Functional MRI Signal Research Articles

Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex

The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.

ФУНКЦИОНАЛЬНАЯ МАГНИТНО-РЕЗОНАНСНАЯ ТОМОГРАФИЯ В ИЗУЧЕНИИ ЦЕНТРОВ НЕЙРОНАЛЬНОЙ АКТИВАЦИИ В ОТВЕТ НА ПСИХОЭМОЦИОНАЛЬНЫЙ СТРЕСС

Poster: ECR 2016 / C-1292 / Functional MRI signal changes in the central nervous system in response to emotional stress. by: M. Zashezova, D. Ustyuzhanin, R. Konovalov, S. K. Ternovoy; Moscow/RU

Functional MRI Correlates of Resting-State Temporal Theta and Delta EEG Rhythms

The EEG rhythms demonstrate changes in frequency and power with spontaneous changes in behavioral state that do not have well-understood metabolic correlates within the brain. To investigate this question and compare the temporal lobe theta and delta rhythms, resting-state functional MRI was obtained with simultaneous EEG. Simultaneous EEG-functional MRI was recorded from 14 healthy sleep-deprived subjects in awake and drowsy states. Scalp electrodes corresponding to bilateral temporal lobes were used to calculate delta and theta band power. The resulting time series was used as input in a general linear model, and the final power curves were convolved with the standard hemodynamic response function. Resulting images were thresholded at Z > 2.0. Positive and negative correlations for unilateral theta and delta rhythms were present bilaterally in different structures and with differing correlation signs. Theta rhythm positive correlation was present in hindbrain, peri-opercular, and frontoparietal regions and subcortical gray structures, whereas negative correlation was present in parietooccipital cortex. Delta rhythm positive correlation was present in parietooccipital cortex, and negative correlation roughly resembled positive correlations for the theta rhythm. Temporal lobe theta and delta rhythms are correlated with functional MRI signal in an almost mutually exclusive distribution. The different distributions indicate different corresponding networks. These normal findings supplement the understanding of theta and delta rhythm significance.

Functional MRI signal fluctuations highlight altered resting brain activity in Huntington's disease.

The fractional Amplitude of Low Frequency Fluctuations (fALFF) and the degree of local synchronization (Regional Homogeneity - ReHo) of resting-state BOLD signal have been suggested to map spontaneous neuronal activity and local functional connectivity, respectively. We compared voxelwise, independent of atrophy, the fALFF and ReHo patterns of 11 presymptomatic (ps-HD) and 28 symptomatic (sHD) Huntington's disease mutation carriers, with those of 40 normal volunteers, and tested their possible correlations with the motor and cognitive subscores of the Unified Huntington's Disease Rating Scale. In sHD patients, fALFF was mainly reduced bilaterally in parietal lobes (right precuneus being already affected in psHD), and in superior frontal gyri, and increased bilaterally in cerebellar lobules VI, VIII and IX, as well as in the right inferior temporal gyrus. In sHD, and to a lesser extent in psHD, ReHo was bilaterally reduced in putamina, cerebellar lobules III to VI, and superior medial frontal gyri, and increased in both psHD and sHD in fronto-basal cortices, and in the right temporal lobe. fALFF correlated inversely with cognitive scores in lobule IX of the cerebellum (mainly with total Stroop score, p<0.0001), and in the medial portions of both thalami. These results are consistent with a reduced neuronal activity in the cortical components of the executive networks, known to be affected in Huntington's Disease, and with reduced local functional integration in subcortical and cerebellar components of the sensori-motor network. Cerebellar clusters of significant correlation of fALFF with executive function scores may be related to compensatory mechanisms.

Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults

In conventional neuroimaging, cerebrovascular reactivity (CVR) is quantified primarily using the blood-oxygenation level-dependent (BOLD) functional MRI (fMRI) signal, specifically, as the BOLD response to intravascular carbon dioxide (CO2) modulations, in units of [%ΔBOLD/mmHg]. While this method has achieved wide appeal and clinical translation, the tolerability of CO2-related tasks amongst patients and the elderly remains a challenge in more routine and large-scale applications. In this work, we propose an improved method to quantify CVR by exploiting intrinsic fluctuations in CO2 and corresponding changes in the resting-state BOLD signal (rs-qCVR). Our rs-qCVR approach requires simultaneous monitoring of PETCO2, cardiac pulsation and respiratory volume. In 16 healthy adults, we compare our quantitative CVR estimation technique to the prospective CO2-targeting based CVR quantification approach (qCVR, the “standard”). We also compare our rs-CVR to non-quantitative alternatives including the resting-state fluctuation amplitude (RSFA), amplitude of low-frequency fluctuation (ALFF) and global-signal regression. When all subjects were pooled, only RSFA and ALFF were significantly associated with qCVR. However, for characterizing regional CVR variations within each subject, only the PETCO2-based rs-qCVR measure is strongly associated with standard qCVR in 100% of the subjects (p≤0.1). In contrast, for the more qualitative CVR measures, significant within-subject association with qCVR was only achieved in 50–70% of the subjects. Our work establishes the feasibility of extracting quantitative CVR maps using rs-fMRI, opening the possibility of mapping functional connectivity and qCVR simultaneously.

Enhancement of functional MRI signal at high‐susceptibility regions of brain using simultaneous multiecho multithin‐slice summation imaging technique

To increase temporal-signal-to-noise ratio (tSNR) and blood oxygen level-dependent (BOLD) sensitivity at high-susceptibility regions of the brain by means of a simultaneous multiecho multithin-slice summation imaging technique. The simultaneous multislice (SMS) technique was implemented with multiecho (SMSME) and multiecho with thin-slice summation (SMSME-thin) at 3T. Multiecho data were summated based on the local apparent T2* weighting factor. Ten healthy subjects were studied for the whole brain activation by breath-holding. The tSNR values and the number of activated pixels acquired with SMSME and SMSME-thin were compared with those acquired with the conventional gradient-echo EPI in multiple brain regions SMS methods accelerated imaging time by 5-fold as compared with the conventional method, resulting in the acquisition of three echoes and four thin-slices during the same TR of 2.5 seconds. At high-susceptibility regions, including the amygdala, inferior and middle temporal, and anterior frontal lobes, SMSME increased tSNR values by up to ∼80% and BOLD activation by up to ∼20% (paired t-test, P < 0.05). SMSME-thin further increased values as compared with SMSME (∼45% for tSNR and ∼20% for activation, P < 0.05). The SMSME-thin imaging technique enhanced the temporal-signal-to-noise ratio and functional activation at high susceptibility regions of the brain. J. Magn. Reson. Imaging 2016;44:478-485.

Strengthened Corticosubcortical Functional Connectivity during Muscle Fatigue.

The present study examined functional connectivity (FC) between functional MRI (fMRI) signals of the primary motor cortex (M1) and each of the three subcortical neural structures, cerebellum (CB), basal ganglia (BG), and thalamus (TL), during muscle fatigue using the quantile regression technique. Understanding activation relation between the subcortical structures and the M1 during prolonged motor performance should help delineate how central motor control network modulates acute perturbations at peripheral sensorimotor system such as muscle fatigue. Ten healthy subjects participated in the study and completed a 20-minute intermittent handgrip motor task at 50% of their maximal voluntary contraction (MVC) level. Quantile regression analyses were carried out to compare the FC between the contralateral (left) M1 and CB, BG, and TL in the minimal (beginning 100 s) versus significant (ending 100 s) fatigue stages. Widespread, statistically significant increases in FC were found in bilateral BG, CB, and TL with the left M1 during significant versus minimal fatigue stages. Our results imply that these subcortical nuclei are critical components in the motor control network and actively involved in modulating voluntary muscle fatigue, possibly, by working together with the M1 to strengthen the descending central command to prolong the motor performance.

Abnormal regional homogeneity in Parkinson's disease: a resting state fMRI study

To examine the functional brain alterations in Parkinson's disease (PD) by measuring blood oxygenation level dependent (BOLD) functional MRI (fMRI) signals at rest while controlling for the structural atrophy. Twenty-three PD patients and 20 age, gender, and education level matched normal controls (NC) were included in this study. Resting state fMRI and structural MRI data were acquired. The resting state brain activity was measured by the regional homogeneity (ReHo) method and the grey matter (GM) volume was attained by the voxel-based morphology (VBM) analysis. Two-sample t-test was then performed to detect the group differences with structural atrophy as a covariate. VBM analysis showed GM volume reductions in the left superior frontal gyrus, left paracentral lobule, and left middle frontal gyrus in PD patients as compared to NC. There were widespread ReHo differences between NC and PD patients. Compared to NC, PD patients showed significant alterations in the motor network, including decreased ReHo in the right primary sensory cortex (S1), while increased ReHo in the left premotor area (PMA) and left dorsolateral prefrontal cortex (DLPFC). In addition, a cluster in the left superior occipital gyrus (SOG) also showed increased ReHo in PD patients. The current findings indicate that significant changes of ReHo in the motor and non-motor cortices have been detected in PD patients, independent of age, gender, education level, and structural atrophy. The present study thus suggests ReHo abnormalities as a potential biomarker for the diagnosis of PD and further provides insights into the biological mechanism of the disease.

Association of specific frequency bands of functional MRI signal oscillations with motor symptoms and depression in Parkinson's disease.

A novel empirical mode decomposition method was adopted to investigate the dissociative or interactive neural impact of depression and motor impairments in Parkinson’s disease (PD). Resting-state fMRI data of 59 PD subjects were first decomposed into characteristic frequency bands, and the main effects of motor severity and depression and their interaction on the energy of blood-oxygen-level-dependent signal oscillation in specific frequency bands were then evaluated. The results show that the severity of motor symptoms is negatively correlated with the energy in the frequency band of 0.10–0.25 Hz in the bilateral thalamus, but positively correlated with 0.01–0.027 Hz band energy in the bilateral postcentral gyrus. The severity of depression, on the other hand, is positively correlated with the energy of 0.10–0.25 Hz but negatively with 0.01–0.027 Hz in the bilateral subgenual gyrus. Notably, the interaction between motor and depressive symptoms is negatively correlated with the energy of 0.10–0.25 Hz in the substantia nigra, hippocampus, inferior orbitofrontal cortex, and temporoparietal junction, but positively correlated with 0.02–0.05 Hz in the same regions. These findings indicate unique associations of fMRI band signals with motor and depressive symptoms in PD in specific brain regions, which may underscore the neural impact of the comorbidity and the differentiation between the two PD-related disorders.

Changes in functional MRI signals after 3D based radiotherapy of glioblastoma multiforme

The purpose of our study was to examine the potential effects of conventional 3D based radiotherapy on functional MRI activation areas following the treatment of glioblastoma multiforme. Seventeen patients with a histologically proven glioblastoma multiforme were enrolled in this study. A functional MRI examination was performed alongside the planning CT and conventional MRI prior to the delivery of conventional 3D based radiotherapy. All patients received 3D based postoperative radiotherapy (up to 60 Gy) combined with temozolomide. Follow-up fMRI examinations were performed after completion of the treatment in the 6th week and in 3 months time. Changes of the task related activation areas were registered and analyzed. The difference in changes of high dose and low dose areas of the brain were also registered and analyzed. The comparison of the pretreatment and 6th week control fMRI activation areas revealed significant changes in motor activation and listening tasks in the case of brain areas which received a high dose (over 40 Gy). Based on the population level statistical parametric images (motor activation tasks) acquired at the 6th week control examination, a significant increase of signal was registered in the precuneus region and in the globus pallidus region. When comparing the 6th week and 3rd month activation signals, no significant changes were registered. Our results demonstrate the influence of radiotherapy on functional MRI signals within the human brain. Based on our findings, functional activation transfers from high dose areas to low dose areas. In case of the motor activation tasks, activations of the secondary motor area were observed following radiotherapy.

Physiologically informed dynamic causal modeling of fMRI data

The functional MRI (fMRI) signal is an indirect measure of neuronal activity. In order to deconvolve the neuronal activity from the experimental fMRI data, biophysical generative models have been proposed describing the link between neuronal activity and the cerebral blood flow (the neurovascular coupling), and further the hemodynamic response and the BOLD signal equation. These generative models have been employed both for single brain area deconvolution and to infer effective connectivity in networks of multiple brain areas. In the current paper, we introduce a new fMRI model inspired by experimental observations about the physiological underpinnings of the BOLD signal and compare it with the generative models currently used in dynamic causal modeling (DCM), a widely used framework to study effective connectivity in the brain. We consider three fundamental aspects of such generative models for fMRI: (i) an adaptive two-state neuronal model that accounts for a wide repertoire of neuronal responses during and after stimulation; (ii) feedforward neurovascular coupling that links neuronal activity to blood flow; and (iii) a balloon model that can account for vascular uncoupling between the blood flow and the blood volume. Finally, we adjust the parameterization of the BOLD signal equation for different magnetic field strengths. This paper focuses on the form, motivation and phenomenology of DCMs for fMRI and the characteristics of the various models are demonstrated using simulations. These simulations emphasize a more accurate modeling of the transient BOLD responses — such as adaptive decreases to sustained inputs during stimulation and the post-stimulus undershoot. In addition, we demonstrate using experimental data that it is necessary to take into account both neuronal and vascular transients to accurately model the signal dynamics of fMRI data. By refining the models of the transient responses, we provide a more informed perspective on the underlying neuronal process and offer new ways of inferring changes in local neuronal activity and effective connectivity from fMRI.

Sensory-Evoked Intrinsic Imaging Signals in the Olfactory Bulb Are Independent of Neurovascular Coupling.

SummaryFunctional brain-imaging techniques used in humans and animals, such as functional MRI and intrinsic optical signal (IOS) imaging, are thought to largely rely on neurovascular coupling and hemodynamic responses. Here, taking advantage of the well-described micro-architecture of the mouse olfactory bulb, we dissected the nature of odor-evoked IOSs. Using in vivo pharmacology in transgenic mouse lines reporting activity in different cell types, we show that parenchymal IOSs are largely independent of neurotransmitter release and neurovascular coupling. Furthermore, our results suggest that odor-evoked parenchymal IOSs originate from changes in light scattering of olfactory sensory neuron axons, mostly due to water movement following action potential propagation. Our study sheds light on a direct correlate of neuronal activity, which may be used for large-scale functional brain imaging.

Abnormal intrinsic brain activity patterns in leukoaraiosis with and without cognitive impairment

The amplitude of low frequency fluctuations (ALFF) from resting-state functional MRI (rs-fMRI) signals can be used to detect intrinsic spontaneous brain activity and provide valuable insights into the pathomechanism of neural disease. In this study, we recruited 56 patients who had been diagnosed as having mild to severe leukoaraiosis. According to the neuropsychological tests, they were subdivided into a leukoaraiosis with cognitive impairment group (n=28) and a leukoaraiosis without cognitive impairment group (n=28). 28 volunteers were included as normal controls. We found that the three groups showed significant differences in ALFF in the brain regions of the right inferior occipital gyrus (IOG_R), left middle temporal gyrus (MTG_L), left precuneus (Pcu_L), right superior frontal gyrus (SFG_R) and right superior occipital gyrus (SOG_R). Compared with normal controls, the leukoaraiosis without cognitive impairment group exhibited significantly increased ALFF in the IOG_R, Pcu_L, SFG_R and SOG_R. While compared with leukoaraiosis without cognitive impairment group, the leukoaraiosis with cognitive impairment group showed significantly decreased ALFF in IOG_R, MTG_L, Pcu_L and SOG_R. A close negative correlation was found between the ALFF values of the MTG_L and the Montreal Cognitive Assessment (MoCA) scores. Our data demonstrate that white matter integrity and cognitive impairment are associated with different amplitude fluctuations of rs-fMRI signals. Leukoaraiosis is related to ALFF increases in IOG_R, Pcu_L, SFG_Orb_R and SOG_R. Decreased ALFF in MTG_L is characteristic of cognitive impairment and may aid in its early detection.

Discovering frequency sensitive thalamic nuclei from EEG microstate informed resting state fMRI

Microstates (MS), the fingerprints of the momentarily and time-varying states of the brain derived from electroencephalography (EEG), are associated with the resting state networks (RSNs). However, using MS fluctuations along different EEG frequency bands to model the functional MRI (fMRI) signal has not been investigated so far, or elucidated the role of the thalamus as a fundamental gateway and a putative key structure in cortical functional networks. Therefore, in the current study, we used MS predictors in standard frequency bands to predict blood oxygenation level dependent (BOLD) signal fluctuations. We discovered that multivariate modeling of BOLD-fMRI using six EEG-MS classes in eight frequency bands strongly correlated with thalamic areas and large-scale cortical networks. Thalamic nuclei exhibited distinct patterns of correlations for individual MS that were associated with specific EEG frequency bands. Anterior and ventral thalamic nuclei were sensitive to the beta frequency band, medial nuclei were sensitive to both alpha and beta frequency bands, and posterior nuclei such as the pulvinar were sensitive to delta and theta frequency bands. These results demonstrate that EEG-MS informed fMRI can elucidate thalamic activity not directly observable by EEG, which may be highly relevant to understand the rapid formation of thalamocortical networks.

Dependence of BOLD signal fluctuation on arterial blood CO2 and O2: Implication for resting-state functional connectivity

Blood oxygenation level dependent (BOLD) functional MRI signal is known to be modulated by the CO2 level. Typically only end-tidal CO2, rather than the arterial partial pressure of CO2 (paCO2), was measured while the arterial partial pressure of O2 (paO2) level was not controlled due to free breathing, making their contribution not separable. Especially, the influences of paO2 and paCO2 on resting-state functional connectivity are not well studied. In this study, we investigated the relationship between paCO2 and resting as well as stimulus-evoked BOLD signals under hyperoxic and hypercapnic manipulation with tight control of arterial paO2. Rats under isoflurane anesthesia were subjected to six inspired gas conditions: 47% O2 in air (Normal), adding 1%, 2% or 5% CO2, carbogen (95% O2/5% CO2), and 100% O2. Somatosensory BOLD activation was significantly increased under 100% O2, while reduced with increased paCO2 levels. However, while resting BOLD connectivity pattern expanded and bilateral correlation increased under 100% O2, the correlation coefficient between the left and right somatosensory cortex was generally not dependent on paCO2 or paO2. Interestingly, the correlation in 0.04–0.07Hz range significantly increased with CO2 levels. Intracortical electrophysiological recordings showed a similar trend as the BOLD but the neurovascular coupling varied. The results suggest that paO2 and paCO2 together rather than paCO2 alone alter the BOLD signal. The response is not purely vascular in nature but has strong neuronal origins. This should be taken into consideration when designing calibrated BOLD experiment and interpreting functional connectivity data especially in aging, under drug, or neurological disorders.

Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study.

Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while performing a reward-related guessing task on two occasions, approximately one week apart. Two main contrasts were examined: right ventral striatum (VS) activation fMRI BOLD signal related to signed prediction errors (PE) and reward expectancy (RE). We also examined bilateral visual cortex activation coupled to outcome anticipation. Significant VS PE-related activity was observed at the first testing session, but at the second testing session, VS PE-related activation was significantly reduced. Conversely, significant VS RE-related activity was observed at time 2 but not time 1. Increases in VS RE-related activity from time 1 to time 2 were significantly associated with decreases in VS PE-related activity from time 1 to time 2 across participants. Intraclass correlations (ICCs) in VS were very low. By contrast, visual cortex activation had much larger ICCs, particularly in individuals with high quality data. Dynamic changes in brain activation are widely predicted, and failure to account for these changes could lead to inaccurate evaluations of the reliability of functional MRI signals. Conventional measures of reliability cannot distinguish between changes specified by algorithmic models of neural function and noisy signal. Here, we provide evidence for the former possibility: reward-related VS activations follow the pattern predicted by temporal difference models of reward learning but have low ICCs.

Metabolic resting-state brain networks in health and disease

The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood flow PET scans acquired at rest and during task performance. Consistent task-related deactivation of the "DMN-like" dominant metabolic RSN was observed in healthy subjects and early PD patients; in contrast, the subordinate RSNs were activated during task performance. Network deactivation was reduced in advanced PD; this abnormality was partially corrected by dopaminergic therapy. Time-course comparisons of DMN loss in longitudinal resting metabolic scans from PD and Alzheimer's disease subjects illustrated that significant reductions appeared later for PD, in parallel with the development of cognitive dysfunction. In contrast, in Alzheimer's disease significant reductions in network expression were already present at diagnosis, progressing over time. Metabolic imaging can directly provide useful information regarding the resting organization of the brain in health and disease.

The contribution of astrocytes to the regulation of cerebral blood flow.

In order to maintain normal brain function, it is critical that cerebral blood flow (CBF) is matched to neuronal metabolic needs. Accordingly, blood flow is increased to areas where neurons are more active (a response termed functional hyperemia). The tight relationships between neuronal activation, glial cell activity, cerebral energy metabolism, and the cerebral vasculature, known as neurometabolic and neurovascular coupling, underpin functional MRI (fMRI) signals but are incompletely understood. As functional imaging techniques, particularly BOLD fMRI, become more widely used, their utility hinges on our ability to accurately and reliably interpret the findings. A growing body of data demonstrates that astrocytes can serve as a “bridge,” relaying information on the level of neural activity to blood vessels in order to coordinate oxygen and glucose delivery with the energy demands of the tissue. It is widely assumed that calcium-dependent release of vasoactive substances by astrocytes results in arteriole dilation and the increased blood flow which accompanies neuronal activity. However, the signaling molecules responsible for this communication between astrocytes and blood vessels are yet to be definitively confirmed. Indeed, there is controversy over whether activity-induced changes in astrocyte calcium are widespread and fast enough to elicit such functional hyperemia responses. In this review, I will summarize the evidence which has convincingly demonstrated that astrocytes are able to modify the diameter of cerebral arterioles. I will discuss the prevalence, presence, and timing of stimulus-induced astrocyte calcium transients and describe the evidence for and against the role of calcium-dependent formation and release of vasoactive substances by astrocytes. I will also review alternative mechanisms of astrocyte-evoked changes in arteriole diameter and consider the questions which remain to be answered in this exciting area of research.

Altered Amplitude of Low-frequency Fluctuations in Early and Late Mild Cognitive Impairment and Alzheimer's Disease

Previous studies have shown that the strength of the low frequency fluctuation in the medial-line brain areas are abnormally reduced in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. The purpose of this study was to explore the functional brain changes in early MCI (EMCI) and late MCI (LMCI) patients by measuring the amplitude of the blood oxygenation level dependent (BOLD) functional MRI (fMRI) signals at rest. 35 elderly normal controls (NC), 24 EMCI, 29 LMCI, and 14 AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI2) were included in this study. Resting state fMRI and 3D structural MRI data were acquired. The spatial patterns of spontaneous brain activity were measured by examining the amplitude of low-frequency fluctuations (ALFF) of BOLD signal during rest. A one-way analysis of variance (ANOVA) was then performed on ALFF maps, with age, sex and regional atrophy as covariates. There were widespread ALFF differences among the four groups. As compared with controls, AD, LMCI and EMCI patients showed decreased ALFF mainly in the posterior cingulate cortex, precuneus, right lingual gyrus and thalamus (with a linear trend: NC>EMCI>LMCI>AD), while there was increased activity in the right parahippocampal gyrus (with a linear trend: NC<EMCI<LMCI<AD). Additionally, we also showed that many regions with ALFF changes had significant correlations with the cognitive performance as measured by mini-mental state examination scores (MMSE) and the emotion states as measured by Geriatric Depression Scale (GD scale) for EMCI, LMCI and AD patients, but not for controls. Our results indicated that the significantly altered ALFF activities can be detected at EMCI stage, independent of age, sex and regional atrophy. The present study thus suggests ALFF abnormalities as a potential biomarker for the early diagnosis of AD and further provides insights into biological mechanisms of the diseases.

Long-term total sleep deprivation reduces thalamic gray matter volume in healthy men

Sleep loss can alter extrinsic, task-related functional MRI signals involved in attention, memory, and executive function. However, the effects of sleep loss on brain structure have not been well characterized. Recent studies with patients with sleep disorders and animal models have demonstrated reduction of regional brain structure in the hippocampus and thalamus. In this study, using T1-weighted MRI, we examined the change of regional gray matter volume in healthy adults after long-term total sleep deprivation (~72 h). Regional volume changes were explored using voxel-based morphometry with a paired two-sample t-test. The results revealed significant loss of gray matter volume in the thalamus but not in the hippocampus. No overall decrease in whole brain gray matter volume was noted after sleep deprivation. As expected, sleep deprivation significantly reduced visual vigilance as assessed by the continuous performance test, and this decrease was correlated significantly with reduced regional gray matter volume in thalamic regions. This study provides the first evidence for sleep loss-related changes in gray matter in the healthy adult brain.