Biology subjects

Woermann, F. G.

Publications and source records attributed to Woermann, F. G..

7 recordsLinked to original sources

bioRxiv2025

Emotional amnesia in humans with focal temporal pole lesions

Memory is typically better for emotional relative to neutral events, a process involving amygdala modulation of hippocampal activity1-6. These structures, however, form part of a larger emotional brain network, which in humans includes the temporal pole7, a cortical node whose functional role in emotional cognition remains poorly understood8-10. Here, we show, in pharmaco-resistant epilepsy patients performing verbal and visual emotional episodic memory tasks, a selective impairment in recalling verbal emotional memories in left ventral temporal pole (vTP) lesioned patients compared with control patients. Memory for neutral words, and verbal comprehension performance on standard neuropsychological testing, were intact in these patients, indicating absence of general episodic memory or semantic impairment. All patients underwent recordings with intracranial electrodes during memory task performance. Left vTP lesioned patients showed no differences in amygdala or hippocampal electrophysiological responses to emotional words, compared with control patients, putatively isolating a vTP role in emotional memory. Unlike verbal emotional recall, left vTP lesioned patients showed memory enhancement for emotional vs. neutral pictures, whereas two patients with right vTP lesions showed the opposite pattern: impaired memory for emotional pictures but intact verbal emotional memory. These observations establish a critical, lateralized, modality-specific role for human vTP in emotional memory, imply emotional memory deficits in neurological conditions affecting this region, and advance the vTP as a target for neuromodulation in diseases characterized by maladaptive emotional memories.

neuroscience↗

bioRxiv2025

No Disconnection Syndrome after Near-Complete Callosotomy

Sensorimotor processing in the human brain is largely lateralized, with the corpus callosum integrating these processes into a unified experience. Following complete callosotomy, this integration breaks down, resulting in disconnection syndromes. We asked how much of the corpus callosum is sufficient to support functional unity--the absence of disconnection syndrome--by comparing three complete callosotomy patients with one retaining only the splenium. Using lateralized tasks across visual, tactile, visuospatial, and language domains, we predicted domain-specific deficits in the splenium-only patient based on established anatomical models of callosal topography. Strikingly, while complete callosotomy patients exhibited disconnection syndromes, the splenium patient demonstrated functional unity across all domains--as if his entire corpus callosum were intact. Our findings highlight the brains remarkable capacity to maintain behavioral integration through minimal preserved pathways, highlighting how the structure-dependent reorganizational capacity of the human brain allows to preserve functional unity.

neuroscience↗

bioRxiv2025

Full inter-hemispheric integration sustained by a fraction of posterior callosal fibers

The dynamic integration of the lateralized and specialized capacities of the cerebral hemispheres constitutes a hallmark feature of human brain function. This inter-hemispheric exchange of information critically depends upon the corpus callosum. Classical descriptions of callosal organization outline a topographic gradient, such that specific fibers integrate distinct aspects of brain function. Here we present a challenge to this conventional model. Using neuroimaging data obtained from a new cohort of adult corpus callosotomy patients, we leverage modern network neuroscience techniques to show--for the first time--that full inter-hemispheric integration can be achieved via a small proportion ([~]1 cm) of intact posterior callosal fibers. Only complete callosotomy patients demonstrated the expected dissolution of typical inter-hemispheric network architectures, aligning with disconnection syndromes long-thought to reflect diminished information propagation and communication across the brain. These findings motivate a novel mechanistic understanding of synchronized inter-hemispheric neural activity for large-scale human brain function and behavior.

neuroscience↗

bioRxiv2020

Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay

Polymicrogyria (PMG) is a developmental cortical malformation characterized by an excess of small and frustrane gyration and abnormal cortical lamination. PMG frequently associates with seizures. The molecular pathomechanisms underlying PMG development are not yet understood. About 40 genes have been associated with PMG, and small copy number variations have also been described in selected patients. We recently provided evidence that epilepsy-associated structural brain lesions can be classified based on genomic DNA methylation patterns. Here we analyzed 26 PMG patients employing array-based DNA-methylation profiling on formalin-fixed paraffin-embedded material. A series of 62 well-characterized non-PMG cortical malformations (focal cortical dysplasia type 2a/b and hemimegalencephaly), temporal lobe epilepsy, and non-epilepsy autopsy controls was used as reference cohort. Unsupervised dimensionality reduction and hierarchical cluster analysis of DNA methylation profiles showed that PMG formed a distinct DNA methylation class. Copy number profiling from DNA methylation data identified a uniform duplication spanning the entire long arm of chromosome 1 in 7 out of 26 PMG patients, which was verified by additional fluorescence in situ hybridization analysis. In respective cases about 50% of nuclei in the center of the PMG lesion were 1q triploid. No chromosomal imbalance was seen in adjacent, architecturally normal-appearing tissue indicating mosaicism. Clinically, PMG 1q patients presented with a unilateral frontal or hemispheric PMG without hemimegalencephaly, a severe form of intractable epilepsy with seizure onset in the first months of life, and severe developmental delay. Our results show that PMG can be classified among other structural brain lesions according to their DNA methylation profile. One subset of PMG with distinct clinical features exhibits a duplication of chromosomal arm 1q.

neuroscience↗

bioRxiv2019

Volume-wise analysis of fMRI time series allows accurate prediction of language lateralization

Using fMRI as a clinical tool, for example for lateralizing language, requires that it provides accurate results on the individual level. However, using a single voxel-wise activity map per patient limits how well the uncertainty associated with a decision can be estimated. Here, we explored how using a "volume-wise" analysis, where the lateralization of each time point of a patients fMRI session is evaluated independently, could support clinical decision making. Ninety-six patients with epilepsy who performed a language fMRI were analyzed retrospectively. Results from Wada testing were used as an indication of true language lateralization. Each patients 200 fMRI volumes were correlated with an independent template of prototypical lateralization. Depending on the strength of correlation with the template, each volume was classified as indicating either left-lateralized, bilateral or right-lateralized language. A decision about the patients language lateralization was then made based on how most volumes were classified. The results show that, using a simple majority vote, accuracies of 84% were reached in a sample of 63 patients with high-quality data. When 33 patients with datasets previously deemed inconclusive were added, the same accuracy was reached when more than 43% of a patients volumes were in agreement with each other. Increasing this cutoff to 51% volumes with agreeing classifications allowed for excluding all inconclusive cases and reaching accuracies over 90% for the remaining cases. Further increasing the cutoff to 65% agreeing volumes resulted in correct predictions for all remaining patients. The study confirms the usefulness of fMRI for language lateralization in patients with epilepsy, by demonstrating high accuracies. Furthermore, it illustrates how the diagnostic yield of individual volumes of fMRI data can be increased using simple similarity measures. The accuracy of our approach increased with the number of agreeing volumes, and thus allowed estimating the uncertainty associated with each individual diagnosis.

neuroscience↗

bioRxiv2019

Quantifying the Confidence in fMRI-based Language Lateralisation through Laterality Index Deconstruction

In epilepsy patients, language lateralisation is an important part of the presurgical diagnostic process. Using task-based fMRI, language lateralisation can be determined by visual inspection of activity patterns or by quantifying the difference in left- and right-hemisphere activity using variations of a basic formula [(L-R)/(L+R)]. However, the values of this laterality index (LI) depend on the choice of activity thresholds and regions of interest. The diagnostic utility of the LI also depends on how its continuous values are translated into categorical decisions about a patients language lateralisation. Here, we analysed fMRI data from 712 epilepsy patients who performed a verbal fluency task. Each fMRI data set was evaluated by a trained human rater as depicting left-sided, right-sided, or bilateral lateralisation or as being inconclusive. We used data-driven methods to define the activity thresholds and regions of interest used for LI computation and to define a classification scheme that allowed us to translate the LI values into categorical decisions. By deconstructing the LI into measures of laterality (L-R) and strength (L+R), we also modelled the relationship between activation strength and conclusiveness of a data set. In a held-out data set, predictions reached 91% correct when using only conclusive data and 82% when inconclusive data were included. Although only trained on human evaluations of fMRIs, the approach generalised to the prediction of language Wada test results, allowing for significant above-chance accuracies. Compared against different existing methods of LI-computation, our approach improved the identification of inconclusive cases and increased the accuracy with which decisions for the remaining data could be made. We discuss how this approach can support clinicians in assessing fMRI data on a single-case level, deciding whether lateralisation can be determined with sufficient certainty or whether additional information is needed.

neuroscience↗

bioRxiv2018

Thought experiment: Decoding cognitive processes from the fMRI data of one individual

Cognitive processes, such as the generation of language, can be mapped onto the brain using fMRI. These maps can in turn be used for decoding the respective processes from the brain activation patterns. Given individual variations in brain anatomy and organization, analyzes on the level of the single person are important to improve our understanding of how cognitive processes correspond to patterns of brain activity. They also allow to advance clinical applications of fMRI, because in the clinical setting making diagnoses for single cases is imperative. In the present study, we used mental imagery tasks to investigate language production, motor functions, visuo-spatial memory, face processing, and resting-state activity in a single person. Analysis methods were based on similarity metrics, including correlations between training and test data, as well as correlations with maps from the NeuroSynth meta-analysis. The goal was to make accurate predictions regarding the cognitive domain (e.g. language) and the specific content (e.g. animal names) of single 30-second blocks. Four teams used the dataset, each blinded regarding the true labels of the test data. Results showed that the similarity metrics allowed to reach the highest degrees of accuracy when predicting the cognitive domain of a block. Overall, 23 of the 25 test blocks could be correctly predicted by three of the four teams. Excluding the unspecific rest condition, up to 10 out of 20 blocks could be successfully decoded regarding their specific content. The study shows how the information contained in a single fMRI session and in each of its single blocks can allow to draw inferences about the cognitive processes an individual engaged in. Simple methods like correlations between blocks of fMRI data can serve as highly reliable approaches for cognitive decoding. We discuss the implications of our results in the context of clinical fMRI applications, with a focus on how decoding can support functional localization.

neuroscience↗