Thomas Bauermann

Occurence and Clinical Predictors of Spasticity After Ischemic Stroke

Background and Purpose— There is currently no consensus on (1) the percentage of patients who develop spasticity after ischemic stroke, (2) the relation between spasticity and initial clinical findings after acute stroke, and (3) the impact of spasticity on activities of daily living and health-related quality of life. Methods— In a prospective cohort study, 301 consecutive patients with clinical signs of central paresis due to a first-ever ischemic stroke were examined in the acute stage and 6 months later. At both times, the degree and pattern of paresis and muscle tone, the Barthel Index, and the EQ-5D score, a standardized instrument of health-related quality of life, were evaluated. Spasticity was assessed on the Modified Ashworth Scale and defined as Modified Ashworth Scale >1 in any of the examined joints. Results— Two hundred eleven patients (70.1%) were reassessed after 6 months. Of these, 42.6% (n=90) had developed spasticity. A more severe degree of spasticity (Modified Ashworth Scale ≥3) was observed in 15.6% of all patients. The prevalence of spasticity did not differ between upper and lower limbs, but in the upper limb muscles, higher degrees of spasticity (Modified Ashworth Scale ≥3) were more frequently (18.9%) observed than in the lower limbs (5.5%). Regression analysis used to test the differences between upper and lower limbs showed that patients with more severe paresis in the proximal and distal limb muscles had a higher risk for developing spasticity (P≤0.001). Spasticity of the upper and lower limb was more frequent in patients with hemihypesthesia than in patients without sensory deficits (P≤0.001). Patients with spasticity showed a lower Barthel Index and EQ-5D score compared with the group without spasticity. Conclusions— Spasticity was present in 42.6% of patients with initial central paresis. However, severe spasticity was relatively rare. Predictors for the development of spasticity were a severe degree of paresis and hemihypesthesia at stroke onset.

Covariations Among fMRI, Skin Conductance, and Behavioral Data During Processing of Concealed Information

Imaging techniques have been used to elucidate the neural correlates that underlie deception. The scientifically best understood paradigm for the detection of deception, however, the guilty knowledge test (GKT), was rarely used in imaging studies. By transferring a GKT‐paradigm to a functional magnetic resonance imaging (fMRI) study, while additionally quantifying reaction times and skin conductance responses (SCRs), this study aimed at identifying the neural correlates of the behavioral and electrodermal response pattern typically found in GKT examinations. Prior to MR scanning, subjects viewed two specific items (probes) and were instructed to hide their knowledge of these. Two other specific items were designated as targets and required a different behavioral response during the experiment and eight items served as irrelevant stimuli. Reaction times and SCR amplitudes differed significantly between all three item types. The neuroimaging data revealed that right inferior frontal and mid‐cingulate regions were more active for probe and target trials compared to irrelevants. Moreover, the differential activation in the right inferior frontal region was modulated by stimulus conflicts. These results were interpreted as an increased top‐down influence on the stimulus‐response‐mapping for concealed and task‐relevant items. Additionally, the influence of working memory and retrieval processes on this activation pattern is discussed. Using parametric analyses, reaction times and SCR amplitudes were found to be linearly related to activity in the cerebellum, the right inferior frontal cortex, and the supplementary motor area. This result provides a first link between behavioral measures, sympathetic arousal, and neural activation patterns during a GKT examination. Hum Brain Mapp 2007.

Asymmetry in the human primary somatosensory cortex and handedness.

Brain asymmetry is a phenomenon well known for handedness and language specialization and has also been studied in motor cortex. Less is known about hemispheric asymmetries in the somatosensory cortex. In the present study, we systematically investigated the representation of somatosensory function analyzing early subcortical and cortical somatosensory-evoked potentials (SEP) after electrical stimulation of the right and left median nerve. In 16 subjects, we compared thresholds, the peripheral neurogram at Erb point, and, using MRI-based EEG source analysis, the P14 brainstem component as well as N20 and P22, the earliest cortical responses from the primary sensorimotor cortex. Handedness was documented using the Edinburgh Inventory and a dichotic listening test was performed as a measure for language dominance. Whereas thresholds, Erb potential, and P14 were symmetrical, amplitudes of the cortical N20 showed significant hemispheric asymmetry. In the left hemisphere, the N20 amplitude was higher, its generator was located further medial, and it had a stronger dipole moment. There was no difference in dipole orientation. As a possible morphological correlate, the size of the left postcentral gyrus exceeded that of the right. The cortical P22 component showed a lower amplitude and a trend toward weaker dipole strength in the left hemisphere. Across subjects, there were no significant correlations between laterality indices of N20, the size of the postcentral gyrus, handedness, or ear advantage. These data show that asymmetry of median nerve SEP occurs at the cortical level, only. However, both functional and morphological cortical asymmetry of somatosensory representation appears to vary independently of motor and language functions.

Cortical representation of saccular vestibular stimulation: VEMPs in fMRI

Short tone bursts trigger a vestibular evoked myogenic potential (VEMP), an inhibitory potential which reflects a component of the vestibulocollic reflex (VCR). These potentials arise as a result of activation of the sacculus and are expressed through the vestibulo-collic reflex (VCR). Up to now, the ascending projections of the sacculus are unknown in humans, only the representation of the semicircular canals or the entire vestibular nerve has been demonstrated. The aim of this study was to determine whether a sacculus stimulus that evoked VEMPs could activate vestibular cortical areas in fMRI. To determine this, we studied the differential effects of unilateral VEMP stimulation in 21 healthy right-handers in a clinical 1.5 T scanner while wearing piezo electric headphones. A unilateral VEMP stimulus and two auditory control stimuli were given in randomized order over the stimulated ear. A random effects statistical analysis was done with SPM2 (p<0.05, corrected). After exclusion of the auditory effects, the major findings were as follows: (i) significant activations were located in the multisensory cortical vestibular network within both hemispheres, including the posterior insular cortex, the middle and superior temporal gyri, and the inferior parietal cortex. (ii) The activation pattern was elicited bilaterally with a predominance of the right hemisphere in right-handers. (iii) Saccular vestibular projection was predominantly ipsilateral, whereas (iv) pure acoustic stimuli were processed with a predominance of the respective contralateral and mainly in the left hemisphere. This is the first demonstration by means of fMRI of the cortical representation of the saccular input at cortical level. The activation pattern is similar to that known from the stimulation of the entire vestibular nerve or the horizontal semicircular canal. Our data give evidence of a task-dependent separation of the processing within the vestibular otolith and the auditory systems in the two hemispheres.

Neural correlates of hemispheric dominance and ipsilaterality within the vestibularsystem

Earlier functional imaging studies on the processing of vestibular information mainly focused on cortical activations due to stimulation of the horizontal semicircular canals in right-handers. Two factors were found to determine its processing in the temporo-parietal cortex: a dominance of the non-dominant hemisphere and an ipsilaterality of the neural pathways. In an investigation of the role of these factors in the vestibular otoliths, we used vestibular evoked myogenic potentials (VEMPs) in a fMRI study of monaural saccular-otolith stimulation. Our aim was to (1) analyze the hemispheric dominance for saccular-otolith information in healthy left-handers, (2) determine if there is a predominance of the ipsilateral saccular-otolith projection, and (3) evaluate the impact of both factors on the temporo-parieto-insular activation pattern. A block design with three stimulation and rest conditions was applied: (1) 102 dB-VEMP stimulation; (2) 65 dB-control-acoustic stimulation, (3) 102 dB-white-noise-control stimulation. After subtraction of acoustic side effects, bilateral activations were found in the posterior insula, the superior/middle/transverse temporal gyri, and the inferior parietal lobule. The distribution of the saccular-otolith activations was influenced by the two factors but with topographic disparity: whereas the inferior parts of the temporo-parietal cortex were mainly influenced by the ipsilaterality of the pathways, the upper parts reflected the dominance of the non-dominant hemisphere. This is in contrast to the processing of acoustic stimulation, which showed a predominance of the contralateral pathways. Our study proves the importance of the hemispheric preponderance also in left-handers, which is of relevance in the superior parts of the insula gyrus V, the inferior parietal lobule, and the superior temporal gyri.

Brainstem and cerebellar fMRI-activation during horizontal and vertical optokinetic stimulation.

Animal studies have shown that not only cortical, but also brainstem and cerebellar areas are involved in the initiation and generation of optokinetic nystagmus (OKN), e.g., cortico-(pretecto)pontine-olivo-cerebellar pathways. The aim of this fMRI study was to identify and differentiate brainstem and cerebellar areas involved in horizontal and vertical OKN (h/vOKN) in humans. In a group of nine healthy volunteers, hOKN and vOKN were statistically compared with a stationary control condition. There were common activated regions for hOKN and vOKN directions located in the transition zone between the posterior thalamus and the mesencephalon bilaterally covering the pretectal nucleus complex, which is known to be a major structure within the afferent branch of the optokinetic system. Furthermore, during hOKN, activation occurred bilaterally in the mediodorsal and dorsolateral ponto-medullary brainstem, which could be best attributed to the reticular formation, especially the paramedian pontine reticular formation (PPRF). For vOKN, additional activated areas in the dorsal mesencephalic brainstem could be best localized to the ocular motor nuclei and the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). For both OKN directions, the cerebellar activation was localized in the oculomotor vermis (declive VI, folium and tuber VIIA/B, in part pyramis VIIIA), and the flocculus bilaterally as well as widespread in the cerebellar hemispheres. In conclusion, fMRI allowed first attributions of neuronal substrates in the cerebellum and brainstem to hOKN and vOKN in humans. Consistent with the animal data, the dorsal ponto-medullary routes were involved bilaterally for hOKN, whereas the rostral mesencephalic routes were involved for vOKN.

fMRI-activation patterns in the detection of concealed information rely on memory-related effects

Recent research on potential applications of fMRI in the detection of concealed knowledge primarily ascribed the reported differences in hemodynamic response patterns to deception. This interpretation is challenged by the results of the present study. Participants were required to memorize probe and target items (a banknote and a playing card, each). Subsequently, these items were repeatedly presented along with eight irrelevant items in a modified Guilty Knowledge Test design and participants were instructed to simply acknowledge item presentation by pressing one button after each stimulus. Despite the absence of response monitoring demands and thus overt response conflicts, the experiment revealed a differential physiological response pattern as a function of item type. First, probes elicited the largest skin conductance responses. Second, differential hemodynamic responses were observed in bilateral inferior frontal regions, the right supramarginal gyrus and the supplementary motor area as a function of item type. Probes and targets were accompanied by a larger signal increase than irrelevant items in these regions. Moreover, the responses to probes differed substantially from targets. The observed neural response pattern seems to rely on retrieval processes that depend on the depth of processing in the encoding situation.

Direction-dependent visual cortex activation during horizontal optokinetic stimulation (fMRI study).

Looking at a moving pattern induces optokinetic nystagmus (OKN) and activates an assembly of cortical areas in the visual cortex, including lateral occipitotemporal (motion‐sensitive area MT/V5) and adjacent occipitoparietal areas as well as ocular motor areas such as the prefrontal cortex, frontal, supplementary, and parietal eye fields. The aim of this functional MRI (fMRI) study was to investigate (1) whether stimulus direction‐dependent effects can be found, especially in the cortical eye fields, and (2) whether there is a hemispheric dominance of ocular motor areas. In a group of 15 healthy subjects, OKN in rightward and leftward directions was visually elicited and statistically compared with the control condition (stationary target) and with each other. Direction‐dependent differences were not found in the cortical eye fields, but an asymmetry of activation occurred in paramedian visual cortex areas, and there were stronger activations in the hemisphere contralateral to the slow OKN phase (pursuit). This can be explained by a shift of the mean eye position of gaze (beating field) in the direction of the fast nystagmus phases of approximately 2.6 degrees, causing asymmetrical visual cortex stimulation. The absence of a significant difference in the activation pattern of the cortical eye fields supports the view that the processing of eye movements in both horizontal directions is mediated in the same cortical ocular motor areas. Furthermore, no hemispheric dominance for OKN processing was found in right‐handed volunteers. Hum Brain Mapp, 2005.

Functional imaging of sympathetic activation during mental stress

Activation of the sympathetic nervous system (SNS) is essential in adapting to environmental stressors and in maintaining homeostasis. This reaction can also turn into maladaptation, associated with a wide spectrum of stress-related diseases. Up to now, the cortical mechanisms of sympathetic activation in acute mental stress have not been sufficiently characterized. We therefore investigated cerebral activation applying functional magnetic resonance imaging (fMRI) during performance of a mental stress task with graded levels of difficulty, i.e. four versions of a Stroop task (Colour Word Interference Test, CWT) in healthy subjects. To analyze stress-associated sympathetic activation, skin conductance and heart rate were continuously recorded. The results show that sympathetic activation through mental stress is associated with distinct cerebral regions being immediately involved in task performance (visual, motor, and premotor areas). Other activated regions (right insula, dorsolateral superior frontal gyrus, cerebellar regions) are unrelated to task performance. These latter regions have previously been considered to be involved in mediating different stress responses. The results might furthermore serve as a basis for future investigations of the connection between these cortical regions in the generation of stress-related diseases.

Comparison of anterior cingulate vs. insular cortex as targets for real-time fMRI regulation during pain stimulation

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network, notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group) for AIC and ACC feedback. First, a functional localizer using block-design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC. Second, subjects were asked to down-regulate the BOLD activation in four neurofeedback runs during identical pain stimulation. Data analysis included task-related and functional connectivity analysis. At the behavioral level, pain ratings significantly decreased during feedback vs. localizer runs, but there was no difference between AIC and ACC groups. Concerning neuroimaging, ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down-regulation (17/28) in both task-related and functional connectivity analysis. The functional connectivity toward the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex. Consequently, the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the caudate nucleus, although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally, the caudate, an important area involved in pain perception and suppression, could be a good rt-fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain perception.