Our goal was to develop a novel technique for measuring a small number of localized spectra simultaneously and in a time-efficient manner.
MATERIALS AND METHODS:
Using appropriate radiofrequency pulses, the magnetization from multiple voxels is excited simultaneously and then separated (reconstructed) by using the individual coil-sensitivity profiles from a multichannel receiver coil. Because no gradients are used for k-space encoding, constrained source space MR spectroscopy provides a time advantage over conventional spectroscopic imaging and an improved signal-to-noise ratio per square root of unit time over single-voxel spectroscopy applied at each successive location. In the present work, we considered prototype application of constrained source space MR spectroscopy for 2 voxels.
RESULTS:
Experimental data from healthy volunteers and simulation results showed that constrained source space MR spectroscopy is effective at extracting 2 independent spectra even in the challenging scenario of the voxels being closely spaced. Also, from 6 patients with various types of brain cancer we obtained 2-voxel constrained source space MR spectroscopy data, which showed spectra of clinical quality in half the time required to perform successive single-voxel MR spectroscopy.
CONCLUSIONS:
Constrained source space MR spectroscopy provides clinical quality spectra and could be used to probe multiple voxels simultaneously in combination with Hadamard encoding for further scan-time reductions.
Abstract/Summary Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked changes in theta (5-8 Hz) power, but only when stimulation was applied in or adjacent to white matter. Furthermore, these power changes aligned with control-theoretic predictions of how exogenous stimulation flows through complex networks, such as a dispersal of induced activity when functional hubs are targeted. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, but that access to structural connections is necessary to observe such effects.
Background and Significance Positron Emission Tomography (PET) using fluorodeoxyglucose (FDG-PET) is a standard imaging modality for detecting areas of hypometabolism associated with the seizure onset zone (SOZ) in temporal lobe epilepsy (TLE). However, FDG-PET is costly and involves the use of a radioactive tracer. Arterial Spin Labeling (ASL) offers an MRI-based quantification of cerebral blood flow (CBF) that could also help localize the SOZ, but its performance in doing so, relative to FDG-PET, is limited. In this study, we seek to improve ASL’s diagnostic performance by developing a deep learning framework for synthesizing FDG-PET-like images from ASL and structural MRI inputs. Methods We included 68 epilepsy patients, out of which 36 had well lateralized TLE. We compared the coupling between FDG-PET and ASL CBF values in different brain regions, as well as the asymmetry of these values across the brain. We additionally assessed each modality’s ability to lateralize the SOZ across brain regions. Using our paired PET-ASL data, we developed FlowGAN, a generative adversarial neural network (GAN) that synthesizes PET-like images from ASL and T1-weighted MRI inputs. We tested our synthetic PET images against the actual PET images of subjects to assess their ability to reproduce clinically meaningful hypometabolism and asymmetries in TLE. Results We found variable coupling between PET and ASL CBF values across brain regions. PET and ASL had high coupling in neocortical temporal and frontal brain regions (Spearman’s r > 0.30, p < 0.05) but low coupling in mesial temporal structures (Spearman’s r < 0.30, p > 0.05). Both whole brain PET and ASL CBF asymmetry values provided good separability between left and right TLE subjects, but PET (AUC = 0.96, 95% CI: [0.88, 1.00]) outperformed ASL (AUC = 0.81; 95% CI: [0.65, 0.96]). FlowGAN-generated images demonstrated high structural similarity to actual PET images (SSIM = 0.85). Globally, asymmetry values were better correlated between synthetic PET and original PET than between ASL CBF and original PET, with a mean correlation increase of 0.15 (95% CI: [0.07, 0.24], p <0.001, Cohen’s d = 0.91). Furthermore, regions that had poor ASL-PET correlation (e.g. mesial temporal structures) showed the greatest improvement with synthetic PET images. Conclusions FlowGAN improves ASL’s diagnostic performance, generating synthetic PET images that closely mimic actual FDG-PET in depicting hypometabolism associated with TLE. This approach could improve non-invasive SOZ localization, offering a promising tool for epilepsy presurgical assessment. It potentially broadens the applicability of ASL in clinical practice and could reduce reliance on FDG-PET for epilepsy and other neurological disorders.
Lewy body disorders (LBD), encompassing Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein pathology but often are accompanied by Alzheimer's disease (AD) neuropathological change (ADNC). The medial temporal lobe (MTL) is a primary locus of tau accumulation and associated neurodegeneration in AD. However, it is unclear the extent to which AD copathology in LBD (LBD/AD+) contributes to MTL-specific patterns of degeneration. We employ a MTL subregional segmentation strategy of T1-weighted (T1w) MRI in biomarker-supported or autopsy-confirmed LBD and LBD/AD+ to investigate the anatomic consequences of co-occurring LBD/AD+ pathology on neurodegeneration.
Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer's disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer's disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer's and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial temporal lobe and its immediate functional neighborhood - the Anterior-Temporal and Posterior-Medial brain networks - in normal agers, individuals with preclinical Alzheimer's disease, and patients with Mild Cognitive Impairment or mild dementia due to Alzheimer's disease. In the Anterior-Temporal network and in the perirhinal cortex, in particular, we observed an inverted 'U-shaped' relationship between functional connectivity and Alzheimer's stage. According to our results, the preclinical phase of Alzheimer's disease is characterized by increased functional connectivity between the perirhinal cortex and other regions of the medial temporal lobe, as well as between the anterior medial temporal lobe and its one-hop neighbors in the Anterior-Temporal system. This effect is no longer present in symptomatic Alzheimer's disease. Instead, patients with symptomatic Alzheimer's disease displayed reduced hippocampal connectivity within the medial temporal lobe as well as hypoconnectivity within the Posterior-Medial system. For normal aging, our results led to three main conclusions: (1) intra-network connectivity of both the Anterior-Temporal and Posterior-Medial networks declines with age; (2) the anterior and posterior segments of the medial temporal lobe become increasingly decoupled from each other with advancing age; and, (3) the posterior subregions of the medial temporal lobe, especially the parahippocampal cortex, are more vulnerable to age-associated loss of function than their anterior counterparts. Together, the current results highlight evolving medial temporal lobe dysfunction in Alzheimer's disease and indicate different neurobiological mechanisms of the medial temporal lobe network disruption in aging vs. Alzheimer's disease.
Abstract Background Tau neurofibrillary tangles (T) are thought to be the primary driver of downstream neurodegeneration (N) and subsequent cognitive impairment in AD. However, there is substantial variability in the T‐N relationship – manifested in higher or lower atrophy than expected for the level of tau in a given brain region. We quantitatively describe and categorize source(s) of variability using region‐based measures of T and N to gain insight into underlying modulatory factors, including polypathology. Method Regional cortical thickness and 18 F‐Flortaucipir SUVR were computed in 108 gray matter ROIs from cognitively‐impaired, amyloid‐positive individuals (n=137) in ADNI. ROI‐specific residuals from a robust linear fit between SUVR and cortical thickness were computed. Using a threshold of +/‐ 1.5 standard deviation (S.D.), ROIs were categorized into “positive”, “negative”, or “neutral” residual (Fig 1). The residual signs for all ROIs were used in a hierarchical clustering framework to partition the dataset. Result Six groups appear to represent different phenotypes summarized in Table 1. Overall, the groups differed in age, burden of white matter hyperintensity (WMH), clinical status, and MMSE. However, they did not differ in tau burden in key brain ROIs (e.g. inferotemporal cortex, precuneus, angular gyrus). Group 1 is largest, consisting of individuals with low residuals described as having a canonical “T‐N” relationship. Group 2 has significantly higher temporolimbic atrophy relative to tau with many cases having a pattern of atrophy suggestive of TDP‐43 copathology. Group 3 appears to be a resilient phenotype with less atrophy relative to tau in lateral cortical regions. Group 4 is similar to Group 2 with high temporal atrophy, but also more diffuse atrophy. Group 5 also displays resilience, particularly in the temporal lobe. Group 6 shows widespread higher atrophy relative to tau, has the lowest MMSE and highest WMH. Conclusion We demonstrate that a measure of deviation from a normative relationship between tau burden and neurodegeneration across brain regions in individuals on the AD continuum captures variability due to multiple underlying factors, and can reveal phenotypes, which if validated, may be helpful for identifying possible contributors to neurodegeneration in addition to tau, which may ultimately be useful for cohort selection in clinical trials.
Abstract Background Finding sensitive outcome measures for disease progression in clinical trials of preclinical Alzheimer’s disease (AD) remains challenging. We hypothesize that longitudinal network connectivity measurements of the medial temporal lobe (MTL) subregions, sites of earliest tau pathology, are more sensitive to progression at early stages than annualized subregional atrophy rates, thus, increasing power to detect a significant effect in a shorter timeframe. Method Longitudinal T1‐weighted MRI scans of 229 amyloid‐β negative (Aβ‐) controls and preclinical AD (Aβ+ controls) from ADNI were included (Table 1). Anterior/posterior hippocampus, entorhinal cortex (ERC), Brodmann areas (BA) 35 and 36, and parahippocampal cortex (PHC) were segmented in baseline MRI (Figure 1, Xie et al . 2019). Deformation‐based morphometry was used to obtain follow‐up volume measurements, which were subsequently entered in a linear regression to estimate an annualized atrophy rate for each subregion. The network measurements of strength, clustering coefficient, and local efficiency (Soto et al . 2016) were obtained from an adjacency matrix (Figure 1) whose elements represented inter‐regional covariance in volume measurements over time. At least three time points were used for each subject. The preclinical AD group was compared to the Aβ‐ controls with ANCOVA and Bonferroni correction, using age as a nuisance covariate. We compared the discriminative power of the network measurements against the atrophy rates for follow‐up MRI scans within 4, 2 and 1.5 years from baseline. Result Discriminative ability of both atrophy rates and network measurements diminishes with decreasing number of follow‐up scans. However, at least one network measurement was still significantly stronger, in absolute terms, than atrophy rates for all three follow‐up scan time periods (Tables 2,3,4, Figure 2). Even with short follow‐up (<1.5 years), a number of network measures were significant while atrophy rate was not (Table 4). Conclusion The longitudinal network measurements of the MTL subregions are sensitive to disease progression in preclinical AD to a greater extent than longitudinal atrophy rates, perhaps because they account for inter‐region interactions in the network which may capture covariance patterns relevant to the neurodegenerative process. As a result, they may serve as efficient outcome measures in clinical trials, potentially allowing treatment effects to be detected earlier.
We present cortical thickness data in amnestic Mild Cognitive Impairment (a-MCI) patients showing atrophyin both anterior and posterior medial temporal lobe (MTL) networks and their correlations with molecular biomarkers.Recent work has described two dissociable networks associated with MTL structures: (1) a 'posterior MTL network' including posterior MTL regions [hippocampal tail, parahippocampus(PHC)], posterior cingulate/precuneus, and posterior lateral parietal regions and (2) an 'anterior MTL network' comprising anterior MTL regions [hippocampal head and perirhinal cortex (PRC)], ventral and polar temporal lobe, and lateral orbitofrontal cortices (Nat Rev Neurosci 13:716-726, 2012). Alzheimer's disease (AD) is often described as a neurodegenerative disease that, at a network level, most early and significantly affects the posterior default mode network (DMN), which is essentially the posterior MTL network. However, earliest appearance of neurofibrillary tangles in anterior MTL regions, such as PRC, suggests potential early involvement of the anterior MTL network. Here we study cortical atrophy in both networks and analyze their relationship with measurements of Aβ and pTauin prodromal AD. We labeled four seed regions in anterior and posterior MTL: PRC and hippocampal head (anterior) and PHC and hippocampal tail (posterior). We used these seeds to map anterior and posterior MTL networks in older healthy controls (OHC) from a Penn cohort using resting-state functional MRI. Defined networks were used as ROIs to calculate mean cortical thickness in a subset of the ADNI2 subjects (37 OHC, 55 MCI) and compared across groups. Correlation of network thickness with CSF tau and Aβwere explored in MCI. Cortical thickness was significantly reduced in MCI not only within posterior MTL networks, but to a similar extent in anterior networks, defined by hippocampal head and PRC. Increased pTau was significantly correlated with greater thinning in both anterior and posterior networks, whereas lowerAβ appeared to be somewhat more strongly correlated with the posterior network. The data presented here argue that atrophy in prodromal AD is not limited to posterior regions of the DMN, but also similarly to cortical regions functionally connected with anterior MTL, sites of earliest tangle pathology, perhaps consistent with models of network level transmission of disease. Cortical regions belonging to anterior and posterior MTL networks defined in a separate cohort of OHC subjects. Magenta shows over lap of networks defined by both seeds.
Psychophysical experiments are described that measure the sensitivity to motion features in point light displays of biological motion. Three motion features were investigated: the relative motion of the thighs, the relative motion of the thigh and leg, and the velocity profile of the leg. The perceptual threshold for discriminating a change in each motion feature was compared in upright and inverted point light displays. We find that subjects are more sensitive to two of the motion features in the upright display configuration (relative motion of thighs, relative motion of thigh and leg), but more sensitive to the third feature (velocity profile of the leg) in the inverted configuration. We propose that perceptual sensitivity to features used in biological motion perception should be greater in upright versus inverted displays. The results suggest that motion features differ in salience in biological motion perception.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
