Michael Luchtmann

Alcohol induced region-dependent alterations of hemodynamic response: implications for the statistical interpretation of pharmacological fMRI studies.

Worldwide, ethanol abuse causes thousands of fatal accidents annually as well as innumerable social dysfunctions and severe medical disorders. Yet, few studies have used the blood oxygenation level dependent functional magnetic resonance imaging method (BOLD fMRI) to map how alcohol alters brain functions, as fMRI relies on neurovascular coupling, which may change due to the vasoactive properties of alcohol. We monitored the hemodynamic response function (HRF) with a high temporal resolution. In both motor cortices and the visual cortex, alcohol prolonged the time course of the HRF, indicating an overall slow-down of neurovascular coupling rather than an isolated reduction in neuronal activity. However, in the supplementary motor area, alcohol-induced changes to the HRF suggest a reduced neuronal activation. This may explain why initiating and coordinating complex movements, including speech production, are often impaired earlier than executing basic motor patterns. Furthermore, the present study revealed a potential pitfall associated with the statistical interpretation of pharmacological fMRI studies based on the general linear model: if the functional form of the HRF is changed between the conditions data may be erroneously interpreted as increased or decreased neuronal activation. Thus, our study not only presents an additional key to how alcohol affects the network of brain functions but also implies that potential changes to neurovascular coupling have to be taken into account when interpreting BOLD fMRI. Therefore, measuring individual drug-induced HRF changes is recommended for pharmacological fMRI.

Building virtual reality fMRI paradigms: A framework for presenting immersive virtual environments

The advantage of using a virtual reality (VR) paradigm in fMRI is the possibility to interact with highly realistic environments. This extends the functions of standard fMRI paradigms, where the volunteer usually has a passive role, for example, watching a simple movie paradigm without any stimulus interactions. From that point of view the combined usage of VR and real-time fMRI offers great potential to identify underlying cognitive mechanisms such as spatial navigation, attention, semantic and episodic memory, as well as neurofeedback paradigms. However, the design and the implementation of a VR stimulus paradigm as well as the integration into an existing MR scanner framework are very complex processes. To support the modeling and usage of VR stimuli we developed and implemented a VR stimulus application based on C++. This software allows the fast and easy presentation of VR environments for fMRI studies without any additional expert knowledge. Furthermore, it provides for the reception of real-time data analysis values a bidirectional communication interface. In addition, the internal plugin interface enables users to extend the functionality of the software with custom programmed C++ plugins. The VR stimulus framework was tested in several performance tests and a spatial navigation study. According to the post-experimental interview, all subjects described immersive experiences and a high attentional load inside the artifical environment. Results from other VR spatial memory studies confirm the neuronal activation that was detected in parahippocampal areas, cuneus, and occipital regions.

Structural brain alterations in patients with lumbar disc herniation: a preliminary study.

Chronic pain is one of the most common health complaints in industrial nations. For example, chronic low back pain (cLBP) disables millions of people across the world and generates a tremendous economic burden. While previous studies provided evidence of widespread functional as well as structural brain alterations in chronic pain, little is known about cortical changes in patients suffering from lumbar disc herniation. We investigated morphometric alterations of the gray and white matter of the brain in patients suffering from LDH. The volumes of the gray and white matter of 12 LDH patients were determined in a prospective study and compared to the volumes of healthy controls to distinguish local differences. High-resolution MRI brain images of all participants were performed using a 3 Tesla MRI scanner. Voxel-based morphometry was used to investigate local differences in gray and white matter volume between patients suffering from LDH and healthy controls. LDH patients showed significantly reduced gray matter volume in the right anterolateral prefrontal cortex, the right temporal lobe, the left premotor cortex, the right caudate nucleus, and the right cerebellum as compared to healthy controls. Increased gray matter volume, however, was found in the right dorsal anterior cingulate cortex, the left precuneal cortex, the left fusiform gyrus, and the right brainstem. Additionally, small subcortical decreases of the white matter were found adjacent to the left prefrontal cortex, the right premotor cortex and in the anterior limb of the left internal capsule. We conclude that the lumbar disk herniation can lead to specific local alterations of the gray and white matter in the human brain. The investigation of LDH-induced brain alterations could provide further insight into the underlying nature of the chronification processes and could possibly identify prognostic factors that may improve the conservative as well as the operative treatment of the LDH.

Increasing the reliability of data analysis of functional magnetic resonance imaging by applying a new blockwise permutation method

A recent paper by Eklund et al. (2012) showed that up to 70% false positive results may occur when analyzing functional magnetic resonance imaging (fMRI) data using the statistical parametric mapping (SPM) software, which may mainly be caused by insufficient compensation for the temporal correlation between successive scans. Here, we show that a blockwise permutation method can be an effective alternative to the standard correction method for the correlated residuals in the general linear model, assuming an AR(1)-model as used in SPM for analyzing fMRI data. The blockwise permutation approach including a random shift developed by our group (Adolf et al., 2011) accounts for the temporal correlation structure of the data without having to provide a specific definition of the underlying autocorrelation model. 1465 publicly accessible resting-state data sets were re-analyzed, and the results were compared with those of Eklund et al. (2012). It was found that with the new permutation method the nominal familywise error rate for the detection of activated voxels could be maintained approximately under even the most critical conditions in which Eklund et al. found the largest deviations from the nominal error level. Thus, the method presented here can serve as a tool to ameliorate the quality and reliability of fMRI data analyses.

Gadolinium-enhanced magnetic resonance angiography in brain death

Confirmatory tests for the diagnosis of brain death in addition to clinical findings may shorten observation time required in some countries and may add certainty to the diagnosis under specific circumstances. The practicability of Gadolinium-enhanced magnetic resonance angiography to confirm cerebral circulatory arrest was assessed after the diagnosis of brain death in 15 patients using a 1.5 Tesla MRI scanner. In all 15 patients extracranial blood flow distal to the external carotid arteries was undisturbed. In 14 patients no contrast medium was noted within intracerebral vessels above the proximal level of the intracerebral arteries. In one patient more distal segments of the anterior and middle cerebral arteries (A3 and M3) were filled with contrast medium. Gadolinium-enhanced MRA may be considered conclusive evidence of cerebral circulatory arrest, when major intracranial vessels fail to fill with contrast medium while extracranial vessels show normal blood flow.

The Travelling-Wave Primate System: A New Solution for Magnetic Resonance Imaging of Macaque Monkeys at 7 Tesla Ultra-High Field.

Introduction Neuroimaging of macaques at ultra-high field (UHF) is usually conducted by combining a volume coil for transmit (Tx) and a phased array coil for receive (Rx) tightly enclosing the monkey’s head. Good results have been achieved using vertical or horizontal magnets with implanted or near-surface coils. An alternative and less costly approach, the travelling-wave (TW) excitation concept, may offer more flexible experimental setups on human whole-body UHF magnetic resonance imaging (MRI) systems, which are now more widely available. Goal of the study was developing and validating the TW concept for in vivo primate MRI. Methods The TW Primate System (TWPS) uses the radio frequency shield of the gradient system of a human whole-body 7 T MRI system as a waveguide to propagate a circularly polarized B1 field represented by the TE11 mode. This mode is excited by a specifically designed 2-port patch antenna. For receive, a customized neuroimaging monkey head receive-only coil was designed. Field simulation was used for development and evaluation. Signal-to-noise ratio (SNR) was compared with data acquired with a conventional monkey volume head coil consisting of a homogeneous transmit coil and a 12-element receive coil. Results The TWPS offered good image homogeneity in the volume-of-interest Turbo spin echo images exhibited a high contrast, allowing a clear depiction of the cerebral anatomy. As a prerequisite for functional MRI, whole brain ultrafast echo planar images were successfully acquired. Conclusion The TWPS presents a promising new approach to fMRI of macaques for research groups with access to a horizontal UHF MRI system.

Ethanol modulates the neurovascular coupling

Despite some evidence of the underlying molecular mechanisms the neuronal basis of ethanol-induced effects on the neurovascular coupling that forms the BOLD (blood oxygenation level dependent) signal is poorly understood. In a recent fMRI (functional magnetic resonance imaging) study monitoring ethanol-induced changes of the BOLD signal a reduction of the amplitude and a prolongation of the BOLD signal were observed. However, the BOLD signal is assumed to consist of a complex superposition of different underlying signals. To gain insight how ethanol influences stimulus efficacy, oxygen extraction, transit time and vessel-related parameters the fMRI time series from the sensori-motor and the visual cortex were analyzed using the balloon model. The results show a region-dependent decrease of the stimulus efficacy to trigger a post-stimulus neurovascular response as well as a prolongation of the transit time through the venous compartment. Oxygen extraction, feedback mechanisms and other vessel-related parameters were not affected. The results may be interpreted as follows: the overall mechanisms of the neurovascular coupling are still acting well at the moderate ethanol level of about 0.8‰ (in particular the vessel-related parts), but the potency to evoke a neurovascular response is already compromised most obviously in the supplementary motor area responsible for complex synchronizing and planning processes.

A proof-of-principle study of multi-site real-time functional imaging at 3T and 7T: Implementation and validation

Real-time functional Magnetic Resonance Imaging (rtfMRI) is used mainly for neurofeedback or for brain-computer interfaces (BCI). But multi-site rtfMRI could in fact help in the application of new interactive paradigms such as the monitoring of mutual information flow or the controlling of objects in shared virtual environments. For that reason, a previously developed framework that provided an integrated control and data analysis of rtfMRI experiments was extended to enable multi-site rtfMRI. Important new components included a data exchange platform for analyzing the data of both MR scanners independently and/or jointly. Information related to brain activation can be displayed separately or in a shared view. However, a signal calibration procedure had to be developed and integrated in order to permit the connecting of sites that had different hardware and to account for different inter-individual brain activation levels. The framework was successfully validated in a proof-of-principle study with twelve volunteers. Thus the overall concept, the calibration of grossly differing signals, and BCI functionality on each site proved to work as required. To model interactions between brains in real-time, more complex rules utilizing mutual activation patterns could easily be implemented to allow for new kinds of social fMRI experiments.

Controversies of diffusion weighted imaging in the diagnosis of brain death.

Imaging techniques as confirmatory tests may add safety to the diagnosis of brain death, but are partly not accepted either because they are too invasive, such as conventional arterial angiography, or because there is still lack of evidence of its reliability, such as magnetic resonance angiography. In this study the reliability of diffusion weighted imaging for the diagnosis of brain death was evaluated according in terms of its sensitivity and specificity. The apparent diffusion coefficients (ADC) of 18 brain dead patients were registered from 14 distinct brain areas. The mean ADC values of the brain dead patients were compared with normal controls of physiological ADC values of unaffected brain tissue. Despite a highly significant decrease of the mean ADC value in 16 patients, two patients showed mean ADC values that were within normal physiological range. An explanation may be the pseudonormalization of ADC values seen in stroke patients that depends on the time of the onset of the brain damage.

Real-time classification of activated brain areas for fMRI-based human-brain-interfaces

Functional MR imaging (fMRI) enables to detect different activated brain areas according to the performed tasks. However, data are usually evaluated after the experiment, which prohibits intra-experiment optimization or more sophisticated applications such as biofeedback experiments. Using a human-brain-interface (HBI), subjects are able to communicate with external programs, e.g. to navigate through virtual scenes, or to experience and modify their own brain activation. These applications require the real-time analysis and classification of activated brain areas. Our paper presents first results of different strategies for real-time pattern analysis and classification realized within a flexible experiment control system that enables the volunteers to move through a 3D virtual scene in real-time using finger tapping tasks, and alternatively only thought-based tasks.