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Herta Flor

Publications and source records attributed to Herta Flor.

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Charting the velocity of brain growth and development

Brain charts have emerged as a highly useful approach for understanding brain development and aging on the basis of brain imaging and have shown substantial utility in describing typical and atypical brain development with respect to a given reference model. However, all existing models are fundamentally cross-sectional and cannot capture change over time at the individual level. We address this using velocity centiles, which directly map change over time and can be overlaid onto cross-sectionally derived population centiles. We demonstrate this by modelling rates of change for 24062 scans from 10795 healthy individuals with up to 8 longitudinal measurements across the lifespan. We provide a method to detect individual deviations from a stable trajectory, generalising the notion of thrive lines, which are used in pediatric medicine to declare failure to thrive. Using this approach, we predict transition from mild cognitive impairment to dementia more accurately than by using either time point alone, replicated across two datasets. Last, by taking into account multiple time points, we improve the sensitivity of velocity models for predicting the future trajectory of brain change. This highlights the value of predicting change over time and makes a fundamental step towards precision medicine.

q-bio.NC

Automatic rating of incomplete hippocampal inversions evaluated across multiple cohorts

Incomplete Hippocampal Inversion (IHI), sometimes called hippocampal malrotation, is an atypical anatomical pattern of the hippocampus found in about 20% of the general population. IHI can be visually assessed on coronal slices of T1 weighted MR images, using a composite score that combines four anatomical criteria. IHI has been associated with several brain disorders (epilepsy, schizophrenia). However, these studies were based on small samples. Furthermore, the factors (genetic or environmental) that contribute to the genesis of IHI are largely unknown. Large-scale studies are thus needed to further understand IHI and their potential relationships to neurological and psychiatric disorders. However, visual evaluation is long and tedious, justifying the need for an automatic method. In this paper, we propose, for the first time, to automatically rate IHI. We proceed by predicting four anatomical criteria, which are then summed up to form the IHI score, providing the advantage of an interpretable score. We provided an extensive experimental investigation of different machine learning methods and training strategies. We performed automatic rating using a variety of deep learning models (conv5-FC3, ResNet and SECNN) as well as a ridge regression. We studied the generalization of our models using different cohorts and performed multi-cohort learning. We relied on a large population of 2,008 participants from the IMAGEN study, 993 and 403 participants from the QTIM/QTAB studies as well as 985 subjects from the UKBiobank. We showed that deep learning models outperformed a ridge regression. We demonstrated that the performances of the conv5-FC3 network were at least as good as more complex networks while maintaining a low complexity and computation time. We showed that training on a single cohort may lack in variability while training on several cohorts improves generalization.

eess.IV

Stress-induced hyperalgesia instead of analgesia in patients with chronic musculoskeletal pain

Many individuals with chronic musculoskeletal pain (CMP) show impairments in their pain-modulatory capacity. Although stress plays an important role in chronic pain, it is not known if stress-induced analgesia (SIA) is affected in patients with CMP. We investigated SIA in 22 patients with CMP and 18 pain-free participants. Pain thresholds, pain tolerance and suprathreshold pain ratings were examined before and after a cognitive stressor that typically induces pain reduction (SIA). Whereas the controls displayed a significant increase in pain threshold in response to the stressor, the patients with CMP showed no analgesia. In addition, increased pain intensity ratings after the stressor indicated hyperalgesia (SIH) in the patients with CMP compared to controls. An exploratory analysis showed no significant association of SIA or SIH with spatial pain extent. We did not observe significant changes in pain tolerance or pain unpleasantness ratings after the stressor in patients with CMP or controls. Our data suggest that altered stress-induced pain modulation is an important mechanism involved in CMP. Future studies need to clarify the psychobiological mechanisms of these stress-induced alterations in pain processing and determine the role of contributing factors such as early childhood trauma, catastrophizing, comorbidity with mental disorders and genetic predisposition.

q-bio.NC

Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective

Phantom limb pain (PLP) has been associated with both the reorganization of the somatotopic map in primary somatosensory cortex (S1) and preserved S1 function. Here we assessed the nature of the information (sensory, motor) that reaches S1 and methodological differences in the assessment of cortical representations that might explain these findings. We used functional magnetic resonance imaging during a virtual hand motor task, analogous to the classical mirror box task, in amputees with and without PLP and in matched controls. We assessed the relationship between task-related activation maxima and PLP intensity in S1 versus motor (M1) maps. We also measured cortical distances between the location of activation maxima using region of interest (ROI), defined from individual or group analyses. Amputees showed significantly increased activity in M1 and S1 compared to controls, which was not significantly related to PLP intensity. The location of activation maxima differed between groups depending on M1 and S1 maps. Neural activity was positively related to PLP only in amputees with pain and only if a group-defined ROI was chosen. These findings show that the analysis of changes in S1 versus M1 yields different results, possibly indicating different pain-related processes.

q-bio.NC

Gamma band oscillations reflect sensory and affective dimensions of pain

Pain is a multidimensional process, which can be modulated by emotions, however, the mechanisms underlying this modulation are unknown. We used pictures with different emotional valence (negative, positive, neutral) as primes and applied electrical painful stimuli as targets to healthy participants. We assessed pain intensity and unpleasantness ratings and recorded electroencephalograms (EEG). We found that pain unpleasantness, and not pain intensity ratings were modulated by emotion, with increased ratings for negative and decreased for positive pictures. We also found two consecutive gamma band oscillations (GBOs) related to pain processing from time frequency analyses of the EEG signals. An early GBO had a cortical distribution contralateral to the painful stimulus, and its amplitude was positively correlated with intensity and unpleasantness ratings, but not with prime valence. The late GBO had a centroparietal distribution and its amplitude was larger for negative compared to neutral and positive pictures. The emotional modulation effect (negative versus positive) of the late GBO amplitude was positively correlated with pain unpleasantness. The early GBO might reflect the overall pain perception, possibly involving the thalamocortical circuit, while the late GBO might be related to the affective dimension of pain and top-down related processes.

q-bio.NC

Disruption of the prefrontal cortex improves implicit contextual memory-guided attention: combined behavioural and electrophysiological evidence

Many studies have shown that the dorsolateral prefrontal cortex (DLPFC) plays an important role in top-down cognitive control over intentional and deliberate behavior. However, recent studies have reported that DLPFC-mediated top-down control interferes with implicit forms of learning. Here we used continuous theta burst stimulation (cTBS) combined with electroencephalography (EEG) to investigate the causal role of DLPFC in implicit contextual memory-guided attention. We aimed to test whether transient disruption of the DLPFC would interfere with implicit learning performance and related electrical brain activity. We applied neuronavigation-guided cTBS to the DLPFC or to the vertex as a control region prior to the performance of an implicit contextual learning task. We found that cTBS applied over the DLPFC significantly improved performance during implicit contextual learning. We also noted that beta-band (13-19 Hz) oscillatory power was reduced at fronto-central channels about 140 to 370 ms after visual stimulus onset in cTBS DLPFC compared with cTBS vertex. Taken together, our results provide evidence that DLPFC-mediated top-down control interferes with contextual memory-guided attention and beta-band oscillatory activity.

q-bio.NC

Nonlinear functional mapping of the human brain

The field of neuroimaging has truly become data rich, and novel analytical methods capable of gleaning meaningful information from large stores of imaging data are in high demand. Those methods that might also be applicable on the level of individual subjects, and thus potentially useful clinically, are of special interest. In the present study, we introduce just such a method, called nonlinear functional mapping (NFM), and demonstrate its application in the analysis of resting state fMRI from a 242-subject subset of the IMAGEN project, a European study of adolescents that includes longitudinal phenotypic, behavioral, genetic, and neuroimaging data. NFM employs a computational technique inspired by biological evolution to discover and mathematically characterize interactions among ROI (regions of interest), without making linear or univariate assumptions. We show that statistics of the resulting interaction relationships comport with recent independent work, constituting a preliminary cross-validation. Furthermore, nonlinear terms are ubiquitous in the models generated by NFM, suggesting that some of the interactions characterized here are not discoverable by standard linear methods of analysis. We discuss one such nonlinear interaction in the context of a direct comparison with a procedure involving pairwise correlation, designed to be an analogous linear version of functional mapping. We find another such interaction that suggests a novel distinction in brain function between drinking and non-drinking adolescents: a tighter coupling of ROI associated with emotion, reward, and interoceptive processes such as thirst, among drinkers. Finally, we outline many improvements and extensions of the methodology to reduce computational expense, complement other analytical tools like graph-theoretic analysis, and allow for voxel level NFM to eliminate the necessity of ROI selection.

q-bio.NC