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Neuromechanics and Spinal Cord: Muscle and Motor Unit Redundancy

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Neuromechanics and Spinal Cord: Muscle and Motor Unit Redundancy Neuromechanics and Spinal Cord: Muscle and Motor Unit Redundancy Jason J. Kutch, Ph.D. Assistant Professor Louise Cosand University of Southern California AMPLAMPLDivision of Biokinesiology & Physical Therapy Dan Kirages, DPT Moheb Yani Overview • Biomechanics to Brain Pain • Muscle Redundancy • Motor Unit Redundancy • Think computation, act experimentation Biomechanics to Brain Pain © Farrar, Straus and Giroux Chronic pain: pain that extends beyond the expected period of healing1 1Turk and Okifuji, 2001 Biomechanics to Brain Pain My Ph.D. training was interdisciplinary Tony Bloch, Ph.D. Art Kuo, Ph.D. Zev Rymer, M.D. Ph.D. Applied Mathematics Biomechanics Neurophysiology Biomechanics to Brain Pain Cycling + Stress = CP/CPPS? Biomechanics to Brain Pain Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) is a clinical condition presenting as chronic pelvic pain for 3 months within a 6-month period, with a variable degree of urinary and sexual dysfunction in the absence of any identifiable pathology.1 • Prevalence: 6 - 12% (Most frequent urological diagnosis for men under 50).2 • Virulence: Accounts for 8% of urological visits and 1% of all primary care visits. QOL scores lower than CHF, diabetes, and Crohn’s disease.2 • Cost: $6,500 per patient per year.2 1. Krieger et al., 1999 2. Allsop et al., 2011 Biomechanics to Brain Pain % office visits 2008 National Ambulatory Medical Care Survey with condition 5.7% Allsop et al., 2011 present 1.7% 0.44% Cancer CP/CPPS CHF Biomechanics to Brain Pain % office visits with condition 5.7% present Other Uterine corpus Thyroid Kidney & renal pelvis Non-Hodgkin lymphoma Urinary bladder Melanoma-skin Colon Lung Breast Prostate 0.44% Cancer By type CP/CPPS Biomechanics to Brain Pain Current (conservative) Treatment Options • Long (3 months+) course of antibiotics.1 • Combination of physical therapy and relaxation techniques.2 • Aerobic exercise.3 1. Allsop et al., 2011 2. Anderson et al., 2005 3. Giubilei 2007 Biomechanics to Brain Pain Problem with current treatments 40 35 30 25 20 15 Percent of Patients 10 5 0 Worse 25-49% No change 50% or greater Less than 25% Improvement in Pain Anderson et al., 2005 Biomechanics to Brain Pain Several approaches, little objective plan “Out-of-tune approach” “In-tune approach” Aerobic exercise Physical therapy and relaxation Giubilei et al., 2007 Anderson et al., 2005 “Pharmaceutical approach” Alpha-blockers, tricyclic anti-depressants, etc. Allsop et al., 2011 Biomechanics to Brain Pain Biomechanics to Brain Pain Biomechanics to Brain Pain Central question in CP/CPPS research A CP/CPPS Phenotype End-organ disease Central pain syndrome End-organ disease and/or Central pain syndrome? Persistent CNS correctly CNS amplifies Pelvic processes normal input or Pain nociceptive creates pain input Kutch et al., In Review Biomechanics to Brain Pain Potential CP/CPPS patient stratification B CP/CPPS Population Central pain syndrome fMRI and other Imaging Modalities End-organ disease Patient-specific combination Kutch et al., In Review Biomechanics to Brain Pain PT targets soft tissues, nerves, and muscles, including neuromuscular education Biomechanics to Brain Pain Our fMRI/PT approach Biomechanics to Brain Pain Our fMRI/PT approach BRAIN FUNCTION AND ANATOMY IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME 119 in figure 2, A. The brain regions activated, their coordinates in standard space and magnitude of ac- tivity are shown in the table. In addition to the pain of CP/CPPS, this task required attention, motor con- trol and evaluation of magnitudes. The visual con- trol task contained all of these same cognitive de- mands without being related to CP/CPPS pain. Therefore, the activity for visual control identified brain areas activated in the task but not related to CP/CPPS (fig. 2, A). More importantly by contrast- ing activity between the pain task and visual task (spontaneous pain – visual), we pinpointed brain regions where activity was preferentially and, thus, more specifically, related to the perception of CP/ CPPS pain. This result is shown in figure 2, B, and Figure 1. Spontaneous pain rating task in patients with CP/ included ant INS and secondary somatosensory cor- CPPS. A, patients used finger-span logging device to continu- tex. The opposite contrast (visual – spontaneous ously rate fluctuations in spontaneous pelvic pain (in absence of pain) revealed visual task related activity. Age and external stimulus) on scale from 0 to 10 by opening and closing depression scores were used as covariates of no in- fingers. B, inside scanner patients received feedback of pain ratings in real time, presented as visual bar projected onto terest (eg confounding variables) in all functional screen that fluctuated on scale from 0 to 10. C, examples of analyses. spontaneous pain ratings from 3 patients with CP/CPPS. Individ- To determine the clinical relevance of these find- ual patients exhibited distinct overall pain magnitudes and vary- ings, average brain activity from regions preferen- ing levels of fluctuations around mean spontaneous pain. Rat- tially involved in CP/CPPS pain were extracted and ings were used as explanatory variables in fMRI analyses to identify related brain activity. correlated with predetermined clinical variables. BiomechanicsAnt INS activity was to significantly Brain positively Pain corre- lated with self-reported spontaneous pelvic pain in- cortex. Peak ROI activity (averaged for 27 voxels) was tensity (r ϭ 0.57, p Ͻ0.05; fig. 3, A), indicating that extracted from each subject and related to clinical param- brain activity characterizing the spontaneous pain eters.BRAIN FUNCTION AND ANATOMY IN CHRONIC PROSTATITIS/CHRONICexperienced by men PELVIC with CP/CPPS PAIN SYNDROME was related to 119 Analysis of global and regional anatomical differences. We investigated global and regional gray differences based on the T1-weighted anatomical images obtained from 16 patients with CP/CPPS and 16 matched controls in figure 2, A. The brain regions activated, their using described methods.11 Brain white matter properties coordinates in standard space and magnitude of ac- were studied based on the DTI images obtained from 10 tivity are shown in the table. In addition to the pain patients with CP/CPPS and 10 matched controls using of CP/CPPS, this task required attention, motor con- described methods. trol and evaluation of magnitudes. The visual con- trol task contained all of these same cognitive de- RESULTS mands without being related to CP/CPPS pain. Participant Characteristics Therefore, the activity for visual control identified Men with CP/CPPS (mean age 36.94 years old) re- brain areas activated in the task but not related to ported pelvic pain for an average of 3 years with a CP/CPPS (fig. 2, A). More importantly by contrast- mean 4.5/10 current pain intensity. Global NIH- ing activity between the pain task and visual task CPSI scores ranged from 19 to 35 (mean 28.56, SE (spontaneous pain – visual), we pinpointed brain 1.17) with an average pain subscore of 13.56 (SE regions where activity was preferentially and, thus, 0.81). Participants reported pelvic (100%), penis tip more specifically, related to the perception of CP/ (75%), perineal (66%) and testicle (58%) pain with no CPPS pain. This result is shown in figure 2, B, and history of other chronic pain. Of the 16 men 7 were Figureincluded 2. Group ant brain INS activity and secondary maps for spontaneous somatosensory pain and cor- Figuretaking 1. Spontaneous medication pain and rating none task used in tricyclics patients withor gaba- CP/ visual rating tasks in CP/CPPS. A, group average brain activity tex. The opposite contrast (visual – spontaneous CPPS.pentinoids.A, patients used finger-span logging device to continu- for spontaneous pain rating task and for visual rating task. B, ously rate fluctuations in spontaneous pelvic pain (in absence of contrastpain) revealed between pain visual and visual task tasks related shows activity. areas that Age were and externalBrain stimulus) Activity on scale for Spontaneous from 0 to 10 by Pain opening in CP/CPPS and closing moredepression specifically scores active were during used spontaneous as covariates pain of CP/CPPS of no in- fingers. B, inside scanner patients received feedback of pain (red-yellow), and included right anterior insula and parietal re- Conscious subjective rating of spontaneous fluctua- terest (eg confounding variables) in all functional ratingstions in real of CP/CPPS time, presented pain during as visual a period bar projected of 10 minutes onto gions. Regions with higher activity during visual task (visual – pain)analyses. are shown as negative activity (blue-green). screenFarmerresulted that et fluctuatedal., in 2011 the group on scale averaged from 0 brain to 10. activityC, examples shown of spontaneous pain ratings from 3 patients with CP/CPPS. Individ- To determine the clinical relevance of these find- ual patients exhibited distinct overall pain magnitudes and vary- ings, average brain activity from regions preferen- ing levels of fluctuations around mean spontaneous pain. Rat- tially involved in CP/CPPS pain were extracted and ings were used as explanatory variables in fMRI analyses to identify related brain activity. correlated with predetermined clinical variables. Ant INS activity was significantly positively corre- lated with self-reported spontaneous pelvic pain in- cortex. Peak ROI activity (averaged for 27 voxels) was tensity (r ϭ 0.57, p Ͻ0.05; fig. 3, A), indicating that extracted from each subject and related to clinical param- brain activity characterizing the spontaneous pain eters. experienced by men with CP/CPPS was related to Analysis of global and regional anatomical differences. We investigated global and regional gray differences based on the T1-weighted anatomical images obtained from 16 patients with CP/CPPS and 16 matched controls using described methods.11 Brain white matter properties were studied based on the DTI images obtained from 10 patients with CP/CPPS and 10 matched controls using described methods. RESULTS Participant Characteristics Men with CP/CPPS (mean age 36.94 years old) re- ported pelvic pain for an average of 3 years with a mean 4.5/10 current pain intensity.
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