Publications using TDT

Purpose The goal was to evaluate the potential effects of increasing hearing loss and advancing age on spectral envelope perception. Method Spectral modulation detection was measured as a function of spectral modulation frequency from 0.5 to 8.0 cycles/octave. The spectral modulation task involved discrimination of a noise carrier (3 octaves wide from 400 to 3200 Hz) with a flat spectral envelope from a noise having a sinusoidal spectral envelope across a logarithmic audio frequency scale. Spectral modulation transfer functions (SMTFs; modulation threshold vs. modulation frequency) were computed and compared 4 listener groups: young normal hearing, older normal hearing, older with mild hearing loss, and older with moderate hearing loss. Estimates of the internal spectral contrast were obtained by computing excitation patterns. Results SMTFs for young listeners with normal hearing were bandpass with a minimum modulation detection threshold at 2 cycles/octave, and older listeners with normal hearing were remarkably similar to those of the young listeners. SMTFs for older listeners with mild and moderate hearing loss had a low-pass rather than a bandpass shape. Excitation patterns revealed that limited spectral resolution dictated modulation detection thresholds at high but not low spectral modulation frequencies. Even when factoring out (presumed) differences in frequency resolution among groups, the spectral envelope perception was worse for the group with moderate hearing loss than the other 3 groups. Conclusions The spectral envelope perception as measured by spectral modulation detection thresholds is compromised by hearing loss at higher spectral modulation frequencies, consistent with predictions of reduced spectral resolution known to accompany sensorineural hearing loss. Spectral envelope perception is not negatively impacted by advancing age at any spectral modulation frequency between 0.5 and 8.0 cycles/octave.

Purpose Human auditory nerve (AN) activity estimated from the amplitude of the first prominent negative peak (N1) of the compound action potential (CAP) is typically quantified using either a peak-to-peak measurement or a baseline-corrected measurement. However, the reliability of these 2 common measurement techniques has not been evaluated but is often assumed to be relatively poor, especially for older adults. To address this question, the current study (a) compared test–retest reliability of these 2 methods and (b) tested the extent to which measurement type affected the relationship between N1 amplitude and experimental factors related to the stimulus (higher and lower intensity levels) and participants (younger and older adults). Method Click-evoked CAPs were recorded in 24 younger (aged 18–30 years) and 20 older (aged 55–85 years) adults with clinically normal audiograms up to 3000 Hz. N1 peak amplitudes were estimated from peak-to-peak measurements (from N1 to P1) and baseline-corrected measurements for 2 stimulus levels (80 and 110 dB pSPL). Baseline-corrected measurements were made with 4 baseline windows. Each stimulus level was presented twice, and test–retest reliability of these 2 measures was assessed using the intraclass correlation coefficient. Linear mixed models were used to evaluate the extent to which age group and click level uniquely predicted N1 amplitude and whether the predictive relationships differed between N1 measurement techniques. Results Both peak-to-peak and baseline-corrected measurements of N1 amplitude were found to have good-to-excellent reliability, with intraclass correlation coefficient values > 0.60. As expected, N1 amplitudes were significantly larger for younger participants compared with older participants for both measurement types and were significantly larger in response to clicks presented at 110 dB pSPL than at 80 dB pSPL for both measurement types. Furthermore, the choice of baseline window had no significant effect on N1 amplitudes using the baseline-corrected method. Conclusions Our results suggest that measurements of AN activity can be robustly and reliably recorded in both younger and older adults using either peak-to-peak or baseline-corrected measurements of the N1 of the CAP. Peak-to-peak measurements yield larger N1 response amplitudes and are the default measurement type for many clinical systems, whereas baseline-corrected measurements are computationally simpler. Furthermore, the relationships between AN activity and stimulus- and participant-related variables were not affected by measurement technique, which suggests that these relationships can be compared across studies using different techniques for measuring the CAP N1.

Background: To confirm levels and detection timing of circulating microRNAs (miRNAs) in the serum of a mouse model for diagnosis of ototoxicity, circulating miR-205 in the serum was evaluated to reflect damages in the cochlear microstructure and compared to a kidney injury model. Method: A microarray for miRNAs in the serum was performed to assess the ototoxic effects of kanamycin-furosemide. Changes in the levels for the selected miRNAs (miR-205, miR-183, and miR-103) were compared in the serum and microstructures of the cochlea (stria vascularis, organ of Corti, and modiolus) between the ototoxicity and normal mouse groups. An acute kidney injury (AKI) mouse model was used to assess changes in miR-205 levels in the kidney by ototoxic drugs. Results: In the mouse model for ototoxicity, the serum levels of circulating miR-205 peaked on day 3 and were sustained from days 7–14. Furthermore, miR-205 expression was highly expressed in the organ of Corti at day 5, continued to be expressed in the modiolus at high levels until day 14, and was finally also in the stria vascularis. The serum miR-205 in the AKI mice did not change significantly compared to the normal group. Conclusions Circulating miR-205 from the cochlea, after ototoxic damage, migrates through the blood vessels to organs, which is then finally found in blood. In conditions of hearing impairment with ototoxic medications, detection of circulating miR-205 in the blood can be used to determine the extent of hearing loss. In the future, inner ear damage can be identified by simply performing a blood test before the hearing impairment due to ototoxic drugs.

Naked mole-rats are extremely social and extremely vocal rodents, displaying a wide range of functionally distinct call types and vocalizing almost continuously. Their vocalizations are low frequency, and a behavioral audiogram has shown that naked mole-rats, like other subterranean mammals, hear only low frequencies. Hence, the frequency range of their hearing and vocalizations appears to be well matched. However, even at low frequencies, naked mole-rats show very poor auditory thresholds, suggesting vocal communication may be effective only over short distances. However, in a tunnel environment where low frequency sounds propagate well and background noise is low, it may be that vocalizations travel considerable distances at suprathreshold intensities. Here, we confirmed hearing sensitivity using the auditory brainstem response; we characterized signature and alarm calls in intensity and frequency domains and we measured the effects of propagation through tubes with the diameter of naked mole-rat tunnels. Signature calls-used for intimate communication-could travel 3-8 m at suprathreshold intensities, and alarm calls (lower frequency and higher intensity), could travel up to 15 m. Despite this species' poor hearing sensitivity, the naked mole-rat displays a functional, coupled auditory-vocal communication system-a hallmark principle of acoustic communication systems across taxa.

Background: Numerous studies have demonstrated that individuals exhibit structured neural activity in many brain regions during rest that is also observed during different tasks, however it is still not clear whether and how resting state activity patterns may relate to underlying tuning for specific stimuli. In the posterior superior temporal gyrus (STG), distinct neural activity patterns are observed during the perception of specific linguistic speech features. We hypothesized that spontaneous resting-state neural dynamics of the STG would be structured to reflect its role in speech perception, exhibiting an organization along speech features as seen during speech perception. Methods: Human cortical local field potentials were recorded from the superior temporal gyrus (STG) in 8 patients undergoing surgical treatment of epilepsy. Signals were recorded during speech perception and rest. Patterns of neural activity (high gamma power: 70-150 Hz) during rest, extracted with spatiotemporal principal component analysis, were compared to spatiotemporal neural responses to speech features during perception. Hierarchical clustering was applied to look for patterns in rest that corresponded to speech feature tuning. Results: Significant correlations were found between neural responses to speech features (sentence onsets, consonants, and vowels) and the spontaneous neural activity in the STG. Across subjects, these correlations clustered into five groups, demonstrating tuning for speech features-most robustly for acoustic onsets. These correlations were not seen in other brain areas, or during motor and spectrally-rotated speech control tasks. Conclusions: In this study, we present evidence that the RS structure of STG activity robustly recapitulates its stimulus-evoked response to acoustic onsets. Further, secondary patterns in RS activity appear to correlate with stimulus-evoked responses to speech features. The role of these spontaneous spatiotemporal activity patterns remains to be elucidated.

To function as a mechanism in premating isolation, the divergent and species-specific calling songs of acoustic insects must be reliably processed by the afferent auditory pathway of receivers. Here, we analysed the responses of interneurons in a katydid species that uses long-lasting acoustic trills and compared these with previously reported data for homologous interneurons of a sympatric species that uses short chirps as acoustic signals. Some interneurons of the trilling species respond exclusively to the heterospecific chirp due to selective, low-frequency tuning and "novelty detection". These properties have been considered as evolutionary adaptations in the sensory system of the chirper, which allow it to detect signals effectively during the simultaneous calling of the sympatric sibling species. We propose that these two mechanisms, shared by the interneurons of both species, did not evolve in the chirper to guarantee its ability to detect the chirp under masking conditions. Instead we suggest that chirpers evolved an additional, 2-kHz component in their song and exploited pre-existing neuronal properties for detecting their song under masking noise. The failure of some interneurons to respond to the conspecific song in trillers does not prevent intraspecific communication, as other interneurons respond to the trill.

Auditory streaming is the process by which environmental sound is segregated into discrete perceptual objects. The auditory system has a remarkable capability in this regard as revealed in psychophysical experiments in humans and other primates. However, little is known about the underlying neuronal mechanisms, in part because of the lack of suitable behavioural paradigms in non-primate species. The mouse is an increasingly popular model for studying the neural mechanisms of perception and action because of the range of molecular tools enabling precise manipulation of neural circuitry. Here we present a novel behavioural task that can be used to assess perceptual aspects of auditory streaming in head-fixed mice. Animals were trained to detect a target sound in a one of two simultaneously presented, isochronous pure tone sequences. Temporal expectation was manipulated by presenting the target sound in a particular stream either early (~2 s) or late (~4 s) with respect to trial onset in blocks of 25-30 trials. Animals reached high performance on this task (d' > 1 overall), and notably their false alarms were very instructive of their behavioural state. Indeed, false alarm timing was markedly delayed for late blocks compared to early ones, indicating that the animals associated a different context to an otherwise identical stimulus. More finely, we observed that the false alarms were timed to the onset of the sounds present in the target stream. This suggests that the animals could selectively follow the target stream despite the presence of a distractor stream. Extracellular electrophysiological recordings during the task revealed that sound processing is flexibly modulated in a manner consistent with the optimisation of behavioural outcome. Together, these results indicate that the perceptual streaming can be inferred via the timing of false alarms in mice, and provide a new paradigm with which to investigate neuronal mechanisms of selective attention.

Auditory hair cells possess stunning cilia structure that composes of a bundle of stereocilia for mechano-electrical transduction and a single kinocilium for guiding the polarity of hair bundle towards maturation. However, the molecules underlying kinocilium function have not yet been fully understood. Hence, the proteins involved in hair bundle development and function are of a large interest. From a fine microarray analysis, we found that kinocilin (Kncn) was enriched in hair cell specific expression profile. Consistently, it has been reported that KNCN was a protein mainly located in the kinocilium of hair cells in the inner ear. However, the hypothesis that KNCN is a kinocilium protein has not been validated in mice with Kncn gene perturbed. In this study, we generated Kncn knockout mouse lines by CRISPR/Cas9 technique and further examined the morphology and function of cochlear hair cells. Our results showed that there was no obvious hearing loss in the knockout mice, determined by audiometry. Histological study demonstrated that the inner ear and hair cell structure were intact. Especially, there was no deficit of mechanotransduction (MET) in cochlear outer hair cells (OHCs). In summary, our work suggests that KNCN is not essential for kinocilium-oriented hair bundle function in cochlear hair cells.

A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2–10 ms), and long latency (10–100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10–20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact. SIGNIFICANCE STATEMENT This is the first physiological demonstration of the corticosubthalamic hyperdirect pathway and its topography at high spatial resolution in humans. We studied cortical potentials evoked by deep-brain stimulation in patients with Parkinson's disease undergoing awake lead implantation surgery. Subthalamic stimulation resulted in multiple short-latency responses consistent with activation of hyperdirect pathway, whereas no such response was present during pallidal stimulation. We contrast these findings with very short latency, direct corticospinal tract activations, and long-latency responses evoked through polysynaptic orthodromic projections. These findings underscore the importance of incorporating the hyperdirect pathway into models of human basal ganglia function.

Objective Age‐related muscle atrophy of the laryngeal muscles contributes to presbyphonia. Remodeling of the neuromuscular junction is one aspect underlying age‐related muscle atrophy. Although muscle disuse has been shown to exacerbate age‐related neuromuscular changes in the limb muscles, it is unknown if reduced vocal use has a similar effect in the laryngeal muscles. The objective of this study was to examine the use of social isolation as a novel method to reduce vocal use in old rats—and the impact of that reduced vocal use on ultrasonic vocalization acoustics and neuromuscular junction morphology in the thyroarytenoid muscle. Study Design Animal group comparison. Methods Old F344/BN rats (31 months of age) were socially isolated (n = 8) or communally housed (n = 8) for 8 weeks. Effect of housing condition on ultrasonic vocalization acoustics was assessed by calculating the changes in vocalization fundamental frequency and amplitude from baseline to 8 weeks. Neuromuscular junction morphology was measured in the lateral and medial portions of the thyroarytenoid muscle at the conclusion of the experiment. Results Vocalization amplitude decreased by a mean of −4.4 dB (standard deviation [SD], 4.49) after social isolation, whereas amplitude increased by a mean of 5.7 dB (SD, 5.07) in the communally housed rats ( P = 0.002). There was no significant difference in the change in fundamental frequency between groups. Furthermore, there were no group differences in any measure of neuromuscular junction morphology. Conclusion These results suggest that neuromuscular junctions in the thyroarytenoid muscle of old rats are unaffected by 8 weeks of social isolation, despite functional changes in vocalizations. Level of Evidence NA Laryngoscope , 129:E9–E14, 2019

Overexposure to loud noise is known to lead to deficits in auditory sensitivity and perception. We studied the effects of noise exposure on sensorimotor behaviors of larval (5-7 days post-fertilization) zebrafish (Danio rerio), particularly the auditory-evoked startle response and hearing sensitivity to acoustic startle stimuli. We observed a temporary 10-15 dB decrease in startle response threshold after 18 h of flat-spectrum noise exposure at 20 dB re·1 ms-2. Larval zebrafish also exhibited decreased habituation to startle-inducing stimuli following noise exposure. The noise-induced sensitization was not due to changes in absolute hearing thresholds, but was specific to the auditory-evoked escape responses. The observed noise-induced sensitization was disrupted by AMPA receptor blockade using DNQX, but not NMDA receptor blockade. Together, these experiments suggest a complex effect of noise exposure on the neural circuits mediating auditory-evoked behaviors in larval zebrafish.

Serine/threonine kinase 33 ( STK 33), a member of the calcium/calmodulin‐dependent kinase ( CAMK ), plays vital roles in a wide spectrum of cell processes. The present study was designed to investigate whether STK 33 expressed in the mammalian cochlea and, if so, what effect STK 33 exerted on aminoglycoside‐induced ototoxicity in House Ear Institute‐Organ of Corti 1 ( HEI ‐ OC 1) cells. Immunofluorescence staining and western blotting were performed to investigate STK 33 expression in cochlear hair cells ( HC s) and HEI ‐ OC 1 cells with or without gentamicin treatment. CCK 8, flow cytometry, immunofluorescence staining and western blotting were employed to detect the effects of STK 33 knockdown, and/or U0126, and/or N‐acetyl‐L‐cysteine ( NAC ) on the sensitivity to gentamicin‐induced ototoxicity in HEI ‐ OC 1 cells. We found that STK 33 was expressed in both mice cochlear HC s and HEI ‐ OC 1 cells, and the expression of STK 33 was significantly decreased in cochlear HC s and HEI ‐ OC 1 cells after gentamicin exposure. STK 33 knockdown resulted in an increase in the cleaved caspase‐3 and Bax expressions as well as cell apoptosis after gentamicin damage in HEI ‐ OC 1 cells. Mechanistic studies revealed that knockdown of STK 33 led to activated mitochondrial apoptosis pathway as well as augmented reactive oxygen species ( ROS ) accumulation after gentamicin damage. Moreover, STK 33 was involved in extracellular signal‐regulated kinase 1/2 pathway in primary culture of HC s and HEI ‐ OC 1 cells in response to gentamicin insult. The findings from this work indicate that STK 33 decreases the sensitivity to the apoptosis dependent on mitochondrial apoptotic pathway by regulating ROS generation after gentamicin treatment, which provides a new potential target for protection from the aminoglycoside‐induced ototoxicity.

Noise is the most common occupational and environmental hazard, and noise-induced hearing loss (NIHL) is the second most common form of sensorineural hearing deficit. Although therapeutics that target the free-radical pathway have shown promise, none of these compounds is currently approved against NIHL by the United States Food and Drug Administration. The present study has demonstrated that tetrandrine (TET), a traditional Chinese medicinal alkaloid and the main chemical isolate of the Stephania tetrandra S. Moore herb, significantly attenuated NIHL in CBA/CaJ mice. TET is known to exert antihypertensive and antiarrhythmic effects through the blocking of calcium channels. Whole-cell patch-clamp recording from adult spiral ganglion neurons showed that TET blocked the transient Ca2+ current in a dose-dependent manner and the half-blocking concentration was 0.6 + 0.1 μM. Consistent with previous findings that modulations of calcium-based signaling pathways have both prophylactic and therapeutic effects against neural trauma, NIHL was significantly diminished by TET administration. Importantly, TET has a long-lasting protective effect after noise exposure (48 weeks) in comparison to 2 weeks after noise exposure. The otoprotective effects of TET were achieved mainly by preventing outer hair cell damage and synapse loss between inner hair cells and spiral ganglion neurons. Thus, our data indicate that TET has great potential in the prevention and treatment of NIHL.

The use of cisplatin (CDDP), the most common chemotherapy drug for head and neck cancer, is limited by its undesirable side effects, especially nephrotoxicity. We investigated ultrasound microbubbles (USMB) as a tool to increase the local intra-tumoral CDDP level while decreasing systemic CDDP cytotoxicity. We allowed CDDP to interact with human serum albumin and then sonicated the resulting CDDP‒albumin complex to generate CDDP-loaded MBs (CDDP-MBs). We then established a head-and-neck tumor-bearing mouse model by implanting FaDu-fLuc/GFP cells into severe combined immunodeficiency mice and used IVIS® bioluminescence imaging to determine the tumor xenograft formation and size. Twice weekly (until Day 33), we administered CDDP only, CDDP + MBs + US, CDDP-MBs, or CDDP-MBs + US intravenously by tail-vein injection. The US treatment was administered at the tumor site immediately after injection. The in vivo systemic distribution of CDDP indicated that the kidney was the most vulnerable organ, followed by the liver, and then the inner ear. However, CDDP uptake into the kidney and liver was significantly decreased in both the CDDP-MBs and CDDP-MBs + US groups, suggesting that MB binding significantly reduced the systemic toxicity of CDDP. The CDDP-MBs + US treatment reduced the tumor size as effectively as conventional CDDP-only chemotherapy. Therefore, the combination of CDDP-MBs with ultrasound is effective and significantly attenuates CDDP-associated nephrotoxicity, indicating a promising clinical potential for this approach.

Auditory sensory outer hair cells are thought to amplify sound-induced basilar membrane vibration through a feedback mechanism to enhance hearing sensitivity. For optimal amplification, the outer hair cell-generated force must act on the basilar membrane at an appropriate time at every cycle. However, the temporal relationship between the outer hair cell-driven reticular lamina vibration and the basilar membrane vibration remains unclear. By measuring sub-nanometer vibrations directly from outer hair cells using a custom-built heterodyne low-coherence interferometer, we demonstrate in living gerbil cochleae that the reticular lamina vibration occurs after, not before, the basilar membrane vibration. Both tone- and click-induced responses indicate that the reticular lamina and basilar membrane vibrate in opposite directions at the cochlear base and they oscillate in phase near the best-frequency location. Our results suggest that outer hair cells enhance hearing sensitivity through a global hydromechanical mechanism, rather than through a local mechanical feedback as commonly supposed.

The perceived pitch of iterated rippled noise (IRN) with negative gain (IRNn) is an octave lower than that of IRN with positive gain (IRNp). IRNp and IRNn have identical waveform envelopes (ENV), but differing stimulus waveform fine structure (TFS), which likely accounts for this perceived pitch difference. Here, we examine whether differences in the temporal pattern of phase-locked activity reflected in the human brainstem Frequency Following Response (FFR) elicited by IRNp and IRNn can account for the differences in perceived pitch for the two stimuli. FFRs using a single onset polarity were measured in 13 normal-hearing, adult listeners in response to IRNp and IRNn stimuli with 2 ms, and 4 ms delay. Autocorrelation functions (ACFs) and Fast Fourier Transforms (FFTs) were used to evaluate the dominant periodicity and spectral pattern (harmonic spacing) in the phase-locked FFR neural activity. For both delays, the harmonic spacing in the spectra corresponded more strongly with the perceived lowering of pitch from IRNp to IRNn, compared to the ACFs. These results suggest that the FFR elicited by a single polarity stimulus reflects phase-locking to both stimulus ENV and TFS. A post-hoc experiment evaluating the FFR phase-locked activity to ENV (FFRENV), and TFS (FFRTFS) elicited by IRNp and IRNn confirmed that only the phase-locked activity to the TFS, reflected in FFRTFS, showed differences in both spectra and ACF that closely matched the pitch difference between the two stimuli. The results of the post-hoc experiment suggests that pitch-relevant information is preserved in the temporal pattern of phase-locked activity and suggests that the differences in stimulus ENV and TFS driving the pitch percept of IRNp and IRNn are preserved in the brainstem neural response. The scalp recorded FFR may provide for a noninvasive analytic tool to evaluate the relative contributions of envelope and temporal fine-structure in the neural representation of complex sounds in humans.

Background: Recent years have witnessed an upsurge in the development of methods for estimating current source densities (CSDs) in the neocortical tissue from their recorded local field potential (LFP) reflections using microelectrode arrays. Among these, methods utilizing linear arrays work under the assumption that CSDs vary as a function of cortical depth; whereas they are constant in the tangential direction, infinitely or in a confined cylinder. This assumption is violated in the analysis of neuronal activity propagating along the neocortical sheet, e.g. propagation of alpha waves or cortical spreading depression. New method: Here, we developed a novel mathematical method (waveCSD) for CSD analysis of LFPs associated with a planar wave of neocortical neuronal activity propagating at a constant velocity towards a linear probe. Results: Results show that the algorithm is robust to the presence of noise in LFP data and uncertainties in knowledge of propagation velocity. Also, results show high level of accuracy of the method in a wide range of electrode resolutions. Using in vivo experimental recordings from the rat neocortex, we employed waveCSD to characterize transmembrane currents associated with cortical spreading depressions. Comparison with existing method(s): Simulation results indicate that waveCSD has a significantly higher reconstruction accuracy compared to the widely-used inverse CSD method (iCSD), and the regularized kernel CSD method (kCSD), in the analysis of CSDs originating from propagating neuronal activity. Conclusions: The waveCSD method provides a theoretical platform for estimation of transmembrane currents from their LFPs in experimental paradigms involving wave propagation.

Background: Current concepts suggest that impaired representation of information in cortical networks contributes to loss of consciousness under anaesthesia. We tested this idea in rat auditory cortex using information theory analysis of multiunit responses recorded under three anaesthetic agents with different molecular targets: isoflurane, propofol, and dexmedetomidine. We reasoned that if changes in the representation of sensory stimuli are causal for loss of consciousness, they should occur regardless of the specific anaesthetic agent. Methods: Spiking responses were recorded with chronically implanted microwire arrays in response to acoustic stimuli incorporating varied temporal and spectral dynamics. Experiments consisted of four drug conditions: awake (pre-drug), sedation (i.e. intact righting reflex), loss of consciousness (a dose just sufficient to cause loss of righting reflex), and recovery. Measures of firing rate, spike timing, and mutual information were analysed as a function of drug condition. Results: All three drugs decreased spontaneous and evoked spiking activity and modulated spike timing. However, changes in mutual information were inconsistent with altered stimulus representation being causal for loss of consciousness. First, direction of change in mutual information was agent-specific, increasing under dexmedetomidine and decreasing under isoflurane and propofol. Second, mutual information did not decrease at the transition between sedation and LOC for any agent. Changes in mutual information under anaesthesia correlated strongly with changes in precision and reliability of spike timing, consistent with the importance of temporal stimulus features in driving auditory cortical activity. Conclusions: The primary sensory cortex is not the locus for changes in representation of information causal for loss of consciousness under anaesthesia.

Past research has identified anatomically specific sites within the posterior inferior temporal gyrus (PITG) and the intraparietal sulcus (IPS) areas that are engaged during arithmetic processing. Although a small region of the PITG (known as the number form area) is selectively engaged in the processing of numerals, its surrounding area is activated during both digit and number word processing. In eight participants with intracranial electrodes, we compared the timing and selectivity of electrophysiological responses in the number form area-surround and IPS regions during arithmetic processing with digits and number words. Our recordings revealed stronger electrophysiological responses in the high-frequency broadband range in both regions to digits than number words, with the difference that number words elicited delayed activity in the IPS but not PITG. Our findings of distinct profiles of responses in the PITG and the IPS to digits compared with number words provide novel information that is relevant to existing theoretical models of mathematical cognition.

Many studies suggest that Parkinson’s disease (PD) is associated with changes in neuronal activity patterns throughout the basal ganglia-thalamocortical motor circuit. There are limited electrophysiological data, however, describing how parkinsonism impacts the presupplementary motor area (pre-SMA) and SMA proper (SMAp), cortical areas known to be involved in movement planning and motor control. In this study, local field potentials (LFPs) were recorded in the pre-SMA/SMAp of a nonhuman primate during a visually cued reaching task. Recordings were made in the same subject in both the naive and parkinsonian state using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism. We found that in the naive animal, well before a go-cue providing instruction of reach onset and direction was given, LFP activity was dynamically modulated in both high (20–30 Hz) and low beta (10–20 Hz) bands, and the magnitude of this modulation (e.g., decrease/increase in beta amplitude for each band, respectively) correlated linearly with reaction time (RT) on a trial-to-trial basis, suggesting it may predictively encode for RT. Consistent with this hypothesis, we observed that this activity was more prominent within the pre-SMA compared with SMAp. In the parkinsonian state, however, pre-SMA/SMAp beta band modulation was disrupted, particularly in the high beta band, such that the predictive encoding of RT was significantly diminished. In addition, the predictive encoding of RT preferentially within pre-SMA over SMAp was lost. These findings add to our understanding of the role of pre-SMA/SMAp in motor behavior and suggest a fundamental role of these cortical areas in early preparatory and premovement processes that are altered in parkinsonism. NEW & NOTEWORTHY Goal-directed movements, such as reaching for an object, necessitate temporal preparation and organization of information processing within the basal ganglia-thalamocortical motor network. Impaired movement in parkinsonism is thought to be the result of pathophysiological activity disrupting information flow within this network. This work provides neurophysiological evidence linking altered motor preplanning processes encoded in pre-SMA/SMAp beta band modulation to the pathogenesis of motor disturbances in parkinsonism.