Eckart Altenmüller

Alteration of digital representations in somatosensory cortex in focal hand dystonia

FOCAL hand dystonia involves a loss of motor control of one or more digits; it is associated with the repetitive, synchronous movements of the digits made by musicians over periods of many years. Magnetic source imaging revealed that there is a er distance (fusion) between the representations of the digits in somatosensory cortex for the affected hand of dystonic musicians than for the hands of non-musician control subjects. The data suggest that use-dependent susceptibility to digital representation fusion in cortex may be involved in the etiology of focal dystonia. A successful therapy for the condition has been developed based on this consideration.

Effects of the anticonvulsant benzodiazepine clonazepam on event-related brain potentials in humans☆

The effects of the benzodiazepine clonazepam (a drug used as anticonvulsant) on event-related brain potentials were investigated in healthy human subjects. Thirty-six male student volunteers (mean age 30 years) received clonazepam or a placebo in a double-blind setting. VEPs (visual evoked potentials) were obtained from the standard checkerboard reversal procedure; AEPs (auditory evoked potentials) and slow cortical potentials (CNV) were measured during a 2-stimulus reaction time paradigm, in which the quality of the acoustic S1 signalled whether the acoustic S2 would follow after 2 sec or after 6 sec. Each S2 requested a speeded button press. Compared to placebo, clonazepam significantly reduced P100 amplitude of the VEP and the amplitudes of the AEP components N1 and P3. On the other hand, clonazepam boosted the development of a distinct N2 which was not apparent in placebo subjects. The CNV was significantly reduced and reaction time increased under clonazepam compared to placebo. Specific versus non-specific damping effects of the benzodiazepine are discussed, comparing the present result with the pattern of ERP effects of the anticonvulsant carbamazepine that had been obtained using the same experimental paradigms.

Language processing in aphasia: changes in lateralization patterns during recovery reflect cerebral plasticity in adults

During single word processing the negative cortical DC-potential reveals a left frontal preponderance in normal right-handers as well as in patients with a history of transient aphasia. Lateralization of DC-negativity therefore provides a reliable and robust method for the assessment of language dominance. In 11 stroke patients with permanent aphasia this physiological pattern changed to bilateral activation reflecting an additional right-hemispheric involvement in compensatory mechanisms in aphasia. Along with complete clinical recovery the classical aphasic syndromes revealed specific differences in changes of their lateralization patterns. In Brocas aphasia the initial right-hemispheric preponderance changed to a left frontal lateralization while in Wernickes aphasia a presumably permanent shift towards the right hemisphere occurred. Differences in lateralization patterns might reflect different mechanisms of recovery such as the initial disinhibition of homologous areas contralaterally and subsequent collateral sprouting and synaptic modulation. The assessment of changes in lateralization of the cortical DC-potential during language tasks in a non-invasive, safe method with excellent time resolution that might provide further insights in the neural basis of recovery from aphasia.

The cortical processing of perceived emotion: a DC-potential study on affective speech prosody.

DIRECT current (DC) components of the EEG signal were recorded in 16 right-handed subjects during presentation of pairs of declarative sentences with either happy, sad or neutral intonation. Each stimulus pair had identical wording, but differed at the acoustic level either in pitch (fundamental frequency = F0) range or in duration of stressed syllables. Subjects were asked, first, to identify the emotional category of each sentence pair and, second, to indicate the utterance displaying stronger emotional expressiveness. Stimuli with happy or sad intonation, as well as F0-manipulated neutral sentences, yielded a significantly lateralized negativity towards the right hemisphere (RH). Compared with F0-varied neutral utterances, the discrimination of time-manipulated neutral stimuli resulted in significantly reduced amplitudes, predominantly over RH areas. These results corroborate the suggestion of a dominant role of the RH for the evaluation of the emotional significance of sensory input.

The cortical representation of object motion in man is interindividually variable.

Corticalareas processing visual motion have been well investigated in monkeys, but comparatively little is known about these areas in man. In order to define such cortical areas in the brains of individuals, the magnetic field was recorded while subjects were watching motion-defined static and moving objects. The magnetic response showed a transient component with a clear dipolar magnetic field followed by a sustained component which exhibited some variation in magnetic field structure over time. For the transient component, the single equivalent current dipoles superimposed upon magnetic resonance images for individual subjects were clearly localized outside the primary visual areas. In most cases the neural generator was found in the region of the temporo-parieto-occipital junction of the lateral cortex. The results also suggest that the activated cortical areas show interindividual variations in location.

Disintegration and reorganization of cortical motor processing in two patients with cerebellar stroke

Cerebello-cerebral interaction plays a fundamental role in movement processing. Extensively studied in monkeys, cerebello-thalamo-cerebral information processing is less clear in humans. Taking advantage of the tight linkage between cerebellum and cerebral motor cortex, the objective of this experiment was to gain information on cerebellar function, dysfunction and recovery by analyzing movement-related cortical potentials (MRCPs). MRCPs were recorded prior to voluntary repetitive finger movements from two cerebellar stroke patients, in the acute phase of cerebellar stroke and after clinical recovery. Ten normal subjects served as controls. The main result was a significant depression of late MRCP components over the contralateral motor cortex when patients performed index finger movements of the affected side in the acute phase, and improvement of depressed components after clinical recovery, 8-10 months later. Topographic maps of late MRCP components showed diffusely enlarged potential fields with ataxic movements in the acute phase, and re-focused fields on follow-up. We conclude that (1) late MRCP components are particularly sensitive to cerebellar input in humans and can reflect different functional states of the cerebellum, (2) disturbance of motor cortex function after cerebellar stroke (diaschisis) can occur as a temporary phenomenon that reverses with good clinical recovery.

Cortical DC-Potentials as Electrophysiological Correlates of Hemispheric Dominance of Higher Cognitive Functions

Cortical activation during cognitive processing was assessed with a new, noninvasive electrophysiological method: Cortical DC-potentials were recorded from frontal, central, temporal and parietal electrode positions on the scalps of 150 normal adult subjects while they performed cognitive tasks involving language, calculation, music and spatial vision. During the 10-s registration period, shifts in DC-potentials were analyzed with reference to a baseline 3-s preperiod. 15-30 trials were averaged. A lateralized preponderance of negativity by more than 3 microV was used as the criterion of hemispheric dominance. Language tasks caused left-sided lateralization in 76% of the right-handers (n = 80), bilaterally equal surface negativity in 15% and right-sided lateralization in 9%. During the same tasks, 22% of the left-handers (n = 45) had right-sided lateralization. Calculation tasks produced left-sided lateralization in 65% of the right-handers and left-handers. Music tasks caused more right-sided (53%) than left-sided (39%) lateralization dependent on musical training. Visuospatial processing yielded a right temporoparietal lateralization in 77%.

Modulation of sural nerve somatosensory evoked potentials during stance and different phases of the step-cycle

In order to investigate the modulation of somatosensory processing during stance and locomotion, sural nerve somatosensory evoked potentials were recorded during both stance and different phases of the step-cycle. Characteristic sequences of negative-positive waves were elicited, consisting of an early component, N40, presumably of subcortical origin, followed by a P50-N80-P220 complex of cortical origin. The N40 and N40-P50 components had similar amplitudes in both gait and stance. However, the P50-N80 component was attenuated whereas the N80-P220 complex became biphasic during gait. Within the step-cycle, amplitudes of the cortical components P50-N80 and N80-P110 were larger prior to footfall and smaller at the beginning of the support phase. The results demonstrate that locomotion produces a modulatory effect on somatosensory input at a cortical level. Within the step-cycle, excitability of the somatosensory cortex is increased during the middle and late swing phases and decreased during the support phase. Such modulation may contribute to an improved detection of foot contact at touchdown.

Coregistration of EEG and fMRI in a simple motor task.

The purpose of this study was to evaluate the adequacy of coregistration of movement‐related cortical potentials (MRCPs) and functional magnetic resonance imaging (fMRI) data in the primary sensorimotor cortex. Data were acquired in four normal subjects during right and left simple index finger movements. In fMRI (single‐slice, 1.5 Tesla, T2*‐weighted FLASH sequence), contralateral primary motor (M1) and primary sensory cortex (S1) were activated in all subjects. Spatiotemporal dipole modelling of electric MRCP generators (BESA) revealed two main sources in the central region contralateral to the moving finger. Both sources were tangentially oriented. Their configuration was consistent with source locations in the anterior (M1) and posterior (S1) banks of the central sulcus. Accordingly, the M1 source generated the pre‐movement, the S1 source largely the immediate post‐movement MRCP component. Taken together, MRCP modelling and fMRI data indicated a phasic sequential activation pattern of mostly sulcal portions of contralateral M1 and S1. After coregistration of anatomical MRI, fMRI, and dipole modelling results, the average 3D‐distance between fMRI activation areas and MRCP source locations was 18.6 mm (SD 7.6), with the largest deviation in the anterior‐posterior direction (12.1 ± 9.5 mm). Coregistration inaccuracies of similar magnitude (∼ 17 mm) have been reported previously with MEG and PET or fMRI. We conclude, therefore, that the combination of EEG and fMRI is a promising technique for validation of electrophysiological source models and for evaluation of human functional brain anatomy with both adequate spatial and temporal resolution.

Cortical potentials reflecting motion processing in humans

Motion processing is a fundamental task of visual systems, and in the monkey cortical areas can be identified which appear to be functionally specialized for motion processing. The human visual system is expected to be organized in a similar way. A noninvasive method to study the functional organization of the visual cortex is the recording of scalp potentials generated by neural activity of the underlying cortical areas. In the present study, we recorded slow cortical potentials from normal subjects in order to investigate how motion stimuli are processed. Three classes of object motion were realized as random dot kinematograms, namely Fourier motion, drift-balanced motion, and theta motion, because they require mechanisms of increasing complexity in order to be extracted. Large-field motion and counterphase flicker were used as control stimuli. Three basic results were obtained: (1) The responses evoked by the three classes of object motion do not differ significantly in their course and distribution of activation. (2) The distributions of cortical activation evoked by object motion, and the control stimuli are different. During object motion the maximum activation occurs over the superior parietal cortex. Large-field motion activates occipital and parietal locations to the same extent, and during counterphase flicker the activity is maximum over the occipital lobe. Thus, the parietal slow potentials are interpreted to specifically reflect the cortical processing of object motion. (3) The time course of the activation reflects changes in the spatial position of the object: the amplitude of a transient negative component (TNC) which occurs 240 ms after motion onset decreases with increasing eccentricity of motion onset. The consecutive sustained negative component (SNC), which persists until the movement stops, decreases during centrifugal and increases during centripetal object motion. These results can be understood on the basis of physiological and anatomical knowledge about the mapping of the visual field on the cortex.