[New aspects of neurorehabilitation: motor and language]. / Neues zur Neurorehabilitation: Motorik und Sprache.

Advancements in medical care over the last decades have contributed to a continuous decline in immediate post-stroke mortality. The flipside of this development is that patients surviving the initial stroke are forced to live with sometimes extreme functional motor and/or language limitations for the remaining life span. The following overview presents evidence-based neurorehabilitative interventions to promote motor and language recovery in the acute and chronic post-stroke stages. Therapeutic approaches comprise intensive training, neuropharmacological drugs and non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) or direct current stimulation (tDCS). Additionally, an outlook on promising future interventions for stroke neurorehabilitation is provided.

Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link?

Epidemiological studies reveal better cognitive function in physically active individuals. Possible mediators for this effect are neurotrophins, which are up-regulated through physical exercise and induce neuronal growth and synaptogenesis in the animal model. Here we cross-sectionally assessed 75 healthy older individuals for levels of physical activity, aerobic fitness, and memory encoding, as well as neurotrophin levels and cerebral gray matter volume. We found that physical activity, but not cardiovascular fitness, was associated with better memory encoding after controlling for age, sex, education, depression, alcohol consumption, and smoking. Higher levels of physical activity were associated with higher levels of the neurotrophin granulocyte colony stimulating factor (G-CSF) and increased cerebral gray matter volume in prefrontal and cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While mediating factors will need to be further elucidated, these findings indicate that even low-level physical activity exerts beneficial effects on memory functions in older individuals.

[Intense language training for aphasia. Contribution of cognitive factors]. / Intensives Sprachtraining bei Aphasie. Einfluss kognitiver Faktoren.

The best predictor of successful language therapy after stroke is a high intensity of treatment (with 5-10 h training per week). However, the necessity of several hours of language exercises each day draws considerably on attentional and cognitive resources of the patients. Thus, not all aphasic patients may be equally suited for intense training approaches. In the present review non-verbal cognitive deficits that often accompany a stroke-induced aphasia are described. Furthermore, initial empirical data on cognitive functions, which predict the success of therapy (intense) after stroke, are summarized. Patients in the acute stage benefit most from intense aphasia treatment, when long-term memory consolidation is relatively preserved. For the chronic stage, indirect evidence suggests that premorbid intelligence as well as attentional functions have positive effects on the success of intense therapy. An empirically based allocation of patients to intense aphasia treatment awaits the results of multicenter trials with sufficiently large sample sizes.

Degree of language lateralization determines susceptibility to unilateral brain lesions.

Language is considered a function of either the left or, in exceptional cases, the right side of the brain. Functional imaging studies show, however, that in the general population a graded continuum from left hemispheric to right hemispheric language lateralization exists. To determine the functional relevance of lateralization differences, we suppressed language regions using transcranial magnetic stimulation (TMS) in healthy human subjects who differed in lateralization of language-related brain activation. Language disruption correlated with both the degree and side of lateralization. Subjects with weak lateralization (more bilaterality) were less affected by either left- or right-side TMS than were subjects with strong lateralization to one hemisphere. Thus in some people, language processing seems to be distributed evenly between the hemispheres, allowing for ready compensation after a unilateral lesion.

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.

D-amphetamine does not improve outcome of somatosensory training.

BACKGROUND: D-amphetamine has been shown to affect early stages of stroke recovery, and may have a beneficial effect on functions when administered later after stroke. OBJECTIVE: To test D-amphetamine effects on skill acquisition after the acute or subacute stages of stroke, when lesion-related structural changes have consolidated. METHODS: Sixteen healthy subjects were treated with D-amphetamine during a 4-week training of tactile frequency discrimination in a placebo-controlled, double-blind design. RESULTS: All subjects improved significantly in tactile temporal acuity. However, improvement did not differ in subjects treated with or without D-amphetamine. CONCLUSION: No beneficial effect of D-amphetamine on somatosensory training improvements was found in healthy subjects.

Role of the striatum and the cerebellum in motor skill acquisition.

Motor skill acquisition was investigated in patients with Parkinson's disease (PD) or cerebellar dysfunction using two sensory-guided tracking tasks. The subjects had to learn to track a visual target (a square) on a computer screen by moving a joystick under two different conditions. In the unreversed task, the horizontal target movements were semi-predictable and could be anticipated. In the reversed task, the horizontal movements of a pointer which had to be kept within the target square were mirror-reversed to the joystick movements. PD patients showed intact learning of the semi-predictable task and reduced learning of the mirror-reversed task; patients with cerebellar dysfunction showed the opposite pattern. These findings are discussed in relation to the differential contribution of the cerebellum and the striatum to motor skill acquisition: the cerebellum appears to participate in the implementation of anticipatory movements, whereas the striatum may be critically involved in types of motor learning which require a high degree of internal elaboration.

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.

[Present status and future possibilities of adjuvant pharmacotherapy for aphasia]. / Pharmakologische Zusatzbehandlung in der Aphasietherapie : Status quo und Perspektiven.

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.

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.

[Language acquisition and statistical learning]. / Spracherwerb und statistisches Lernen.

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.

Impaired perception of vocal emotions in Parkinson's disease: influence of speech time processing and executive functioning.

Little is known about the underlying dimensions of impaired recognition of emotional prosody that is frequently observed in patients with Parkinson's disease (PD). Because patients with PD also suffer from working memory deficits and impaired time perception, the present study examined the contribution of (a) working memory (frontal executive functioning) and (b) processing of the acoustic parameter speech rate to the perception of emotional prosody in PD. Two acoustic parameters known to be important for emotional classifications (speech duration and pitch variability) were systematically varied in prosodic utterances. Twenty patients with PD and 16 healthy controls (matched for age, sex, and IQ) participated in the study. The findings imply that (1) working memory dysfunctions and perception of emotional prosody are not independent in PD, (2) PD and healthy control subjects perceived vocal emotions categorically along two acoustic manipulation continua, and (3) patients with PD show impairments in processing of speech rate information.

Classical eyeblink conditioning in Parkinson's disease.

Patients with Parkinson's disease (PD) show impairments of a range of motor learning tasks, including tracking or serial reaction time task learning. Our study investigated whether such deficits would also be seen on a simple type of motor learning, classic conditioning of the eyeblink response. Medicated and unmediated patients with PD showed intact unconditioned eyeblink responses and significant learning across acquisition; the learning rates did not differ from those of healthy control subjects. The overall frequency of conditioned responses was significantly higher in the medicated patients with PD relative to control subjects, and there was also some evidence of facilitation in the unmedicated patients with PD. Conditioning of electrodermal and electrocortical responses was comparable in all groups. The findings are discussed in terms of enhanced excitability of brainstem pathways in PD and of the involvement of different neuronal circuits in different types of motor learning.

Behavioural relevance of atypical language lateralization in healthy subjects.

In most humans, language is lateralized to the left side of the brain. It has been speculated that this hemispheric specialization is a prerequisite for the full realization of linguistic potential. Using standardized questionnaires and performance measures, we attempted to determine if there are behavioural correlates of atypical, i.e. right-hemispheric and bilateral, language lateralization. The side and degree of language lateralization were determined by measuring the hemispheric perfusion differences by functional transcranial Doppler ultrasonography during a word generation task in healthy volunteers. Subjects with left (n = 264), bilateral (n = 31) or right (n = 31) hemisphere language representation did not differ significantly with respect to mastery of foreign languages, academic achievement, artistic talents, verbal fluency or (as assessed in a representative subgroup) in intelligence or speed of linguistic processing. These findings suggest that atypical hemispheric specialization for language, i.e. right-hemisphere or bilateral specialization, is not associated with major impairments of linguistic faculties in otherwise healthy subjects.

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.