Saša Radovanović

Efficient neuroplasticity induction in chronic stroke patients by an associative brain-computer interface

Brain-computer interfaces (BCIs) have the potential to improve functionality in chronic stoke patients when applied over a large number of sessions. Here we evaluated the effect and the underlying mechanisms of three BCI training sessions in a double-blind sham-controlled design. The applied BCI is based on Hebbian principles of associativity that hypothesize that neural assemblies activated in a correlated manner will strengthen synaptic connections. Twenty-two chronic stroke patients were divided into two training groups. Movement-related cortical potentials (MRCPs) were detected by electroencephalography during repetitions of foot dorsiflexion. Detection triggered a single electrical stimulation of the common peroneal nerve timed so that the resulting afferent volley arrived at the peak negative phase of the MRCP (BCIassociative group) or randomly (BCInonassociative group). Fugl-Meyer motor assessment (FM), 10-m walking speed, foot and hand tapping frequency, diffusion tensor imaging (DTI) data, and the excitability of the corticospinal tract to the target muscle [tibialis anterior (TA)] were quantified. The TA motor evoked potential (MEP) increased significantly after the BCIassociative intervention, but not for the BCInonassociative group. FM scores (0.8 ± 0.46 point difference, P = 0.01), foot (but not finger) tapping frequency, and 10-m walking speed improved significantly for the BCIassociative group, indicating clinically relevant improvements. Corticospinal tract integrity on DTI did not correlate with clinical or physiological changes. For the BCI as applied here, the precise coupling between the brain command and the afferent signal was imperative for the behavioral, clinical, and neurophysiological changes reported. This association may become the driving principle for the design of BCI rehabilitation in the future. Indeed, no available BCIs can match this degree of functional improvement with such a short intervention.

Classification of walking patterns in Parkinson's disease patients based on inertial sensor data

The gait disturbances in Parkinsons disease (PD) patients occur occasionally and intermittently, appearing in a random, inexplicable manner. These disturbances include festinations, shuffling, and complete freezing of gait (FOG). Alternation of walking pattern decreases the quality of life and may result in falls. In order to recognize disturbances during walking in PD patients, we recorded gait kinematics with wireless inertial measurement system and designed an algorithm for automatic recognition and classification of walking patterns. The algorithm combines a perceptron neural network with simple signal processing and rule-based classification. In parallel, gait was recorded with video camera. Medical experts identified FOG episodes from videos and their results were used for comparison and validation of this method. The summary result shows that the error in recognition and classification of walking patterns is up to 16%.

A simple method to assess freezing of gait in Parkinson's disease patients

Freezing of gait (FOG) can be assessed by clinical and instrumental methods. Clinical examination has the advantage of being available to most clinicians; however, it requires experience and may not reveal FOG even for cases confirmed by the medical history. Instrumental methods have an advantage in that they may be used for ambulatory monitoring. The aim of the present study was to describe and evaluate a new instrumental method based on a force sensitive resistor and Pearsons correlation coefficient (Pcc) for the assessment of FOG. Nine patients with Parkinsons disease in the on state walked through a corridor, passed through a doorway and made a U-turn. We analyzed 24 FOG episodes by computing the Pcc between one regular/normal step and the rest of the steps. The Pcc reached ±1 for normal locomotion, while correlation diminished due to the lack of periodicity during FOG episodes. Gait was assessed in parallel with video. FOG episodes determined from the video were all detected with the proposed method. The computed duration of the FOG episodes was compared with those estimated from the video. The method was sensitive to various types of freezing; although no differences due to different types of freezing were detected. The study showed that Pcc analysis permitted the computerized detection of FOG in a simple manner analogous to human visual judgment, and its automation may be useful in clinical practice to provide a record of the history of FOG.

Gait characteristics in patients with major depression performing cognitive and motor tasks while walking

Depressed patients demonstrate alterations in motor and cognitive functioning that can affect their adjustments to the variations in everyday life environment. The objective was to explore gait parameters and variability of patients with major depressive disorder in dual task walking situations. Eight patients and 20 healthy controls performed motor, mental and combined motor+mental tasks while walking. Calculated parameters were cycle time, stride length, swing time, double support time and their coefficients of variation (CV). Patients demonstrated greater gait variability (swing time CV) than controls during baseline walk (t(26)=2.64, p<0.05) and motor dual task (t(26)=3.68, p<0.05). Moreover, the transition from mental to combined task decreased stride length (M=126.48±15.35 and M=121.19±13.55, p<0.001) and increased double support time (M=0.266±0.072 and M=0.287±0.076, p<0.01) only in controls. Also, gait variability increased in controls during the combined task, while remaining the same or decreasing in patients. Tasks that required greater cognitive involvement affected gait variability in patients more than controls, but only up to a certain level, after which patients׳ stability appeared unaffected by the increase of cognitive demand. This could be explained by a tendency of patients to neglect complex cognitive tasks while walking in order to preserve stability and prevent possible falls.

Gait in amyotrophic lateral sclerosis: Is gait pattern differently affected in spinal and bulbar onset of the disease during dual task walking?

Abstract Amyotrophic lateral sclerosis (ALS) is characterized by weakness, fatigue, loss of balance and coordination. The purpose of the study was to examine gait in ALS patients. Gait was compared in ALS with spinal and bulbar onset, while performing dual mental and motor tasks. Dual-task walking was performed by 27 ALS patients, 13 with spinal- and 14 with bulbar-onset disease. Twenty-nine healthy subjects were used as a control group. The subjects performed a basic, simple walking task, dual-motor task, dual-mental task, and combined motor and mental tasks. Results showed that dual-task paradigm has an effect on gait in ALS patients. Gait was differently affected in spinal and bulbar onset of ALS by some of the given tasks. Mental tasks had a larger effect than motor tasks in all gait parameters. In conclusion, both ALS forms have impaired gait in dual tasks. Simple walk in patients with spinal onset shows higher variability of certain gait parameters compared to bulbar-onset patients and controls. Differences in gait could also indicate postural instability and possible falls in complex walking situations.

Finger tapping analysis in patients with Parkinson’s disease and atypical parkinsonism

The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinsons disease (PD), progressive supranuclear palsy-Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n=13), PSP-R (n=15), and MSA-P (n=14) patients and matched healthy controls (HC; n=14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of -0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (-0.21°/cycle, p=0.032), and particularly from PD (-0.56°/cycle, p=0.001), and MSA-P patients (-1.48°/cycle, p=0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (pmsa-pd=0.726, pmsa-psp=0.363, ppsp-pd=0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism.

The impact of functional electrical stimulation (FES) on freezing of gait (FOG) in patients with Parkinson's disease

Patients with Parkinsons disease (PD) frequently exhibit problems with gait initiation, maintaining rhythmicity of the gait, turning, and may suffer from motor blocks, i.e., freezing of gait (FOG). All these issues contribute to higher risk of stumbling and falling. In this study, we tested the influence of functional electrical stimulation (FES) on gait in 9 patients with PD with history of freezing episodes. Patients were walking along the given path comprising standing up from the chair, passing through narrow doorways and turning. Besides regular walking, protocol also comprised walking while carrying tray with glass of water (dual-tasking). Patients peroneal nerve of the leg which was estimated to be from the weaker side was stimulated during the swing phase in moments when gait normal pattern was impaired. Stimulation was triggered automatically based on heel switch placed in the shoe. Gait sequences with and without FES were recorded successively, and these gait patterns were compared afterwards. Results showed that FES decreased duration of double support phase and variability of stride duration and stride length. While stimulated, two patients did not experience motor blocks in a few places along the path where they otherwise had problems with FOG.

Influence of attention alternation on movement-related cortical potentials in healthy individuals and stroke patients

OBJECTIVEnIn this study, we analyzed the influence of artificially imposed attention variations using the auditory oddball paradigm on the cortical activity associated to motor preparation/execution.nnnMETHODSnEEG signals from Cz and its surrounding channels were recorded during three sets of ankle dorsiflexion movements. Each set was interspersed with either a complex or a simple auditory oddball task for healthy participants and a complex auditory oddball task for stroke patients.nnnRESULTSnThe amplitude of the movement-related cortical potentials (MRCPs) decreased with the complex oddball paradigm, while MRCP variability increased. Both oddball paradigms increased the detection latency significantly (p<0.05) and the complex paradigm decreased the true positive rate (TPR) (p=0.04). In patients, the negativity of the MRCP decreased while pre-phase variability increased, and the detection latency and accuracy deteriorated with attention diversion.nnnCONCLUSIONnAttention diversion has a significant influence on MRCP features and detection parameters, although these changes were counteracted by the application of the laplacian method.nnnSIGNIFICANCEnBrain-computer interfaces for neuromodulation that use the MRCP as the control signal are robust to changes in attention. However, attention must be monitored since it plays a key role in plasticity induction. Here we demonstrate that this can be achieved using the single channel Cz.

Selection of gait parameters for differential diagnostics of patients with de novo Parkinson’s disease

Abstract Background: Gait disturbances are an integral part of clinical manifestations of Parkinson’s disease (PD), even in the initial stages of the disease. Our goal was to identify the set of spatio-temporal gait parameters that bear the highest relevance for characterizing de novo PD patients. Methods: Forty patients with de novo PD and forty healthy controls were recorded while walking over an electronic walkway in three different conditions: (1) base walking, (2) walking with an additional motor task, (3) walking with an additional mental task. Both groups were well balanced concerning age and gender. To select a smaller number of relevant parameters, affinity propagation clustering was applied on parameter pairwise correlation. The exemplars were then sorted by importance using the random forest algorithm. Classification accuracy of a support vector machine was tested using the selected parameters and compared to the accuracy of the model using a set of parameters derived from literature. Results: Final selection of parameters included: stride length and stride length coefficient of variation (CV), stride time and stride time CV, swing time and swing time CV, step time asymmetry, and heel-to-heel base support CV. Classification performed using these parameters showed higher overall accuracy (85%) than classification using the common parameter set containing: stride time, stride length, swing time and double support time, along with their CVs (78%). Conclusion: In early stages of PD, double support time and its CV appear to be weak indicators of the disease. We instead found step time asymmetry and support base CV to significantly contribute to classification accuracy.

Effect of Attention Variation in Stroke Patients: Analysis of Single Trial Movement-Related Cortical Potentials

We have previously developed a Brain-computer interface (BCI) for neuromodulation based on movement related cortical potentials (MRCP). Since successful induction of plasticity is dependent on the attention of the user, the aim of this study was to analyze the changes in MRCPs during imposed attentional shifts in patients. We recorded EEG signals from Cz and its surrounding channels in seven chronic stroke patients, who were asked to attempt ankle dorsiflexion in two subsets of 30 repetitions. Each subset was separated from the other by an auditory oddball task comprised of three tones. Patients were asked to detect the target tone by pressing a button. Nine temporal features were extracted from single trial MRCPs and compared between the two subsets of dorsiflexion that were interspersed by the oddball task. The amplitude of the MRCP negativity, pre-movement slopes, pre-movement variability and movement detection latency and accuracy changed significantly when attention was diverted from the main task of dorsiflexion. This has significant implications for BCIs designed to induce plasticity since detection failure will result in inappropriate device control.