Can brain signals and anatomy refine contact choice for deep brain stimulation in Parkinson's disease?

INTRODUCTION: Selecting the ideal contact to apply subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease is time-consuming and reliant on clinical expertise. The aim of this cohort study was to assess whether neuronal signals (beta oscillations and evoked resonant neural activity (ERNA)), and the anatomical location of electrodes, can predict the contacts selected by long-term, expert-clinician programming of STN-DBS. METHODS: We evaluated 92 hemispheres of 47 patients with Parkinson's disease receiving chronic monopolar and bipolar STN-DBS. At each contact, beta oscillations and ERNA were recorded intraoperatively, and anatomical locations were assessed. How these factors, alone and in combination, predicted the contacts clinically selected for chronic deep brain stimulation at 6 months postoperatively was evaluated using a simple-ranking method and machine learning algorithms. RESULTS: The probability that each factor individually predicted the clinician-chosen contact was as follows: ERNA 80%, anatomy 67%, beta oscillations 50%. ERNA performed significantly better than anatomy and beta oscillations. Combining neuronal signal and anatomical data did not improve predictive performance. CONCLUSION: This work supports the development of probability-based algorithms using neuronal signals and anatomical data to assist programming of deep brain stimulation.

Lesser-Known Aspects of Deep Brain Stimulation for Parkinson's Disease: Programming Sessions, Hardware Surgeries, Residential Care Admissions, and Deaths.

OBJECTIVE: The long-term treatment burden, duration of community living, and survival of patients with Parkinson's disease (PD) after deep brain stimulation (DBS) implantation are unclear. This study aims to determine the frequency of programming, repeat hardware surgeries (of the intracranial electrode, implantable pulse generator [IPG], and extension-cable), and the timings of residential care and death in patients with PD treated with DBS. MATERIALS AND METHODS: In this cross-sectional, population-based study, individual-level data were collected from the Australian government covering a 15-year period (2002-2016) on 1849 patients with PD followed from DBS implantation. RESULTS: The mean DBS implantation age was 62.6 years and mean follow-up 5.0 years. Mean annual programming rates were 6.9 in the first year and 2.8 in subsequent years. 51.4% of patients required repeat hardware surgery. 11.3% of patients had repeat intracranial electrode surgery (including an overall 1.1% of patients who were completely explanted). 47.6% of patients had repeat IPG/extension-cable surgery including for presumed battery depletion. 6.2% of patients had early repeat IPG/extension-cable surgery (within one year of any previous such surgery). Thirty-day postoperative mortality was 0.3% after initial DBS implantation and 0.6% after any repeat hardware surgery. 25.3% of patients were admitted into residential care and 17.4% died. The median interval to residential care and death was 10.2 years and 11.4 years, respectively. Age more than 65 years was associated with fewer repeat hardware surgeries for presumed complications (any repeat surgery of electrodes, extension-cables, and early IPG surgery) and greater rates of residential care admission and death. CONCLUSIONS: Data from a large cohort of patients with PD treated with DBS found that the median life span after surgery is ten years. Repeat hardware surgery, including of the intracranial electrodes, is common. These findings support development of technologies to reduce therapy burden such as enhanced surgical navigation, hardware miniaturization, and improved battery efficiency.

Deep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activity.

Deep brain stimulation is an established therapy for Parkinson's disease; however, its effectiveness is hindered by limited understanding of therapeutic mechanisms and the lack of a robust feedback signal for tailoring stimulation. We recently reported that subthalamic nucleus deep brain stimulation evokes a neural response resembling a decaying high-frequency (200-500 Hz) oscillation that typically has a duration of at least 10 ms and is localizable to the dorsal sub-region. As the morphology of this response suggests a propensity for the underlying neural circuitry to oscillate at a particular frequency, we have named it evoked resonant neural activity. Here, we determine whether this evoked activity is modulated by therapeutic stimulation - a critical attribute of a feedback signal. Furthermore, we investigated whether any related changes occurred in spontaneous local field potentials. Evoked and spontaneous neural activity was intraoperatively recorded from 19 subthalamic nuclei in patients with Parkinson's disease. Recordings were obtained before therapeutic stimulation and during 130 Hz stimulation at increasing amplitudes (0.67-3.38 mA), 'washout' of therapeutic effects, and non-therapeutic 20 Hz stimulation. Therapeutic efficacy was assessed using clinical bradykinesia and rigidity scores. The frequency and amplitude of evoked resonant neural activity varied with the level of 130 Hz stimulation (p < .001). This modulation coincided with improvement in bradykinesia and rigidity (p < .001), and correlated with spontaneous beta band suppression (p < .001). Evoked neural activity occupied a similar frequency band to spontaneous high-frequency oscillations (200-400 Hz), both of which decreased to around twice the 130 Hz stimulation rate. Non-therapeutic stimulation at 20 Hz evoked, but did not modulate, resonant activity. These results indicate that therapeutic deep brain stimulation alters the frequency of evoked and spontaneous oscillations recorded in the subthalamic nucleus that are likely generated by loops within the cortico-basal ganglia-thalamo-cortical network. Evoked resonant neural activity therefore has potential as a tool for providing insight into brain network function and has key attributes of a dynamic feedback signal for optimizing therapy.

Subthalamic nucleus deep brain stimulation evokes resonant neural activity.

Deep brain stimulation (DBS) is a rapidly expanding treatment for neurological and psychiatric conditions; however, a target-specific biomarker is required to optimize therapy. Here, we show that DBS evokes a large-amplitude resonant neural response focally in the subthalamic nucleus. This response is greatest in the dorsal region (the clinically optimal stimulation target for Parkinson disease), coincides with improved clinical performance, is chronically recordable, and is present under general anesthesia. These features make it a readily utilizable electrophysiological signal that could potentially be used for guiding electrode implantation surgery and tailoring DBS therapy to improve patient outcomes. Ann Neurol 2018;83:1027-1031.

The effect of presentation level and stimulation rate on speech perception and modulation detection for cochlear implant users.

In order to improve speech understanding for cochlear implant users, it is important to maximize the transmission of temporal information. The combined effects of stimulation rate and presentation level on temporal information transfer and speech understanding remain unclear. The present study systematically varied presentation level (60, 50, and 40 dBA) and stimulation rate [500 and 2400 pulses per second per electrode (pps)] in order to observe how the effect of rate on speech understanding changes for different presentation levels. Speech recognition in quiet and noise, and acoustic amplitude modulation detection thresholds (AMDTs) were measured with acoustic stimuli presented to speech processors via direct audio input (DAI). With the 500 pps processor, results showed significantly better performance for consonant-vowel nucleus-consonant words in quiet, and a reduced effect of noise on sentence recognition. However, no rate or level effect was found for AMDTs, perhaps partly because of amplitude compression in the sound processor. AMDTs were found to be strongly correlated with the effect of noise on sentence perception at low levels. These results indicate that AMDTs, at least when measured with the CP910 Freedom speech processor via DAI, explain between-subject variance of speech understanding, but do not explain within-subject variance for different rates and levels.

Clinical outcomes for adult cochlear implant recipients experiencing loss of usable acoustic hearing in the implanted ear.

OBJECTIVES: The first aim of the study was to quantify the change in clinical performance after cochlear implantation for adults who had pre-operative levels of acoustic hearing in each ear of greater than or equal to 46% phoneme score on an open-set monosyllabic word test, and who subsequently experienced loss of useable acoustic hearing in the implanted ear. Pre- and postoperative spatial hearing abilities were assessed, because a clinical consideration for candidates with bilateral acoustic hearing is the potential for post-operative reduction in spatial hearing ability. Second, it was of interest to examine whether preoperative localization ability, as an indicator of access to interaural timing and level cues preoperatively, might be correlated with post-operative change in spatial hearing abilities. DESIGN: Clinical performance measures in the binaural condition were obtained preoperatively and at 12 months postoperatively in 19 postlinguistically hearing-impaired adult subjects. Preoperative localization ability was investigated as a potential correlate with post-operative change in spatial hearing abilities. RESULTS: Significant postoperative group mean improvement in speech perception was observed on measures of open-set monosyllabic word perception in quiet and on an adaptive sentence test presented in coincident 4-talker babble. Observed benefit was greater for a lower presentation level of 55 dB SPL as compared with a conversational speech level of 65 dB SPL. Self-reported ratings of benefit also improved for all questionnaires administered. Objective assessment of localization ability revealed poorer localization postoperatively, although subjective ratings of post-operative change in localization ability in real-world environments were more variable. Postoperative spatial release from masking was not different to that measured preoperatively for the configuration where the side of the head with the hearing aid was advantaged, but improved postoperatively for the configuration that advantaged the implanted side. Preoperative binaural localization ability was not correlated with postoperative spatial hearing abilities. CONCLUSIONS: The findings from this study support cochlear implantation for candidates with pre-operative levels of binaural acoustic hearing within the range examined within the present study. This includes subjects with preoperative open-set monosyllabic word scores ranging from 11 to 62% in the implanted ear, and from 16 to 75% on the contralateral side. Post-operative improvement would be expected for those subjects on a range of clinical measures, even when acoustic hearing was lost in the implanted ear after implantation.

Loudness of time-varying stimuli with electric stimulation.

McKay, Henshall, Farrell, and McDermott [J. Acoust. Soc. Am. 113, 2054-2063 (2003)] developed a practical method to estimate the loudness of periodic electrical signals presented through a cochlear implant. In the present work, this method was extended to time-varying sounds based on two models of time-varying loudness for normal listeners. To fit the model parameters, loudness balancing data was collected with six cochlear implant listeners. The pulse rate of a modulated pulse train was adjusted to equalize its loudness to a reference stimulus. The stimuli were single-electrode time-limited pulse bursts, repeated at a rate of 50 Hz, with on-times varying between 2 and 20 ms. The parameters of two different models of time-varying loudness were fitted to the results. For each model, parameters defining the time windows over which the electrical pulses contribute to instantaneous loudness were optimized. In each case, a good fit was obtained with the loudness balancing results. Therefore, the practical method was successfully extended to time-varying sounds by combining it with existing models of time-varying loudness for acoustic stimulation.

Factors influencing electrical place pitch perception in bimodal listeners.

Factors that might affect perceptual pitch match between acoustic and electric stimulation were examined in 25 bimodal listeners using magnitude estimation. Pre-operative acoustic thresholds in both ears, and duration of severe-profound loss, were first examined as correlates with degree of match between the measured pitch and that predicted by the spiral ganglion frequency-position model. The degree of match was examined with respect to (1) the ratio between the measured and predicted pitch percept on the most apical electrode and (2) the ratio between the slope of the measured and predicted pitch function. Second, effect of listening experience was examined to assess whether adaptation occurred over time to match the frequency assignment to electrodes. Pre-experience pitch estimates on the apical electrode were within the predicted range in only 28% of subjects, and the slope of the electrical pitch function was lower than predicted in all except one subject. Subjects with poorer hearing tended to have a lower pitch and a shallower electrical pitch function than predicted by the model. Pre-operative hearing thresholds in the contralateral ear and hearing loss duration were not correlated with the degree of pitch match, and there was no significant group effect of listening experience.

Psychophysics, fitting, and signal processing for combined hearing aid and cochlear implant stimulation.

The addition of acoustic stimulation to electric stimulation via a cochlear implant has been shown to be advantageous for speech perception in noise, sound quality, music perception, and sound source localization. However, the signal processing and fitting procedures of current cochlear implants and hearing aids were developed independently, precluding several potential advantages of bimodal stimulation, such as improved sound source localization and binaural unmasking of speech in noise. While there is a large and increasing population of implantees who use a hearing aid, there are currently no generally accepted fitting methods for this configuration. It is not practical to fit current commercial devices to achieve optimal binaural loudness balance or optimal binaural cue transmission for arbitrary signals and levels. There are several promising experimental signal processing systems specifically designed for bimodal stimulation. In this article, basic psychophysical studies with electric acoustic stimulation are reviewed, along with the current state of the art in fitting, and experimental signal processing techniques for electric acoustic stimulation.

A beamformer post-filter for cochlear implant noise reduction.

Cochlear implant users have limited ability to understand speech in noisy conditions. Signal processing methods to address this issue that use multiple microphones typically use beamforming to perform noise reduction. However, the effectiveness of the beamformer is diminished as the number of interfering noises increases and the acoustic environment becomes more diffuse. A multi-microphone noise reduction algorithm that aims to address this issue is presented in this study. The algorithm uses spatial filtering to estimate the signal-to-noise ratio (SNR) and attenuates time-frequency elements that have poor SNR. The algorithm was evaluated by measuring intelligibility of speech embedded in 4-talker babble where the interfering talkers were spatially separated and changed location during the test. Twelve cochlear implant users took part in the evaluation, which demonstrated a significant mean improvement of 4.6 dB (standard error 0.4, P < 0.001) in speech reception threshold compared to an adaptive beamformer. The results suggest that a substantial improvement in performance can be gained for cochlear implant users in noisy environments where the noise is spatially separated from the target speech.

Discrimination of intonation contours by adolescents with cochlear implants.

OBJECTIVE: Differences in fundamental frequency (F0) contour peak alignment contribute to the perception of pitch accents in speech intonation. The present study assessed the discrimination of differences in F0 contour peak alignment by adolescent users of cochlear implants (CIs). DESIGN: In Experiment 1, subjects discriminated between rise-fall F0 contours located early in the syllable and those aligned late. Recorded utterances with manipulated F0 were used as stimuli and all subjects wore a unilateral CI. In Experiment 2, bilaterally-implanted subjects repeated Experiment 1 in the bilateral condition. STUDY SAMPLE: Twenty-one CI users aged 12-21 years participated. A normally-hearing control group (n = 20) also completed Experiment 1. RESULTS: Listeners with normal hearing (NH) could discriminate between F0 peaks differing by 80 ms or more. Results varied among the CI users, with only four users displaying a pattern of results similar to that of the NH listeners. Sixteen CI users responded inconsistently or at chance levels (p > 0.05; binomial test). Ten CI users who were bilaterally implanted completed the tests in unilateral and bilateral listening conditions. CONCLUSIONS: Results suggest that CI users may have difficulty discriminating between F0 alignment and that use of bilateral implants did not provide an advantage to discrimination.

Evaluation of the PaCER Algorithm for Postoperative Subthalamic Nucleus Deep Brain Stimulation Electrode Localization.

Deep Brain Stimulation (DBS) is an established therapy for many movement disorders. DBS entails electrical stimulation of precise brain structures using permanently implanted electrodes. Following implantation, locating the electrodes relative to the target brain structure assists patient outcome optimization. Here we evaluated an open-source automatic algorithm (PaCER) to localize individual electrodes on Computed Tomography imaging (co-registered to Magnetic Resonance Imaging). In a dataset of 111 participants, we found a modified version of the algorithm matched manual-markups with median error less than 0.191 mm (interquartile range 0.698 mm). Given the error is less than the voxel resolution (1 mm3) of the images, we conclude that the automatic algorithm is suitable for DBS electrode localizations.Clinical Relevance- Automated DBS electrode localization identifies the closest electrode to the target brain structure; allowing the neurologist to direct electrical stimulation to maximize patient outcomes. Further, if none of the electrodes are deemed suitable, localization will guide re-implantation.

Towards guided and automated programming of subthalamic area stimulation in Parkinson's disease.

Selecting the ideal contact to apply subthalamic nucleus deep brain stimulation in Parkinson's disease can be an arduous process, with outcomes highly dependent on clinician expertise. This study aims to assess whether neuronal signals recorded intraoperatively in awake patients, and the anatomical location of contacts, can assist programming. In a cohort of 14 patients with Parkinson's disease, implanted with subthalamic nucleus deep brain stimulation, the four contacts on each lead in the 28 hemispheres were ranked according to proximity to a nominated ideal anatomical location and power of the following neuronal signals: evoked resonant neural activity, beta oscillations and high-frequency oscillations. We assessed how these rankings predicted, on each lead: (i) the motor benefit from deep brain stimulation applied through each contact and (ii) the 'ideal' contact to apply deep brain stimulation. The ranking of contacts according to each factor predicted motor benefit from subthalamic nucleus deep brain stimulation, as follows: evoked resonant neural activity; r 2 = 0.50, Akaike information criterion 1039.9, beta; r 2 = 0.50, Akaike information criterion 1041.6, high-frequency oscillations; r 2 = 0.44, Akaike information criterion 1057.2 and anatomy; r 2 = 0.49, Akaike information criterion 1048.0. Combining evoked resonant neural activity, beta and high-frequency oscillations ranking data yielded the strongest predictive model (r 2 = 0.61, Akaike information criterion 1021.5). The 'ideal' contact (yielding maximal benefit) was ranked first according to each factor in the following proportion of hemispheres; evoked resonant neural activity 18/28, beta 17/28, anatomy 16/28, high-frequency oscillations 7/28. Across hemispheres, the maximal available deep brain stimulation benefit did not differ from that yielded by contacts chosen by clinicians for chronic therapy or contacts ranked first according to evoked resonant neural activity. Evoked resonant neural activity, beta oscillations and anatomy similarly predicted how motor benefit from subthalamic nucleus deep brain stimulation varied across contacts on each lead. This could assist programming by providing a probability ranking of contacts akin to a 'monopolar survey'. However, these factors identified the 'ideal' contact in only a proportion of hemispheres. More advanced signal processing and anatomical techniques may be needed for the full automation of contact selection.

Electrically evoked and spontaneous neural activity in the subthalamic nucleus under general anesthesia.

OBJECTIVE: Deep brain stimulation (DBS) surgery is commonly performed with the patient awake to facilitate assessments of electrode positioning. However, awake neurosurgery can be a barrier to patients receiving DBS. Electrode implantation can be performed with the patient under general anesthesia (GA) using intraoperative imaging, although such techniques are not widely available. Electrophysiological features can also aid in the identification of target neural regions and provide functional evidence of electrode placement. Here we assess the presence and positional variation under GA of spontaneous beta and high-frequency oscillation (HFO) activity, and evoked resonant neural activity (ERNA), a novel evoked response localized to the subthalamic nucleus. METHODS: ERNA, beta, and HFO were intraoperatively recorded from DBS leads comprising four individual electrodes immediately after bilateral awake implantation into the subthalamic nucleus of 21 patients with Parkinson's disease (42 hemispheres) and after subsequent GA induction deep enough to perform pulse generator implantation. The main anesthetic agent was either propofol (10 patients) or sevoflurane (11 patients). RESULTS: GA reduced the amplitude of ERNA, beta, and HFO activity (p < 0.001); however, ERNA amplitudes remained large in comparison to spontaneous local field potentials. Notably, a moderately strong correlation between awake ERNA amplitude and electrode distance to an "ideal" therapeutic target within dorsal STN was preserved under GA (awake: ρ = -0.73, adjusted p value [padj] < 0.001; GA: ρ = -0.69, padj < 0.001). In contrast, correlations were diminished under GA for beta (awake: ρ = -0.45, padj < 0.001; GA: ρ = -0.13, padj = 0.12) and HFO (awake: ρ = -0.69, padj < 0.001; GA: ρ = -0.33, padj < 0.001). The largest ERNA occurred at the same electrode (awake vs GA) for 35/42 hemispheres (83.3%) and corresponded closely to the electrode selected by the clinician for chronic therapy at 12 months (awake ERNA 77.5%, GA ERNA 82.5%). The largest beta amplitude occurred at the same electrode (awake vs GA) for only 17/42 (40.5%) hemispheres and 21/42 (50%) for HFO. The electrode measuring the largest awake beta and HFO amplitudes corresponded to the electrode selected by the clinician for chronic therapy at 12 months in 60% and 70% of hemispheres, respectively. However, this correspondence diminished substantially under GA (beta 20%, HFO 35%). CONCLUSIONS: ERNA is a robust electrophysiological signal localized to the dorsal subthalamic nucleus subregion that is largely preserved under GA, indicating it could feasibly guide electrode implantation, either alone or in complementary use with existing methods.

Slim electrodes for improved targeting in deep brain stimulation.

OBJECTIVE: The efficacy of deep brain stimulation can be limited by factors including poor selectivity of stimulation, targeting error, and complications related to implant reliability and stability. We aimed to improve surgical outcomes by evaluating electrode leads with smaller diameter electrode and microelectrodes incorporated which can be used for assisting targeting. APPROACH: Electrode arrays were constructed with two different diameters of 0.65 mm and the standard 1.3 mm. Micro-electrodes were incorporated into the slim electrode arrays for recording spiking neural activity. Arrays were bilaterally implanted into the medial geniculate body (MGB) in nine anaesthetised cats for 24-40 h using stereotactic techniques. Recordings of auditory evoked field potentials and multi-unit activity were obtained at 1 mm intervals along the electrode insertion track. Insertion trauma was evaluated histologically. MAIN RESULTS: Evoked auditory field potentials were recorded from ring and micro-electrodes in the vicinity of the medial geniculate body. Spiking activity was recorded from 81% of the microelectrodes approaching the MGB. Histological examination showed localized surgical trauma along the implant. The extent of haemorrhage surrounding the track was measured and found to be significantly reduced with the slim electrodes (541 ± 455 µm vs. 827 ± 647 µm; P < 0.001). Scoring of the trauma, focusing on tissue disruption, haemorrhage, oedema of glial parenchyma and pyknosis, revealed a significantly lower trauma score for the slim electrodes (P < 0.0001). SIGNIFICANCE: The slim electrodes reduced the extent of acute trauma, while still providing adequate electrode impedance for both stimulating and recording, and providing the option to target stimulate smaller volumes of tissue. The incorporation of microelectrodes into the electrode array may allow for a simplified, single-step surgical approach where confirmatory micro-targeting is done with the same lead used for permanent implantation.

Comparison of two frequency-to-electrode maps for acoustic-electric stimulation.

The fitting of a cochlear implant together with aided residual hearing was evaluated by means of matching frequency and/or perceived pitch between acoustic and electric modalities. Five cochlear implant users with the Nucleus Freedom electrode array with residual acoustic hearing participated. Psychophysical procedures were used to create a map in which the implant was programmed to provide the listener with high-frequency information only above the frequency at which acoustic hearing was no longer considered useful. This was compared to a second map which provided the full frequency range. Listeners wore each map for a number of weeks before speech recognition was measured in quiet and noise. Post-operatively across subjects, average hearing thresholds worsened by 27 dB. However, cochlear implantation provided superior recognition of speech compared to pre-operative scores, with the best results found when subjects were wearing their hearing aids together with the implant. No significant differences were found between the two maps on speech tests when subjects were wearing their implant together with hearing aid/s. In conclusion, the combination of a cochlear implant together with hearing aid/s was effective at providing speech perception benefits for the listeners of the current study, regardless of the frequency-to-electrode allocation selected.

A palm-worn device to quantify rigidity in Parkinson's disease.

BACKGROUND: Parkinsonian rigidity is identified on clinical examination as resistance to passive movement. Measurement of rigidity commonly relies on ordinal rating scales (MDS-UPDRS), however instrumented objective measures may provide greater mechanistic insight. NEW METHOD: We present a palm-worn instrument to objectively quantify rigidity on a continuous scale. The device employs a miniature motor to flex the third digit of the hand about the metacarpophalangeal joint whilst transducers record flexion/extension forces. We aim to determine congruence with the MDS-UPDRS, investigate sensitivity to the impact of deep brain stimulation (DBS) and contralateral movement, and make comparisons with healthy individuals. Eight participants with Parkinson's disease underwent evaluation during conditions: on and off DBS, and with and without contralateral limb movement to activate rigidity. During each DBS condition, wash-in/out effects were tracked using both our instrument and two blinded clinical raters. Sixteen healthy volunteers (age-matched/young) served as controls. RESULTS: Rigidity measured using our instrument had moderate agreement with the MDS-UPDRS and showed differences between therapeutic state, activation conditions, and disease/healthy cohorts. Rigidity gradually worsened over a one-hour period after DBS cessation, but improved more rapidly with DBS resumption. COMPARISON WITH EXISTING METHODS: Previous attempts to quantify rigidity include manual approaches where a clinician is required to manipulate limbs while sensors passively gather information, or large automated instruments to move the wrist or elbow. CONCLUSION: Given its ability to track changes in rigidity due to therapeutic intervention, our technique could have applications where continuous measurement is required or where a suitably qualified rater is absent.

Objective evaluation of bradykinesia in Parkinson's disease using an inexpensive marker-less motion tracking system.

OBJECTIVE: Quantification of bradykinesia (slowness of movement) is crucial for the treatment and monitoring of Parkinson's disease. Subjective observational techniques are the de-facto 'gold standard', but such clinical rating scales suffer from poor sensitivity and inter-rater variability. Although various technologies have been developed for assessing bradykinesia in recent years, most still require considerable expertise and effort to operate. Here we present a novel method to utilize an inexpensive off-the-shelf hand-tracker (Leap Motion) to quantify bradykinesia. APPROACH: Eight participants with Parkinson's disease receiving benefit from deep brain stimulation were recruited for the study. Participants were assessed 'on' and 'off' stimulation, with the 'on' condition repeated to evaluate reliability. Participants performed wrist pronation/supination, hand open/close, and finger-tapping tasks during each condition. Tasks were simultaneously captured by our software and rated by three clinicians. A linear regression model was developed to predict clinical scores and its performance was assessed with leave-one-subject-out cross validation. MAIN RESULTS: Aggregate bradykinesia scores predicted by our method were in strong agreement (R = 0.86) with clinical scores. The model was able to differentiate therapeutic states and comparison between the test-retest conditions yielded no significant difference (p  = 0.50). SIGNIFICANCE: These findings demonstrate that our method can objectively quantify bradykinesia in agreement with clinical observation and provide reliable measurements over time. The hardware is readily accessible, requiring only a modest computer and our software to perform assessments, thus making it suitable for both clinic- and home-based symptom tracking.

Pitch ranking of complex tones by normally hearing subjects and cochlear implant users.

The ability of 10 normally hearing (NH) adults and eight cochlear implant (CI) users to pitch-rank pairs of complex tones was assessed. The acoustically presented stimuli differed in fundamental frequency (F0) by either one or six semitones (F0 range: 98 to 740 Hz). The NH group obtained significantly higher mean scores for both experiments: (NH: one semitone - 81.2%, six semitones - 89.0%; CI: one semitone - 49.0%, six semitones - 60.2%; p<0.001). Prior musical experience was found to be associated with higher pitch-ranking scores for the NH subjects. Those with musical experience ratings <3 obtained significantly lower scores for both interval sizes (p<0.001) than those with higher ratings. Nevertheless, the scores obtained by the musically inexperienced, NH adults were significantly higher than those obtained by the CI group for both the one-semitone (p=0.022) and six-semitone (p=0.018) intervals. These results suggest that the pitch information CI users obtain from their implant systems is less accurate than that obtained by NH listeners when listening to the same complex sounds. Furthermore, the relatively poor pitch-ranking ability of at least some CI users may be associated with a more-limited experience of music in general.

Perceptual dissimilarities among acoustic stimuli and ipsilateral electric stimuli.

Five users of cochlear implants who had residual acoustic hearing in the implanted ear postoperatively participated in a study comparing the percepts elicited by acoustic and electric stimuli. The stimuli comprised pulse trains delivered to single electrodes and pure tones presented ipsilaterally. In the experiments, 12 equally loud stimuli with differing frequencies, electrode positions, and pulse rates were generated. Subjects listened to all of the possible pairs of stimuli in each set, and provided a relative dissimilarity rating for the members of each stimulus pair. The data were analyzed using non-metric multi-dimensional scaling techniques. Stimulus spaces were plotted in two dimensions to represent the results for each subject with each stimulus set. The results suggested that one dimension was associated with a pitch-like percept, related to the acoustic tone frequency and the active electrode position. The second dimension separated the acoustic stimuli from the electric stimuli. Generally, the electric pulse rate seemed to have a relatively small perceptual effect in this experimental context. Overall, the results show that acoustic pure tones are perceived as very different from electric pulse trains delivered to single electrode positions with constant rate, even when both the acoustic and the electric stimuli are presented to the same ear.