Biomedical subjects

Thomas Witzel

Publications and source records attributed to Thomas Witzel.

9 recordsLinked to original sources

PubMed2007

Spatiotemporal cortical dynamics underlying abstract and concrete word reading.

The current study used whole-head anatomically constrained magnetoencephalography (aMEG) to spatiotemporally map brain responses while subjects made abstract/concrete judgments on visually presented words. Both word types evoked a similar posterior-to-anterior sequence of cortical recruitment involving occipital, temporal, parietal, and frontal areas from approximately 100 to 900 ms poststimulus. A prominent left temporofrontal N400m was smaller to abstract words, while the right temporal N400m was smaller to concrete words, suggesting that differences may exist in their semantic representation. The left temporofrontal decrease for abstract words is consistent with EEG studies, indicating a smaller N400 for abstract words based on a more extensive or accessible lexicosemantic network. Furthermore, the N400m peaked at approximately 420 ms and was followed by a large right hemisphere medial occipitoparietal as well as lateral parietal response to concrete words peaking at approximately 550 ms, perhaps embodying imagistic processing. These data suggest that words may be initially understood using a left-lateralized (frontotemporal) verbal-linguistic system that for concrete words is supplemented after a short delay by a right parietal and medial occipital imagistic network.

Adolescent↗

PubMed2006

Task-modulated "what" and "where" pathways in human auditory cortex.

Human neuroimaging studies suggest that localization and identification of relevant auditory objects are accomplished via parallel parietal-to-lateral-prefrontal "where" and anterior-temporal-to-inferior-frontal "what" pathways, respectively. Using combined hemodynamic (functional MRI) and electromagnetic (magnetoencephalography) measurements, we investigated whether such dual pathways exist already in the human nonprimary auditory cortex, as suggested by animal models, and whether selective attention facilitates sound localization and identification by modulating these pathways in a feature-specific fashion. We found a double dissociation in response adaptation to sound pairs with phonetic vs. spatial sound changes, demonstrating that the human nonprimary auditory cortex indeed processes speech-sound identity and location in parallel anterior "what" (in anterolateral Heschl's gyrus, anterior superior temporal gyrus, and posterior planum polare) and posterior "where" (in planum temporale and posterior superior temporal gyrus) pathways as early as approximately 70-150 ms from stimulus onset. Our data further show that the "where" pathway is activated approximately 30 ms earlier than the "what" pathway, possibly enabling the brain to use top-down spatial information in auditory object perception. Notably, selectively attending to phonetic content modulated response adaptation in the "what" pathway, whereas attending to sound location produced analogous effects in the "where" pathway. This finding suggests that selective-attention effects are feature-specific in the human nonprimary auditory cortex and that they arise from enhanced tuning of receptive fields of task-relevant neuronal populations.

Adaptation, Physiological↗

PubMed2006

Assessing and improving the spatial accuracy in MEG source localization by depth-weighted minimum-norm estimates.

Cerebral currents responsible for the extra-cranially recorded magnetoencephalography (MEG) data can be estimated by applying a suitable source model. A popular choice is the distributed minimum-norm estimate (MNE) which minimizes the l2-norm of the estimated current. Under the l2-norm constraint, the current estimate is related to the measurements by a linear inverse operator. However, the MNE has a bias towards superficial sources, which can be reduced by applying depth weighting. We studied the effect of depth weighting in MNE using a shift metric. We assessed the localization performance of the depth-weighted MNE as well as depth-weighted noise-normalized MNE solutions under different cortical orientation constraints, source space densities, and signal-to-noise ratios (SNRs) in multiple subjects. We found that MNE with depth weighting parameter between 0.6 and 0.8 showed improved localization accuracy, reducing the mean displacement error from 12 mm to 7 mm. The noise-normalized MNE was insensitive to depth weighting. A similar investigation of EEG data indicated that depth weighting parameter between 2.0 and 5.0 resulted in an improved localization accuracy. The application of depth weighting to auditory and somatosensory experimental data illustrated the beneficial effect of depth weighting on the accuracy of spatiotemporal mapping of neuronal sources.

Adult↗

PubMed2005

Spatiotemporal brain maps of delayed word repetition and recognition.

Whole-head magnetoencephalography (MEG) was used to spatiotemporally map the brain response underlying episodic retrieval of words studied a single time following a long delay (approximately 40 min). Recognition following a long delay occurs as a strong, sustained, differential response, within bilateral, ventral, and lateral prefrontal cortex, anterior temporal and medial parietal regions from approximately 500 ms onward, as well as ventral occipitotemporal regions from approximately 700 ms onward. In comparison with previous tasks using multiple repetitions at short delays, these effects were centered within the same areas (anteroventral temporal and ventral prefrontal) but were shifted to longer latencies (approximately 500 ms vs. approximately 200 ms), were less left-lateralized, and appear more in anterolateral prefrontal regions and less in lateral temporal cortex. Furthermore, comparison of correctly classified words with misclassified, novel and repeated words, suggests that these frontotemporal-parietocingulate responses are sensitive to actual as well as perceived repetition. The results also suggest that lateral prefrontal regions may participate more in controlled effortful retrieval, while left ventral frontal and anterior temporal responses may support sustained lexicosemantic processing. Additionally, left ventromedial temporal sites may be relatively more involved in episodic retrieval, while lateral temporal sites may participate more in automatic priming.

Adolescent↗

PubMed2004

Spectral spatiotemporal imaging of cortical oscillations and interactions in the human brain.

This paper presents a computationally efficient source estimation algorithm that localizes cortical oscillations and their phase relationships. The proposed method employs wavelet-transformed magnetoencephalography (MEG) data and uses anatomical MRI to constrain the current locations to the cortical mantle. In addition, the locations of the sources can be further confined with the help of functional MRI (fMRI) data. As a result, we obtain spatiotemporal maps of spectral power and phase relationships. As an example, we show how the phase locking value (PLV), that is, the trial-by-trial phase relationship between the stimulus and response, can be imaged on the cortex. We apply the method to spontaneous, evoked, and driven cortical oscillations measured with MEG. We test the method of combining MEG, structural MRI, and fMRI using simulated cortical oscillations along Heschl's gyrus (HG). We also analyze sustained auditory gamma-band neuromagnetic fields from MEG and fMRI measurements. Our results show that combining the MEG recording with fMRI improves source localization for the non-noise-normalized wavelet power. In contrast, noise-normalized spectral power or PLV localization may not benefit from the fMRI constraint. We show that if the thresholds are not properly chosen, noise-normalized spectral power or PLV estimates may contain false (phantom) sources, independent of the inclusion of the fMRI prior information. The proposed algorithm can be used for evoked MEG/EEG and block-designed or event-related fMRI paradigms, or for spontaneous MEG data sets. Spectral spatiotemporal imaging of cortical oscillations and interactions in the human brain can provide further understanding of large-scale neural activity and communication between different brain regions.

Acoustic Stimulation↗

PubMed2004

Prednisone reduces muscle degeneration in dystrophin-deficient Caenorhabditis elegans.

Duchenne muscular dystrophy is a degenerative muscular disease caused by mutations in the dystrophin gene. There is no curative treatment against Duchenne muscular dystrophy. In several countries, the steroid prednisone (or analogs) is prescribed as a palliative treatment. In the model animal Caenorhabditis elegans, mutations of the dys-1 dystrophin-like gene lead to a muscular degenerative phenotype when they are associated with a mild MyoD mutation. This cheap and fast-growing model of dystrophinopathy may be used to screen for molecules able to slow muscle degeneration. In a blind screen of approximately 100 compounds covering a wide spectrum of targets, we found that prednisone is beneficial to the C. elegans dystrophin-deficient muscles. Prednisone reduces by 40% the number of degenerating cells in this animal. This result is a proof-of-principle for the use of C. elegans as a tool in the search for molecules active against the effects of dystrophin-deficiency. Moreover, since C. elegans is not susceptible to inflammation, this suggests that prednisone exerts a direct effect on muscle survival.

Animals↗

PubMed2004

Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation.

Catatonia is a psychomotor syndrome characterized by concurrent emotional, behavioral, and motor anomalies. Pathophysiological mechanisms of psychomotor disturbances may be related to abnormal emotional-motor processing in prefrontal cortical networks. We therefore investigated prefrontal cortical activation and connectivity patterns during emotional-motor stimulation using functional magnetic resonance imaging (FMRI). We investigated 10 akinetic catatonic patients in a postacute state and compared them with 10 noncatatonic postacute psychiatric controls (age-, sex-, diagnosis-, and medication-matched) and 10 healthy controls. Positive and negative pictures from the International Affective Picture System were used for emotional stimulation. FMRI measurements covered the whole frontal lobe, activation signals in various frontal cortical regions were obtained, and functional connectivity between the different prefrontal cortical regions was investigated using structural equation modeling. Catatonic patients showed alterations in the orbitofrontal cortical activation pattern and in functional connectivity to the premotor cortex in negative and positive emotions compared to psychiatric and healthy controls. Catatonic behavioral and affective symptoms correlated significantly with orbitofrontal activity, whereas catatonic motor symptoms were rather related to medial prefrontal activity. It is concluded that catatonic symptoms may be closely related to dysfunction in the orbitofrontal cortex and consequent alteration in the prefrontal cortical network during emotional processing. Because we investigated postacute patients, orbitofrontal cortical alterations may be interpreted as a trait marker predisposing for development of catatonic syndrome in schizophrenic or affective psychosis.

Acute Disease↗

PubMed2003

Spatiotemporal maps of past-tense verb inflection.

Does the brain inflect verbs by applying rules, by associative retrieval of the inflected form, or both? We used whole-head magnetoencephalography to spatiotemporally map the brain response underlying verb past-tense inflection. Placing either regular or irregular verbs into the past tense sequentially modulates the bilateral visual, left inferotemporal, posterior superior temporal (Wernicke's area), left inferior prefrontal (Broca's area), and right prefrontal cortices. Although irregular and regular verb inflection evokes similar cortical response patterns, differences in specific frontotemporal regions are observed. At approximately 340 ms, irregular verbs evoke greater response modulation in left occipitotemporal cortex. This modulation occurs when widespread areas are simultaneously active, suggesting that it reflects associative activation necessary for generation of past-tense forms. Subsequently, regular verbs show increased response at approximately 470 ms within left inferior prefrontal regions associated with rule-based inflection. Increased right dorsolateral prefrontal response at approximately 570 ms may represent directed/effortful retrieval of irregular past-tense forms. Thus, the brain inflects verbs by dynamically modulating different functional divisions of an integrated language system.

Adult↗

PubMed2002

GABA-ergic modulation of prefrontal spatio-temporal activation pattern during emotional processing: a combined fMRI/MEG study with placebo and lorazepam.

Various prefrontal cortical regions have been shown to be activated during emotional stimulation, whereas neurochemical mechanisms underlying emotional processing in the prefrontal cortex remain unclear. We therefore investigated the influence of the GABA-A potentiator lorazepam on prefrontal cortical emotional-motor spatio-temporal activation pattern in a combined functional magnetic resonance imaging/magnetoencephalography study. Lorazepam led to the reversal in orbito-frontal activation pattern, a shift of the early magnetic field dipole from the orbito-frontal to medial prefrontal cortex, and alterations in premotor/motor cortical function during negative and positive emotional stimulation. It is concluded that negative emotional processing in the orbito-frontal cortex may be modulated either directly or indirectly by GABA-A receptors. Such a modulation of orbito-frontal cortical emotional function by lorazepam has to be distinguished from its effects on cortical motor function as being independent from the kind of processing either emotional or nonemotional.

Adult↗