Publications using TDT

A new parylene-based microfabrication process is presented for neural recording and drug delivery applications. We introduce a large design space for electrode placement and structural flexibility with a six mask process. By using chemical mechanical polishing, electrode sites may be created top-side, back-side, or on the edge of the device having three exposed sides. Added surface area was achieved on the exposed edge through electroplating. Poly(3,4-ethylenedioxythiophene) (PEDOT) modified edge electrodes having an 85-μm(2) footprint resulted in an impedance of 200 kΩ at 1 kHz. Edge electrodes were able to successfully record single unit activity in acute animal studies. A finite element model of planar and edge electrodes relative to neuron position reveals that edge electrodes should be beneficial for increasing the volume of tissue being sampled in recording applications.

Purpose In this study, the authors investigated the effects of age on the use of fundamental frequency differences (ΔF 0 ) in the perception of competing synthesized vowels in simulations of electroacoustic and cochlear-implant hearing. Method Twelve younger listeners with normal hearing and 13 older listeners with (near) normal hearing were evaluated in their use of ΔF 0 in the perception of competing synthesized vowels for 3 conditions: unprocessed synthesized vowels (UNP), envelope-vocoded synthesized vowels that simulated a cochlear implant (VOC), and synthesized vowels processed to simulate electroacoustic stimulation (EAS) hearing. Tasks included (a) multiplicity, which required listeners to identify whether a stimulus contained 1 or 2 sounds and (b) double-vowel identification, which required listeners to attach phonemic labels to the competing synthesized vowels. Results Multiplicity perception was facilitated by ΔF 0 in UNP and EAS but not in VOC, with no age-related deficits evident. Double-vowel identification was facilitated by ΔF 0 , with ΔF 0 benefit largest in UNP, reduced in EAS, and absent in VOC. Age adversely affected overall identification and ΔF 0 benefit on the double-vowel task. Conclusions Some but not all older listeners derived ΔF 0 benefit in EAS hearing. This variability may partly be due to how listeners are able to draw on higher-level processing resources in extracting and integrating cues in EAS hearing.

Many cochlear models assign zero longitudinal coupling in the cochlea. Although this is consistent with the transverse basilar membrane (BM) fibers, the cochlear partition contains cellular longitudinal coupling. In cochlear models, longitudinal coupling diminishes passive BM tuning; however, it has recently been employed in theories of active mechanics to enhance tuning. Our goal in this study was to probe passive longitudinal coupling by comparing BM responses in damaged cochleae with passive responses in normal cochleae. The cochleae of gerbils were damaged with intratympanic neomycin followed by a waiting period to ensure that all of the cells of the partition were missing or severely disrupted. We then measured BM motion and examined the cochleae histologically. In comparison with passive responses in normal cochleae, we observed a downward shift in characteristic frequency, an expected consequence of reduced stiffness from cellular damage. However, we did not observe enhanced passive tuning in the damaged cochleae, as would be expected if longitudinal coupling were substantially greater in the normal cochleae. Thus, we conclude that cell-based longitudinal coupling is not large enough to influence passive cochlear mechanics. This finding constrains theories of active mechanics.

Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.

Fluctuations in sound amplitude provide important cues to the identity of many sounds including speech. Of interest here was whether the ability to detect these fluctuations can be improved with practice, and if so whether this learning generalizes to untrained cases. To address these issues, normal-hearing adults (n = 9) were trained to detect sinusoidal amplitude modulation (SAM; 80-Hz rate, 3–4 kHz bandpass carrier) 720 trials/day for 6–7 days and were tested before and after training on related SAM-detection and SAM-rate-discrimination conditions. Controls (n = 9) only participated in the pre- and post-tests. The trained listeners improved more than the controls on the trained condition between the pre- and post-tests, but different subgroups of trained listeners required different amounts of practice to reach asymptotic performance, ranging from 1 (n = 6) to 4–6 (n = 3) sessions. This training-induced learning did not generalize to detection with two untrained carrier spectra (5 kHz low-pass and 0.5–1.5 kHz bandpass) or to rate discrimination with the trained rate and carrier spectrum, but there was some indication that it generalized to detection with two untrained rates (30 and 150 Hz). Thus, practice improved the ability to detect amplitude modulation, but the generalization of this learning to untrained cases was somewhat limited.

Some individuals complain of hearing difficulties in the presence of background noise even in the absence of clinically significant hearing loss (obscure auditory dysfunction). Previous evidence suggests that these listeners have impaired frequency resolution, but there has been no thorough characterization of auditory filter shapes in this population. Here, the filter shapes of adults (n = 14) who self-reported speech recognition problems in noise and performed poorly on a sentence-in-noise perception test despite having clinically normal audiograms were compared to those of controls (n = 10). The filter shapes were evaluated using a 2-kHz probe with a fixed level of 30, 40, or 50 dB sound pressure level (SPL) and notched-noise simultaneous maskers that were varied in level to determine the masker level necessary to just mask the probe. The filters of the impaired group were significantly wider than those of controls at all probe levels owing to an unusual broadening of the upper slope of the filter. In addition, absolute thresholds were statistically indistinguishable between the groups at the standard audiometric frequencies, but were elevated in the impaired listeners at higher frequencies. These results strengthen the idea that this population has a variety of hearing deficits that go undetected by standard audiometry.

Objectives: Recent research suggests that older listeners may have difficulty processing information related to the fundamental frequency (F0) of voiced speech. In this study, the focus was on the mechanisms that may underlie this reduced ability. We examined whether increased age resulted in decreased ability to perceive F0 using fine-structure cues provided by the harmonic structure of voiced speech sounds or cues provided by high-rate envelope fluctuations (periodicity). Design: Younger listeners with normal hearing and older listeners with normal to near-normal hearing completed two tasks of F0 perception. In the first task (steady state F0), the fundamental frequency difference limen (F0DL) was measured adaptively for synthetic vowel stimuli. In the second task (time-varying F0), listeners relied on variations in F0 to judge intonation of synthetic diphthongs. For both tasks, three processing conditions were created: eight-channel vocoding that preserved periodicity cues to F0; a simulated electroacoustic stimulation condition, which consisted of high-frequency vocoder processing combined with a low-pass-filtered portion, and offered both periodicity and fine-structure cues to F0; and an unprocessed condition. Results: F0 difference limens for steady state vowel sounds and the ability to discern rising and falling intonations were significantly worse in the older subjects compared with the younger subjects. For both older and younger listeners, scores were lowest for the vocoded condition, and there was no difference in scores between the unprocessed and electroacoustic simulation conditions. Conclusions: Older listeners had difficulty using periodicity cues to obtain information related to talker fundamental frequency. However, performance was improved by combining periodicity cues with (low frequency) acoustic information, and that strategy should be considered in individuals who are appropriate candidates for such processing. For cochlear implant candidates, this effect might be achieved by partial electrode insertion providing acoustic stimulation in the low frequencies or by the combination of a traditional implant in one ear and a hearing aid in the opposite ear.

The speech signal may be divided into frequency bands, each containing temporal properties of the envelope and fine structure. For maximal speech understanding, listeners must allocate their perceptual resources to the most informative acoustic properties. Understanding this perceptual weighting is essential for the design of assistive listening devices that need to preserve these important speech cues. This study measured the perceptual weighting of young normal-hearing listeners for the envelope and fine structure in each of three frequency bands for sentence materials. Perceptual weights were obtained under two listening contexts: (1) when each acoustic property was presented individually and (2) when multiple acoustic properties were available concurrently. The processing method was designed to vary the availability of each acoustic property independently by adding noise at different levels. Perceptual weights were determined by correlating a listener’s performance with the availability of each acoustic property on a trial-by-trial basis. Results demonstrated that weights were (1) equal when acoustic properties were presented individually and (2) biased toward envelope and mid-frequency information when multiple properties were available. Results suggest a complex interaction between the available acoustic properties and the listening context in determining how best to allocate perceptual resources when listening to speech in noise.

Low-frequency masking by intense high-frequency noise bands, referred to as remote masking (RM), was the first evidence to challenge energy-detection models of signal detection. Its underlying mechanisms remain unknown. RM was measured in five normal-hearing young-adults at 250, 350, 500, and 700 Hz using equal-power, spectrally matched random-phase noise (RPN) and low-noise noise (LNN) narrowband maskers. RM was also measured using equal-power, two-tone complex (TC2) and eight-tone complex (TC8). Maskers were centered at 3000 Hz with one or two equivalent rectangular bandwidths (ERBs). Masker levels varied from 80 to 95 dB sound pressure level in 5 dB steps. LNN produced negligible masking for all conditions. An increase in bandwidth in RPN yielded greater masking over a wider frequency region. Masking for TC2 was limited to 350 and 700 Hz for one ERB but shifted to only 700 Hz for two ERBs. A spread of masking to 500 and 700 Hz was observed for TC8 when the bandwidth was increased from one to two ERBs. Results suggest that high-frequency noise bands at high levels could generate significant low-frequency masking. It is possible that listeners experience significant RM due to the amplification of various competing noises that might have significant implications for speech perception in noise.

Background: Difficulty understanding in background noise is a common complaint of cochlear implant (CI) recipients. Programming options are available to improve speech recognition in noise for CI users including automatic dynamic range optimization (ADRO), autosensitivity control (ASC), and a two-stage adaptive beamforming algorithm (BEAM). However, the processing option that results in the best speech recognition in noise is unknown. In addition, laboratory measures of these processing options often show greater degrees of improvement than reported by participants in everyday listening situations. To address this issue, Compton-Conley and colleagues developed a test system to replicate a restaurant environment. The R-SPACE™ consists of eight loudspeakers positioned in a 360 degree arc and utilizes a recording made at a restaurant of background noise. Purpose: The present study measured speech recognition in the R-SPACE with four processing options: standard dual-port directional (STD), ADRO, ASC, and BEAM. Research Design: A repeated-measures, within-subject design was used to evaluate the four different processing options at two noise levels. Study Sample: Twenty-seven unilateral and three bilateral adult Nucleus Freedom CI recipients. Intervention: The participants’ everyday program (with no additional processing) was used as the STD program. ADRO, ASC, and BEAM were added individually to the STD program to create a total of four programs. Data Collection and Analysis: Participants repeated Hearing in Noise Test sentences presented at 0 degrees azimuth with R-SPACE restaurant noise at two noise levels, 60 and 70 dB SPL. The reception threshold for sentences (RTS) was obtained for each processing condition and noise level. Results: In 60 dB SPL noise, BEAM processing resulted in the best RTS, with a significant improvement over STD and ADRO processing. In 70 dB SPL noise, ASC and BEAM processing had significantly better mean RTSs compared to STD and ADRO processing. Comparison of noise levels showed that STD and BEAM processing resulted in significantly poorer RTSs in 70 dB SPL noise compared to the performance with these processing conditions in 60 dB SPL noise. Bilateral participants demonstrated a bilateral improvement compared to the better monaural condition for both noise levels and all processing conditions, except ASC in 60 dB SPL noise. Conclusions: The results of this study suggest that the use of processing options that utilize noise reduction, like those available in ASC and BEAM, improve a CI recipient's ability to understand speech in noise in listening situations similar to those experienced in the real world. The choice of the best processing option is dependent on the noise level, with BEAM best at moderate noise levels and ASC best at loud noise levels for unilateral CI recipients. Therefore, multiple noise programs or a combination of processing options may be necessary to provide CI users with the best performance in a variety of listening situations.

CBA/CaJ and CBA/J inbred mouse strains appear relatively resistant to age- and noise-related cochlear pathology, and constitute the predominant 'good hearing' control strains in mouse studies of hearing and deafness. These strains have often been treated as nearly equivalent in their hearing characteristics, and have even been mixed in some studies. Nevertheless, we recently showed that their trajectories with regard to age-associated cochlear pathology diverge after one year of age (Ohlemiller et al., 2010a). We also recently reported that they show quite different susceptibility to cochlear noise injury during the 'sensitive period' of heightened vulnerability to noise common to many models, CBA/J being far more vulnerable than CBA/CaJ (Fernandez et al., 2010 J. Assoc. Res. Otolaryngol. 11:235-244). Here we explore this relation in a side-by-side comparison of the effect of varying noise exposure duration in young (6 week) and older (6 month) CBA/J and CBA/CaJ mice, and in F1 hybrids formed from these. Both the extent of permanent noise-induced threshold shifts (NIPTS) and the probability of a defined NIPTS were determined as exposure to intense broadband noise (4-45 kHz, 110 dB SPL) increased by factors of two from 7 s to 4 h. At 6 months of age the two strains appeared very similar by both measures. At 6 weeks of age, however, both the extent and probability of NIPTS grew much more rapidly with noise duration in CBA/J than in CBA/CaJ. The 'threshold' exposure duration for NIPTS was <1.0 min in CBA/J versus >4.0 min in CBA/CaJ. F1 hybrid mice showed both NIPTS and hair cell loss similar to that in CBA/J. This suggests that dominant-acting alleles at unknown loci distinguish CBA/J from CBA/CaJ. These loci have novel effects on hearing phenotype, as they come into play only during the sensitive period, and may encode factors that demarcate this period. Since the cochlear cells whose fragility defines the early window appear to be hair cells, these loci may principally impact the mechanical or metabolic resiliency of hair cells or the organ of Corti.

Two mouse models, the Coch(G88E/G88E) or "knock-in" and the Coch(-/-) or "knock-out" (Coch null), have been developed to study the human late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. This disorder results from missense and in-frame deletion mutations in COCH (coagulation factor C homology), encoding cochlin, the most abundantly detected protein in the inner ear. We have performed hearing and vestibular analyses by auditory brainstem response (ABR) and vestibular evoked potential (VsEP) testing of the Coch(-/-) and Coch(G88E/G88E) mouse models. Both Coch(-/-) and Coch(G88E/G88E) mice show substantially elevated ABRs at 21 months of age, but only at the highest frequency tested for the former and all frequencies for the latter. At 21 months, 9 of 11 Coch(-/-) mice and 4 of 8 Coch(G88E/G88E) mice have absent ABRs. Interestingly Coch(-/+) mice do not show hearing deficits, in contrast to Coch(G88E/+), which demonstrate elevated ABR thresholds similar to homozyotes. These results corroborate the DFNA9 autosomal dominant mode of inheritance, in addition to the observation that haploinsufficiency of Coch does not result in impaired hearing. Vestibular evoked potential (VsEP) thresholds were analyzed using a two factor ANOVA (Age X Genotype). Elevated VsEP thresholds are detected in Coch(-/-) mice at 13 and 21 months, the two ages tested, and as early as seven months in the Coch(G88E/G88E) mice. These results indicate that in both mouse models, vestibular function is compromised before cochlear function. Analysis and comparison of hearing and vestibular function in these two DFNA9 mouse models, where deficits occur at such an advanced age, provide insight into the pathology of DFNA9 and age-related hearing loss and vestibular dysfunction as well as an opportunity to investigate potential interventional therapies.

Conductive hearing loss (CHL) is known to produce hearing deficits, including deficits in sound localization ability. The differences in sound intensities and timing experienced between the two tympanic membranes are important cues to sound localization (ILD and ITD, respectively). Although much is known about the effect of CHL on hearing levels, little investigation has been conducted into the actual impact of CHL on sound location cues. This study investigated effects of CHL induced by earplugs on cochlear microphonic (CM) amplitude and timing and their corresponding effect on the ILD and ITD location cues. Acoustic and CM measurements were made in 5 chinchillas before and after earplug insertion, and again after earplug removal using pure tones (500 Hz to 24 kHz). ILDs in the unoccluded condition demonstrated position and frequency dependence where peak far-lateral ILDs approached 30 dB for high frequencies. Unoccluded ear ITD cues demonstrated positional and frequency dependence with increased ITD cue for both decreasing frequency (±420 μs at 500 Hz, ±310 μs for 1-4 kHz) and increasingly lateral sound source locations. Occlusion of the ear canal with foam plugs resulted in a mild, frequency-dependent conductive hearing loss of 10-38 dB (mean 31 ± 3.9 dB) leading to a concomitant frequency dependent increase in ILDs at all source locations. The effective ITDs increased in a frequency dependent manner with ear occlusion as a direct result of the acoustic properties of the plugging material, the latter confirmed via acoustical measurements using a model ear canal with varying volumes of acoustic foam. Upon ear plugging with acoustic foam, a mild CHL is induced. Furthermore, the CHL induced by acoustic foam results in substantial changes in the magnitudes of both the ITD and ILD cues to sound location.

Combinations of aminoglycosides and loop diuretics have been known to have a synergistic effect in ototoxic injury. Because murine hair cells are relatively resistant to ototoxicity compared to those of other mammals, investigators have turned to combination therapies to create ototoxic lesions in the mouse inner ear. In this paper, we perform a systematic comparison of hearing thresholds, hair cell damage and monocyte migration into the mouse cochlea after kanamycin versus combined kanamycin/furosemide and explore the pathophysiology of enhanced hair cell loss in aminoglycoside ototoxicity in the presence of loop diuretic. Combined kanamycin-furosemide resulted in elevation of threshold not only in the high frequencies, but across all frequencies with more extensive loss of outer hair cells when compared to kanamycin alone. The stria vascularis was severely atrophied and stellate cells in the spiral limbus were missing in kanamycin-furosemide exposed mice while these changes were not observed in mice receiving kanamycin alone. Monocytes and macrophages were recruited in large numbers to the spiral ligament and spiral ganglion in these mice. Combination therapy resulted in a greater number of macrophages in total, and many more macrophages were present further apically when compared to mice given kanamycin alone. Combined kanamycin-furosemide provides an effective method of addressing the relative resistance to ototoxicity that is observed in most mouse strains. As the mouse becomes increasingly more common in studies of hearing loss, and combination therapies gain popularity, recognition of the overall effects of combined aminoglycoside-loop diuretic therapy will be critical to interpretation of the interventions that follow.

There are three main cues to sound location: the interaural differences in time (ITD) and level (ILD) as well as the monaural spectral shape cues. These cues are generated by the spatial- and frequency-dependent filtering of propagating sound waves by the head and external ears. Although the chinchilla has been used for decades to study the anatomy, physiology, and psychophysics of audition, including binaural and spatial hearing, little is actually known about the sound pressure transformations by the head and pinnae and the resulting sound localization cues available to them. Here, we measured the directional transfer functions (DTFs), the directional components of the head-related transfer functions, for 9 adult chinchillas. The resulting localization cues were computed from the DTFs. In the frontal hemisphere, spectral notch cues were present for frequencies from ∼6-18 kHz. In general, the frequency corresponding to the notch increased with increases in source elevation as well as in azimuth towards the ipsilateral ear. The ILDs demonstrated a strong correlation with source azimuth and frequency. The maximum ILDs were <10 dB for frequencies <5 kHz, and ranged from 10-30 dB for the frequencies >5 kHz. The maximum ITDs were dependent on frequency, yielding 236 μs at 4 kHz and 336 μs at 250 Hz. Removal of the pinnae eliminated the spectral notch cues, reduced the acoustic gain and the ILDs, altered the acoustic axis, and reduced the ITDs.

Objective: This study aimed to provide guidelines to optimize perception of soft speech and speech in noise for Advanced Bionics cochlear implant (CI) users. Design: Three programs differing in T-levels were created for ten subjects. Using the T-level setting that provided the lowest FM-tone, sound-field threshold levels for each subject, three additional programs were created with input dynamic range (IDR) settings of 50, 65 and 80 dB. Study sample: Subjects were postlinguistically deaf adults implanted with either the Clarion CII or 90K CI devices. Results: Sound-field threshold levels were lowest with T-levels set higher than 10% of M-levels and with the two widest IDRs. Group data revealed significantly higher scores for CNC words presented at a soft level with an IDR of 80 dB and 65 dB compared to 50 dB. Although no significant group differences were seen between the three IDRs for sentences in noise, significant individual differences were present. Conclusions: Setting Ts higher than the manufacturer's recommendation of 10% of M-levels and providing IDR options can improve overall speech perception; however, for some users, higher Ts and wider IDRs may not be appropriate. Based on the results of the study, clinical programming recommendations are provided.

Cells of the inner ear face constant metabolic and structural stress. Exposure to intense sound or certain drugs destroys cochlea hair cells, which in mammals do not regenerate. Thus, an endogenous stress response system may exist within the cochlea to protect it from everyday stressors. We recently described the existence of corticotropin-releasing factor (CRF) in the mouse cochlea. The CRF receptor type 1 (CRFR1) is considered the primary and canonical target of CRF signaling, and systemically it plays an essential role in coordinating the body-wide stress response via activation of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we describe an essential role for CRFR1 in auditory system development and function, and offer the first description of a complete HPA equivalent signaling system resident within the cochlea. To reveal the role of CRFR1 activation in the cochlea, we have used mice carrying a null ablation of the CRFR1 gene. CRFR1 −/− mice exhibited elevated auditory thresholds at all frequencies tested, indicating reduced sensitivity. Furthermore, our results suggest that CRFR1 has a developmental role affecting inner hair cell morphology and afferent and efferent synapse distribution. Given the role of HPA signaling in maintaining local homeostasis in other tissues, the presence of a cochlear HPA signaling system suggests important roles for CRFR1 activity in setting cochlear sensitivity, perhaps both neural and non-neural mechanisms. These data highlight the complex pleiotropic mechanisms modulated by CRFR1 signaling in the cochlea.

Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative effectiveness of the affected eye to drive V2 neurons was drastically reduced in the amblyopic monkeys. The spatial resolution and the orientation bias of V2, but not V1, neurons were subnormal for the affected eyes. Binocular suppression was robust in both cortical areas, and the magnitude of suppression in individual monkeys was correlated with the depth of their amblyopia. These results suggest that the reduced functional connections beyond V1 and the subnormal spatial filter properties of V2 neurons might have substantially limited the sensitivity of the amblyopic eyes and that interocular suppression was likely to have played a key role in the observed alterations of V2 responses and the emergence of amblyopia.

Normal brain function requires constant adaptation, as an organism learns to associate important sensory stimuli with the appropriate motor actions. Neurological disorders may disrupt these learned associations and require the nervous system to reorganize itself. As a consequence, neural plasticity is a crucial component of normal brain function and a critical mechanism for recovery from injury. Associative, or Hebbian, pairing of pre- and post-synaptic activity has been shown to alter stimulus-evoked responses in vivo; however, to date, such protocols have not been shown to affect the animal's subsequent behavior. We paired stimulus trains separated by a brief time delay to two electrodes in rat sensorimotor cortex, which changed the statistical pattern of spikes during subsequent behavior. These changes were consistent with strengthened functional connections from the leading electrode to the lagging electrode. We then trained rats to respond to a microstimulation cue, and repeated the paradigm using the cue electrode as the leading electrode. This pairing lowered the rat's ICMS-detection threshold, with the same dependence on intra-electrode time lag that we found for the functional connectivity changes. The timecourse of the behavioral effects was very similar to that of the connectivity changes. We propose that the behavioral changes were a consequence of strengthened functional connections from the cue electrode to other regions of sensorimotor cortex. Such paradigms might be used to augment recovery from a stroke, or to promote adaptation in a bidirectional brain-machine interface.

Kinematic state feedback is important for neuroprostheses to generate stable and adaptive movements of an extremity. State information, represented in the firing rates of populations of primary afferent (PA) neurons, can be recorded at the level of the dorsal root ganglia (DRG). Previous work in cats showed the feasibility of using DRG recordings to predict the kinematic state of the hind limb using reverse regression. Although accurate decoding results were attained, reverse regression does not make efficient use of the information embedded in the firing rates of the neural population. In this paper, we present decoding results based on state-space modeling, and show that it is a more principled and more efficient method for decoding the firing rates in an ensemble of PA neurons. In particular, we show that we can extract confounded information from neurons that respond to multiple kinematic parameters, and that including velocity components in the firing rate models significantly increases the accuracy of the decoded trajectory. We show that, on average, state-space decoding is twice as efficient as reverse regression for decoding joint and endpoint kinematics.