Matthias Witkowski

In vivo assessment of human brain oscillations during application of transcranial electric currents

Brain oscillations reflect pattern formation of cell assemblies’ activity, which is often disturbed in neurological and psychiatric diseases like depression, schizophrenia and stroke. In the neurobiological analysis and treatment of these conditions, transcranial electric currents applied to the brain proved beneficial. However, the direct effects of these currents on brain oscillations have remained an enigma because of the inability to record them simultaneously. Here we report a novel strategy that resolves this problem. We describe accurate reconstructed localization of dipolar sources and changes of brain oscillatory activity associated with motor actions in primary cortical brain regions undergoing transcranial electric stimulation. This new method allows for the first time direct measurement of the effects of non-invasive electrical brain stimulation on brain oscillatory activity and behavior.

Mapping entrained brain oscillations during transcranial alternating current stimulation (tACS)

Transcranial alternating current stimulation (tACS), a non-invasive and well-tolerated form of electric brain stimulation, can influence perception, memory, as well as motor and cognitive function. While the exact underlying neurophysiological mechanisms are unknown, the effects of tACS are mainly attributed to frequency-specific entrainment of endogenous brain oscillations in brain areas close to the stimulation electrodes, and modulation of spike timing dependent plasticity reflected in gamma band oscillatory responses. tACS-related electromagnetic stimulator artifacts, however, impede investigation of these neurophysiological mechanisms. Here we introduce a novel approach combining amplitude-modulated tACS during whole-head magnetoencephalography (MEG) allowing for artifact-free source reconstruction and precise mapping of entrained brain oscillations underneath the stimulator electrodes. Using this approach, we show that reliable reconstruction of neuromagnetic low- and high-frequency oscillations including high gamma band activity in stimulated cortical areas is feasible opening a new window to unveil the mechanisms underlying the effects of stimulation protocols that entrain brain oscillatory activity.

Enhancing Hebbian Learning to Control Brain Oscillatory Activity

Sensorimotor rhythms (SMR, 8-15 Hz) are brain oscillations associated with successful motor performance, imagery, and imitation. Voluntary modulation of SMR can be used to control brain-machine interfaces (BMI) in the absence of any physical movements. The mechanisms underlying acquisition of such skill are unknown. Here, we provide evidence for a causal link between function of the primary motor cortex (M1), active during motor skill learning and retention, and successful acquisition of abstract skills such as control over SMR. Thirty healthy participants were trained on 5 consecutive days to control SMR oscillations. Each participant was randomly assigned to one of 3 groups that received either 20 min of anodal, cathodal, or sham transcranial direct current stimulation (tDCS) over M1. Learning SMR control across training days was superior in the anodal tDCS group relative to the other 2. Cathodal tDCS blocked the beneficial effects of training, as evidenced with sham tDCS. One month later, the newly acquired skill remained superior in the anodal tDCS group. Thus, application of weak electric currents of opposite polarities over M1 differentially modulates learning SMR control, pointing to this primary cortical region as a common substrate for acquisition of physical motor skills and learning to control brain oscillatory activity.

Learned EEG-based brain self-regulation of motor-related oscillations during application of transcranial electric brain stimulation: feasibility and limitations

Objective: Transcranial direct current stimulation (tDCS) improves motor learning and can affect emotional processing and attention. However, it is unclear whether learned electroencephalography (EEG)-based brain-machine interface (BMI) control during tDCS is feasible, how application of transcranial electric currents during BMI control would interfere with feature-extraction of physiological brain signals and how it affects brain control performance. Here we tested this combination and evaluated stimulation-dependent artifacts across different EEG frequencies and stability of motor imagery-based BMI control. Approach: Ten healthy volunteers were invited to two BMI-sessions, each comprising two 60-trial blocks. During the trials, learned desynchronization of mu-rhythms (8–15 Hz) associated with motor imagery (MI) recorded over C4 was translated into online cursor movements on a computer screen. During block 2, either sham (session A) or anodal tDCS (session B) was applied at 1 mA with the stimulation electrode placed 1 cm anterior of C4. Main results: tDCS was associated with a significant signal power increase in the lower frequencies most evident in the signal spectrum of the EEG channel closest to the stimulation electrode. Stimulation-dependent signal power increase exhibited a decay of 12 dB per decade, leaving frequencies above 9 Hz unaffected. Analysis of BMI control performance did not indicate a difference between blocks and tDCS conditions. Conclusion: Application of tDCS during learned EEG-based self-regulation of brain oscillations above 9 Hz is feasible and safe, and might improve applicability of BMI systems.

tACS Phase Locking of Frontal Midline Theta Oscillations Disrupts Working Memory Performance

Background: Frontal midline theta (FMT) oscillations (4–8 Hz) are strongly related to cognitive and executive control during mental tasks such as memory processing, arithmetic problem solving or sustained attention. While maintenance of temporal order information during a working memory (WM) task was recently linked to FMT phase, a positive correlation between FMT power, WM demand and WM performance was shown. However, the relationship between these measures is not well understood, and it is unknown whether purposeful FMT phase manipulation during a WM task impacts FMT power and WM performance. Here we present evidence that FMT phase manipulation mediated by transcranial alternating current stimulation (tACS) can block WM demand-related FMT power increase (FMTΔpower) and disrupt normal WM performance. Methods: Twenty healthy volunteers were assigned to one of two groups (group A, group B) and performed a 2-back task across a baseline block (block 1) and an intervention block (block 2) while 275-sensor magnetoencephalography (MEG) was recorded. After no stimulation was applied during block 1, participants in group A received tACS oscillating at their individual FMT frequency over the prefrontal cortex (PFC) while group B received sham stimulation during block 2. After assessing and mapping phase locking values (PLV) between the tACS signal and brain oscillatory activity across the whole brain, FMT power and WM performance were assessed and compared between blocks and groups. Results: During block 2 of group A but not B, FMT oscillations showed increased PLV across task-related cortical areas underneath the frontal tACS electrode. While WM task-related FMTΔpower and WM performance were comparable across groups in block 1, tACS resulted in lower FMTΔpower and WM performance compared to sham stimulation in block 2. Conclusion: tACS-related manipulation of FMT phase can disrupt WM performance and influence WM task-related FMTΔpower. This finding may have important implications for the treatment of brain disorders such as depression and attention deficit disorder associated with abnormal regulation of FMT activity or disorders characterized by dysfunctional coupling of brain activity, e.g., epilepsy, Alzheimer’s or Parkinson’s disease (AD/PD).

Enhancing brain-machine interface (BMI) control of a hand exoskeleton using electrooculography (EOG)

BackgroundBrain-machine interfaces (BMIs) allow direct translation of electric, magnetic or metabolic brain signals into control commands of external devices such as robots, prostheses or exoskeletons. However, non-stationarity of brain signals and susceptibility to biological or environmental artifacts impede reliable control and safety of BMIs, particularly in daily life environments. Here we introduce and tested a novel hybrid brain-neural computer interaction (BNCI) system fusing electroencephalography (EEG) and electrooculography (EOG) to enhance reliability and safety of continuous hand exoskeleton-driven grasping motions.Findings12 healthy volunteers (8 male, mean age 28.1 ± 3.63y) used EEG (condition #1) and hybrid EEG/EOG (condition #2) signals to control a hand exoskeleton. Motor imagery-related brain activity was translated into exoskeleton-driven hand closing motions. Unintended motions could be interrupted by eye movement-related EOG signals. In order to evaluate BNCI control and safety, participants were instructed to follow a visual cue indicating either to move or not to move the hand exoskeleton in a random order. Movements exceeding 25% of a full grasping motion when the device was not supposed to be moved were defined as safety violation. While participants reached comparable control under both conditions, safety was frequently violated under condition #1 (EEG), but not under condition #2 (EEG/EOG).ConclusionEEG/EOG biosignal fusion can substantially enhance safety of assistive BNCI systems improving their applicability in daily life environments.

Hybrid EEG/EOG-based brain/neural hand exoskeleton restores fully independent daily living activities after quadriplegia

A noninvasive, hybrid brain/neural hand exoskeleton restored intuitive control of grasping motion, restoring independent activities to quadriplegics. Direct brain control of advanced robotic systems promises substantial improvements in health care, for example, to restore intuitive control of hand movements required for activities of daily living in quadriplegics, like holding a cup and drinking, eating with cutlery, or manipulating different objects. However, such integrated, brain- or neural-controlled robotic systems have yet to enter broader clinical use or daily life environments. We demonstrate full restoration of independent daily living activities, such as eating and drinking, in an everyday life scenario across six paraplegic individuals (five males, 30 ± 14 years) who used a noninvasive, hybrid brain/neural hand exoskeleton (B/NHE) to open and close their paralyzed hand. The results broadly suggest that brain/neural-assistive technology can restore autonomy and independence in quadriplegic individuals’ everyday life.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields.

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior.

An EEG/EOG-based hybrid brain-neural computer interaction (BNCI) system to control an exoskeleton for the paralyzed hand

Abstract The loss of hand function can result in severe physical and psychosocial impairment. Thus, compensation of a lost hand function using assistive robotics that can be operated in daily life is very desirable. However, versatile, intuitive, and reliable control of assistive robotics is still an unsolved challenge. Here, we introduce a novel brain/neural-computer interaction (BNCI) system that integrates electroencephalography (EEG) and electrooculography (EOG) to improve control of assistive robotics in daily life environments. To evaluate the applicability and performance of this hybrid approach, five healthy volunteers (HV) (four men, average age 26.5±3.8 years) and a 34-year-old patient with complete finger paralysis due to a brachial plexus injury (BPI) used EEG (condition 1) and EEG/EOG (condition 2) to control grasping motions of a hand exoskeleton. All participants were able to control the BNCI system (BNCI control performance HV: 70.24±16.71%, BPI: 65.93±24.27%), but inclusion of EOG significantly improved performance across all participants (HV: 80.65±11.28, BPI: 76.03±18.32%). This suggests that hybrid BNCI systems can achieve substantially better control over assistive devices, e.g., a hand exoskeleton, than systems using brain signals alone and thus may increase applicability of brain-controlled assistive devices in daily life environments.

Controlling assistive machines in paralysis using brain waves and other biosignals

The extent to which humans can interact with machines significantly enhanced through inclusion of speech, gestures, and eye movements. However, these communication channels depend on a functional motor system. As many people suffer from severe damage of the motor system resulting in paralysis and inability to communicate, the development of brain-machine interfaces (BMI) that translate electric or metabolic brain activity into control signals of external devices promises to overcome this dependence. People with complete paralysis can learn to use their brain waves to control prosthetic devices or exoskeletons. However, information transfer rates of currently available noninvasive BMI systems are still very limited and do not allow versatile control and interaction with assistive machines.Thus, using brain waves in combination with other biosignals might significantly enhance the ability of people with a compromisedmotor system to interact with assistivemachines.Here, we give an overview of the current state of assistive, noninvasive BMI research and propose to integrate brain waves and other biosignals for improved control and applicability of assistive machines in paralysis. Beside introducing an example of such a system, potential future developments are being discussed.