Examining the resting-state vascular connectivity using fMRA in comparison with fMRI: a preliminary study.

Unprecedented 4D spatiotemporal infant regional cerebral blood flow framework and region-specific physiology–function coupling across infancy were elucidated, highlighting strong physiology–function coupling specifically at the default-mode network to meet extraneuronal metabolic demand for network emergence.

Resting-state networks including the DMN have been shown to be abnormal in adults with temporal lobe epilepsy. However, little is known about the DMN in children with medically refractory epilepsy. The aim was to determine whether there was a difference in the DMN in children with medically refractory epilepsy relative to controls. Eleven children with medically refractory epilepsy and 11 age-matched healthy controls underwent resting-state fMRI. IC analysis was used to identify the DMN. A random-effects analysis was performed on the Z-maps of the DMN within each group and between groups. We calculated the temporal correlation coefficients of pairs of ROIs: PCC/PCUN, mPFC, and left and right lateral parietal cortices. The relations between z scores of temporal correlation coefficients of pairs of ROIs and clinical seizure parameters and IQ were assessed. The patients demonstrated decreased DMN connectivity in the PCC/PCUN, bilateral lateral parietal cortex, and anterior and midcingulate relative to controls. There was reduced connectivity between the mPFC-right lateral parietal cortex, the PCC/PCUN-left lateral parietal cortex, and the PCC/PCUN-right lateral parietal cortex pairs of ROIs in patients compared with controls. There were no significant correlations between the z scores of temporal correlation coefficients of the 6 pairs of ROIs in patients and age of seizure onset, duration of epilepsy, number of medications, seizure frequency, and IQ. We have found reduced connectivity in the DMN in children with medically refractory epilepsy. Further studies are needed to determine whether different seizure types have different effects on the DMN and whether the impaired connectivity is related to cognitive functions subserved by the DMN.

Measurement of correlations between brain regions (functional connectivity) using blood oxygen level dependent (BOLD) fMRI has proven to be a powerful tool for studying the functional organization of the brain. Recently, dynamic functional connectivity has emerged as a major topic in the resting-state BOLD fMRI literature. Here, using simulations and multiple sets of empirical observations, we confirm that imposed task states can alter the correlation structure of BOLD activity. However, we find that observations of "dynamic" BOLD correlations during the resting state are largely explained by sampling variability. Beyond sampling variability, the largest part of observed "dynamics" during rest is attributable to head motion. An additional component of dynamic variability during rest is attributable to fluctuating sleep state. Thus, aside from the preceding explanatory factors, a single correlation structure-as opposed to a sequence of distinct correlation structures-may adequately describe the resting state as measured by BOLD fMRI. These results suggest that resting-state BOLD correlations do not primarily reflect moment-to-moment changes in cognitive content. Rather, resting-state BOLD correlations may predominantly reflect processes concerned with the maintenance of the long-term stability of the brain's functional organization.

There is substantial overlap between the brain regions supporting episodic memory and the default network. However, in humans, the impact of bilateral medial temporal lobe (MTL) damage on a large-scale neural network such as the default mode network is unknown. To examine this issue, resting fMRI was performed with amnesic patients and control participants. Seed-based functional connectivity analyses revealed robust default network connectivity in amnesia in cortical default network regions such as medial prefrontal cortex, posterior medial cortex, and lateral parietal cortex, as well as evidence of connectivity to residual MTL tissue. Relative to control participants, decreased posterior cingulate cortex connectivity to MTL and increased connectivity to cortical default network regions including lateral parietal and medial prefrontal cortex were observed in amnesic patients. In contrast, somatomotor network connectivity was intact in amnesic patients, indicating that bilateral MTL lesions may selectively impact the default network. Changes in default network connectivity in amnesia were largely restricted to the MTL subsystem, providing preliminary support from MTL amnesic patients that the default network can be fractionated into functionally and structurally distinct components. To our knowledge, this is the first examination of the default network in amnesia.

Impaired functional default mode network in patients with mild neurological Wilson’s disease

Electroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration has recently revealed that several brain structures are involved in generalized spike and wave discharges (GSWDs) in idiopathic generalized epilepsies (IGEs). In particular, deactivations and activations have been observed within the so-called brain default mode network (DMN) and thalamus, respectively. In the present study we analyzed the dynamic time course of blood oxygen level-dependent (BOLD) changes preceding and following 3 Hz GSWDs in a group of adolescent and adult patients with IGE who presented with absence seizures (AS). Our aim was to evaluate cortical BOLD changes before, during, and after GSWD onset. Twenty-one patients with IGE underwent EEG-fMRI coregistration. EEG-related analyses were run both at the single-subject and at group level (random effect). The time-course analysis was conducted for 3 s time windows before, during, and after GSWDs, and they were included until no further BOLD signal changes were observed. Fifteen patients (nine female, mean age 28 years) had GSWDs during EEG-fMRI coregistration (262 total events, mean duration 4 s). Time-course group analysis showed BOLD increments starting approximately 10 s before GSWD onset located in frontal and parietal cortical areas, and especially in the precuneus-posterior cingulate region. At GSWD onset, BOLD increments were located in thalamus, cerebellum, and anterior cingulate gyrus, whereas BOLD decrements were observed in the DMN regions persisting until 9 s after onset. Hemodynamic changes (BOLD increments) occurred in specific cortical areas, namely the precuneus/posterior cingulate, lateral parietal, and frontal cortices, several seconds before EEG onset of GSWD. A dysfunction of these brain regions, some of which belongs to the DMN, may be crucial in generating GSWDs in patients with IGE.

Lesion studies indicate that the lateral and inferior temporal cortex is a critical area of semantic memory storage, but little is known about the cortical organization of semantics within this area. One proposition has been that dominant physical characteristics of objects (structure, motility) are determining factors. A positron emission tomography experiment using the H2(15)O bolus method was performed to test this hypothesis by contrasting activation for concrete and abstract concepts. Unlike previous studies that considered this question, the task required explicit word meaning judgments, and blocks of trials were designed to be of equal difficulty for the two word classes. The task required elderly participants to read aloud the pair of words that was closer in meaning (e.g., spade-shovel vs. spade-carpet). Subtraction analyses that compared the semantic judgment tasks with a baseline condition indicated that both abstract and concrete concepts activated the left lateral temporal cortex. A direct comparison of abstract versus concrete scans indicated differences in the lateralization of fusiform activation. We conclude that although concreteness might be a critical factor in the fusiform cortex, it is not dominant in the lateral temporal cortex. A multistudy overview suggests that tasks that focus on one concept per trial activate areas posterior to y = -40, whereas those that invoke several concepts, as in the present study, activate areas anterior to this. Increased processing complexity may proceed in a posterior-anterior direction in the lateral temporal cortex.

Dissociative convulsions represent complex biopsychosocial etiopathogenesis and have semiological similarities with epilepsy, which leads to delays in definitive diagnosis as well as treatment. We explored the neurobiological underpinnings of dissociative convulsions using a functional magnetic resonance imaging (fMRI) design targeting cognitive, affective, and resting state characteristics in our subjects. Seventeen female patients with dissociative convulsions without any co-morbid psychiatric or neurological illness and 17 matched healthy controls underwent standardized task-based (affective and cognitive) and resting state fMRI. Blood oxygen level-dependent (BOLD) activation results were compared across the groups, and correlation with the severity of dissociation was measured. Patients with dissociative convulsions had lower activation in the left cingulate gyrus, left paracentral lobule, right middle and inferior frontal gyrus, right caudate nucleus, and right thalamus. There was increased resting state functional connectivity (FC) between the left posterior superior temporal gyrus and left superior parietal lobule; left amygdala and Default Mode Network (DMN) of right lateral parietal cortex; right supramarginal gyrus and left cuneus in the patient group. Patients also had decreased FC between the anterior cingulate cortex (ACC) and left thalamus; ACC and right central opercular cortex; DMN of PCC, posterior cingulate gyrus, and right middle temporal lobe. Patients with dissociative convulsions have significant deficits in the areas associated with the processing of emotional, cognitive, memory, and sensory-motor functions. There is a significant correlation between dissociative severity and the functioning of areas involving the processing of emotions, cognition, and memory.

Maintaining optimal cognitive functioning throughout the lifespan is a public health priority. Evaluation of cognitive outcomes following interventions to promote and preserve brain structure and function in older adults, and associated neural mechanisms, are therefore of critical importance. In this randomized controlled trial, we examined the behavioral and neural outcomes following mindfulness training (n = 72), compared to a cognitive fitness program (n = 74) in healthy, cognitively normal, older adults (65–80 years old). To assess cognitive functioning, we used the Preclinical Alzheimer Cognitive Composite (PACC), which combines measures of episodic memory, executive function, and global cognition. We hypothesized that mindfulness training would enhance cognition, increase intrinsic functional connectivity measured with magnetic resonance imaging (MRI) between the hippocampus and posteromedial cortex, as well as promote increased gray matter volume within those regions. Following the 8-week intervention, the mindfulness training group showed improved performance on the PACC, while the control group did not. Furthermore, following mindfulness training, greater improvement on the PACC was associated with a larger increase in intrinsic connectivity within the default mode network, particularly between the right hippocampus and posteromedial cortex and between the left hippocampus and lateral parietal cortex. The cognitive fitness training group did not show such effects. These findings demonstrate that mindfulness training improves cognitive performance in cognitively intact older individuals and strengthens connectivity within the default mode network, which is particularly vulnerable to aging affects.Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT02628548], identifier [NCT02628548].

Local brain atrophy accounts for functional activity differences in normal aging

Relative regional cerebral blood flow was measured with single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) in 16 patients with major depression while they were in the depressed state as well as in remission. All patients were closely matched with regard to medication status. In the depressed state, significant reductions in tracer uptake were found in the left superior frontal, bilateral parietal and right lateral temporal cortex. During remission, significant increases in uptake were found in the left superior frontal, right parietal and right lateral temporal cortex. There were no significant differences in tracer uptake between patients in remission and controls. These findings suggest that the regional decreases in tracer uptake observed in the depressed state might be a state-related abnormality.

Imaging of amyloid β in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism

ASSOCIATION BETWEEN ODOR IDENTIFICATION AND REGIONAL GRAY MATTER IN EARLY PRECLINICAL ALZHEIMER'S DISEASE

To investigate whether default mode network (DMN) spatial properties can be directly affected by pain, with a comparison of painful and nonpainful conditions. The authors performed a functional magnetic resonance (MR) imaging study, approved by the local institutional ethics committee, involving 10 healthy male subjects (age range, 18-45 years) who gave written informed consent. The subjects underwent two experimental sessions of median nerve electrical stimulation at painful and nonpainful levels. Independent component analysis of the functional MR imaging data was performed to determine the DMN spatiotemporal pattern. Group-level DMN connectivity maps for painful and nonpainful conditions were obtained (P < .001, corrected with false discovery rate). The contrast between the connectivity maps in the two conditions was also computed (P < .05, corrected with false discovery rate). The DMN maintained its typical temporal properties but was subject to modifications in connectivity pattern during painful stimulation, affecting the brain areas associated with pain processing. Increased connectivity in painful conditions was found mainly in the left prefrontal cortex and posterior cingulate cortex-precuneus, and decreased connectivity was found in the lateral parietal cortex. Study findings were in line with the impairments of the DMN reported in patients with chronic pain. They support the hypothesis that alteration of the DMN connectivity pattern localized in specific brain areas during acute pain, if repeated across time, might induce permanent changes that could disrupt the DMN functional architecture.

Identifying individuals with early stage Alzheimer’s disease (AD) at greater risk of steeper clinical decline would allow professionals and loved ones to make better-informed medical, support, and life planning decisions. Despite accumulating evidence on the clinical prognostic value of tau PET in typical late-onset amnestic AD, its utility in predicting clinical decline in individuals with atypical forms of AD remains unclear. In this study, we examined the relationship between baseline tau PET signal and the rate of subsequent clinical decline in a sample of 48 A+/T+/N+ patients with mild cognitive impairment or mild dementia due to AD with atypical clinical phenotypes (Posterior Cortical Atrophy, logopenic variant Primary Progressive Aphasia, and amnestic syndrome with multi-domain impairment and age of onset < 65 years). All patients underwent structural magnetic resonance imaging (MRI), tau (18F-Flortaucipir) PET, and amyloid (either 18F-Florbetaben or 11C-Pittsburgh Compound B) PET scans at baseline. Each patient’s longitudinal clinical decline was assessed by calculating the annualized change in the Clinical Dementia Rating Sum-of-Boxes (CDR-SB) scores from baseline to follow-up (mean time interval = 14.55 ± 3.97 months). Our sample of early atypical AD patients showed an increase in CDR-SB by 1.18 ± 1.25 points per year: t(47) = 6.56, p < .001, d = 0.95. These AD patients showed prominent baseline tau burden in posterior cortical regions including the major nodes of the default mode network, including the angular gyrus, posterior cingulate cortex/precuneus, and lateral temporal cortex. Greater baseline tau in the broader default mode network predicted faster clinical decline. Tau in the default mode network was the strongest predictor of clinical decline, outperforming baseline clinical impairment, tau in other functional networks, and the magnitude of cortical atrophy and amyloid burden in the default mode network. Overall, these findings point to the contribution of baseline tau burden within the default mode network of the cerebral cortex to predicting the magnitude of clinical decline in a sample of atypical early AD patients one year later. This simple measure based on a tau PET scan could aid the development of a personalized prognostic, monitoring, and treatment plan tailored to each individual patient, which would help clinicians not only predict the natural evolution of the disease but also estimate the effect of disease-modifying therapies on slowing subsequent clinical decline given the patient’s tau burden while still early in the disease course.