Marom Bikson

Background: Transcranial direct current stimulation (tDCS) devices adjust output voltage to maintain the target current despite varying impedance. Pulsatile blood flow produces beat-synchronous changes in tissue impedance. Objective: To determine whether impedance-derived heart rate (IHR), heart rate variability (IHRV), and respiration (IDR) can be estimated from tDCS output voltage without additional physiological sensors. Methods: A custom analog front-end acquires the tDCS output voltage across its full dynamic DC range and superimposed AC fluctuations with high precision. Beats detected from the AC-coupled signal yielded normal-to-normal intervals for HR, HRV, and interval-derived respiration. Accuracy was quantified as mean absolute error (MAE) in 10 healthy laboratory participants against ECG and respiration-monitor references, and against chest-strap RR intervals in 19 at-home sessions from 10 participants with mild-to-moderate depression. Results: Laboratory MAEs versus ECG were 0.57 bpm for HR, 9.40 ms for SDNN, and 18.90 ms for RMSSD (r = 0.995, 0.859, and 0.778; N = 10); respiratory-rate MAE was 1.36 breaths/min (r = 0.852; N = 6). Across 1-5 mA of tDCS, the cardiac voltage ΔV _cardiac (t) amplitude scaled linearly with current (slope, 0.073 mV/mA; p < 0.001). The pulsatile impedance ΔZ _cardiac (t) = (ΔV _cardiac (t)/I _applied ) amplitude averaged 0.080 ± 0.029 Ω (mean ± SD) across 50 participant-current observations, with no significant dependence on intensity (slope, −0.002 Ω/mA; p = 0.086). At-home MAEs were 1.43 bpm for HR, 8.86 ms for SDNN, and 24.92 ms for RMSSD (r = 0.995, 0.767, and 0.680; 19 sessions). Conclusions: tDCS output voltage contains a recoverable cardiac-synchronous signal arising from pulsatile impedance, enabling HR, HRV, and respiratory monitoring without additional physiological sensors.

We present an overview of a novel, patented, approach for creating personalized 3D-printed headgear that enables multi-electrode transcranial electrical stimulation, even in the home. A structural magnetic resonance imaging (MRI) scan is used to optimize a montage that targets key brain areas/networks and is then uploaded to a secure server to design customized headgear that is ultimately 3D-printed. The headgear allows rapid multi-electrode placement (<1 min per electrode) with comparable accuracy as manual 10-10 measurements. We performed over 1,400 sessions across 63 older adults with neurological injury or disease. We describe an efficient training program for study partners (e.g., spouses) that enabled a 100% success rate and over 900 remotely administered sessions. Study partners and participants reported high levels of confidence and satisfaction with the experience. Because the electrode locations are based on personalized computational modeling, the headgear is ideal for techniques requiring precision (e.g., temporal interference stimulation, transcranial focused ultrasound, transcranial magnetic stimulation).

We present an overview of a novel, patented, approach for creating personalized 3D-printed headgear that enables multi-electrode transcranial electrical stimulation, even in the home. A structural magnetic resonance imaging (MRI) scan is used to optimize a montage that targets key brain areas/networks and is then uploaded to a secure server to design customized headgear that is ultimately 3D-printed. The headgear allows rapid multi-electrode placement (<1 min per electrode) with comparable accuracy as manual 10-10 measurements. We performed over 1,400 sessions across 63 older adults with neurological injury or disease. We describe an efficient training program for study partners (e.g., spouses) that enabled a 100% success rate and over 900 remotely administered sessions. Study partners and participants reported high levels of confidence and satisfaction with the experience. Because the electrode locations are based on personalized computational modeling, the headgear is ideal for techniques requiring precision (e.g., temporal interference stimulation, transcranial focused ultrasound, transcranial magnetic stimulation).

Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following repeated tDCS sessions) on the regional brain activity during rest need further investigation, especially in MS. This study aims to elucidate tDCS’ underpinnings, alongside its therapeutic impact in MS patients, using concurrent tDCS-MRI methods. In total, 20 MS patients (age = 48 ± 12 years; 8 males) and 28 healthy controls (HCs; age = 36 ± 15 years; 12 males) were recruited. They participated in a tDCS-MRI session, during which resting-state functional MRI (rs-fMRI) was used to measure the levels of the fractional amplitude of low-frequency fluctuations (fALFFs), which is an index of regional neuronal activity, before and during left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA for 15 min). MS patients were then asked to return for an identical tDCS-MRI visit (follow-up) after 20 identical at-home tDCS sessions. Simultaneous tDCS-induced changes in fALFF are seen across cortical and subcortical areas in both HC and MS patients, with some regions showing increased and others decreased brain activity. In HCs, fALFF increased in the right pre- and post-central gyrus whilst it decreased in subcortical regions. Conversely, MS patients initially displayed increases in more posterior cortical regions but decreases in the superior and temporal cortical regions. At follow-up, MS patients showed reversed patterns, emphasizing significant cumulative effects of tDCS treatment upon brain excitation. Such long-lasting changes are further supported by greater pre-tDCS fALFFs measured at follow-up compared to baseline, especially around the cuneus. The results were significant after correcting for multiple comparisons (p-FDR < 0.05). Our study shows that tDCS has both simultaneous and cumulative effects on neuronal activity measured with rs-fMRI, especially involving major brain areas distant from the site of stimulation, and it is responsible for fatigue and cognitive and motor skills.

Background: Enhancing tDCS technology can support the delivery of higher current intensities, enabling broader dose-response studies in human trials. Methods: High-Capacity tDCS (HC-tDCS) integrates novel electrodes and adaptive current/voltage controlled electronics. Multi-layer HC electrodes include polarity-specific redox layers and designed hydrogel interfaces, shaped for a bifrontotemporal montage. The stimulator design includes adaptive ramps with hybrid voltage-current control and low (7.5 V) compliance voltage. Scanning electron microscopy (SEM) and electrical impedance spectroscopy (EIS) were used to characterize electrode properties. Tolerability of HD-tDCS was tested for target currents 1-6 mA (in 1 mA increments) for 30 min on 5 healthy subjects, and compared with conventional tDCS using 2 mA F3-F4 sponge-electrodes. MRI-derived computational models predicted cortical electric fields. Tolerability was assessed according to the 100 mm visual analogue scale for pain (VASP-100), skin erythema assessment, thermal imaging, and adverse event questionnaires. Results: The electrode design including high-roughness polarity-specific capacity, electrochemically supports high-charge direct current stimulation. In all subjects, HC-tDCS was well tolerated at all tested doses (1-6 mA) with minor transient adverse events and average VASP-100 less than 15. VASP-100 during sponge-electrode tDCS at 2 mA was comparable to 5 and 6 mA HC-tDCS. HC-tDCS operates at significantly lower voltage than sponge-tDCS, impacting tolerability and efficiency. Modeling predicts peak frontal electric fields of 0.65-1.08 V/m for 2 mA HC-tDCS and 1.95-3.25 V/m for 6 mA HC-tDCS, compared to 0.49-0.95 V/m for 2 mA sponge-tDCS. Conclusions: HC-tDCS allows increased cortical stimulation; at 6 mA achieving double the 1 V/m electric field threshold in all subjects. Enabled by pre-stimulation procedures, specialized electrodes, and adaptive low-voltage stimulators, HC-tDCS is well tolerated at intensities up to at least 6 mA.

An interview with J. Thomas Mortimer by Marom Bikson on the origins of spinal cord stimulation.

An interview in five parts of Harold Sackeim by Marom Bikson.