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Klaus Willmes

Publications and source records attributed to Klaus Willmes.

At least 19 recordsLinked to original sources

Analysis of intersubject variability in activation: an application to the incidental episodic retrieval during recognition test.

Since the brain may engage different neuronal systems for a single behavioral goal, activation may show intersubject variability expressed in the systematic recruitment of multiple distinct networks. We apply a principal component analysis (PCA) to activation over task conditions and subjects to reveal cortical networks that may underlie this intersubject variability. Normal subjects were presented with novel meaningless objects, which appeared in personally familiar or unfamiliar places. During a subsequent, event-related functional MRI (fMRI) experiment, each subject was presented with learned or novel objects in isolation and performed a learned/novel judgment. Recollection of places was not essential for the task, and may exhibit large intersubject variations. The right posterodorsal posterior cingulate cortex (pPCC) and left retrosplenial cortex, whose involvement in place-recognition has been previously established, were selected as regions of interest for the PCA. Neural responses to objects associated with familiar relative to unfamiliar places in pPCC, but not in the retrosplenial cortex, were negatively correlated with task-related activation (common over all objects) in the right anterolateral prefrontal cortex and the left intraparietal sulcus. The latter areas have been implicated previously in cognitive control and object recognition, respectively. These results suggest right prefrontal control over neural processes both in the left parietal cortex, related to object-recognition (enhancement), and pPCC, related to nonessential recollection of place-memory (suppression), but not in the retrosplenial cortex, related to the sense of familiarity. This analysis revealed an important aspect of functional anatomy that was not detectable using a conventional analysis of average activations.

Adolescent↗

On the functional role of human parietal cortex in number processing: How gender mediates the impact of a 'virtual lesion' induced by rTMS.

Areas around the horizontal part of the intraparietal sulcus (hIPS) have repeatedly been reported to participate in processing numerical magnitude. Using transcranial magnetic stimulation (TMS), we investigated the functional role of the hIPS by examining two effects from the domain of numerical cognition: in magnitude comparison tasks response latencies are inversely related to the numerical distance between two numbers. This distance effect indexes access to the mental number representation. In magnitude comparison tasks responses are faster when decade and unit comparison would lead to the same decision (e.g. 42_57, 4 < 5 and 2 < 7) than when they would not (e.g. 47_62, 4 < 6 but 7 > 2). This compatibility effect reflects unit-decade integration processes. Differential susceptibility of (fe)male participants to TMS was examined. We applied repetitive TMS (rTMS; 1Hz for 10 min) over the left hIPS in 12 participants (6 female). No stimulation and vertex stimulation served as control conditions. The effect of rTMS was mediated by gender: in male participants, the distance effect decreased after TMS over hIPS. For female participants distance and compatibility effect both increased. This modulation of the compatibility effect was limited in duration to no more than 4 min. The hIPS seems to be functionally involved both in number magnitude processing and in integrating unit-decade magnitude information of two-digit numbers. Relative hemispheric specialization of the hIPS with respect to two-digit magnitude comparison is discussed.

Adult↗

Dynamics of language reorganization after stroke.

Previous functional imaging studies of chronic stroke patients with aphasia suggest that recovery of language occurs in a pre-existing, bilateral network with an upregulation of undamaged areas and a recruitment of perilesional tissue and homologue right language areas. The present study aimed at identifying the dynamics of reorganization in the language system by repeated functional MRI (fMRI) examinations with parallel language testing from the acute to the chronic stage. We examined 14 patients with aphasia due to an infarction of the left middle cerebral artery territory and an age-matched control group with an auditory comprehension task in an event-related design. Control subjects were scanned once, whereas patients were scanned repeatedly at three consecutive dates. All patients recovered clinically as shown by a set of aphasia tests. In the acute phase [mean: 1.8 days post-stroke (dps)], patients' group analysis showed little early activation of non-infarcted left-hemispheric language structures, while in the subacute phase (mean: 12.1 dps) a large increase of activation in the bilateral language network with peak activation in the right Broca-homologue (BHo) was observed. A direct comparison of both examinations revealed the strongest increase of activation in the right BHo and supplementary motor area (SMA). These upregulated areas also showed the strongest correlation between improved language function and increased activation (r(BHo) = 0.88, r(SMA) = 0.92). In the chronic phase (mean: 321 dps), a normalization of activation with a re-shift of peak activation to left-hemispheric language areas was observed, associated with further language improvement. The data suggest that brain reorganization during language recovery proceeds in three phases: a strongly reduced activation of remaining left language areas in the acute phase is followed by an upregulation with recruitment of homologue language zones, which correlates with language improvement. Thereafter, a normalization of activation is observed, possibly reflecting consolidation in the language system.

Acute Disease↗

The hyperdense posterior cerebral artery sign: a computed tomography marker of acute ischemia in the posterior cerebral artery territory.

BACKGROUND AND PURPOSE: In the anterior circulation, the hyperdense middle cerebral artery (MCA) sign is a well-established marker for early ischemia. Similarly, the hyperdense basilar artery sign or the MCA "dot" sign may be a diagnostic clue for basilar artery or distal MCA branch thrombosis. The purpose of this study was to define the hyperdense posterior cerebral artery (PCA) sign and determine its incidence, diagnostic value, and reliability as a marker for ischemia in the territory of the PCA. METHODS: Cranial computed tomographies (CCTs) of 48 patients with proven acute ischemia (<12 hours) in the PCA territory were compared by 3 independent and blinded readers to the CCTs of 86 age-matched patients without PCA infarction. Using follow-up imaging, the correlation of the hyperdense PCA (HPCA) with infarct size, thalamic infarction, and bleeding were investigated. RESULTS: An HPCA was found in 35.4% of all patients with PCA infarction, typically within the ambient cistern, with a specificity of 95.4%. The thalamus was affected significantly more often (P=0.009) and the size of the infarct was significantly more often large than medium (P=0.018) or small (P<0.001) when an HPCA was present. Hemorrhagic transformation tended to occur more often when the HPCA was present. CONCLUSIONS: An HPCA was detected in more than one third of all patients with PCA ischemia, suiting the incidence of the hyperdense MCA. Based on our results, this sign may not only be helpful in the early diagnosis of PCA infarction but might also act as a prognostic marker in acute PCA territory ischemic stroke.

Adult↗

Crossed hands and the SNARC effect: a failure to replicate Dehaene, Bossini and Giraux (1993).

Dehaene et al. (1993, Experiment 6) presented evidence that the mental number line is left-to-right oriented with respect to representational associations and not with respect to left and right hands. Here we tried to replicate the study of Dehaene et al. (1993) in a larger sample (n = 32) using four different stimulus notations (Arabic numbers, number words, auditory number words, and dice patterns). As in the study by Dehaene et al. (1993), the spatial numerical association of response codes (SNARC) effect was examined with an incongruent hand assignment to left/right response keys (crossed hands). In contrast to Dehaene et al. (1993), we did not observe a SNARC effect in any condition. Power analyses revealed that n = 32 should have been large enough to detect SNARC effects of usual size. Furthermore, time-course analyses revealed no SNARC slope in faster and slower responses, so that the null effect could not be due to relatively slow responses with crossed hands. Joint analyses with previous data (Nuerk et al., 2005b) revealed significantly steeper SNARC slopes with congruent hand assignment, and no interaction between hand assignment and notation. Altogether, these findings suggest that the results of Dehaene et al. (1993) only hold under specific conditions. Differences between studies are discussed. We suggest that spatial context has an influence on the SNARC effect and that hand-based associations (and not only representational associations) are relevant for the SNARC effect.

Adolescent↗

What do semi-illiterate adults know about 2-digit Arabic numbers?

Brazilian semi-illiterates (n=19) with 1 to 4 years of academic training compared 2-digit Arabic numbers. Like competent readers, semi-illiterates responded faster and more accurately when the larger number also had the larger unit digit (unit-decade compatibility). Even semi-illiterates with minimal academic training were sensitive to the unit-decade compatibility on number comparison. Probably semi-illiterates derive their ability to automatically activate unit-decade segmentation directly from the oral/verbal number representation. Interestingly, processing speed had an effect on two-digit number comparison. Faster participants showed a smaller or even inverted unit-decade compatibility. Processing speed reflects increased automatization of number segmentation and better selection of the decade-digits for comparison, what eliminates the semantic interference of units. In line with previous research, our data suggest that unit-decade segmentation plays a pervasive role in Arabic number comparison.

Adolescent↗

Language lateralization in temporal lobe epilepsy: a comparison between fMRI and the Wada Test.

PURPOSE: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI-based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT). METHODS: To establish the power of language fMRI to detect language lateralization during presurgical assessment, we compared the findings of a semantic decision paradigm with the results of a standard IAT in 68 patients with chronic intractable right and left temporal lobe epilepsy (rTLE, n=28; lTLE, n=40) who consecutively underwent a presurgical evaluation program. The patient group also included 14 (20.6%) subjects with atypical (bilateral or right hemisphere) speech. Four raters used a visual analysis procedure to determine the laterality of speech-related activation individually for each patient. RESULTS: Overall congruence between fMRI-based laterality and the laterality quotient of the IAT was 89.3% in rTLE and 72.5% in lTLE patients. Concordance was best in rTLE patients with left speech. In lTLE patients, language fMRI identified atypical, right hemisphere speech dominance in every case, but missed left hemisphere speech dominance in 17.2%. Frontal activations had higher concordance with the IAT than did activations in temporoparietal or combined regions of interest (ROIs). Because of methodologic problems, recognition of bilateral speech was difficult. CONCLUSIONS: These data provide evidence that language fMRI as used in the present study has limited correlation with the IAT, especially in patients with lTLE and with mixed speech dominance. Further refinements regarding the paradigms and analysis procedures will be needed to improve the contribution of language fMRI for presurgical assessment.

Adolescent↗

The influence of an external symbol system on number parity representation, or what's odd about 6?

The aim of this study was to investigate whether language-specific properties influence mental number processing. German Sign Language (DGS) numbers differ from those in spoken German not only in terms of modality but also in their basic language structure. A group of 20 congenitally deaf German signers participated in a number parity (odd/even) judgment task with DGS and printed German number words. The results indicated that two-handed DGS number signs are processed in a decomposed way. This language-specific effect also generalized to another linguistic number notation, German number words, but not to Arabic digit notation. These differences are discussed with respect to two possible routes to number parity.

Adult↗

Neural representations of two-digit numbers: a parametric fMRI study.

When participants are asked to decide which of a pair of two-digit Arabic numbers is larger, they compare units and decades, even when units are irrelevant. Typically, behavioral responses are slower when units are incongruent with the decade comparison (e.g. 81_26, because 8 > 2 but 1 < 6; unit-decade compatibility effect, [Nuerk, H.-C., Weger, U., Willmes, K. 2001. Decade breaks in the mental number line? Putting the tens and units back in different bins. Cognition 82, B25-B33.]). We defined parametric regressors to examine the effect of decade digit distance and unit distance-based compatibility processing on the fMRI signal to investigate the neural correlates of two-digit magnitude processing. Fourteen male right-handed volunteers (mean age = 27, range 21-38 years) took part in the study. In a rapid event-related design, participants had to decide which of two two-digit Arabic numbers was larger. Data were preprocessed and analyzed statistically in SPM2. Activation in the anterior portion of the right IPS was significantly modulated by compatibility-based unit distance processing. Furthermore, decade distance predicted an increase in the fMRI signal from cortex around the left IPS, right anterior and right posterior IPS. These results indicate that magnitude representations of unit-decade compatibility and decade distance are subserved by the intraparietal cortex and that the symbolic structure of the Arabic number system is an important determinant of multi-digit number magnitude processing. Implications of the present results in terms of general symbolic information processing are discussed.

Adult↗

Systems level modeling of a neuronal network subserving intrinsic alertness.

Cognitive control of alertness in unwarned situations (intrinsic alertness) relies on a predominantly right hemisphere cortical and subcortical network. In a previous functional activation study, we have demonstrated that this network comprises the anterior cingulate gyrus, the dorsolateral and polar frontal as well as the inferior parietal cortex, the thalamus and ponto-mesencephalic parts of the brain stem. The aim of this study was to study effective connectivity of this network by employing structural equation modeling. Fifteen right-handed male subjects participated in the PET study. The functional network showed stronger connectivity in the right hemisphere. Furthermore, there were strong effective connections between thalamus and brainstem on the one hand and between thalamus and anterior cingulate on the other. Our results suggest that the anterior cingulate functions as the central coordinating structure for the right hemispheric neural network of intrinsic alertness and that the anterior cingulate gyrus is modulated mainly by prefrontal and parietal cortex.

Adult↗

A special role for numbers in working memory? An fMRI study.

Although numbers carry averbal semantics (i.e., magnitude), they are often utilized in verbal Working Memory (vWM) tasks. However, vWM is thought to rely on a purely phonological code. Here, we tested the influence of (a) averbal semantics and (b) different tasks on performance in a vWM context by examining stimulus and task-specific variation of activity in the horizontal parts of the intraparietal sulcus (hIPS). The hIPS has previously been shown to subserve magnitude processing modulated by (a) specific stimuli and (b) specific tasks. Two variants of an n-back paradigm (comparison and identity match tasks) utilizing letters and numbers as stimulus material at different levels of vWM load were administered in 16 participants. Behavioral and functional imaging data reveal stimulus-specific modulation of activity in the hIPS suggesting a semantic influence of numbers. In the identity match task, numbers induced additional hIPS activation compared to letters while letters never induced additional hIPS activation when compared to numbers. Letters as compared to numbers only induced additional hIPS activation in the comparison task. These results question the assumption of a purely phonological code in vWM because hIPS activation subserving magnitude processing is modulated by stimulus semantics and task demands.

Adult↗

Prospective demonstration of short-term motor plasticity following acquired central pareses.

The effect of newly acquired central pareses on functional MRI (fMRI) signal pattern is not known, since up to now all investigated patients were examined while they already experienced the motor weakness. We describe the first prospective and controlled study demonstrating the impact of new, acquired central pareses on fMRI motor activation pattern. Six patients suffering from a new central paresis after resection of a brain tumor infiltrating the central region were prospectively compared with a control group of five patients without postoperative paresis and a group of six healthy, age-matched controls who were investigated at two time points. fMRI signal was postoperatively analyzed during the performance of hand motor tasks and compared to the preoperative fMRI results. The relative signal change between rest and activation was evaluated for five cortical regions: the primary motor cortex (M1) and the ipsilateral primary motor cortex (M1i), the supplementary motor area (SMA), the premotor area (PMA), and the superior parietal lobule (SPL). In the patients with new postoperative central pareses, significant (P = 0.0313) decreases in fMRI activation were found in M1, whereas significant (P = 0.0313) increases were found in SMA and PMA. For M1i and SPL, there was a signal increase on average as well, but it failed to reach significance (P = 0.1250). In both control groups, no significant changes between both examinations were seen. Even though the number of investigated patients is too small to draw definite conclusions, our results support the concept of short-term motor plasticity being mediated by redundant systems that may take over function after damage of the primary motor cortex. The findings potentially also reflect increased functional demands imposed upon the motor network subsequent to a loss of dexterity.

Adult↗

Language effects in magnitude comparison: small, but not irrelevant.

It is assumed that number magnitude comparison is performed by assessing magnitude representation on a single analog mental number line. However, we have observed a unit-decade-compatibility effect in German which is inconsistent with this assumption (Nuerk, Weger, & Willmes, 2001). Incompatible magnitude comparisons in which decade and unit comparisons lead to different responses (e.g., 37_52 for which 3<5, but 7>2) are slower and less accurately responded to than compatible trials in which decade and unit comparisons lead to the same response (e.g., 42_57, for which 4<5 and 2<7). As overall distance was held constant, a single holistic magnitude representation could not account for this compatibility effect. However, because of the inversion property of the corresponding German two-digit number words ("einundzwanzig" ), the language-generality of the effect is questionable. We have therefore examined the compatibility effect with native English speakers. We were able to replicate the compatibility effect using Arabic notation. Thus, the compatibility effect is not language-specific. However, in cross-linguistic analyses language-specific modulations were observed not only for number words but also for Arabic numbers. The constraints imposed on current models by the verbal mediation of Arabic number comparison are discussed.

Adult↗

The universal SNARC effect: the association between number magnitude and space is amodal.

It is thought that number magnitude is represented in an abstract and amodal way on a left-to-right oriented mental number line. Major evidence for this idea has been provided by the SNARC effect (Dehaene, Bossini, & Giraux, 1993): responses to relatively larger numbers are faster for the right hand, those to smaller numbers for the left hand, even when number magnitude is irrelevant. The SNARC effect has been used to index automatic access to a central semantic and amodal magnitude representation. However, this assumption of modality independence has never been tested and it remains uncertain if the SNARC effect exists in other modalities in a similar way as in the visual modality. We have examined this question by systematically varying modality/notation (auditory number word, visual Arabic numeral, visual number word, visual dice pattern) in a within-participant design. The SNARC effect was found consistently for all modality/notation conditions, including auditory presentation. The size of the SNARC effect in the auditory condition did not differ from the SNARC effect in any visual condition. We conclude that the SNARC effect is indeed a general index of a central semantic and amodal number magnitude representation.

Adolescent↗

The neural correlate of very-long-term picture priming.

Repetition priming denotes a behavioural change caused by prior exposure to a stimulus. The effect is known to last for weeks. This study addresses the underlying neural mechanisms for very-long-term picture priming by using event-related functional magnetic resonance imaging complemented by a behavioural paradigm. Previous functional imaging studies with shorter retention intervals have shown that priming is associated with changes in the activity of both the occipital and posterior temporal cortex. In this study we compared retention intervals of 1 day and 6 weeks after initial exposure to a picture stimulus. Priming-related decreases in cortical activity in posterior extrastriate and dorsal left inferior frontal areas were found only for the shorter retention interval. In contrast, fMRI activation in the inferior posterior temporal and anterior left inferior frontal cortex was reduced following priming for both retention intervals. In the behavioural paradigm, the priming effect was stable over time. We conclude that the left inferior frontal and inferior posterior temporal cortex play a key role in the very-long-term priming effect.

Adult↗

Process dissociation between contextual retrieval and item recognition.

We employed a source memory task in an event related fMRI study to dissociate MTL processes associated with either contextual retrieval or item recognition. To introduce context during study, stimuli (photographs of buildings and natural landscapes) were transformed into one of four single-color-scales: red, blue, yellow, or green. In the subsequent old/new recognition memory test, all stimuli were presented as gray scale photographs, and old-responses were followed by a four-alternative source judgment referring to the color in which the stimulus was presented during study. Our results suggest a clear-cut process dissociation within the human MTL. While an activity increase accompanies successful retrieval of contextual information, an activity decrease provides a familiarity signal that is sufficient for successful item recognition.

Adult↗

Do normal D-dimer levels reliably exclude cerebral sinus thrombosis?

BACKGROUND AND PURPOSE: Cerebral sinus thrombosis (CST) needs to be considered in the differential diagnosis of all patients with acute headache. Early diagnosis is essential because early treatment may prevent morbidity and may even be life-saving. Definite exclusion, however, needs advanced neuroradiologic diagnostics, which are not readily available in many hospitals. Because measurement of D-dimers has been demonstrated to be helpful in excluding thromboembolic disease, our aim was to investigate whether D-dimers would be also sensitive enough to exclude CST. METHODS: We undertook a prospective multicenter study over a 2.5-year period including all patients who came to the emergency departments with symptoms suggestive of CST. All patients were diagnosed either by magnetic resonance venography, spiral computed tomography scan venography, or intra-arterial digital subtraction angiography. D-dimer levels were measured at admission and analyzed by the same method in all patients. RESULTS: A total of 343 patients were included. CST was diagnosed in 35 patients, of whom 34 had D-dimers above the cutoff value (>500 microg/L). From the 308 patients not having CST, D-dimers were elevated in 27. Sensitivity of D-dimers was 97.1%, with a negative predictive value of 99.6%. Specificity was 91.2%, with a positive predictive value of 55.7%. D-dimers were positively correlated with the extent of the thrombosis and negatively correlated with the duration of symptoms (Spearman rank correlation coefficients 0.76, -0.58, respectively). CONCLUSIONS: D-dimer measurement is useful in patients with suspected CST. Normal D-dimers make the presence of CST very unlikely.

Adult↗