Detection and identification of speech sounds using cortical activity patterns.

We have developed a classifier capable of locating and identifying speech sounds using activity from rat auditory cortex with an accuracy equivalent to behavioral performance and without the need to specify the onset time of the speech sounds. This classifier can identify speech sounds from a large speech set within 40 ms of stimulus presentation. To compare the temporal limits of the classifier to behavior, we developed a novel task that requires rats to identify individual consonant sounds from a stream of distracter consonants. The classifier successfully predicted the ability of rats to accurately identify speech sounds for syllable presentation rates up to 10 syllables per second (up to 17.9 ± 1.5 bits/s), which is comparable to human performance. Our results demonstrate that the spatiotemporal patterns generated in primary auditory cortex can be used to quickly and accurately identify consonant sounds from a continuous speech stream without prior knowledge of the stimulus onset times. Improved understanding of the neural mechanisms that support robust speech processing in difficult listening conditions could improve the identification and treatment of a variety of speech-processing disorders.

Knockdown of the dyslexia-associated gene Kiaa0319 impairs temporal responses to speech stimuli in rat primary auditory cortex.

One in 15 school age children have dyslexia, which is characterized by phoneme-processing problems and difficulty learning to read. Dyslexia is associated with mutations in the gene KIAA0319. It is not known whether reduced expression of KIAA0319 can degrade the brain's ability to process phonemes. In the current study, we used RNA interference (RNAi) to reduce expression of Kiaa0319 (the rat homolog of the human gene KIAA0319) and evaluate the effect in a rat model of phoneme discrimination. Speech discrimination thresholds in normal rats are nearly identical to human thresholds. We recorded multiunit neural responses to isolated speech sounds in primary auditory cortex (A1) of rats that received in utero RNAi of Kiaa0319. Reduced expression of Kiaa0319 increased the trial-by-trial variability of speech responses and reduced the neural discrimination ability of speech sounds. Intracellular recordings from affected neurons revealed that reduced expression of Kiaa0319 increased neural excitability and input resistance. These results provide the first evidence that decreased expression of the dyslexia-associated gene Kiaa0319 can alter cortical responses and impair phoneme processing in auditory cortex.

Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.

Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery.

Complex mixture discrimination and the role of contaminants.

Rats were trained in a 2-alternative odor choice task to discriminate between a 10-component odor mixture and the same mixture with one component removed and replaced with 1 of 3 concentrations of a different monomolecular odor (contaminant). All stimuli were presented within a training session, thus the rat essentially had to learn to discriminate the 10-component mixture from "not" the 10-component mixture. Rats performed most poorly discriminating the complete mixture from the mixture with one component removed and no contaminant added. As the concentration of the contaminant increased from 10 ppm to a concentration equal to the other components (100 ppm), discrimination improved linearly. In analyses of individual differences, rats that spent more time in the sampling port (sampling and making a decision) were more accurate than rats that spent less time. Together, these results emphasize the balance between perceptual stability and perceptual discrimination expressed by the olfactory system dealing with dynamic mixtures and the robust effects of contamination on those processes. In addition, they provide further support that modification of sampling/decision time is a strategy used by rats to deal with difficult discriminations of complex odors.

Anesthesia suppresses nonsynchronous responses to repetitive broadband stimuli.

Although many aspects of sensory processing are qualitatively similar in awake and anesthetized subjects, important state-dependent differences are known to exist. To investigate the effects of anesthesia on temporal processing in rat auditory cortex, multi-unit neural responses to trains of broadband clicks were recorded prior to, 15 min following, and 5 h following the administration of a ketamine-based anesthetic. While responses to clicks in isolation were relatively stable between states, responses to subsequent clicks exhibited increases in latency, peak latency, response duration, and post-onset suppression under anesthesia. Ketamine anesthetic reduced the maximum rate at which multi-unit clusters entrained to repeated clicks. No multi-unit clusters entrained to stimulus presentation rates greater than 33 Hz under anesthesia, compared with 85% and 81% in the pre- and post-anesthetic condition, respectively. Anesthesia also induced oscillatory activity that was not present in awake subjects. Finally, ketamine anesthesia abolished all tonic excitatory and suppressive nonsynchronous responses to click trains. The results of this study suggest that ketamine-based anesthesia significantly alters neural coding of broadband click trains in auditory cortex.

Response to broadband repetitive stimuli in auditory cortex of the unanesthetized rat.

This study examines the ability of multi-unit clusters (MUCs) in layer IV/V of primary auditory cortex of the awake rat to respond to a series of broadband click trains. The data from 113 multi-unit clusters were analyzed for synchronous and nonsynchronized responses using several methods. Synchronous responses were measured using window analysis, circular statistics and spectral analysis. Nonsynchronous responses were measured during different time intervals during the click train (first 50 ms, 50-450 ms, and the entire click train). The results demonstrate that multi-unit clusters are capable of synchronizing to clicks at rates up to 166 Hz. The mean synchronization boundary (limiting rate) for the group was found to be 72 Hz. Mean peak response rate, mean response duration, and mean time-to-peak response decreased as the stimulus presentation rate (SPR) increased, resulting in a temporal sharpening of the population response. For fast SPRs (>50 Hz), 50% of MUCs exhibited nonsynchronous responses in which the firing rate increased with SPR, although this activity was most prevalent during the first 50 ms of the response. Sustained increases in firing rate with SPR were seen in 8% of the MUCs, while another 38% of MUCs exhibited sustained decreases during the click train.

A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.

High-density multi-channel intra-cortical electrode arrays allow researchers to record simultaneously from populations of neurons for the purpose of understanding neural coding and plasticity. These devices have tens to hundreds of electrodes spaced within a few square millimeters. During insertion, the high-density probes can compress the cortex several millimeters prior to breaking through the pia. Compression of cortical tissue has been demonstrated to result in traumatic brain injury (TBI) which may be a major contributor to low electrode yield and decreased recording longevity. Two insertion techniques for chronically implanting multi-wire electrode arrays in layer IV of primary auditory cortex were compared. A mechanical insertion device, capable of rapidly inserting the electrode array without visible compression of the brain, was constructed. The neural responses to broadband clicks and pure tones recorded from the arrays inserted with the mechanical device were compared to the results from a manual insertion method using a micromanipulator. Both techniques result in a similar number of active channels directly following surgery with a mean signal-to-noise ratio of approximately 4.5. Over 60% of the animals implanted with the mechanical insertion device had driven activity at week 6 whereas none of the animals with manually inserted arrays exhibited functional responses after 3 weeks. This report provides initial evidence that mechanical insertion devices, which prevent cortical compression, increase electrode recording longevity.

An economical multi-channel cortical electrode array for extended periods of recording during behavior.

We report the development of a low-cost chronic multi-channel microwire electrode array for recording multi-unit cortical responses in behaving rodents. The design was motivated by three issues. First, standard connector systems tended to disconnect from the head-stage during extended periods of behavior. Disconnections resulted in a loss of data and an interruption of the animals' behavior. Second, the use of low insertion force connectors with locking mechanisms was cost prohibitive. Finally, connecting the head-stage to a skull-mounted connector on an unrestrained animal was highly stressful for both the researcher and animal. The design developed uses a high insertion force DIP socket separated from the skullcap that prevents inadvertent disconnects, is inexpensive, and simplifies connecting unrestrained rodents. Electrodes were implanted in layer IV of primary auditory cortex in 11 Sprague-Dawley rats. Performance of the electrodes was monitored for 6 weeks. None of the behaving animals became disconnected from the recording system during recording sessions lasting 6 h. The mean signal-to-noise ratio on all channels (154) following surgery was 3.9+/-0.2. Of the 154 channels implanted, 130 exhibited driven activity following surgery. Forty percent of the arrays continued to exhibit driven neural activity at 6 weeks.

Abnormal hormone levels in men with coronary artery disease.

Plasma concentrations and urinary excretions of various hormones and hormone metabolites were measured in four groups. Group 1 was composed of 13 men with prior myocardial infarction; Group 2 contained 35 clinically normal men; Group 3 consisted of 44 men with normal coronary arteriograms; and Group 4 was composed of 25 men with severe coronary artery disease shown on arteriogram but no infarction. There were four major findings: Group 1 had significantly higher 24-hour mean plasma concentrations of estrone (E1), dehydroisoandrosterone (DHA), and dehydroisoandrosterone sulfate (DHAS) than Group 2, while Group 3 had the same levels as Group 4; Group 4 had significantly lower urinary excretion of androsterone glucuronide (AG) than Group 3, while Group 1 excreted normal amounts. There are three possible explanations for these findings: 1) myocardial infarction occurring in men with coronary artery disease may elevate the plasma levels of E1, DHA, and DHAS and eliminate the preinfarction depression of urinary AG levels; 2) higher than average levels of E1, DHA, DHAS, and AG may favor the development of infarction in men with coronary artery disease; 3) higher than average levels of E1, DHA, DHAS, and AG may favor survival from any infarction that occurs in men with coronary artery disease. Experimental and epidemiological evidence seems to favor the third possibility.