Background: Maladaptive neuroplasticity related learned response in substance use disorder (SUD) can be ameliorated using non-invasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on competing neurobehavioral decision systems model. Next objective was to conduct computational simulation of NIBS of cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD) related dysfunctional “cue-reactivity” – a closely related construct of “craving” that is a core symptom. Our third objective was to test the feasibility of our neuroimaging guided rational NIBS approach in healthy humans. Methods: “Cue-reactivity” can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG), metrics of sensorimotor gating. Therefore, we conducted computational simulation of NIBS, including transcranial direct current stimulation(tDCS) and transcranial alternating current stimulation(tACS) of the cerebellar cortex and deep cerebellar nuclei(DCN), of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging guided NIBS approach for cerebellar lobule (VII) and prefrontal cortex based on healthy human study. Results: Simulation study of cerebellar tDCS induced gamma oscillations in the cerebral cortex while tTIS induced gamma-to-beta frequency shift. Experimental fNIRS study found that 2mA cerebellar tDCS evoked similar oxyhemoglobin(HbO) response in-the-range of 5x10-6M across cerebellum and PFC brain regions (=0.01); however, infra-slow (0.01–0.10 Hz) prefrontal cortex HbO driven(phase-amplitude-coupling, PAC) 4Hz, ±2mA (max.) cerebellar tACS evoked HbO in-the-range of 10-7M that was statistically different (=0.01) across those brain regions. Conclusion: Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC as well as fNIRS-driven ctACS at 4Hz that may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging.

Fundamentals of Laparoscopic Surgery (FLS) is a training module designed to provide basic surgical skills. During skill training of the FLS "suturing and intracorporeal knot-tying" task – the most difficult among the five psychomotor FLS tasks, learning from errors is one of the basic principles of motor skill acquisition where appropriate contextual switching of the brain state on error is postulated. This study investigated changes in the brain state following an error event based on the fusion of simultaneously acquired functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) signals. Here, human error processing is postulated to differentiate experts from novices based on the differences in the error-related chain of mental processes. Thirteen right-handed novice medical students and nine expert surgeons participated in this study. Error-related microstate analysis was performed using 32-channel EEG data at a high temporal resolution. Six microstate prototypes were identified from combined EEG data from experts and novices during the FLS task. Analysis of variance (ANOVA) found that the proportion of the total time spent in different microstates during the 10 sec error epoch was significantly affected by the skill level (p<0.01), microstate type (p<0.01), and the interaction between the skill level and the microstate type (p<0.01). Then, the EEG band power (1-40Hz) related to slower oxyhemoglobin (HbO) changes were found using regularized temporally embedded Canonical Correlation Analysis of the fNIRS-EEG signals. The HbO signal from the fNIRS channel overlying ‘Frontal_Inf_Oper_L’, ‘Frontal_Mid_Orb_L’, ‘Postcentral_L’, ‘Temporal_Sup_L’, ‘Frontal_Mid_Orb_R’ cortical areas from Automatic Anatomical Labelling showed significant (p<0.05) difference between experts and novices in the 10-sec error epoch. Here, the frontal/prefrontal cortical areas are postulated to be related to the perception and the activation of the primary somatosensory cortex at the postcentral cortical area is hypothesized to be related to the action underpinning perception-action coupling model for the error-related chain of mental processes. Therefore, our study highlighted the importance of error-related brain states from portable brain imaging when comparing complex surgical skill levels.