Ryan C.N. D'Arcy

Does functional MRI detect activation in white matter? A review of emerging evidence, issues, and future directions

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows for visualization of activated brain regions. Until recently, fMRI studies have focused on gray matter. There are two main reasons white matter fMRI remains controversial: (1) the blood oxygen level dependent (BOLD) fMRI signal depends on cerebral blood flow and volume, which are lower in white matter than gray matter and (2) fMRI signal has been associated with post-synaptic potentials (mainly localized in gray matter) as opposed to action potentials (the primary type of neural activity in white matter). Despite these observations, there is no direct evidence against measuring fMRI activation in white matter and reports of fMRI activation in white matter continue to increase. The questions underlying white matter fMRI activation are important. White matter fMRI activation has the potential to greatly expand the breadth of brain connectivity research, as well as improve the assessment and diagnosis of white matter and connectivity disorders. The current review provides an overview of the motivation to investigate white matter fMRI activation, as well as the published evidence of this phenomenon. We speculate on possible neurophysiologic bases of white matter fMRI signals, and discuss potential explanations for why reports of white matter fMRI activation are relatively scarce. We end with a discussion of future basic and clinical research directions in the study of white matter fMRI.

Exploratory data analysis reveals visuovisual interhemispheric transfer in functional magnetic resonance imaging

We used an exploratory data analysis approach to detect interhemispheric processing of complex visual stimuli in functional magnetic resonance imaging (fMRI). A crossed–uncrossed visual field paradigm was used to elicit interhemispheric transfer of picture/word information. Under the uncrossed (control) condition, the stimuli were presented to the preferential hemispheres (pictures to the left visual field/right hemisphere and words to the right visual field/left hemisphere). Under the crossed condition, the visual field presentation was switched in order to elicit increased interhemispheric processing. Fuzzy cluster analysis revealed significantly more crossed activity in cortical areas near the splenium of the corpus callosum. As expected, examination of the activation revealed smaller responses in perisplenial regions (relative to visual responses in the medial extrastriate regions). The exploratory results were compared with those obtained from parametric and masked analyses. The findings confirm that fMRI can be used to detect interhemispheric transfer of picture/word information. The activation was optimally characterized using exploratory data analysis. Magn Reson Med, 2006.

Improving fMRI reliability in presurgical mapping for brain tumours

Purpose Functional MRI (fMRI) is becoming increasingly integrated into clinical practice for presurgical mapping. Current efforts are focused on validating data quality, with reliability being a major factor. In this paper, we demonstrate the utility of a recently developed approach that uses receiver operating characteristic-reliability (ROC-r) to: (1) identify reliable versus unreliable data sets; (2) automatically select processing options to enhance data quality; and (3) automatically select individualised thresholds for activation maps. Methods Presurgical fMRI was conducted in 16 patients undergoing surgical treatment for brain tumours. Within-session test–retest fMRI was conducted, and ROC-reliability of the patient group was compared to a previous healthy control cohort. Individually optimised preprocessing pipelines were determined to improve reliability. Spatial correspondence was assessed by comparing the fMRI results to intraoperative cortical stimulation mapping, in terms of the distance to the nearest active fMRI voxel. Results The average ROC-r reliability for the patients was 0.58±0.03, as compared to 0.72±0.02 in healthy controls. For the patient group, this increased significantly to 0.65±0.02 by adopting optimised preprocessing pipelines. Co-localisation of the fMRI maps with cortical stimulation was significantly better for more reliable versus less reliable data sets (8.3±0.9 vs 29±3 mm, respectively). Conclusions We demonstrated ROC-r analysis for identifying reliable fMRI data sets, choosing optimal postprocessing pipelines, and selecting patient-specific thresholds. Data sets with higher reliability also showed closer spatial correspondence to cortical stimulation. ROC-r can thus identify poor fMRI data at time of scanning, allowing for repeat scans when necessary. ROC-r analysis provides optimised and automated fMRI processing for improved presurgical mapping.

Functional MRI activation in white matter during the Symbol Digit Modalities Test.

Background: Recent evidence shows that functional magnetic resonance imaging (fMRI) can detect activation in white matter (WM). Such advances have important implications for understanding WM dysfunction. A key step in linking neuroimaging advances to the evaluation of clinical disorders is to examine whether WM activation can be detected at the individual level during clinical tests associated with WM function. We used an adapted Symbol Digit Modalities Test (SDMT) in a 4T fMRI study of healthy adults. Results: Results from 17 healthy individuals revealed WM activation in 88% of participants (15/17). The activation was in either the corpus callosum (anterior and/or posterior) or internal capsule (left and/or right). Conclusions: The findings link advances in fMRI to an established clinical test of WM function. Future work should focus on evaluating patients with WM dysfunction.

Waist circumference is correlated with poorer cognition in elderly type 2 diabetes women

Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood.

Spontaneous Blinks Activate the Precuneus: Characterizing Blink-Related Oscillations Using Magnetoencephalography

Spontaneous blinking occurs 15–20 times per minute. Although blinking has often been associated with its physiological role of corneal lubrication, there is now increasing behavioral evidence suggesting that blinks are also modulated by cognitive processes such as attention and information processing. Recent low-density electroencephalography (EEG) studies have reported so-called blink-related oscillations (BROs) associated with spontaneous blinking at rest. Delta-band (0.5–4 Hz) BROs are thought to originate from the precuneus region involved in environmental monitoring and awareness, with potential clinical utility in evaluation of disorders of consciousness. However, the neural mechanisms of BROs have not been elucidated. Using magnetoencephalography (MEG), we characterized delta-band BROs in 36 healthy individuals while controlling for background brain activity. Results showed that, compared to pre-blink baseline, delta-band BROs resulted in increased global field power (p < 0.001) and time-frequency spectral power (p < 0.05) at the sensor level, peaking at ~250 ms post-blink maximum. Source localization showed that spontaneous blinks activated the bilateral precuneus (p < 0.05 FWE), and source activity within the precuneus was also consistent with sensor-space results. Crucially, these effects were only observed in the blink condition and were absent in the control condition, demonstrating that results were due to spontaneous blinks rather than as part of the inherent brain activity. The current study represents the first MEG examination of BROs. Our findings suggest that spontaneous blinks activate the precuneus regions consistent with environmental monitoring and awareness, and provide important neuroimaging support for the cognitive role of spontaneous blinks.

CHANGES IN PREFRONTAL ACTIVATION IN EARLY ALZHEIMER'S DISEASE: A MAGNETOENCEPHALOGRAPHY (MEG) STUDY

are sometimes considered mere radiological finding with uncertain clinical significance. This paper studies the relationship of WMH to the cognitive function of healthy Filipino adults with normal hippocampal volume and with no previous history of stroke.Methods: 202 patients with MRI hippocampal volumetry, neurocognitive tests (MMSE, MoCA) and normal metabolic parameters were studied. Hippocampal volume was determined using NeuroQuant software. Those with low hippocampal volume and MRI evidence of stroke of any age were excluded. MR images were reviewed and WMH were graded using Fazekas scale. Correlational statistical analysis was made on the relationship of WMH to neurocognitive scores. Results: There is significant relationship between age and Fazekas score. The higher the age, the higher is the Fazekas score, and the greater is the non-specific white matter change (p1⁄40.004). There is a clinically significant correlation between Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA) with the degree of WMH, worst between advanced Fazekas 3 and 4. (see Figure 1) Conclusions: This paper to the best of our knowledge is the first to use hippocampal volumetry and exclude subjects with Alzheimer and vascular dementia to get a pure sample of healthy adults with only WMH on MRI. Our results show that there is a clinically significant drop in neurocognitive scores with increasing WMH. This paper is also the first to explore cognitive impairment in Asian Filipino population with no apparent neurocognitive impairment but only has WMH on MRI.

Cognitive loading via mental arithmetic modulates effects of blink-related oscillations on precuneus and ventral attention network regions

Blink‐related oscillations (BROs) have been linked with environmental monitoring processes associated with blinking, with cortical activations in the bilateral precuneus. Although BROs have been described under resting and passive fixation conditions, little is known about their characteristics under cognitive loading. To address this, we investigated BRO effects during both mental arithmetic (MA) and passive fixation (PF) tasks using magnetoencephalography (n =20), while maintaining the same sensory environment in both tasks. Our results confirmed the presence of BRO effects in both MA and PF tasks, with similar characteristics including blink‐related increase in global field power and blink‐related activation of the bilateral precuneus. In addition, cognitive loading due to MA also modulated BRO effects by decreasing BRO‐induced cortical activations in key brain regions including the bilateral anterior precuneus. Interestingly, blinking during MA—but not PF—activated regions of the ventral attention network (i.e., right supramarginal gyrus and inferior frontal gyrus), suggesting possible recruitment of these areas for blink processing under cognitive loading conditions. Time–frequency analysis revealed a consistent pattern of BRO‐related effects in the precuneus in both tasks, but with task‐related functional segregation within the anterior and posterior subregions. Based on these findings, we postulate a potential neurocognitive mechanism for blink processing in the precuneus. This study is the first investigation of BRO effects under cognitive loading, and our results provide compelling new evidence for the important cognitive implications of blink‐related processing in the human brain.

Functional MRI on executive functioning in aging and dementia: A scoping review of cognitive tasks

Cognitive decline with aging and dementia is especially poignant with regard to the executive functioning that is necessary for activities of daily independent living. The relationship between age‐related neurodegeneration in the prefrontal cortex and executive functioning has been uniquely investigated using task‐phase functional magnetic resonance imaging (fMRI) to detect brain activity in response to stimuli; however, a comprehensive list of task designs that have been implemented to task‐phase fMRI is absent in the literature. The purpose of this review was to recognize what methods have been used to study executive functions with aging and dementia in fMRI tasks, and to describe and categorize them. The following cognitive subdomains were emphasized: cognitive flexibility, planning and decision‐making, working memory, cognitive control/inhibition, semantic processing, attention and concentration, emotional functioning, and multitasking. Over 30 different task‐phase fMRI designs were found to have been implemented in the literature, all adopted from standard neuropsychological assessments. Cognitive set‐shifting and decision‐making tasks were particularly well studied in regard to age‐related neurodegeneration, while emotional functioning and multitasking designs were found to be the least utilized. Summarizing the information on which tasks have shown the greatest usability will assist in the future design and implementation of effective fMRI experiments targeting executive functioning.

Functional MRI technologies in the study of medication treatment effect on Alzheimer's disease

Alzheimers disease (AD) is the most common cause of late‐life dementia. Characterized by progressive neurodegeneration, the disease is expressed as gradual memory loss together with decline in cognitive abilities and other brain functions. Despite extensive research over the past decade, the cause and cure of AD both remain largely unknown. Several AD‐associated deficits have been targeted for interventions, including those based on amyloid‐beta, tau, and inflammation hypotheses. Only 2 types of medications—cholinesterase inhibitors and memantine—have been approved, to control the cognitive symptoms of AD such as the loss of memory, language, and executive function. Noninvasive in vivo functional magnetic resonance imaging (MRI) technologies, including the blood oxygen level‐dependent functional MRI, arterial spin labeling‐based perfusion MRI, and the proton magnetic resonance spectroscopy have been used to study the effect of ChEIs and memantine in the brain. Most of these studies have demonstrated increased functional activation and connectivity, increased regional brain blood flow and volume post‐treatment, and positive responses of critical brain metabolites reflecting neuronal status and functionality in patients with AD and mild cognitive impairment. The findings have contributed to the understanding of the mechanisms underlying the medication treatments and support the crucial role of functional MRI technologies in the development and refinement of AD medication therapies.