Brain and Nerve Stimulation for Hand Muscles in Spinal Cord Injury and ALS
Condition: Spinal Cord Injury (SCI); Amyotrophic Lateral Sclerosis (ALS)
MeSH terms: Spinal Cord Injuries; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional

Summary: 
      Most neurological injuries such as spinal cord injuries (SCI) and amyotrophic lateral
      sclerosis (ALS) spare a portion of nerve circuitry. Strengthening spared nerve circuits may
      be an important method to improve functional recovery.

      In this study, the investigators aim to use non-invasive magnetic and electrical stimulation
      to strengthen motor circuits between the brain and hands. Magnetic stimulation will be used
      over the motor cortex (scalp). Two methods of electrical stimulation will be compared:
      stimulation of the median nerve at the wrist; or direct stimulation of the cervical spinal
      cord across the skin on the back of the neck. Several different combinations of magnetic and
      electrical stimulation will be compared to find the conditions that best strengthen nerve
      circuits between the brain and hands - "Fire Together, Wire Together".

      PLEASE NOTE, THIS IS A PRELIMINARY STUDY. This study is testing for temporary changes in
      nerve transmission and hand function. THERE IS NO EXPECTATION OF LONG-TERM BENEFIT FROM THIS
      STUDY. If we see temporary changes in this study, then future studies would focus on how to
      prolong that effect.
    

Detailed description: 
      Most neurological injuries such as spinal cord injuries (SCI) and amyotrophic lateral
      sclerosis (ALS) spare a portion of nerve circuitry. Strengthening spared nerve circuits
      represents a critical method to improve functional recovery. Different forms of magnetic and
      electrical stimulation have been used to activate brain, spinal cord, nerve, or muscle
      tissue. Although in some cases, surgically implanted electrical stimulation has delivered
      tremendous benefit, a non-invasive approach to nerve stimulation is preferable.

      In this proposed study, the investigators aim to use non-invasive magnetic and electrical
      stimulation to strengthen motor circuits between the brain and hands. Transcranial magnetic
      stimulation (TMS) will be combined with either electrical stimulation of the median nerve at
      the wrist; or electrical transcutaneous stimulation of the cervical spinal cord. Magnetic and
      electrical stimulation will be precisely timed so that the pulses arrive at the target spinal
      motor neurons at roughly the same time - this precise timing is responsible for the
      phenomenon of "spike timing-dependent plasticity".

      Three groups of participants will be studied: individuals with chronic incomplete cervical
      SCI (n=12), individuals with definite or probable ALS (n=6), and individuals without
      neurological injury or disease (n=12). Subjects with SCI or ALS will have one screening visit
      to confirm eligibility for the study. All subjects will then undergo one baseline testing
      session followed by 7 sessions of unpaired or paired magnetic and electrical stimulation.
      Functional and physiological testing will be conducted prior to each stimulation session,
      then at 0, 15, 30, and 90 minutes post each session. Key measures include grip strength
      dynamometry, timed performance on a hand dexterity test, amplitude of abductor pollicis
      brevis (APB) response to TMS, integrated amplitude of APB F-wave responses, and duration of
      the 'cortical silent period' after TMS stimulation during APB contraction.

      PLEASE NOTE, THIS IS A PRELIMINARY STUDY. This study is testing for temporary changes in
      nerve transmission and hand function. THERE IS NO EXPECTATION OF LONG-TERM BENEFIT FROM THIS
      STUDY. If we see temporary changes in this study, then future studies would focus on how to
      prolong that effect.
    

Intervention name(s): Transcranial magnetic stimulation; Median nerve stimulation; Cervical transcutaneous stimulation
Intervention type(s): Device; Device; Device
Intervention description(s): One TMS pulse every 10 seconds for 20 minutes; One median nerve pulse every 10 seconds for 20 minutes; One cervical pulse every 10 seconds for 20 minutes
Other intervention name(s): MagPro R30; Digitimer DS7A; Digitimer DS7A
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Spinal Cord Injuries; Amyotrophic Lateral Sclerosis; Transcranial magnetic stimulation, single pulse; non-invasive brain stimulation