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Arno Villringer

Publications and source records attributed to Arno Villringer.

At least 37 records · Page 2Linked to original sources

Subcortical lesions after transient thread occlusion in the rat: T2-weighted magnetic resonance imaging findings without corresponding sensorimotor deficits.

PURPOSE: To investigate infarct evolution and functional consequences of exclusive subcortical or cortico-subcortical strokes, transient middle cerebral artery occlusion (MCAO) was conducted in Wistar rats. MATERIALS AND METHODS: MCAO was induced in male Wistar rats (260-300 g) for 60 minutes. Lesion volumes and absolute T2 times on magnetic resonance imaging (MRI) were assessed 1 and 14 days after MCAO using a 4.7-T MRI animal scanner in conjunction with functional testing (adhesive tape removal, cylinder test, and ledged beam walking). RESULTS: Functional test scores were not distinguishable between sham-operated animals (N = 5) and those with exclusive caudoputaminal infarct (N = 8; group cp), but showed significant deficits in animals with cortico-subcortical infarction (N = 10; group cp+). The cp group had lower absolute T2 times and a more pronounced reduction in T2 lesion volume over time than the subcortical component in the cp+ group. There was no correlation of T2 lesion size or absolute T2 times and functional impairment in either group. CONCLUSION: When judged from functional tests alone, subcortical ischemic lesions may not be diagnosed reliably. Furthermore, T2-weighted (T2-w) MRI does not well anticipate functional deficits in primarily striatal lesions.

Animals↗

Gender differences in knowledge of stroke in patients with atrial fibrillation.

BACKGROUND: A limiting factor for immediate initiation of stroke therapy is delayed hospital arrival. We assessed general knowledge on and behavior during an acute stroke with particular emphasis on prehospital temporal delays and a focus on the high-risk group of patients with atrial fibrillation (AF). METHODS: As part of the Berlin Acute Stroke Study (BASS), we interviewed patients admitted to hospital with symptoms of stroke using a standardized questionnaire. Cardiac rhythm was assessed by ECG and Holter monitor. Data analysis included additional stratification for age and gender. RESULTS: Of a total of 558 patients (66.8 +/- 13.5 years; 45% female) diagnosed with TIA or stroke 28% interpreted their own symptoms correctly as due to stroke. Female patients reporting cardiac arrhythmias and having AF more often correctly interpreted their symptoms as stroke (P = 0.03), considered their symptoms urgent (P = 0.02), considered stroke a medical emergency (P < 0.05) and had shorter prehospital delay times (P = 0.001) compared to female patients not reporting cardiac arrhythmias. Male, younger (< 65 years) and older patient groups showed no such effect, respectively. CONCLUSION: Females who know to have AF demonstrate better knowledge of stroke symptoms compared to females unaware or without this risk factor. This better knowledge translates into more appropriate behavior during an acute stroke.

Age Distribution↗

Influence of bodily harm on neural correlates of semantic and moral decision-making.

Moral decision-making is central to everyday social life because the evaluation of the actions of another agent or our own actions made with respect to the norms and values guides our behavior in a community. There is previous evidence that the presence of bodily harm--even if irrelevant for a decision--may affect the decision-making process. While recent neuroimaging studies found a common neural substrate of moral decision-making, the role of bodily harm has not been systematically studied so far. Here we used event-related functional magnetic resonance imaging (fMRI) to investigate how behavioral and neural correlates of semantic and moral decision-making processes are modulated by the presence of direct bodily harm or violence in the stimuli. Twelve participants made moral and semantic decisions about sentences describing actions of agents that either contained bodily harm or not and that could easily be judged as being good or bad or correct/incorrect, respectively. During moral and semantic decision-making, the presence of bodily harm resulted in faster response times (RT) and weaker activity in the temporal poles relative to trials devoid of bodily harm/violence, indicating a processing advantage and reduced processing depth for violence-related linguistic stimuli. Notably, there was no increase in activity in the amygdala and the posterior cingulate cortex (PCC) in response to trials containing bodily harm. These findings might be a correlate of limited generation of the semantic and emotional context in the anterior temporal poles during the evaluation of actions of another agent related to violence that is made with respect to the norms and values guiding our behavior in a community.

Adult↗

Time-resolved multidistance near-infrared spectroscopy of the adult head: intracerebral and extracerebral absorption changes from moments of distribution of times of flight of photons.

We report on multidistance time-resolved diffuse reflectance spectroscopy of the head of a healthy adult after intravenous administration of a bolus of indocyanine green. Intracerebral and extracerebral changes in absorption are deduced from moments (integral, mean time of flight, and variance) of the distributions of times of flight of photons (DTOFs), recorded simultaneously at four different source-detector separations. We calculate the sensitivity factors converting depth-dependent changes in absorption into changes of moments of DTOFs by Monte Carlo simulations by using a layered model of the head. We validate our method by analyzing moments of DTOFs simulated for the assumed changes in absorption in different layers of the head model.

Algorithms↗

Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study.

BACKGROUND AND PURPOSE: We investigated whether transient ischemic attacks (TIAs) before stroke can induce tolerance by raising the threshold of tissue vulnerability in the human brain. METHODS: Sixty-five patients with first-ever ischemic territorial stroke received diffusion- and perfusion-weighted MRI within 12 hours of symptom onset. Epidemiological and clinical data, lesion volumes in T2, apparent diffusion coefficient (ADC) maps and perfusion maps, and cerebral blood flow and cerebral blood volume values were compared between patients with and without a prodromal TIA. RESULTS: Despite similar size and severity of the perfusion deficit, initial diffusion lesions tended to be smaller and final infarct volumes were significantly reduced (final T2: 9.1 [interquartile range, 19.7] versus 36.5 [91.2] mL; P=0.014) in patients with a history of TIA (n=16). This was associated with milder clinical deficits. CONCLUSIONS: The beneficial effect of TIAs on lesion size in ADC and T2 suggests the existence of endogenous neuroprotection in the human brain.

Blood Flow Velocity↗

Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage: a multicenter study on the validity of stroke imaging.

BACKGROUND AND PURPOSE: Although modern multisequence stroke MRI protocols are an emerging imaging routine for the diagnostic assessment of acute ischemic stroke, their sensitivity for intracerebral hemorrhage (ICH), the most important differential diagnosis, is still a matter of debate. We hypothesized that stroke MRI is accurate in the detection of ICH. To evaluate our hypotheses, we conducted a prospective multicenter trial. METHODS: Stroke MRI protocols of 6 university hospitals were standardized. Images from 62 ICH patients and 62 nonhemorrhagic stroke patients, all imaged within the first 6 hours after symptom onset (mean, 3 hours 18 minutes), were analyzed. For diagnosis of hemorrhage, CT served as the "gold standard." Three readers experienced in stroke imaging and 3 final-year medical students, unaware of clinical details, separately evaluated sets of diffusion-, T2-, and T2*-weighted images. The extent and phenomenology of the hemorrhage on MRI were assessed separately. RESULTS: Mean patient age was 65.5 years; median National Institutes of Health Stroke Scale score was 10. The experienced readers identified ICH with 100% sensitivity (confidence interval, 97.1 to 100) and 100% overall accuracy. Mean ICH size was 17.3 mL (range, 1 to 101.5 mL). The students reached a mean sensitivity of 95.16% (confidence interval, 90.32 to 98.39). CONCLUSIONS: Hyperacute ICH causes a characteristic imaging pattern on stroke MRI and is detectable with excellent accuracy. Even raters with limited film-reading experience reached good accuracy. Stroke MRI alone can rule out ICH and demonstrate the underlying pathology in hyperacute stroke.

Acute Disease↗

Neurovascular coupling analyzed non-invasively in the human brain.

Most functional brain imaging methods detect neuronal activations indirectly through the accompanying neurovascular response. Here, we demonstrate that a novel methodological approach, the combination of DC-magnetoencephalography (DC-MEG) and near-infrared spectroscopy (NIRS), allows non-invasive assessment of the dynamics of neurovascular coupling in the human brain: detecting directly slow neuronal processes (with time constants of 30s), DC-MEG revealed, even in unaveraged recordings, sustained neuronal activations at pericentral hand cortices contralateral to repetitive finger movements; these were accompanied by the ensuing local vascular response showing similar dynamical features as quantified by simultaneously recorded NIRS. This non-invasive approach opens a new avenue for the understanding of neurovascular coupling during physiological tasks as well as in diseases involving slow neuronal depolarization shifts and alterations of blood flow, such as stroke or migraine.

Adult↗

Decrease in haemoglobin oxygenation during absence seizures in adult humans.

Near-infrared spectroscopy (NIRS) is a noninvasive method that allows the assessment of activation-induced cortical oxygenation changes in humans. It has been demonstrated that an increase in oxygenated and a decrease in deoxygenated haemoglobin can be expected over an area activated by functional stimulation. Likewise, an inverse oxygenation pattern has been shown to be associated with cortical deactivation. The aim of the current study was to determine the oxygenation changes that occur during absence seizures. We performed ictal NIRS simultaneously with video-EEG telemetry in three adult patients with typical absence seizures. NIRS probes were placed over the frontal cortex below the F1/F2 leads. During all absence seizures studied, pronounced changes in cerebral Hb-oxygenation were noted and there were no changes in the interval. We observed a reproducible decrease in [oxy-Hb] and an increase in [deoxy-Hb] during absence seizures indicating a reduction of cortical activity. Oxygenation changes started several seconds after the EEG-defined absence onset and outlasted the clinically defined event by 20-30 s.

Adult↗

Neural correlates of syntactic transformations.

Many agrammatic aphasics have a specific syntactic comprehension deficit involving processing syntactic transformations. It has been proposed that this deficit is due to a dysfunction of Broca's area, an area that is thought to be critical for comprehension of complex transformed sentences. The goal of this study was to investigate the role of Broca's area in processing canonical and non-canonical sentences in healthy subjects. The sentences were presented auditorily and were controlled for task difficulty. Subjects were asked to judge the grammaticality of the sentences while their brain activity was monitored using event-related functional magnetic resonance imaging. Processing both kinds of sentences resulted in activation of language-related brain regions. Comparison of non-canonical and canonical sentences showed greater activation in bilateral temporal regions; a greater activation of Broca's area in processing antecedent-gap relations was not found. Moreover, the posterior part of Broca's area was conjointly activated by both sentence conditions. Broca's area is thus involved in general syntactic processing as required by grammaticality judgments and does not seem to have a specific role in processing syntactic transformations.

Adult↗

Out-of-hospital delays in patients with acute stroke.

STUDY OBJECTIVE: We determine the interval between stroke symptom onset and time to emergency department (ED) arrival and factors associated with delays in presentation. METHODS: All patients with acute stroke presenting at 4 hospitals in a metropolitan area and consenting to an interview were prospectively included over a 12-month period, excluding patients with presentation greater than 7 days after onset of symptoms and discharge or death within 24 hours after ED arrival. Initially, National Institutes of Health Stroke Scale and times of symptom onset and of ED arrival were registered by a neurologist. Sociodemographic factors and data about the course of events were obtained by standardized interview conducted with patients or proxies. In a multivariable analysis, an extended Cox proportional hazards model was used, and hazard ratios were determined. RESULTS: Primary analyses were performed for 558 interviewed patients (mean age 66.8+/-13.5 years, 45% female patients) with confirmed stroke; 452 (81%) patients had a known onset of symptoms. Median interval between symptom onset and ED arrival was 151 minutes (range 5 to 9,590 minutes). Transport by emergency medical services (adjusted hazard ratio 0.28 [95% confidence interval (CI) 0.19 to 0.41]), increasing age (hazard ratio 0.99 [95% CI 0.98 to 0.99]), greater stroke severity (National Institutes of Health Stroke Scale score; hazard ratio 0.93 [95% CI 0.90 to 0.96]), having transient ischemic attack rather than persistent symptoms (hazard ratio 0.32 [95% CI 0.22 to 0.46]) and symptoms considered urgent (hazard ratio 0.68 [95% CI 0.55 to 0.84]) were the factors most strongly associated with a shorter out-of-hospital interval. CONCLUSION: There are considerable delays between stroke symptom onset and ED arrival. Programs to improve awareness of patients with stroke to seek medical help immediately may reduce unnecessary delays to ED arrival.

Aged↗

Cytochrome-c-oxidase redox changes during visual stimulation measured by near-infrared spectroscopy cannot be explained by a mere cross talk artefact.

The detection of redox changes in cytochrome-c-oxidase ([Cyt-ox]) in response to cerebral activation by non-invasive NIRS is hampered by methodological spectroscopic issues related to the modification of the Beer-Lambert law. Also, the question whether a change in the enzyme's redox-state is elicited by functional stimulation is unresolved. In a previous study, we found physiological evidence in favour of an activation-induced increase in oxidation of the enzyme [J. Cereb. Blood Flow Metab. 19 (1999) 592], while in a second study on spectroscopic cross talk, we found that the [Cyt-ox] changes to potentially be an artefact of the spectroscopic approach [J. Biomed. Opt. 7 (2002) 51]. Here, we use two different stimuli which differentially activate areas either rich or poor in [Cyt-ox] content (blob/interblob in visual cortex V1 and pale/thin stripes in V2) to further clarify this apparent discrepancy. In a first experiment, two stimuli were presented in an alternating fashion for 20 s and all stimulation periods were separated by resting periods of 40 s. We observed similar changes in [Cyt-ox] for both stimuli. To become more sensitive to the potentially very small optical changes related to changes in [Cyt-ox], we tried to minimise global haemodynamic and metabolic effects in a second experiment by omitting the resting periods. Our hypothesis was that [Cyt-ox] changes could be fully explained by cross talk as it is predicted from our last study [J. Biomed. Opt. 7 (2002) 51]. However, in more than half of the experiments, we were not able to model the changes in Cyt-ox calculated from measured attenuation spectra as a cross talk artefact. We interpret this finding as an argument in favour of the existence of [Cyt-ox] changes in response to functional stimulation. This finding, however, does not lessen the liability of the [Cyt-ox] changes to cross talk and calls for great caution when [Cyt-ox] changes are derived from NIRS measurements based on the modified Beer-Lambert approach. Further (invasive) validation studies are required.

Adult↗

Towards a standard analysis for functional near-infrared imaging.

Functional near-infrared spectroscopy (fNIRS) allows the ability to monitor brain activation by measuring changes in the concentration of oxy- and deoxy-hemoglobin. Until now no standardized approach for fNIRS data analysis has been established, although this has to be regarded as a precondition for future application. Hence, we applied the well-established general linear model to optical imaging data. Further, fNIRS data were analyzed in the frequency domain. Two visual tasks were investigated with optical imaging: a checkerboard paradigm supposed to activate the primary and secondary visual cortex, and a paradigm consisting of moving colored stimuli (rotating 'L's) additionally involving the motion area V5. Analysis with the general linear model detected the activation focus in the primary and secondary visual cortex during the first paradigm. For the second paradigm, a second laterally localized activated brain region was found, most likely representing V5. Spatially resolved spectral analysis confirmed the results by showing maxima of power spectral density and coherence in the same respective brain regions. Moreover, it demonstrated a delay of the hemodynamic response in the motion area. In summary, the present study suggests that the general linear model and spatially resolved spectral analysis can be used as standard statistical approaches for optical imaging data, particularly because they are almost independent of the assumed differential path length factors.

Adult↗

Separability and cross talk: optimizing dual wavelength combinations for near-infrared spectroscopy of the adult head.

By means of noninvasive near-infrared spectroscopy (NIRS), cerebral concentration changes in oxygenated and deoxygenated hemoglobin ([oxy-Hb] and [deoxy-Hb]) can be determined. The quality of the concentration changes' assessment critically depends on the wavelength combination used. Trying to optimize this combination, two spectroscopic effects must be taken into account: cross talk and separability. Cross talk between [oxy-Hb] and [deoxy-Hb] occurs because the assumption made in the analysis-that there is a homogeneous concentration change-does not hold true for the adult human head. Separability-to be introduced in this paper-is a measure for the degree of physical noise of the measurement that will influence the noise of the concentration changes' assessment. In other words, high separability corresponds to a low noise with respect to the concentration changes assessed. Here, we present analytical expressions for both measures and provide model-based estimates of cross talk and separability for any combination of two wavelengths between 610 and 920 nm. These theoretical considerations allow for two predictions: (a) if both wavelengths used are greater than approximately 780 nm, cross talk is high and separability is low resulting in erroneous and noisy concentration data. (b) If one wavelength is chosen below 720 nm while the other is greater than 730 nm, cross talk is low and separability is high resulting in accurate concentration changes. We show the relevance of these theoretical results for noninvasive NIRS by testing the predictions on experimental data obtained in adults undergoing visual stimulation.

Adult↗

Progressive change in primary progressive multiple sclerosis normal-appearing white matter: a serial diffusion magnetic resonance imaging study.

In spite of marked disability, patients with primary progressive multiple sclerosis (PPMS) display smaller lesion volumes on conventional magnetic resonance imaging (MRI) compared with other forms of multiple sclerosis (MS). Hence, damage to the normal-appearing brain tissue (NABT) may play an important role in explaining the pathogenesis of disability in PPMS. Diffusion-weighted MRI (DW-MRI) probes water diffusion in vivo that can be altered by pathologic changes. Using DW-MRI we investigated diffusion in the NABT of 15 patients with PPMS over one year. The average apparent diffusion coefficient (ADCav) was measured in 10 regions of interest located in the normal-appearing thalamus and the normal-appearing white matter (NAWM). Six healthy subjects served as a reference. In contrast to healthy subjects, patients with PPMS showed an increment within 12 months of the ADCav in NAWM which was associated with an increase of the T2- and T1-lesion volumes. The ADCav in frontal NAWM was associated with disability as measured by the MS Functional Composite Measure. Serial DW-MRI depicts progressive changes in the NAWM of patients with PPMS. Our preliminary findings suggest that the processes causing structural damage in NAWM and lesions in patients with PPMS are partially linked and that changes of water diffusion in NAWM depicted by DW-MRI are clinically relevant.

Adult↗

Parietal activation during visual search in the absence of multiple distractors.

Search for a target object embedded in a visual scene involves the posterior parietal cortex. This region is thought to play a role in visual attention by counteracting the effects of distractors on targets or by inhibiting distractors. Using fMRI, we investigated whether the parietal cortex is also engaged in visual search without distractors. Cortical activation was compared between two 'single object' search tasks differing only in difficulty. Activation differences between both tasks were found in the anterior and inferior part of the intraparietal sulcus, but in neither its posterior part nor the frontal eye fields. Thus a subset of parietal regions participates in the control of visual search even in the absence of distractors.

Adult↗

Functional assessment of Broca's area using near infrared spectroscopy in humans.

We used near-infrared spectroscopy (NIRS) to compare functional hemoglobin concentration changes (delta[oxy-Hb] and delta[deoxy-Hb]) over human language and motor cortices. Eight subjects performed finger opposition, tongue movement, and covert visual object naming in an interleaved block paradigm design. NIRS revealed paradigm specific patterns of delta[oxy-Hb] and delta[deoxy-Hb] providing cortical localization of each function. During each task, significant response overlap was observed when comparing the [oxy-Hb] signals, whereas delta[deoxy-Hb] seemed more localized. Furthermore, by applying magnitude and time to significance measures to the delta[deoxy-Hb] response profile, Broca's area was easily distinguished from neighboring tongue (and hand) motor representation. Delta[oxy-Hb] did not provide this level of specificity. These findings suggest delta[deoxy-Hb] as the preferential NIRS parameter to map language cortices.

Adult↗

Changes in cerebral perfusion precede plaque formation in multiple sclerosis: a longitudinal perfusion MRI study.

New MRI techniques such as the analysis of magnetization transfer or diffusion have provided evidence for subtle progressive alterations in tissue integrity prior to focal leakage of the blood-brain barrier (BBB) as part of plaque formation in multiple sclerosis. Since inflammation is capable of modulating the microcirculation, we investigated the hypothesis that changes in the local perfusion might be one of the earliest signs of lesion development. 20 patients with definite relapsing-remitting multiple sclerosis were analysed with regard to cerebral blood volume, cerebral blood flow, mean transit time and apparent diffusion coefficient (ADC), as well as conventional MRI parameters, on monthly follow-up scans. Among 89 gadolinium-enhancing lesions, we selected 18 that developed during the study and met strict inclusion criteria. In these, changes of perfusion parameters were detectable not only prior to the BBB breakdown, but also prior to increases in the ADC. Our data indicate that inflammation is accompanied by altered local perfusion, which can be detected prior to permeability of the BBB.

Adult↗