsequently stabilize these adaptations by training premotor cortical areas.

Acoustic activation of the vestibular system has been well documented in humans and animal models. In the past decade, sound-evoked myogenic potentials in the sternocleidomastoid muscle (cVEMP) and the extraocular muscles (oVEMP) have been extensively studied, and their potentials as new tests for vestibular function have been widely recognized. However, the extent to which sound activates the otolith and canal pathways remains controversial. In the present study, we examined this issue in a recently developed nonhuman primate model of acoustic activation of the vestibular system, i.e., sound-evoked vestibulo-ocular reflexes (VOR) in behaving monkeys. To determine whether the canal and otolith VOR pathways are activated by sound, we analyzed abducens neurons' responses to clicks that were delivered into either ear. The main finding was that clicks evoked short-latency excitatory responses in abducens neurons on both sides. The latencies of the two responses, however, were different. The mean latency of the contralateral and ipsilateral abducens neurons was 2.44 +/- 0.4 and 1.65 +/- 0.28 ms, respectively. A further analysis of the excitatory latencies, in combination with the known canal and otolith VOR pathways, suggests that the excitatory responses of the contralateral abducens neurons were mediated by the contralateral disynaptic VOR pathways that connect the lateral canal to the contralateral abducens neurons, and the excitatory responses of the ipsilateral abducens neurons were mediated by the ipsilateral monosynaptic VOR pathways that connect the utricle to the ipsilateral abducens neurons. These results provide new insights into the understanding of the neural basis for sound-evoked vestibular responses, which is essential for developing new tests for both canal and otolith functions in humans.

Developmental malformations of neocortex—including microgyria, ectopias, and periventricular nodular heterotopia (PNH)—have been associated with language learning impairments in humans. Studies also show that developmental language impairments are frequently associated with deficits in processing rapid acoustic stimuli, and rodent models have linked cortical developmental disruption (microgyria, ectopia) with rapid auditory processing deficits. We sought to extend this neurodevelopmental model to evaluate the effects of embryonic (E) day 15 exposure to the anti-mitotic teratogen methylazoxymethanol acetate (MAM) on auditory processing and maze learning in rats. Extensive cortical anomalies were confirmed in MAM-treated rats post mortem. These included evidence of laminar disruption, PNH, and hippocampal dysplasia. Juvenile auditory testing (P21–42) revealed comparable silent gap detection performance for MAM-treated and control subjects, indicating normal hearing and basic auditory temporal processing in MAM subjects. Juvenile testing on a more complex two-tone oddball task, however, revealed a significant impairment in MAM-treated as compared to control subjects. Post hoc analysis also revealed a significant effect of PNH severity for MAM subjects, with more severe disruption associated with greater processing impairments. In adulthood (P60–100), only MAM subjects with the most severe PNH condition showed deficits in oddball two-tone processing as compared to controls. However, when presented with a more complex and novel FM sweep detection task, all MAM subjects showed significant processing deficits as compared to controls. Moreover, post hoc analysis revealed a significant effect of PNH severity on FM sweep processing. Water Maze testing results also showed a significant impairment for spatial but not non-spatial learning in MAM rats as compared to controls. Results lend further support to the notions that: (1) generalized cortical developmental disruption (stemming from injury, genetic or teratogenic insults) leads to auditory processing deficits, which in turn have been suggested to play a causal role in language impairment; (2) severity of cortical disruption is related to the severity of processing impairments; (3) juvenile auditory processing deficits appear to ameliorate with maturation, but can still be elicited in adulthood using increasingly complex acoustic stimuli; and (4) malformations induced with MAM are also associated with generalized spatial learning deficits. These cumulative findings contribute to our understanding of the behavioral consequences of cortical developmental pathology, which may in turn elucidate mechanisms contributing to developmental language learning impairment in humans.

Various clinical populations display atypical volume asymmetry of language structures and also the auditory M100 source. Although such atypical volume asymmetries have also been observed in autism, M100 source asymmetries have not yet been investigated. We examined M100 asymmetry in autism and its relationship with language functioning. Evoked neural activity to a 1 kHz tone was recorded using whole-cortex 151-channel magnetoencephalography in three groups of individuals. A single-dipole model identified the M100 generator in auditory cortex in each hemisphere. Healthy adults and control children displayed the expected right-sided M100 anteriority, whereas children with autism showed no such asymmetry. An association was found between language functioning and the degree of asymmetry across the two groups of children, suggesting a possible relationship between functional-structural asymmetry and language ability.

Sensory hair cells of the inner ear are sensitive to death from aging, noise trauma, and ototoxic drugs. Ototoxic drugs include the aminoglycoside antibiotics and the antineoplastic agent cisplatin. Exposure to aminoglycosides results in hair cell death that is mediated by specific apoptotic proteins, including c-Jun N-terminal kinase (JNK) and caspases. Induction of heat shock proteins (Hsps) can inhibit JNK- and caspase-dependent apoptosis in a variety of systems. We have previously shown that heat shock results in robust upregulation of Hsps in the hair cells of the adult mouse utricle in vitro. In addition, heat shock results in significant inhibition of both cisplatin- and aminoglycoside-induced hair cell death. In this system, Hsp70 is the most strongly induced Hsp, which is upregulated over 250-fold at the level of mRNA 2 h after heat shock. Hsp70 overexpression inhibits aminoglycoside-induced hair cell death in vitro. In this study, we utilized Hsp70-overexpressing mice to determine whether Hsp70 is protective in vivo. Both Hsp70-overexpressing mice and their wild-type littermates were treated with systemic kanamycin (700 mg/kg body weight) twice daily for 14 days. While kanamycin treatment resulted in significant hearing loss and hair cell death in wild-type mice, Hsp70-overexpressing mice were significantly protected against aminoglycoside-induced hearing loss and hair cell death. These data indicate that Hsp70 is protective against aminoglycoside-induced ototoxicity in vivo.

Clownfish live in social groups in which there is a size-based dominance hierarchy. In such a context, sonic cues could play a role in social organisation because dominant frequency and pulse length of sounds are strongly correlated with fish size. Data on the hearing ability of these fish are, however, needed to show that they have the sensory ability to detect the frequencies in their sounds. The present study determines the hearing sensitivity in three different anemonefish species (Amphiprion frenatus,Amphiprion ocellaris and Amphiprion clarkii), and compares it with the frequencies in their calls. The frequency range over which the three species can detect sounds was between 75 and 1800 Hz, and they were most sensitive to frequencies below 200 Hz. During sound production, dominant frequency is clearly related (R=0.95) to the fish size, whatever the species. Dominant frequency extends from 370 to 900 Hz for specimens having a size between 55 and 130 mm. The best hearing sensitivity of small specimens were found to be lower than the dominant frequency of their own calls. However, they were found to be close to the dominant frequency of larger fish calls. The interest of juveniles lies in localising the adults and thus their location on the reef.

A gene causing autosomal-recessive, nonsyndromic hearing loss, DFNB39, was previously mapped to an 18 Mb interval on chromosome 7q11.22-q21.12. We mapped an additional 40 consanguineous families segregating nonsyndromic hearing loss to the DFNB39 locus and refined the obligate interval to 1.2 Mb. The coding regions of all genes in this interval were sequenced, and no missense, nonsense, or frameshift mutations were found. We sequenced the noncoding sequences of genes, as well as noncoding genes, and found three mutations clustered in intron 4 and exon 5 in the hepatocyte growth factor gene (HGF). Two intron 4 deletions occur in a highly conserved sequence that is part of the 3' untranslated region of a previously undescribed short isoform of HGF. The third mutation is a silent substitution, and we demonstrate that it affects splicing in vitro. HGF is involved in a wide variety of signaling pathways in many different tissues, yet these putative regulatory mutations cause a surprisingly specific phenotype, which is nonsydromic hearing loss. Two mouse models of Hgf dysregulation, one in which an Hgf transgene is ubiquitously overexpressed and the other a conditional knockout that deletes Hgf from a limited number of tissues, including the cochlea, result in deafness. Overexpression of HGF is associated with progressive degeneration of outer hair cells in the cochlea, whereas cochlear deletion of Hgf is associated with more general dysplasia.

Neuroanatomical studies have revealed a vast network of corticocortical connections among the various fields that form cat auditory cortex. However, few studies have explored the functional communicative properties of these connections. The purpose of the present study was to examine the bidirectional processing contributions between the primary auditory cortex (A1) and the nonprimary anterior auditory field (AAF). Using acute recording techniques, multiunit neuronal activity was collected from the right hemisphere of nine mature cats. Cortical maps were generated, and the precise location of A1 and AAF was identified. Subsequently, the synaptic activity of A1 or AAF was suppressed with reversible thermal deactivation procedures while the neuronal response to tonal stimuli of the non-inactivated area (A1 or AAF) was measured. We examined response strength and latency, characteristic frequency, bandwidth, and neuronal threshold of A1 and AAF receptive fields before and during epochs of deactivation. Three major changes in A1 response properties were observed during AAF neuronal suppression: a decrease in response strength, an increase in neuronal thresholds, and a sharpening of receptive field bandwidths. In contrast, A1 deactivation did not produce any discernible changes in AAF neuronal responses. Collectively, these results suggest that the modulation of acoustic information between A1 and AAF in cat auditory cortex is dominated by a unidirectional AAF to A1 pathway.

Object Control signals for brain-machine interfaces may be obtained from a variety of sources, each with their own relative merits. Electrocorticography (ECoG) provides better spatial and spectral resolution than scalp electroencephalography and does not include the risks attendant upon penetration of the brain parenchyma associated with single and multiunit recordings. For these reasons, subdural electrode recordings have been proposed as useful primary or adjunctive control signals for brain-machine interfaces. The goal of the present study was to determine if 2D control signals could be decoded from ECoG. Methods Six patients undergoing invasive monitoring for medically intractable epilepsy using subdural grid electrodes were asked to perform a motor task involving moving a joystick in 1 of 4 cardinal directions (up, down, left, or right) and a fifth condition (“trigger”). Evoked activity was synchronized to joystick movement and analyzed in the theta, alpha, beta, gamma, and high-gamma frequency bands. Results Movement-related cortical potentials could be accurately differentiated from rest with very high accuracy (83–96%). Further distinguishing the movement direction (up, down, left, or right) could also be resolved with high accuracy (58–86%) using information only from the high-gamma range, whereas distinguishing the trigger condition from the remaining directions provided better accuracy. Conclusions Two-dimensional control signals can be derived from ECoG. Local field potentials as measured by ECoG from subdural grids will be useful as control signals for a brain-machine interface.

Object The availability of sophisticated neural probes is a key prerequisite in the development of future brain-machine interfaces (BMIs). In this study, the authors developed and validated a neural probe design capable of simultaneous drug delivery and electrophysiology recordings in vivo. Focal drug delivery promises to extend dramatically the recording lives of neural probes, a limiting factor to clinical adoption of BMI technology. Methods To form the multifunctional neural probe, the authors affixed a 16-channel microfabricated silicon electrode array to a fused silica catheter. Three experiments were conducted in rats to characterize the performance of the device. Experiment 1 examined cellular damage from probe insertion and the drug distribution in tissue. Experiment 2 measured the effects of saline infusions delivered through the probe on concurrent electrophysiological measurements. Experiment 3 demonstrated that a physiologically relevant amount of drug can be delivered in a controlled fashion. For these experiments, Hoechst and propidium iodide stains were used to assess insertion trauma and the tissue distribution of the infusate. Artificial CSF (aCSF) and tetrodotoxin (TTX) were injected to determine the efficacy of drug delivery. Results The newly developed multifunctional neural probes were successfully inserted into rat cortex and were able to deliver fluids and drugs that resulted in the expected electrophysiological and histological responses. The damage from insertion of the device into brain tissue was substantially less than the volume of drug dispersion in tissue. Electrophysiological activity, including both individual spikes as well as local field potentials, was successfully recorded with this device during real-time drug delivery. No significant changes were seen in response to delivery of aCSF as a control experiment, whereas delivery of TTX produced the expected result of suppressing all spiking activity in the vicinity of the catheter outlet. Conclusions Multifunctional neural probes such as the ones developed and validated within this study have great potential to help further understand the design space and criteria for the next generation of neural probe technology. By incorporating integrated drug delivery functionality into the probes, new treatment options for neurological disorders and regenerative neural interfaces using localized and feedback-controlled delivery of drugs can be realized in the near future.