TURN-IT: a novel turning intervention program to improve quality of turning in daily life in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have a high fall rate and many falls are associated with turns. Despite this, there is minimal research on effects of rehabilitation on the quality of turns. Further, quantifying turns in the home may have broader implications since rehabilitation of turns would ideally improve turning in real world mobility. METHODS: Sixty people with PD and a history of falls will be randomized to receive either a novel TURNing InTervention (TURN-IT) or no intervention (control group). The TURN-IT group will be seen for 6 weeks (18 visits) for an individualized, progressive program that is based on the specific constraints of turning in PD. Wearable sensors will be used to measure 7 days of mobility, including turns, before and after intervention or control period. In addition, blinded assessments of gait, mobility and turns will occur before and after intervention for both groups and falls will be monitored for twelve months post intervention with bimonthly email questionnaires. DISCUSSION: This study has the potential to change how we rehabilitate and assess turning in people with PD and falls. There are several novel aspects to our study including a comprehensive turning-focused intervention that is tailored to the underlying constraints that impair turning in people with PD. Further, our outcome measure of turning quality during 7 days of daily life is novel and has implications for determining real-life changes after rehabilitation. The ultimate goal of this rehabilitation intervention is to improve how patients turn in daily life and to reduce falls. TRIALS REGISTRATION: This protocol is registered at clinicaltrials.gov; #NCT04897256; https://clinicaltrials.gov/ct2/show/NCT04897256?term=Horak&cond=Parkinson+Disease&draw=2&rank=4 .

Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease: a randomized clinical trial.

BACKGROUND: There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. METHODS/DESIGN: This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. DISCUSSION: The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. TRIAL REGISTRATION: This trial is registered at clinical trials.gov (NCT02231073).

Compensatory stepping in Parkinson's disease is still a problem after deep brain stimulation randomized to STN or GPi.

The effects of deep brain stimulation (DBS) on balance in people with Parkinson's disease (PD) are not well established. This study examined whether DBS randomized to the subthalamic nucleus (STN; n = 11) or globus pallidus interna (GPi; n = 10) improved compensatory stepping to recover balance after a perturbation. The standing surface translated backward, forcing subjects to take compensatory steps forward. Kinematic and kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS, combined with off and on levodopa medication. Responses were compared with PD-control subjects (n = 8) tested over the same timescale and 17 healthy control subjects. Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before surgery (DOPA) for the PD-GPi group and the PD-control group. For the PD-STN group, there were more lateral weight shifts, a delayed foot-off, and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery. Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery, whereas the number of falls in the GPi and PD-control groups were unchanged. DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group.

Anticipatory postural adjustments prior to step initiation are hypometric in untreated Parkinson's disease: an accelerometer-based approach.

BACKGROUND AND PURPOSE: Anticipatory postural adjustments (APAs), prior to step initiation, are bradykinetic in advanced Parkinson's disease (PD) and may be one of the factors associated with 'start hesitation'. However, little is known about APAs in the early stage of PD. In this study, we determined whether body-worn accelerometers could be used to characterize step initiation deficits in subjects with early-to-moderate, untreated PD. METHODS: Eleven PD and 12 healthy control subjects were asked to take two steps. Postural adjustments were compared from center of pressure (COP) and from acceleration of the trunk at the center of mass level (L5). RESULTS: Our findings show that APAs measured from the peak COP displacement toward the swing leg and the peak trunk acceleration toward the stance leg were smaller in untreated PD compared with control subjects. The magnitude of APAs measured from peak COP displacements and accelerations were correlated. CONCLUSION: These results suggest that quantitative analysis of step initiation from one accelerometer on the trunk could provide useful information for the characterization of patients in early stages of PD, when clinical evidence of start hesitation may not be detectable. Ambulatory monitoring of step initiation is also promising for monitoring patient progression in the home environment, and eventually providing feedback for preventing freezing of gait episodes.

Feedback equilibrium control during human standing.

Equilibrium maintenance during standing in humans was investigated with a 3-joint (ankle, knee and hip) sagittal model of body movement. The experimental paradigm consisted of sudden perturbations of humans in quiet stance by backward displacements of the support platform. Data analysis was performed using eigenvectors of motion equation. The results supported three conclusions. First, independent feedback control of movements along eigenvectors (eigenmovements) can adequately describe human postural responses to stance perturbations. This conclusion is consistent with previous observations (Alexandrov et al., 2001b) that these same eigenmovements are also independently controlled in a feed-forward manner during voluntary upper-trunk bending. Second, independent feedback control of each eigenmovement is sufficient to provide its stability. Third, the feedback loop in each eigenmovement can be modeled as a linear visco-elastic spring with delay. Visco-elastic parameters and time-delay values result from the combined contribution of passive visco-elastic mechanisms and sensory systems of different modalities.

A critical maturational period of reduced brain vulnerability to developmental injury. I. Behavioral studies in cats.

Groups of cats with resection of the neocortex of the left cerebral hemisphere at postnatal (P) ages (in days) 5-15 (P10), 30 (P30), 60 (P60), 90 (P90), 120 (P120), and in adulthood, were compared using a comprehensive battery of 16 neurobehavioral tests administered when they were at least 6 months post-lesion. For all behaviors, except 3 (including the paw contact placing reaction which never recovered), the performance was significantly better for the cats lesioned between P10 and P30 compared to cats lesioned at older ages. For 10 of the behaviors, the transition from age-at-lesion P30 to P60 was rather abrupt and characterized by a significant increment in impairments. However, cats with the resection at ages P90 and P120 still showed some behavioral advantage over the adult-lesioned animals. Overall, for most of the behaviors tested, there was a significant linear trend for an increase in the magnitude of impairments across the entire age-at-lesion range. We previously reported that cats with a unilateral frontal cortical lesion sustained during the late fetal life showed substantial behavioral impairments, while animals with a similar resection sustained early postnatally exhibited minimal abnormalities. These findings, together with the present results, indicate that the long-term behavioral outcome of neocortical injury is best when the lesion is sustained during a discrete period of the life of the cat. This period extends from about fetal age 55 days (the oldest lesion age in our fetal studies) to about P60, as shown in the present paper. For these reasons, we propose that there is a Critical Maturational Period (CMP) for optimal post injury brain and behavioral restoration. We hypothesize that this span of reduced vulnerability is linked to specific developmental morphological events which occur during the same time period. Since, as discussed, such ontogenetic events also occur in other mammal species (albeit at different chronological ages), we further propose that the timing of the CMP as delineated in cats, can be extrapolated to other higher mammals species including humans.

Forms of forward quadrupedal locomotion. II. A comparison of posture, hindlimb kinematics, and motor patterns for upslope and level walking.

To gain insight into the neural mechanisms controlling different forms of quadrupedal walking of normal cats, data on postural orientation, hindlimb kinematics, and motor patterns of selected hindlimb muscles were assessed for four grades of upslope walking, from 25 to 100% (45 degrees incline), and compared with similar data for level treadmill walking (0.6 m/s). Kinematic data for the hip, knee, ankle, and metatarsophalangeal joints were obtained from digitizing ciné film that was synchronized with electromyographic (EMG) records from 13 different hindlimb muscles. Cycle periods, the structure of the step cycle, and paw-contact sequences were similar at all grades and typical of lateral-sequence walking. Also, a few half-bound and transverse gallop steps were assessed from trials at the 100% grade; these steps had shorter cycle periods than the walking steps and less of the cycle (68 vs. 56%) was devoted to stance. Each cat assumed a crouched posture at the steeper grades of upslope walking and stride length decreased, whereas the overall position of the stride shifted caudally with respect to the hip joint. At the steeper grades, the range and duration of swing-related flexion increased at all joints, the stance-phase yield was absent at the knee and ankle joints, and the range of stance-phase extension at knee and ankle joints increased. Patterns of muscle activity for upslope and level walking were similar with some notable exceptions. At the steeper grades, the EMG activity of muscles with swing-related activity, such as the digit flexor muscle, the flexor digitorum longus (FDL), and the knee flexor muscle, the semitendinosus (ST), was prolonged and continued well into midswing. The EMG activity of stance-related muscles also increased in amplitude with grade, and three muscles not active during the stance phase of level walking had stance activity that increased in amplitude and duration at the steepest grades; these muscles were the ST, FDL, and extensor digitorum brevis. Overall the changes in posture, hindlimb kinematics, and the activity patterns of hindlimb muscles during upslope walking reflected the need to continually move the body mass forward and upward during stance and to ensure that the paw cleared the inclined slope during swing. The implications of these changes for the neural control of walking and expected changes in hindlimb kinetics for slope walking are discussed.

Forms of forward quadrupedal locomotion. III. A comparison of posture, hindlimb kinematics, and motor patterns for downslope and level walking.

To gain further insight into the neural mechanisms for different forms of quadrupedal walking, data on postural orientation, hindlimb kinematics, and motor patterns were assessed for four grades of downslope walking, from 25% (14 degrees slope) to 100% (45 degrees), and compared with data from level and downslope walking at five grades (5-25%) on the treadmill (0.6 m/s). Kinematic data were obtained by digitizing ciné film, and electromyograms (EMGs) synchronized with kinematic records were taken from 13 different hindlimb muscles. At grades from 25 to 75%, cycle periods were similar, but at the steepest grade the cycle was shorter because of a reduced stance phase. Paw-contact sequences at all grades were consistent with lateral-sequence walking, but pace walking often occurred at the steepest grades. The cats crouched at the steeper grades, and crouching was associated with changes in fore- and hindlimb orientation that were consistent with increasing braking forces and decreasing propulsive forces during stance. The average ranges of motion at the hindlimb joints, except at the hip, were often different at the two steepest slopes. During swing, the range of knee- and ankle-joint flexion decreased, and the range and duration of extension increased at the ankle joint to lower the paw downward for contact. During stance the range of flexion during yield increased at the ankle joint, and the range of extension decreased at the knee and metatarsophalangeal joints. Downslope walking was also associated with EMG changes for several muscles. The hip extensors were not active during stance; instead, hip flexors were active, presumably to slow the rate of hip extension. Although ankle extensors were active during stance, their burst durations were truncated and centered around paw contact. Ankle flexors were active after midstance at the steeper slopes before the need to initiate swing, whereas flexor and extensor digit muscles were coactive throughout stance. Overall the changes in posture, hindlimb kinematics, and activity patterns of hindlimb muscles during stance reflected a need to counteract external forces that would accelerate angular displacements at some joints. Implications of these changes are discussed by using current models for the neural control of walking.

Innervation of the caudate nucleus, thalamus and red nucleus by the remaining sensorimotor cortex in cats with fetal or neonatal unilateral frontal cortex removal.

We studied the projections to the caudate nuclei, thalami and red nuclei from the remaining sensorimotor cortex in adult cats that had sustained a unilateral frontal cortex resection prenatally or neonatally. Four cats had the lesion at age E 50-55 and six animals sustained the ablation at age P 8-14 (seven cats were intact controls). All cats grew to young adulthood and then received injections of tritiated leucine-proline in the remaining sensorimotor cortex. Injection sites and axon terminal fields were reconstructed using autoradiography-processed tissue. In all cats the label filled a similar extent of the right pericruciate cortex. Terminal field densities in the subcortical nuclei were estimated using computer-based video software. Three medial-lateral sectors at five coronal levels were examined in the caudate nucleus. Three nuclear groups were analyzed in the thalamus (intralaminary, ventralis lateralis and ventrobasal complex). For the red nucleus, the four quadrants were examined at four coronal levels. The main goal of the study was to assess possible changes in the cortical innervation of the nuclei ipsilateral to the lesion. Therefore, the mean particle counts per nucleus (and per area or sector of nuclei) and per animal group were used to calculate percentage values for the decussated (crossed, or contralateral to the injection site) as a function of the non-decussated (uncrossed, or ipsilateral to the injection site) innervation. The percentage values for the crossed projections were: (a) for the entire caudate nucleus, 61.3% for the intact. 56.7% for the fetal-lesioned and 42.7% for the neonatal-lesioned cats, with no statistical differences between groups; (b) for the thalamus the proportion of crossed projections was minimal fluctuating between a low 0.06-0.16% for the nucleus ventralis lateralis and a high of 2.01-3.46% for the intralaminary nuclei, with the highest values belonging to the lesioned groups but with no significant differences between groups: (c) for the entire red nucleus, 1.98%, 12.74% (P < 0.05) and 6.76% for the intact, fetal- and neonatal-lesioned cats respectively. In the lesioned cats, the topography of the distribution of the axon terminals was bilaterally the same as in the controls. In conclusion, only the red nucleus of the frontal-lesioned cats showed an increased crossed innervation from the remaining sensorimotor cortex but this was relatively weak and statistically significant only for the fetal-lesioned animals. These results as well as the literature suggest that: (a) the crossed corticorubral projections in fetal cats may represent true reinnervation (i.e., newly originated, no preexisting terminals); (b) the relative paucity of the crossed projections in the present cats as compared to the extensive reorganization of subcortical terminals seen after cerebral hemispherectomy (our original postnatal lesion model) may be due to the much smaller size of the present cortical lesion which presumably induced only a limited amount of subcortical nuclear deafferentation.

Unexpected motor patterns for hindlimb muscles during slope walking in the cat.

1. Hindlimb kinematics and motor patterns were assessed from high-speed ciné film synchronized with electromyographic (EMG) data from cats trained to walk on a walkway placed at four grades (25, 50, 75, and 100%). 2. Flexor muscles of the hip (iliopsoas) and ankle (tibialis anterior) had similar activity patterns for the swing phase of up- and down-slope walking; both flexor muscles also had stance-related activity during down-slope walking and this was unexpected. Extensor muscles of the hip (anterior biceps femoris and anterior semimembranosus), knee [vastus lateralis (VL)], and ankle [lateral gastrocnemius (LG)] were active during the stance phase of up-slope walking. The VL and LG activity was reduced in duration during stance of down-slope walking and centered around paw contact. Hip extensors, however, were totally inactive during stance of down-slope walking, and this was not expected. 3. Flexor muscles at the hip and ankle (not extensor muscles) dominated the stance phase of down-slope walking, especially at the steeper slopes. This switch in motor patterns may be required to counterbalance external forces that produced extension at the hip and ankle joints during the stance phase of down-slope walking. Neural mechanisms for programming stance-related activity of flexor muscles are discussed.

Coordination between head and hindlimb motions during the cat scratch response.

Coordination between motions of the head and the hindlimb paw ipsilateral to the stimulated pinna were assessed during the scratch cycle in freely moving cats. Motor patterns were determined by electromyographic (EMG) recordings made from epimysial-patch electrodes surgically implanted on the biventer cervicis (BC), complexus (CM), obliquus capitis inferior (OC), and splenius (SP) muscles and by fine-wire EMG electrodes implanted in two ankle muscles, medial gastrocnemius (MG), and tibialis anterior (TA). To assess head motions during the three phases of the scratch cycle (precontact, contact, postcontact), several responses were filmed, and in some cats an in vivo force transducer was implanted on an ankle extensor muscle (MG or plantaris, PL) to determine the tension profile during the scratch cycle. During the scratch cycle, the head's trajectory was usually characterized by a small oscillation in which the head was pushed away during paw contact (as hindlimb joints extended) and then repositioned during the noncontact phases (as hindlimb joints flexed). Neck muscle activity did not occur during all responses or during all cycles of a single multicycle scratch response, and when it occurred, neck muscle EMG was characterized as phasic (a single burst during the cycle) or tonic (low-level activity during the entire cycle). Neck muscles ipsilateral (i) to the scratching limb exhibited phasic bursts more than contralateral (c) muscles, and phasic activity was most frequently observed in the iBC, iSP, iOC, and cOC muscles. The cOC was reciprocally active with the ipsilateral muscles, and its burst coincided with the postcontact phase and the ankle flexor (TA) burst. The ipsilateral muscles (iOC, iSP, iBC) were active during paw contact, and the termination of all three bursts occurred synchronously just after peak tension of the ankle extensor was reached. The iBC was active before the onset of paw contact and may have been responsible for repositioning the head, along with the cOC, during the precontact phase. The iOC became active after the onset of paw contact (22 ms) and was recruited more often when the peak extensor tendon force was high (10-16 N). The iSP, in contrast, was active during the contact phase of most scratch cycles examined and its recruitment appeared to be unrelated to tendon forces. Our data suggest that phasic neck muscle activity is not obligatory during the cat scratch response, but is related to certain conditions such as a higher than average tendon force of an ankle extensor during contact and the need to reposition the head during the noncontact phases of the cycle.(ABSTRACT TRUNCATED AT 400 WORDS)