EEG Changes and DNA Markers Related to taVNS in Stroke Patients: a Preliminary Study

To date, there are only few treatments available to help improve recovery after a stroke. Vagus nerve stimulation (VNS) is FDA approved for the treatment of epilepsy, migraines, and refractory depression. However, there are many novel applications that are being actively researched and show great promise. One such application is to enhance neurologic recovery after stroke. Dawson et al performed a clinical trial that showed implanted VNS improved motor recovery in patients with upper extremity motor deficits following an ischemic stroke. Due to its invasive nature, implanted VNS is often viewed as an impractical option. An alternative is to stimulate the vagus nerve externally, thus avoiding surgery and surgical complications. One approach is transcutaneous auricular VNS (taVNS) at the tragus. This region of the external ear is partially innervated by the auricular branch of the vagus nerve, making it a good site for cutaneous stimulation. The tragus also offers some advantages in terms of ease of applying electricity to the anterior wall of the external ear canal by being able to clip onto the tragus. Furthermore, studies have shown that stimulation through the auricular canal causes activation of the vagus nerve pathway, comparable to direct stimulation of the nerve itself. Thus far, the available literature has focused mostly on patients with chronic stroke (>6 months) showing preliminary safety and efficacy for such technique. Time-window might be an important factor impacting treatment efficacy. Applying taVNS in acute patients where neural plasticity is still occurring in a stable but healing brain might be more impactful than in chronic patients where most of the damages have occurred and neural plasticity has slow down drastically. One double-blinded randomized controlled study by Li and co-workers (2022) in 60 acute stroke patients showed that combining taVNS with conventional rehabilitation improved safely the recovery of motor functions at follow-up (until one year post-treatment) as compared to sham. However, that study does not investigate the biomechanisms of such recovery. Understanding how taVNS changes neural functioning is nevertheless crucial in order to understand its mechanisms of action in the acute stage. In this study, electroencephalography (EEG) will be used since this technique is easily implementable in clinical settings and, since a substantial amount of research have linked EEG recordings at rest (e.g., delta to alpha power ratio) to later recovery after stroke. Previous research was also limited to assessing motor recovery and could benefit from a more holistic approach including the assessment of its impact on cognitive recovery. Our study will also use genetic markers. Indeed, genetic markers have been highlighted in more recent years as potentially yielding precious information on how predisposing factors related to brain structure and functioning can impact an individual's outcome. Prior research suggests that presence of DNA markers, such as brain-derived neurotrophic factor (BDNF), and/or catechol-O-methyltransferase (COMT) influence stroke patients' recovery (8-14). Specific BDNF polymorphisms can be associated with motor deficits (i.e., altered short-term plasticity and motor learning) (9, 11), while some of COMT polymorphisms can be associated with lower dopamine levels in the prefrontal cortex (12-13). Finally, taVNS sessions were given to acute patients while hospitalized over the course of 4 weeks while the average length of stay in the US is between 1 and 3 weeks depending on the severity of impairments in stroke patients. Therefore, this sham-controlled study will also assess if both motor and cognitive improvements can be obtained in stroke patients using a shorter time frame (2 weeks).

Inclusion criteria

• First-time Cerebrovascular Accident (Ischemic or Hemorrhagic)
• Within a month post-injury
• Presence of motor impairments (FMA-U≤62)

Exclusion criteria

• Advanced cardiac, pulmonary, liver, or kidney disease
• Bradycardia (Resting HR < 60)
• Presence of Apraxia, Aphasia or confusion
• Other musculoskeletal or neurologic diseases that could interfere with the outcome measures
• Previous surgical intervention on the vagus nerve
• Participation in other clinical trials
• Alcohol or drug abuse