Gozde Unal, a PhD candidate in the lab of Dr. Marom Bikson will defend her dissertation thesis on Friday, May 13, 2022 at 11am. A copy of her abstract is below. If you would like to attend, please contact Gozde at gunal000@citymail.cuny.edu for the Zoom meeting ID. The meeting is also taking place in person in the Center for Discovery & Innovation 3rd floor conference room (CDI 3.352)

Abstract

Improvements in electroconvulsive therapy (ECT) outcomes have followed refinement in device electrical output and electrode montage. The physical properties of the ECT stimulus, together with those of the patient’s head, determine the impedances measured by the device and govern current delivery to the brain and ECT outcomes. However, the precise relations among physical properties of the stimulus, patient head anatomy, and patient-specific impedance to the passage of current are long-standing questions in ECT research and practice. In this thesis, we develop a computational framework based on diverse clinical data sets. We developed anatomical MRI-derived models of transcranial electrical stimulation (tES) that included changes in tissue conductivity due to local electrical current flow. These “adaptive” models simulate ECT both during therapeutic stimulation using high current and when dynamic impedance is measured, as well as prior to stimulation when low current is used to measure static impedance. We modeled two scalp layers: a superficial scalp layer with adaptive conductivity that increases with electric field up to a subject-specific maximum (σSS̅̅̅̅), and a deep scalp layer with a subject-specific fixed conductivity (σDS). We demonstrated that variation in these scalp parameters may explain clinical data on subject-specific static impedance and dynamic impedance, their imperfect correlation across subjects, their relationships to seizure threshold, and the role of head anatomy. Adaptive tES models demonstrated that current flow changes local tissue conductivity which in turn shapes current delivery to the brain in a manner not accounted for in fixed tissue conductivity models. Our predictions that variation in individual skin properties, rather than other aspects of anatomy, largely govern the relationship between static impedance, dynamic impedance, and ECT current delivery to the brain, themselves depend on assumptions about tissue properties. Broadly, our novel modeling pipeline opens the door to explore how adaptive-scalp conductivity may impact transcutaneous electrical stimulation (tES). Lastly, we incorporate the (device specific) role of frequency with a single overall assumption allowing quasi-static stimulations of ECT: appropriately parametrizing effective resistivity at single representative frequency (e.g., at 1 kHz), including subject-specific and adaptive skin resistivities. We only stipulate that our functions for (adaptive) resistivity at 1 kHz explain local tissue resistivity as they impact the static and dynamic impedance measures by specific ECT devices (e.g., Thymatron).

Zeinab Esmaeilpour, a PhD candidate in the lab of Dr. Marom Bikson will defend her dissertation thesis on Monday, April 4, 2022 at 3pm. A copy of her abstract is below. If you would like to attend, please contact Zeinab at zesmaeilpour@ccny.cuny.edu for the Zoom meeting ID. The meeting is also taking place in person in the Center for Discovery & Innovation 3rd floor conference room (CDI 3.352)

Abstract

There is a tremendous interest in the use of non-invasive electrical stimulation for enhancing brain function in a healthy population as well as treating brain disorders in patients. Understanding the cellular mechanism of direct current (DC) and kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation. More specifically, there is a large mismatch between enthusiasm for clinical applications of the method and understanding of DC and kHz novel mechanisms of action. This dissertation is centered around two main fundamental aims: 1) systematic study of the acute and long-term effects of kilohertz electrical stimulation and amplitude modulated waveform with kHz carrier frequency using a well-established animal model, hippocampal brain slice, 2) study the effect of tDCS on water exchange rate across the blood-brain barrier using an advanced MRI imaging technique in a healthy population to investigate effect of tDCS stimulation on Blood brain barrier.

The neuronal membrane has a well-established low pass filtering characteristic. This feature attenuates the sensitivity of the nervous system to any waveforms with high-frequency components. On the contrary, kilohertz stimulation has recently revolutionized spinal cord stimulation and even generated promising results in transcranial electrical stimulation. Investigating the effect of low kilohertz stimulation for neuromodulation is of huge interest. In this study we developed experimental designs to systematically investigate the frequency and dose-response of neuronal activity to unmodulated and amplitude modulated waveforms in low kilohertz range. The results support the theory of membrane attenuation of high-frequency stimulation. While supported by membrane characteristics of neurons, we uncovered that using low kilohertz stimulation diminishes the sensitivity of hippocampal neurons to electrical stimulation. Moreover, Amplitude-Modulated waveforms can generate a different pattern of modulation with even higher sensitivity to stimulation. However, the required electric field, in this case, is still significantly higher than low-frequency stimulation methods such as tACS.

Effects of DC stimulation have been studied in neuronal depolarization/hyperpolarization, synaptic plasticity, and neuronal network modulation. Recent evidence suggests that DC stimulation can induce polarity-dependent water exchange rate across the blood-brain barrier (BBB) in cell culture experiments through a mechanism called electroosmosis. Modulating the water exchange rate across BBB is of broad interest in neurological diseases such as dementia, Alzheimer’s, and stroke where the brain clearance system is disrupted. Investigating the effect of electrical stimulation on water exchange across BBB can potentially lead to complimentary treatment options. We used an advanced MRI technique to investigate induced changes in cerebral blood flow (CBF) and water exchange rate across BBB during stimulation in areas under electrodes. Contrary to our hypothesis, we could not detect changes in the water exchange rate across BBB.

In conclusion, in our efforts to investigate effects of high frequency stimulation we found that sensitivity of neuronal networks to oscillating electrical stimulation is governed by time constant of neuronal membrane. Moreover, neuronal networks are selective to different kilohertz waveforms (i.e., amplitude modulated) which is governed by nonlinear adaptive mechanisms in the network. For the effect of DC stimulation on neurovascular units, we hypothesized that stimulation affects water exchange rate across BBB through a mechanism known as electroosmosis which is a very small portion of a large water exchange across BBB through active transport. We believe that this may be the answer to our negative results in experiments.

Below please find information in regards to BME PhD student Jason Ki’s dissertation defense, which is open to all and will take place on Tuesday, March 30th at 3:00pm via Zoom. Please email Jason at jki00@citymail.cuny.edu for the Zoom link. Jason’s abstract is also below.

When the Brain Plays a Game:

Neural responses to visual dynamics during naturalistic visual tasks.

Department of Biomedical Engineering

Jason Ki

Mentor: Lucas C Parra

ABSTRACT

Many day-to-day tasks involve processing of complex visual information in a continuous stream. While much of our knowledge on visual processing has been established from reductionist approaches in lab-controlled settings, very little is known about the processing of complex dynamic stimuli experienced in everyday scenarios. Traditional investigations employ event-related paradigms that involve presentation of simple stimuli at select locations in visual space or discrete moments in time. In contrast, visual stimuli in real-life are highly dynamic, spatially-heterogeneous, and semantically rich. Moreover, traditional experiments impose unnatural task constraints (e.g. inhibited saccades), thus, it is unclear whether theories developed under the reductionist approach apply in naturalistic settings. Given these limitations, alternative experimental paradigms and analysis methods are necessary. Here, we introduce a new approach for investigating visual processing, applying the system identification (SI) framework. We investigate the modulation of stimulus-evoked responses during a naturalistic task (i.e. kart race game) using non-invasive scalp recordings.

In recent years, multivariate modeling approaches have become increasingly popular for assessing neural response to naturalistic stimulus. Encoding models use stimulus patterns to predict brain responses and decoding models use patterns of brain responses to predict stimulus that drove these responses. In this dissertation, we employ a hybrid method that “encodes” the stimulus to predict “decoded” brain responses. With this approach, we measure the stimulus-response correlation (SRC, i.e. temporal correlation of neural response and dynamic stimulus) to assess the strength of stimulus-evoked activity to uniquely experienced naturalistic stimulus. To demonstrate this, we measured the SRC during a kart race videogame. We find that SRC increased with active play of the game, suggesting that stimulus-evoked activity is modulated by the visual task demands. Furthermore, we analyzed the selectivity of neural response across the visual space. While it is well-established that neural response is spatially selective to discrete stimulus, it is unclear whether this is true during naturalistic stimulus presentation. To assess this, we measured the correlation of neural response with optical flow magnitude at individual locations on the screen during the videogame. We find that the SRC is greater for locations in space that are task-relevant, enhancing during active play. Moreover, the spatial selectivity differs across scalp locations, which suggest that individual brain regions are spatially selective to different visual dynamics.

Overall, we leveraged the SI framework to investigate visual processing during a naturalistic stimulus presentation, extending visual research to ecologically valid paradigms. Our findings shed new insights about the stimulus-evoked neural response to visual dynamics during a uniquely experienced naturalistic visual task. We show that selectivity of neural response can be spatially-resolved at pixel-level from a low-SNR EEG. In the future, by further probing other spatial and temporal dimensions of the stimuli (beyond optical flow), we may gain new insights into how neural signals convey visual processing during dynamic natural visual experiences.