Pitfalls in fMRI

Several different techniques allow a functional assessment of neuronal activations by magnetic resonance imaging (fMRI). The by far most influential fMRI technique is based on a local T2*-sensitive hemodynamic response to neuronal activation, also known as the blood oxygenation level dependent or BOLD effect. Consequently, the term ‘fMRI' is often used synonymously with BOLD imaging. Because interpretations of fMRI brain activation maps often appear intuitive and compelling, the reader might be tempted not to critically question the fundamental processes and assumptions. We review some essential processes and assumptions of BOLD fMRI and discuss related confounds and pitfalls in fMRI - from the underlying physiological effect, to data acquisition, data analysis and the interpretation of the results including clinical fMRI. A background framework is provided for the systematic and critical interpretation of fMRI result

Functional MRI, DTI and neurophysiology in horizontal gaze palsy with progressive scoliosis

Introduction: Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disease due to a mutation in the ROBO3 gene. This rare disease is of particular interest because the absence, or at least reduction, of crossing of the ascending lemniscal and descending corticospinal tracts in the medulla predicts abnormal ipsilateral sensory and motor systems. Methods: We evaluated the use of functional magnetic resonance imaging (fMRI) for the first time in this disease and compared it to diffusion tensor imaging (DTI) tractography and neurophysiological findings in the same patient with genetically confirmed ROBO3 mutation. Results: As expected, motor fMRI, somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP) were dominantly ipsilateral to the stimulation side. DTI tractography revealed ipsilateral ascending and descending connectivity in the brainstem yet normal interhemispheric connections in the corpus callosum. Auditory fMRI revealed bilateral auditory activation to monaural left-sided auditory stimulation. No significant cortical activation was observed after monaural right-sided stimulation, a hearing defect having been excluded. Prosaccades fMRI showed no activations in the eye-movement network. Conclusion: Motor fMRI confirmed the established findings of DTI and neurophysiology in the same patient. In suspected HGPPS, any technique appears appropriate for further investigation. Auditory fMRI suggests that a monaural auditory system with bilateral auditory activations might be a physiological advantage as compared to a binaural yet only unilateral auditory system, in analogy to anisometropic amblyopia. Moving-head fMRI studies in the future might show whether the compensatory head movements instead of normal eye movements activate the eye-movement networ

Real-time fMRI feedback training may improve chronic tinnitus

Objectives: Tinnitus consists of a more or less constant aversive tone or noise and is associated with excess auditory activation. Transient distortion of this activation (repetitive transcranial magnetic stimulation, rTMS) may improve tinnitus. Recently proposed operant training in real-time functional magnetic resonance imaging (rtfMRI) neurofeedback allows voluntary modification of specific circumscribed neuronal activations. Combining these observations, we investigated whether patients suffering from tinnitus can (1) learn to voluntarily reduce activation of the auditory system by rtfMRI neurofeedback and whether (2) successful learning improves tinnitus symptoms. Methods: Six participants with chronic tinnitus were included. First, location of the individual auditory cortex was determined in a standard fMRI auditory block-design localizer. Then, participants were trained to voluntarily reduce the auditory activation (rtfMRI) with visual biofeedback of the current auditory activation. Results: Auditory activation significantly decreased after rtfMRI neurofeedback. This reduced the subjective tinnitus in two of six participants. Conclusion: These preliminary results suggest that tinnitus patients learn to voluntarily reduce spatially specific auditory activations by rtfMRI neurofeedback and that this may reduce tinnitus symptoms. Optimized training protocols (frequency, duration, etc.) may further improve the result

White Matter Changes in Bipolar Disorder, Alzheimer Disease, and Mild Cognitive Impairment: New Insights from DTI

Neuropathological and neuroimaging studies have reported significant changes in white matter in psychiatric and neurodegenerative diseases. Diffusion tensor imaging (DTI), a recently developed technique, enables the detection of microstructural changes in white matter. It is a noninvasive in vivo technique that assesses water molecules' diffusion in brain tissues. The most commonly used parameters are axial and radial diffusivity reflecting diffusion along and perpendicular to the axons, as well as mean diffusivity and fractional anisotropy representing global diffusion. Although the combination of these parameters provides valuable information about the integrity of brain circuits, their physiological meaning still remains controversial. After reviewing the basic principles of DTI, we report on recent contributions that used this technique to explore subtle structural changes in white matter occurring in elderly patients with bipolar disorder and Alzheimer disease

Automatic MRI volumetry in asymptomatic cases at risk for normal pressure hydrocephalus

The occurrence of significant Alzheimer’s disease (AD) pathology was described in approximately 30% of normal pressure hydrocephalus (NPH) cases, leading to the distinction between neurodegenerative and idiopathic forms of this disorder. Whether or not there is a specific MRI signature of NPH remains a matter of debate. The present study focuses on asymptomatic cases at risk for NPH as defined with automatic machine learning tools and combines automatic MRI assessment of cortical and white matter volumetry, risk of AD (AD-RAI), and brain age gap estimation (BrainAge). Our hypothesis was that brain aging and AD process-independent volumetric changes occur in asymptomatic NPH-positive cases. We explored the volumetric changes in normal aging-sensitive (entorhinal cortex and parahippocampal gyrus/PHG) and AD-signature areas (hippocampus), four control cortical areas (frontal, parietal, occipital, and temporal), and cerebral and cerebellar white matter in 30 asymptomatic cases at risk for NPH (NPH probability >30) compared to 30 NPH-negative cases (NPH probability <5) with preserved cognition. In univariate regression models, NPH positivity was associated with decreased volumes in the hippocampus, parahippocampal gyrus (PHG), and entorhinal cortex bilaterally. The strongest negative association was found in the left hippocampus that persisted when adjusting for AD-RAI and Brain Age values. A combined model including the three parameters explained 36.5% of the variance, left hippocampal volumes, and BrainAge values, which remained independent predictors of the NPH status. Bilateral PHG and entorhinal cortex volumes were negatively associated with NPH-positive status in univariate models but this relationship did not persist when adjusting for BrainAge, the latter remaining the only predictor of the NPH status. We also found a negative association between bilateral cerebral and cerebellar white matter volumes and NPH status that persisted after controlling for AD-RAI or Brain Age values, explaining between 50 and 65% of its variance. These observations support the idea that in cases at risk for NPH, as defined by support vector machine assessment of NPH-related MRI markers, brain aging-related and brain aging and AD-independent volumetric changes coexist. The latter concerns volume loss in restricted hippocampal and white matter areas that could be considered as the MRI signature of idiopathic forms of NPH

Risk attitude, beliefs, and information in a corruption game: An experimental analysis

For our experiment on corruption we designed a coordination game to model the influence of risk attitudes, beliefs, and information on behavioral choices and determined the equilibria. We observed that the participants' risk attitudes failed to explain their choices between corrupt and non-corrupt behavior. Instead, beliefs appeared to be a better predictor of whether or not they would opt for the corrupt alternative. Furthermore, varying the quantity of information available to players (modeled by changing the degree of uncertainty) provided additional insight into the players' propensity to engage in corrupt behavior. The experimental results show that a higher degree of uncertainty in the informational setting reduces corruption. --Corruption,game theory,experiment,risk attitude,beliefs

Neural activation associated with corrective saccades during tasks with fixation, pursuit and saccades

Corrective saccades are small eye movements that redirect gaze whenever the actual eye position differs from the desired eye position. In contrast to various forms of saccades including pro-saccades, recentering-saccades or memory guided saccades, corrective saccades have been widely neglected so far. The fMRI correlates of corrective saccades were studied that spontaneously occurred during fixation, pursuit or saccadic tasks. Eyetracking was performed during the fMRI data acquisition with a fiber-optic device. Using a combined block and event-related design, we isolated the cortical activations associated with visually guided fixation, pursuit or saccadic tasks and compared these to the activation associated with the occurrence of corrective saccades. Neuronal activations in anterior inferior cingulate, bilateral middle and inferior frontal gyri, bilateral insula and cerebellum are most likely specifically associated with corrective saccades. Additionally, overlapping activations with the established pro-saccade and, to a lesser extent, pursuit network were present. The presented results imply that corrective saccades represent a potential systematic confound in eye-movement studies, in particular because the frequency of spontaneously occurring corrective saccades significantly differed between fixation, pursuit and pro-saccade

Neuroimaging in Dementia:More than Typical Alzheimer Disease

Alzheimer disease (AD) is the most common cause of dementia. The prevailing theory of the underlying pathology assumes amyloid accumulation followed by tau protein aggregation and neurodegeneration. However, the current antiamyloid and antitau treatments show only variable clinical efficacy. Three relevant points are important for the radiologic assessment of dementia. First, besides various dementing disorders (including AD, frontotemporal dementia, and dementia with Lewy bodies), clinical variants and imaging subtypes of AD include both typical and atypical AD. Second, atypical AD has overlapping radiologic and clinical findings with other disorders. Third, the diagnostic process should consider mixed pathologies in neurodegeneration, especially concurrent cerebrovascular disease, which is frequent in older age. Neuronal loss is often present at, or even before, the onset of cognitive decline. Thus, for effective emerging treatments, early diagnosis before the onset of clinical symptoms is essential to slow down or stop subsequent neuronal loss, requiring molecular imaging or plasma biomarkers. Neuroimaging, particularly MRI, provides multiple imaging parameters for neurodegenerative and cerebrovascular disease. With emerging treatments for AD, it is increasingly important to recognize AD variants and other disorders that mimic AD. Describing the individual composition of neurodegenerative and cerebrovascular disease markers while considering overlapping and mixed diseases is necessary to better understand AD and develop efficient individualized therapies.</p

Neuroimaging in Dementia: More than Typical Alzheimer Disease

Alzheimer disease (AD) is the most common cause of dementia. The prevailing theory of the underlying pathology assumes amyloid accumulation followed by tau protein aggregation and neurodegeneration. However, the current antiamyloid and antitau treatments show only variable clinical efficacy. Three relevant points are important for the radiologic assessment of dementia. First, besides various dementing disorders (including AD, frontotemporal dementia, and dementia with Lewy bodies), clinical variants and imaging subtypes of AD include both typical and atypical AD. Second, atypical AD has overlapping radiologic and clinical findings with other disorders. Third, the diagnostic process should consider mixed pathologies in neurodegeneration, especially concurrent cerebrovascular disease, which is frequent in older age. Neuronal loss is often present at, or even before, the onset of cognitive decline. Thus, for effective emerging treatments, early diagnosis before the onset of clinical symptoms is essential to slow down or stop subsequent neuronal loss, requiring molecular imaging or plasma biomarkers. Neuroimaging, particularly MRI, provides multiple imaging parameters for neurodegenerative and cerebrovascular disease. With emerging treatments for AD, it is increasingly important to recognize AD variants and other disorders that mimic AD. Describing the individual composition of neurodegenerative and cerebrovascular disease markers while considering overlapping and mixed diseases is necessary to better understand AD and develop efficient individualized therapies