PubMed Health⌕ Search

Biomedical subjects

John W Krakauer

Publications and source records attributed to John W Krakauer.

18 recordsLinked to original sources
PubMed2007

Stroke and the statistics of the aspirin/clopidogrel secondary prevention trials.

PURPOSE OF REVIEW: Four randomized trials have investigated the combination of clopidogrel plus aspirin for secondary prevention of vascular outcomes in 54,949 patients. Here we argue that attempts to translate the results of these trials into clinical practice have proven frustrating because of the following statistical considerations: differences in study populations and study design make comparisons difficult (comparisons of 'apples and oranges'), incomplete factorial designs prevent proper contrasts (examining 'bits and pieces' of a larger picture), results concern widely different vascular diseases ('puzzling subgroups'), and negative results are easily misinterpreted. RECENT FINDINGS: Between 1996 and 2004 three major randomized trials assessed combinations of aspirin and clopidogrel, finding: Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) in favor of clopidogrel alone versus aspirin alone, Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) in favor of clopidogrel plus aspirin versus aspirin alone, and Management of Atherothombosis with Clopidogrel in High-risk Patients (MATCH) in favor of clopidogrel plus aspirin versus clopidogrel alone. A recently completed fourth trial (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance; CHARISMA) was a 'negative study' comparing aspirin alone to aspirin plus clopidogrel. SUMMARY: Even after four large randomized trials we still do not know the optimal treatment for secondary prevention of stroke. We suggest that subsequent trials should focus on a particular vascular disease and test hypotheses that relate to a specific mechanism.

Aspirin↗
PubMed2007

The complex dynamics of stroke onset and progression.

PURPOSE OF REVIEW: The aim of this article is to discuss the dynamic nature of cerebrovascular ischemia. RECENT FINDINGS: Acute risk factors are superimposed on chronic risk factors to precipitate plaque rupture in myocardial infarction. The interaction between external triggers, such as stress, with internal triggers, such as vasoconstriction, is mediated to a large part by the autonomic nervous system. Numerous algorithms have been developed to describe physiological time-series data, for example heartbeat variability, and reveal complex structure that has diagnostic and prognostic significance. Much of this structure is mediated by the autonomic nervous system. Recent data on stroke triggers, carotid stenosis, transient ischemic attack, and infarct expansion suggest a similar need for detailed physiological measurement and non-linear dynamics in order to understand stroke onset and progression. SUMMARY: The picture emerging is that stroke arises as a result of multiple processes with different time constants. The nature and timing of interventions should be tailored to these complex interacting processes. This will require more frequent and varied physiological measurement accompanied by non-linear analytical methods. This new approach, which stresses complex within-subject measurements, will likely make 'one size fits all' solutions to stroke care untenable.

Autonomic Nervous System↗
PubMed2006

Impaired anticipatory control of fingertip forces in patients with a pure motor or sensorimotor lacunar syndrome.

We examined planning and execution of precision grasp in eight right-handed patients with a right pure motor or sensorimotor lacunar syndrome after a subcortical stroke and eight age-matched controls as they grasped and lifted an instrumented object whose weight could be varied without altering its visual appearance. Grip (normal) and load (tangential) forces at the fingertip-object interface were measured and the grip force rate (GFR) and load force rate (LFR) were derived. Planning of precision grasp was assessed by measurement of anticipatory scaling of peak GFR and peak LFR to object weight. Execution of precision grasp was assessed by measurement of both the timing and efficiency of grip-load force coordination: the pre-load phase duration (PLD) and the load phase duration (LPD) measured timing, whereas the grip force at load force onset (GFO) and the grip force at lift-off (GFL) measured efficiency. Subjects lifted a light and heavy object five times first with the RIGHT hand, then with the LEFT hand, and then once more with the RIGHT AFTER LEFT hand. Patients with stroke did not scale the peak LFR or peak GFR to object weight with the RIGHT hand even with repeated attempts; however, they scaled the peak LFR to object weight on the first lift with the RIGHT AFTER LEFT hand (P = 0.01). Patients also prolonged the PLD and LPD and produced excessive GFO and GFL for RIGHT hand lifts, but decreased the GFL for the heavy object (P = 0.016) with the RIGHT AFTER LEFT hand. Correlation of precision grasp variables from lifts with the RIGHT hand with clinical measures showed that anticipatory scaling of peak LFR and peak GFR did not correlate with clinical measures of hand function, whereas the PLD did (r = 0.88, P = 0.004). The results suggest that patients with right hemiparesis from a subcortical lesion of the corticospinal tract have a higher-order motor planning deficit. This planning deficit is dissociable from deficits in motor execution, is not captured by routine clinical assessment, and is correctable by transfer of information from the unaffected hemisphere. A rehabilitation strategy that involves practice with the left hand prior to practice with the right hand may improve planning of grasping behaviour in patients with right hemiparesis.

Adult↗
PubMed2006

An implicit plan overrides an explicit strategy during visuomotor adaptation.

The relationship between implicit and explicit processes during motor learning, and for visuomotor adaptation in particular, is poorly understood. We set up a conflict between implicit and explicit processes by instructing subjects to counter a visuomotor rotation using a cognitive strategy in a pointing task. Specifically, they were told the exact nature of the directional perturbation, a rotation that directed them 45 degrees counterclockwise from the desired target, and they were instructed to counter it by aiming for the neighboring clockwise target, 45 degrees away. Subjects were initially successful in completely negating the rotation with this strategy. Surprisingly, however, they were unable to sustain explicit control and made increasingly large errors to the desired target. The cognitive strategy failed because subjects simultaneously adapted unconsciously to the rotation to the neighboring target. Notably, the rate of implicit adaptation to the neighboring target was not significantly different from rotation adaptation in the absence of an opposing explicit strategy. These results indicate that explicit strategies cannot substitute for implicit adaptation to a visuomotor rotation and are in fact overridden by the motor planning system. This suggests that the motor system requires that planned and executed trajectories remain congruous in visual space, and enforces this correspondence even at the expense of an opposing explicit task goal.

Adaptation, Physiological↗
PubMed2006

An optimization principle for determining movement duration.

Movement duration is an integral component of motor control, but nearly all extant optimization models of motor planning prefix duration instead of explaining it. Here we propose a new optimization principle that predicts movement duration. The model assumes that the brain attempts to minimize movement duration under the constraint of meeting an accuracy criterion. The criterion is task and context dependent but is fixed for a given task and context. The model determines a unique duration as a trade-off between speed (time optimality) and accuracy (acceptable endpoint scatter). We analyzed the model for a linear motor plant, and obtained a closed-form equation for determining movement duration. By solving the equation numerically with specific plant parameters for the eye and arm, we found that the model can reproduce saccade duration as a function of amplitude (the main sequence), and arm-movement duration as a function of the ratio of target distance to size (Fitts's law). In addition, it explains the dependency of peak saccadic speed on amplitude and the dependency of saccadic duration on initial eye position. Furthermore, for arm movements, the model predicts a scaling relationship between peak velocity and distance and a reduction in movement duration with a moderate increase in viscosity. Finally, for a linear plant, our model predicts a neural control signal identical to that of the minimum-variance model set to the same movement duration. This control signal is a smooth function of time (except at the endpoint), in contrast to the discontinuous bang-bang control found in the time-optimal control literature. We suggest that one aspect of movement planning, as revealed by movement duration, may be to assign an endpoint accuracy criterion for a given task and context.

Algorithms↗
PubMed2006

Hemodynamic impairment as a stimulus for functional brain reorganization.

We used functional magnetic resonance imaging to investigate whether hemispheral hemodynamic impairment can play an independent role in the functional reorganization of motor-related activity in the brain. Fourteen patients with large vessel occlusion but no infarct performed a simple motor task with the hand contralateral to the occluded vessel. Statistical parametric maps of regional activity were generated to compare the distribution of motor-related activity among patients with that of control subjects. Patients were classified into normal or abnormal cerebral hemodynamics on the basis of intracerebral vasomotor reactivity using transcranial Doppler and carbon dioxide inhalation. Controls and patients with normal vasomotor reactivity showed typical motor activity in contralateral motor areas. When the 9 patients with abnormal vasomotor reactivity were compared with the 14 control subjects in a single analysis, unique motor activation was identified in ipsilateral motor regions in the nonhypoperfused hemisphere. In a confirmatory analysis, blood oxygen level-dependent (BOLD) signal intensity was averaged in prespecified motor regions of interest. A significant group by hemisphere interaction was identified, driven by higher ipsilateral and lower contralateral hemisphere BOLD signal in patients with abnormal vasomotor reactivity compared with controls (F=12.40, P=0.002). The average ipsilateral motor region signal intensity was also significantly higher in the subgroup of patients with abnormal vasoreactivity and no TIA compared with controls (P=0.04). Our results suggest that hemodynamic impairment in one hemisphere, even in the absence of any focal lesion or any symptoms can be associated with a functional reorganization to the opposite hemisphere.

Adult↗
PubMed2006

Multiple reversible episodes of subcortical ischemia following postcoital middle cerebral artery dissection.

BACKGROUND: Subcortical transient ischemic attacks are usually seen in individuals with small-vessel disease. They are often refractory to medical treatment and progress to infarction in many cases. PATIENT: We describe a young man with an unusual and protracted case of recurrent capsular ischemia due to postcoital middle cerebral artery dissection. CONCLUSION: Spontaneous middle cerebral artery dissection should be considered in young patients presenting with subcortical transient ischemic attacks.

Adult↗
PubMed2006

Motor learning: its relevance to stroke recovery and neurorehabilitation.

PURPOSE OF REVIEW: Much of neurorehabilitation rests on the assumption that patients can improve with practice. This review will focus on arm movements and address the following questions: (i) What is motor learning? (ii) Do patients with hemiparesis have a learning deficit? (iii) Is recovery after injury a form of motor learning? (iv) Are approaches based on motor learning principles useful for rehabilitation? RECENT FINDINGS: Motor learning can be broken into kinematic and dynamic components. Studies in healthy subjects suggest that retention of motor learning is best accomplished with variable training schedules. Animal models and functional imaging in humans show that the mature brain can undergo plastic changes during both learning and recovery. Quantitative motor control approaches allow differentiation between compensation and true recovery, although both improve with practice. Several promising new rehabilitation approaches are based on theories of motor learning. These include impairment oriented-training (IOT), constraint-induced movement therapy (CIMT), electromyogram (EMG)-triggered neuromuscular stimulation, robotic interactive therapy and virtual reality (VR). SUMMARY: Motor learning mechanisms are operative during spontaneous stroke recovery and interact with rehabilitative training. For optimal results, rehabilitation techniques should be geared towards patients' specific motor deficits and possibly combined, for example, CIMT with VR. Two critical questions that should always be asked of a rehabilitation technique are whether gains persist for a significant period after training and whether they generalize to untrained tasks.

Electric Stimulation Therapy↗
PubMed2006

Generalization of motor learning depends on the history of prior action.

Generalization of motor learning refers to our ability to apply what has been learned in one context to other contexts. When generalization is beneficial, it is termed transfer, and when it is detrimental, it is termed interference. Insight into the mechanism of generalization may be acquired from understanding why training transfers in some contexts but not others. However, identifying relevant contextual cues has proven surprisingly difficult, perhaps because the search has mainly been for cues that are explicit. We hypothesized instead that a relevant contextual cue is an implicit memory of action with a particular body part. To test this hypothesis we considered a task in which participants learned to control motion of a cursor under visuomotor rotation in two contexts: by moving their hand through motion of their shoulder and elbow, or through motion of their wrist. Use of these contextual cues led to three observations: First, in naive participants, learning in the wrist context was much faster than in the arm context. Second, generalization was asymmetric so that arm training benefited subsequent wrist training, but not vice versa. Third, in people who had prior wrist training, generalization from the arm to the wrist was blocked. That is, prior wrist training appeared to prevent both the interference and transfer that subsequent arm training should have caused. To explain the data, we posited that the learner collected statistics of contextual history: all upper arm movements also move the hand, but occasionally we move our hands without moving the upper arm. In a Bayesian framework, history of limb segment use strongly affects parameter uncertainty, which is a measure of the covariance of the contextual cues. This simple Bayesian prior dictated a generalization pattern that largely reproduced all three findings. For motor learning, generalization depends on context, which is determined by the statistics of how we have previously used the various parts of our limbs.

Adult↗
PubMed2005

Consolidation of motor memory.

An issue of great recent interest is whether motor memory consolidates in a manner analogous to declarative memory--that is, with the formation of a memory that progresses over time from a fragile state, which is susceptible to interference by a lesion or a conflicting motor task, to a stabilized state, which is resistant to such interference. Here, we first review studies that examine the anatomical basis for motor consolidation. Evidence implicates cerebellar circuitry in two types of associative motor learning--eyelid conditioning and vestibulo-ocular reflex adaptation--and implicates primary motor cortex in skilled finger movements. We also review evidence for and against a consolidation process for adaptation of arm movements. We propose that contradictions have arisen because consolidation can be masked by inhibition of memory retrieval.

Adaptation, Physiological↗
PubMed2005

Patterns of impairment in digit independence after subcortical stroke.

The nature of impairment in hand motor control after stroke and its relationship to hand function are still not well understood. In this study, we investigated digit independence in patients with subcortical stroke (n = 8) and moderate hand impairment, defined by wrist and hand Fugl-Meyer scale scores < or =25/33, and age-matched controls (n = 8). Subjects made cyclical flexion-extension movements of an instructed digit while keeping the other digits as still as possible. Movements of the metacarpo-phalangeal (MCP) joints of the five digits were measured using an instrumented glove. The ability to move an instructed digit individually (individuation index), and the ability to keep a noninstructed digit as still as possible (stationarity index) were determined for each digit. Contrary to the finding of normal thumb individuation in a recent study of patients with variable hand motor impairment after stroke, we found that independent movement for all digits was significantly impaired, although individuation and stationarity were differentially affected for each digit. All the digits, including the thumb, showed a similar impairment in individuation. In contrast, stationarity was affected in a digit-dependent pattern: the thumb was affected least, and the middle finger was most impaired. Stroke subjects did not extend their digits fully to the baseline position, and the angular displacement at maximum digit extension correlated significantly with digit individuation. Contrary to expectation, digit independence correlated weakly with clinical tests of hand function, which emphasize grasp. This suggests that corticospinal projections might be separated with respect to function rather than finger topography.

Adult↗
PubMed2005

Adaptation to visuomotor transformations: consolidation, interference, and forgetting.

The paradigm task A-->task B-->task A, which varies the time interval between task A and task B, has been used extensively to investigate the consolidation of motor memory. Consolidation is defined as resistance to retrograde interference (interference by task B on initial learning of task A). Consolidation has been demonstrated for simple skills, motor sequencing, and learning of force fields. In contrast, evidence to date suggests that visuomotor learning does not consolidate. We have shown previously that adaptation to a 30 degrees screen-cursor rotation is faster and more complete on relearning 24 hr later. This improvement is prevented if a 30 degrees counter-rotation is learned 5 min after the original rotation. Here, we sought to identify conditions under which rotation learning becomes resistant to interference by a counter-rotation. In experiment 1, we found that interference persists even when the counter-rotation is learned 24 hr after the initial rotation. In experiment 2, we removed potential anterograde interference (interference by task B on relearning of task A) by introducing washout blocks before all of the learning blocks. In contrast to experiment 1, we found resistance to interference (i.e., consolidation) when the counter-rotation was learned after 24 hr but not after 5 min. In experiment 3, we doubled the amount of initial rotation learning and found resistance to interference even after 5 min. Our results suggest that persistent interference is attributable to anterograde effects on memory retrieval. When anterograde effects are removed, rotation learning consolidates both over time and with increased initial training.

Adaptation, Physiological↗
PubMed2005

Arm function after stroke: from physiology to recovery.

There are varying degrees of spontaneous improvement in arm paresis over the first 6 months after stroke. The degree of improvement at 6 months is best predicted by the motor deficit at 1 month despite standard rehabilitative interventions in the ensuing 5 months. Animal studies indicate that the loss of fine motor control, especially individuation of the digits, is due to interruption of monosynaptic corticomotoneuronal connections. Spasticity occurs because of loss of cortical modulatory control on descending brain stem pathways and spinal segmental circuits but is not a major cause of motor dysfunction. Quantitative studies of reaching movements in patients suggest that arm paresis consists of higher-order motor planning and sensorimotor integration deficits that cannot be attributed to weakness or presence of synergies. Cortical stimulation experiments in animals and functional imaging studies in humans indicate that motor learning and recovery after stroke share common brain reorganization mechanisms. Rehabilitation techniques enhance learning-related changes after stroke and contribute to recovery. Future research will benefit from using quantitative methods to characterize the motor impairment after stroke and by applying concepts in motor learning to devise more physiologically based rehabilitation techniques.

Arm↗
PubMed2005

A new approach to spatial covariance modeling of functional brain imaging data: ordinal trend analysis.

In neuroimaging studies of human cognitive abilities, brain activation patterns that include regions that are strongly interactive in response to experimental task demands are of particular interest. Among the existing network analyses, partial least squares (PLS; McIntosh, 1999; McIntosh, Bookstein, Haxby, & Grady, 1996) has been highly successful, particularly in identifying group differences in regional functional connectivity, including differences as diverse as those associated with states of awareness and normal aging. However, we address the need for a within-group model that identifies patterns of regional functional connectivity that exhibit sustained activity across graduated changes in task parameters. For example, predictions of sustained connectivity are commonplace in studies of cognition that involve a series of tasks over which task difficulty increases (Baddeley, 2003). We designed ordinal trend analysis (OrT) to identify activation patterns that increase monotonically in their expression as the experimental task parameter increases, while the correlative relationships between brain regions remain constant. Of specific interest are patterns that express positive ordinal trends on a subject-by-subject basis. A unique feature of OrT is that it recovers information about functional connectivity based solely on experimental design variables. In particular, there is no requirement by OrT to provide either a quantitative model of the uncertain relationship between functional brain circuitry and subject variables (e.g., task performance and IQ) or partial information about the regions that are functionally connected. In this letter, we provide a step-by-step recipe of the computations performed in the new OrT analysis, including a description of the inferential statistical methods applied. Second, we describe applications of OrT to an event-related fMRI study of verbal working memory and H(2)15O-PET study of visuo-motor learning. In sum, OrT has potential applications to not only studies of young adults and their cognitive abilities, but also studies of normal aging and neurological and psychiatric disease.

Adult↗
PubMed2004

Hypoperfusion without stroke alters motor activation in the opposite hemisphere.

To specifically investigate the effect that large-vessel disease may have on cortical reorganization, we used functional magnetic resonance imaging to study patients with unilateral hemispheric hypoperfusion and impaired vasomotor reactivity from critical internal carotid or middle cerebral artery disease but without stroke. We hypothesized that when these patients used the hand contralateral to the hypoperfused hemisphere they would show unique activation in motor-related areas of the normally perfused hemisphere, that is, ipsilateral activation. We found that normal performance of two motor tasks was associated with increased ipsilateral hemispheric activation in the patients compared with age-matched controls. In addition, although task difficulty had an effect on ipsilateral activation, the increased ipsilateral activation seen in patients was not dependent on task difficulty. Our findings demonstrate that hemodynamic compromise alone is sufficient to cause atypical ipsilateral activation. This activation may serve to maintain normal motor performance.

Adult↗
PubMed2004

Functional imaging of motor recovery after stroke: remaining challenges.

Stroke is a leading cause of disability in the United States and is likely to have an increasing impact on disability worldwide. In order to develop more effective rehabilitation techniques, it is critical to understand the mechanisms underlying the mature brain's capacity to reorganize and restore neurologic function. Over the past decade, functional brain imaging has been a principal investigational tool in elucidating mechanisms of stroke recovery. Functional imaging studies of motor performance in patients with stroke consistently demonstrate areas of brain activation not present in healthy subjects. The role of these additional areas in recovery after stroke remains uncertain. This review discusses methodologic and theoretical issues that impact on interpreting functional imaging studies of motor recovery after stroke.

Humans↗
PubMed2003

Differential cortical and subcortical activations in learning rotations and gains for reaching: a PET study.

Previous studies suggest that horizontal reaching movements are planned vectorially with independent specification of direction and extent. The transformation from visual to hand-centered coordinates requires the learning of a task-specific reference frame and scaling factor. We studied learning of a novel reference frame by imposing a screen-cursor rotation and learning of a scaling factor by imposing a novel gain. Previous work demonstrates that rotation and gain learning have different time courses and patterns of generalization. Here we used PET to identify and compare brain areas activated during rotation and gain learning, with a baseline motor-execution task as the subtracted control. Previous work has shown that the time courses of rotation and gain adaptation have a short rapid phase followed by a longer slow phase. We therefore also sought to compare activations associated with the rapid and slower phases of adaptation. We isolated the rapid phase by alternating opposite values of the rotation or gain every 16 movements. The rapid phase of rotation adaptation activated the preSMA. More complete adaptation to the rotation activated right ventral premotor cortex, right posterior parietal cortex, and the left lateral cerebellum. The rapid phase of gain learning only activated subcortical structures: bilateral putamen and left cerebellum. More complete gain learning failed to show any significant activation. We conclude that the time course of rotation adaptation is paralleled by a frontoparietal shift in activated cortical regions. In contrast, early gain adaptation involves only subcortical structures, which we suggest reflects a more automatic process of contextual recalibration of a scaling factor.

Adaptation, Physiological↗