Burkhard Pleger

The neural processes underlying tactile decisions in the human brain remain elusive. We addressed this question in a functional magnetic resonance imaging study using a somatosensory discrimination task, requiring participants to compare the frequency of two successive tactile stimuli. Tactile stimuli per se engaged somatosensory, parietal, and frontal cortical regions. Using a statistical model that accounted for the relative difference in frequencies (i.e., Weber fraction) and discrimination accuracy (i.e., correct or incorrect), we show that trial-by-trial relative frequency difference is represented linearly by activity changes in the left dorsolateral prefrontal cortex (DLPFC), the dorsal anterior cingulate cortex, and bilateral anterior insular cortices. However, a circumscribed region within the left DLPFC showed a different response pattern expressed as activity changes that were monotonically related to relative stimulation difference only for correct but not for incorrect trials. Our findings suggest that activity in the left DLPFC encodes stimulus representations that underlie veridical tactile decisions in humans.

Abstract: The administration of numerous facilitatory drugs in combination with appropriate physiotherapeutic approaches is reported to facilitate neurorehabilitation. First evidence of the possible beneficial influence of facilitatory drugs in neurorehabilitation arose from studies investigating the pharmacology of learning in healthy humans. Amphetamine, for example, has shown to improve performance of different somatosensory and motor skills. Paired with physical therapy in stroke patients, it also increases the rate and extent of motor recovery and supports treatment of aphasia. Amphetamine is however known as a "dirty drug", because it acts non-specifically by increasing centrally the levels of dopamine, serotonin, and noradrenaline. Thus, first approaches intend to scrutinize the role of more specifically acting pharmacological agents on learning and neurorehabilitation. In this review, focus is placed on two main topics: (i) studies that aimed to investigate the pharmacological basis of motor and sensory skills in healthy humans and (ii) studies investigating whether the same drugs may also support neurorehabilitation. First, different sensorimotor paradigms are discussed, which were introduced to investigate basic influences of facilitatory pharmaceuticals on cortical plasticity. Then, emphasis is placed on the role of these drugs acting to gate synaptic plasticity in neurorehabilitation. It is concluded that further studies in large populations should focus on more specifically acting pharmaceuticals, their side effects and their capacity in supporting different patterns of physical therapy.

The pharmacological basis of changes in human behaviour and associated cortical reorganization remains poorly understood. Different paradigms have been introduced to alter motor and somatosensory skills in humans. The underlying changes in synaptic efficacy can be modulated by pharmacological agents acting to gate synaptic plasticity. Non-invasive imaging techniques offer the possibility to assess parallel changes in cortical processing. Cellular studies suggest that there might be only few, but very basic mechanisms that control regulation of synaptic transmission. In particular, the γ-aminobutyric acid (GABA) and the N-methyl-D-aspartic acid (NMDA) receptor, a specific subtype of the glutamatergic receptors, are thought to be crucial in synaptic plasticity. Thus, the application of benzodiazepines facilitating the binding of GABA on GABA(A) receptors, and NMDA receptor blockers, were found to prevent learning and associated cortical reorganization. While there are many approaches to block plastic processes, less is known about drugs, which enhance learning and cortical plasticity. Growing evidence from human studies support the suggestion that learning is subject to amplification by amphetamine. Amphetamine however acts non-specific by increasing centrally the levels of dopamine, serotonin, and noradrenaline. Thus, first approaches that intend to scrutinize the apparently ubiquitous role of only one of these neurotransmitter systems used more specifically acting pharmacological agents. In this review we focus on studies that aimed to investigate the pharmacology of the motor and somatosensory system. First, we introduce standards for testing potential effects of a substance. Then, we focus on biochemical mechanisms of learning, before discussing different motor and somatosensory paradigms which were introduced to elicit changes in cortical excitability or organization in animals and humans. Emphasis is placed on the role of inhibitory and excitatory pharmacological agents acting to gate synaptic plasticity in healthy subjects and patients. It is concluded that future studies that investigate the interaction between artificially modulated receptor activity and specific patterns of behaviour in various neurological disorders may help to improve our understanding of how to support recovery of motor and somatosensory function pharmacologically.