Instability of default mode network connectivity in major depression: a two-sample confirmation study.

Major depression is associated with altered static functional connectivity in various brain networks, particularly the default mode network (DMN). Dynamic functional connectivity is a novel tool with little application in affective disorders to date, and holds the potential to unravel fluctuations in connectivity strength over time in major depression. We assessed stability of connectivity in major depression between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), key nodes in the DMN that are implicated in ruminative cognitions. Functional connectivity stability between the mPFC and PCC over the course of a resting-state functional magnetic resonance imaging (fMRI) scan was compared between medication-free patients with major depression and healthy controls matched for age, sex and handedness. We tested replicability of the results in an independent sample using multi-echo resting-state fMRI. The primary sample included 20 patients and 19 controls, while the validation sample included 19 patients and 19 controls. Greater connectivity variability was detected in major depression between mPFC and PCC. This was demonstrated in both samples indicating that the results were reliable and were not influenced by the fMRI acquisition approach used. Our results demonstrate that alterations within the DMN in major depression go beyond changes in connectivity strength and extend to reduced connectivity stability within key DMN regions. Findings were robustly replicated across two independent samples. Further research is necessary to better understand the nature of these fluctuations in connectivity and their relationship to the aetiology of major depression.

Assessment of temporal state-dependent interactions between auditory fMRI responses to desired and undesired acoustic sources.

A confounding factor in auditory functional magnetic resonance imaging (fMRI) experiments is the presence of the acoustic noise inherently associated with the echo planar imaging acquisition technique. Previous studies have demonstrated that this noise can induce unwanted neuronal responses that can mask stimulus-induced responses. Similarly, activation accumulated over multiple stimuli has been demonstrated to elevate the baseline, thus reducing the dynamic range available for subsequent responses. To best evaluate responses to auditory stimuli, it is necessary to account for the presence of all recent acoustic stimulation, beginning with an understanding of the attenuating effects brought about by interaction between and among induced unwanted neuronal responses, and responses to desired auditory stimuli. This study focuses on the characterization of the duration of this temporal memory and qualitative assessment of the associated response attenuation. Two experimental parameters--inter-stimulus interval (ISI) and repetition time (TR)--were varied during an fMRI experiment in which participants were asked to passively attend to an auditory stimulus. Results present evidence of a state-dependent interaction between induced responses. As expected, attenuating effects of these interactions become less significant as TR and ISI increase and in contrast to previous work, persist up to 18s after a stimulus presentation.

Characterizing the amplitude and spatial extent of the cortical response in auditory cortex to acoustic scanner noise generated during echo-planar image acquisition in functional magnetic resonance imaging.

Acoustic scanner noise produced during event-related functional magnetic resonance imaging (ER-fMRI) studies can hinder auditory fMRI research analysis by altering the properties of the acquired time-series data. Given the desire to obtain the most accurate results possible using ER-fMRI experiments, this study seeks to characterize the amplitude and spatial extent of the auditory fMRI cortical response, in isolation, generated by the acoustic scanner noise associated with echo-planar acquisition. Results from this study indicate that the pure cortical response is non-trivial, is comparable to a standard hemodynamic response function, and should be accounted for in analysis using ER-fMRI models.

Using Johnson's transformation and robust estimators with heteroscedastic test statistics: an examination of the effects of non-normality and heterogeneity in the non-orthogonal two-way ANOVA design.

The present study proposes a procedure that combines Johnson's transformation and the trimmed means method to deal with the problem of non-normality. An approximate test such as the Alexander-Govern test or Welch-James type test is then employed to deal with the heterogeneity of cell variance in the non-orthogonal two-way fixed effects completely randomized design. Both unweighted and weighted means analyses are considered. The empirical Type I error rates and the statistical power for comparing population means are investigated by Monte Carlo simulation. The simulated results show that Johnson's transformation with trimmed mean and the approximate test is valid in terms of Type I error rate control, and that the magnitude of the statistical power for non-normal distributions is better than that of conventional methods.

Nonlinear temporal dynamics of the cerebral blood flow response.

The linearity of the cerebral perfusion response relative to stimulus duration is an important consideration in the characterization of the relationship between regional cerebral blood flow (CBF), cerebral metabolism, and the blood oxygenation level dependent (BOLD) signal. It is also a critical component in the design and analysis of functional neuroimaging studies. To study the linearity of the CBF response to different duration stimuli, the perfusion response in primary motor and visual cortices was measured during stimulation using an arterial spin labeling technique with magnetic resonance imaging (MRI) that allows simultaneous measurement of CBF and BOLD changes. In each study, the perfusion response was measured for stimuli lasting 2, 6, and 18 sec. The CBF response was found in general to be nonlinearly related to stimulus duration, although the strength of nonlinearity varied between the motor and visual cortices. In contrast, the BOLD response was found to be strongly nonlinear in both regions studied, in agreement with previous findings. The observed nonlinearities are consistent with a model with a nonlinear step from stimulus to neural activity, a linear step from neural activity to CBF change, and a nonlinear step from CBF change to BOLD signal change.

T(1) and T(2) selective method for improved SNR in CSF-attenuated imaging: T(2)-FLAIR.

We present here a method for improving SNR in CSF-attenuated imaging relative to the standard technique of using an inversion pulse and imaging at the null point of CSF. In this new method the inversion pulse is replaced with a 90(x)-180(y)-90(x) preparation sequence that provides T(1) and T(2) selectivity. This allows the tissue magnetization to recover more rapidly, allows for the use of shorter TR values, and reduces T(1) weighting. Magn Reson Med 45:529-532, 2001.

Transformation works for non-normality? On one-sample transformation trimmed t methods.

If the assumption of normality is not satisfied, there is no simple solution to this problem for the one-sample t test. The present study proposes Hall's or Johnson's transformation in conjunction with the trimmed mean to deal with the problem. Computer simulation is carried out to evaluate the small-sample behaviour of the proposed methods in terms of Type I error rate and statistical power. The proposed methods are compared with the conventional Student t, Yuen's trimmed t, Johnson's transformation untrimmed t, and Hall's transformation untrimmed t statistics for one-sided and two-sided tests. The simulation results indicate that the proposed methods can control Type I error well in very extreme conditions and are more powerful than the conventional methods.

Turbo ASL: arterial spin labeling with higher SNR and temporal resolution.

A modified pulsed arterial spin labeling (ASL) technique is introduced here that has both higher temporal resolution and higher SNR per unit time than existing ASL techniques. In this technique, the time TI between the application of the tag and image acquisition is longer than the repetition time TR, allowing for the use of greatly reduced TR values without a significant decrease in the amplitude of the ASL signal. This improves both the temporal resolution and the sensitivity of ASL for functional brain mapping.

Comparison of simultaneously measured perfusion and BOLD signal increases during brain activation with T(1)-based tissue identification.

Perfusion and blood oxygenation level-dependent (BOLD) signals were simultaneously measured during a finger-tapping task at 3T using QUIPSS II with thin-slice TI(1) periodic saturation, a modified pulsed arterial spin labeling technique that provides quantitative measurement of perfusion. Perfusion and BOLD signal changes due to motor activation were obtained and correlated with the T(1) values estimated from echo-planar imaging (EPI)-based T(1) maps on a voxel-by-voxel basis. The peak perfusion signal occurs in voxels with a T(1) of brain parenchyma while the peak BOLD signal occurs in voxels with a T(1) characteristic of blood and cerebrospinal fluid. The locations of the peak signals of functional BOLD and perfusion only partially overlap on the order of 40%. Perfusion activation maps will likely represent the sites of neuronal activity better than do BOLD activation maps. Magn Reson Med 44:137-143, 2000.

QUIPSS II with thin-slice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling.

Quantitative imaging of perfusion using a single subtraction, second version (QUIPSS II) is a pulsed arterial spin labeling (ASL) technique for improving the quantitation of perfusion imaging by minimizing two major systematic errors: the variable transit delay from the distal edge of the tagged region to the imaging slices, and the contamination by intravascular signal from tagged blood that flows through the imaging slices. However, residual errors remain due to incomplete saturation of spins over the slab-shaped tagged region by the QUIPSS II saturation pulse, and spatial mismatch of the distal edge of the saturation and inversion slice profiles. By replacing the original QUIPSS II saturation pulse with a train of thin-slice periodic saturation pulses applied at the distal end of the tagged region, the accuracy of perfusion quantitation is improved. Results of single and multislice studies are reported.

Articular cartilage in the knee: mapping of the physiologic parameters at MR imaging with a local gradient coil--preliminary results.

The authors designed and constructed a local gradient coil that produces large gradients and short rise times and connects to their clinical system. In a cadaveric patellar cartilage specimen, the coil was used to acquire images of the physiologic parameters T1, T2, proton density, and apparent diffusion coefficient. Variations in these parameters were evident in regions of normal and abnormal cartilage.

Simultaneous gradient-echo/spin-echo EPI of graded ischemia in human skeletal muscle.

The goal of this study was to evaluate the usefulness of blood oxygenation level-dependent (BOLD) methodologies to provide temporal and spatial information about skeletal muscle perfusion. A simultaneous gradient echo (GE) and spin-echo (SE) imaging sequence (GE/SE) with alternating TE was used to acquire images of leg skeletal muscle throughout a stepped reactive hyperemia paradigm. The change in both the GE and SE relaxation rates (deltaR2*, deltaR2) measured during ischemia and reactive hyperemia scaled with the duration of cuff inflation (the ischemic period) plateaued for cuff inflations lasting longer than 120 seconds and were greater in soleus muscle than in gastrocnemius. The ratio deltaR2*/deltaR2 was found to be less during the reactive hyperemia period relative to ischemia. Considering that a greater proportion of capillary vessels are perfused during reactive hyperemia than during ischemia, this finding suggests that magnetic susceptibility methodologies, with their dependence on compartment size, may provide a measure of the relative distribution of small and large vessels in skeletal muscle.

Context availability and the recall of abstract and concrete words.

Predictions of an automatic-imagery, strategic-imagery, and context-availability hypothesis of concreteness effects in free recall were examined. In each experiment, recall of abstract and concrete words controlled for rated context availability was compared with the typical situation in which context availability is confounded with imageability. In Experiment 1, a directed intentional-recall task produced concreteness effects in recall. Experiment 2 compared concreteness effects in recall following three orienting tasks: imagery rating, context-availability rating, and a directed intentional-memory task. Concreteness effects in the context-availability-controlled condition were found following the imagery-rating and the directed intentional-memory tasks, but not after the context-availability-rating task. In Experiment 3, subjects reported the strategies that they used to encode the list. Subjects reporting an imagery strategy showed concreteness effects for words controlled for rated context availability, but those not reporting it did not. These results support a strategic-imagery view of concreteness effects in free recall.

Effect of aging on phosphate metabolites of rat brain as revealed by the in vivo and in vitro 31P NMR measurements.

Changes of phosphate metabolism in brains of neonate, weaning and adult rats were compared using both in vivo and in vitro nuclear magnetic resonance spectra. Ratios of phosphocreatine/nucleoside triphosphate (PCr/NTP) were the same in neonatal brain in both in vivo and in vitro studies, but not in weaning and adult brains. This discrepancy may have resulted from extended cerebral hypoxia due to slowed freezing of the brain by the increased skull thickness and brain mass in the weaning and adult rats. Variations in in vitro extraction condition for this age-related study may lead to systematic errors in the adult rats. Nevertheless, the phosphomonoester/nucleoside triphosphate (PME/NTP) ratios in extracts of brain from neonatal rats were higher than those obtained in vivo. In addition, the glycerophosphorylethanolamine plus glycerophosphorylcholine/nucleoside triphosphate (GPE+GPC/NTP) ratios, which were not measurable in vivo, showed age-dependent increase in extracts of rat brain. Some of the phosphomonoester and phosphodiester molecules in rat brain may be undetectable in in vivo NMR analysis because of their interaction with cellular components. The total in vitro GPE and GPC concentration in brain from neonatal rat was estimated to be 0.34 mmole/g wet tissue.