Imaging treatment effects in Alzheimer's disease

Alzheimer's disease (AD) is the commonest form of degenerative dementia and is characterised by progressive cognitive decline. Despite extensive research, the cause of AD is unknown and there is no cure at present. Of the deficits found in AD, that affecting the cholinergic neurotransmitter system is the best established and the only one translated into symptomatic treatment. Cholinergic enhancement with cholinesterase inhibitor (ChEI) drugs has been achieved and their efficacy and safety ascertained by conventional clinical trials. The mechanism of action of these drugs, however, is not well understood. Imaging with SPECT, PET, MRI and fMRI after treatment has clarified what happens in the brains of those AD patients treated with ChEI drugs. Studies with these techniques have identified increases in brain blood flow and glucose metabolism, restoration of nicotinic receptor function and re-establishment of task-related regional brain activation in response to cognitive stimulation after treatment. Structural MRI studies have explained, to some degree, why only a proportion of patients benefits from ChEI treatment and there is some evidence that some ChEI drugs might be neuroprotective. There are, however, many unsolved problems. Timing of treatment intervention to obtain maximum response and the determinants of treatment response are mostly unknown. It is also unclear whether administration of treatment in those patients who have no potential for response accelerates disease progression. These issues cannot be solved by conventional clinical trials. Pharmacoimaging studies could assist the development and refinement of drugs to treat those diseases, such as AD, which affect the central nervous system.     

Functional dissociation of the left ventral occipito-temporal cortex in the direct and indirect retrieval of color features

Previous studies suggest that the storage/retrieval of object features is related to brain regions that are involved in the processing of these features. However, it remains unclear whether, and under what conditions, retrieving information about a feature reactivates the same region that specifically supports that feature’s perception. In this functional magnetic resonance imaging (fMRI) study, we compared brain activation in the left ventral occipito-temporal cortex during subjects performing a color perception task, and direct and indirect color retrieval tasks. After performing the color perception task to localize the regions responsible for color perception, subjects were intensively trained (outside of the scanner) to remember associations between colors and motion directions, and associations between colors and letters. Then, they were asked to perform two color retrieval tasks in the scanner, with stationary and gray scaled images as control stimuli. The results showed that the bilateral posterior occipito-temporal cortex was activated during the color perception task. When color information was retrieved by direct cues (motion direction), the same bilateral occipito-temporal region was activated. When color information was retrieved indirectly (judging whether a motion direction matched a letter by their associated colors), a region anterior to the color perception region in the left ventral occipito-temporal cortex was additionally activated. Our results provided evidence for the functional dissociation in the two subregions of the ventral occipito-temporal cortex during retrieval of color features: the posterior area might relate to perceptual features of color, while the anterior region might relate to the knowledge of associations with color.     

Functional Connectivity Methods and Their Applications in fMRI Data

The availability of powerful non-invasive neuroimaging techniques has given rise to various studies that aim to map the human brain. These studies focus on not only finding brain activation signatures but also on understanding the overall organization of functional communication in the brain network. Based on the principle that distinct brain regions are functionally connected and continuously share information with each other, various approaches to finding these functional networks have been proposed in the literature. In this paper, we present an overview of the most common methods to estimate and characterize functional connectivity in fMRI data. We illustrate these methodologies with resting-state functional MRI data from the Human Connectome Project, providing details of their implementation and insights on the interpretations of the results. We aim to guide researchers that are new to the field of neuroimaging by providing the necessary tools to estimate and characterize brain circuitry.     

fMRI-constrained source analysis of visual P300 in Landolt ring task

An fMRI-constrained source analysis was applied to investigate visual P300 in the Landolt ring task. To study the localization and relative activation timing of P300 generators, we implemented simultaneous EEG/fMRI to identify BOLD signal changes and record 64-channel EEG in 10 subjects during a Landolt ring task inside a 1.5-T fMRI scanner using an MR-compatible EEG recording system. MRI artifact subtraction software was applied to obtain continuous EEG data. Then, the simultaneous collecting of EEG and fMRI was validated in preserving relevant ERPs. The fMRI-constrained source analysis resulted in an 8-dipole solution. The bilateral middle frontal and the right inferior parietal dipole waveforms showed a short latency peak corresponding to the early P300 activity, while the four parietal and the anterior cingulate dipole waveforms showed a long latency peak corresponding to the late P300 activity. The longest latency peak of the anterior cingulate dipole agrees with its role in initiation of motor response after successful target recognition. Target detection in the Landolt ring task produces the strongest and most extensive parietal activation （especially superior parietal activation）, which might be due to its particular visual attention switching.     

一种磁共振脑功能成像的头部移动校正方法

在磁共振脑功能成像（functional magnetic resonance imaging,fMRI)试验中，头部很小的移动就会对试验结果产生不良影响，因此在对数据统计分析之前要求进行移动校正。本文利用LMF（levenberg-mrquardt-fletcher)算法极小化参考图像和校正图像之间的残差平方和自动校正fMRI图像，根据多分辨率金字塔结构由粗到细地搜索最优解，既可以较快的收敛，又可以考虑较大的移动。     

Functional MRI detection of hemodynamic response of repeated median nerve stimulation

Median nerve stimulation is a commonly used technique in the clinical setting to determine areas of neuronal function in the brain. Neuronal activity of repeated median nerve stimulation is well studied. The cerebral hemodynamic response of the stimulation, on the other hand, is not very clear. In this study, we investigate how cerebral hemodynamics behave over time using the same repeated median nerve stimulation. Ten subjects received constant repeated electrical stimulation to the right median nerve. Each subject had functional magnetic resonance imaging scans while receiving said stimulations for seven runs. Our results show that the blood oxygen level-dependent (BOLD) signal significantly decreases across each run. Significant BOLD signal decreases can also be seen within runs. These results are consistent with studies that have studied the hemodynamic habituation effect with other forms of stimulation. However, the results do not completely agree with the findings of studies where evoked potentials were examined. Thus, further inquiry of how evoked potentials and cerebral hemodynamics are coupled when using constant stimulations is needed.     

Neural and vascular variability and the fMRI-BOLD response in normal aging

Neural, vascular and structural variables contributing to the blood oxygen level-dependent (BOLD) signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (six male and six female; mean age: 24 years; range: 19–27 years) and 12 older healthy subjects (five male and seven female; mean age: 58 years; range: 55–71 years) with no history of head trauma and neurological disease were scanned. Functional magnetic resonance imaging measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold (BH) task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45%, 40% and 38% in the elderly group during the motor, cognitive and BH tasks, respectively, compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the intersubject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response.     

In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change

Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast — attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility — has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed “signal enhancement by extravascular water protons” (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air–tissue and/or bone–tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory.     

A new approach to estimating the signal dimension of concatenated resting-state functional MRI data sets

Estimating the effective signal dimension of resting-state functional MRI (fMRI) data sets (i.e., selecting an appropriate number of signal components) is essential for data-driven analysis. However, current methods are prone to overestimate the dimensions, especially for concatenated group data sets. This work aims to develop improved dimension estimation methods for group fMRI data generated by data reduction and grouping procedure at multiple levels. We proposed a “noise-blurring” approach to suppress intragroup signal variations and to correct spectral alterations caused by the data reduction, which should be responsible for the group dimension overestimation. This technique was evaluated on both simulated group data sets and in vivo resting-state fMRI data sets acquired from 14 normal human subjects during five different scan sessions. Reduction and grouping procedures were repeated at three levels in either “scan–session–subject” or “scan–subject–session” order. Compared with traditional estimation methods, our approach exhibits a stronger immunity against intragroup signal variation, less sensitivity to group size and a better agreement on the dimensions at the third level between the two grouping orders.     

Functional connectivity in the rat brain: a complex network approach

Functional connectivity analyses of fMRI data can provide a wealth of information on the brain functional organization and have been widely applied to the study of the human brain. More recently, these methods have been extended to preclinical species, thus providing a powerful translational tool. Here, we review methods and findings of functional connectivity studies in the rat. More specifically, we focus on correlation analysis of pharmacological MRI (phMRI) responses, an approach that has enabled mapping the patterns of connectivity underlying major neurotransmitter systems in vivo. We also review the use of novel statistical approaches based on a network representation of the functional connectivity and their application to the study of the rat brain functional architecture.