A patient's socioeconomic status (SES) should not predict their post-stroke disability but individuals with low SES are more disabled and have higher mortality rates compared to individuals with high SES. These inequities are not isolated to low- and middle-income countries. In the United States, individuals with low SES are more disabled at 3 months and less likely to be independently ambulatory or discharged to their own homes. There are many factors contributing to these outcomes; however, one critical feature is access to affordable care. Many newly developed rehabilitation therapies and technologies require expensive equipment (e.g. instrumented treadmills, transcranial magnetic stimulation) and extensive training for clinical staff. The extra costs (financial and training) ensure that these state-of-the-art options are only available at metropolitan, well-funded institutions or to individuals who can afford additional healthcare costs. There is an urgent need for accessible, low-cost solutions capable of being delivered at underfunded hospitals and to individuals with no or low insurance coverage.

Startle Adjuvant Rehabilitation Therapy (START) represents an accessible and low-cost solution that can be delivered to rural and socioeconomically disadvantaged populations. START is the application of a startling, acoustic stimulus alongside traditional therapy. Distinct from other auditory treatments (e.g. metronome, music), administration of a START represents an endogenous activation of the brainstem (i.e. reticular formation) a phenomenon referred to as startReact. Rather than being a standalone treatment, START is adjuvant. An adjuvant is considered the introduction of an agent (traditionally pharmacological) that contributes to or enhances an existing medical regimen. Similarly, START is applied within a standard clinical practice to enhance and accelerate skill re-learning through activation of the brainstem.

START has been advanced as an adjuvant therapy tool because of the profound way it enhances training outcomes in individuals with stroke, in particular severe stroke. This is particularly compelling given the high degree of difficulty in generating functional changes in individuals with chronic, severe stroke. There is emerging evidence that individuals with stroke strengthen ipsilateral reticulospinal connections during the process of recovery. Thus, START may represent a priming of the nervous system to engage the reticular formation, which is nearly always spared post-stroke, during therapy to enhance both training and long-term outcomes. Though provocative, there are critical gaps in the literature that are required before START can be deployed in the clinic. Here, the investigators propose to 1) perform a rigorous randomized controlled trial during tasks of functional significance (Aim 1), and 2) assess the capacity of START training to generalize to untrained tasks (Aim 2).

Aim 1: Evaluate the capacity of START to enhance training outcomes in individuals with stroke (iwS). The objective of this aim is to demonstrate that START can enhance tasks of clinical and functional significance like those performed during therapy. The investigators propose a randomized, single-blind, parallel, controlled trial evaluating the impact of START on training outcomes of a functional reaching task in iwS. Hypothesis 1: The rate of learning and retention will be larger during training with START compared to control (training without START).

Aim 2: Evaluate the generalizability of START training to untrained tasks. To be viable as an adjuvant clinical tool to enhance activities of daily living, training benefits attributable to START must translate beyond the specific tasks trained during therapy. The investigators propose to evaluate skill transference using sorting and dressing tasks. Hypothesis 2: Training with START will show higher skill transfer (e.g. time to complete sorting/dressing task) compared to training without START.

SIGNIFICANCE \& IMPACT Imagine the transformative impact of an inexpensive tool that could be implemented not only in well-funded, metropolitan hospitals but also in small, rural, and socioeconomically disadvantaged hospitals enhancing recovery for iwS regardless of disability severity, socioeconomic status, or location. Every year, $43,000,000,000 is paid for care and therapy of the 7,000,000 stroke survivors living in the US but six months post-stroke 65% of patients cannot use their impaired hand during activities of daily living (e.g. feeding, toileting) and 63.5% of stroke survivors will never achieve a total Fugl-Meyer score greater than 90/226 - i.e. severe disability. These statistics are worse for individuals with low SES. A recent, 2018 study demonstrated that patients from low SES backgrounds received less in-patient and out-patient care and were discharged more quickly leading to higher levels of disability and mortality.

If successful, this study will revolutionize treatment for stroke survivors because START is non-invasive, inexpensive, and mobile making it accessible to rural and socioeconomically disadvantaged populations. START's application is a loud, acoustic stimulus timed with planned motor activity and can be administered via headphones. Unlike many new rehabilitation devices/techniques, START represents an extremely safe intervention (the application is a loud sound well beneath OSHA (Occupational Safety and Health Administration) regulations with no reported adverse reactions since its discovery. Thus, clinical staff training and safety protocols are minimal further decreasing application costs. Finally, it is mobile and easily packaged, so it can be administered via the increasing number of telemedicine programs designed for rural populations. Finally, START allows severe stroke survivors to participate in and benefit from therapy. The benefits of START are not contained to severe stroke survivors (e.g. improvement of hand extension in mildly disabled patients) but the capacity of START to work in severe patients significantly increases the potential of this tool to assist patients across all levels of disability.