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Biomedical subjects

Klaus Willmes

Publications and source records attributed to Klaus Willmes.

32 records · Page 2Linked to original sources

Recovery of semantic word processing in global aphasia: a functional MRI study.

One important issue concerning the recovery of higher cognitive functions-such as word comprehension in aphasia-is to what extent impairments can be compensated for by intact parts of the network of areas normally involved in a closely related function ("redundancy recovery"). In a previous functional MRI investigation, we were able to show that left hemispheric redundancy recovery within a distributed system of related lexical-semantic functions was the most probable basis of recovery of comprehension from transcortical sensory aphasia. The question remained, however, whether redundancy recovery may play a more general role in the recovery of comprehension after large left hemispheric lesions and severe aphasia. We had the possibility, using the same fMRI paradigm, to study seven cases with left middle cerebral artery (MCA) infarction and partial recovery of comprehension > or =6 months after presentation with global aphasia on acute assessment. Lateralization of activation did not differ significantly between patients and controls. The most consistent regions of activation included the left extrasylvian posterior temporal and the right posterior parietal cortex. Recovery of language comprehension was associated predominantly with activations in regions, which were also activated in several normal subjects. We suggest that a redundancy recovery mechanism within multiple representations of closely related functions was more important than take-over of function by previously unrelated areas (vicariation) as the basis of recovery of word comprehension in our patients in spite of extensive left hemispheric damage. We conclude that redundancy within the lexical-semantic system seems to make an important contribution to recovery of comprehension even in severe aphasia.

Acoustic Stimulation↗

Functional reorganisation in patients with right hemisphere stroke after training of alertness: a longitudinal PET and fMRI study in eight cases.

In patients with alertness deficits due to right hemispheric vascular brain damage, training induced changes in the individual functional networks involved in intrinsic alertness were assessed in a longitudinal positron emission tomography (PET)/fMRI activation study. Patients were trained by administering the alertness routine of the AIXTENT computerized attention training or, in the control condition, by using a computerized training of verbal and topological memory. Before and after the training, both a PET/fMRI and a neuropsychological assessment were carried out. In this paper, we are presenting four patients after alertness training: three, whose alertness performance improved significantly after training, and one, who did not improve. In the patients showing behavioural improvement, the PET/fMRI activation after training revealed partial restitution of the right hemisphere (RH) functional network known to subserve intrinsic alertness in normal subjects, especially in the right dorsolateral or medial frontal cortex. For the patient without behavioural improvement, the PET activation after training showed an increase of activation only in the left hemisphere. Out of the four patients in the memory training control group only one showed significant improvement of alertness. Another patient had an increase of right frontal activation after the training but this did not correspond to behavioural improvement. In a control group of six normal participants, repetition of the alertness activation paradigm in fMRI revealed a decrease of right frontal and parietal activation from the first to a second measurement after 3 weeks, in contrast to the observed training induced effects in the patients.

Adult↗

Network for auditory intrinsic alertness: a PET study.

Intrinsic alertness designates the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time (RT) measurements without preceding warning stimuli. Until now, cerebral networks subserving alertness after visual and somatosensory stimulation have been reported. Studies concerning other intensity aspects of alertness like sustained attention and vigilance, on the other hand, have been performed in the auditory modality, too. In a 15O-butanol PET-activation study in 10 right-handed young healthy male volunteers an intrinsic alertness network was studied for the auditory modality. In contrast with a sensorimotor control condition we found an extended predominantly right-hemisphere network similar to those reported for other sensory modalities including frontal, cingular, inferior parietal, temporal and thalamic structures, when subjects waited for and rapidly responded to a 1000 Hz tone signal by pressing a response key with the right-hand thumb. There were, however, some differences in the topography of the frontal, temporal and thalamic activations between auditory and visual stimulation which are discussed with respect to similar results for auditory vigilance and auditory selective attention tasks reported in the literature.

Acoustic Stimulation↗

On the perceptual generality of the unit-decade compatibility effect.

Number magnitude is assumed to be holistically represented along a single mental number line. Recently, we have observed a unit-decade-compatibility effect which is inconsistent with that assumption (Nuerk, Weger, & Willmes, 2001). In two-digit Arabic number comparison, we have demonstrated that compatible comparisons in which separate decade and unit comparisons lead to the same decision (32_47, 3 < 4 and 2 < 7) were faster than incompatible trials (37_52, 3 < 5, but 7 > 2). Because overall distance was matched, a holistic model could not account for the compatibility effect. However, one could argue that the compatibility effect was due to the specific vertical perceptual arrangement of the two-digit numbers in Nuerk et al.'s (2001) experiment where the decade digits and unit digits were presented column-wise above each other. To examine this objection, we studied the perceptual generality of the compatibility effect with diagonal presentation. We replicated the compatibility effect with diagonal presentation. It is concluded that the compatibility effect is not due to encoding characteristics imposed by the perceptual setting of the original experiment. In particular, the assumption of an overall analog magnitude representation for two-digit numbers is not consistent with these data.

Adult↗

On the development of the mental number line: more, less, or never holistic with increasing age?

Magnitude is assumed to be represented along a holistic mental number line in adults. However, the authors recently observed a unit-decade compatibility effect for 2-digit numbers that is inconsistent with this "holisticness" assumption (H.-C. Nuerk, U. Weger, & K. Willmes, 2001). This study used the compatibility effect to examine whether the mental number line representation of magnitude changes toward greater or less holisticness in children from Grades 2-5. The results indicate that decades and units of 2-digit numbers are processed separately rather than holistically from Grade 2 on. However, this separate processing seems to develop from a more sequential (left-to-right) to a more parallel processing mode. Moreover, children may use different strategies depending on task demands. The results are interpreted in the framework of Siegler's overlapping waves model.

Child↗

Notational modulation of the SNARC and the MARC (linguistic markedness of response codes) effect.

Number magnitude and number parity representation are fundamental number representations. However, the representation of parity is much less understood than that of magnitude: Therefore, we investigated it by examining the (new) Linguistic Markedness of Response Codes (MARC) effect: Responses are facilitated if stimuli and response codes both have the same (congruent) linguistic markedness (even-right, odd-left) while incongruent conditions (even-left, odd-right) lead to interference. We examined systematically the MARC (for parity) and the Spatial Numerical Association of Response Codes (SNARC; for magnitude) effect for different number notations (positive Arabic, negative Arabic, number words) and with different methods of data analysis. In a parity judgement task, the SNARCeffect indicating a magnitude representation was replicated for all notations except for negative numerals. The MARCeffect was found for number words in all analyses, but less consistently for the other notations. In contrast, a correlational analysis of the reaction time (RT) data, as suggested by Sternberg (1969) using a nonmetric multi-dimensional scaling (MDS) procedure, produced a clear association of parity and response code for all notations (MARCeffect), but little evidence of the SNARCeffect. We discuss the extent to which these notation-specific MARC and SNARC effects constrain current models of number processing and elaborate on the possible functional locus of the MARC effect.

Adult↗

Lexical decision of nonwords and pseudowords in humans: a positron emission tomography study.

In this functional positron emission tomography study brain activations during an auditory lexical decision task with two experimental conditions were investigated. First, the subjects had to discriminate between real words and nonwords; second, real words varied with pseudowords. Comparing each of these tasks to an auditory control condition we found bilateral activation of the superior temporal and inferior frontal gyrus, lateralized to the left in the pseudoword condition. The comparison of the lexical decision tasks revealed higher rCBF during the pseudo-/real word decisions within BA 47, adjacent to Broca's area, and the anterior cingulate. The data support the notion that the lexical decision during a nonword task is mainly based on a phonological discrimination process, whereas a pseudoword task more strongly requires lexical access resulting in activation of BA 47.

Acoustic Stimulation↗

Assessment of reliability in functional imaging studies.

PURPOSE: To investigate the reliability of functional magnetic resonance imaging (fMRI), an approach for mapping and quantifying reliably activated voxels was developed. MATERIALS AND METHODS: First, a SPM99 analysis was performed, and the resulting statistical maps were taken as the basis for subsequent analyses of reliability. Several approaches were demonstrated using 1). a voxel-wise intraclass correlation coefficient (ICC); 2). an analysis of scatter plots, calculating the correlation of contrast t-values for pairs of activation maps; and 3). the ratio of overlapping volumes as suggested in the literature. The methods were applied to an fMRI study in which subjects were asked to vary their attentional effort during watching a flickering checkerboard pattern with varying letters in the center. The subjects had to ignore or attend to the presentation, or they had to detect a target letter within the checkerboard. RESULTS: The imaging data showed good reliability in terms of ICC for regions of visual processing, as well as for frontal areas, especially in the letter detection task. Furthermore, the size of reliable clusters depended on the presumed attentional effort of the subjects. CONCLUSION: Application of the method demonstrated that the activation due to visual stimulation could also be detected very consistently during a no-attend condition, but the reliability of the activations were best during the attended tasks.

Adult↗

Cerebral activation in abstinent ecstasy (MDMA) users during a working memory task: a functional magnetic resonance imaging (fMRI) study.

The popular recreational drug ecstasy (3,4-methylenedioxymethamphetamine=MDMA and related congeners) is neurotoxic upon central serotonergic systems in animal studies. So far, the most convincing evidence for neurotoxicity-related functional deficits in humans derives from neurocognitive studies demonstrating dose-related long-term learning and memory problems in ecstasy users. In our study we used functional magnetic resonance imaging (fMRI) and a working memory task to investigate cerebral activation in eleven heavy, but currently abstinent MDMA users and two equally sized groups of moderate users and non-users. There were no significant group differences in working memory performance and no differences in cortical activation patterns for a conservative level of significance. However, for a more liberal statistical criterion, both user groups showed stronger activations than controls in right parietal cortex. Furthermore, heavy users had a weaker blood oxygenation level-dependent (BOLD) response than moderate users and controls in frontal and temporal areas. Our results may indicate subtle altered brain functioning associated with prior MDMA use, although alternative interpretations of these group differences must be considered.

Adult↗

Power grip disinhibits the ipsilateral sensorimotor cortex: a TMS and fMRI study.

Electrophysiological studies have shown that forceful activation of the hand muscles (power grip) is accompanied by an increased excitability of the ipsilateral corticospinal system. This increase in excitability may be due to spinal or cortical mechanisms. Here we show with fMRI that this phenomenon is at least in part mediated at a cortical level. We used TMS to show that the increased ipsilateral excitability during a forceful maneuver leads to enhanced stimulus-response curves. fMRI was used to compare the activation during a repetitive hand movement with or without an accompanying power grip on the opposite site. The power grip reduced movement-related activation in the ipsilateral sensorimotor cortex. Peak deactivation was located in the left postcentral gyrus extending into the adjacent precentral gyrus. This finding suggests that a forceful activation of the hand muscles disinhibits a distinct functional representation in the ipsilateral sensorimotor cortex. Consequently, the excitability of the corticospinal system increases and less neuronal excitatory activity is needed to perform a given task. The results may be important for a variety of studies as they suggest that fMRI may show decreased hemodynamic response under conditions in which other neurophysiological methods have shown increased functional activity.

Brain Mapping↗

On the impact of different number representations in the number bisection task.

The number bisection task--in which the numerical middle of two other numbers has to be determined (e.g., 6 is the numerical middle of 4 and 8)--has recently been used in neuropsychological case studies in addition to the number comparison task to assess quantitative capabilities in number processing. While factors determining difficulty in normal participants have often been systematically investigated in the number comparison task, this has not yet been done in the number bisection task. Based on a pilot study by van Herten (1999), we extracted four factors that we hypothesized to modulate difficulty in a verification version of the number bisection task in normal participants: Multiplicativity (whether or not the three numbers are part of a multiplication table), range (distance between the smallest and the largest number) for bisectable number triplets as well as distance of the middle number to the numerical middle, and bisection possibility for non-bisectable triplets. In the current study, we obtained large effects for all four factors on RT and accuracy data and some interesting interactions in normal participants. In a regression analysis, we additionally observed inhibitory effects of decade crossing and of ten inclusion (whether or not one of the three numbers was a decade number). We discuss the impact of these results for the use of the number bisection task as an assessment tool in neuropsychology. Finally, we examine the consequences of these results for models of number processing.

Adult↗

Number representation deficit: a bilingual case of failure to access written verbal numeral representations.

This study reports the case of a Greek-German bilingual patient (S.V.) with specific deficit in Arabic number production from written German number words. S.V. was able to successfully complete the reverse task, i.e. to convert Arabic numerals into written or oral German number words. She also showed preserved ability to produce both German and Greek numbers and to accurately make oral magnitude judgments in both languages. However, when transcoding two-digit numbers from German written numerals to Arabic numbers she consistently reversed the digits. A series of in-house tasks were used to test her general abilities of number processing, i.e. number synesthesia and calculation. Moreover, a number magnitude comparison task was developed specifically for pairs of numbers with reverse digits and we found that out of pairs of numbers with reverse digits with magnitude less than 100, there exist 19 pair combinations for which distance and relative distance are not concordant. The results suggest that S.V.'s performance was significantly worse as the absolute distance between the numbers in the number pairs increased. These investigations are discussed in analogy with a grammatical rule problem related to absolute and relative distance effects.

Brain Neoplasms↗

Recovery of semantic word processing in transcortical sensory aphasia: a functional magnetic resonance imaging study.

In a previous functional magnetic resonance imaging (fMRI) study with normal subjects, we demonstrated regions related to conceptual-semantic word processing around the first frontal sulcus (BA 9) and the posterior parietal lobe (BA 7/40) in agreement with several previous reports. We had the possibility, using the same fMRI paradigm, to study two consecutive cases with left middle cerebral artery (MCA) infarction (RC and HP) and lesions affecting either solely the pre-frontal (HP) or both the pre-frontal and posterior parietal part of the network activated in normal subjects (RC). Both patients showed transcortical sensory aphasia (TSA) on acute assessment. This contradicts classical disconnection accounts of the syndrome stating intact conceptual representations in TSA. Their recovery of language comprehension was associated with activation of a left hemispheric network. Mainly activations of left perilesional pre-frontal regions (RC), left Wernicke's area (RC and HP) or the left posterior middle and inferior temporal cortex (HP) were demonstrated in the TSA patients. The latter findings suggest that in our cases of TSA functional take-over has occurred in regions with related functions ('redundancy recovery') rather than in previously unrelated areas ('vicarious functioning'). Our data support distributed models of conceptual-semantic word processing and multiple left hemispheric representations of closely related functions.

Adult↗