Analysis of human locomotion using analytic wavelets applied to electromyographic data from healthy controls and Parkinson's patients

Human locomotion is controlled by the dynamic interaction between the human brain and spinal cord. An understanding of the basic control strategies and paradigms of normal locomotion could provide opportunity to understand and help characterise early stages of movement disorders such as Parkinson's disease. Locomotion is a stereotyped action and highly non-stationary which needs time-varying analyses. Analytic wavelets provide a powerful time-frequency analysis framework for studying time-varying properties of non-stationary neurophysiological signals, and are used in this thesis. A unified framework, which includes coherence, phase locking value (PLV), and time-resolved phase-amplitude coupling (tPAC) using generalized Morse wavelets, is developed to analyse electromyographic (EMG) recordings obtained from leg muscles during treadmill and overground walking in healthy controls and Parkinson's disease (PD) patients. A novel technique applied to coherence and PLV for removal of low frequency components due to EMG envelope modulation is then proposed. All measures have successfully been applied to three data sets, healthy human treadmill walking and human overground walking including a comparison of control subjects and PD patients. All measures provide a clear description of data from healthy treadmill locomotion. In comparison, more variability in time and frequency values are observed in analysis of overground walking data sets. The results provide new insights into the rhythmic control of locomotion in health and disease. Significant differences in features between healthy subjects and PD patients are observed in 12-20 Hz frequency range for all measures. The results from our novel technique for removal of low frequency EMG envelope modulation confirm the expectation for separating physiological mechanisms from effects due to low frequency envelope modulation of surface EMG during walking. Our results suggest that a combination of these measures could be suitable for investigating and characterising non-stationary neurophysiological data, and might be important for understanding the basic principles of human locomotion in health and disease

Wavelet-based method for coherence analysis with suppression of low frequency envelope modulation in non-stationary signals

Techniques for non-stationary signal analysis are important in understanding dynamical behaviour of complex systems. Time-frequency coherence is widely used to analyse time-varying characteristics in non-stationary signals. This paper presents wavelet-based methods, using Airy wavelet, to estimate coherence. We incorporate a novel technique for removal of low frequency components due to envelope modulation in non-stationary signals. The technique is demonstrated on synthetic and real neurophysiological data. Results not only provide a clear description of desired features in non-stationary signals, but also suppress low frequency components due to envelope modulation. Our novel technique shows an effectiveness in extracting features hidden within the signals. It may lead to improved results in coherence analysis of medical, biological, physical and geophysical data containing low frequency envelope modulation besides non-stationarities

Spatial encoding in primate hippocampus during free navigation.

The hippocampus comprises two neural signals-place cells and θ oscillations-that contribute to facets of spatial navigation. Although their complementary relationship has been well established in rodents, their respective contributions in the primate brain during free navigation remains unclear. Here, we recorded neural activity in the hippocampus of freely moving marmosets as they naturally explored a spatial environment to more explicitly investigate this issue. We report place cells in marmoset hippocampus during free navigation that exhibit remarkable parallels to analogous neurons in other mammalian species. Although θ oscillations were prevalent in the marmoset hippocampus, the patterns of activity were notably different than in other taxa. This local field potential oscillation occurred in short bouts (approximately .4 s)-rather than continuously-and was neither significantly modulated by locomotion nor consistently coupled to place-cell activity. These findings suggest that the relationship between place-cell activity and θ oscillations in primate hippocampus during free navigation differs substantially from rodents and paint an intriguing comparative picture regarding the neural basis of spatial navigation across mammals

Intramuscular coherence enables robust assessment of modulated supra-spinal input in human gait: an inter-dependence study of visual task and walking speed

Intramuscular high-frequency coherence is increased during visually guided treadmill walking as a consequence of increased supra-spinal input. The influence of walking speed on intramuscular coherence and its inter-trial reproducibility need to be established before adoption as a functional gait assessment tool in clinical settings. Here, fifteen healthy controls performed a normal and a target walking task on a treadmill at various speeds (0.3 m/s, 0.5 m/s, 0.9 m/s, and preferred) during two sessions. Intramuscular coherence was calculated between two surface EMG recordings sites of the Tibialis anterior muscle during the swing phase of walking. The results were averaged across low-frequency (5-14 Hz) and high-frequency (15-55 Hz) bands. The effect of speed, task, and time on mean coherence was assessed using three-way repeated measures ANOVA. Reliability and agreement were calculated with the intra-class correlation coefficient and Bland-Altman method, respectively. Intramuscular coherence during target walking was significantly higher than during normal walking across all walking speeds in the high-frequency band as obtained by the three-way repeated measures ANOVA. Interaction effects between task and speed were found for the low- and high-frequency bands, suggesting that task-dependent differences increase at higher walking speeds. Reliability of intramuscular coherence was moderate to excellent for most normal and target walking tasks in all frequency bands. This study confirms previous reports of increased intramuscular coherence during target walking, while providing first evidence for reproducibility and robustness of this measure as a requirement to investigate supra-spinal input.Trial registration Registry number/ClinicalTrials.gov Identifier: NCT03343132, date of registration 2017/11/17

Phase Dynamics in Human Visuomotor Control - Health & Disease

In this thesis, comprised of four publications, I investigated phase dynamics of visuomotor control in humans during upright stance in response to an oscillatory visual drive. For this purpose, I applied different versions of a ‘moving room’ paradigm in virtual reality while stimulating human participants with anterior-posterior motion of their visual surround and analyzed their bodily responses. Human balance control constitutes a complex interplay of interdependent processes. The main sensory contributors include vision, vestibular input, and proprioception, with a dominant role attributed to vision. The purpose of the balance control system is to keep the body’s center of mass (COM) within a certain spatial range around the current base of support. Ever-changing environmental circumstances along with sensory noise cause the body to permanently sway around its point of equilibrium. Considering this sway, the human body can be modelled as a (multi-link) inverted pendulum. To maintain balance while being exposed to perturbations of the visual environment, humans adjust their sway to counteract the perceived motion of their bodies. Neurodegenerative diseases like Parkinson’s impair balance control and thus are likely to affect these mechanisms. Hence, investigation of bodily responses to a visual drive gives insight into visuomotor control in health and disease. In my first study, I introduced inter-trial phase coherence (ITPC) as a novel method to investigate postural responses to periodical visual stimulation. I found that human participants phase-locked the motion of their center of pressure (COP) to a 3-D dot cloud which oscillated in the anterior-posterior direction. This effect was equally strong for a low frequency of visual stimulation at 0.2 Hz and a high frequency of 1.5 Hz, the latter exceeding the previously assumed frequency range associated with coherent postural sway responses to periodical oscillations of the visual environment (moving room). Moreover, I was able to show that ITPC reliably captured responses in almost all participants, thereby addressing the common problem of inter-subject variability in body sway research. Based on the results of my first study, I concluded phase locking to be an essential feature in human postural control. For the second study, I introduced a mobile and cost-effective setup to apply a visual paradigm consisting of a virtual tunnel which stretched in the anterior-posterior direction and oscillated back and forth at three distinct frequencies (0.2 Hz, 0.8 Hz, and 1.2 Hz). Because tracking of the COP alone neglects crucial information about how COM shifts are arranged across the body, I included additional full-body motion tracking here to evaluate sway of individual body segments. Using a modified measure of phase locking, the phase locking value (PLV), allowed me to find participants phase-locking not only their COP, but also additional segments of their body to the visual drive. While their COP exhibited a strong phase locking to all frequencies of visual stimulation, distribution of phase locking across the body underwent a shift as the frequency of the visual stimulation increased. For the lowest frequency of 0.2 Hz, participants phase-locked almost their entire body to the stimulus. At higher frequencies, this phase locking shifted towards the lower torso and hip, with subjects almost exclusively phase-locking their hip to the visual drive at the highest frequency of 1.2 Hz. Having introduced a novel and reliable measurement along with a mobile setup, these results allowed me to empirically confirm shifts in postural strategies previously proposed in the literature. In the third study, a collaboration with the neurology department of the Universitätsklinikum Gießen und Marburg (UKGM), I used the same setup and paradigm as in the previous study and additionally derived the trajectory of the COM from a weighted combination of certain body segments. The aim was to investigate phase locking of body sway in a group of patients suffering from Parkinson’s disease (PD) to find potential means for an early diagnosis of the illness. For this purpose, I recruited a group of PD patients, an age-matched control group, and a group of young healthy adults. Even though the sway amplitude of PD patients was significantly larger than that of both other groups, they phase-locked their COP and COM in a similar manner as the control groups. However, considering individual body segments, the shift in PLV distribution differed between groups. While young healthy adults, analogous to the participants in the second study, exhibited a shift towards exclusive phase locking of their hips as frequency of the stimulation increased, both PD patients and age-matched controls maintained a rather homogeneous phase locking across their body. This suggested increased body stiffness, although being an effect of age rather than disease. Overall, I concluded that patients of early-to-mid stage PD exhibit impaired motor control, reflected in their increased sway amplitude, but intact visuomotor processing, indicated by their ability to phase-lock the motion of their body to a visual drive. The fourth study, to which I contributed as second author, used experimental data collected from an additional visual condition in the course of the third study. This condition consisted of unpredictable back and forward motion of the simulated tunnel. Here, we investigated the velocity profiles of the COP and COM in response to the unpredictable visual motion and a baseline condition at which the tunnel remained static. We found PD patients to exhibit larger velocities of their COP and COM under both conditions when compared to the control groups. When examining the net increase that unpredictable motion had on the velocity of both parameters, we found a significantly higher increase in COP velocity for both PD patients and age-matched controls, but no increase in COM velocity in any of the groups. These results suggested that all groups successfully maintained their balance under unpredictable visual perturbations, but that PD patients and older adults required more effort to accomplish this task, as reflected by the increased velocity of their COP. Again, these results indicated an effect of age rather than disease on the observed postural responses. In summary, using innovative phase-locking techniques and simultaneously tracking multiple body sway parameters, I was able to provide novel insight into visuomotor control in humans. First, I overcame previous issues of inconsistent sway parameters in groups of participants; Second, I found phase-locking to be an essential feature of visuomotor processing, which also allowed me to empirically confirm previously established theories of postural control; Third, through studies in collaboration with the neurology department of the UKGM, I was able to uncover new aspects of visuomotor processing in Parkinson’s, contributing to a better understanding of the sensorimotor aspects of the disease

Intramuscular coherence enables robust assessment of modulated supra-spinal input in human gait : an inter-dependence study of visual task and walking speed

Intramuscular high-frequency coherence is increased during visually guided treadmill walking as a consequence of increased supra-spinal input. The influence of walking speed on intramuscular coherence and its inter-trial reproducibility need to be established before adoption as a functional gait assessment tool in clinical settings. Here, fifteen healthy controls performed a normal and a target walking task on a treadmill at various speeds (0.3 m/s, 0.5 m/s, 0.9 m/s, and preferred) during two sessions. Intramuscular coherence was calculated between two surface EMG recordings sites of the Tibialis anterior muscle during the swing phase of walking. The results were averaged across low-frequency (5-14 Hz) and high-frequency (15-55 Hz) bands. The effect of speed, task, and time on mean coherence was assessed using three-way repeated measures ANOVA. Reliability and agreement were calculated with the intra-class correlation coefficient and Bland-Altman method, respectively. Intramuscular coherence during target walking was significantly higher than during normal walking across all walking speeds in the high-frequency band as obtained by the three-way repeated measures ANOVA. Interaction effects between task and speed were found for the low- and high-frequency bands, suggesting that task-dependent differences increase at higher walking speeds. Reliability of intramuscular coherence was moderate to excellent for most normal and target walking tasks in all frequency bands. This study confirms previous reports of increased intramuscular coherence during target walking, while providing first evidence for reproducibility and robustness of this measure as a requirement to investigate supra-spinal input.Trial registration Registry number/ClinicalTrials.gov Identifier: NCT03343132, date of registration 2017/11/17

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)