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Andreas R Luft

Publications and source records attributed to Andreas R Luft.

At least 19 recordsLinked to original sources
PubMed2006

Cortical stimulation mapping using epidurally implanted thin-film microelectrode arrays.

Stimulation mapping of motor cortex is an important tool for assessing motor cortex physiology. Existing techniques include intracortical microstimulation (ICMS) which has high spatial resolution but damages cortical integrity by needle penetrations, and transcranial stimulation which is non-invasive but lacks focality and spatial resolution. A minimally invasive epidural microstimulation (EMS) technique using chronically implanted polyimide-based thin-film microelectrode arrays (72 contacts) was tested in rat motor cortex and compared to ICMS within individual animals. Results demonstrate reliable mapping with high reproducibility and validity with respect to ICMS. No histological evidence of cortical damage and the absence of motor deficits as determined by performance of a motor skill reaching task, demonstrate the safety of the method. EMS is specifically suitable for experiments integrating electrophysiology with behavioral and molecular biology techniques.

Analysis of Variance↗
PubMed2006

Statistical mapping of speckle autocorrelation for visualization of hyperaemic responses to cortical stimulation.

Statistically mapped speckle autocorrelation images (SAR) were used to track the hemodynamically active perfusion regions in the rat cortex during and following DC current stimulation with high transverse spatial resolution (38 um). The SAR images provided a spatio-temporal information about the net activation patterns of Cerebral Blood Flow (CBF) changes over a period of time as against those changes for each frame interval estimated using spatial contrasts derived from the first order spatial statistics. Thus the information about the relative maxima of perfusion during a Transient Hyperaemic Episode (THE) across different regions in the imaging window could be identified without the need for actually having to estimate the spatial contrast maps of the imaged region for each frame contained in the time window of observation. With the application of DC stimulation, the regions with a high correlation in the temporal fluctuations were representative of the areas that underwent least changes in activation. By varying the intensity of stimulation, THEs were observed for stimulation current densities in the range 0.1-3.8 mA/mm2 using both the derived speckle contrast maps and concurrently on a Laser Doppler Flow meter, with its probe positioned 1 mm from the site of stimulation. For current densities below the lower threshold of stimulation, the SAR images revealed an unprecedented reduction in the surge amplitude at sites distal to the region of stimulation. This was accompanied by an increase in pixel areas representing minimally active regions of perfusion ("perfusion islets") with no identifiable peak in the hemodynamic responses estimated from speckle contrast variations. The SAR images can be a useful tool for visualization of slow wave perfusion dynamics during cortical stimulation.

Animals↗
PubMed2006

Modulation of excitability as an early change leading to structural adaptation in the motor cortex.

The excitability of the motor cortex is a function of single cell excitability, synaptic strength, and the balance between excitatory cells and inhibitory cells. Sustained periods of sensory stimulation enhance the excitability in the motor cortex. This adaptation, which represents an early change in cortical network function effective in motor learning and recovery from a motor deficit, is followed by longer-lasting changes, such as modifications in cortical somatotopy, and by structural plasticity. Interventions aiming at increasing excitability also positively affect learning processes. Recent studies highlight that the cerebellum, especially the interpositus nucleus, plays a key function in the adaptation of the motor cortex to repeated trains of peripheral stimulation. Interpositus neurons, which receive inputs from the sensorimotor cortex and the spinal cord, are involved in somesthetic reflex behaviors and assist the cerebral cortex in transforming sensory signals to motor-oriented commands by acting via the cerebello-thalamo-cortical projections. Moreover, climbing fibers originating in the inferior olivary complex and innervating the nucleus interpositus mediate highly integrated sensorimotor information derived from spinal modules. The intermediate cerebellum allows the motor cortex to tune the gain of polysynaptic responses originating from the spinal cord after repetitive trains of peripheral stimulation, allowing an online calibration of cutaneo-muscular responses.

Adaptation, Physiological↗
PubMed2005

Imaging the development of an ischemic core following photochemically induced cortical infarction in rats using Laser Speckle Contrast Analysis (LASCA).

Laser Speckle Contrast Analysis (LASCA) has been used to image the development of an ischemic core following photochemically induced infarction in rats up to 1 h post-lesion. Using LASCA, we have been able to image a central ischemic core which had little or no perfusion surrounded by a penumbral region with reduced perfusion. In addition, we have shown the existence of a surrounding region of hyperemic tissue. A potential feature of this imaging approach is its capability to track cerebral blood flow (CBF) changes in the region within and outside the ischemic core besides demonstrating the real-time progression of the ischemic core into the penumbral region. We have demonstrated the continuous disruption of CBF to the ischemic core that eventually affected the blood supply to the surrounding regions. The penumbral flow is shown to exhibit a sudden increase post-ischemic induction followed by a slow decline to the final baseline level. Interestingly, we observed an interaction (P < 0.03) between penumbral flow peak and the time effects of increase in pixel area from the infarct region to the surrounding penumbral region. Using a paired-sample t test, we observed that the mean pixel area was larger for the infarct region than for the penumbral region (P < 0.004) during the time interval between the induction of ischemia and the time point of peak flow in the penumbral region.

Algorithms↗
PubMed2005

Early adaptations in somatosensory cortex after focal ischemic injury to motor cortex.

In response to a lesion, intact regions of cortex in both hemispheres undergo adaptive changes in network function. For example, changes in excitability and intracortical inhibition in primary motor cortex (M1) were reported after lesioning contralateral or ipsilateral brain regions. Close interactions exist between M1 and primary somatosensory cortex (S1) within one hemisphere. Therefore, we hypothesized that lasting modifications would occur in S1 excitability after lesioning ipsilateral M1. Imaging of intrinsic optical signals (IOS, at 570 nm) was used to investigate the evolution of the somatosensory cortical response evoked by contralateral median nerve stimulation during the first hour after a photothrombotic lesion to M1 (caudal motor cortex) of the rat (n=10). Control rats (n=6) received no lesion. Perfusion was monitored by Laser speckle imaging and the extent of the resulting lesion was determined histologically. Control animals did not show evidence for reduced perfusion, infarction, or changes in IOS. M1 infarction led to a significant increase in evoked response amplitude, duration, and area of activation, and a shortening of latencies. These parameters reached a plateau around 50 min after ischemia. These results indicate S1 hyperexcitability after M1 injury. Whether these adaptations contribute to functional deficits or play a role in recovery, remains to be determined.

Adaptation, Physiological↗
PubMed2005

Brain activation of lower extremity movement in chronically impaired stroke survivors.

Lower extremity paresis poses significant disability to chronic stroke survivors. Unlike for the upper extremity, cortical adaptations in networks controlling the paretic leg have not been characterized after stroke. Here, the hypotheses are that brain activation associated with unilateral knee movement in chronic stroke survivors is abnormal, depends on lesion location, and is related to walking ability. Functional magnetic resonance imaging of unilateral knee movement was obtained in 31 patients 26.9 months (mean, IQ range: 11.3-68.1) after stroke and in 10 age-matched healthy controls. Strokes were stratified according to lesion location. Locomotor disability (30 ft walking speed) did not differ between patient groups (9 cortical, 12 subcortical, 10 brainstem lesions). Significant differences in brain activation as measured by voxel counts in 10 regions of interest were found between controls and patients with brainstem (P = 0.006) and cortical strokes (P = 0.002), and between subcortical and cortical patients (P = 0.026). Statistical parametric mapping of data per group revealed similar activation patterns in subcortical patients and controls with recruitment of contralateral primary motor cortex (M1), supplementary motor area (SMA), and bilateral somatosensory area 2 (S2). Cortical recruitment was reduced in brainstem and cortical stroke. Better walking was associated with lesser contralateral sensorimotor cortex activation in brainstem, but stronger recruitment of ipsilateral sensorimotor and bilateral somatosensory cortices in subcortical and cortical patients, respectively. A post hoc comparison of brainstem patients with and without mirror movements (50%) revealed lesser recruitment of ipsilateral cerebellum in the latter. Subcortical patients with mirror movements (58%) showed lesser bilateral sensorimotor cortex activation. No cortical patient had mirror movements. The data reveal adaptations in networks controlling unilateral paretic knee movement in chronic stroke survivors. These adaptations depend on lesion location and seem to have functional relevance for locomotion.

Aged↗
PubMed2005

Modulation of motor cortex excitability by sustained peripheral stimulation: the interaction between the motor cortex and the cerebellum.

The excitability of cortical neurons in the motor cortex is determined by their membrane potential and by the level of intracortical inhibition. The excitability of the motor cortex as a whole is a function of single cell excitability, synaptic strength, and the balance between excitatory cells and inhibitory cells. It is now established that a sustained period of somatosensory stimulation increases the excitability of motor cortex areas controlling muscles in those body parts that received the stimulation prior to excitability testing. So far, it has been supposed that the sensorimotor cortex was the anatomical substrate of these excitability changes, which could represent an early change in cortical network function before structural plasticity occurs. Recent experimental studies highlight that the cerebellum, especially the interpositus nucleus, plays a key role in the adaptation of the motor cortex to repeated trains of stimulation. Interpositus neurons, which receive inputs from both sensorimotor cortex and the spinal cord, are involved in somesthetic reflex behaviors and assist the cerebral cortex in transforming sensory signals to motor-oriented commands by acting via the cerebello-thalamo-cortical projections. Moreover, climbing fibers originating in the inferior olivary complex and innervating the nucleus interpositus mediate highly integrated sensorimotor information derived from spinal modules. It appears that the interpositus nucleus is a main subcortical modulator of the excitability changes occurring in the motor cortex, which may be a substrate of early plasticity effective in motor learning and recovery from lesion.

Afferent Pathways↗
PubMed2005

Stages of motor skill learning.

Successful learning of a motor skill requires repetitive training. Once the skill is mastered, it can be remembered for a long period of time. The durable memory makes motor skill learning an interesting paradigm for the study of learning and memory mechanisms. To gain better understanding, one scientific approach is to dissect the process into stages and to study these as well as their interactions. This article covers the growing evidence that motor skill learning advances through stages, in which different storage mechanisms predominate. The acquisition phase is characterized by fast (within session) and slow learning (between sessions). For a short period following the initial training sessions, the skill is labile to interference by other skills and by protein synthesis inhibition, indicating that consolidation processes occur during rest periods between training sessions. During training as well as rest periods, activation in different brain regions changes dynamically. Evidence for stages in motor skill learning is provided by experiments using behavioral, electrophysiological, functional imaging, and cellular/molecular methods.

Animals↗
PubMed2004

Characterization of motor skill and instrumental learning time scales in a skilled reaching task in rat.

Successful motor skill learning requires repetitive training interrupted by rest periods. In humans, improvement occurs within and between training sessions reflecting fast and slow components of motor learning [Karni A, Meyer G, Rey-Hipolito C, Jezzard P, Adams MM, Turner R, et al. The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex. Proc Natl Acad Sci USA 1998;95:861-8]. Here, these components are characterized in male and female rats using a model of skilled forelimb reaching and are compared to time scales of instrumental learning. Twenty female and 14 male adult Long-Evans rats were pre-trained to operate a motorized door (via a sensor in the opposite cage wall) to access a food pellet by tongue. Latencies between pellet removal and door opening were recorded as measures of instrumental learning. After criterion performance was achieved, skilled forelimb reaching was requested by increasing the pellet-window distance to 1.5cm. Reaching success was recorded per trial. Mean latencies decreased exponentially over sessions and no improvement within-session was found. Skill learning over eight training sessions followed an exponential course in females and a sigmoid course in males. Females acquired the skill significantly faster than males starting at higher baseline levels (P < 0.001) but reaching similar plateaus. Within-session improvement was found during the sessions 1-3 in females and 1-4 in males. Performance at the end of session 1 was not carried over to session 2. Learning curves of individual animals were highly variable. These findings confirm in rat that motor skill learning has fast and slow components. No within-session improvement is seen in instrumental learning.

Animals↗
PubMed2004

Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial.

CONTEXT: Reorganization in central motor networks occurs during early recovery from hemiparetic stroke. In chronic stroke survivors, specific rehabilitation therapy can improve upper extremity function. OBJECTIVE: To test the hypothesis that in patients who have chronic motor impairment following stroke, specific rehabilitation therapy that improves arm function is associated with reorganization of cortical networks. DESIGN, SETTING, AND PATIENTS: A randomized controlled clinical trial conducted in a US ambulatory rehabilitation program with 21 patients (median [IQR], 50.3 [34.8-77.3] months after unilateral stroke). Data were collected between 2001 and 2004. INTERVENTIONS: Patients were randomly assigned to bilateral arm training with rhythmic auditory cueing (BATRAC) (n = 9) or standardized dose-matched therapeutic exercises (DMTE) (n = 12). Both were conducted for 1 hour, 3 times a week, for 6 weeks. MAIN OUTCOME MEASURES: Within 2 weeks before and after the intervention, brain activation during elbow movement assessed by functional magnetic resonance imaging (fMRI) and functional outcome assessed using arm function scores. RESULTS: Patients in the BATRAC group but not in the DMTE group increased hemispheric activation during paretic arm movement (P = .03). Changes in activation were observed in the contralesional cerebrum and ipsilesional cerebellum (P = .009). BATRAC was associated with significant increases in activation in precentral (P<.001) and postcentral gyri (P = .03) and the cerebellum (P<.001), although 3 BATRAC patients showed no fMRI changes. Considering all patients, there were no differences in functional outcome between groups. When only BATRAC patients with fMRI response were included (n = 6), BATRAC improved arm function more than DMTE did (P = .02). CONCLUSIONS: These preliminary findings suggest that BATRAC induces reorganization in contralesional motor networks and provide biological plausibility for repetitive bilateral training as a potential therapy for upper extremity rehabilitation in hemiparetic stroke.

Aged↗
PubMed2004

Motor skill learning depends on protein synthesis in motor cortex after training.

The role of protein synthesis in memory consolidation is well established for hippocampus-dependent learning and synaptic plasticity. Whether protein synthesis is required for motor skill learning is unknown. We hypothesized that skill learning is interrupted by protein synthesis inhibition (PSI). We intended to test whether local protein synthesis in motor cortex or cerebellum is required during skill acquisition and consolidation. Anisomycin (ANI; 100 microg/microl in 1 microl of PBS) injected into motor cortex, posterior parietal cortex, or cerebellum produced 84.0 +/- 1.44% (mean +/- SEM), 85.9 +/- 2.31%, and 87.3 +/- 0.17% of PSI 60 min after administration, respectively. In motor cortex, protein synthesis was still reduced at 24 hr (72.0 +/- 4.68% PSI) but normalized at 48 hr after a second injection given 24 hr after the first. To test for the effects of PSI on learning of a skilled reaching task, ANI was injected into motor cortex contralateral to the trained limb or into ipsilateral cerebellum immediately after daily training sessions 1 and 2. Two control groups received motor cortex injections of vehicle or ANI injections into contralateral parietal cortex. Control and cerebellar animals showed a sigmoid learning curve, which plateaued after day 4. PSI in motor cortex significantly reduced learning during days 1-4. Thereafter, when protein synthesis normalized, learning was reinitiated. ANI injections into motor cortex did not induce a motor deficit, because animals injected during the performance plateau did not deteriorate. This demonstrates that motor skill learning depends on de novo synthesis of proteins in motor cortex after training.

Animals↗
PubMed2004

Effects of somatosensory electrical stimulation on neuronal injury after global hypoxia-ischemia.

Electrical stimulation (ES) is used after cardiac arrest (CA) for diagnostic and therapeutic purposes. The effects of ES on brain damage induced by hypoxic-ischemic brain injury (HI) has not been investigated. Stimulation of afferent pathways by ES may increase neural injury by releasing excitatory neurotransmitters (glutamate) and thereby exacerbating excitotoxicity. To test this hypothesis, ES was applied to the median nerve (2 h) of adult male Wistar rats after 5 min of asphyxic CA and cardiopulmonary resuscitation. Control animals received no ES. Assessment of neuronal damage in five regions of interest was performed in survivors (ESn=15, Control n=10, Sham n=3) after 48 h using H&E, Cresyl-Violet, and TUNEL stains, and Caspase-3 and activated ERK 1/2 immunohistochemistry. Ratios of injured to normal cells were calculated. Most injury was found in hippocampus and cerebellum. ES animals showed significantly lower injury ratios in bilateral hippocampus as compared with controls (F=20.8, p<0.00001). TUNEL staining, caspase-3 and activated ERK 1/2 showed no differences between groups. It is concluded that ES during the acute phase of HI does not amplify neuronal damage at 48 h, but may have a protective effect that requires further investigation.

Afferent Pathways↗
PubMed2004

Lesion location alters brain activation in chronically impaired stroke survivors.

Recovery of motor function after stroke is associated with reorganization in central motor networks. Functional imaging has demonstrated recovery-dependent alterations in brain activation patterns when compared to healthy controls. These alterations are variable across stroke subjects. Factors identified as contributing to this variability are the degree of functional impairment, the time interval since stroke, and rehabilitative therapies. Here, the hypothesis is tested that lesion location influences the activation patterns. Using functional magnetic resonance imaging, the objective was to characterize similarities or differences in movement-related activation patterns in patients chronically disabled by cortical plus subcortical or subcortical lesions only. Brain activation was mapped during paretic and non-paretic movement in 11 patients with subcortical stroke, in nine patients with stroke involving sensorimotor cortex, and in eight healthy volunteers. Patient groups had similar average motor deficit as measured by a battery of scores and strength measures. Substantial differences between patients groups were found in activation patterns associated with paretic limb movement: whereas contralateral motor cortex, ipsilateral cerebellum (relative to moving limb), bilateral mesial (cingulate, SMA), and perisylvian regions were active in subcortical stroke, cortical patients recruited only ipsilateral postcentral mesial hemisphere regions, and areas at the rim of the stroke cavity. For both groups, activation in ipsilateral postcentral cortex correlated with motor function; in subcortical stroke, the same was found for mesial and perisylvian regions. Overall, brain activation in cortical stroke was less, while in subcortical patients, more than in healthy controls. For non-paretic movement, activation patterns were similar to control in cortical patients. In subcortical patients, however, activation patterns differed: the activation of non-paretic movement was similar to that of paretic movement (corrected for side). The data demonstrate more differences than similarities in the central control of paretic and non-paretic limb movement in patients chronically disabled by subcortical versus cortical stroke. Whereas standard motor circuitry is utilized in subcortical stroke, alternative networks are recruited after cortical stroke. This finding proposes lesion-specific mechanisms of reorganization. Optimal activation of these distinct networks may require different rehabilitative strategies.

Aged↗
PubMed2004

Short and long-term motor skill learning in an accelerated rotarod training paradigm.

Rodent models of motor skill learning include skilled forelimb reaching and acrobatic locomotor paradigms. This study characterizes motor skill learning in the accelerated rotarod task. Thirty Long-Evans rats (300-400 g) were trained on an accelerated rotarod (1cm/s(2)) over eight consecutive sessions (=days, 20 trials each). Improvement in rotarod velocities mastered before falling off the rod was observed within and between sessions (plateau after five sessions). Intrasession improvement was incompletely retained at the beginning of the next day's session. Over several training sessions, intrasession improvement diminished, suggesting a ceiling effect. After 1 week of pause, the rotarod skill was retained. Locomotor exercise in a running wheel for 30 min before the first rotarod session did not affect intrasession improvement. Running-wheel exposure for 6 days did not diminish the rate of rotarod skill learning (steepness of the learning curve) but improved overall performance (upward shift of curve). Video analysis of gait on the rotarod showed that rats developed a motor strategy by modifying their gait patterns during training. The data demonstrate that rotarod improvement is not the result of enhanced general locomotor ability or fitness, which are trained in the running wheel, but requires a change in the motor strategy to master the task. Accelerated rotarod training can be regarded a valid paradigm for motor skill learning over short (intrasession, minutes) and long time frames (intersession, days).

Analysis of Variance↗
PubMed2004

Biphasic cerebral blood flow velocity profile in patients with aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Increases in cerebral blood flow velocity (CBFV) as measured by transcranial Doppler (TCD) sonography are reflective of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). In serial TCD measurements, some patients exhibit CBFV temporal profiles with two peaks (biphasic). The significance of this finding remains unclear. This retrospective case-control study was conducted to investigate the characteristics and possible predictors of biphasic CBFV profiles. METHODS: Biphasic CBFV profiles were identified in serial TCD examinations (every 1-2 days) of 182 consecutive patients admitted for aneurysmal SAH based on CBFV profiles of the middle cerebral artery on the side of higher maximum velocity. Patients undergoing angioplasty were excluded. Patients meeting these criteria (study patients) were compared to control patients matched for age and Hunt and Hess grade. RESULTS: Eighteen patients (9.9%) demonstrated biphasic CBFV profiles. The first CBFV (134 +/- 11 cm/second) peak occurred on post-SAH day 6 +/- 1, and the second peak (148 +/- 12 cm/second) on day 13 +/- 1. Study patients more often exhibited focal (p < 0.05) symptoms at the time of the first peak. No patient deteriorated neurologically at the time of the second peak. No correlation was observed between CBVF and mean arterial pressure or central venous pressure trends. CONCLUSION: Serial TCD assessment identifies patients with SAH and a biphasic CBFV temporal profile. Although the second peak usually is not associated with a worsening of symptoms, these patients were more likely to exhibit clinical symptoms during the first CBFV peak.

Blood Flow Velocity↗
PubMed2002

Modulation of human corticomotor excitability by somatosensory input.

In humans, somatosensory stimulation results in increased corticomotoneuronal excitability to the stimulated body parts. The purpose of this study was to investigate the underlying mechanisms. We recorded motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) from abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles. MEP amplitudes, recruitment curves (RC), intracortical inhibition (ICI), intracortical facilitation (ICF), resting (rMT) and active motor thresholds (aMT) were recorded before and after a 2-h period of ulnar nerve electrical stimulation at the wrist. Somatosensory input was monitored by recording somatosensory evoked potentials. To differentiate excitability changes at cortical vs. subcortical sites, we recorded supramaximal peripheral M-responses and MEPs to brainstem electrical stimulation (BES). In order to investigate the involvement of GABAergic mechanisms, we studied the influence of lorazepam (LZ) (a GABA(A) receptor agonist) relative to that of dextromethorphan (DM) (an NMDA receptor antagonist) and placebo in a double-blind design. We found that somatosensory stimulation increased MEP amplitudes to TMS only in the ADM, confirming a previous report. This effect was blocked by LZ but not by either DM or placebo and lasted between 8 and 20 min in the absence of (i) changes in MEPs elicited by BES, (ii) amplitudes of early somatosensory-evoked potentials or (iii) M-responses. We conclude that somatosensory stimulation elicited a focal increase in corticomotoneuronal excitability that outlasts the stimulation period and probably occurs at cortical sites. The antagonistic effect of LZ supports the hypothesis of GABAergic involvement as an operating mechanism.

Adolescent↗
PubMed2002

Modulation of rodent cortical motor excitability by somatosensory input.

It is assumed that somatosensory input is required for motor learning and recovery from focal brain injury. In rodents and other mammals, corticocortical projections between somatosensory and motor cortices are modified by patterned input. Whether and how motor cortex function is modulated by somatosensory input to support motor learning is largely unknown. Recent human evidence suggests that input changes motor excitability. Using transcranial magnetic stimulation (TMS), this study tested whether motor cortex excitability is affected by patterned somatosensory stimulation in rodents. Motor potentials evoked in gastrocnemius muscles in response to TMS (MEP(TMS)) and to cervical electrical stimulation (MEP(CES)) were recorded bilaterally. Initially, the first negative peak of the MEP(TMS) was identified as a cortical component because it disappeared after decortication in three animals. Subsequently, we studied the effects of 2 h of electrical stimulation of one sciatic nerve on the cortical component of the MEP(TMS), i.e., on motor cortex excitability. After stimulation, its amplitude increased by 117 +/- 45% ( P<0.01) in the stimulated limb. A significantly smaller effect was found in the unstimulated limb ( P<0.02) and no effect was observed in unstimulated control animals. The subcortically evoked MEP(CES) were not affected by stimulation. It is concluded that somatosensory input increases motor excitability in rat. This increase outlasts the stimulation period and is mediated by supraspinal structures, likely motor cortex. Modulation of motor cortex excitability by somatosensory input may play a role in motor learning and recovery from lesion.

Action Potentials↗