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Functional Brain Imaging of Mind-Body Interaction in Stroke Recovery

S.G. Diamond, R. Howe*, D. Boas**, G. Stanley*, J. Dennerlein*
*Biorobotics Laboratory, Harvard University
**Photon Migration Laboratory, Massachusetts General Hospital

Support provided by the Charles A. Dana Foundation

Every year approximately 730,000 Americans have a new or recurrent stroke leaving 160,000 dead and nearly 300,000 with moderate to severe impairments requiring special care (National Stroke Association, 1998). The 4 million stroke survivors in America are cared for at an estimated annual cost of $30 billion. Both humans and other mammals can experience considerable recovery of motor function after surviving a stroke. Neurophysiological studies in human and animal models have repeatedly demonstrated the extensive potential of the adult cerebral cortex for functional and structural plasticity (Nudo, 1999; Jacobs, 1991). Functional imaging and lesion studies suggest that adjacent undamaged cortex and the contralateral hemisphere system assume the functions of the necrotic tissue (Chollet, 1991; Fisher 1992). Recently, the reorganization of motor cortex during recovery from stroke has been documented with fMRI (Cramer, 1997).


Physical impairments resulting from stroke arise from damage to the motor control components of the central nervous system. The standard of care is to treat the damaged motor control system with intensive physical therapy. Physical therapy for the treatment of stroke relies on sensory feedback to stimulate the motor learning that is required. The observation that motor learning is both a physical and mental process can help explain why factors such as personality and outlook are known to influence recovery (Kelly-Hayes, 1995). The proposed research uses hypnosis to affect the mental state of stroke patients to improve the efficacy of motor learning.
Case reports documenting the use of hypnosis in conjunction with stroke rehabilitation therapy date back to the 1950ís (Shires, 1954). Some of the reports describe extraordinary improvements leg and arm functional that occurred spontaneously during the hypnotic sessions and were retained during the following months (Manganiello, 1986; Chappell, 1964; Crasilnech, 1970). Others document dramatic increases in limb strength or range of motion occurring from 6 to 18 months after the stroke event when further functional improvement was not expected (Holroyd, 1989). Hypnosis has also been used to improve patient tolerance of standard therapy (Appel, 1990). Although the published reports are case studies, the positive trend suggests that hypnosis may tap into cognitive resources that improve motor learning beyond standard physical therapy.

Hypnosis is a mental state characterized by dissociation, focused attention and suggestibility. Many specific theories on what actually happens during hypnosis have been published but the explanations vary widely. Standard methods for determining if a subject is hypnotized rely on subjectively grading responses to a series of suggestions. One of the fundamental problems with studying hypnosis is that a subject's response to hypnotic suggestions can vary depending on the context and specific nature of the suggestion and the skill of the investigator. Hypnosis is sometimes described as a state wherein the electroencephalography (EEG) contains an increase in theta brainwaves (Hammond, 1998). Studies of the hypnotic state with positron emition tomography (PET) have characterized neuronal correlates of certain hypnotic suggestions (Rainville, 1999; Maquet 1999).

Diffuse Optical Tomography
A potentially powerful tool for studying hypnosis and stroke recovery is diffuse optical tomography (DOT). DOT is a noninvasive optical imaging wherein near-infrared light is applied to the tissue surface and then detected some distance from the source. Changes in the intensity of remitted light indicate changes in the optical properties of the tissue between the source and detector. Near-infrared light in the wavelength range of 600-900 nm scatter through biological tissues relatively well because water absorption and hemoglobin absorption effects are small. This optical imaging window used by DOT is illustrated in the absorption spectra for hemoglobin and water in figure 1. The biological basis of DOT contrast is that the concentration of oxygenated and deoxygenated hemoglobin in the tissue will change in response to neurological activity through what is called neurovascular coupling. DOT uses a pattern of near-infrared light sources and detectors positioned on the scalp to generate maps of spatially variant hemodynamics in the underlying tissue.

Specific Aims
  1. Define physiological changes that can be used to quantify the depth of the hypnotic state during experiments.
  2. Contribute to DOT technology development to improve its spatial resolution and the accuracy images reconstructed from hemodynamic changes.
  3. Conduct a clinical study on the effects of hypnosis on stroke recovery.
    1. Quantify the effects of hypnosis on motor task performance by stroke patients.
    2. Seek evidence of the effects of hypnosis on motor cortex reorganization in stroke patients using fMRI and DOT.
    3. Determine if hypnotic-induced gains in motor performance are maintained at follow up.

This will be the first study to investigate the effects of hypnosis on stroke patients with functional brain imaging.The research also will be the first to correlate the depth of hypnotic state during experiments with measured outcomes.

Research Plan
Quantification of the Hypnotic State
Research on hypnosis would be greatly enhanced by using physiological measures to quantify the depth of the hypnotic trance during experiments. This has not been done in previous research because no method for quantifying the hypnotic state is available. One possible measure of hypnotic depth is the control of the heart rate by the autonomic nervous system. Variations in the time between beats of the heart is termed heart rate variability (HRV). Entrainment of the heart rate at the respiratory rhythm via vagal innervation of the sino atrial node is a well-documented phenomenon called respiratory sinus arrhythmia (RSA). A study by Peng et al. (1999) found that RSA was significantly larger during meditation than during the control conditions of rhythmic breathing, sleeping, or spontaneous respiration by elite athletes. Another study found increased RSA in the HRV power spectrum during hypnosis (DeBenedittis, 1994). When viewed as a measure of cognitively mediated parasympathetic control over the heart, RSA changes during hypnosis are a good candidate for quantifying the depth of the hypnotic state. The use of HRV to quantify the hypnotic state will first be studied with normal subjects and later expanded to include elderly stroke patients.

Pseudo phase-space plots of filtered heart rate variability (HRV) data for the same subject during baseline and hypnosis conditions. The lag k is 10 data points which corresponds to approximately 1 second. The attractor formed by the hypnosis condition HRV is more clearly defined.
Histogram of Lyapunov exponents calculated from heart rate variability (HRV) data from baseline and hypnosis conditions. The two conditions are clearly separated into different distributions.

Technology Development for DOT
Diffuse optical tomography (DOT) has tremendous potential as a functional brain imaging modality for the investigation of hypnosis and stroke recovery. The Photon Migration Laboratory headed by David Boas, Ph.D. is developing DOT for clinical use. I have become involved in the design of the cap that holds the optodes on the subject's head. My current design holds 25 optical fibers in various patterns covering most of the scalp. Future DOT imaging systems will require a cap that supports as many as 64 optodes. The cap design for future DOT systems will integrate the optodes and optic fibers directly into the cap. An integrated cap requires that the pattern of source and detector fibers remains fixed. At the present time a fixed pattern has been avoided because it is not known what arrangement will provide for optimal image reconstruction of the functional brain activity in the underlying tissue. The logical progression is to first optimize the optode array geometry and image reconstruction algorithms through analytical analysis and computational modeling. The integrated DOT cap can then be designed to the resulting specifications. In addition to working on the cap design I am working to improve the homonymic signal to noise ratio by modeling physiological artifacts and I am experimenting with different methods of image reconstruction and visualization.

[pic] Simulated image reconstruction.
Top Row: Simulated "true" image to be reconstructed; arrangement of sources and detectors; total sensitivity from all source-detector pairs.
Middle Row: Image reconstruction by back projection; back projection normalized by dividing by total sensitivity; and by inversion of the sensitivity functions.
Bottom Row: Spatial errors resulting from the three image reconstruction techniques. The inversion technique has the least error.

Clinical Research on Hypnosis and Stroke
The clinical research is based on the hypothesis that hypnotic regression to time periods prior to the stroke event will enhance motor cortex reorganization and improve limb performance in chronic stroke patients. Ten subjects with a unilateral stroke affecting the upper extremity will participate. Subjects will be selected who had a stroke at least one year ago so that spontaneous recovery is not expected. Since upper extremity function will be the focus of the intervention, subjects must be able to perform the functional tasks but with some deficit. Each subjects is expected to undergo 12 testing sessions over a period of 2 to 3 months.

A repeated measures experimental design will be used wherein motor function is repeatedly assessed during the initial sessions prior to beginning the hypnosis intervention to establish a stable baseline. The hypnotic intervention will then be applied for 4 to 8 sessions and will be followed by up to 4 post-intervention sessions. Functional brain imaging will be conducted during the baseline and intervention periods. Standardized physical therapy tests will be used to assess upper extremity range of motion, strength, coordination and dexterity. Induction of the hypnotic state will be accomplished by standard methods involving sequential relaxation of the body combined with mental imagery. The hypnotic suggestions will focus on mental rehearsal and revivification of successful task performance. The control condition for the hypnotic intervention will be conversation with the subject to build and maintain rapport and encouragement for maximal task performance.

The simplicity and low cost of the hypnosis intervention creates a tremendous potential for broad clinical application and lasting benefits to stroke survivors. The proposed research will provide the strongest evidence to date and new insights into exactly how brain plasticity can be stimulated with an easily applied psychological intervention. The role of belief and expectancy is paramount in the brain-body interaction that occurs during recovery after stroke. This is an opportunity to produce the first quantitative evidence for a mechanistic explanation of how this interaction takes place.


National Stroke Association, Brain Attack Statistics,

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Chollet, F., V. DiPiero, et al. (1991). The Functional Anatomy of Motor Recovery After Stroke in Humans: A Study With Positron Emission Tomography. Ann. Neurol. 29(1): 63-71.

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