Juha Gogulski (MD, PhD) works as a Postdoc at Keller Laboratory (Stanford University, Department of Psychiatry and Behavioral Sciences in the School of Medicine). He is interested in the development of novel personalized neuromodulation treatments. In his PhD thesis, he used tractography-guided transcranial magnetic stimulation to study the neural mechanisms of tactile working memory, metacognition, and tactile temporal perception.
Doctor of Philosophy, University Of Helsinki (2018)
PhD, University of Helsinki, Finland (2018)
MD, University of Helsinki, Finland (2014)
Corey Keller, Postdoctoral Faculty Sponsor
Mapping cortical excitability in the human dorsolateral prefrontal cortex.
bioRxiv : the preprint server for biology
Background: Repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (dlPFC) is an effective treatment for depression, but the neural response to rTMS remains unclear. TMS with electroencephalography (TMS-EEG) can probe these neural effects, but variation in TMS-evoked potentials (TEPs) across the dlPFC are not well characterized and often obscured by muscle artifact. Mapping TEPs and artifacts across dlPFC targets is needed to identify high fidelity subregions that can be used for rTMS treatment monitoring.Objective: To characterize 'early TEPs' anatomically and temporally close (20-50 ms) to the TMS pulse and associated muscle artifacts (<20 ms) across the dlPFC. We hypothesized that TMS location and angle would affect these early TEPs and that TEP size would be inversely related to muscle artifact. We sought to identify an optimal TMS target / angle for the group and asked if individualization would be beneficial.Methods: In 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses.Results: Early TEPs were sensitive to stimulation location, with posterior and medial targets yielding larger early TEPs. Regions with high early TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger TEP responses compared to other standard targets. Optimal TMS target differed across subjects, suggesting that a personalized targeting approach could boost the early TEP by additional 36%.Conclusions: The early TEPs can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. A personalized targeting approach may further enhance the signal quality of the early TEP.Highlights: Early TEPs varied significantly across the dlPFC as a function of TMS target.TMS targets with less muscle artifact had significantly larger early TEPs.Selection of a postero-medial target increased early TEPs by 102% compared to anterior targets.Retrospective target and angle optimization increased early TEPs by an additional 36%.
View details for DOI 10.1101/2023.01.20.524867
View details for PubMedID 36711689
Reliability of the TMS-evoked potential in dorsolateral prefrontal cortex
Background: We currently lack a robust and reliable method to probe cortical excitability noninvasively from the human dorsolateral prefrontal cortex (dlPFC), a region heavily implicated in psychiatric disorders. We recently found that the strength of early and local dlPFC single pulse transcranial magnetic stimulation (TMS)-evoked potentials (EL-TEPs) varied widely depending on the anatomical subregion probed, with more medial regions eliciting stronger responses than anterolateral sites. Despite these differences in amplitude of response, the reliability at each target is not known. Objective: To evaluate the reliability of EL-TEPs across the dlPFC. Methods: In 15 healthy subjects, we quantified within-session reliability of dlPFC EL-TEPs after single pulse TMS to six dlPFC subregions. We evaluated the concordance correlation coefficient (CCC) across targets and analytical parameters including time window, quantification method, region of interest, sensor- vs. source-space, and number of trials. Results: At least one target in the anterior and posterior dlPFC produced reliable EL-TEPs (CCC>0.7). The medial target was most reliable (CCC = 0.78) and the most anterior target was least reliable (CCC = 0.24). ROI size and type (sensor vs. source space) did not affect reliability. Longer (20-60 ms, CCC = 0.62) and later (30-60 ms, CCC = 0.61) time windows resulted in higher reliability compared to earlier and shorter (20-40 ms, CCC 0.43; 20-50 ms, CCC = 0.55) time windows. Peak-to-peak quantification resulted in higher reliability than the mean of the absolute amplitude. Reliable EL-TEPs (CCC up to 0.86) were observed using only 25 TMS trials for a medial dlPFC target. Conclusions: Medial TMS location, wider time window (20-60ms), and peak-to-peak quantification improved reliability. Highly reliable EL-TEPs can be extracted from dlPFC after only a small number of trials.
Reliability and Validity of Transcranial Magnetic Stimulation-Electroencephalography Biomarkers.
Biological psychiatry. Cognitive neuroscience and neuroimaging
Noninvasive brain stimulation and neuroimaging have revolutionized human neuroscience with a multitude of applications, including diagnostic subtyping, treatment optimization, and relapse prediction. It is therefore particularly relevant to identify robust and clinically valuable brain biomarkers linking symptoms to their underlying neural mechanisms. Brain biomarkers must be reproducible (i.e., have internal reliability) across similar experiments within a laboratory and be generalizable (i.e., have external reliability) across experimental setups, laboratories, brain regions, and disease states. However, reliability (internal and external) is not alone sufficient; biomarkers also must have validity. Validity describes closeness to a true measure of the underlying neural signal or disease state. We propose that these metrics, reliability and validity, should be evaluated and optimized before any biomarker is used to inform treatment decisions. Here, we discuss these metrics with respect to causal brain connectivity biomarkers from coupling transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We discuss controversies around TMS-EEG stemming from the multiple large off-target components (noise) and relatively weak genuine brain responses (signal), as is unfortunately often the case in noninvasive human neuroscience. We review the current state of TMS-EEG recordings, which consist of a mix of reliable noise and unreliable signal. We describe methods for evaluating TMS-EEG biomarkers, including how to assess internal and external reliability across facilities, cognitive states, brain networks, and disorders and how to validate these biomarkers using invasive neural recordings or treatment response. We provide recommendations to increase reliability and validity, discuss lessons learned, and suggest future directions for the field.
View details for DOI 10.1016/j.bpsc.2022.12.005
View details for PubMedID 36894435
Personalized Repetitive Transcranial Magnetic Stimulation for Depression.
Biological psychiatry. Cognitive neuroscience and neuroimaging
Personalized treatments are gaining momentum across all fields of medicine. Precision medicine can be applied to neuromodulatory techniques, in which focused brain stimulation treatments such as repetitive transcranial magnetic stimulation (rTMS) modulate brain circuits and alleviate clinical symptoms. rTMS is well tolerated and clinically effective for treatment-resistant depression and other neuropsychiatric disorders. Despite its wide stimulation parameter space (location, angle, pattern, frequency, and intensity can be adjusted), rTMS is currently applied in a one-size-fits-all manner, potentially contributing to its suboptimal clinical response (∼50%). In this review, we examine components of rTMS that can be optimized to account for interindividual variability in neural function and anatomy. We discuss current treatment options for treatment-resistant depression, the neural mechanisms thought to underlie treatment, targeting strategies, stimulation parameter selection, and adaptive closed-loop treatment. We conclude that a better understanding of the wide and modifiable parameter space of rTMS will greatly improve the clinical outcome.
View details for DOI 10.1016/j.bpsc.2022.10.006
View details for PubMedID 36792455
Neural Substrate for Metacognitive Accuracy of Tactile Working Memory
2017; 27 (11): 5343-5352
The human prefrontal cortex (PFC) has been shown to be important for metacognition, the capacity to monitor and control one's own cognitive processes. Here we dissected the neural architecture of somatosensory metacognition using navigated single-pulse transcranial magnetic stimulation (TMS) to modulate tactile working memory (WM) processing. We asked subjects to perform tactile WM tasks and to give a confidence rating for their performance after each trial. We circumvented the challenge of interindividual variability in functional brain anatomy by applying TMS to two PFC areas that, according to tractography, were neurally connected with the primary somatosensory cortex (S1): one area in the superior frontal gyrus (SFG), another in the middle frontal gyrus (MFG). These two PFC locations and a control cortical area were stimulated during both spatial and temporal tactile WM tasks. We found that tractography-guided TMS of the SFG area selectively enhanced metacognitive accuracy of tactile temporal, but not spatial WM. Stimulation of the MFG area that was also neurally connected with the S1 had no such effect on metacognitive accuracy of either the temporal or spatial tactile WM. Our findings provide causal evidence that the PFC contains distinct neuroanatomical substrates for introspective accuracy of tactile WM.
View details for DOI 10.1093/cercor/bhx219
View details for Web of Science ID 000413209200024
View details for PubMedID 28968804
A Segregated Neural Pathway for Prefrontal Top-Down Control of Tactile Discrimination
2015; 25 (1): 161-166
It has proven difficult to separate functional areas in the prefrontal cortex (PFC), an area implicated in attention, memory, and distraction handling. Here, we assessed in healthy human subjects whether PFC subareas have different roles in top-down regulation of sensory functions by determining how the neural links between the PFC and the primary somatosensory cortex (S1) modulate tactile perceptions. Anatomical connections between the S1 representation area of the cutaneous test site and the PFC were determined using probabilistic tractography. Single-pulse navigated transcranial magnetic stimulation of the middle frontal gyrus-S1 link, but not that of the superior frontal gyrus-S1 link, impaired the ability to discriminate between single and twin tactile pulses. The impairment occurred within a restricted time window and skin area. The spatially and temporally organized top-down control of tactile discrimination through a segregated PFC-S1 pathway suggests functional specialization of PFC subareas in fine-tuned regulation of information processing.
View details for DOI 10.1093/cercor/bht211
View details for Web of Science ID 000347417600015
View details for PubMedID 23960209
Two-point tactile discrimination ability is influenced by temporal features of stimulation
EXPERIMENTAL BRAIN RESEARCH
2014; 232 (7): 2179-2185
Two-point discrimination threshold is commonly used for assessing tactile spatial resolution. Since the effect of temporal features of cutaneous test stimulation on spatial discrimination ability is not yet well known, we determined whether the ability to discriminate between two stimulus locations varies with the interstimulus interval (ISI) of sequentially presented tactile stimuli or the length of the stimulus train. Electrotactile stimuli were applied to one or two locations on the skin of the thenar eminence of the hand in healthy human subjects. Tactile discrimination ability was determined using methods based on the signal detection theory allowing the assessment of sensory performance, independent of the subject's response criterion. With stimulus pairs, the ability to discriminate spatial features of stimulation (one location vs. two stimulus locations 4 cm apart) was improved when the ISI was equal to or longer than that required for tactile temporal discrimination. With stimulus trains, the ability to discriminate spatial features of stimulation was significantly improved with an increase in the stimulus train (from 3 to 11 pulses corresponding to train lengths from 40 to 200 ms). These results indicate that temporal features of tactile stimulation significantly influence sensory performance in a tactile spatial discrimination task. Precise control of temporal stimulus parameters should help to reduce variations in results on the two-point discrimination threshold.
View details for DOI 10.1007/s00221-014-3908-y
View details for Web of Science ID 000337788600012
View details for PubMedID 24668131