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Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of −25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2; susceptometry‐based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: −0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function. [ABSTRACT FROM AUTHOR]

Putative MRI markers of iron in deep gray matter have demonstrated age related changes during discrete periods of healthy childhood or adulthood, but few studies have included subjects across the lifespan. This study reports both transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) of four primary deep gray matter regions (thalamus, putamen, caudate, and globus pallidus) in 498 healthy individuals aged 5–90 years. In the caudate, putamen, and globus pallidus, increases of QSM and R2* were steepest during childhood continuing gradually throughout adulthood, except caudate susceptibility which reached a plateau in the late 30s. The thalamus had a unique profile with steeper changes of R2* (reflecting additive effects of myelin and iron) than QSM during childhood, both reaching a plateau in the mid‐30s to early 40s and decreasing thereafter. There were no hemispheric or sex differences for any region. Notably, both R2* and QSM values showed more inter‐subject variability with increasing age from 5 to 90 years, potentially reflecting a common starting point in iron/myelination during childhood that diverges as a result of lifestyle and genetic factors that accumulate with age. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the clinical stratification of amyotrophic lateral sclerosis (ALS) patients in relation to in vivo cerebral degeneration. One hundred forty-nine ALS patients and one hundred forty-four healthy controls (HCs) were recruited from the Canadian ALS Neuroimaging Consortium (CALSNIC). Texture analysis was performed on T1-weighted scans to extract the texture feature "autocorrelation" (autoc), an imaging biomarker of cerebral degeneration. Patients were stratified at baseline into early and advanced disease stages based on criteria adapted from ALS clinical trials and the King's College staging system, as well as into slow and fast progressors (disease progression rates, DPR). Patients had increased autoc in the internal capsule. These changes extended beyond the internal capsule in early-stage patients (clinical trial-based criteria), fast progressors, and in advanced-stage patients (King's staging criteria). Longitudinal increases in autoc were observed in the postcentral gyrus, corticospinal tract, posterior cingulate cortex, and putamen; whereas decreases were observed in corpus callosum, caudate, central opercular cortex, and frontotemporal areas. Both longitudinal increases and decreases of autoc were observed in non-overlapping regions within insula and precentral gyrus. Within-criteria comparisons of autoc revealed more pronounced changes at baseline and longitudinally in early- (clinical trial-based criteria) and advanced-stage (King's staging criteria) patients and fast progressors. In summary, comparative patterns of baseline and longitudinal progression in cerebral degeneration are dependent on sub-group selection criteria, with clinical trial-based stratification insufficiently characterizing disease stage based on pathological cerebral burden. [ABSTRACT FROM AUTHOR]

The role played by medial prefrontal cortex (MPFC) glutamate (Glu) and gamma-aminobutyric acid (GABA) in the pathophysiology and the treatment of major depression (MD) is increasingly recognized. Although measurements of MPFC GABA and Glu have been shown to be sensitive to physiological fluctuations of female hormones, none of the magnetic resonance spectroscopy (MRS) investigations of MPFC Glu and GABA in MD have controlled for possible bias effect of the reproductive stage of the women included. MPFC Glu and GABA+ (which include homocarnosine and macromolecules) referenced to creatine and phosphocreatine, were measured via magnetic resonance spectroscopy (MRS) using a 3-Tesla magnet in 24 women with MD and 24 healthy women paired for reproductive status. All participants were unmedicated. There were no statistical differences in either MPFC Glu [95 % CI: (−0.025, 0.034)] or MPFC GABA+ [95 % CI: (−0.005, 0.017)] between women with MD and healthy controls. Our investigation does not support abnormalities in measurement of MPFC Glu and GABA in MD women when stringent control for reproductive status is performed. As a result of the inherent limitations of MRS methodology, our results do not preclude glutamatergic and GABAergic dysregulations in the MPFC of women with MD. • A stringent control for reproductive status was performed for healthy females and females experiencing depression. • All participants were age and sex matched. • MPFC Glu and GABA+ were not significantly different between groups when reproductive status was controlled. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether textures computed from T1‐weighted (T1W) images of the corticospinal tract (CST) in amyotrophic lateral sclerosis (ALS) are associated with degenerative changes evaluated by diffusion tensor imaging (DTI). Nineteen patients with ALS and 14 controls were prospectively recruited and underwent T1W and diffusion‐weighted magnetic resonance imaging. Three‐dimensional texture maps were computed from T1W images and correlated with the DTI metrics within the CST. Significantly correlated textures were selected and compared within the CST for group differences between patients and controls using voxel‐wise analysis. Textures were correlated with the patients' clinical upper motor neuron (UMN) signs and their diagnostic accuracy was evaluated. Voxel‐wise analysis of textures and their diagnostic performance were then assessed in an independent cohort with 26 patients and 13 controls. Results showed that textures autocorrelation, energy, and inverse difference normalized significantly correlated with DTI metrics (p < .05) and these textures were selected for further analyses. The textures demonstrated significant voxel‐wise differences between patients and controls in the centrum semiovale and the posterior limb of the internal capsule bilaterally (p < .05). Autocorrelation and energy significantly correlated with UMN burden in patients (p < .05) and classified patients and controls with 97% accuracy (100% sensitivity, 92.9% specificity). In the independent cohort, the selected textures demonstrated similar regional differences between patients and controls and classified participants with 94.9% accuracy. These results provide evidence that T1‐based textures are associated with degenerative changes in the CST. [ABSTRACT FROM AUTHOR]

Objective: To evaluate cerebral degenerative changes in ALS and their correlates with survival using 3D texture analysis. Methods: A total of 157 participants were included in this analysis from four neuroimaging studies. Voxel‐wise texture analysis on T1‐weighted brain magnetic resonance images (MRIs) was conducted between patients and controls. Patients were divided into long‐ and short‐survivors using the median survival of the cohort. Neuroanatomical differences between the two survival groups were also investigated. Results: Whole‐brain analysis revealed significant changes in image texture (FDR P < 0.05) bilaterally in the motor cortex, corticospinal tract (CST), insula, basal ganglia, hippocampus, and frontal regions including subcortical white matter. The texture of the CST correlated (P < 0.05) with finger‐ and foot‐tapping rate, measures of upper motor neuron function. Patients with a survival below the media of 19.5 months demonstrated texture change (FDR P < 0.05) in the motor cortex, CST, basal ganglia, and the hippocampus, a distribution which corresponds to stage 4 of the distribution TDP‐43 pathology in ALS. Patients with longer survival exhibited texture changes restricted to motor regions, including the motor cortex and the CST. Interpretation: Widespread gray and white matter pathology is evident in ALS, as revealed by texture analysis of conventional T1‐weighted MRI. Length of survival in patients with ALS is associated with the spatial extent of cerebral degeneration. [ABSTRACT FROM AUTHOR]

Background: To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI). Methods: Twenty‐seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract‐based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole‐brain microstructural abnormalities in patients. Results: In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p <.017). Along‐the‐tract analysis revealed changes concentrated in the posterior limb of the internal capsule, corona radiata, and primary motor cortex (false‐discovery rate p <.05). FA of the left CST correlated with disease progression rate, whereas MK of the bilateral CST correlated with UMN burden (p <.01). TBSS results corroborated along‐tract analysis findings and additionally revealed reduced RK and MK in the fornix, where diffusion tensor imaging (DTI) changes were absent. Conclusion: DKI abnormalities in the CST and CC are present in patients with UMN dysfunction, potentially revealing complementary information to DTI regarding the pathology and microstructural alterations occurring in such patients. DKI shows promise as a potential in vivo biomarker for cerebral degeneration in amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

Background: Deep gray matter (DGM) is affected in relapsing–remitting multiple sclerosis (RRMS) and may be studied using short-term longitudinal MRI. Objective: To investigate two-year changes in spin-echo transverse relaxation rate (R2) and atrophy in DGM, and its relationship with disease severity in RRMS patients. Methods: Twenty six RRMS patients and 26 matched controls were imaged at 4.7 T. Multiecho spin-echo R2 maps and atrophy measurements were obtained in DGM at baseline and two-year follow-up. Differences between MRI measures and correlations to disease severity were examined. Results: After two years, mean R2 values in the globus pallidus and pulvinar increased by ~4% (p<0.001) in patients and <1.7% in controls. Two-year changes in R2 showed significant correlation to disease severity in the globus pallidus, pulvinar, substantia nigra, and thalamus. Multiple regression of the two-year R2 difference using these four DGM structures as variables, yielded high correlation with disease severity (r=0.83, p<0.001). Two-year changes in volume and R2 showed significant correlation only for the globus pallidus in multiple sclerosis (MS) (p<0.05). Conclusions: Two-year difference R2 measurements in DGM correlate to disease severity in MS. R2 mapping and atrophy measurements over two years can be used to identify changes in DGM in MS. [ABSTRACT FROM AUTHOR]

Background: In addition to neuronal injury, inflammatory, and demyelinating processes, evidence suggests multiple sclerosis (MS) is also associated with increased iron deposition in the basal ganglia. Magnetic resonance imaging (MRI), particularly at very high field strengths, is sensitive to iron accumulation and may enable visualization and quantification of iron associated with MS.Objectives: To investigate the sub-cortical gray matter in patients with early-stage relapsing–remitting MS using multiple, and novel, quantitative MRI measures at very high field.Methods: In total, 22 patients with relapsing–remitting MS and 22 control subjects were imaged at 4.7 Tesla. Transverse relaxation rates (R2 and R2*) and susceptibility phase were quantified in four basal ganglia nuclei, the thalamus, and the red nuclei. Parameters in patients with MS were compared with those in healthy subjects and correlated with clinical scores.Results: Significant abnormalities were observed in most structures, most notably in the pulvinar sub-nucleus. Significant correlations with disability were observed in the pulvinar; marginally significant correlations were also observed in the thalamus and red nucleus. No significant correlations were observed with duration since index relapse.Conclusions: Widespread abnormalities are present in the deep gray matter nuclei of patients recently diagnosed with MS; these abnormalities can be detected via multi-modal high-field MRI. Imaging metrics, particularly R2*, relate to disease severity in the pulvinar and other gray matter regions. [ABSTRACT FROM AUTHOR]

Background: Previous magnetic resonance imaging (MRI) studies of patients with major depressive disorder (MDD) have consistently shown bilateral and unilateral reductions in hippocampal volume relative to healthy controls. Recent structural MRI studies have addressed the question of whether changes in the volume of hippocampal subregions may be associated with MDD. Methods: We used a comprehensive and reliable 3-dimensional tracing protocol that enables delineation of hippocampal subregions (head, body, tail) to study changes in the hippocampus of patients with MDD. We recruited 39 MDD patients (16 medicated, 23 unmedicated) and 34 healthy age- and sex-matched controls. We acquired images using a magnetization-prepared rapid acquisition gradient echo sequence on a 1.5-T scanner with a spatial resolution of 1.5 mm x 0.5 mm x 0.5 mm. We performed volumetric analyses, blinded to diagnosis, using the interactive software package Display. All volumes were adjusted for intracranial volume. Results: We found a significant reduction in the volume of the hippocampal tail bilaterally, right hippocampal head and right total hippocampus in MDD patients. Medicated MDD patients showed increased hippocampal body volume compared with both healthy controls and unmedicated patients. Limitations: This study was cross-sectional. Further prospective studies are needed to determine the direct effect of antidepressant treatment. Conclusion: Our results suggest that decreased hippocampal tail and hippocampal head volumes could be trait changes, whereas hippocampal body changes may be dependent on treatment. We showed that long-term antidepressant treatment may affect hippocampal volume in patients with MDD. [ABSTRACT FROM AUTHOR]

Abstract: Diffusion tensor imaging (DTI) provides the opportunity to study white matter tracts in vivo. The goal was to estimate the reliability of DTI tractography for the analysis of limbic and paralimbic white matter. Normative data from 24 healthy subjects and reliability data from four healthy and four depressed subjects were acquired at 1.5 Tesla, using twice-refocused spin-echo, echoplanar DTI and Fluid-Attenuated Inversion Recovery (FLAIR) DTI sequences. Fiber tracking was performed using the Fiber Assignment by Continuous Tracking algorithm. Fractional Anisotropy (FA), trace Apparent Diffusion Coefficient and tract volumes were calculated. The inter-rater (and intra-rater) intraclass correlation coefficients for FA values were as follows: rostral cingulum 0.89 (0.87), dorsal cingulum 0.85 (0.90), parahippocampal cingulum 0.85 (0.95), uncinate fasciculus 0.85 (0.87), medial prefrontal white matter 0.97 (0.99), ventromedial prefrontal white matter 0.92 (0.93), crus of fornix 0.80 (0.81). The reported DTI protocol provides a reliable method to analyze limbic and paralimbic white matter tracts relevant to psychiatric disorders. [Copyright &y& Elsevier]

Objective: High-field strength proton magnetic resonance spectroscopy (¹H-MRS) and peripheral blood analyses reported in the literature reveal glutamate (Glu) and glutamine (Gln) abnormalities in schizophrenia. Given the relative ease and feasibility of using peripheral measures, the present study investigates the relation between peripheral and brain Glu and Gln levels. Methods: We recruited healthy volunteers (n = 17, mean age 21.9 [standard deviation 2.9, range 18-29] yr) between May and December 2005. All participants underwent 3 Tesla ¹H-MRS analysis with segmentation (grey matter, white matter, cerebrospinal fluid) at the Nuclear Magnetic Resonance Centre at the University of Alberta Hospital to quantify medial prefrontal cortical (mPFC) Glu and Glx (i.e., combination of Glu and Gln). Within 1 week of ¹H-MRS analysis, we collected plasma from the same participants for Glu and Gln quantification, using high-performance liquid chromatography at the Neurochemical Research Unit at the University of Alberta. Results: There was no correlation between plasma Glu and either medial prefrontal cortical Glu or Glx (R1,15 = 0.019, p = 0.944 and R1,15 = 0.081, p = 0.757, respectively). Similarly, there was no correlation between plasma Gln and either mPFC Glu or Glx (R1,15 = 0.029, p = 0.911 and R1,15 = 0.025, p = 0.925, respectively). Conclusion: Our findings support the use of ¹H-MRS, instead of peripheral blood analysis, for investigating glutamatergic dysfunction in the brain. [ABSTRACT FROM AUTHOR]

Background: Medically-refractory trigeminal neuralgia (TN) can be treated successfully with operative intervention, but a significant proportion of patients are non-responders despite undergoing technically successful surgery. The thalamus is a key component of the trigeminal sensory pathway involved in transmitting facial pain, but the role of the thalamus in TN, and its influence on durability of pain relief after TN surgery, are relatively understudied. We aimed to test the hypothesis that variations in thalamic structure and metabolism are related to surgical non-response in TN.Methods: We performed a longitudinal, peri-operative neuroimaging study of the thalamus in medically-refractory TN patients undergoing microvascular decompression or percutaneous balloon compression rhizotomy. Patients underwent structural MRI and MR spectroscopy scans pre-operatively and at 1-week following surgery, and were classified as responders or non-responders based on 1-year post-operative pain outcome. Thalamus volume, shape, and metabolite concentration (choline/creatine [Cho/Cr] and N-acetylaspartate/creatine [NAA/Cr]) were evaluated at baseline and 1-week, and compared between responders, non-responders, and healthy controls.Results: Twenty healthy controls and 23 patients with medically-refractory TN treated surgically (17 responders, 6 non-responders) were included. Pre-operatively, TN patients as a group showed significantly larger thalamus volume contralateral to the side of facial pain. However, vertex-wise shape analysis showed significant contralateral thalamus volume reduction in non-responders compared to responders in an axially-oriented band spanning the outer thalamic circumference (peak p = 0.019). Further, while pre-operative thalamic metabolite concentrations did not differ between responders and non-responders, as early as 1-week after surgery, long-term non-responders showed a distinct decrease in contralateral thalamic Cho/Cr and NAA/Cr, irrespective of surgery type, which was not observed in responders.Conclusions: Atrophy of the contralateral thalamus is a consistent feature across patients with medically-refractory TN. Regional alterations in preoperative thalamic structure, and very early post-operative metabolic changes in the thalamus, both appear to influence the durability of pain relief after TN surgery. [ABSTRACT FROM AUTHOR]

Functional changes in the aging human brain have been previously reported using functional magnetic resonance imaging (fMRI). Earlier resting-state fMRI studies revealed an age-associated weakening of intra-system functional connectivity (FC) and age-associated strengthening of inter-system FC. However, the majority of such FC studies did not investigate the relationship between age and network amplitude, without which correlation-based measures of FC can be challenging to interpret. Consequently, the main aim of this study was to investigate how three primary measures of resting-state fMRI signal—network amplitude, network topography, and inter-network FC—are affected by healthy cognitive aging. We acquired resting-state fMRI data on a 4.7 T scanner for 105 healthy participants representing the entire adult lifespan (18–85 years of age). To study age differences in network structure, we combined ICA-based network decomposition with sparse graphical models. Older adults displayed lower blood-oxygen-level-dependent (BOLD) signal amplitude in all functional systems, with sensorimotor networks showing the largest age differences. Our age comparisons of network topography and inter-network FC demonstrated a substantial amount of age invariance in the brain's functional architecture. Despite architecture similarities, old adults displayed a loss of communication efficiency in our inter-network FC comparisons, driven primarily by the FC reduction in frontal and parietal association cortices. Together, our results provide a comprehensive overview of age effects on fMRI-based FC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study is to assess amide concentration changes in ALS patients compared with healthy controls by using quantitative amide proton transfer (APT) and multiparameter magnetic resonance imaging, and testing its correlation with clinical scores. Methods: Sixteen ALS patients and sixteen healthy controls were recruited as part of the Canadian ALS Neuroimaging Consortium, and multimodal magnetic resonance imaging was performed at 3 T, including APT and diffusion imaging. Lorentz fitting was used to quantify the amide effect. Clinical disability was evaluated using the revised ALS functional rating scale (ALSFRS-R), and its correlation with image characteristics was assessed. The diagnostic performance of different imaging parameters was evaluated with receiver operating characteristic analysis. Results: Our results showed that the amide peak was significantly different between the motor cortex and other gray matter territories within the brain of ALS patients (p < 0.001). Compared with controls, amide signal intensities in ALS were significantly reduced in the motor cortex (p < 0.001) and corticospinal tract (p = 0.046), while abnormalities were not detected using routine imaging methods. There was no significant correlation between amide and ALSFRS-R score. The diagnostic accuracy of the amide peak was superior to that of diffusion imaging. Conclusions: This study demonstrated changes of amide signal intensities in the motor cortex and corticospinal tract of ALS patients. Key Points: • The neurodegenerative disease amyotrophic lateral sclerosis (ALS) has a lack of objective imaging indicators for diagnosis and assessment. • Analysis of amide proton transfer imaging revealed changes in the motor cortex and corticospinal tract of ALS patients that were not visible on standard magnetic resonance imaging. • The diagnostic accuracy of the amide peak was superior to that of diffusion imaging. [ABSTRACT FROM AUTHOR]

The overall goal of this work was to create a high-resolution MRI atlas of the lumbosacral enlargement of the spinal cord of the rat (Sprague–Dawley), cat, domestic pig, rhesus monkey, and human. These species were chosen because they are commonly used in basic and translational research in spinal cord injuries and diseases. Six spinal cord specimens from each of the studied species (total of 30 specimens) were fixed, extracted, and imaged. Sizes of the spinal cord segments, cross-sectional dimensions, and locations of the spinal cord gray and white matter were quantified and compared across species. The lumbar enlargement spans spinal cord levels L3-S1 in rats, L4-S1 in cats, L3-S1 in pigs, L2/L3-L7/S1 in monkeys, and T12/L1-S1/S2 in humans. The enlargements in pigs and humans are largest and most similar in size (length and cross-sectional area); followed by monkeys and cats; and followed by rats. The obtained atlas establishes a neuroanatomical reference for the intact lumbosacral spinal cord in these species. It can also be used to guide the planning of surgical procedures of the spinal cord and technology design and development of spinal cord neuroprostheses, as well as precise delivery of cells/drugs into target regions within the spinal cord parenchyma. [ABSTRACT FROM AUTHOR]

Background: Reductions in total hippocampus volume have frequently been reported in MRI studies in major depressive disorder (MDD), but reports of differences in total amygdala volume have been inconsistent. Childhood maltreatment is an important risk factor for MDD in adulthood and may affect the volume of the hippocampus and amygdala. In the present study, we examined associations between the volumes of the amygdala subnuclei and hippocampal subfields and history of childhood maltreatment in participants with MDD. Methods: We recruited 35 patients who met the DSM-IV criteria for MDD and 35 healthy controls. We acquired MRI data sets on a 4.7 T Varian Inova scanner. We manually delineated the amygdala subnuclei (lateral, basal and accessory basal nuclei, and the cortical and centromedial groups) and hippocampal subfields (cornu ammonis, subiculum and dentate gyrus) using reliable volumetric methods. We assessed childhood maltreatment using the Childhood Trauma Questionnaire in participants with MDD. Results: In participants with MDD, a history of childhood maltreatment had significant negative associations with volume in the right amygdala, anterior hippocampus and total cornu ammonis subfield bilaterally. For volumes of the amygdala subnuclei, such effects were limited to the basal, accessory basal and cortical subnuclei in the right hemisphere, but they did not survive correction for multiple comparisons. We did not find significant effects of MDD or antidepressant treatment on volumes of the amygdala subnuclei. Limitations: Our study was a cross-sectional study. Conclusion: Our results provide evidence of negative associations between history of childhood maltreatment and volumes of medial temporal lobe structures in participants with MDD. This may help to identify potential mechanisms by which maltreatment leads to clinical impacts. [ABSTRACT FROM AUTHOR]

Abstract The functional role of the hippocampal formation in episodic memory has been studied using functional magnetic resonance imaging (fMRI) for many years. The hippocampus can be segmented into three major anteroposterior sections, called head, body and tail, and into the Cornu Ammonis (CA), dentate gyrus (DG), and subiculum (Sub) subfields based on its transverse axis. However, the exact role of these subregions and subfields in memory processes is less understood. In the present study we combined ultra-high-resolution structural Magnetic Resonance Imaging (MRI) at 4.7 T with an event-related high-resolution fMRI paradigm based on the 'Designs' subtest of the Wechsler Memory Scale to investigate how the hippocampal subfields and longitudinal subregions are involved in encoding and retrieval of item, spatial, and associative memories. Our results showed that during memory encoding, regardless of the type of memory being learned, all subregions and all subfields were active. During the retrieval phase, on the other hand, we observed an anterior to posterior gradient in hippocampal activity for all subfields and all types of memory. Our findings also confirmed presence of an anterior to posterior gradient in hippocampal activity during spatial learning. Comparing subfield activities to each other revealed that the DG was more active than the CA1-3 and Sub during both encoding and retrieval. Finally, our results showed that for every subfield, encoding vs. retrieval activity differences were larger in the hippocampal head than in the hippocampal body and tail. Furthermore, these encoding vs. retrieval activity differences were similar in all subfields, highlighting the importance of studying both the longitudinal and transverse axis specialization simultaneously. Current findings further elucidate the structure–function relationship between the human hippocampus and episodic memory. Highlights • Hippocampus responded similarly during item, spatial, and associative learning. • The entire hippocampus was active during memory encoding. • Retrieval activity was characterized by an anterior to posterior gradient. • Dentate gyrus showed the largest BOLD activity during both encoding and retrieval. • Both the longitudinal and transverse properties characterize hippocampal function. [ABSTRACT FROM AUTHOR]

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by motor neuron degeneration. Significant research has begun to establish brain magnetic resonance imaging (MRI) as a potential biomarker to diagnose and monitor the state of the disease. Deep learning has emerged as a prominent class of machine learning algorithms in computer vision and has shown successful applications in various medical image analysis tasks. However, deep learning methods applied to neuroimaging have not achieved superior performance in classifying ALS patients from healthy controls due to insignificant structural changes correlated with pathological features. Thus, a critical challenge in deep models is to identify discriminative features from limited training data. To address this challenge, this study introduces a framework called S F 2 F o r m e r , which leverages the power of the vision transformer architecture to distinguish ALS subjects from the control group by exploiting the long-range relationships among image features. Additionally, spatial and frequency domain information is combined to enhance the network's performance, as MRI scans are initially captured in the frequency domain and then converted to the spatial domain. The proposed framework is trained using a series of consecutive coronal slices and utilizes pre-trained weights from ImageNet through transfer learning. Finally, a majority voting scheme is employed on the coronal slices of each subject to generate the final classification decision. The proposed architecture is extensively evaluated with multi-modal neuroimaging data (i.e., T1-weighted, R2*, FLAIR) using two well-organized versions of the Canadian ALS Neuroimaging Consortium (CALSNIC) multi-center datasets. The experimental results demonstrate the superiority of the proposed strategy in terms of classification accuracy compared to several popular deep learning-based techniques. • We propose a novel vision transformer model to classify ALS from healthy controls. • We analyze two independent and extensive datasets of 120 and 232 MRI scans. • We leverage multi-center and multi-modal neuroimaging data (T1W, R2*, and FLAIR). • The proposed method demonstrates state-of-the-art classification accuracy. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data connecting the metabolic and cognitive functioning of abstinent cocaine users. This is a pressing public health concern as approximately 1% of the Canadian population and 0.4% of the global population is estimated to have used cocaine in the past year.Methods: Our clinical study compared the in vivo neurochemical profiles in the prefrontal cortex to cognitive tests associated with the same region in 21 moderate term abstinent cocaine users (average 187days abstinent, range 15-1432days), and 30 healthy controls using 3T 1H MRS.Results: The abstinent cocaine users exhibited a 10% decrease in N-acetylaspartate (NAA) relative to healthy control subjects (p<0.01, Cohen's d=1.15). When subdivided by method of administration, a significant decrease in glutamate levels in former crack smokers compared to healthy controls (p<0.05) was observed, this decrease was not present in powder users. Abstinent users were significantly worse than healthy controls on the Trail Making Test B (p<0.05), and performance on this task was inversely related to NAA levels (p<0.05). Abstinent cocaine users showed deficits in the Wisconsin card sorting test with failures to maintain set (p<0.01).Conclusions: Our work suggests that there are subtle but important changes in the brain that remain even with the moderate term cessation of cocaine use. [ABSTRACT FROM AUTHOR]

Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract-based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain-specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co-localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249-1268, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis in major depressive disorder (MDD) is among the most consistently replicated biological findings in psychiatry. Magnetic resonance imaging (MRI) studies have consistently demonstrated that hippocampal (HC) volume is decreased in patients with MDD. The improved spatial resolution of high field strength MRI has recently enabled measurements of HC subfield volumes in vivo. The main goal of the present study was to examine the relationship between cortisol concentrations over a day and HC subfield volumes in patients with MDD compared to healthy controls and to investigate whether diurnal cortisol measures are related to memory performance. Fourteen MDD patients with moderate or severe episodes were recruited, together with 14 healthy controls. Imaging was performed using a 4.7T whole-body imaging system. HC subfields and subregions were segmented manually using previously defined protocol. Memory performance was assessed using the Wechsler Memory Scale IV. The salivary cortisol levels were measured over the course of one day. We found that cortisol awakening response to 8h (CAR-8h) was higher in MDD patients compared to controls and that this increase in CAR-8h in MDD patients correlated negatively with left total Cornu Ammonis (CA)1-3 and left HC head volume. In healthy controls mean cortisol levels were negatively associated with right total CA1-3, right HC head, and right total HC volume. In addition, in healthy controls higher CAR-8h was related to worse performance on the immediate content memory. These results provide the first in vivo evidence of the negative associations between cortisol level, CA1-3 HC subfield volume and memory performance in patients with MDD and healthy controls. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by degeneration of upper motor neurons (UMN) arising from the motor cortex in the brain and lower motor neurons (LMN) in the brainstem and spinal cord. Cerebral changes create differences in brain activity captured by functional magnetic resonance imaging (fMRI), including the spontaneous and simultaneous activity occurring between regions known as the resting state networks (RSNs). Progressive neurodegeneration as observed in ALS may lead to a disruption of RSNs which could provide insights into the disease process. Previous studies have reported conflicting findings of increased, decreased, or unaltered RSN functional connectivity in ALS and do not report the contribution of UMN changes to RSN connectivity. We aimed to bridge this gap by exploring two networks, the default mode network (DMN) and the sensorimotor network (SMN), in 21 ALS patients and 40 age-matched healthy volunteers. An UMN score dichotomized patients into UMN+ and UMN- groups. Subjects underwent resting state fMRI scan on a high field MRI operating at 4.7 tesla. The DMN and SMN changes between subject groups were compared. Correlations between connectivity and clinical measures such as the ALS Functional Rating Scale—Revised (ALSFRS-R), disease progression rate, symptom duration, UMN score and finger tapping were assessed. Significant group differences in resting state networks between patients and controls were absent, as was the dependence on degree of UMN burden. However, DMN connectivity was increased in patients with greater disability and faster progression rate, and SMN connectivity was reduced in those with greater motor impairment. These patterns of association are in line with literature supporting loss of inhibitory interneurons. [ABSTRACT FROM AUTHOR]

The involvement of the human amygdala in emotion-related processing has been studied using functional magnetic resonance imaging (fMRI) for many years. However, despite the amygdala being comprised of several subnuclei, most studies investigated the role of the entire amygdala in processing of emotions. Here we combined a novel anatomical tracing protocol with event-related high-resolution fMRI acquisition to study the responsiveness of the amygdala subnuclei to negative emotional stimuli and to examine intra-amygdala functional connectivity. The greatest sensitivity to the negative emotional stimuli was observed in the centromedial amygdala, where the hemodynamic response amplitude elicited by the negative emotional stimuli was greater and peaked later than for neutral stimuli. Connectivity patterns converge with extant findings in animals, such that the centromedial amygdala was more connected with the nuclei of the basal amygdala than with the lateral amygdala. Current findings provide evidence of functional specialization within the human amygdala. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Patients with MDD have consistently demonstrated worse performance than healthy controls a number of memory tests. Memory functions within the hippocampus in healthy younger subjects appear to be linked to cornu ammonis (CA1-3) and dentate gyrus (DG) subfields. Therefore, the main goal of the present study was to investigate whether memory deficits in MDD patients are related to reduction in hippocampal subfields volumes, particularly DG and CA 1-3.Methods: 15 MDD patients meeting DSM-IV criteria for MDD with moderate or severe episodes were recruited, together with 15 healthy controls. We used T2-weighted 2D Fast Spin Echo (FSE) and T1-weighted 3D MPRAGE sequences at 4.7 T to compare hippocampal subfield volumes at 0.09 μl voxel volume. Participants were administered the Wechsler Memory Scale.Results: MDD patients underperformed in several episodic visual memory tasks, as well as in visual working memory, compared to healthy controls. Global hippocampal volumes were similar between groups; however, MDD patients showed significantly reduced DG volumes within the hippocampal body. Duration of depression correlated with MDD patients׳ total volumes in the hippocampal body and CA1-3 and DG subfields within it.Limitations: Our study sample was relatively small and the majority of patients were on antidepressant treatment.Conclusions: Our findings suggest that DG volumes in particular may be worthy of further study to further elucidate their precise role in MDD, both by itself as well as in relation to memory. [ABSTRACT FROM AUTHOR]

The presence of metallic compounds in facial cosmetics and permanent tattoos may affect the quality of magnetic resonance imaging. We report a case study describing a signal artifact due to the use of a leave-on powdered hair dye. On reviewing the ingredients of the product, it was found to contain several metallic compounds. In lieu of this observation, we suggest that MRI centers include the use of metal- or mineral-based facial cosmetics or hair products in their screening protocols. [ABSTRACT FROM AUTHOR]

Acute symptoms of methamphetamine-induced psychosis are similar to those of primary schizophrenia. Understanding similarities or differences in the biological substrate of these psychoses could lead to early differentiation of these two clinical conditions resulting in more efficient treatment strategies. Proton magnetic resonance spectroscopy was acquired from the medial prefrontal cortex in 29 unmedicated patients with first episode of psychosis (FEP), 29 abstinent methamphetamine-addicted people (METH) and 45 healthy controls (HCs) (age range 17.3 to 29.9years old). The METH group displayed robust reductions in concentration levels of glutamate (Glu) relative to FEP (Cohen's d=1.20) and HC (d=0.87). The METH group also displayed reduced levels of N-acetylaspartate (NAA) relative to FEP (d=0.53) and HC (d=0.76). The HC group displayed a positive association between levels of Glu and NAA, r(45)=0.52, p<0.001, while the two clinical groups failed to show this normal association. This suggests that the cellular metabolism is altered in both conditions. These data support the assumption that cellular abnormalities differ between primary schizophrenia and methamphetamine addiction despite the overlap in clinical presentation. [ABSTRACT FROM AUTHOR]

Acute symptoms of methamphetamine-induced psychosis are similar to those of primary schizophrenia. Understanding similarities or differences in the biological substrate of these psychoses could lead to early differentiation of these two clinical conditions resulting in more efficient treatment strategies. Proton magnetic resonance spectroscopy was acquired from the medial prefrontal cortex in 29 unmedicated patients with first episode of psychosis (FEP), 29 abstinent methamphetamine-addicted people (METH) and 45 healthy controls (HCs) (age range 17.3 to 29.9 years old). The METH group displayed robust reductions in concentration levels of glutamate (Glu) relative to FEP (Cohen's d = 1.20) and HC (d = 0.87). The METH group also displayed reduced levels of N-acetylaspartate (NAA) relative to FEP (d = 0.53) and HC (d = 0.76). The HC group displayed a positive association between levels of Glu and NAA, r(45) = 0.52, p < 0.001, while the two clinical groups failed to show this normal association. This suggests that the cellular metabolism is altered in both conditions. These data support the assumption that cellular abnormalities differ between primary schizophrenia and methamphetamine addiction despite the overlap in clinical presentation. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Preclinical and postmortem studies show that chronic stress and MDD may affect hippocampal subfields differently, but MRI spatial resolution has previously been insufficient to measure subfield volumes. Methods: Twenty MDD participants (9 unmedicated and 11 medicated, both>6 months) and 27 healthy control subjects were studied. We used T2-weighted two-dimensional fast spin echo and T1-weighted three-dimensional magnetization prepared rapid acquisition gradient-echo sequences at 4.7 T to compare hippocampal subfield volumes at .09 μL voxel volume. Results: Unmedicated MDD participants had a lower dentate gyrus volume than control subjects or medicated MDD participants and a lower cornu ammonis (CA1–3) volume in the hippocampal body subregion than control subjects. Conclusions: Hippocampal volumes in unmedicated MDD showed evidence of localization to specific subfields and subregions, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. Strengths include in vivo measurement of entire hippocampal subfields and separation between unmedicated and medicated MDD. Limitations include power to control for multiple comparisons and that MRI landmarks approximate the subfields defined by cellular microstructure. [Copyright &y& Elsevier]

The medial prefrontal cortex (MPFC) is a key brain area in depressive symptomatology; specifically, glutamate (Glu) has been reported to play a significant role in major depression (MD) in this area. MPFC Glu levels are sensitive to ovarian hormone fluctuations and pregnancy and the postpartum period are associated with the most substantial physiological alterations of female hormones. It is therefore logical to measure MPFC Glu levels in women with postpartum depression (PPD). Using in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 T, we acquired single-voxel spectra from the MPFC of 12 women with PPD and 12 healthy controls (HCs) matched for postpartum scan timing. Water-referenced MPFC Glu levels were measured using a MRS technique that allowed us to be specific for Glu with very little glutamine contamination. The concentrations of other water-quantified brain metabolites such as glycerophosphorylcholine plus phosphorylcholine, N-acetylaspartate (NAA), and creatine plus phosphocreatine were measured in the same MR spectra. MPFC Glu levels were higher in women with PPD (7.21±1.20) compared to matched HCs (6.04±1.21). There were no differences between groups for other brain metabolites measured. These findings suggest an association between Glu dysregulation in the MPFC and PPD. Whether the pathophysiology of PPD differs from the pathophysiology of MD remains to be determined. Further investigations are needed to determine the chronological associations between the occurrence of symptoms of PPD and the onset of changes in MPFC Glu levels. [ABSTRACT FROM AUTHOR]

Abstract: Background: Fronto-limbic dysregulation in major depressive disorder (MDD) may be influenced by early life stress and antidepressant treatment. The present structural MRI study aimed to determine the relationship between amygdala, cingulate and subgenual prefrontal cortex volumes in MDD and their associations with child abuse and antidepressants. Methods: Right-handed subjects (21–50years), meeting DSM-IV criteria for MDD, either with (n=19) or without (n=20) childhood sexual or physical abuse. Healthy controls (n=34) were matched for age, sex, education and smoking. 3D-MPRAGE images with a spatial resolution of 1.5mm×1.0mm×1.0mm were acquired with a Siemens Sonata 1.5T system. Volumes of subgenual prefrontal cortex, amygdala and affective, cognitive, superior and posterior divisions of cingulate cortex were analyzed using DISPLAY software using reliable volumetric protocols. Groups were compared using ANCOVA, with intracranial volume as a covariate. Results: MDD subjects had low cingulate (cognitive division) and high amygdala volumes. Low cingulate volume was related to abuse and treatment history. Amygdala volume was predicted by subgenual prefrontal and cingulate (cognitive division) volumes and the presence of paracingulate cortex. Limitations: This study was cross sectional and the sample size was limited for subgroup and correlational analyses. Summary: Our data suggest that MDD may be associated with alterations in anterior cingulate cortex and amygdala. Morphological variation, early stress and stress-protective factors may contribute to differences in fronto-limbic structures in MDD. [Copyright &y& Elsevier]

Previous diffusion tensor imaging (DTI) studies confirmed the vulnerability of frontal callosal fibers to normal aging. The present study extended this examination systematically to other prefrontal white matter regions. Structural magnetic resonance imaging and DTI datasets were acquired from 69 healthy subjects aged 22-84 years. The prefrontal white matter was parcellated into several anatomical sub-regions: medial and lateral orbitofrontal white matter, dorsolateral prefrontal white matter, and medial prefrontal white matter, using reliable DTI-tractography protocols. Tract-specific characteristics were calculated using Matlab. Regression models were used to determine the relationship between age and structural integrity of white matter tracts. The results of our study demonstrate regional age-related changes in the prefrontal white matter tracts of the human brain. This study was cross-sectional and therefore additional longitudinal studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

A pressure ulcer is a medical complication that arises in persons with decreased mobility and/or sensation. Deep pressure ulcers starting at the bone-muscle interface are the most dangerous, as they can cause extensive damage before showing any signs at the skin surface. We previously proposed a novel intervention called intermittent electrical stimulation (IES) for the prevention of deep tissue injury (DTI). In this study, we tested the effects of four paradigms of IES and one conventional pressure relief paradigm in preventing the formation of deep pressure ulcers in rats. Loading equivalent to 18, 28, or 38% of the body weight (BW) of each rat was applied to the triceps surae muscle in one hind limb. Treatment groups received IES every 10 min for either (i) 5 or 10 s with moderate or maximal contraction, or (ii) complete pressure removal every 10 min for 10 s (conventional pressure relief). The results showed that conventional pressure relief, emulating a wheelchair push-up every 10 min, was inadequate for the prevention of DTI. In contrast, all IES paradigms were equally effective in significantly reducing the extent of deep muscle damage caused by 28 or 38% BW pressure application. These findings suggest that, in conjunction with existing techniques, IES may be an effective intervention for the prophylactic prevention of DTI. [ABSTRACT FROM AUTHOR]

Abstract: We examined age-related changes in the cerebral white matter. Structural magnetic resonance images (MRIs) and diffusion tensor images (DTIs) were acquired from 69 healthy subjects aged 22–84years. Quantitative DTI tractography was performed for nine different white matter tracts to determine tract volume, fractional anisotropy (FA), mean diffusivity (MD), axial, and radial diffusivities. We used automated and manual segmentation to determine volumes of gray matter (GM), white mater (WM), cerebrospinal fluid (CSF), and intracranial space. The results showed significant effects of aging on WM, GM, CSF volumes, and selective effects of aging on structural integrity of different white matter tracts. WM of the prefrontal region was the most vulnerable to aging, while temporal lobe connections, cingulum, and parieto-occipital commissural connections showed relative preservation with age. This study was cross-sectional, and therefore, additional longitudinal studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Abstract: The search for genes conferring liability for schizophrenia may be aided by the identification of endophenotypes. Response selection is a heritable cognitive function that is impaired in patients with schizophrenia and their unaffected siblings. The abnormalities in cerebral function that presumably underlie the deficit in patients and unaffected siblings remain to be elucidated. Cerebral neurophysiology during performance of a 4-choice reaction time (CRT) task in 25 patients with schizophrenia (15 medication free first episode (FEP) and 10 chronic patients), 32 controls, and 12 unaffected siblings of individuals with schizophrenia was investigated using fMRI. CRT was impaired in both medication free FEP and chronic patients with schizophrenia, and unaffected siblings. FEP patients, chronic patients, and unaffected siblings demonstrated greater BOLD response in the right dorsolateral prefrontal cortex (dlPFC) during CRT task blocks. The nature of the altered activation in the dlPFC was further examined using functional connectivity analysis. This revealed marked reductions in connectivity between the right dlPFC and multiple brain regions in both patient groups and, to a lesser degree, unaffected siblings. The magnitude of connectivity between right dlPFC and inferior parietal lobule correlated with task performance in the combined patient/unaffected siblings group, but not controls suggesting that the network of brain regions recruited to perform the task differed as a function of genetic liability for schizophrenia. The findings suggest that altered activity and connectivity of the right dlPFC appears to be related to genetic vulnerability for schizophrenia and may represent a potential endophenotype of the disorder. [Copyright &y& Elsevier]

Abstract: The pathophysiological underpinnings of bipolar disorder are not fully understood. However, they may be due in part to changes in the phosphatidylinositol second messenger system (PI-cycle) generally, or changes in myo-inositol concentrations more specifically. Dextro-amphetamine has been used as a model for mania in several human studies as it causes similar subjective and physiological symptoms. We wanted to determine if dextro-amphetamine altered myo-inositol concentrations in vivo as it would clearly define a mechanism linking putative changes in the PI-cycle to the subjective psychological changes seen with dextro-amphetamine administration. Fifteen healthy human volunteers received a baseline scan, followed by second scan 75min after receiving a 25mg oral dose of dextro-amphetamine. Stimulated echo proton magnetic resonance spectroscopy (MRS) scans were preformed at 3.0Tesla (T) in the dorsal medial prefrontal cortex (DMPFC). Metabolite data were adjusted for tissue composition and analyzed using LCModel. Twelve adult male rats were treated acutely with a 5-mg/kg intraperitoneal dose of dextro-amphetamine. After 1h rats were decapitated and the brains were rapidly removed and frozen until dissection. Rat brains were dissected into frontal, temporal, and occipital cortical areas, as well as hippocampus. Tissue was analyzed using a Varian 18.8T spectrometer. Metabolites were identified and quantified using Chenomx Profiler software. The main finding in the present study was that myo-inositol concentrations in the DMPFC of human volunteers and in the four rat brain regions were not altered by acute dextro-amphetamine. While it remains possible that the PI-cycle may be involved in the pathophysiology of bipolar disorder, it is not likely that the subjective and physiological of dextro-amphetamine are mediated, directly or indirectly, via alternations in myo-inositol concentrations. [Copyright &y& Elsevier]

Background: Women who suffer from premenstrual dysphoric disorder (PMDD) classically display depressive and anxiety symptoms in the premenstrum. Preclinical and clinical studies have suggested a role of glutamate in anxiety and depression. This investigation aims at demonstrating fluctuations of glutamate across the menstrual cycle in the medial prefrontal cortex of women who suffer from PMDD and healthy control subjects (HCs). Methods: Twelve PMDD women and 13 HCs were randomized to two single-voxel 3 Tesla proton magnetic resonance spectroscopy examinations of the medial prefrontal cortex during the follicular phase and the luteal phase. Results: A phase effect was observed; the levels of glutamate/creatine plus phosphocreatine (Cr) were significantly lower during the luteal phase compared with the follicular phase. However, no statistically significant diagnosis or phase × diagnosis effects were found. Conclusions: The optimized stimulated echo acquisition mode (STEAM) pulse timings selected in this study (echo time [TE], mixing time [TM] = 240, 27 msec) allow us to interpret our results as the first report of alterations of brain glutamate levels across the menstrual cycle. Hormonal fluctuations associated with the menstrual cycle likely contribute to these glutamate level variations. Although PMDD women undergo a similar decrease in glutamate during the luteal phase as the HCs, PMDD women may display an increased behavioral sensitivity to those phase-related alterations. These menstrual cycle-related variations of glutamate levels may also contribute to the influence of the phases of the menstrual cycle in other neuropsychiatric disorders. [Copyright &y& Elsevier]

Abstract: Glutamate was quantified by proton magnetic resonance spectroscopy (1H-MRS) in the medial frontal lobes of 15 adult siblings of individuals with schizophrenia (HR) and 14 healthy volunteers (HV), all of whom also completed a Continuous Performance Test (CPT). Subjects were free of psychopathology but the HR group showed greater variability in glutamate levels. After median stratification, the high glutamate group contained a larger proportion of HR than HV subjects and scored lower on the CPT. Elevated glutamate may relate to poor sustained attention and elevated risk of schizophrenia, suggesting a potential role for glutamate in an endophenotype for schizophrenia. [Copyright &y& Elsevier]

Abstract: Volumetric changes in the amygdala and hippocampus are relevant to many disorders, but their close proximity makes it difficult to separate these structures by magnetic resonance imaging, leading many volumetric protocols to exclude problematic slices from analysis, or to analyze the amygdalo–hippocampal complex conjointly. The hippocampus tail is also often excluded, because of the difficulty in separating it from the thalamus. We have developed a reliable protocol for volumetric analysis and 3-D reconstruction of the amygdala and hippocampus (as a whole and in its anatomical parts). Twenty volunteers from clinical and healthy populations were recruited. T1-weighted images were acquired at 1.5 Tesla with native spatial resolution of 1.5 mm×1.0 mm×1.0 mm. Volumetric analyses were performed blind to diagnosis, using the interactive software package DISPLAY. Inter-rater (intrarater) intraclass correlations for the method were: 0.95 (0.88) for hippocampus tail, 0.83 (0.93) for hippocampus body, 0.95 (0.92) for hippocampus head, 0.96 (0.86) for total hippocampus and 0.86 (0.94) for amygdala. Volumes (mean±S.D.) corrected for intracranial volume for this mixed group were for the hippocampal tail: 0.325±0.087 cm3; hippocampal body: 0.662±0.120 cm3; hippocampal head: 1.23±0.174 cm3; total hippocampus: 2.218±0.217 cm3, and amygdala: 0.808±0.185 cm3. In conclusion, the study demonstrates that the amygdala and hippocampal parts can be quantified reliably. [Copyright &y& Elsevier]

Background: Postmortem studies have shown robust prefrontal cortex glial losses and more subtle neuronal changes in major depressive disorder (MDD). Earlier proton magnetic resonance spectroscopy (1H-MRS) studies of the glial marker myo-inositol in MDD were subject to potential confounds. The primary hypothesis of this study was that MDD patients would show reduced prefrontal/anterior cingulate cortex levels of myo-inositol. Methods: Thirteen nonmedicated moderate–severe MDD patients and 13 matched control subjects were studied (six male, seven female per group). Proton magnetic resonance spectroscopy stimulated echo acquisition mode spectra (3.0 T; echo time = 168 msec; mixing time = 28 msec; repetition time = 3000 msec) were obtained from prefrontal/anterior cingulate cortex. Metabolite data were adjusted for tissue composition. Results: Patients with MDD showed significantly lower myo-inositol/creatine ratios (.94 ± .23) than control subjects (1.32 ± .37) [F(1,23) = 6.9; p = .016]. Conclusions: These data suggest a reduction of myo-inositol in prefrontal/anterior cingulate cortex in MDD, which could be a consequence of glial loss or altered glial metabolism. Additional in vivo studies of glial markers could add to the understanding of the pathophysiology of MDD. [Copyright &y& Elsevier]