Konrad J. Werhahn

Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans

1 Blockade of uptake carriers of γ‐aminobutyric acid (GABA) has been shown to modulate inhibition in cortical slices of experimental animals, although little is known about this mechanism in vivo and, in particular, in humans. 2 The effects of blockade of GABA uptake were studied using transcranial magnetic stimulation (TMS) in humans. In eight healthy volunteers several measures of cortical excitation and inhibition were obtained before and ≈2 h after ingestion of 5‐15 mg of tiagabine (TGB). 3 After TGB ingestion, the duration of the TMS‐induced silent period observable in the electromyogram of the voluntarily contracted target muscle was prolonged. Similarly, paired‐pulse inhibition of the motor‐evoked potential (MEP), as tested by delivering two magnetic shocks of equal suprathreshold intensities at 160 ms interstimulus interval (ISI), was more pronounced. In apparent contradistinction, paired‐pulse inhibition of the MEPs produced by a subthreshold conditioning stimulus delivered 3 ms prior to a suprathreshold stimulus was reduced. Paired‐pulse facilitation elicited by the same double‐shock protocol at an ISI of 10 ms was increased. 4 The prolongation of the GABAB receptor‐mediated component of the inhibitory postsynaptic potential observed with TGB in in vitro studies probably underlies the increase in cortical silent period duration. The reduction of the paired‐pulse inhibition at 3 ms, in turn, probably reflects inhibition of GABAA receptor‐mediated inhibition via presynaptic GABAB receptors. 5 These data provide in vivo evidence of differential modulation of cortical inhibition by blockade of GABA uptake. Presynaptic GABA autoreceptors may be involved in modulating cortical inhibition in the human motor cortex.

Contribution of the ipsilateral motor cortex to recovery after chronic stroke

It has been proposed that the intact (ipsilateral) motor cortex play a significant role mediating recovery of motor function in the paretic hand of chronic stroke patients, but this hypothesis has not been tested experimentally. Here, we evaluated the effects of transcranial magnetic stimulation (TMS) on motor performance of the paretic hand of chronic stroke patients and healthy controls. We hypothesized that, if activity in the intact hemisphere contributes to functional recovery, TMS should result in abnormal motor behavior in the paretic hand. We found that stimulation of the intact hemisphere resulted in delayed simple reaction times (RTs) in the contralateral healthy but not in the ipsilateral paretic hand, whereas stimulation of the lesioned hemisphere led to a marked delay in RT in the contralateral paretic hand but not in the ipsilateral healthy hand. RT delays in the paretic hand correlated well with functional recovery. Finger tapping in the paretic hand was affected by TMS of the lesioned but not the intact hemisphere. These results are consistent with the idea that recovered motor function in the paretic hand of chronic stroke patients relies predominantly on reorganized activity within motor areas of the affected hemisphere.

Electroencephalography during functional echo-planar imaging: detection of epileptic spikes using post-processing methods.

EEG has been used to trigger functional MRI of patients with focal epilepsy, but EEG can be obscured by artifacts during MR data acquisition, and no continuous correlation of EEG and MRI has been possible without limiting the image time. Artifacts caused by an MRI sequence were investigated in five healthy subjects, and an EEG of five patients with epileptic discharges was recorded during echo‐planar imaging. All interfering frequencies in the EEG were discrete and defined by loop structures in the MRI sequence. In post‐processing of the EEG interfering frequencies were automatically detected by comparing the frequency spectra of the EEG recorded before and during imaging. After elimination of interfering frequencies by filters in the time domain or by Fourier transform, reliable spike detection in the EEG recorded during MR data acquisition became feasible, without loss of EEG quality. Magn Reson Med 44:791–798, 2000.

Enhanced tactile spatial acuity and cortical processing during acute hand deafferentation

Acute deafferentation of a limb results in bilateral cortical reorganization, but the behavioral consequences of this phenomenon are unknown. Here we found rapid improvements in tactile spatial acuity and changes in cortical processing for the left hand during cutaneous anesthesia of the right hand. The site-specific improvement in tactile spatial acuity may represent a behavioral compensatory gain.

Functional connectivity between somatosensory and visual cortex in early blind humans

Crossmodal plasticity occurs when loss of input in one sensory modality leads to reorganization in brain representations of other sensory modalities. In congenital blindness the visual cortex becomes responsive to somatosensory input such as occurs during Braille reading. The route by which somatosensory information reaches the visual cortex is not known. Here, we used repetitive transcranial magnetic stimulation (rTMS) to probe the connection between primary somatosensory cortex (S1) and early visual cortex (V1 and neighboring areas), combining rTMS with positron emission tomography (PET). We applied stimulation over S1 in sighted, early blind and late blind individuals. Baseline regional cerebral blood flow in occipital cortex was highest in early blind and lowest in late blind individuals. Only the early blind group showed significant activation of early visual areas when rTMS was delivered over S1. This activation was significantly higher in early than in late blind, but not relative to sighted controls. These results are consistent with the hypothesis that tactile information may reach early visual areas in early blind humans through cortico‐cortical pathways, possibly supporting enhanced tactile information processing.

Influence of somatosensory input on motor function in patients with chronic stroke

In healthy volunteers, reduction of somatosensory input from one hand leads to rapid performance improvements in the other hand. Thus, it is possible that reduction of somatosensory input from the healthy hand can influence motor function in the paretic hand of chronic stroke patients with unilateral hand weakness. To test this hypothesis, we had 13 chronic stroke patients perform motor tasks with the paretic hand and arm during cutaneous anesthesia of the healthy hand and healthy foot in separate sessions. Performance of a finger tapping task, but not a wrist flexion task, improved significantly with anesthesia of the hand, but not the foot. This effect progressed with the duration of anesthesia and correlated with baseline motor function. We conclude that cutaneous anesthesia of the healthy hand elicits transient site‐specific improvements in motor performance of the moderately paretic hand in patients with chronic stroke, consistent with interhemispheric competition models of sensorimotor processing. Ann Neurol 2004;56:206–212

Multimodal output mapping of human central motor representation on different spatial scales

1 Non‐invasive mapping by focal transcranial magnetic stimulation (TMS) is frequently used to investigate cortical motor function in the intact and injured human brain. We examined how TMS‐derived maps relate to the underlying cortical anatomy and to cortical maps generated by functional imaging studies. 2 The centres of gravity (COGs) of TMS maps of the first dorsal intersosseus muscle (FDI) were integrated into 3‐D magnetic resonance imaging (MRI) data sets in eleven subjects. In seven of these subjects the TMS‐derived COGs were compared with the COG of regional cerebral blood flow increases using positron emission tomography (PET) in an index finger flexion protocol. 3 Mean TMS‐derived COG projections were located on the posterior lip of the precentral gyrus and TMS‐derived COG projections were in close proximity to the mean PET‐derived COG, suggesting that the two methods reflect activity of similar cortical elements. 4 Criteria for a reliable assessment of the COG and the number of positions with a minimum amplitude of two‐thirds of the maximum motor‐evoked potential (T3Ps) were determined as a function of the number of stimuli and extension of the stimulation field. COGs and T3Ps were compared with an estimate of the size of the human motor cortex targeting α‐motoneurons of forearm muscles. This comparison suggests that TMS can retrieve spatial information on cortical organization below the macroanatomic scale of cortical regions. 5 Finally, we studied the cortical representation of hand muscles in relation to facial and foot muscle representations and investigated hemispherical asymmetries. We did not find any evidence for a different ipsi‐ or contralateral representation of the mentalis muscle. Also, no difference was found between FDI representations on the dominant versus the non‐dominant hemisphere.

Decreased Dopamine D2/D3‐Receptor Binding in Temporal Lobe Epilepsy: An [18F]Fallypride PET Study

Summary:  Purpose: Although animal data are suggestive, evidence for an alteration of the extrastriatal dopaminergic system in human focal epilepsy is missing.

Die semiologische Klassifikation epileptischer Anfälle

ZusammenfassungIn den letzten Jahren wird zunehmend diskutiert, daß die 1981 vorgestellte Klassifikation epileptischer Anfälle der Internationalen Liga gegen Epilepsie revisionsbedürftig ist. Insbesondere von epilepsiechirurgisch tätigen Zentren wurden Verbesserungsvorschläge gemacht. Die hier vorgestellte semiologische Anfallsklassifikation basiert ausschließlich auf der klinischen Anfallssemiologie und bietet theroetische und praktische Vorteile, die im einzelnen erläutert werden. Sie soll als Diskussionsgrundlage dafür dienen, neue Aspekte in die Klassifikation epileptischer Anfälle einzuführen, die praktische Konsequenzen für die Diagnostik und Behandlung der Patienten haben.SummaryRecent advances in epileptology and epilepsy surgery require revision of the currently used International Classification of Epileptic Seizures, which was published 1981. We present a classification of epileptic seizures which is based purely on the clinical seizure semiology. The advantages of a semiological seizure classification are stressed.

A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy.

To compare the effectiveness of controlled‐released carbamazepine (CR‐CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy.