Robust Bayesian estimation of the hemodynamic response function in event-related BOLD fMRI using basic physiological information

In BOLD fMRI data analysis, robust and accurate estimation of the Hemodynamic Response Function (HRF) is still under investigation. Parametric methods assume the shape of the HRF to be known and constant throughout the brain, whereas non-parametric methods mostly rely on artificially increasing the signal-to-noise ratio. We extend and develop a previously proposed method that makes use of basic yet relevant temporal information about the underlying physiological process of the brain BOLD response in order to infer the HRF in a Bayesian framework. A general hypothesis test is also proposed, allowing to take advantage of the knowledge gained regarding the HRF to perform activation detection. The performances of the method are then evaluated by simulation. Great improvement is shown compared to the Maximum-Likelihood estimate in terms of estimation error, variance, and bias. Robustness of the estimators with regard to the actual noise structure or level, as well as the stimulus sequence, is also proven. Lastly, fMRI data with an event-related paradigm are analyzed. As suspected, the regions selected from highly discriminating activation maps resulting from the method exhibit a certain inter-regional homogeneity in term of HRF shape, as well as noticeable inter-regional differences.     

The hemodynamic response in children with Simplex Autism

BackgroundNumerous functional magnetic resonance imaging (fMRI) studies of the brain-bases of autism have demonstrated altered cortical responses in subjects with autism, relative to typical subjects, during a variety of tasks. These differences may reflect altered neuronal responses or altered hemodynamic response. This study searches for evidence of hemodynamic response differences by using a simple visual stimulus and elementary motor actions, which should elicit similar neuronal responses in patients and controls.MethodsWe acquired fMRI data from two groups of 16 children, a typical group and a group with Simplex Autism, during a simple visuomotor paradigm previously used to assess this question in other cross-group comparisons. A general linear model estimated the blood-oxygen-level-dependent (BOLD) signal time course, and repeated-measures analysis of variance tested for potential cross-group differences in the BOLD signal.ResultsThe hemodynamic response in Simplex Autism is similar to that found in typical children. Although the sample size was small for a secondary analysis, medication appeared to have no effect on the hemodynamic response within the Simplex Autism group.ConclusionsWhen fMRI studies show BOLD response differences between autistic and typical subjects, these results likely reflect between-group differences in neural activity and not an altered hemodynamic response.     

Lexical retrieval in healthy aging

Lexical retrieval for common nouns and verbs was measured using 2 picture naming tests in 162 healthy female and male subjects aged 30 to 79 years. Responses were scored for correctness, responsivity to cueing, and response type. The ability to name both word types declined with age, especially after age 70 in healthy subjects. More errors were made on object names than action names, especially for older subjects. Subjects of all ages were equally able to utilize phonemic cues. With increasing age subjects produced more circumlocutions and fewer semantic errors. Response type difference need not reflect qualitative differences in lexical retrieval; rather, they reflect the quantitatively greater difficulty of the task for healthy older people as compared to younger adults. The naming difficulty for healthy aging, we conclude, is at the label retrieval stage.     

BOLD neurovascular coupling does not change significantly with normal aging

Studies of cognitive function that compare the blood oxygenation level dependent (BOLD) signal across age groups often require the assumption that neurovascular coupling does not change with age. Tests of this assumption have produced mixed results regarding the strength of the coupling and its relative time course. Using deconvolution, we found that age does not have a significant effect on the time course of the hemodynamic impulse response function or on the slope of the BOLD versus stimulus duration relationship. These results suggest that in cognitive studies of healthy aging, group differences in BOLD activation are likely due to age‐related changes in cognitive–neural interactions and information processing rather than to impairments in neurovascular coupling. Hum Brain Mapp 38:3538–3551, 2017. © 2017 Wiley Periodicals, Inc.     

Effects of aging on BOLD fMRI during prosaccades and antisaccades

Age affects the ability to inhibit saccadic eye movements. According to current theories, this may be associated with age-induced neurophysiological changes in the brain and with compensatory activation in frontal brain areas. In the present study, the effects of aging are assessed on brain systems that subserve generation and inhibition of saccadic eye movements. For this purpose, an event-related functional magnetic resonance imaging design was used in adults covering three age ranges (18-30, 30-55, and 55-72 years). Group differences were controlled for task performance. Activity associated with saccadic inhibition was represented by the contrast between prosaccade and antisaccade activation. The tasks activated well-documented networks of regions known to be involved in generation and inhibition of saccadic eye movements. There was an age-related shift in activity from posterior to frontal brain regions after young adulthood. In addition, old adults demonstrated an overall reduction in the blood oxygenation level dependent (BOLD) signal in the visual and oculomotor system. Age, however, did not affect saccade inhibition activity. Mid and old adults appear to increase frontal activation to maintain performance even during simple prosaccades. The global reduction of the BOLD response in old adults could reflect a reduction in neural activity, as well as changes in the neuronal-vascular coupling. Future research should address the impact of altered vascular dynamics on neural activation and the BOLD signal.     

The Oregon brain aging study: neuropathology accompanying healthy aging in the oldest old

OBJECTIVE: To describe the relationship between neuropathologic aging and longitudinal measures of cognitive function in healthy oldest old individuals. METHODS: Nondemented individuals without cardiovascular or other age-associated diseases of age > or =85 years were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to clinical status, cognitive measures, and rate of cognitive change. RESULTS: Among 19 healthy individuals, 10 became demented or had incipient dementia develop. Clinical status and rate of change in cognitive scores correlated with increasing brain lesion burden, particularly in neocortical regions. Compared to demented individuals, nondemented individuals had few or no neocortical NFT (p = 0.009) or SP (p = 0.001). There was a strong correlation between rate of cognitive change on Mini-Mental State Examination (MMSE) and neocortical NFT (r = 0.859, p = 0.001). The few NFT and SP in nondemented patients had a predilection for limbic areas. CONCLUSIONS: These results support a continuum in which AD is infrequent in the healthy, cognitively stable, oldest old. The minimal abnormalities in cognitively stable individuals are consistent with the notion that preclinical pathologic AD precedes obvious cognitive impairment. Longitudinal cognitive testing shows an increased burden of neuropathologic changes in those who have cognitive decline but are not functionally impaired and do not meet criteria for the diagnosis of dementia. The strong relationship between cumulative pathologic changes and rate of cognitive decline suggests that these lesions may have clinical consequences at any age and are not likely to be benign senescent changes.     

The BOLD response: a new look at an old riddle

Functional imaging has struggled for two decades to establish a quantitative link between the neuronal activity and the change in signal obtained. This review proposes a division of neuronal activity into a component relating to the electrical discharge activity and a component relating to the size of the activated neuronal population. These two components are argued to have opposing influences on the BOLD signal. The influence of these two components on the BOLD signal, are summarised in the standard model.     

Understanding variability in the BOLD signal and why it matters for aging

Recent work in neuroscience supports the idea that variability in brain function is necessary for optimal brain responsivity to a changing environment. In this review, we discuss a series of functional magnetic resonance imaging (fMRI) studies in younger and older adults to assess age-related differences in variability of the fMRI signal. This work shows that moment-to-moment brain signal variability represents an important “signal” within what is typically considered measurement-related “noise” in fMRI. This accumulation of evidence suggests that moving beyond the mean will provide a complementary window into aging-related neural processes.     

Modelling hemodynamic response function in epilepsy

Objective

Electroencephalography and functional magnetic resonance imaging (fMRI) can be combined to noninvasively map abnormal brain activation elicited by epileptic processes. A major aim was to investigate the impact of a subject-specific hemodynamic response function (HRF) to describe the differences across patients versus the use of a standard model.

Methods

We developed and applied on simulated and real data a method designed to choose optimum HRF model for identifying fMRI activation maps. In simulation, the ability of five models to reproduce data was assessed: four standard and an individual-based HRF model (ibHRF). In clinical data, drug-resistant epileptic patients underwent fMRI to investigate hemodynamic responses evoked by interictal activity.

Results

When data are simulated with models different from the standard ones, the results obtained with ibHRF are superior to those obtained with the standard HRFs. Results on real data indicate an increase in extent and degree of activation with the ibHRF in comparison of the results obtainable using standard HRFs.

Conclusions

The use of the same HRF in all patients is inappropriate and resolves in biased extension of the activation maps.

Significance

The new method could represent an useful diagnostic tool for other clinical studies that may be biased because of misspecification of HRF.     

Impulsivity and BOLD fMRI activation in MDMA users and healthy control subjects

The correlation between scores on the Barratt Impulsiveness Scale (BIS) and activation measured by functional magnetic resonance imaging in a dorsolateral prefrontal cortical (DLPFC) activating task was examined in 15 MDMA-using subjects and 19 controls. A significant correlation between BIS scores and DLPFC activation was found, supporting a role for the DLPFC in BIS-measured impulsivity.     

Attenuation of brain BOLD response following lipid ingestion

A great deal of heterogeneity exists in fMRI data. Even within the same subject, results on successive days or scan sessions often differ in the number of significantly activated pixels and/or the intensity of activation. We sought to assess whether controllable physiologic modulators, such as dietary factors, could influence the outcome of fMRI data. A high fat diet, for example, prior to a fMRI scan could change microvascular blood rheologic factors and potentially alter brain blood oxygen-level dependent (BOLD) signal patterns. In healthy adult volunteers, we measured brain BOLD signal during bilateral finger tapping (2 Hz) in the fasted state, and at 40 and 100 minutes post-ingestion of a 235 mL can of Ensure Plus (Ross Labs), alone or supplemented with either 25 cc or 50 cc of canola oil. Both the 25 cc and 50 cc Canola oil treatments produced a significant bilateral decrease in BOLD signal 40 and 100 minutes postprandial. No significant effect was observed with Ensure in the absence of oil. Therefore, to decrease fMRI within and between subject heterogeneity, and thereby increase fMRI statistical power, it is suggested that scanning within 2 hours post high fat ingestion should be avoided. As a corollary, a thorough understanding of a subject's physiological state, prior to an fMRI exam, may reduce the impact of other confounding variables.     

Dishabituation of the BOLD response to speech sounds

Background  

Neural systems show habituation responses at multiple levels, including relatively abstract language categories. Dishabituation – responses to non-habituated stimuli – can provide a window into the structure of these categories, without requiring an overt task.     

Repetition-induced changes in BOLD response reflect accumulation of neural activity

Recent exposure to a stimulus improves performance with subsequent identification of that same stimulus. This ubiquitous, yet simple, memory phenomenon is termed priming and has been linked to another widespread phenomenon called repetition suppression, which is a repetition-induced reduction in human brain activation as measured using fMRI. Here, competing models of the neural basis of repetition suppression were tested empirically. In a backward masking paradigm, we found that effectively masked object stimuli showed repetition enhancement of brain activation instead of suppression. This finding is consistent with an Accumulation model, but is inconsistent with a Suppression model of neural activity. Enhanced activation and the improved behavioral performance usually associated with priming are both explained by a shift in peak latency of the population neural activity elicited during identification.     

BOLD response in dorsal areas varies with relative disparity level

Using fMRI, we explored cortical responses to dichoptically presented random-dot (RD) stimuli which formed a checkerboard by means of horizontal disparity (Julesz). Depth reversals occurred every 800 ms by appropriate horizontal shifting of a subset of the RD pattern. We compared cortical blood oxygen level dependent (BOLD) responses of five subjects under conditions with and without binocular disparity. The results indicate that only extrastriate, but not striate, areas responded more to the stimuli with binocular disparity. We further found that the BOLD signal increased with increasing disparity level only in dorsal areas of occipito-parietal and prefrontal cortex. These results suggest that the fMRI BOLD response can reflect the processing of relative binocular disparity in extrastriate cortex.     

Measuring the hemodynamic response in chronic hypoperfusion

Although structural brain scans help assess brain injury in stroke, they cannot identify regions that are functionally disabled due to disrupted perfusion. Perfusion and functional MRI have the potential for determining the functional consequences of stroke. Here we examine the effectiveness of functional MRI to measure brain function in a single patient (LB) with chronic hypoperfusion. When LB made sustained hand movements we observed a sustained decrease in the fMRI signal, while normal individuals exhibit a sustained increase in signal while conducting this task. This work has clear implications for understanding stroke using functional MRI.     

The postprandial increase in blood triglycerides has no direct effect on the brain BOLD response

A previous study showed that ingestion of a liquid meal high in polyunsaturated lipids decreased the blood-oxygenation-level-dependent (BOLD) response measured by functional magnetic resonance imaging (fMRI) during a finger-tapping motor task, and suggested that this effect was due to a direct effect of blood lipids on the cerebral vasculature. This study compared the time course and magnitude of the BOLD response in fixed anatomic locations before and 3 h after ingestion of high versus low lipid content liquid meals (235 ml Ensure Plus [Abbot Labs] with or without 50 ml added canola oil). Blood triglyceride content peaked 3 h after the high lipid meal and was elevated by 33% compared with the low lipid meal. There was no significant effect of meal composition on the time course or magnitude of the BOLD response in fixed-location clusters of voxels which were activated during either a motor (finger-tapping), a visual (flashing checkerboard), or an integrative/cognitive (number addition) block-design task paradigm. The results indicate that increased blood total triglyceride content after a meal with relatively high polyunsaturated fat does not directly alter the hemodynamic BOLD response to neural activity. However, the postprandial effect on BOLD response of other meals with varying fat types and amounts, as well as other nutrients and phytochemicals, remains to be determined.     

BOLD response during visual perception of biological motion in obsessive-compulsive disorder

Objective  

Although research has shown that deficits in various cognitive functions may underlie obsessive-compulsive disorder (OCD), studies have not yet clarified the specificity and etiology of perception processing, particularly the perception of biological motion that is correlated with social cognition. We used functional magnetic resonance imaging (fMRI) to investigate neural activity associated with the perception of biological motion in OCD patients.     

Factors affecting the hippocampal BOLD response during spatial memory

The hippocampus has long been implicated in spatial memory, from work in rodents to imaging and brain lesion studies in humans. However, recent evidence has pointed to the recruitment of areas outside the hippocampus proper on spatial memory tasks, including the parahippocampal gyrus and precuneus, possibly suggesting a more focused role for the hippocampus proper. In this study, a virtual version of the standard rodent spatial memory assessment, the Morris water task, has been employed during fMRI to investigate the differential involvement of these distinct brain areas. Twenty-eight healthy participants completed a block designed version of the virtual Morris water task (vMWT) which consisted of three conditions: (1) a hippocampal dependent condition during which the participants were forced to use distal room cues in the virtual environment to navigate to a hidden platform; (2) a non-hippocampal dependent condition during which participants were to navigate to a visible platform; (3) a fixation period. Activations of the BOLD signal were evident in the hidden condition as compared to the visible condition in the parahippocampal gyrus, precuneus, and fusiform when analyzed using to a blocked analysis. Moreover, this blocked analysis revealed increases in the right hippocampal BOLD signal during fixation. However, when hidden trials were compared to visible trials using a post hoc event-related analysis focused on the beginning of each trial, activations of the right hippocampus are evident. These results support the theory that extra-hippocampal structures contribute to spatial memory behavior and identify a temporally specific involvement of the hippocampus. Furthermore, they substantiate previous results reporting hippocampal BOLD increases during fixation.