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S Knecht

Publications and source records attributed to S Knecht.

At least 19 recordsLinked to original sources
PubMed2006

Levodopa increases memory encoding and dopamine release in the striatum in the elderly.

Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training. This study examined the link between both phenomena. We hypothesized that levodopa would (a) ameliorate aging-dependent deficits in motor memory formation, and (b) increase dopamine availability at the dopamine type 2-like (D2) receptor during training in task-relevant brain structures. The effects of training plus levodopa (100mg, plus 25mg carbidopa) on motor memory formation and striatal dopamine availability were measured with [(11)C]raclopride (RAC) positron emission tomography (PET). We found that levodopa did not alter RAC-binding potential at rest but it enhanced training effects on motor memory formation as well as dopamine release in the dorsal caudate nucleus. Motor memory formation during training correlated with the increase of dopamine release in the caudate nucleus. These results demonstrate that levodopa may ameliorate dopamine deficiencies in the elderly by replenishing dopaminergic presynaptic stores, actively engaged in phasic dopamine release during motor training.

Aged↗
PubMed2006

The assessment of hemispheric lateralization in functional MRI--robustness and reproducibility.

Various methods have been proposed to calculate a lateralization index (LI) on the basis of functional magnetic resonance imaging (fMRI) data. Most of them are either based on the extent of the activated brain region (i.e., the number of "active" voxels) or the magnitude of the fMRI signal change. The purpose of the present study was to investigate the characteristics of various variants of these approaches and to identify the one that yields the most robust and reproducible results. Robustness was assessed by evaluating the dependence on arbitrary external parameters, reproducibility was assessed by Pearson's correlation coefficient. LIs based on active voxels counts at one single fixed statistical threshold as well as LIs based on unthresholded signal intensity changes (i.e., based on all voxels in a region of interest) yielded neither robust nor reproducible laterality results. Instead, the lateralization of a cognitive function was best described by "thresholded" signal intensity changes where the activity measure was based on signal intensity changes in those voxels in a region of interest that exceeded a predefined activation level. However, not all other approaches should be discarded completely since they have their own specific application fields. First, LIs based on active voxel counts in the form of p-value-dependent lateralization plots (LI=LI(p)) can be used as a straightforward measure to describe hemispheric dominance. Second, LIs based on active voxel counts at variable thresholds (standardized by the total number of active voxels) are a good alternative for big regions of interest since LIs based on signal intensity changes are restricted to small ROIs.

Adult↗
PubMed2006

Subcortical reorganization in amyotrophic lateral sclerosis.

The cerebral cortex reorganizes in response to central or peripheral lesions. Although basal ganglia and cerebellum are key components of the network dedicated to movement control, their role in motor reorganization remains elusive. We therefore tested if slowly progressive neurodegenerative motor disease alters the subcortical functional anatomy of the basal ganglia-thalamo-cerebellar circuitry. Ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls underwent functional magnetic resonance imaging (fMRI), while executing a simple finger flexion task. Cued by an acoustic trigger, they squeezed a handgrip force transducer with their right hand at 10% of their maximum voluntary contraction force. Movement frequency, amplitude, and force were controlled. Statistical parametric mapping of task-related BOLD-response revealed increased activation in ALS patients as compared to healthy controls. The main activation increases were found in the supplementary motor area, basal ganglia, brainstem, and cerebellum. These findings suggest that degeneration of cortical and spinal motor neurons in ALS leads to a recruitment of subcortical motor structures. These subcortical activation patterns strongly resemble functional activation in motor learning and might therefore represent adaptations of cortico-subcortical motor loops as a - albeit finally ineffective - mechanism to compensate for the ongoing loss of motor neurons in ALS.

Acoustic Stimulation↗
PubMed2006

[Present status and future possibilities of adjuvant pharmacotherapy for aphasia].

Aphasia is one of the most frequent and disabling consequences of stroke. Poor spontaneous recovery and the limited success of conventional speech therapy bring up the question of how current treatment approaches can be improved. Besides increasing training frequency-with daily sessions lasting several hours and high repetition rates of language materials ("massed training")-adjuvant drug therapy may help to increase therapy efficacy. In this article, we illuminate the potential of monoaminergic (bromocriptine, levodopa, d-amphetamine) and cholinergic (donepezil) substances for treating aphasia. For a final evaluation of combined massed training and adjuvant pharmacotherapy, randomized, placebo-controlled (multicenter) clinical trials with sufficient numbers of patients are needed. Furthermore, results of experimental animal studies of functional recovery in brain damage raise hopes that neurotrophic factors or stem cells might find a place in recovery from aphasia in the intermediate future.

Aphasia↗
PubMed2005

Dopaminergic effects on encoding of a motor memory in chronic stroke.

The effects of a single oral dose of levodopa administered in a randomized, double-blind, placebo-controlled cross-over design on formation of a motor memory were studied by a training protocol in patients with chronic stroke. Levodopa enhanced the ability of motor training to encode an elementary motor memory relative to placebo. Up-regulation of dopaminergic function may enhance motor memory formation, crucial for successful rehabilitative treatments in patients with chronic stroke.

Aged↗
PubMed2005

Hemispheric lateralization of spatial attention in right- and left-hemispheric language dominance.

Hemispheric lateralization of the neural systems supporting language and spatial attention most commonly dissociate in healthy individuals. However, the reverse pattern with association of language and attention within the right hemispheres has also been observed. We investigated in 75 healthy volunteers (37 right-handed, 38 left-handed) if language and spatial attention may associate not only in individuals with an atypical pattern of language lateralization, but also in subjects showing the standard, i.e. left-hemispheric dominance for language. Hemispheric lateralization of cerebral perfusion was determined with functional transcranial Doppler ultrasonography during a visuospatial attention, and a word generation task. We found that language and visuospatial attention associated within the left hemisphere in five subjects and within the right hemisphere in eight subjects. We conclude that all combinations of cerebral lateralization for language and attention may exist in the healthy brain.

Adolescent↗
PubMed2005

Dehydration confounds the assessment of brain atrophy.

Computerized brain volumetry has potential value for diagnosis and the follow-up evaluation of degenerative disorders. A potential pitfall of this method is the extent of physiologic variations in brain volume. The authors show that dehydration and rehydration can significantly change brain volume: lack of fluid intake for 16 hours decreased brain volume by 0.55% (SD, +/-0.69), and after rehydration total cerebral volume increased by 0.72% (SD, +/-0.21).

Adult↗
PubMed2005

Language lateralization in young children assessed by functional transcranial Doppler sonography.

Compared to adults, children show superior recovery of language function after damage to the dominant brain hemisphere. Possible explanations are that children have different patterns of language representation or display different patterns of reorganization. Information about language lateralization in children could provide insights into the repair mechanisms of the young brain. While functional magnetic resonance imaging (fMRI) is usually difficult to perform in children younger than 5 years, functional transcranial Doppler sonography (fTCD) is nonfrightening and readily applicable in young and very young children. However, for serial examinations, sufficient validity and reliability are required. To this end, we designed a picture-description language task (PDLT) for fTCD examinations in children, compared the outcome to established protocols and determined the 1 month retest-reliability of the measurement in 16 children aged 2-9 years. The dependent variable was the task-related hemispheric perfusion difference based on averaged relative cerebral blood flow velocity (CBFV) increases in the middle cerebral arteries. This picture-description language lateralization index was compared to language lateralization by a phonetic word generation task (PWGT) in adults revealing good intermethod validity (r=0.70; P <or= 0.05). The 1 month retest-reliability of the PDLT in the children was r=0.87 (P <or= 0.05). With this degree of reliability, fTCD seems a promising tool for the assessment of changes in hemispheric involvement in language in young and very young children.

Algorithms↗
PubMed2005

Scalp position and efficacy of transcranial magnetic stimulation.

OBJECTIVE: To assess the impact of the scalp site on the biological effects of TMS. METHODS: We performed high-resolution, three-dimensional whole head magnetic resonance imaging (MRI) in a healthy subject, systematically measured the scalp-to-cortex distance across the head and calculated the resulting electric field in the superficial cortex. RESULTS: The variability in scalp-to-cortex distance led to differences in calculated cortical electric field strengths of a factor of two. A major portion of this variability was explained by a lateral to medial gradient with scalp-to-cortex distances being greatest close to the midline and smallest towards the temporal coordinates. CONCLUSIONS: Because of the medio-lateral gradient in scalp-to-cortex distance interventions tailored on the basis of effects of TMS in the motor system will systematically induce stronger than expected electric currents when performed laterally to the motor spot. SIGNIFICANCE: The biological effects of TMS outside the motor spot may be markedly different from those observed in the motor system and this should be taken into account to optimize TMS for the evaluation or treatment of neuropsychiatric disorders.

Adult↗
PubMed2004

Familial aggregation of strong hemispheric language lateralization.

The most conspicuous aspect of the neural basis of language is the uneven involvement of the cerebral hemispheres. The familial distribution of variable degrees of left-hemispheric language lateralization was investigated. A significant familial aggregation of strong left-hemispheric language lateralization and a positive association of the degree of language lateralization between parents and their children were found. These data strongly suggest a genetic determination of the degree of language lateralization.

Adolescent↗
PubMed2004

How does the brain accommodate to increased task difficulty in word finding? A functional MRI study.

In functional imaging of the brain, the difficulty of a task may be critical for the pattern of activation. Increased task difficulty could lead to increased activation in task-specific regions or to activation of additional, "compensatory" regions. A previous study with functional transcranial Doppler sonography (fTCD) showed no evidence that increased difficulty in word retrieval leads to a recruitment of areas homologous to language-related regions. The question remains how the brain accommodates increasing task difficulty. Because of limitations of fTCD method, we used functional magnetic resonance imaging (fMRI) in this study. We manipulated word retrieval difficulty in healthy subjects (n = 14) to determine whether the classical language-related brain regions are activated with increasing difficulty in word retrieval. fMRI demonstrated that with increased task difficulty (I) the lateralization of language-associated brain activation remained constant, (II) no additional activation of language-related regions of the dominant hemisphere, nor of homologous regions of the subdominant hemisphere, was evident, (III) additional activation was found in right posterior parietal cortex--typically associated with sustained attention and executive control. Thus, increased difficulty in word retrieval leads to coactivation of distinct brain areas, working together in a large cognitive network, rather than to increased activation of typically language-related areas.

Adult↗
PubMed2004

Orthopedic and neurological complications of cervical dystonia--review of the literature.

Cervical dystonia is the most frequent form of focal dystonia. Further, cervical dystonia can occur as a feature of segmental or generalized dystonias and cerebral palsy. Treatment with botulinum toxin to relieve pain and improve functional and psychological outcome is effective, but expensive. However, pharmacoeconomic studies evaluating treatment and disease costs have not taken into consideration the long-term complications of cervical dystonia. Here we present a review of the medical literature on orthopedic and neurological complications arising from cervical dystonia, including cervical spine degeneration, spondylosis, disk herniation, vertebral subluxations and fractures, radiculopathies and myelopathies. In summary, complications are more often reported in generalized dystonia and cerebral palsy than in focal dystonia. The prevalence is not well established, published estimations go from 18 to 41% in selected populations. Awareness of the frequent occurrence of complications and screening for symptoms of radiculomyelopathy in patients with dystonia is essential to avoid irreversible spinal cord damage. Complications of cervical dystonia need to be taken into consideration when weighting risks and calculating costs of the disease and its treatment.

Humans↗
PubMed2004

A method for the automated assessment of temporal characteristics of functional hemispheric lateralization by transcranial Doppler sonography.

BACKGROUND AND PURPOSE: Transcranial Doppler sonography (TCD) can guide and complement investigations based on functional magnetic resonance and positron emission tomography imaging by providing continuous information on cerebral perfusion changes correlated to cerebral activation. So far, however, the role of functional TCD has been limited by a lack of sensitivity. METHODS: Here, the authors present an outline of a method that increases the potential of TCD to detect perfusion changes within a vascular territory. Sensitivity on the order of 1% can be achieved by transformation of Doppler envelope curves, which accounts for systemic quasi-periodic and irregular spontaneous blood flow modulations and artificial disturbances related to the recording. A statistical technique is introduced that allows the automatic detection of time periods of significant hemispheric lateralization in evoked flow studies. Furthermore, an index of laterality is defined quantifying the extent of hemispheric dominance during stimulus processing. RESULTS AND DISCUSSION: The analysis technique described in this article has been successfully employed in recent examinations on vision, motor activation, language, language recovery, and other cognitive tasks. CONCLUSION: The novel functional TCD technique permits valid and reproducible assessments of the temporal characteristics of functional hemispheric lateralization.

Blood Flow Velocity↗
PubMed2003

[Language acquisition and statistical learning].

Statistical learning is a basic mechanism of information processing in the human brain. The purpose lies in the extraction of probabilistic regularities from the multitude of sensory inputs. Principles of statistical learning contribute significantly to language acquisition and presumably also to language recovery following stroke. The empirical database presented in this manuscript demonstrates that the process of word segmentation, acquisition of a lexicon, and acquisition of simple grammatical rules can be entirely explained through statistical learning. Statistical learning is mediated by changes in synaptic weights in neuronal networks. The concept therefore stands at the transition to molecular biology and pharmacology of the neuronal synapse. It still remains to be shown if all aspects of language acquisition can be explained through statistical learning and which regions of the brain are involved in or capable of statistical learning. Principles of effective language training are obvious already. Most important is the massive, repeated interactive exposure. Conscious processing of the stimulus material may not be essential. The crucial principle is a high cooccurrence of language and corresponding sensory processes. This requires a more intense training frequency than traditional aphasia treatment programs provide.

Adult↗
PubMed2003

How atypical is atypical language dominance?

Atypical, right-hemisphere language dominance is poorly understood. It is often observed in patients with brain reorganization due to lesions early in life. It can also be encountered in seemingly normal individuals. We compared the patterns of neural language activation in 7 individuals with left- and 7 with right-hemisphere language dominance, none of whom had any evidence of brain lesions. We speculated that incongruencies in the activation patterns in atypical, right-hemisphere language dominance could indicate a reorganized neural language system after undetected early brain damage. Functional magnetic resonance imaging analysis of brain activation during phonetic word generation demonstrated (1). no increased activation in the subdominant hemisphere in right compared to left language dominance, (2). a similar variability in the pattern of activation in both groups, and (3). a mirror reverse pattern of activation in right- compared to left-hemisphere dominant subjects. These findings support the view that in individuals with an unrevealing medical history right-hemispheric dominance constitutes a natural rather than an abortive variant of language lateralization.

Adult↗