Caroline Paquette

The Temporal Dynamics of Poststroke Neuroinflammation: A Longitudinal Diffusion Tensor Imaging–Guided PET Study with 11C-PK11195 in Acute Subcortical Stroke

Animal experiments suggest that 2 different types of activated microglia (AMG) cells occur in the brain after a stroke: local AMG in the area of the infarct and remote AMG, which occurs along affected fiber tracts. We used 11C-PK11195 PET to image AMG in vivo after stroke in humans in a prospective longitudinal study to investigate the temporal dynamics of AMG and relate local and remote AMG activity to pyramidal tract (PT) damage using diffusion tensor imaging (DTI). Methods: Eighteen patients underwent DTI–MRI, 11C-PK11195 PET, and behavioral testing within 2 wk and 6 mo of acute subcortical stroke. In 12 patients, the PT was affected by the stroke (PT group), and in 6 patients it was not (non-PT group). Standardized volumes of interest (VOIs) were placed along the PT at the level of the brain stem, semioval center, and infarct. Tracer uptake ratios (ipsilateral to contralateral) were calculated for each VOI and related to tract damage (measured as fractional anisotropy ratio) and clinical outcome. Six controls underwent the same protocol but only once. Results: In both patient groups, local AMG activity in the infarct was increased initially and significantly decreased over the follow-up period. In contrast, remote AMG was detected only in the PT group in the brain stem along the affected tract and persisted during follow-up. No AMG was observed retrograde to the lesion at any time. Remote AMG activity along the affected PT in the brain stem correlated with initial PT damage as measured by DTI in the same tract portion. Local AMG activity in the infarct correlated with anterograde PT damage only at follow-up. After controlling for PT damage, initial AMG activity in the brain stem showed a positive correlation with clinical outcome, whereas persisting AMG activity in the infarct tended to be negatively correlated. Conclusion: DTI-guided 11C-PK11195 PET in acute subcortical stroke demonstrates differential temporal dynamics of local and remote AMG. Activity of both types related to anterograde PT damage as measured by DTI and might contribute differently to clinical outcome.

Reduced Performance in Balance, Walking and Turning Tasks is Associated with Increased Neck Tone in Parkinson's Disease

Rigidity or hypertonicity is a cardinal symptom of Parkinsons disease (PD). We hypothesized that hypertonicity of the body axis affects functional performance of tasks involving balance, walking and turning. The magnitude of axial postural tone in the neck, trunk and hip segments of 15 subjects with PD (both ON and OFF levodopa) and 15 control subjects was quantified during unsupported standing in an axial twisting device in our laboratory as resistance to torsional rotation. Subjects also performed six functional tests (walking in a figure of eight [Figure of Eight], Timed Up and Go, Berg Balance Scale, supine rolling task [rollover], Functional Reach, and standing 360-deg turn-in-place) in the ON and OFF state. Results showed that PD subjects had increased tone throughout the axis compared to control subjects (p=0.008) and that this increase was most prominent in the neck. In PD subjects, axial tone was related to functional performance, but most strongly for tone at the neck and accounted for an especially large portion of the variability in the performance of the Figure of Eight test (r(OFF)=0.68 and r(ON)=0.74, p<0.05) and the Rollover test (r(OFF)=0.67 and r(ON)=0.55, p<0.05). Our results suggest that neck tone plays a significant role in functional mobility and that abnormally high postural tone may be an important contributor to balance and mobility disorders in individuals with PD.

Bilateral transcranial direct current stimulation modulates activation-induced regional blood flow changes during voluntary movement.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces changes in cortical excitability: anodal stimulation increases while cathodal stimulation reduces excitability. Imaging studies performed after unilateral stimulation have shown conflicting results regarding the effects of tDCS on surrogate markers of neuronal activity. The aim of this study was to directly measure these effects on activation-induced changes in regional cerebral blood flow (⊿rBF) using positron emission tomography (PET) during bilateral tDCS. Nine healthy subjects underwent repeated rCBF measurements with 15O-water and PET during a simple motor task while receiving tDCS or sham stimulation over the primary motor cortex (M1). Motor evoked potentials (MEPs) were also assessed before and after real and sham stimulation. During tDCS with active movement, ⊿rBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation. This decrease in ⊿rBF was accompanied by a decrease in MEP amplitude on the cathodal side. No effect was observed on resting or activated rCBF relative to sham stimulation. We thus conclude that it is the interaction of cathodal tDCS with activation-induced ⊿rBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS.

Old age affects gaze and postural coordination

Visual tracking of the surrounding environment is an important daily task, often executed simultaneously with the regulation of upright balance. Visual and postural coordination may be affected by aging which is associated with a decline in sensory and motor functions. The aim of the present study was to assess the effects of aging on the control of saccadic and smooth pursuit eye movements when standing on a moving surface. Nineteen young and 12 elderly subjects tracked a visual target presented as unpredictable smooth pursuit or saccadic displacements. Subjects were instructed to maintain gaze on target during quiet stance with or without yaw surface rotations. Elderly subjects followed both saccadic and pursuit targets with less accuracy than young subjects. Moreover, elderly subjects responded with longer time lags during saccadic target shifts and executed more catch-up saccades during smooth pursuits than younger subjects. Standing on a moving surface induced larger target-gaze errors. Catch-up saccades during pursuit occurred more frequently during surface perturbations. Our results suggest that visual tracking abilities decline with age and that postural challenge affects accuracy but not timing of gaze responses. Such declines observed with aging may result from multiple but minor sensory and motor deficits.

Stroke Affects the Coordination of Gaze and Posture During Preplanned Turns While Walking

Background In healthy subjects, the act of walking and turning is accomplished by a sequential horizontal reorientation of gaze, head, and body toward the direction of the turn. Subjects with stroke, however, have difficulty altering their walking direction and present with loss of balance when performing a head turn or whole body rotation. Objective. To study, in a pilot case study, the spatial and temporal coordination of gaze and posture during preplanned turns executed while walking in severely disabled and mildly disabled subjects with stroke as compared to a healthy control walking at slow speed. Methods. Horizontal plane orientations of gaze, head, thorax, pelvis, and feet as well as the body’s center of mass (CoM) trajectory were analyzed as subjects were walking straight or executing a 90-deg turn. Results. Subjects with stroke revealed altered orientation and sequencing of gaze body segments. These alterations were more pronounced in the most severely disabled subject with stroke, especially when turning to the nonparetic side as compared to the paretic side. Conclusions. These findings suggest an altered coordination of gaze and posture during steering of locomotion in subjects with stroke. This altered coordination is likely due to a complex interaction of motor, sensory, and biomechanical factors that may explain the poor balance and poor control of heading direction during walking and turning in stroke.

Stroke Affects Locomotor Steering Responses to Changing Optic Flow Directions

Background. Stroke patients manifest steering difficulties during walking, which may arise from an altered perception of visual motion. Objective. To examine the ability of stroke patients to control their heading direction while walking in a virtual environment (VE) describing translational optic flows (OFs) expanding from different directions. Methods. The authors evaluated 10 stroke patients and 11 healthy people while they were walking overground and visualizing a VE in a helmet-mounted display. Participants were instructed to walk straight in the VE and were randomly exposed to an OF having a focus of expansion (FOE) located in 5 possible locations (0°, ±20°, and ±40° to the right or left). The body’s center of mass (CoM) trajectory, heading direction, and horizontal body reorientation were recorded with a Vicon-512 system. Results. Healthy participants veered opposite to the FOE location in the physical world, with larger deviations occurring at the most eccentric FOE locations. Stroke patients displayed altered steering behaviors characterized either by an absence of CoM trajectory corrections, multiple errors in the heading direction, or systematic veering to the nonparetic side. Both groups displayed relatively small CoM trajectory corrections that led to large virtual heading errors. Conclusions. The control of heading of locomotion in response to different OF directions is affected by stroke. An altered perception of heading direction and/or a poor integration of sensory and motor information are likely causes. This altered response to OF direction while walking may contribute to steering difficulties after stroke.

Walking in circles: Navigation deficits from Parkinson's disease but not from cerebellar ataxia

Little is known on the role of neuronal structures for spatial navigation. Our goal was to examine how Parkinsons disease (PD) and cerebellar ataxia, as human lesion models of the basal ganglia and cerebellum, affect spatial navigation round a circular walking path, blindfolded. Twelve subjects with idiopathic PD (ON and OFF medication), eight subjects with cerebellar ataxia and a control group of 20 age-matched healthy subjects participated. All groups performed well when walking around the circle with eyes open. In the eyes-closed condition, control subjects overshot the outlined trajectory but returned to their initial position, thus walking a further distance with eyes closed than with eyes open. When OFF medication, PD subjects navigated a larger radius than controls with eyes closed. When ON levodopa, PD subjects walked a similar distance as controls but with even larger errors in endpoint. Surprisingly, cerebellar patients navigated the circular walking task in the eyes closed condition with even more accuracy (i.e. following the outlined circle) than control and PD subjects. We conclude that blindfolded navigation around a previously seen circle requires intact basal ganglia, but not cerebellar input.

Light and heavy touch reduces postural sway and modifies axial tone in Parkinson's disease.

Background. Light touch with a stable object reduces postural sway by increasing axial postural tone in healthy subjects. However, it is unknown whether subjects with Parkinson’s disease (PD), who have more postural sway and higher axial postural tone than healthy subjects, can benefit from haptic touch. Objective. To investigate the effect of light and heavy touch on postural stability and hip tone in subjects with PD. Methods. Fourteen subjects with mid-stage PD and 14 healthy control subjects were evaluated during quiet standing with eyes closed with their arms (a) crossed, (b) lightly touching a fixed rigid bar in front of them, and (c) firmly gripping the bar. Postural sway was measured with a forceplate, and axial hip tone was quantified using a unique device that measures the resistance of the hips to yaw rotation while maintaining active stance. Results. Subjects with PD significantly decreased their postural sway with light or heavy touch (P < .001 vs arms crossed), similarly as control subjects. Without touch, hip tone was larger in PD subjects. With touch, however, tone values were similar in both groups. This change in hip tone with touch was highly correlated with the initial amount of tone (PD, r = −.72 to −.95; controls, r = −.74 to −.85). Conclusions. The authors showed, for the first time, that subjects with PD benefit from touch similarly to control subjects and that despite higher axial postural tone, PD subjects are able to modulate their tone with touch. Future studies should investigate the complex relationship between touch and postural tone.

Temporal facilitation of gaze in the presence of postural reactions triggered by sudden surface perturbations

Saccadic reaction times can be shortened by an additional sensory modality (e.g. auditory, tactile) presented in temporal proximity to the triggering cue. Whereas somatosensory cues given by sudden perturbations of the support surface can trigger appropriate postural adjustments to maintain upright stance, it is not known how gaze executions are affected by the dual task of maintaining upright balance while redirecting gaze. It was hypothesized that the onset latency of gaze movements toward visual targets will be shortened by sudden surface perturbations following visual target shifts to prompt a stable visual anchor for postural stabilization. Eight subjects stood on a movable platform with gaze fixated on a central target 2 m directly in front, and were instructed to shift their gaze to lateral targets located along a 63 degrees arc to the right and left. The trials began with the central target lit followed randomly by either the right, left or center target. Fifty or 250 ms following this target shift, balance was perturbed by a sudden yaw movement of the support surface (15.5 degrees over 210 ms at 130 degrees /s), with no stepping or large arm reactions observed. The latency of the gaze shifts was significantly shortened (by approximately 72 ms) when executed simultaneously with a surface perturbation. A decrease in excitation latency was also observed in the cervical paraspinals and sternocleidomastoid muscles. Postural responses in the ankle and knee muscles were not affected by gaze shifts. Pelvic horizontal angular motion closely followed surface motion whereas head motion was influenced by gaze shifts. During the combined gaze shift and surface motion conditions, thorax movement excursion was larger and not correlated with either the surface motion or visual target shift. In conclusion, postural adjustments in response to sudden surface yaws facilitate voluntary gaze shift execution and this enhancement may result from the sensory fusion of somatosensory and visual information.

Surface-based partial-volume correction for high-resolution PET.

Tissue radioactivity concentrations, measured with positron emission tomography (PET) are subject to partial volume effects (PVE) due to the limited spatial resolution of the scanner. Last generation high-resolution PET cameras with a full width at half maximum (FWHM) of 2-4mm are less prone to PVEs than previous generations. Corrections for PVEs are still necessary, especially when studying small brain stem nuclei or small variations in cortical neuroreceptor concentrations which may be related to cytoarchitectonic differences. Although several partial-volume correction (PVC) algorithms exist, these are frequently based on a priori assumptions about tracer distribution or only yield corrected values of regional activity concentrations without providing PVE corrected images. We developed a new iterative deconvolution algorithm (idSURF) for PVC of PET images that aims to overcome these limitations by using two innovative techniques: 1) the incorporation of anatomic information from a cortical gray matter surface representation, extracted from magnetic resonance imaging (MRI) and 2) the use of anatomically constrained filtering to attenuate noise. PVE corrected images were generated with idSURF implemented into a non-interactive processing pipeline. idSURF was validated using simulated and clinical PET data sets and compared to a frequently used standard PVC method (Geometric Transfer Matrix: GTM). The results on simulated data sets show that idSURF consistently recovers accurate radiotracer concentrations within 1-5% of true values. Both radiotracer concentrations and non-displaceable binding potential (BPnd) values derived from clinical PET data sets with idSURF were highly correlated with those obtained with the standard PVC method (R(2) = 0.99, error = 0%-3.2%). These results suggest that idSURF is a valid and potentially clinically useful PVC method for automatic processing of large numbers of PET data sets.