Multimodal assessment of tinnitus using functional near-infrared spectroscopy and psychophysiological measures.

OBJECTIVE: To use a multimodal approach to classify individuals with tinnitus from controls, and individuals with mild versus severe tinnitus. DESIGN: We have previously shown feasibility of a non-invasive imaging technique called functional near-infrared spectroscopy (fNIRS) to detect tinnitus-related changes in cortical activity and classify individuals with tinnitus from controls, as well as individuals with mild versus severe tinnitus. In this study we have used a multimodal approach by recording heart rate, heart rate variability and skin conductance, in addition to fNIRS signals, from individuals with tinnitus and controls. STUDY SAMPLE: Twenty-seven participants with tinnitus and 21 controls were recruited. RESULTS: Our findings show, addition of heart rate measures can improve accuracy of classifying tinnitus severity, in particular loudness as rated subjectively. The f1-score, a measure of classification accuracy, increased from 0.73 to 0.86 when using a support vector machine classifier for differentiating low versus high tinnitus loudness. CONCLUSIONS: Subjective tinnitus is a condition that can only be described by the individual experiencing it, as there are currently no objective measures to determine tinnitus presence and severity, or assess the effectiveness of treatments. Objective measurement of tinnitus is a critical step in developing reliable treatments for this debilitating condition.

Cortical fNIRS Responses Can Be Better Explained by Loudness Percept than Sound Intensity.

OBJECTIVES: Functional near-infrared spectroscopy (fNIRS) is a brain imaging technique particularly suitable for hearing studies. However, the nature of fNIRS responses to auditory stimuli presented at different stimulus intensities is not well understood. In this study, we investigated whether fNIRS response amplitude was better predicted by stimulus properties (intensity) or individually perceived attributes (loudness). DESIGN: Twenty-two young adults were included in this experimental study. Four different stimulus intensities of a broadband noise were used as stimuli. First, loudness estimates for each stimulus intensity were measured for each participant. Then, the 4 stimulation intensities were presented in counterbalanced order while recording hemoglobin saturation changes from cortical auditory brain areas. The fNIRS response was analyzed in a general linear model design, using 3 different regressors: a non-modulated, an intensity-modulated, and a loudness-modulated regressor. RESULTS: Higher intensity stimuli resulted in higher amplitude fNIRS responses. The relationship between stimulus intensity and fNIRS response amplitude was better explained using a regressor based on individually estimated loudness estimates compared with a regressor modulated by stimulus intensity alone. CONCLUSIONS: Brain activation in response to different stimulus intensities is more reliant upon individual loudness sensation than physical stimulus properties. Therefore, in measurements using different auditory stimulus intensities or subjective hearing parameters, loudness estimates should be examined when interpreting results.

Comparisons of Electroencephalographically Derived Measures of Hypnosis and Antinociception in Response to Standardized Stimuli During Target-Controlled Propofol-Remifentanil Anesthesia.

BACKGROUND: Current electroencephalogram (EEG)-derived measures provide information on cortical activity and hypnosis but are less accurate regarding subcortical activity, which is expected to vary with the degree of antinociception. Recently, the neurophysiologically based EEG measures of cortical input (CI) and cortical state (CS) have been shown to be prospective indicators of analgesia/antinociception and hypnosis, respectively. In this study, we compared CI and an alternate measure of CS, the composite cortical state (CCS), with the Bispectral Index (BIS) and another recently developed measure of antinociception, the composite variability index (CVI). CVI is an EEG-derived measure based on a weighted combination of BIS and estimated electromyographic activity. By assessing the relationship between these indices for equivalent levels of hypnosis (as quantified using the BIS) and the nociceptive-antinociceptive balance (as determined by the predicted effect-site concentration of remifentanil), we sought to evaluate whether combining hypnotic and analgesic measures could better predict movement in response to a noxious stimulus than when used alone. METHODS: Time series of BIS and CVI indices and the raw EEG from a previously published study were reanalyzed. In our current study, the data from 80 patients, each randomly allocated to a target hypnotic level (BIS 50 or BIS 70) and a target remifentanil level (Remi-0, -2, -4 or -6 ng/mL), were included in the analysis. CCS, CI, BIS, and CVI were calculated or quantified at baseline and at a number of intervals after the application of the Observer's Assessment of Alertness/Sedation scale and a subsequent tetanic stimulus. The dependency of the putative measures of antinociception CI and CVI on effect-site concentration of remifentanil was then quantified, together with their relationship to the hypnotic measures CCS and BIS. Finally, statistical clustering methods were used to evaluate the extent to which simple combinations of antinociceptive and hypnotic measures could better detect and predict response to stimulation. RESULTS: Before stimulation, both CI and CVI differentiated patients who received remifentanil from those who were randomly allocated to the Remi-0 group (CI: Cohen's d = 0.65, 95% confidence interval, 0.48-0.83; CVI: Cohen's d = 0.72, 95% confidence interval, 0.56-0.88). Strong correlations between BIS and CCS were found (at different periods: 0.55 < R2 < 0.68, P < 0.001). Application of the Observer's Assessment of Alertness/Sedation stimulus was associated with changes in CI and CCS, whereas, subsequent to the application of both stimuli, changes in all measures were seen. Pairwise combinations of CI and CCS showed higher sensitivity in detecting response to stimulation than CVI and BIS combined (sensitivity [99% confidence interval], 75.8% [52.7%-98.8%] vs 42% [15.4%-68.5%], P = 0.006), with specificity for CI and CCS approaching significance (52% [34.7%-69.3%] vs 24% [9.1%-38.9%], P = 0.0159). CONCLUSIONS: Combining electroencephalographically derived hypnotic and analgesic quantifiers may enable better prediction of patients who are likely to respond to tetanic stimulation.

Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl.

The brain anaesthesia response (BAR) monitor uses a method of EEG analysis, based on a model of brain electrical activity, to monitor the cerebral response to anaesthetic and sedative agents via two indices, composite cortical state (CCS) and cortical input (CI). It was hypothesised that CCS would respond to the hypnotic component of anaesthesia and CI would differentiate between two groups of patients receiving different doses of fentanyl. Twenty-five patients scheduled to undergo elective first-time coronary artery bypass graft surgery were randomised to receive a total fentanyl dose of either 12 µg/kg (fentanyl low dose, FLD) or 24 µg/kg (fentanyl moderate dose, FMD), both administered in two divided doses. Propofol was used for anaesthesia induction and pancuronium for intraoperative paralysis. Hemodynamic management was protocolised using vasoactive drugs. BIS, CCS and CI were simultaneously recorded. Response of the indices (CI, CCS and BIS) to propofol and their differences between the two groups at specific points from anaesthesia induction through to aortic cannulation were investigated. Following propofol induction, CCS and BIS but not CI showed a significant reduction. Following the first dose of fentanyl, CI, CCS and BIS decreased in both groups. Following the second dose of fentanyl, there was a significant reduction in CI in the FLD group but not the FMD group, with no significant change found for BIS or CCS in either group. The BAR monitor demonstrates the potential to monitor the level of hypnosis following anaesthesia induction with propofol via the CCS index and to facilitate the titration of fentanyl as a component of balanced anaesthesia via the CI index.

Towards non-invasive peripheral stimulation as a treatment for Parkinson's disease gait.

Non-invasive coordinated reset stimulation (CRS) to the hands has been shown to improve motor ability in Parkinson's patients, but not specific for gait disturbances. The overall aim of the project is the application of vibrotactile CRS to the feet to improve gait impairments in Parkinson's disease. As a first step towards this objective, we showed that vibrotactile stimulation to the feet can elicit a cortical response and have identified differences in younger and older individuals. Our findings suggest the potential for non-invasive peripheral stimulation as a therapeutic technique.Clinical Relevance- This is an important step towards developing a non-invasive stimulation technique for the management of gait disturbances in Parkinson's disease.

Examination of central gait control mechanisms in Parkinson's disease using movement-related potentials.

Gait disorders are common in people with Parkinson's disease. The pathophysiology of these disorders is not fully understood. Movement-related potentials reflect supplementary motor area activity associated with the preparation and execution of voluntary movement. Our aim was to investigate movement-related potentials associated with gait disturbances in patients with Parkinson's disease, as reflected by gait hypokinesia and initiation difficulties, in order to better understand the role of the basal ganglia in the pathogenesis of these conditions. Movement-related potentials were back-averaged from electroencephalography recordings performed on 11 participants with Parkinson's disease with no gait initiation difficulties, 9 participants with Parkinson's disease who suffered from gait initiation difficulties, 12 young healthy adults, and 8 healthy older adults. Participants took 3 steps forward, stepping off a force plate. Trigger signals from the force plate and electromyographic activity of the tibialis anterior muscle were used to identify gait initiation time. Participants' stride length was also measured using a 3-dimensional motion analysis system. Movement-related potentials showed significant group differences between the healthy young adults and the 2 Parkinson's disease groups as well as the Parkinson's disease group as a whole. No significant difference was found between the participants with Parkinson's disease and age-matched controls. A significant inverse relationship between movement-related potentials and stride length was found in patients with Parkinson's disease who did not experience gait initiation difficulties but not in those who did have this symptom. Gait-generated movement-related potentials appear to show electrical evidence of cortical disturbances correlated with stride length reduction in patients with Parkinson's disease without gait initiation difficulties.

Objective measurement of tinnitus using functional near-infrared spectroscopy and machine learning.

Chronic tinnitus is a debilitating condition which affects 10-20% of adults and can severely impact their quality of life. Currently there is no objective measure of tinnitus that can be used clinically. Clinical assessment of the condition uses subjective feedback from individuals which is not always reliable. We investigated the sensitivity of functional near-infrared spectroscopy (fNIRS) to differentiate individuals with and without tinnitus and to identify fNIRS features associated with subjective ratings of tinnitus severity. We recorded fNIRS signals in the resting state and in response to auditory or visual stimuli from 25 individuals with chronic tinnitus and 21 controls matched for age and hearing loss. Severity of tinnitus was rated using the Tinnitus Handicap Inventory and subjective ratings of tinnitus loudness and annoyance were measured on a visual analogue scale. Following statistical group comparisons, machine learning methods including feature extraction and classification were applied to the fNIRS features to classify patients with tinnitus and controls and differentiate tinnitus at different severity levels. Resting state measures of connectivity between temporal regions and frontal and occipital regions were significantly higher in patients with tinnitus compared to controls. In the tinnitus group, temporal-occipital connectivity showed a significant increase with subject ratings of loudness. Also in this group, both visual and auditory evoked responses were significantly reduced in the visual and auditory regions of interest respectively. Naïve Bayes classifiers were able to classify patients with tinnitus from controls with an accuracy of 78.3%. An accuracy of 87.32% was achieved using Neural Networks to differentiate patients with slight/ mild versus moderate/ severe tinnitus. Our findings show the feasibility of using fNIRS and machine learning to develop an objective measure of tinnitus. Such a measure would greatly benefit clinicians and patients by providing a tool to objectively assess new treatments and patients' treatment progress.

Assessing hearing by measuring heartbeat: The effect of sound level.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive brain imaging technique that measures changes in oxygenated and de-oxygenated hemoglobin concentration and can provide a measure of brain activity. In addition to neural activity, fNIRS signals contain components that can be used to extract physiological information such as cardiac measures. Previous studies have shown changes in cardiac activity in response to different sounds. This study investigated whether cardiac responses collected using fNIRS differ for different loudness of sounds. fNIRS data were collected from 28 normal hearing participants. Cardiac response measures evoked by broadband, amplitude-modulated sounds were extracted for four sound intensities ranging from near-threshold to comfortably loud levels (15, 40, 65 and 90 dB Sound Pressure Level (SPL)). Following onset of the noise stimulus, heart rate initially decreased for sounds of 15 and 40 dB SPL, reaching a significantly lower rate at 15 dB SPL. For sounds at 65 and 90 dB SPL, increases in heart rate were seen. To quantify the timing of significant changes, inter-beat intervals were assessed. For sounds at 40 dB SPL, an immediate significant change in the first two inter-beat intervals following sound onset was found. At other levels, the most significant change appeared later (beats 3 to 5 following sound onset). In conclusion, changes in heart rate were associated with the level of sound with a clear difference in response to near-threshold sounds compared to comfortably loud sounds. These findings may be used alone or in conjunction with other measures such as fNIRS brain activity for evaluation of hearing ability.

Cortical Processing Related to Intensity of a Modulated Noise Stimulus-a Functional Near-Infrared Study.

Sound intensity is a key feature of auditory signals. A profound understanding of cortical processing of this feature is therefore highly desirable. This study investigates whether cortical functional near-infrared spectroscopy (fNIRS) signals reflect sound intensity changes and where on the brain cortex maximal intensity-dependent activations are located. The fNIRS technique is particularly suitable for this kind of hearing study, as it runs silently. Twenty-three normal hearing subjects were included and actively participated in a counterbalanced block design task. Four intensity levels of a modulated noise stimulus with long-term spectrum and modulation characteristics similar to speech were applied, evenly spaced from 15 to 90 dB SPL. Signals from auditory processing cortical fields were derived from a montage of 16 optodes on each side of the head. Results showed that fNIRS responses originating from auditory processing areas are highly dependent on sound intensity level: higher stimulation levels led to higher concentration changes. Caudal and rostral channels showed different waveform morphologies, reflecting specific cortical signal processing of the stimulus. Channels overlying the supramarginal and caudal superior temporal gyrus evoked a phasic response, whereas channels over Broca's area showed a broad tonic pattern. This data set can serve as a foundation for future auditory fNIRS research to develop the technique as a hearing assessment tool in the normal hearing and hearing-impaired populations.

Parkinson's disease: disturbed vestibular function and levodopa.

Evidence indicates Levodopa effects central postural control. As electrophysiological postural control biomarkers, sensory oto-acoustic features were extracted from Electrovestibulography (EVestG) data to identify 20 healthy age and gender matched individuals as Controls from 20 PD subjects before (PDlowmed) and 18 after (PDmed) morning doses of Levodopa. EVestG data was collected using a single tilt stimulus applied in the pitch plane. The extracted features were based on the measured firing pattern, interval histogram and the shape of the average field potential response. An unbiased cross validated classification accuracy of 88%, 88% and 79% was achieved using combinations of 2 features for separating PDlowmed from control, control from PD (combined PDlowmed and PDmed), and PDlowmed from PDmed groups respectively. One feature showed significant correlations (p<0.05) with the Modified Hoehn and Yahr PD staging scale. The results indicate disturbed vestibular function is observed in both the PDmed and PDlowmed conditions, and these are separable. The implication is that Levodopa may also affect peripheral as well as central postural control.

The relationship between electrovestibulography and Parkinson's disease severity.

Parkinson's disease (PD) is the second largest neurodegenerative disorder worldwide. This disease results from the loss of dopamine producing neurons in parts of the basal ganglia of the brain. Previous studies have shown the involvement of the dopamine system in the basal ganglia in balance control. Sensations of balance in the body are detected by the vestibular apparatus. In this project, electrovestibulography (EVestG) has been used to measure neuronal activity of the vestibular apparatus and nuclei from Parkinson's patients. A wavelet based signal processing technique, a Neural Event Extraction Routine, has been used to extract biomarkers from these EVestG recordings. These measurements appear to be correlated with scores from mobility tests which indicate disease progression and mobility impairment in Parkinson's patients.