Tass Lab Research
The goal of our computational research - the bedrock of our approach - is to predict how we might counteract abnormal neuronal synchrony by inducing desynchronization, in this way restoring physiological information processing and symptom reduction. Several brain disorders are characterized by abnormal neuronal synchronization processes. In these disorders, instead of being involved in normal physiological task- and context-dependent information processing, large numbers of neurons are engaged in or influenced by detrimentally synchronized neuronal activity leading to an array of symptoms. The goal of our computational research is to predict how we might counteract abnormal neuronal synchrony by inducing desynchronization, in this way restoring physiological information processing and symptom reduction. Accordingly, we develop stimulation techniques that aim at creating desynchronization which persists long after the cessation of stimulation. It should be noted that we do not aim at suppressing neuronal activity or at inducing artificial neural rhythms.
EEG Recordings: Our electroencephalography (EEG) recordings are carried out using brain products antiCAP, a high-density (160 channel), research grade, EEG system that uses active gel-based electrodes for high quality recordings. For the most optimal recordings, all experiments are carried out in a soundproof electrically shielded chamber.
Neurofeedback uses ongoing brain activity to provide feedback to a patient about active brain states. Over multiple training sessions, the patient can learn to control brain activity through the process of conditioning to feedback cues (Sterman, 1977). In conjunction with stimulation techniques, we hope to develop a noninvasive neurotherapy technique that can help patients with motor disorders control their symptoms with less reliance on medication. In a feasibility study, Parkinson’s Disease (PD) patients were shown a visual representation of their ongoing sensorimotor rhythm (SMR: 12-15 Hz) from ongoing EEG electrodes place on the scalp (Figure 1, Cook et al., 2021). After two days of training, the patients were able to increase their SMR power as evidenced by increased threshold for feedback cues (Figure 2). Likewise, recorded EEG activity showed an increase in SMR amplitude and short-acting burst activity as well as a decrease in beta burst activity (17-30 Hz). Highly synchronized beta activity is associated with motor impairment in PD (Eusebio et al., 2009). Cortical activity in many behaviorally relevant EEG bands (Theta, Alpha, SMR, and Beta) underwent noticeable changes over the two days of training (Figure 3, Cook et al., 2021).
Deep brain stimulation
Deep brain stimulation (DBS) is the standard therapy for patients suffering from medically refractory Parkinson’s disease (Benabid et al., 2009). For this treatment, depth electrodes are implanted in targeted areas of the brain and electrical pulses are continuously administered at high frequencies (> 100Hz) (Benabid et al., 2009). DBS may cause side effects as the stimulation of the targeted areas impacts fibers that run through that areas. It can also adversely impact surrounding regions of the brain. Accordingly, it is desirable to reduce the total amount of current delivered to the brain tissue.
Through Dr. Tass’s research it was found that CR deep brain stimulation (CR-DBS) caused long-lasting therapeutic after-effects in parkinsonian monkeys (Tass et al. 2012, Wang et al, 2016). After 2 h of CR-DBS per day, delivered to the subthalamic nucleus (STN), on five consecutive days (Tass et al, 2012). In contrast, classical DBS did not induce any sustained effects after the stimulation was discontinued.
Vibrotactile stimulation for the treatment of Parkinson’s disease and stroke
Our computational studies predicted that CR stimulation can be delivered non-invasively, i.e. without implanting electrodes in patients’ brains (Popovych & Tass 2012; Tass & Popovych 2012; Pfeifer et al., 2021). To this end, we have developed vibrotactile CR stimulation (Tass 2017): We use pre-existing neuronal pathways that deliver sensory information to specific, well-defined brain areas by replacing electrical stimuli delivered through implanted depth electrodes with weak (i.e., non-painful) vibratory stimuli administered to the fingertips through mechanical stimulators mounted in a glove. This enables to stimulate specific target brain areas without inadvertently stimulating brain tissue surrounding the target or fibers passing through the latter. In a first-in-human study, five idiopathic Parkinson’s disease patients received vCR fingertip stimulation for 4 h per day on 3 consecutive days (Syrkin-Nikolau et al., 2018). Kinematic assessments revealed improved gait and bradykinesia during stimulation and after one month after cessation of stimulation.
In a 6+ months long case series in three patients and a 3-month pilot study in six patients with idiopathic Parkinson’s disease with further developed vibrotactile CR stimulation we revealed clinically and statistically significant therapeutic motor effects as assessed by the MDS-UPDRS part III (Pfeifer et al., 2021). In addition, the 3-month pilot study revealed a significant decrease of Parkinson-related abnormal neuronal synchrony in the sensorimotor cortex (Pfeifer et al., 2021). Clinical as well as EEG recordings were performed after withdrawal of dopaminergic medication, demonstrating promising acute and cumulative long-lasting effects persisting cessation of stimulation delivery (Pfeifer et al., 2021).
Acoustic stimulation for tinnitus therapy
Tinnitus, or the perception of sound in the absence of any external stimuli (Henry et al., 2005), affects approximately 10% of the adult population (Bhatt et al., 2016). In the majority of cases, there are very few, if any, treatment options for the symptom. Acoustic coordinated reset (CR) stimulation uses low-intensity sounds to disrupt the abnormal neuronal synchrony in the brains of patients with tinnitus.
For this treatment, pure tones adapted to the patient’s dominant tinnitus pitch are administered according to the CR algorithm (Tass et al., 2012). In a proof-of-concept study in patients with chronic subjective tinnitus it was shown that acoustic CR treatment was safe, well-tolerated and caused a significant decrease of tinnitus loudness, annoyance and pervasiveness of symptoms (Tass et al., 2012). Therapeutic effects achieved in 12 weeks of treatment persisted through a preplanned 4-week therapy pause and showed sustained long-term effects after 10 months of therapy, with a 75 % responder rate. EEG recordings performed before and after 12 weeks of CR treatment revealed a number of CR-induced changes of brain activity: Neuronal synchrony was significantly reduced in a tinnitus-associated network of brain areas (Tass et al. 2012, Admachic et al. 2012, Adamchic et al. 2014a). Abnormal interactions between different brain areas (Silchenko et al. 2013) and between different brain rhythms (Adamchic et al., 2014b) were significantly reduced. Already short epochs of acoustic CR stimulation specifically counteract the abnormal brain wave pattern characteristic for tinnitus sufferers. Short (16 min) epochs of acoustic CR stimulation caused the longest significant reduction of delta (slow waves, 1.0-4.0 Hz) and gamma (30.0-48.0 Hz) and increase of alpha (8.0-13.0 Hz) power in the auditory cortex region (Adamchic et al., 2017).
While CR effectively leads to a clinically meaningful relief and objective activity changes in a widespread network of brain areas, we hypothesized that the spacing of the therapeutic tones could be further optimized. To that end, we re-analyzed the data of 18 patients (Adamchic et al., 2017) previously treated with two types of CR (regular CR and noisy CR) to determine the relationships between tone spacing and tinnitus loudness using a metric we call the “gap index”, which is based on the fundamental audiological concept of auditory filters. We found that higher gap indices, indicative of more loosely spaced tones, were associated with significant reductions in tinnitus loudness during both regular and noisy CR (Munjal et al, 2021). These findings will be helpful in developing more robust CR paradigms in order to provide relief to a larger number of patients and for longer periods of time.