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Christopher Rorden

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11 papers

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YNICL Journal 2022 Journal Article

Right hemispheric white matter hyperintensities improve the prediction of spatial neglect severity in acute stroke

Lisa Röhrig
Christoph Sperber
Leonardo Bonilha
Christopher Rorden
Hans-Otto Karnath

White matter hyperintensities (WMH) are frequently observed in brain scans of elderly people. They are associated with an increased risk of stroke, cognitive decline, and dementia. However, it is unknown yet if measures of WMH provide information that improve the understanding of poststroke outcome compared to only state-of-the-art stereotaxic structural lesion data. We implemented high-dimensional machine learning models, based on support vector regression, to predict the severity of spatial neglect in 103 acute right hemispheric stroke patients. We found that (1) the additional information of right hemispheric or bilateral voxel-based topographic WMH extent indeed yielded a significant improvement in predicting acute neglect severity (compared to the voxel-based stroke lesion map alone). (2) Periventricular WMH appeared more relevant for prediction than deep subcortical WMH. (3) Among different measures of WMH, voxel-based maps as measures of topographic extent allowed more accurate predictions compared to the use of traditional ordinally assessed visual rating scales (Fazekas-scale, Cardiovascular Health Study-scale). In summary, topographic WMH appear to be a valuable clinical imaging biomarker for predicting the severity of cognitive deficits and bears great potential for rehabilitation guidance of acute stroke patients.

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YNIMG Journal 2019 Journal Article

Lead-DBS v2: Towards a comprehensive pipeline for deep brain stimulation imaging

Andreas Horn
Ningfei Li
Till A. Dembek
Ari Kappel
Chadwick Boulay
Siobhan Ewert
Anna Tietze
Andreas Husch

Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead-DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural/functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead-DBS using a single patient example with state-of-the-art high-field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1. 5T. Imaging data of the 3T example patient is co-registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole-brain tractography algorithms are applied to the patient‘s preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the preprocessing method of choice. This work represents a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field.

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YNIMG Journal 2019 Journal Article

Reprint of: Mapping human brain lesions and their functional consequences

Hans-Otto Karnath
Christoph Sperber
Christopher Rorden

Neuroscience has a long history of inferring brain function by examining the relationship between brain injury and subsequent behavioral impairments. The primary advantage of this method over correlative methods is that it can tell us if a certain brain region is necessary for a given cognitive function. In addition, lesion-based analyses provide unique insights into clinical deficits. In the last decade, statistical voxel-based lesion behavior mapping (VLBM) emerged as a powerful method for understanding the architecture of the human brain. This review illustrates how VLBM improves our knowledge of functional brain architecture, as well as how it is inherently limited by its mass-univariate approach. A wide array of recently developed methods appear to supplement traditional VLBM. This paper provides an overview of these new methods, including the use of specialized imaging modalities, the combination of structural imaging with normative connectome data, as well as multivariate analyses of structural imaging data. We see these new methods as complementing rather than replacing traditional VLBM, providing synergistic tools to answer related questions. Finally, we discuss the potential for these methods to become established in cognitive neuroscience and in clinical applications.

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YNIMG Journal 2019 Journal Article

Using machine learning-based lesion behavior mapping to identify anatomical networks of cognitive dysfunction: Spatial neglect and attention

Daniel Wiesen
Christoph Sperber
Grigori Yourganov
Christopher Rorden
Hans-Otto Karnath

Previous lesion behavior studies primarily used univariate lesion behavior mapping techniques to map the anatomical basis of spatial neglect after right brain damage. These studies led to inconsistent results and lively controversies. Given these inconsistencies, the idea of a wide-spread network that might underlie spatial orientation and neglect has been pushed forward. In such case, univariate lesion behavior mapping methods might have been inherently limited in detecting the presumed network due to limited statistical power. By comparing various univariate analyses with multivariate lesion-mapping based on support vector regression, we aimed to validate the network hypothesis directly in a large sample of 203 newly recruited right brain damaged patients. If the exact same correction factors and parameter combinations (FDR correction and dTLVC for lesion size control) were used, both univariate as well as multivariate approaches uncovered the same complex network pattern underlying spatial neglect. At the cortical level, lesion location dominantly affected the temporal cortex and its borders into inferior parietal and occipital cortices. Beyond, frontal and subcortical gray matter regions as well as white matter tracts connecting these regions were affected. Our findings underline the importance of a right network in spatial exploration and attention and specifically in the emergence of the core symptoms of spatial neglect.

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YNIMG Journal 2018 Journal Article

Image processing and Quality Control for the first 10,000 brain imaging datasets from UK Biobank

Fidel Alfaro-Almagro
Mark Jenkinson
Neal K. Bangerter
Jesper L.R. Andersson
Ludovica Griffanti
Gwenaëlle Douaud
Stamatios N. Sotiropoulos
Saad Jbabdi

UK Biobank is a large-scale prospective epidemiological study with all data accessible to researchers worldwide. It is currently in the process of bringing back 100, 000 of the original participants for brain, heart and body MRI, carotid ultrasound and low-dose bone/fat x-ray. The brain imaging component covers 6 modalities (T1, T2 FLAIR, susceptibility weighted MRI, Resting fMRI, Task fMRI and Diffusion MRI). Raw and processed data from the first 10, 000 imaged subjects has recently been released for general research access. To help convert this data into useful summary information we have developed an automated processing and QC (Quality Control) pipeline that is available for use by other researchers. In this paper we describe the pipeline in detail, following a brief overview of UK Biobank brain imaging and the acquisition protocol. We also describe several quantitative investigations carried out as part of the development of both the imaging protocol and the processing pipeline.

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YNIMG Journal 2018 Journal Article

Mapping human brain lesions and their functional consequences

Hans-Otto Karnath
Christoph Sperber
Christopher Rorden

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YNICL Journal 2018 Journal Article

Removal of artifacts from resting-state fMRI data in stroke

Grigori Yourganov
Julius Fridriksson
Brielle Stark
Christopher Rorden

We examined the effect of lesion on the resting-state functional connectivity in chronic post-stroke patients. We found many instances of strong correlations in BOLD signal measured at different locations within the lesion, making it hard to distinguish from the connectivity between intact and strongly connected regions. Regression of the mean cerebro-spinal fluid signal did not alleviate this problem. The connectomes computed by exclusion of lesioned voxels were not good predictors of the behavioral measures. We came up with a novel method that utilizes Independent Component Analysis (as implemented in FSL MELODIC) to identify the sources of variance in the resting-state fMRI data that are driven by the lesion, and to remove this variance. The resulting functional connectomes show better correlations with the behavioral measures of speech and language, and improve the out-of-sample prediction accuracy of multivariate analysis. We therefore advocate this preprocessing method for studies of post-stroke functional connectivity, particularly in samples with large lesions.

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YNIMG Journal 2013 Journal Article

Subject position affects EEG magnitudes

Justin K. Rice
Christopher Rorden
Jessica S. Little
Lucas C. Parra

EEG (electroencephalography) has been used for decades in thousands of research studies and is today a routine clinical tool despite the small magnitude of measured scalp potentials. It is widely accepted that the currents originating in the brain are strongly influenced by the high resistivity of skull bone, but it is less well known that the thin layer of CSF (cerebrospinal fluid) has perhaps an even more important effect on EEG scalp magnitude by spatially blurring the signals. Here it is shown that brain shift and the resulting small changes in CSF layer thickness, induced by changing the subject's position, have a significant effect on EEG signal magnitudes in several standard visual paradigms. For spatially incoherent high-frequency activity the effect produced by switching from prone to supine can be dramatic, increasing occipital signal power by several times for some subjects (on average 80%). MRI measurements showed that the occipital CSF layer between the brain and skull decreases by approximately 30% in thickness when a subject moves from prone to supine position. A multiple dipole model demonstrated that this can indeed lead to occipital EEG signal power increases in the same direction and order of magnitude as those observed here. These results suggest that future EEG studies should control for subjects' posture, and that some studies may consider placing their subjects into the most favorable position for the experiment. These findings also imply that special consideration should be given to EEG measurements from subjects with brain atrophy due to normal aging or neurodegenerative diseases, since the resulting increase in CSF layer thickness could profoundly decrease scalp potential measurements.

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YNIMG Journal 2012 Journal Article

Age-specific CT and MRI templates for spatial normalization

Christopher Rorden
Leonardo Bonilha
Julius Fridriksson
Benjamin Bender
Hans-Otto Karnath

Spatial normalization reshapes an individual's brain to match the shape and size of a template image. This is a crucial step required for group-level statistical analyses. The most popular standard templates are derived from MRI scans of young adults. We introduce specialized templates that allow normalization algorithms to be applied to stroke-aged populations. First, we developed a CT template: while this is the dominant modality for many clinical situations, there are no modern CT templates and popular algorithms fail to successfully normalize CT scans. Importantly, our template was based on healthy individuals with ages similar to what is commonly seen in stroke (mean 65years old). This template allows studies where only CT scans are available. Second, we derived a MRI template that approximately matches the shape of our CT template as well as processing steps that aid the normalization of scans from older individuals (including lesion masking and the ability to generate high quality cortical renderings despite brain injury). The benefit of this strategy is that the resulting templates can be used in studies where mixed modalities are present. We have integrated these templates and processing algorithms into a simple SPM toolbox (http: //www. mricro. com/clinical-toolbox/spm8-scripts).

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YNIMG Journal 2011 Journal Article

Distinct anatomy for visual search and bisection: A neuroimaging study

Kathleen Pirog Revill
Hans-Otto Karnath
Christopher Rorden

Individuals with spatial neglect following brain injury often show biased performance on landmark bisection tasks (judging if a single item is transected at its midpoint) and search tasks (where they seek target(s) from an array of items). Interestingly, it appears that bisection deficits dissociate from other measures of neglect (including search tasks), and neglect patients with bisection deficits typically have more posterior injury than those without these symptoms. While previous studies in healthy adults have examined each of these tasks independently, our aim was to directly contrast brain activity between these two tasks. Our design used displays that were interpreted as landmark bisection stimuli in some blocks of trials and as search arrays on other trials. Therefore, we used a design where low-level perceptual and motor responses were identical across tasks. Both tasks generated significant activity in bilateral midfusiform gyrus, largely right lateralized activity in the posterior parietal cortex, left lateralized activity in the left motor cortex (consistent with right handed response) and generally right lateralized insular activation. Several brain areas showed task-selective activations when the two tasks were directly compared. Specifically, the superior parietal cortex was selectively activated during the landmark task. On the other hand, the search task caused stronger bilateral activation in the anterior insula, along with midfusiform gyrus, medial superior frontal areas, thalamus and right putamen. This work demonstrates that healthy adults show an anatomical dissociation for visual search and bisection behavior similar to that reported in neurological patients, and provides coordinates for future brain stimulation studies.

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YNIMG Journal 2011 Journal Article

Mapping anterior temporal lobe language areas with fMRI: A multicenter normative study

Jeffrey R. Binder
William L. Gross
Jane B. Allendorfer
Leonardo Bonilha
Jessica Chapin
Jonathan C. Edwards
Thomas J. Grabowski
John T. Langfitt

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story–Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.

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