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Christian Gerloff

Publications and source records attributed to Christian Gerloff.

At least 19 recordsLinked to original sources

Substantia nigra hypoechogenicity: definition and findings in restless legs syndrome.

Pathological studies demonstrate a decreased iron content in the substantia nigra (SN) contributing to the pathophysiology of restless legs syndrome (RLS). SN echogenicity as measured by transcranial sonography (TCS) correlates with the SN iron content. The objective of this study was to determine a critical value to define SN hypoechogenicity as a potential marker for RLS. There were 49 RLS patients (39 idiopathic, 10 secondary) and 49 age- and sex-matched controls who underwent TCS by 2 independent and blinded examiners to determine the area of SN echogenicity. We found that SN echogenicity is significantly decreased in RLS patients compared to healthy controls (P < 0.001). SN hypoechogenicity (sum area of SN echogenicity of both sides < 0.2 cm(2)) is more common in idiopathic than in secondary RLS patients. The area under curve for idiopathic RLS versus controls (receiver operating characteristics) is 0.91, specificity is 0.90, and sensitivity is 0.82. TCS provides an interesting additional instrument in the diagnosis of RLS. Therefore, SN hypoechogenicity (SN sum area < 0.2 cm(2)), which is supposed to indicate a decreased SN iron content, is a marker for RLS. Further studies are needed to investigate its significance for the pathophysiology of this frequent movement disorder and possible clinical applications.

Female↗

Dose-dependent attenuation of auditory phantom perception (tinnitus) by PET-guided repetitive transcranial magnetic stimulation.

Recent data suggest that chronic tinnitus is a "phantom auditory perception" caused by maladaptive neuroplasticity and subsequent hyperactivity in an extended neuronal network including the primary auditory cortex, higher-order association areas, and parts of the limbic system. It was suggested that attenuation of this tinnitus-associated hyperactivity may offer a rational option for lasting tinnitus reduction. Here, we tested the hypothesis that tinnitus loudness can be attenuated by low-frequency repetitive transcranial magnetic stimulation (rTMS) individually navigated to cortical areas with excessive tinnitus-related activity as assessed by [(15)O]H(2)O positron-emission tomography (PET). Nine patients with chronic tinnitus underwent this combined functional imaging and rTMS-study. Group analysis of the PET data showed tinnitus-related increases of regional cerebral blood flow in the left middle and inferior temporal as well as right temporoparietal cortex and posterior cingulum. Repetitive TMS was performed at 1 Hz and 120% of the motor threshold for 5, 15, and 30 min, navigated to the individual maximum of tinnitus-related cortical hyperactivity. A noncortical stimulation site with the same distance to the ear served as sham control. Tinnitus loudness was reduced after temporoparietal, PET-guided low-frequency rTMS. This reduction, lasting up to 30 min, was dependent on the number of stimuli applied, differed from sham stimulation, and was negatively correlated with the length of the medical history of tinnitus in our patients. These data show the feasibility and effectiveness of rTMS guided by individual functional imaging to induce a lasting, dose-dependent attenuation of tinnitus. Of note, these effects were related to stimulation of cortical association areas, not primary auditory cortex, emphasizing the crucial role of higher-order sensory processing in the pathophysiology of chronic tinnitus.

Aged↗

Effects of brain polarization on reaction times and pinch force in chronic stroke.

BACKGROUND: Previous studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1affected hemisphere) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design. RESULTS: Anodal tDCS shortened reaction times and improved pinch force in the paretic hand relative to Sham stimulation, an effect present in patients with higher impairment. CONCLUSION: tDCS of M1affected hemisphere can modulate performance of motor tasks simpler than those previously studied, a finding that could potentially benefit patients with relatively higher impairment levels.

Adult↗

No effects of enhanced central norepinephrine on finger-sequence learning and attention.

RATIONALE: When paired with training, substances that increase monoaminergic transmission in the brain support motor and language learning in healthy subjects and in rehabilitation after brain lesions. OBJECTIVES: To test the hypotheses that enhancement of central norepinephrine by the selective norepinephrine reuptake inhibitor reboxetine (1) improves skilled motor performance, (2) promotes skilled motor learning, and (3) does not exert these effects by modulation of attention. METHODS: In a double blind, placebo-controlled, crossover study in healthy, adult subjects (n=16), finger-sequence performance and learning was measured after the stimulation of the central noradrenergic system with a single dose (8 mg) of reboxetine and placebo. Effects on attention were assessed by the standardized continuous performance test "CPT-M". RESULTS: No differential effects of reboxetine or placebo on finger-sequence performance, learning and parameters of attention were found. CONCLUSION: Selective stimulation of the central noradrenergic system did not promote skilled motor learning or performance as assessed by finger-sequences. The plasticity-enhancing effect of reboxetine, documented in other studies, appears to be dependent on specific neurophysiological and neuropsychological characteristics of the task, and cannot be generalized to other behavioral paradigms.

Adrenergic Uptake Inhibitors↗

The role of multiple contralesional motor areas for complex hand movements after internal capsular lesion.

Imaging techniques document enhanced activity in multiple motor areas of the damaged and contralesional (intact) hemisphere (CON-H) after stroke. In the subacute stage, increased activity within motor areas in the CON-H during simple movements of the affected hand has been shown to correlate with poorer motor outcome. For those patients in the chronic stage who recovered well, the functional relevance of an increased activation within the CON-H is unclear. Using trains of repetitive transcranial magnetic stimulation (TMS) during performance of complex finger movements, we tested the behavioral relevance of regional functional magnetic resonance imaging (fMRI) activation within the CON-H for sequential finger movement performance of the recovered hand in seven patients who had experienced a subcortical stroke. TMS was navigated over fMRI activation maxima within anatomically preselected regions of the CON-H, and effects were compared with those of healthy controls. Stimulation over the dorsal premotor cortex (dPMC), the primary motor cortex (M1), and the superior parietal lobe (SPL) resulted in significant interference with recovered performance in patients. Interference with the dPMC and M1 induced timing errors only, SPL stimulation caused both timing and accuracy deficits. The present results argue for a persistent beneficial role of the dPMC, M1, and SPL of the CON-H on some aspects of effectively recovered complex motor behavior after subcortical stroke.

Aged↗

Influence of gain of function epithelial chloride channel ClC-Kb mutation on hearing thresholds.

Hearing depends on functional ClC-K-type chloride channels composed of barttin with ClC-Ka or ClC-Kb. Loss-of-function mutations of the barttin gene BSND or of both, the ClC-Ka gene CLNKA and the ClC-Kb gene CLNKB lead to congenital deafness and renal salt wasting. Recently, we identified the gain-of-function mutation ClC-Kb(T481S) which is associated with increased blood pressure. To explore the impact of ClC-Kb(T481S) on hearing, healthy volunteers (n=329) and individuals suffering from tinnitus (n=246) volunteered for hearing tests (n=348) and genetic analysis (n=575). 19.1% of the individuals were heterozygote (ClC-Kb(T481S)/ClC-Kb) and 1.7% homozygote carriers. Pure tone average hearing threshold (PTAt) for air conduction was significantly (p<0.033) lower in ClC-Kb(T481S) carriers (13.2+/-1.2dB) than in wild-type individuals (17.1+/-0.9dB). The prevalence of ClC-Kb(T481S) carriers was significantly increased (29.7%) in individuals with PTAt<15dB (p<0.05) and significantly decreased (13.2%) in individuals with PTAt>30 dB (p<0.017). The difference was largely due to the female population. Bone conduction was less affected pointing to an effect of the mutation on middle ear function. Tinnitus tended to be more frequent in ClC-Kb(T481S) carriers, a difference, however, not statistically significant. In conclusion, hearing thresholds are slightly lower in carriers of ClC-Kb(T481S), i.e., the gain-of-function polymorphism ClC-Kb(T481S) exerts a subtle but significant protective effect against hearing loss.

Adult↗

Coherent corticomuscular oscillations originate from primary motor cortex: evidence from patients with early brain lesions.

Coherent oscillations of neurons in the primary motor cortex (M1) have been shown to be involved in the corticospinal control of muscle activity. This interaction between M1 and muscle can be measured by the analysis of corticomuscular coherence in the beta-frequency range (beta-CMCoh; 14-30 Hz). Largely based on magnetoencephalographic (MEG) source-modeling data, it is widely assumed that beta-CMCoh reflects direct coupling between M1 and muscle. Deafferentation is capable of modulating beta-CMCoh, however, and therefore the influence of reafferent somatosensory signaling and corresponding neuronal activity in the somatosensory cortex (S1) has been unclear. We present transcranial magnetic stimulation (TMS) and MEG data from three adult patients suffering from congenital hemiparesis due to pre- and perinatally acquired lesions of the pyramidal tract. In these patients, interhemispheric reorganization had resulted in relocation of M1 to the contralesional hemisphere, ipsilateral to the paretic hand, whereas S1 had remained in the lesioned hemisphere. This topographic dichotomy allowed for an unequivocal topographic differentiation of M1 and S1 with MEG (which is not possible if M1 and S1 are directly adjacent within one hemisphere). In all patients, beta-CMCoh originated from the contralesional M1, in accordance with the TMS-evoked motor responses, and in contrast to the somatosensory evoked fields (SEFs) for which the sources (N20m) were localized in S1 of the lesioned hemisphere. These data provide direct evidence for the concept that beta-CMCoh reflects the motorcortical efferent drive from M1 to the spinal motoneuron pool and muscle. No evidence was found for a relevant contribution of neuronal activity in S1 to beta-CMCoh.

Adult↗

Spinocerebellar ataxia type 1, 2, and 3 and restless legs syndrome: striatal dopamine D2 receptor status investigated by [11C]raclopride positron emission tomography.

In spinocerebellar ataxias (SCAs), up to 30% of patients complain of restless legs syndrome (RLS). In primary RLS, a putative role of the dopaminergic system has been postulated. To assess dopaminergic function in SCA1, 2, and 3, dopamine D(2) receptor binding potential (BP) was assessed by [(11)C]raclopride positron emission tomography in 10 SCA patients, 4 of whom suffered from RLS as demonstrated by polysomnography. BP was compared to 9 age-matched control subjects. In 2 SCA patients, striatal BP was clearly reduced (<2 SD below the mean of controls). However, there were no significant group differences between SCA and controls, largely owing to a significantly higher variance of striatal BP in SCA. BP was negatively correlated with disease duration. The fit suggests an increased BP in early stages, followed by a moderate decline in all quantified regions (caudate, dorsal putamen, ventral striatum) presumably reflecting a progressive loss of D(2) receptors. RLS in SCA was not accompanied by a significant reduction of D(2) receptor availability in the striatum. This missing correlation may point to an extrastriatal origin of RLS.

Adult↗

Interregional long-range and short-range synchrony: a basis for complex sensorimotor processing.

Communication of distant brain areas provides the basis for integration of complex information in order to adapt to changes in the environment, to process this information, and to generate appropriate behavioral responses necessary for successful behavior in daily life. How is interregional communication realized in the brain? Perceptions and actions are likely to be represented in the brain by large numbers of distributed neurons firing in synchrony. This synchronous activity of distributed neuronal networks can be noninvasively evaluated by multichannel surface electroencephalography (EEG) and the event-related analysis of synchronous EEG signals in the frequency domain. In this chapter we will discuss the role of interregional synchronous activity and its relevance as a mechanism for implementation of successful human complex behavior exemplified within studies of complex finger movements, context-dependent control of complex motor behavior, bimanual motor tasks, visuo-tactile integration, and recovery of motor functions after stroke. These studies provide evidence that synchronous interregional neuronal activity, determined by event-related synchronization (ERS) and desynchronization (ERD), task-related power increases (TRPI) and decreases (TRPD), and event- and task-related coherence (ERCoh, TRCoh) analysis, is one important mechanism for cortical implementation of successful human complex behavior and adaptation to changes in daily life. These results are discussed in the light of recent findings in animal models, substantiating the view of the relevance of interregional synchronous activity for information coding and control of behavior.

Animals↗

Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke.

Clinical recovery after stroke can be significant and has been attributed to plastic reorganization and recruitment of novel areas previously not engaged in a given task. As equivocal results have been reported in studies using single imaging or electrophysiological methods, here we applied an integrative multimodal approach to a group of well-recovered chronic stroke patients (n = 11; aged 50-81 years) with left capsular lesions. Focal activation during recovered hand movements was assessed with EEG spectral analysis and H2(15)O-PET with EMG monitoring, cortico-cortical connectivity with EEG coherence analysis (cortico-cortical coherence) and corticospinal connectivity with transcranial magnetic stimulation (TMS). As seen from comparisons with age-matched controls, our patients showed enhanced recruitment of the lateral premotor cortex of the lesioned hemisphere [Brodmann area (BA) 6], lateral premotor and to a lesser extent primary sensorimotor and parietal cortex of the contralesional hemisphere (CON-H; BA 4 and superior parietal lobule) and left cerebellum (patients versus controls, Z > 3.09). EEG coherence analysis showed that after stroke cortico-cortical connections were reduced in the stroke hemisphere but relatively increased in the CON-H (ANOVA, contrast analysis, P < 0.05), suggesting a shift of functional connectivity towards the CON-H. Nevertheless, fast conducting corticospinal transmission originated exclusively from the lesioned hemisphere. No direct ipsilateral motor evoked potentials (MEPs) could be elicited with TMS over the contralesional primary motor cortex (iM1) in stroke patients. We conclude that (i) effective recovery is based on enhanced utilization of ipsi- and contralesional resources, (ii) basic corticospinal commands arise from the lesioned hemisphere without recruitment of ('latent') uncrossed corticospinal tract fibres and (iii) increased contralesional activity probably facilitates control of recovered motor function by operating at a higher-order processing level, similar to but not identical with the extended network concerned with complex movements in healthy subjects.

Aged↗

Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke.

Stroke is a leading cause of adult motor disability. Despite recent progress, recovery of motor function after stroke is usually incomplete. This double blind, Sham-controlled, crossover study was designed to test the hypothesis that non-invasive stimulation of the motor cortex could improve motor function in the paretic hand of patients with chronic stroke. Hand function was measured using the Jebsen-Taylor Hand Function Test (JTT), a widely used, well validated test for functional motor assessment that reflects activities of daily living. JTT measured in the paretic hand improved significantly with non-invasive transcranial direct current stimulation (tDCS), but not with Sham, an effect that outlasted the stimulation period, was present in every single patient tested and that correlated with an increment in motor cortical excitability within the affected hemisphere, expressed as increased recruitment curves (RC) and reduced short-interval intracortical inhibition. These results document a beneficial effect of non-invasive cortical stimulation on a set of hand functions that mimic activities of daily living in the paretic hand of patients with chronic stroke, and suggest that this interventional strategy in combination with customary rehabilitative treatments may play an adjuvant role in neurorehabilitation.

Activities of Daily Living↗

Larger interregional synchrony is associated with greater behavioral success in a complex sensory integration task in humans.

Successful behavior depends on effective communication between distant brain regions. Moreover, disturbance of effective communication can cause neurological symptoms like apraxia, dyslexia or object agnosia. Interregional communication can be assessed by coherence analysis of synchronized neuronal oscillations, and has been referred to as synchrony or "binding". The concept of synchrony as a means of information coding is attractive, but its functional relevance has been challenged. We hypothesized that if synchrony is functionally relevant in humans, then more synchrony should determine better behavioral performance. Here, we show in a visuotactile integration task that the amount of low-frequency (7-13Hz), long-range electroencephalographic coherence between visual and sensorimotor cortex is significantly correlated with the level of performance. Trials with highest coherences were the most successful ones and vice versa in the absence of differences in regional activation measured as task-related spectral power. In summary, quantitatively linking the amount of long-range synchrony with the degree of behavioral success in humans, the present data suggest that the ability to generate topographically specific synchrony of high amplitude is functionally relevant for behavioral success. They also raise the possibility that the magnitude of regional activation is less representative of the efficacy of brain functioning than interregional synchrony.

Adult↗

Improved motor skill acquisition after selective stimulation of central norepinephrine.

It has been proposed that the beneficial effects of training on motor function can be enhanced by stimulation of alpha-adrenergic mechanisms. Consistent with this view, a single oral dose of the selective norepinephrine reuptake inhibitor reboxetine was found to enhance motor skill acquisition (rapid elbow flexion) and corticomotor excitability tested with transcranial magnetic stimulation in the absence of effects on basal motor performance. Therefore, alpha-adrenergic mechanisms could possibly be manipulated to magnify training effects in neurorehabilitation.

Administration, Oral↗

Cortical involvement in the generation of "involuntary" movements in restless legs syndrome.

The pathophysiology of the restless legs syndrome (RLS) is poorly understood. One index symptom is the urge to move, increasing at night. It is largely accepted that movement in RLS is "involuntary" and that the generators are below the level of the neocortex. Here the authors provide evidence that characteristic leg movements in RLS are preceded by preparatory cortical activation that cannot be attributed to sensory processing or to the expectancy of movement.

Adult↗

Reorganization in congenital hemiparesis acquired at different gestational ages.

It is well established that the reorganizational potential of the developing human brain is superior to that of the adult brain, but whether age-dependent differences exist already in the prenatal and perinatal period is not known. We have studied sensorimotor reorganization in 34 patients with congenital hemiparesis (age range, 5-27 years), using transcranial magnetic stimulation and functional magnetic resonance imaging during simple hand movements. Underlying pathologies were brain malformations (first and second trimester lesions; n = 10), periventricular brain lesions (early third trimester lesions; n = 12), and middle cerebral artery infarctions (late third trimester lesions; n = 12). Of this cohort, eight patients with malformations and all patients with periventricular lesions have been published previously. In all three groups of pathologies, transcranial magnetic stimulation identified patients in whom the paretic hand was controlled via ipsilateral corticospinal projections from the contralesional hemisphere (n = 16). In these patients, the motor dysfunction of the paretic hand correlated significantly with the timing period of the underlying brain lesion. This demonstrates that the efficacy of reorganization with ipsilateral corticospinal tracts indeed decreases during pregnancy.

Adolescent↗

To act or not to act. Neural correlates of executive control of learned motor behavior.

Successful behavior requires contextual modulation of learned "programs", that is, the retrieval or nonretrieval (inhibition) of behavioral elements depending on situative context. Here we report neural correlates of these elementary aspects of behavior as identified with functional magnetic resonance imaging (fMRI). Inhibition of a "ready-to-go" behavioral program was represented in the brain by reduction of net synaptic activity in the cerebro-cerebellar pathway. The metabolic correlate of inhibition was a multifocal (premotor, primary sensorimotor, superior parietal, cingulate cortex, and cerebellum) decrease of the blood oxygenation level-dependent (BOLD) signal to below the resting state (negative BOLD) with a concomitant decrease of motor cortical excitability. The reverse was true for retrieval. We propose that contextual modulation of learned behavioral programs depends on an interplay of focal increases and decreases of neural activity and that the inhibitory changes are reflected by negative BOLD responses in an extended cerebro-cerebellar network of sensorimotor structures.

Adult↗