Publications using TDT

In analyzing neurophysiologic data, individual experimental trials are usually assumed to be statistically independent. However, many studies employing functional imaging and electrophysiology have shown that brain activity during behavioral tasks includes temporally correlated trial-to-trial fluctuations. This could lead to spurious results in statistical significance tests used to compare data from different interleaved behavioral conditions presented throughout an experiment. We characterize trial-to-trial fluctuations in local field potentials recorded from the frontal cortex of a macaque monkey performing an oculomotor delayed response task. Our analysis identifies slow fluctuations (<0.1 Hz) of spectral power in 22/27 recording sessions. These trial-to-trial fluctuations are non-Gaussian, and call into question the statistical utility of standard trial shuffling. We compare our results with evidence for slow fluctuations in human functional imaging studies and other electrophysiologic studies in nonhuman primates.

Vision and audition represent the outside world in spatial synergy that is crucial for guiding natural activities. Input conveying eye-in-head position is needed to maintain spatial congruence because the eyes move in the head while the ears remain head-fixed. Recently, we reported that the human perception of auditory space shifts with changes in eye position. In this study, we examined whether this phenomenon is 1) dependent on a visual fixation reference, 2) selective for frequency bands (high-pass and low-pass noise) related to specific auditory spatial channels, 3) matched by a shift in the perceived straight-ahead (PSA), and 4) accompanied by a spatial shift for visual and/or bimodal (visual and auditory) targets. Subjects were tested in a dark echo-attenuated chamber with their heads fixed facing a cylindrical screen, behind which a mobile speaker/LED presented targets across the frontal field. Subjects fixated alternating reference spots (0, ±20°) horizontally or vertically while either localizing targets or indicating PSA using a laser pointer. Results showed that the spatial shift induced by ocular eccentricity is 1) preserved for auditory targets without a visual fixation reference, 2) generalized for all frequency bands, and thus all auditory spatial channels, 3) paralleled by a shift in PSA, and 4) restricted to auditory space. Findings are consistent with a set-point control strategy by which eye position governs multimodal spatial alignment. The phenomenon is robust for auditory space and egocentric perception, and highlights the importance of controlling for eye position in the examination of spatial perception and behavior.

Background: Surveys of ontogenetic development of hearing and sound production in fish are scarce, and the ontogenetic development of acoustic communication has been investigated in only two fish species so far. Studies on the labyrinth fish Trichopsis vittata and the toadfish Halobatrachus didactylus show that the ability to detect conspecific sounds develops during growth. In otophysine fish, which are characterized by Weberian ossicles and improved hearing sensitivities, the ontogenetic development of sound communication has never been investigated. We analysed the ontogeny of the auditory sensitivity and vocalizations in the mochokid catfish Synodontis schoutedeni. Mochokid catfishes of the genus Synodontis are commonly called squeakers because they produce broadband stridulation sounds during abduction and adduction of pectoral fin spines. Fish from six different size groups - from 22 mm standard length to 126 mm - were studied. Hearing thresholds were measured between 50 Hz and 6 kHz using the auditory evoked potentials recording technique; stridulation sounds were recorded and their sound pressure levels determined. Finally, absolute sound power spectra were compared to auditory sensitivity curves within each size group. Results: The smallest juveniles showed the poorest hearing abilities of all size groups between 50 and 1,000 Hz and highest hearing sensitivity at 5 and 6 kHz. The duration of abduction and adduction sounds and the pulse period increased and sound pressure level (in animals smaller than 58 mm) increased, while the dominant frequency of sounds decreased with size in animals larger than 37 mm. Comparisons between audiograms and sound spectra revealed that the most sensitive frequencies correlate with the dominant frequencies of stridulation sounds in all S. schoutedeni size groups and that all specimens are able to detect sounds of all size groups. Conclusions: This study on the squeaker catfish S. schoutedeni is the first to demonstrate that absolute hearing sensitivity changes during ontogeny in an otophysine fish. This contrasts with prior studies on two cypriniform fish species in which no such change could be observed. Furthermore, S. schoutedeni can detect conspecific sounds at all stages of development, again contrasting with prior findings in fishes.

Functional and anatomical studies suggest that acoustic signals are processed hierarchically in auditory cortex. Although most regions of acoustically responsive cortex are not tonotopically organized, all previous electrophysiological investigations of interfield interactions have only examined tonotopically represented areas. The purpose of the present study was to investigate the functional interactions between tonotopically and nontonotopically organized fields in auditory cortex. We accomplished this goal by examining the bidirectional contributions between the cochleotopically organized primary auditory cortex (A1) and the noncochleotopically organized second auditory field (A2). Multiunit acute recording procedures in combination with reversible cooling deactivation techniques were used in eight mature cats. The synaptic activity of A1 or A2 was suppressed while the neuronal response to tonal stimuli of the noninactivated area (A1 or A2) was measured. Response strength, neuronal threshold, receptive field bandwidths, and latency measures were collected at each recorded site before, during, and after cooling deactivation epochs. Our analysis revealed comparable changes in A1 and A2 neuronal response properties. Specifically, significant decreases in neuronal response strength, increases in neuronal threshold, and shortening of response latency were found in both fields during periods of cooling deactivation. The weak anatomical connections between the two fields investigated make these findings unexpected. Furthermore, the observed neuronal changes suggest a model of corticocortical interaction among auditory fields in which neither differences in the magnitude of anatomical projections nor cortical representation of sensory stimuli are reliable determinants of modulatory functions.

Animal studies indicate that a combination of kanamycin (KM) and noise produces a synergistic effect, whereby the threshold shift from the combination is greater than the sum of the shifts caused by either agent alone. Most such studies have focused on adult animals, and it has remained unclear whether younger, presumably more susceptible, animals show an even greater synergistic effect. The present study tested the hypothesis that young CBA/J mice receiving a low dose of KM (300 mg/kg, 2x/day, s.c.) from 20 to 30 days post-gestational age followed by brief noise exposure (110 dB SPL; 4-45 kHz, 30 s) would show greater noise-induced permanent threshold shifts (NIPTS) than mice receiving either treatment alone. Noise exposure produced 30-40 dB of NIPTS and moderate hair cell loss in young saline-treated mice. KM alone at this dose had no effect on thresholds. Surprisingly, mice receiving KM plus noise were protected from NIPTS, showing ABR thresholds not significantly different from unexposed controls. Mice receiving KM prior to noise exposure also showed significantly less outer hair cell loss than saline-treated mice. Additional experiments indicated protection by KM when the noise was applied either 24 or 48 h after the last KM injection. Our results demonstrate a powerful protective effect of sub-chronic low-dose kanamycin against NIPTS in young CBA/J mice. Repeated kanamycin exposure may establish a preconditioned protective state, the molecular bases of which remain to be determined.

Previous studies have shown that hand translation is well represented by neuronal activity in the proximal arm area of primary motor cortex (M1). However, little is known about cortical representation of hand rotation in M1. In this study, single-unit activity was recorded from monkeys while they performed a “center-out with rotation” task. When reaching for a target, subjects had to match four separate kinematic parameters: three-dimensional location and one-dimensional orientation of the target. Among the 512 neurons modulated by hand movement, 446 were tuned to hand translation, 326 were tuned to hand rotation, and 260 neurons were tuned to both hand translation and hand rotation. Approximately half of the neurons that encoded both translation and rotation did so in a nonlinear manner. This nonlinear interaction can be modeled as a gain-field type of encoding whereby hand rotational velocity modulated the hand translational cosine tuning curves in a multiplicative manner. Furthermore, this study demonstrated that both hand translation and hand rotation can be decoded simultaneously from a population of motor cortical neurons.

Humans are much better in relative than in absolute judgments. This common assertion is based on findings that discrimination thresholds are much lower when measured with methods that allow interstimuli comparisons than when measured with methods that require classification of one stimulus at a time and are hence sensitive to memory load. We now challenged this notion by measuring discrimination thresholds and evoked potentials while listeners performed a two-tone frequency discrimination task. We tested various protocols that differed in the pattern of cross-trial tone repetition. We found that best performance was achieved only when listeners effectively used cross-trial repetition to avoid interstimulus comparisons with the repeated reference tone. Instead, they classified one tone, the nonreference tone, as either high or low by comparing it with a recently formed internal reference. Listeners were not aware of the switch from interstimulus comparison to classification. Its successful use was revealed by the conjunction of improved behavioral performance and an event-related potential component (P3), indicating an implicit perceptual decision, which followed the nonreference tone in each trial. Interestingly, tone repetition itself did not suffice for the switch, implying that the bottleneck to discrimination does not reside at the lower, sensory stage. Rather, the temporal consistency of repetition was important, suggesting the involvement of higher-level mechanisms with longer time constants. These findings suggest that classification is based on more automatic and accurate mechanisms than interstimulus comparisons and that the ability to effectively use them depends on a dynamic interplay between higher- and lower-level cortical mechanisms.

An important question in sensory neuroscience is what coding strategies and mechanisms are used by the brain to detect and discriminate among behaviorally relevant stimuli. There is evidence that sensory systems migrate from a distributed and redundant encoding strategy at the periphery to a more heterogeneous encoding in cortical structures. It has been hypothesized that heterogeneity is an efficient encoding strategy that minimizes the redundancy of the neural code and maximizes information throughput. Evidence of this mechanism has been documented in cortical structures. In this study, we examined whether heterogeneous encoding of complex sounds contributes to efficient encoding in the auditory midbrain by characterizing neural responses to behaviorally relevant vocalizations in the mouse inferior colliculus (IC). We independently manipulated the frequency, amplitude, duration, and harmonic structure of the vocalizations to create a suite of modified vocalizations. Based on measures of both spike rate and timing, we characterized the heterogeneity of neural responses to the natural vocalizations and their perturbed variants. Using information theoretic measures, we found that heterogeneous response properties of IC neurons contribute to efficient encoding of behaviorally relevant vocalizations.

To program a goal-directed orienting response toward a sound source embedded in an acoustic scene, the audiomotor system should detect and select the target against a background. Here, we focus on whether the system can segregate synchronous sounds in the midsagittal plane (elevation), a task requiring the auditory system to dissociate the pinna-induced spectral localization cues. Human listeners made rapid head-orienting responses toward either a single sound source (broadband buzzer or Gaussian noise) or toward two simultaneously presented sounds (buzzer and noise) at a wide variety of locations in the midsagittal plane. In the latter case, listeners had to orient to the buzzer (target) and ignore the noise (nontarget). In the single-sound condition, localization was accurate. However, in the double-sound condition, response endpoints depended on relative sound level and spatial disparity. The loudest sound dominated the responses, regardless of whether it was the target or the nontarget. When the sounds had about equal intensities and their spatial disparity was sufficiently small, endpoint distributions were well described by weighted averaging. However, when spatial disparities exceeded ∼45°, response endpoint distributions became bimodal. Similar response behavior has been reported for visuomotor experiments, for which averaging and bimodal endpoint distributions are thought to arise from neural interactions within retinotopically organized visuomotor maps. We show, however, that the auditory-evoked responses can be well explained by the idiosyncratic acoustics of the pinnae. Hence basic principles of target representation and selection for audition and vision appear to differ profoundly.

Ocular dominance plasticity (ODP) following monocular deprivation (MD) is a model of activity-dependent neural plasticity that is restricted to an early critical period regulated by maturation of inhibition. Unique developmental plasticity mechanisms may improve outcomes following early brain injury. Our objective was to determine the effects of neonatal cerebral hypoxia–ischemia (HI) on ODP. The rationale extends from observations that neonatal HI results in death of subplate neurons, a transient population known to influence development of inhibition. In rodents subjected to neonatal HI and controls, maps of visual response were derived from optical imaging during the critical period for ODP and changes in the balance of eye-specific response following MD were measured. In controls, MD results in a shift of the ocular dominance index (ODI) from a baseline of 0.15 to −0.10 ( p < 0.001). Neonatal HI with moderate cortical injury impairs this shift, ODI = 0.14 ( p < 0.01). Plasticity was intact in animals with mild injury and in those exposed to hypoxia alone. Neonatal HI resulted in decreased parvalbumin expression in hemispheres receiving HI compared with hypoxia alone: 23.4 versus 35.0 cells/high-power field ( p = 0.01), with no change in other markers of inhibitory or excitatory neurons. Despite abnormal inhibitory neuron phenotype, spontaneous activity of single units and development of orientation selective responses were intact following neonatal HI, while overall visual responses were reduced. Our data suggest that specific plasticity mechanisms are impaired following early brain injury and that the impairment is associated with altered inhibitory neuronal development and cortical activation.

There is evidence that reactive oxygen species (ROS) are formed in the cochlea during acoustic injury. However, very little is known about the involvement of ROS signals in the spiral ligament (SL) during such injury. The purpose of this study was to determine the effect of the multifunctional antioxidant tempol and the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) on acoustic injury and the c-Jun N-terminal kinase (JNK) pathway in the SL. Exposure of adult mice to noise (8-kHz octave band, 110-dB SPL for 1 h) produced permanent hearing loss. Noise exposure increased not only the formation of a protein modified by 4-hydroxynonenal and formation of nitrotyrosine, but also the level of phospho-JNK in the SL. Pretreatment with tempol or L-NAME was effective in protecting the noise-exposed animals from hearing loss, as well as in abolishing the noise-induced activation of the JNK signaling pathway. Interestingly, noise exposure caused a dramatic decrease in connexin26 level in the SL. This decrease was prevented by tempol or L-NAME. Taken together, our data suggest that noise-induced hearing loss is due at least in part to ROS / nitric oxide-mediated activation of the JNK pathway and down-regulation of connexin26 in the SL of mice.

Phase-locked spikes in various types of neurons encode temporal information. To quantify the degree of phase-locking, the metric called vector strength (VS) has been most widely used. Since VS is derived from spike timing information, error in measurement of spike occurrence should result in errors in VS calculation. In electrophysiological experiments, the timing of an action potential is detected with finite temporal precision, which is determined by the sampling frequency. In order to evaluate the effects of the sampling frequency on the measurement of VS, we derive theoretical upper and lower bounds of VS from spikes collected with finite sampling rates. We next estimate errors in VS assuming random sampling effects, and show that our theoretical calculation agrees with data from electrophysiological recordings in vivo. Our results provide a practical guide for choosing the appropriate sampling frequency in measuring VS.

Terminals containing vesicular glutamate transporter (VGLUT) 2 make dense axosomatic synapses on tectothalamic GABAergic neurons. These are one of the three types of glutamatergic synapses in the inferior colliculus (IC) identified by one of three combinations of transporter protein: VGLUT1 only, VGLUT2 only, or both VGLUT1 and 2. To identify the source(s) of these three classes of glutamatergic terminals, we employed the injection of Fluorogold (FG) into the IC and retrograde transport in combination with in situ hybridization for VGLUT1 and VGLUT2 mRNA. The distribution of FG-positive soma was consistent with previous reports. In the auditory cortex, all FG-positive cells expressed only VGLUT1. In the IC, the majority of FG-positive cells expressed only VGLUT2. In the intermediate nucleus of the lateral lemniscus, most FG-positive cells expressed VGLUT2, and a few FG-positive cells expressed both VGLUT1 and 2. In the superior olivary complex (SOC), the majority of FG-positive cells expressing VGLUT2 were in the lateral superior olive, medial superior olive, and some periolivary nuclei. Fewer FG-positive cells expressed VGLUT1&2. In the ventral cochlear nucleus, almost all FG-positive cells expressed VGLUT1&2. On the other hand in the dorsal cochlear nucleus, the vast majority of FG-positive cells expressed only VGLUT2. Our data suggest that (1) the most likely sources of VGLUT2 terminals in the IC are the intermediate nucleus of the lateral lemniscus, the dorsal cochlear nucleus, the medial and lateral superior olive, and the IC itself, (2) VGLUT1 terminals in the IC originate only in the ipsilateral auditory cortex, and (3) VGLUT1&2 terminals in IC originate mainly from the VCN with minor contributions from the SOC and the lateral lemniscal nuclei.

Insulin-like growth factor-I (IGF-I) belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1(-/-) null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss) is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1(+/+) and null Igf1(-/-) mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR) recordings and in vivo MRI brain imaging. Igf1(-/-) null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1(+/+) wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1(-/-) null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to prevent or ameliorate age-related hearing loss.

Descending cortical inputs to the superior colliculus (SC) contribute to the unisensory response properties of the neurons found there and are critical for multisensory integration. However, little is known about the relative contribution of different auditory cortical areas to this projection or the distribution of their terminals in the SC. We characterized this projection in the ferret by injecting tracers in the SC and auditory cortex. Large pyramidal neurons were labeled in layer V of different parts of the ectosylvian gyrus after tracer injections in the SC. Those cells were most numerous in the anterior ectosylvian gyrus (AEG), and particularly in the anterior ventral field, which receives both auditory and visual inputs. Labeling was also found in the posterior ectosylvian gyrus (PEG), predominantly in the tonotopically organized posterior suprasylvian field. Profuse anterograde labeling was present in the SC following tracer injections at the site of acoustically responsive neurons in the AEG or PEG, with terminal fields being both more prominent and clustered for inputs originating from the AEG. Terminals from both cortical areas were located throughout the intermediate and deep layers, but were most concentrated in the posterior half of the SC, where peripheral stimulus locations are represented. No inputs were identified from primary auditory cortical areas, although some labeling was found in the surrounding sulci. Our findings suggest that higher level auditory cortical areas, including those involved in multisensory processing, may modulate SC function via their projections into its deeper layers.

Implantable microelectrode arrays (MEAs) have been a boon for neural stimulation and recording experiments. Commercially available MEAs have high impedances, due to their low surface area and small tip diameters, which are suitable for recording single unit activity. Lowering the electrode impedance, but preserving the small diameter, would provide a number of advantages, including reduced stimulation voltages, reduced stimulation artifacts and improved signal-to-noise ratio. Impedance reductions can be achieved by electroplating the MEAs with platinum (Pt) black, which increases the surface area but has little effect on the physical extent of the electrodes. However, because of the low durability of Pt black plating, this method has not been popular for chronic use. Sonicoplating (i.e. electroplating under ultrasonic agitation) has been shown to improve the durability of Pt black on the base metals of macro-electrodes used for cyclic voltammetry. This method has not previously been characterized for MEAs used in chronic neural implants. We show here that sonicoplating can lower the impedances of microwire multi-electrode arrays (MMEA) by an order of magnitude or more (depending on the time and voltage of electroplating), with better durability compared to pulsed plating or traditional DC methods. We also show the improved stimulation and recording performance that can be achieved in an in vivo implantation study with the sonicoplated low-impedance MMEAs, compared to high-impedance unplated electrodes.

Background: Noise-induced hearing loss (NIHL) is one of the most common occupational injuries in the United States. It would be extremely valuable if a safe, inexpensive compound could be identified which protects worker hearing from noise. In a series of experiments, Kopke has shown that the compound N-acetyl-L-cysteine (L-NAC) can protect the hearing of chinchillas from the effects of a single exposure to noise. L-NAC is used in clinical medicine and is very safe. Although L-NAC was reported to be promising, it has not been successful in other studies (Kramer et al., 2006; Hamernik et al., 2008). The present study was undertaken to determine if L-NAC could protect C57BL/6J (B6) mice from the permanent effects of noise. Method: Two groups of five B6 mice were injected with either 300 or 600 mg/kg L-NAC approximately 1 hr prior to a 104 dB broadband noise exposure and again immediately after the exposure. A control group (N = 7) was exposed to the same noise level but injected with vehicle (sterile saline). Auditory brainstem response measurements were made at 4, 8, 16 and 32 kHz one week prior to and 12 days after exposure. Conclusions: There were no statistically significant differences in ABR threshold shifts between the mice receiving L-NAC and the control mice. This indicates that L-NAC was not effective in preventing permanent threshold shift in this mouse model of NIHL.

Underwater vibratory sources simultaneously present acoustic and hydrodynamic disturbances. Because vibratory dipole sources are poor sonic projectors, most researchers have assumed that such sources are of greatest relevance to the lateral line system. Both hydroacoustic principles and empirical studies have shown that dipole sources are also a potent stimulus to the inner ear. Responses to vibratory sources in mottled sculpin (Cottus bairdi) were assessed using unconditioned orienting, differential and nondifferential conditioning. Orienting responses are dominated by lateral line inputs and eliminated by lateral line inactivation. Simple conditioning depends on inputs from other systems and was not affected by lateral line inactivation. Differential conditioning alters behavioral control, and sculpin could be conditioned to ignore substrate-borne vibrations and respond only to hydroacoustic stimulation of the ear. The lateral line and inner ear of mottled sculpin do not necessarily exhibit range fractionation, as both systems operate over a similar distance (within 1.5 body lengths) and respond to many of the same sources. Vibratory dipole sources generate compound stimuli that simultaneously activate multiple octavolateralis systems, and sculpin make use of the channels differentially under different behavioral tasks.