Biomedical subjects

Arno Villringer

Publications and source records attributed to Arno Villringer.

At least 19 recordsLinked to original sources

PubMed2006

Neural correlates of vibrotactile working memory in the human brain.

Recent neurophysiological studies in macaques identified a network of brain regions related to vibrotactile working memory (WM), including somatosensory, motor, premotor, and prefrontal cortex. In these studies, monkeys decided which of two vibrotactile stimuli that were sequentially applied to their fingertips and separated by a short delay had the higher vibration frequency. Using the same task, the objective of the present study was to identify the neural correlates related to the different task periods (encoding, maintenance, and decision making) of vibrotactile WM in the human brain. For this purpose, we used event-related functional magnetic resonance imaging and contrasted WM trials with a control condition of vibrotactile stimulation that did not require maintenance and decision making. We found that vibrotactile WM has a similar but not identical neural organization in humans and monkeys. Consistent with neurophysiological data in monkeys and behavioral studies in humans, the primary somatosensory and the ventral premotor cortex exhibited increased activity during encoding. Maintenance of a vibrotactile memory trace evoked activity in the premotor and ventrolateral prefrontal cortex. Decision making caused activation in the somatosensory, premotor, and lateral prefrontal cortex. However, human vibrotactile WM recruited additional areas. Decision making activated a broader network than that studied thus far in monkeys. Maintenance and decision making additionally activated the inferior parietal lobe. Although the different task components evoked activity in distinctive neural networks, there was considerable overlap of activity, especially regarding maintenance and decision making, indicating that similar neural mechanisms are required for the subprocesses related to these task components.

Adult↗

PubMed2006

A neural network reflecting individual differences in cognitive processing of emotions during perceptual decision making.

Even simple perceptual decisions are influenced by the emotional content of a stimulus. Recent neuroimaging studies provide evidence about the neural mechanisms of perceptual decision making on emotional stimuli. However, the effect of individual differences in cognitive processing of emotions on perceptual decision making remains poorly understood. Here, we investigated how changes in the fMRI signal during perceptual decision making on facial stimuli covaried with individual differences in the ability to identify and communicate one's emotional state. Although this personality trait covaried with changes in activity in the dorsal anterior cingulate cortex (dACC) during gender decisions on facial expressions, there was no correlation during emotion decisions. Further, we investigated whether individual differences in the ability to cognitively process emotions depend on differences in the functional integration of emotional and cognitive brain regions. We therefore compared task-dependent changes in effective connectivity of dACC in individuals with good and with poor ability to cognitively process emotions using a psychophysiological interaction analysis. We found greater coupling of dACC with prefrontal regions in individuals with good ability to identify and communicate their emotional state. Conversely, individuals with poor ability in this domain showed greater coupling of dACC with the amygdala. Our data indicate that individual differences in the ability to identify and communicate one's emotional state are reflected by altered effective connectivity of the dACC with prefrontal and limbic regions. Thus, we provide neurophysiological evidence for a theoretical model that posits that a discommunication between limbic areas and the neocortex impairs cognitive processing of emotions.

Adult↗

PubMed2006

Simultaneous EEG-fMRI.

Acquisition of electroencephalogram (EEG) during functional magnetic resonance imaging (fMRI) provides an additional monitoring tool for the analysis of brain state fluctuations. The exploration of brain responses following inputs or in the context of state changes is crucial for a better understanding of the basic principles governing large-scale neuronal dynamics. State-of-the-art techniques allow EEG activity-from DC (direct current) up to high frequencies in the gamma range-to be acquired simultaneously with fMRI data. In the interleaved mode, spiking activities can also be assessed during concurrent fMRI. The utilization of fMRI evidence to better constrain solutions of the inverse problem of source localization of EEG activity is an exciting possibility. Nonetheless, this approach should be applied cautiously since the degree of overlap between underlying neuronal activity sources is variable and, for the most part, unknown. The ultimate goal is to make joint inferences about the activity, dynamics, and functions by exploiting complementary information from multimodal data sets.

Animals↗

PubMed2006

Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics.

RATIONALE: Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia. OBJECTIVE: We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation. METHODS: Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence. RESULTS: Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms. CONCLUSIONS: Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.

Adult↗

PubMed2006

Synchronization between background activity and visually evoked potential is not mirrored by focal hyperoxygenation: implications for the interpretation of vascular brain imaging.

We performed an electroencephalography and optical topography study simultaneously exploring electrophysiological and vascular response magnitude as a function of stimulus frequency. To elicit a response in the visual cortex, subjects were exposed to flicker frequencies varying from 1 to 25 Hz (1 Hz steps, eyes closed). Extending the standard view to compare magnitudes of the evoked neuronal to the evoked vascular response, we additionally investigated modulations of alpha-power, a marker of "background" EEG activity. The results show two discrepancies between the electrophysiological and vascular response: (1) VEP and alpha-power exhibit a discontinuous peak when stimulating at the individual alpha-frequency (IAF) (approximately 10-11 Hz), indicating resonance between background oscillations and evoked response; this is not mirrored by the vascular response. (2) The vascular response, in contrast, steadily increases up to a maximum at 7-8 Hz and slightly decreases with higher frequencies. This continuous frequency dependence is partly reflected by the decrease in alpha-power up to frequencies of 8-9 Hz and a slight increase in alpha-power beyond the IAF resonance. Although indicating an inverse relationship between alpha-power and vascular response, the frequency dependence of the evoked response does not show such a correlation. Thus, electrophysiological resonance between an individual's alpha-frequency and isofrequent stimulation is not mirrored by the vascular response. Also, spontaneous background EEG activity is an important modulator of the vascular response magnitude. We discuss these deviations from a simple one-to-one translation between evoked potential and vascular response amplitude in the light of questions concerning synchronization, attenuation, and induction of background oscillations such as the alpha-rhythm.

Adolescent↗

PubMed2006

Illuminating the BOLD signal: combined fMRI-fNIRS studies.

Functional magnetic resonance imaging (fMRI) is currently combined with electrophysiological methods to identify the relationship between neuronal activity and the blood oxygenation level-dependent (BOLD) signal. Several processes like neuronal activity, synaptic activity, vascular dilation, blood volume and oxygenation changes underlie both response modalities, that is, the electrophysiological signal and the vascular response. However, accessing single process relationships is absolutely mandatory when aiming at a deeper understanding of neurovascular coupling and necessitates studies on the individual building blocks of the vascular response. Combined fMRI and functional near-infrared spectroscopy studies have been performed to validate the correlation of the BOLD signal to the hemodynamic changes in the brain. Here we review the current status of the integration of both technologies and judge these studies in the light of recent findings on neurovascular coupling.

Blood Volume↗

PubMed2006

[The German competence network stroke: researching -- promoting -- networking].

BACKGROUND: Stroke is the most frequent neurologic disease, one of the most frequent reasons for disability and the third most frequent cause of death in Germany. Only the coordination of prevention, therapy in the acute setting and rehabilitation will improve the socioeconomic burden of stroke. IMPLEMENTATION AND RESULTS: The Competence Net Stroke (www.schlaganfallnetz.de) substantially contributes to these efforts by linking leading research groups together, improving communication, exchanging knowledge between clinicians, researchers and patients, as well as advancing public health science and quality assurance. Since the initiation of the Competence Net Stroke by the German Ministry of Education and Research in 1999, researchers and clinicians have implemented and expanded corporate databanks that jointly answer pressing questions in stroke imaging, epidemiology, and genetics. The progress that has been made is largely due to the formation of joint standard protocols at several independent institutions. The multicenter approach enabled the competence net to build up specialized criteria in magnetic resonance imaging (MRI). These criteria guide the clinician to those patients, who profit from thrombolysis beyond the 3-h time window. In addition, the Competence Net Stroke succeeded in reliably detecting cerebral hemorrhage with MRI. PROGRESSION AND PERSPECTIVES: Since 2005, and the beginning of the third funding period, the Competence Net Stroke consists of nine sub-nets. The integrative, rather than dominating, structure eases flexible reactions to new developments and findings in research. The Competence Net Stroke can more straightforwardly adopt new, promising research areas and end funding of those which are unsuccessful. The future and continuity of the Competence Net Stroke are secured by the acquisition of alternative funding such as "Sonderforschungsbereiche", the sixth European framework program, industrial partners, and health insurance.

Clinical Competence↗

PubMed2006

Knowledge about risk factors for stroke: a population-based survey with 28,090 participants.

BACKGROUND AND PURPOSE: Increased knowledge of stroke risk factors in the general population may lead to improved prevention of stroke. The objective of the present study was to assess knowledge of stroke risk factors and to determine factors associated with knowledge. METHODS: In a population-based survey, we sent a questionnaire to randomly selected residents in Berlin who were > or =50 years of age enquiring about knowledge of stroke risk factors. Knowledge was assessed in an open-ended question. In addition, we enquired about the source of participants' information. Sociodemographic factors, including age, sex, educational level, and nationality, were also assessed. RESULTS: A total of 28,090 of 75,720 residents (response rate, 37%) responded to the questionnaire. Of all respondents, 68% were able to name > or =1 correct stroke risk factor, and 13% named 4 correct risk factors. The majority of respondents named mass media as source of information (82%), followed by family/friends (45%) and by general physicians (20%). In multivariable analysis, increased knowledge of stroke risk factors was significantly associated with younger age, a higher educational level, not living alone, a German nationality, and having received any information about stroke during the last year. However, characteristics of respondents using the respective sources of information varied significantly. CONCLUSIONS: Mass media was most frequently named as a source of information about stroke risk factors. Source of information used varied according to population characteristics. Health education programs should take this into account and be adapted accordingly.

Aged↗

PubMed2006

Medical management in patients following stroke and transitory ischemic attack: a comparison between men and women.

STUDY OBJECTIVE: Differences between men and women in management and outcome following cerebrovascular events have been described. However, most of the differences observed have only been partially adjusted for baseline differences, or not at all. The objective of the present study was to compare acute and follow-up management between men and women after stroke and transitory ischemic attacks, adjusting for potential confounders. DESIGN: Patients with symptoms of stroke were included at admission to one of four participating hospitals in the inner city of Berlin, Germany. Risk factors, clinical characteristics, and acute management were assessed from medical records. Patients were asked about socioeconomic factors and follow-up management in a baseline interview and by postal questionnaire, respectively. The follow-up was 12 months. Multiple logistic regression analyses were used to assess odds ratios for management variables. RESULTS: A total of 558 patients were included (55% men, mean age 65+/-13 years; 45% women, 69+/-14 years). Indications for admission were stroke (74%) and transitory ischemic attacks (26%). In multivariable analyses, there were no differences in diagnostic procedures performed at baseline and in follow-up management between men and women. However, women were significantly more likely to receive hypoglycemic drugs (odds ratio 2.49; 95% confidence interval 1.33-4.63) in the acute management period. Regarding the need for nursing support/a nursing home after 12 months, there were no significant differences between men and women. CONCLUSIONS: After adjustment for differences in baseline characteristics, we only found few differences in acute and long-term management between men and women following hospital admission after suffering a cerebrovascular event.

Aftercare↗

PubMed2006

Neural correlates of the interaction between transient and sustained processes: a mixed blocked/event-related fMRI study.

Complete understanding of the neural correlates of cognitive processes requires investigation of both event- and state-related correlates of cognitive performance as well as their interaction. Neuroimaging studies using blocked designs confound these two types of processes and studies using event-related designs focus exclusively on the detection of transient effects. Recent fMRI studies used mixed blocked/event-related designs and found that transient and sustained activity can be dissociated, but it is not yet known how event-related and state-related processing interact. Here we used a phonological categorization paradigm in a mixed blocked/event-related design to investigate where in the brain transient activity interacts with sustained activity. Task difficulty was parametrically manipulated based on individually determined categorization thresholds. We found an interaction effect of transient and sustained activity in the left precuneus. In this cortical structure transient activity increased with increasing task difficulty, while sustained neural activity decreased with increasing task difficulty. Our data suggest that sustained activity is enhanced during processing of an easy task, presumably because of ongoing internally cued endogenous processing, still allowing effortless processing of transient stimuli. During performance of a difficult task, sustained activity in the precuneus is reduced to provide resources for processing incoming stimuli. Processing of stimuli that are expected to be difficult elicits increased transient responses independent of the actual physical properties of the stimuli. In showing an interaction between transient and sustained activity in the precuneus, the present results accommodate seemingly diverging results from previous studies using event-related or blocked designs and expand the knowledge emerging from previous studies using mixed blocked/event-related designs.

Acoustic Stimulation↗

PubMed2006

Temporal profile of T2-weighted MRI distinguishes between pannecrosis and selective neuronal death after transient focal cerebral ischemia in the rat.

Transient middle cerebral artery occlusion (MCAO) by an intraluminal thread leads to primarily subcortical infarctions with little sensorimotor impairment in the Wistar rat strain. We investigated the course of infarct development in this lesion type for 10 weeks using magnetic resonance imaging (MRI) along with histological characterization. MCAO was induced in male Wistar rats (260 to 300 g) for 60 mins. Animals received follow-up T1- and T2-weighted MRI from day 1 until week 10. Separate groups of animals were analyzed histologically after 2, 6, and 10 weeks. Histology included immunohistochemistry for neuronal and astrocytic markers as well as hematoxylin eosin and luxol fast blue-cresyl violet staining. In contrast to lesions involving the cortex, exclusively subcortical infarctions were characterized by a complete resolution of initially increased T1 and T2 relaxation times by 10 weeks. Between 2 and 10 weeks, neuronal death and gliosis as well as a dense inflammatory infiltrate were evident in these lesions, without damage to fiber tracts or development of cystic cavities. Exclusively subcortical lesions in Wistar rats are characterized by normalization of T1 and T2 relaxation times, which might, however, not be mistaken for tissue recovery. Despite this MRI normalization, selective neuronal death and gliosis develop. Although MRI at individual time points might therefore be ambiguous, the temporal profile of relaxation time changes over the chronic time period allows discrimination of the lesion development into selective neuronal death or pannecrosis.

Animals↗

PubMed2006

Now you feel it--now you don't: ERP correlates of somatosensory awareness.

We investigated correlates of somatosensory awareness for supra theshold stimuli using event-related potentials in a masking paradigm: Conscious perception of a weak, but suprathreshold "target" stimulus was suppressed in a significant number of trials when followed by a higher-intensity "mask" stimulus. ERPs were compared for trials with perceived versus unperceived target stimuli. Early ERPs (P60, N80), generated in the contralateral S1, were found independent of stimulus perception. In contrast, for consciously perceived target stimuli, amplitude enhancements were observed for the P100 and N140. Thus, early activation of S1 is not sufficient to warrant conscious stimulus perception. Conscious stimulus processing differs significantly from unconscious processing starting around 100 ms after stimulus presentation when the signal is processed in parietal and frontal cortices, brain regions crucial for stimulus access into conscious perception.

Adult↗

PubMed2005

Preserved responsiveness of secondary somatosensory cortex in patients with thalamic stroke.

Cortical representations may change when somatosensory input is altered. Here, we investigated the functional consequences of partial "central" deafferentation of the somatosensory cortex due to a lesion of the ventroposterior lateral nucleus (VPL) in patients at a chronic stage after solitary infarction of the thalamus. Event-related functional magnetic resonance imaging during electrical index finger stimulation of the affected and nonaffected side was performed in 6 patients exhibiting contralesional sensory deficits (mainly hypesthesia). Involvement of the VPL and additional nuclei was determined by high-resolution magnetic resonance imaging (MRI) and subsequent MRI-to-atlas coregistration. For the group, statistical parametric maps showed a reduced activation of contralateral primary somatosensory cortex (SI) in response to stimulation of the affected side. However, no significant difference in the activation of contralateral secondary somatosensory cortex (SII) compared with stimulation of the nonaffected side was detected. Correspondingly, the ratio of SII-to-SI activation for the ipsilesional hemisphere was markedly elevated as compared with the contralesional hemisphere. For preserved responsiveness of SII in thalamic stroke comparable with that of the contralesional hemisphere, possible explanations are a direct thalamocortical input to SII mediating parallel information processing, nonlinear response behavior of SII in serial processing, or reorganizational processes that evolved over time.

Aged↗

PubMed2005

Sub-area-specific Suppressive Interaction in the BOLD responses to simultaneous finger stimulation in human primary somatosensory cortex: evidence for increasing rostral-to-caudal convergence.

In the primary somatosensory cortex (SI) of non-human primates, receptive field properties have been shown to differ between its sub-areas with increasing convergence in areas 1 and 2 as compared with area 3b. In this study, we searched for a similar functional organization of human SI. We performed fMRI in healthy subjects during separate or simultaneous electrical stimulation of the second and third finger of the right hand. Activation patterns in response to stimulation of single fingers reflected the somatotopical arrangement within the hand area of SI. Somatotopy was more clear-cut in area 3b as compared with areas 1 and 2. The response to simultaneous stimulation was considerably smaller than the summed responses to separate stimulation of each finger alone, pointing to a suppressive interaction effect. A region-of-interest analysis in the representational areas of the second and third finger revealed sub-area-specific differential suppressive interaction with an increase along the rostral-caudal axis (areas 3b, 1 and 2: 26, 32.7 and 42.2%, respectively). These findings on differences in the topographic as well as functional organization between sub-areas of SI support the notion of increasing convergence and integration from area 3b to areas 1 and 2 in human subjects.

Adult↗

PubMed2005

Dysfunction of ventral striatal reward prediction in schizophrenia.

BACKGROUND: Negative symptoms may be associated with dysfunction of the brain reward system in schizophrenia. We used functional magnetic resonance imaging (fMRI) to assess the BOLD response in the ventral striatum of unmedicated schizophrenics during presentation of reward-indicating and loss-indicating stimuli. METHODS: A total of 10 schizophrenic men (7 never medicated, 3 unmedicated for at least 2 years) and 10 age-matched healthy male volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or loss or would have no consequence. RESULTS: Compared to healthy controls, unmedicated schizophrenics showed reduced ventral striatal activation during the presentation of reward-indicating cues. Decreased activation of the left ventral striatum was inversely correlated with the severity of negative (and trendwise positive) symptoms. DISCUSSION: Reduced activation in one of the central areas of the brain reward system, the ventral striatum, was correlated with the severity of negative symptoms in medication-free schizophrenics. In unmedicated schizophrenic patients, a high striatal dopamine turnover may increase the "noise" in the reward system, thus interfering with the neuronal processing of reward-predicting cues by phasic dopamine release. This, in turn, may contribute to negative symptoms as such as anhedonia, apathy, and loss of drive and motivation.

Adult↗

PubMed2005

The fast optical signal--robust or elusive when non-invasively measured in the human adult?

Near infrared spectroscopy (NIRS) can detect vascular changes in cerebral cortical tissue elicited by functional stimulation. For some 10 years, another optical signal has been reported to be accessible by NIRS. This signal has been reported to correlate to the electrophysiological response rendering NIRS an exquisite non-invasive approach to investigate neurovascular coupling in the human adult. Due to their typical latency of up to hundreds of milliseconds, these signals have been termed "fast" optical signals and have been postulated to stem from scatter changes in neuronal tissue, as a fingerprint of the electrophysiological response. Here, we utter a less optimistic view on the non-invasive detectability of these changes in the human, motivated by an upper limit signal size estimation, predicting a signal size by orders of magnitude smaller than those previously reported. Also, we discuss the influence of small stimulus correlated movement artifacts potentially mimicking a fast optical signal. Based on invasive studies, we perform an upper limit estimation for changes in intensity and mean time of flight, which can be expected assuming a scatter change in the cerebral cortex while measuring on the surface of the head of an adult subject. Since the resulting numbers are far below those previously reported, we constructed a simple system, which minimizes technical noise. The system allows us to detect rather small intensity changes (2 x 10(-3)%) when averaging over approximately 3000 stimuli. Despite this outstandingly low noise level of the system, we find a reliable change in response to a sub-motor-threshold steady state median nerve stimulation in just one single subject (8 subjects examined, 4 subjects twice). Exceeding the motor threshold leads to large stimulus related artifacts, on a similar time scale and with comparable amplitude as previously reported signals. To check for potential modality specific problems, we next performed a visual stimulation study, avoiding potential motor artifacts. For the steady state visually evoked response, no subject yielded a reliable result (11 subjects examined, 4 subjects twice). The paper discusses these findings by a review of the literature on fast optical signals and their being accessible in the adult human.

Adult↗

PubMed2005

The use of the 12-item short-form health status instrument in a longitudinal study of patients with stroke and transient ischaemic attack.

The 36-item short-form health survey (SF-36) is one of the most commonly used health status instruments in patients with cerebrovascular disease. However, responsiveness to change in health-related quality of life (HRQoL) has not yet been assessed for the SF-36 and its shortened version, the SF-12. The main objective of the present study was to determine responsiveness to change of the SF-12 in patients with cerebrovascular disease. Patients with stroke/transient ischaemic attack (TIA) were included at admission to one of four participating hospitals. HRQoL was assessed with the Physical (PCS-12) and Mental (MCS-12) Component Summary scales at baseline (referring to the status prior to the event) and after 12 months. Responsiveness to change was determined with the standardized response mean (SRM) and classified as small (SRM 0.20-0.49), moderate (0.50-0.79) or large (> or =0.80). A total of 558 patients were included [55% men, mean age 65 (SD, 13) years; 45% women, mean age 69 (SD, 14) years]. Indications for admission were stroke (74%) and TIA (26%). In patients with stroke, SRMs were small for the PCS-12 [SRM 0.49; absolute change -5.9 (SD, 12)] and moderate for the MCS-12 [SRM 0.52; absolute change -6.6 (SD, 13)]. In patients with TIA, SRMs were below 0.2 for the PCS-12 [absolute change -0.7 (SD, 11)] and small for the MCS-12 [SRM 0.34; absolute change -3.7 (SD, 11)]. SRMs increased with stroke severity as indicated by the NIHSS score. The SF-12 summary scales showed a small to moderate responsiveness to change in patients after stroke. Responsiveness to change was higher in patients with increased symptom severity.

Aged↗

PubMed2005

Visual evoked potentials recovered from fMRI scan periods.

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may allow functional imaging of the brain at high temporal and spatial resolution. Artifacts generated in the EEG signal during MR acquisition, however, continue to pose a major challenge. Due to these artifacts, an interleaved modus has often been used for "evoked potential" experiments, i.e., only EEG signals recorded between MRI scan periods were assessed. An obvious disadvantage of this approach is the loss of a portion of the EEG information, which might be relevant for the specific scientific issue. In this study, continuous, simultaneous EEG-fMRI measurements were carried out. Visual evoked potentials (VEPs) could be reconstructed reliably from periods during MR scanning and in between successive scans. No significant differences between both VEPs were detected. This indicates sufficient artifact removal as well as physiological correspondence of VEPs in both periods. Simultaneous continuous VEP-fMRI recordings are thus shown to be feasible.

Adult↗