RESPIRATORY-MOTOR INTERACTION AND ITS POTENTIAL APPLICATION IN SPASTICITY MANAGEMENT

Until this is written in protocol format with easily understood instructions it is useless. 

 RESPIRATORY-MOTOR INTERACTION AND ITS POTENTIAL APPLICATION IN SPASTICITY MANAGEMENT

Sheng Li, MD, PhD
Objective:
 During voluntary breathing, humans suppress automatic control of breathing through cortical activation. Brain imaging studies have demonstrated extensive activation of cortical areas bilaterally during voluntary breathing, including the primary motor cortex (M1), the premotor cortex and the supplementary motor area. These breathing associated M1 areas are distinctly different from the M1 areas for nonrespiratory skeletal muscles. The descending respiratory corticospinal pathways activated during voluntary breathing can bypass the brain stem respiratory centers and provide direct cortical control to the spinal respiratory motoneurons. During normal functioning, spinal motoneu-rons are able to integrate different sources, including descending cortico and bulbo spinal inputs and peripheral afferent inputs into a segmental interneuronal network. As such, it is hypothesized that the voluntary breathing associated M1 cortical areas could act in concert directly and/or indirectly with the descending skeletal motor drive to the nonrespiratory skeletal muscles, thus modulating corticospinal excitability of, and subsequently influencing the motor functions of these muscles. My previous studies have demonstrated that voluntary breathing could influence behaviors of nonrespiratory finger muscles. The objectives of this study were to: 1) objectively quantify modulation of corticospinal excitability of finger flexors and extensors during voluntary breathing using transcranial magnetic stimulation (TMS) and electrical stimulation (ES), and 2)explore the potential clinical application of the newly discovered phenomenon in patients with chronic neurologic disorders.
 Design:
 There were three experiments in this study (experiments 1 and 2 with normals, and experiment 3 with neurologic diseases). In experiments (Exp) 1 and 2, young and healthy subjects were instructed to breathe via a face mask normally (NORM); to exhale (OUT) or inhale (IN) as fast as possible in a self paced manner; or to voluntarily hold breath (HOLD). Subjects were comfortably seated with forearm and wrist joint secured. Fingers were stabilized against force sensors. In Exp 1 (n=14, 5 male, 9 females,mean: 25.5 yrs of age; age range: 23 to 28), TMS was applied to the M1hand area during 10% maximal voluntary contraction (MVC) fingerflexion force production or at rest. Similarly, in Exp 2 (3 males, 8 females,mean: 28.2 yrs of age; age range: average: 24–39), ES to the finger flexorsor extensors was delivered during the above 4 breathing conditions while subjects maintained 10% MVC of finger flexion or extension and at rest. Inthe exploratory clinical experiments (Exp 3), four patients with chronic neurologic disorders (3 strokes: 53–75 yrs of age, stroke: 19–48 months;1 traumatic brain injury: 27 yrs of age, TBI: 13 yrs) received a 30-minsession of breathing controlled electrical stimulation to finger extensors of the impaired side. Data analysis: In Exp 1, motor-evoked potentials (MEP) were recorded from flexor digitorum superficialis (FDS), extensor digitorum communis (EDC) and abductor digiti minimi (ADM) muscles.In Exp 2, finger force responses to ES were measured. Dependent variables (MEPs, force responses) were analyzed using Repeated measure ANOVAs. The significance level was  p≤0.05. In Exp 3, descriptive statistics were used to compare pre and post intervention changes infinger flexor spasticity using modified Ashworth scale (MAS).
 Results:
 InExp 1, The EDC MEP magnitudes increased significantly during IN andOUT at both 10% MVC and rest, the FDS MEPs were enhanced only at10% MVC; while the ADM MEP increased only during OUT, as comparedto NORM for both at rest and 10% MVC (FDS, F[3,39]=6.98, p<0.001;EDC, F[3,39]=14.00, p<0.0001; ADM, F[3,39]=4.71, p=0.007, respectively). No difference was found between NORM and HOLD for all three muscles. The results suggested that voluntary breathing associated increase in corticospinal excitability be a muscle specific modulation,rather than an overflow of excitability from cortical respiratory center to primary motor cortex. In Exp 2, when the finger flexors were stimulated at rest or during 10% MVC finger flexion force, force response was enhanced during both IN and OUT only at 10% MVC (F[3,39]=6.22,p=0.002). When the extensors were stimulated, force response increased at both 10% MVC and rest, only during IN, but not OUT (F[3,30]=3.46,p=0.028). The averaged response latency was 83 ms for the fingerextensors and 79 ms for the finger flexors. These results demonstrated further that voluntary breathing-associated modulation of corticospinal excitability for finger flexors and extensors were respiratory phase dependent, i.e., there was a coupling between finger extension and forced inhalation. As such, when electrical stimulation to the finger extensors is triggered by and delivered only during forced inhalation, the induced-response is hypothesized to be enhanced by voluntary breathing. A new intervention technique – breathing controlled electrical stimulation was developed and explored in Exp 3. After a 30-min intervention, a remarkable reduction in finger flexor spasticity (MAS from 2.9 to 1.4) was observed. The reduction has lasted for at least 4 wks in all 4 patients. This exploratory clinical study further supported neurophysiological mechanisms mediating the respiratory motor interaction. The ES-induced enhancement in finger extensor excitability during forced inhalation, likely via reciprocal inhibition, resulted in reduction of finger flexor spasticity.This mechanism, however, needs to be investigated further.
 Conclusions:
Collectively, TMS and ES data demonstrate a muscle specific, phase-dependent modulation of corticospinal excitability of finger flexors and extensors during voluntary breathing. Specifically, there is a finger extension forced inhalation coupling. The newly developed intervention,breathing controlled electrical stimulation, has potential clinical application in spasticity management. Further randomized control studies,however, are needed to validate the effect of breathing controlled electrical stimulation on spasticity management.