[Official experimental testing of biomedical products. Regulatory frame and importance of for quality, safety and efficacy]. / Staatliche experimentelle Produktprüfung von biomedizinischen Arzneimitteln. Regulatorischer Rahmen und Bedeutung für die Qualität, Sicherheit und Wirksamkeit.

The official experimental testing of biomedicinal products provides a very significant contribution to ensuring quality, safety and efficacy of these indispensable medicines. Already in the prelicensing phase or to elucidate clusters of increased adverse effects, official medicinal control laboratories are committed to perform experimental testing. The official batch release can be seen as external quality control of the manufacturer's release testing. For proficient performance in these tasks, scientific research is required, in particular on the development and refinement of test methods, and considering the continuous development of innovative biomedicinal products. This article is aimed at introducing the present thematic issue and in particular the regulatory basis of experimental product testing, and illustrates by means of several examples its great importance for the sake of the patients.

Representational cortical plasticity associated with brain tumours: evidence from laser-induced interstitial thermotherapy.

OBJECTIVES: To test the hypothesis that cortical plasticity related to destructive tumour growth is functionally relevant. This hypothesis predicts that function is dependent on the intactness of tissue surrounding the tumour. MATERIAL AND METHODS: Eight patients underwent laser-induced interstitial thermotherapy (LITT) for minimally invasive palliative treatment of brain tumours located in eloquent frontal motor regions including the primary motor cortex. A multimodal approach was used to assess the functional outcome of patients after LITT in detail. RESULTS: Following LITT, motor function deteriorated in four patients. In three of these four patients the LITT-induced lesion involved minimal parts of adjacent non-tumorous tissue. By contrast, the other four patients whose LITT-induced signal changes were confined to the tumour, showed no functional deficits. CONCLUSION: These findings support the idea that peri-tumorous neuronal circuitry in motor competent areas may permanently take over those functions that were formerly represented in the neuronal tissue destroyed by the tumour.

Conscious and subconscious sensorimotor synchronization--prefrontal cortex and the influence of awareness.

One of the most compelling challenges for modern neuroscience is the influence of awareness on behavior. We studied prefrontal correlates of conscious and subconscious motor adjustments to changing auditory rhythms using regional cerebral blood flow measurements. At a subconscious level, movement adjustments were performed employing bilateral ventral mediofrontal cortex. Awareness of change without explicit knowledge of the nature of change led to additional ventral prefrontal and premotor but not dorsolateral prefrontal activations. Only fully conscious motor adaptations to a changing rhythmic pattern showed prominent involvement of anterior cingulate and dorsolateral prefrontal cortex. These results demonstrate that while ventral prefrontal areas may be engaged in motor adaptations performed subconsciously, only fully conscious motor control which includes motor planning will involve dorsolateral prefrontal cortex.

Reorganized cerebral metabolic interactions in temporal lobe epilepsy.

Patients with left temporal lobe epilepsy demonstrate language impairments that are not well understood. To explore abnormal patterns of brain functional connections with respect to language processing, we applied a principal component analysis to resting regional cerebral metabolic data obtained with positron emission tomography in patients with right- and left-sided temporal lobe epilepsy and controls. Two principal components were expressed differentially among the groups. One principal component comprised a pattern of metabolic interactions involving left inferior frontal and left superior temporal regions-corresponding to Broca's and Wernicke's areas, respectively-and right mesial temporal cortex and right thalamus. Functional couplings between these brain regions were abnormally enhanced in the left-sided epilepsy patients. The right thalamic left superior temporal coupling was also abnormally enhanced in the right-sided epilepsy patients, but differentially from that in the left-sided patients. The other principal component was characterized by a pattern of metabolic interactions involving right and left mid prefrontal and right superior temporal cortex. Although both the right- and left-sided epilepsy patients showed decreased functional couplings between left mid prefrontal and the other brain regions, a weaker right-left mid prefrontal coupling in the left-sided epilepsy patients best distinguished them from the right-sided patients. The two mutually independent, abnormal metabolic patterns each predicted verbal intelligence deficits in the patients. The findings suggest a site-dependent reorganization of two independent, language-subserving pathways in temporal lobe epilepsy.

Representations of graphomotor trajectories in the human parietal cortex: evidence for controlled processing and automatic performance.

The aim of this study was to identify the cerebral areas activated during kinematic processing of movement trajectories. We measured regional cerebral blood flow (rCBF) during learning, performance and imagery of right-hand writing in eight right-handed volunteers. Compared with viewing the writing space, increases in rCBF were observed in the left motor, premotor and frontomesial cortex, and in the right anterior cerebellum in all movement conditions, and the increases were related to mean tangential writing velocity. No rCBF increases occurred in these areas during imagery. Early learning of new ideomotor trajectories and deliberately exact writing of letters both induced rCBF increases in the cortex lining the right intraparietal sulcus. In contrast, during fast writing of overlearned trajectories and in the later phase of learning new ideograms the rCBF increased bilaterally in the posterior parietal cortex. Imagery of ideograms that had not been practised previously activated the anterior and posterior parietal areas simultaneously. Our results provide evidence suggesting that the kinematic representations of graphomotor trajectories are multiply represented in the human parietal cortex. It is concluded that different parietal subsystems may subserve attentive sensory movement control and whole-field visuospatial processing during automatic performance.

Thalamic metbolism and corticospinal tract integrity determine motor recovery in stroke.

We studied the role of remote metabolic depressions and pyramidal tract involvement regarding motor recovery following a first hemiparetic ischemic stroke. In 23 patients the regional cerebral glucose metabolism (rCMRGlu) was measured with positron emission tomography and the location and spatial extent of the stroke lesions were assessed by magnetic resonance imaging. Motor impairment during the acute and chronic stages (4 weeks after stroke) was determined by a motor score and recordings of magnetic evoked motor potentials. Twelve patients recovered significantly, whereas 11 patients retained a disabling hemiparesis. In contrast to patients with good motor recovery, rCMRGlu was severely depressed in the thalamus on the lesion side in patients with poor motor recovery. This patient group also showed more severe damage to the pyramidal tract on magnetic resonance images and a more pronounced reduction of the magnetic evoked motor potential amplitude. Neither the size of the stroke lesions nor the spatial extent of the lesional and remote rCMRGlu depressions outside the thalamus correlated with the thalamic hypometabolism and the improvement of the motor score. We conclude that preservation both of parts of the pyramidal tract and of the thalamic circuitry is a major determinant for the quality of hand motor recovery following acute brain ischemia in the adult.

Representation and identity - convergence of brain research and mind-brain philosophy.

The localization or representation of mental abilities in the brain have always been considered as key questions for understanding the organization of the human nervous system. Particularly with the advent of modern electrophysiological and imaging techniques that provide maps of electromagnetic fields and metabolic processes on the living central nervous system, the representation theory is experiencing a scientific renaissance in neurology, but is only one theory, however, in the succession of a long philosophical tradition dealing with the possible identification of mental phenomena and brain processes. This dichotomy was formulated at the latest in the Cartesian dualism of res cogitans and res extensa of the mind-body problem. Nowadays philosophical discussion, on the contrary, is dominated by monistic concepts that attempt to explain the mental realm on an organic foundation in order not to succumb to the problem of a psychophysical dualism. Of these, the identity theory offers a philosophically plausible concept postulating that the identity of brain conditions and mental phenomena is based on organic foundations. In this theory, the efforts of brain research converge on the representations of mental phenomena in the human nervous system. In a comprehensive approach, both concepts could complement each other.