Faculty Bibliography

High co-morbidity and substantial overlap across psychiatric disorders encourage a transition in psychiatry research from categorical to dimensional approaches that integrate neuroscience and psychopathology. Converging evidence suggests that the cerebellum is involved in a wide range of cognitive functions and mental disorders. An important question thus centers on the extent to which cerebellar function can be linked to transdiagnostic dimensions of psychopathology. To address this question, we used a multivariate data-driven statistical technique (partial least squares) to identify latent dimensions linking human cerebellar connectome as assessed by functional MRI to a large set of clinical, cognitive, and trait measures across 198 participants, including healthy controls (n = 92) as well as patients diagnosed with attention-deficit/hyperactivity disorder (n = 35), bipolar disorder (n = 36), and schizophrenia (n = 35). Macroscale spatial gradients of connectivity at voxel level were used to characterize cerebellar connectome properties, which provide a low-dimensional representation of cerebellar connectivity, i.e., a sensorimotor-supramodal hierarchical organization. This multivariate analysis revealed significant correlated patterns of cerebellar connectivity gradients and behavioral measures that could be represented into four latent dimensions: general psychopathology, impulsivity and mood, internalizing symptoms and executive dysfunction. Each dimension was associated with a unique spatial pattern of cerebellar connectivity gradients across all participants. Multiple control analyses and 10-fold cross-validation confirmed the robustness and generalizability of the yielded four dimensions. These findings highlight the relevance of cerebellar connectivity as a necessity for the study and classification of transdiagnostic dimensions of psychopathology and call on researcher to pay more attention to the role of cerebellum in the dimensions of psychopathology, not just within the cerebral cortex.

Coronavirus 19 (COVID-19) has infected over 400 million people worldwide. Although COVID-19 causes predominantly respiratory symptoms, it can affect other organs including the brain, producing neurological symptoms. People with epilepsy (PWE) have been particularly impacted during the pandemic with decreased access to care, increased stress, and worsening seizures in up to 22% of them probably due to multiple factors. COVID-19 vaccines were produced in a record short time and have yielded outstanding protection with very rare serious side effects. Studies have found that COVID-19 vaccination does not increase seizures in the majority of PWE. COVID-19 does not produce a pathognomonic EEG or seizure phenotype, but rather 1 that can be seen in other types of encephalopathy. COVID-19 infection and its complications can lead to seizures, status epilepticus and post-COVID inflammatory syndrome with potential multi-organ damage in people without pre-existing epilepsy. The lack of access to care during the pandemic has forced patients and doctors to rapidly implement telemedicine. The use of phone videos and smart telemedicine are helping to treat patients during this pandemic and are becoming standard of care. Investment in infrastructure is important to make sure patients can have access to care even during a pandemic.

Background and Purpose/UNASSIGNED:The vascular tortuosity (VT) of the internal carotid artery (ICA), and vertebral artery (VA) can impact blood flow and neuronal function. However, few studies involved quantitative investigation of VT based on magnetic resonance imaging (MRI). The main purpose of our study was to evaluate the age and gender effects on ICA and VA regarding the tortuosity and flow changes by applying automatic vessel segmentation, centerline tracking, and phase mapping on MR angiography. Methods/UNASSIGNED:A total of 247 subjects (86 males and 161 females) without neurological diseases participated in this study. All subjects obtained T1-weighted MRI, 3D time-of-flight MR angiography, and 2D phase-contrast (PC) MRI scans. To generate quantitative tortuosity metrics from TOF images, the vessel segmentation and centerline tracking were implemented based on Otsu thresholding and fast marching algorithms, respectively. Blood flow and velocity were measured using PC MRI. Among the 247 subjects, 144 subjects (≤ 60 years, 49 males/95 females) were categorized as the young group; 103 subjects (>60 years, 37 males/66 females) were categorized as the old group. Results/UNASSIGNED:< 0.001). The age was observed to be positively correlated with the VT metrics. Compared to the males, the females demonstrated higher geometric indices within VAs as well as faster age-related vascular profile changes. After adjusting age and gender as covariates, maximum blood velocity is negatively correlated with geometric measurements. No association was observed between blood flux and geometric measures. Conclusions/UNASSIGNED:Vascular auto-segmentation, centerline tracking, and phase mapping provide promising quantitative assessments of tortuosity and its effects on blood flow. The neck arteries demonstrate quantifiable and significant age-related morphological and hemodynamic alterations. Moreover, females showed more distinct vascular changes with age. Our work is built upon a comprehensive quantitative investigation of a large cohort of populations covering adult lifespan using MRI, the results can serve as reference ranges of each decade in the general population.

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state ("cytokine storm") observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic.

One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue. We have previously developed novel thin-film, subdural electrode arrays with hundreds of microelectrodes over a 100-1000 mm² area to enable high-resolution mapping of neural activity. Here, we used these high-density arrays to study microscale properties of human epileptiform activity. We performed intraoperative micro-electrocorticographic recordings in nine patients with epilepsy. In addition, we recorded from four patients with movement disorders undergoing deep brain stimulator implantation as non-epileptic controls. A board-certified epileptologist identified microseizures, which resembled electrographic seizures normally observed with clinical macroelectrodes. Recordings in epileptic patients had a significantly higher microseizure rate (2.01 events/min) than recordings in non-epileptic subjects (0.01 events/min; permutation test, P = 0.0068). Using spatial averaging to simulate recordings from larger electrode contacts, we found that the number of detected microseizures decreased rapidly with increasing contact diameter and decreasing contact density. In cases in which microseizures were spatially distributed across multiple channels, the approximate onset region was identified. Our results suggest that micro-electrocorticographic electrode arrays with a high density of contacts and large coverage are essential for capturing microseizures in epilepsy patients and may be beneficial for localizing epileptogenic tissue to plan surgery or target brain stimulation.

Objective/UNASSIGNED:To identify and compare patient and procedural variables that are associated with a high radiation dose exposure and worse clinical outcomes between transradial arterial (TRA) and transfemoral arterial (TFA) approaches. Design/UNASSIGNED:This was a retrospective analysis. Setting/UNASSIGNED:A community hospital during the initial phase of adopting a TRA-first approach. Participants/UNASSIGNED:A resultant 215 subjects who only underwent diagnostic cerebral angiograms (DCA) after excluding all therapeutic procedures and patients under 18 years. Interventions/UNASSIGNED:Only DCA from 1 May 2018 to 31 January 2021. Main outcome measures/UNASSIGNED:We compared radiation exposure parameters (total fluoroscopy time (FT), total radiation dose (TD) and dose area product (DAP), number of vessels injected and Patient-Reported Global Health Physical and Mental Outcome Scores (PROGHS) at 30 days postprocedure between groups. Results/UNASSIGNED:FT was significantly greater in TRA compared with TFA (p<0.001). In addition, TRA had a significantly higher TD (p=0.002) and DAP (p=0.005) when compared with TFA. Analysis of only 6-vessel DCAs also showed that TRA had a significantly higher FT, DAP and TD in comparison to TFA. Despite observing a longer FT in TRA, results showed fewer vessels injected and a notably lower success rate in acquiring a 6-vessel DCA using the TRA. Further analysis of the effect of vessel number on FT using general linear models showed that with every increase of one vessel, the FT increases by 2.2 min for TRA (p<0.001; 95% CI 1.03 to 3.36) and by 1.3 min for TFA (p<0.001; 95% CI 0.72 to 1.83). There was no significant difference between groups in PROGHS mental and physical t-scores at 30 days postprocedure, even though our cohort showed a significantly greater percentage of TRA procedures done in the outpatient setting. Conclusions/UNASSIGNED:Adopting a TRA first approach for DCAs may be initially associated with a higher radiation dose for the patient. Better strategies and devices are needed to mitigate this effect.

Although mRNA vaccine responses following previous coronavirus disease 2019 (COVID-19) infection have not been assessed in trials, it has been shown that serological evidence of previous COVID-19 generates strong humoral and cellular responses to one dose of mRNA vaccine. We describe a patient with prior COVID-19 infection who developed acute transient encephalopathy with elevated inflammatory markers within 24 h of her first injection of Moderna COVID-19 vaccine. A 69-year-old cognitively normal woman presented with intermittent inattention, disorientation, left/right confusion, weakness, gait instability, and decreased speech. Head CT, brain MRI and MRA, complete blood count, liver enzymes, hepatitis B serology, ammonia, thyroid function, vitamin B12, and pulse oximetry were normal. Electroencephalography performed 48 h after symptom onset showed diffuse triphasic waves, diffuse theta and delta slowing, and no posterior dominant rhythm. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG was positive and inflammatory markers were elevated. On day 5 post-vaccine, she returned to her baseline, without neurological sequelae. The reported patient likely developed a transient inflammatory encephalopathy associated with an abnormal immunologic reaction to one dose of COVID-19 vaccine, in the setting of remote COVID-19 infection (1 year prior), SARS-CoV-2 IgG-positivity, and multiple comorbidities. Physicians should be alert to possible postvaccination reactogenicity in individuals with SARS-CoV-2 IgG-positivity, including risk of neuro-inflammation.