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Production of metal debris from implant wear and corrosion processes is now a well understood occurrence following hip arthroplasty. Evidence has shown that metal ions can enter the bloodstream and travel to distant organs including the brain, and in extreme cases, can induce sensorial and neurological diseases. Our objective was tosimultaneously analyze brain anatomy and physiology in patients with long-term and well-functioning implants. Included were subjects who had received total hip or hip resurfacing arthroplastywith an implantation time of a minimum of 7 years (n = 28) and age- and sex-matched controls (n = 32). Blood samples were obtained to measure ion concentrations of cobalt and chromium, and the Montreal Cognitive Assessment was performed. 3T MRI brain scans were completed with an MPRAGE sequence for ROI segmentation and multiecho gradient echo sequences to generate QSM and R2* maps. Mean QSM and R2* values were recorded for five deep brain and four middle and cortical brain structures on both hemispheres: pallidum, putamen, caudate, amygdala, hippocampus, anterior cingulate, inferior temporal, and cerebellum. No differences in QSM or R2* or cognition scores were found between both groups (p > 0.6654). No correlation was found between susceptibility and blood ion levels for cobalt or chromium in any region of the brain. No correlation was found between blood ion levels and cognition scores. Clinical significance: Results suggest that metal ions released by long-term and well-functioning implants do not affect brain integrity., (© 2024 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Social cognition is a dynamic process that requires the perception and integration of a complex set of idiosyncratic features between interacting conspecifics. Here we present a method for simultaneously measuring the whole-brain activation of two socially interacting marmoset monkeys using functional magnetic resonance imaging. MRI hardware (a radiofrequency coil and peripheral devices) and image-processing pipelines were developed to assess brain responses to socialization, both on an intra-brain and inter-brain level. Notably, the brain activation of a marmoset when viewing a second marmoset in-person versus when viewing a pre-recorded video of the same marmoset-i.e., when either capable or incapable of socially interacting with a visible conspecific-demonstrates increased activation in the face-patch network. This method enables a wide range of possibilities for potentially studying social function and dysfunction in a non-human primate model., (© 2021. The Author(s).)

The common marmoset has enormous promise as a nonhuman primate model of human brain functions. While resting-state functional MRI (fMRI) has provided evidence for a similar organization of marmoset and human cortices, the technique cannot be used to map the functional correspondences of brain regions between species. This limitation can be overcome by movie-driven fMRI (md-fMRI), which has become a popular tool for noninvasively mapping the neural patterns generated by rich and naturalistic stimulation. Here, we used md-fMRI in marmosets and humans to identify whole-brain functional correspondences between the two primate species. In particular, we describe functional correlates for the well-known human face, body, and scene patches in marmosets. We find that these networks have a similar organization in both species, suggesting a largely conserved organization of higher-order visual areas between New World marmoset monkeys and humans. However, while face patches in humans and marmosets were activated by marmoset faces, only human face patches responded to the faces of other animals. Together, the results demonstrate that higher-order visual processing might be a conserved feature between humans and New World marmoset monkeys but that small, potentially important functional differences exist., Competing Interests: The authors declare no competing interest.

Recent methodological advances in MRI have enabled substantial growth in neuroimaging studies of non-human primates (NHPs), while open data-sharing through the PRIME-DE initiative has increased the availability of NHP MRI data and the need for robust multi-subject multi-center analyses. Streamlined acquisition and analysis protocols would accelerate and improve these efforts. However, consensus on minimal standards for data acquisition protocols and analysis pipelines for NHP imaging remains to be established, particularly for multi-center studies. Here, we draw parallels between NHP and human neuroimaging and provide minimal guidelines for harmonizing and standardizing data acquisition. We advocate robust translation of widely used open-access toolkits that are well established for analyzing human data. We also encourage the use of validated, automated pre-processing tools for analyzing NHP data sets. These guidelines aim to refine methodological and analytical strategies for small and large-scale NHP neuroimaging data. This will improve reproducibility of results, and accelerate the convergence between NHP and human neuroimaging strategies which will ultimately benefit fundamental and translational brain science., (Copyright © 2021. Published by Elsevier Inc.)

Changes in resting-state functional connectivity (rs-FC) under general anesthesia have been widely studied with the goal of identifying neural signatures of consciousness. This work has commonly revealed an apparent fragmentation of whole-brain network structure during unconsciousness, which has been interpreted as reflecting a break-down in connectivity and a disruption of the brain's ability to integrate information. Here we show, by studying rs-FC under varying depths of isoflurane-induced anesthesia in nonhuman primates, that this apparent fragmentation, rather than reflecting an actual change in network structure, can be simply explained as the result of a global reduction in FC. Specifically, by comparing the actual FC data to surrogate data sets that we derived to test competing hypotheses of how FC changes as a function of dose, we found that increases in whole-brain modularity and the number of network communities - considered hallmarks of fragmentation - are artifacts of constructing FC networks by thresholding based on correlation magnitude. Taken together, our findings suggest that deepening levels of unconsciousness are instead associated with the increasingly muted expression of functional networks, an observation that constrains current interpretations as to how anesthesia-induced FC changes map onto existing neurobiological theories of consciousness., (Copyright © 2021. Published by Elsevier Inc.)

Most neuroanatomical studies are based on T 1 -weighted MR images, whose intensity profiles are not solely determined by the tissue's longitudinal relaxation times (T 1 ), but also affected by varying non-T 1 contributions, hampering data reproducibility. In contrast, quantitative imaging using the MP2RAGE sequence, for example, allows direct characterization of the brain based on the tissue property of interest. Combined with 7 Tesla (7T) MRI, this offers unique opportunities to obtain robust high-resolution brain data characterized by a high reproducibility, sensitivity and specificity. However, specific MP2RAGE parameter choices - e.g., to emphasize intracortical myelin-dependent contrast variations - can substantially impact image quality and cortical analyses through remnants of B 1 + -related intensity variations, as illustrated in our previous work. To follow up on this: we (1) validate this protocol effect using a dataset acquired with a particularly B 1 + insensitive set of MP2RAGE parameters combined with parallel transmission excitation; and (2) extend our analyses to evaluate the effects on hippocampal morphometry. The latter remained unexplored initially, but can provide important insights related to generalizability and reproducibility of neurodegenerative research using 7T MRI. We confirm that B 1 + inhomogeneities have a considerably variable effect on cortical T 1 estimates, as well as on hippocampal morphometry depending on the MP2RAGE setup. While T 1 differed substantially across datasets initially, we show the inter-site T 1 comparability improves after correcting for the spatially varying B 1 + field using a separately acquired Sa2RAGE B 1 + map. Finally, removal of B 1 + residuals affects hippocampal volumetry and boundary definitions, particularly near structures characterized by strong intensity changes (e.g. cerebral spinal fluid). Taken together, we show that the choice of MP2RAGE parameters can impact T 1 comparability across sites and present evidence that hippocampal segmentation results are modulated by B 1 + inhomogeneities. This calls for careful (1) consideration of sequence parameters when setting acquisition protocols, as well as (2) acquisition of a B 1 + map to correct MP2RAGE data for potential B 1 + variations to allow comparison across datasets., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The magnetization-prepared two-rapid-gradient-echo (MP2RAGE) sequence is used for structural T 1 -weighted imaging and T 1 mapping of the human brain. In this sequence, adiabatic inversion RF pulses are commonly used, which require the B 1 magnitude to be above a certain threshold. Achieving this threshold in the whole brain may not be possible at ultra-high fields because of the short RF wavelength. This results in low-inversion regions especially in the inferior brain (eg cerebellum and temporal lobes), which is reflected as regions of bright signal in MP2RAGE images. This study aims at eliminating the low-inversion-efficiency induced artifacts in MP2RAGE images at 7 T. The proposed technique takes advantage of parallel RF transmission systems by splitting the brain into two overlapping slabs and calculating the complex weights of transmit channels (ie RF shims) on these slabs for excitation and inversion independently. RF shims were calculated using fast methods implemented in the standard workflow. The excitation RF pulse was designed to obtain slabs with flat plateaus and sharp edges. These slabs were joined into a single volume during the online image reconstruction. The two-slab strategy naturally results in a signal-to-noise ratio loss; however, it allowed the use of independent shims to make the B + field exceed the adiabatic threshold in the inferior brain, eliminating regions of low inversion efficiency. Accordingly, the normalized root-mean-square errors in the inversion were reduced to below 2%. The two-slab strategy was found to outperform subject-specific k 1 + -weighted structural images were obtained in the whole brain at 7 T.T -point inversion RF pulses in terms of inversion error. The proposed strategy is a simple yet effective method to eliminate low-inversion-efficiency artifacts; consequently, MP2RAGE-based, artifact-free T 1 -weighted structural images were obtained in the whole brain at 7 T., (© 2020 John Wiley & Sons, Ltd.)

The common marmoset (Callithrix jacchus) is a New World primate that is becoming increasingly popular as a preclinical model. To assess functional connectivity (FC) across the marmoset brain, resting-state functional MRI (RS-fMRI) is often performed under isoflurane anesthesia to avoid the effects of motion, physiological stress, and training requirements. In marmosets, however, it remains unclear how isoflurane anesthesia affects patterns of FC. Here, we investigated the effects of isoflurane on FC when delivered with either medical air or 100% pure oxygen, two canonical methods of inhalant isoflurane anesthesia delivery. The results demonstrated that when delivered with either medical air or 100% oxygen, isoflurane globally decreased FC across resting-state networks that were identified in awake marmosets. Generally, although isoflurane globally decreased FC in resting-state networks, the spatial structure of the networks was preserved. Outside of the context of RS networks, we indexed pair-wise functional connectivity between regions across the brain and found that isoflurane substantially altered interhemispheric and thalamic FC. Taken together, these findings indicate that RS-fMRI under isoflurane anesthesia is useful to evaluate the global structure of functional networks, but may obfuscate important nodes of some network components when compared to data acquired in fully awake marmosets., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

General anesthetics are routinely used to induce unconsciousness, and much is known about their effects on receptor function and single neuron activity. Much less is known about how these local effects are manifest at the whole-brain level nor how they influence network dynamics, especially past the point of induced unconsciousness. Using resting-state functional magnetic resonance imaging (fMRI) with nonhuman primates, we investigated the dose-dependent effects of anesthesia on whole-brain temporal modular structure, following loss of consciousness. We found that higher isoflurane dose was associated with an increase in both the number and isolation of whole-brain modules, as well as an increase in the uncoordinated movement of brain regions between those modules. Conversely, we found that higher dose was associated with a decrease in the cohesive movement of brain regions between modules, as well as a decrease in the proportion of modules in which brain regions participated. Moreover, higher dose was associated with a decrease in the overall integrity of networks derived from the temporal modules, with the exception of a single, sensory-motor network. Together, these findings suggest that anesthesia-induced unconsciousness results from the hierarchical fragmentation of dynamic whole-brain network structure, leading to the discoordination of temporal interactions between cortical modules., (© The Author(s) 2020. Published by Oxford University Press.)

Objective: To longitudinally assess brain microstructure and function in female varsity athletes participating in contact and noncontact sports., Methods: Concussion-free female rugby players (n = 73) were compared to age-matched (ages 18-23) female swimmers and rowers (n = 31) during the in- and off-season. Diffusion and resting-state fMRI (rs-fMRI) measures were the primary outcomes. The Sports Concussion Assessment Tool and head impact accelerometers were used to monitor symptoms and impacts, respectively., Results: We found cross-sectional (contact vs noncontact) and longitudinal (in- vs off-season) changes in white matter diffusion measures and rs-fMRI network connectivity in concussion-free contact athletes relative to noncontact athletes. In particular, mean, axial, and radial diffusivities were increased with decreased fractional anisotropy in multiple white matter tracts of contact athletes accompanied with default mode and visual network hyperconnectivity ( p < 0.001). Longitudinal diffusion changes in the brainstem between the in- and off-season were observed for concussion-free contact athletes only, with progressive changes observed in a subset of athletes over multiple seasons. Axial diffusivity was significantly lower in the genu and splenium of the corpus callosum in those contact athletes with a history of concussion., Conclusions: Together, these findings demonstrate longitudinal changes in the microstructure and function of the brain in otherwise healthy, asymptomatic athletes participating in contact sport. Further research to understand the long-term brain health and biological implications of these changes is required, in particular to what extent these changes reflect compensatory, reparative, or degenerative processes., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

An object that is looming toward a subject or receding away contains important information for determining if this object is dangerous, beneficial or harmless. This information (motion, direction, identity, time-to-collision, size, velocity) is analyzed by the brain in order to execute the appropriate behavioral responses depending on the context: fleeing, freezing, grasping, eating, exploring. In the current study, we performed ultra-high-field functional MRI (fMRI) at 9.4T in awake marmosets to explore the patterns of brain activation elicited by visual stimuli looming toward or receding away from the monkey. We found that looming and receding visual stimuli activated a large cortical network in frontal, parietal, temporal and occipital cortex in areas involved in the analysis of motion, shape, identity and features of the objects. Looming stimuli strongly activated a network composed of portions of the pulvinar, superior colliculus, putamen, parietal, prefrontal and temporal cortical areas. These activations suggest the existence of a network that processes visual stimuli looming toward peripersonal space to predict the consequence of these stimuli. Together with previous studies in macaque monkeys, these findings indicate that this network is preserved across Old and New World primates., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Arterial spin labeling (ASL) is an established noninvasive MRI technique used for cerebral blood flow measurement, which generally suffers from a low signal-to-noise ratio (SNR). The use of ultra-high fields to enhance sensitivity inevitably results in an increase in TR because of specific absorption rate (SAR) constraints, causing inadequate sampling of hemodynamic response in functional MRI, and adversely affecting concurrent measurement such as blood oxygen level dependent. To address this problem, variable-rate selective excitation (VERSE) radiofrequency (RF) pulses were used., Methods: The conventional (sinc) selective RF pulses of the Q2TIPS block in the PICORE pulsed ASL (PASL) sequence used for blood saturation were replaced by their equivalent VERSE RF waveforms. Nine healthy volunteers were scanned using the conventional and VERSE PASL sequences on a head-only 7T scanner operating in parallel transmit mode., Results: VERSE PASL sequence provides perfusion images similar to the conventional version, with comparable perfusion SNR (conventional, 3.33 ± 0.48; VERSE, 3.26 ± 0.55) and temporal SNR (conventional, 1.02 ± 0.20; VERSE, 1.05 ± 0.12) for TR = 3.5 seconds and 70 measurements. With shorter acquisition time (TR = 2.5 seconds), VERSE PASL sequence still provides similar results to those acquired using the conventional PASL sequence with longer TR = 3.5 seconds., Conclusion: The use of VERSE RF pulses in the Q2TIPS block of a PASL sequence allowed for the reduction of RF power deposition and, consequently, an increase in the temporal resolution and/or perfusion SNR., (© 2019 International Society for Magnetic Resonance in Medicine.)

Resting-state functional MRI (RS-fMRI) is widely used to assess how strongly different brain areas are connected. However, this connection obtained by RS-fMRI, which is called functional connectivity (FC), simply refers to the correlation of blood oxygen level-dependent (BOLD) signals across time it has yet to be quantified how accurately FC reflects cellular connectivity (CC). In this study, we elucidated this relationship using RS-fMRI and quantitative tracer data in marmosets. In addition, we also elucidated the effects of distance between two brain regions on the relationship between FC and CC across seed region. To calculate FC, we used full correlation approach that is considered to reflect not only direct (monosynaptic connections) but also indirect pathways (polysynaptic connections). Our main findings are that: (1) overall FC obtained by RS-fMRI was highly correlated with tracer-based CC, but correlation coefficients varied remarkably across seed regions; (2) the strength of FC decreased with increase in the distance between two regions; (3) correlation coefficients between FC and CC after regressing out the effects of the distance between two regions still varied across seed regions, but some regions have strong correlations. These findings suggest that although FC reflects the strength of monosynaptic pathways, it is strongly affected by the distance between regions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings., Methods: Clinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement., Results: A wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design., Conclusions: Imaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms., (© 2019 American Academy of Neurology.)

Background: Small-animal MRI is an important investigative tool for basic and preclinical research. High-resolution anatomical and functional studies of the brain require artifact-free images that are acquired with a highly sensitive radiofrequency (RF) coil., New Method: The animal holder plays an important role in mitigating image artifacts: motion artifacts are reduced by immobilizing the animal and geometric-distortion artifacts are reduced by accurately positioning the animal to improve static-field shimming. The RF coil, in turn, must provide high sensitivity over the whole brain and not physically interfere with the animal holder. To accomplish these tasks, the animal holder and RF coil should be designed in tandem. In this manuscript, animal holders and RF coils for mice, rats, and marmoset monkeys are described. Each animal holder includes components for anesthesia delivery and animal immobilization, as well as a compatible receive coil., Results/comparison With Existing Method(s): Animal holders were capable of accurate and reproducible positioning (for the marmoset, this was in the stereotactic plane), consequently reducing geometric distortion in echo-planar images. Ear bars were designed in conjunction with receive-coil formers, thereby maximizing the sensitive region of coils, while concurrently reducing motion to less than a pixel over EPI time series. Motion and SNR were quantified to facilitate direct comparison to existing animal holders and RF coils. All computer-aided-design (CAD) files of animal holders and RF coils are provided to promote dissemination., Conclusions: The confluence of design between the animal holder and RF coil provides a pragmatic solution for routine imaging of small animals., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Acute brain changes are expected after concussion, yet there is growing evidence of persistent abnormalities well beyond clinical recovery and clearance to return to play. Multiparametric MRI is a powerful approach to non-invasively study structure-function relationships in the brain, however it remains challenging to interpret the complex and heterogeneous cascade of brain changes that manifest after concussion. Emerging conjunctive, data-driven analysis approaches like linked independent component analysis can integrate structural and functional imaging data to produce linked components that describe the shared inter-subject variance across images. These linked components not only offer the potential of a more comprehensive understanding of the underlying neurobiology of concussion, but can also provide reliable information at the level of an individual athlete. In this study, we analyzed resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) within a cohort of female varsity rugby players (n = 52) through the in- and off-season, including concussed athletes (n = 21) who were studied longitudinally at three days, three months and six months after a diagnosed concussion. Linked components representing co-varying white matter microstructure and functional network connectivity characterized (a) the brain's acute response to concussion and (b) persistent alterations beyond clinical recovery. Furthermore, we demonstrate that these long-term brain changes related to specific aspects of a concussion history and allowed us to monitor individual athletes before and longitudinally after a diagnosed concussion., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The close homology of monkeys and humans has increased the prevalence of non-human-primate models in functional MRI studies of brain connectivity. To improve upon the attainable resolution in functional MRI studies, a commensurate increase in the sensitivity of the radiofrequency receiver coil is required to avoid a reduction in the statistical power of the analysis. Most receive coils are comprised of multiple loops distributed equidistantly over a surface to produce spatially independent sensitivity profiles. A larger number of smaller elements will in turn provide a higher signal-to-noise ratio (SNR) over the same field of view. As the loops become physically smaller, noise originating from the sample is reduced relative to noise originating from the coil. In this coil-noise-dominated regime, coil elements can have overlapping sensitivity profiles, yet still possess only mildly correlated noise. In this manuscript, we demonstrate that inductively decoupled, concentric coil arrays can improve temporal SNR when operating in the coil-noise-dominated regime-in contrast to what is expected for the more ubiquitous sample-noise-dominated array. A small, thin, 7-channel flexible coil is developed and operated in conjunction with an existing whole-head monkey coil. The mean and maximum noise correlation between the two arrays was 5% and 23%, respectively. When the flex coil was placed over the sensorimotor cortex, the temporal SNR improved by up to 2.3-fold in the peripheral cortex and up to 1.3-fold at a 2- to 3-cm depth within the brain. When the flex coil was placed over the frontal eye fields, resting-state maps showed substantially elevated sensitivity to correlations in the prefrontal cortex (54%), supplementary eye fields (39%), and anterior cingulate cortex (41%). The concentric-coil topology provided a pragmatic and robust means to significantly improve local temporal SNR and the statistical power of functional connectivity maps., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The purpose of this study was to use non-invasive proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) to monitor changes in prefrontal white matter metabolite levels and tissue microstructure in female rugby players with and without concussion (ages 18-23, n = 64). Evaluations including clinical tests and 3 T MRI were performed at the beginning of a season (in-season) and followed up at the end of the season (off-season). Concussed athletes were additionally evaluated 24-72 hr (n = 14), three months (n = 11), and six months (n = 8) post-concussion. Reduced glutamine at 24-72 hr and three months post-concussion, and reduced glutamine/creatine at three months post-concussion were observed. In non-concussed athletes (n = 46) both glutamine and glutamine/creatine were lower in the off-season compared to in-season. Within the MRS voxel, an increase in fractional anisotropy (FA) and decrease in radial diffusivity (RD) were also observed in the non-concussed athletes, and correlated with changes in glutamine and glutamine/creatine. Decreases in glutamine and glutamine/creatine suggest reduced oxidative metabolism. Changes in FA and RD may indicate neuroinflammation or re-myelination. The observed changes did not correlate with clinical test scores suggesting these imaging metrics may be more sensitive to brain injury and could aid in assessing recovery of brain injury from concussion., (© 2017 Wiley Periodicals, Inc.)

Background and Purpose: Radiation necrosis remains an irreversible long-term side-effect following radiotherapy to the brain. The ability to predict areas that could ultimately develop into necrosis could lead to prevention and management of radiation necrosis., Materials and Methods: Fischer 344 rats were irradiated using two platforms (micro-CT irradiator and x-Rad 225 IGRT) with radiation up to 30 Gy for the micro-CT and 40 Gy for the xRAD-224 to half the brain. Animals were subsequently imaged using a 9.4 T MRI scanner every 2-4 weeks for up to 28 weeks using a 7-echo gradient echo sequence. The apparent transverse relaxation constant ([Formula: see text]) was calculated and retrospectively analyzed., Results: Animals irradiated with the low-dose rate micro-CT did not exhibit any symptoms or imaging changes associated with RN. Animals irradiated with the xRAD-225 exhibited imaging changes consistent with RN at week 24. Analysis of the [Formula: see text] coefficient within the lesion and hippocampus shows the potential for detection of RN up to 10 weeks prior to morphological changes., Conclusions: The ability to predict areas of RN and increases of [Formula: see text] within the hippocampus provides a method for long-term monitoring and prediction of RN.

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes., Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11-14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n = 26) and longitudinally in concussed athletes within 24 to 72 hours (n = 17) and 3 months (n = 14) after a diagnosed concussion., Results: There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption., Conclusions: Changes persisted well after players' clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The common marmoset ( Callithrix jacchus ) is a small New World primate that is becoming increasingly popular in the neurosciences as an animal model of preclinical human disease. With several major disorders characterized by alterations in neural white matter (e.g., multiple sclerosis, Alzheimer's disease, schizophrenia), proposed to be transgenically modeled using marmosets, the ability to isolate and characterize reliably major white matter fiber tracts with MRI will be of use for evaluating structural brain changes related to disease processes and symptomatology. Here, we propose protocols for isolating major white matter fiber tracts in the common marmoset using in vivo ultrahigh-field MRI (9.4T) diffusion-weighted imaging (DWI) data. With the use of a high angular-resolution DWI (256 diffusion-encoding directions) sequence, collected on four anesthetized marmosets, we provide guidelines for manually drawing fiber-tracking regions of interest, based on easily identified anatomical landmarks in DWI native space. These fiber-tract isolation protocols are expected to be experimentally useful for visualization and quantification of individual white matter fiber tracts in both control and experimental groups of marmosets (e.g., transgenic models). As disease models in the marmoset advance, the determination of how macroscopic white matter anatomy is altered as a function of disease state will be relevant in bridging the existing translational gap between preclinical rodent models and human patients. NEW & NOTEWORTHY Although significant progress has been made in mapping white matter connections in the marmoset brain using ex vivo tracing techniques, the application of in vivo virtual dissection of major white matter fiber tracts has been established by few studies in the marmoset literature. Here, we demonstrate the feasibility of whole-brain diffusion-weighted tractography in anesthetized marmosets at ultrahigh-field MRI (9.4T) and propose protocols for isolating nine major white matter fiber tracts in the marmoset brain., (Copyright © 2017 the American Physiological Society.)

In contrast to the well established macaque monkey, little is known about functional connectivity patterns of common marmoset monkey (Callithrix jacchus) that is poised to become the leading transgenic primate model. Here, we used resting-state ultra-high-field fMRI data collected from anesthetized marmosets and macaques along with awake human subjects, to examine and compare the brain's functional organization, with emphasis on the saccade system. Exploratory independent component analysis revealed eight resting-state networks in marmosets that greatly overlapped with corresponding macaque and human networks including a distributed frontoparietal network. Seed-region analyses of the superior colliculus (SC) showed homolog areas in macaques and marmosets. The marmoset SC displayed the strongest frontal functional connectivity with area 8aD at the border to area 6DR. Functional connectivity of this frontal region revealed a similar functional connectivity pattern as the frontal eye fields in macaques and humans. Furthermore, areas 8aD, 8aV, PG,TPO, TE2, and TE3 were identified as major hubs based on region-wise evaluation of betweeness centrality, suggesting that these cortical regions make up the functional core of the marmoset brain. The results support an evolutionarily preserved frontoparietal system and provide a starting point for invasive neurophysiological studies in the marmoset saccade and visual systems., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To implement and optimize a new approach for susceptibility-weighted image (SWI) generation from multi-echo multi-channel image data and compare its performance against optimized traditional SWI pipelines., Materials and Methods: Five healthy volunteers were imaged at 7 Tesla. The inter-echo-variance (IEV) channel combination, which uses the variance of the local frequency shift at multiple echo times as a weighting factor during channel combination, was used to calculate multi-echo local phase shift maps. Linear phase masks were combined with the magnitude to generate IEV-SWI. The performance of the IEV-SWI pipeline was compared with that of two accepted SWI pipelines-channel combination followed by (i) Homodyne filtering (HPH-SWI) and (ii) unwrapping and high-pass filtering (SVD-SWI). The filtering steps of each pipeline were optimized. Contrast-to-noise ratio was used as the comparison metric. Qualitative assessment of artifact and vessel conspicuity was performed and processing time of pipelines was evaluated., Results: The optimized IEV-SWI pipeline (σ = 7 mm) resulted in continuous vessel visibility throughout the brain. IEV-SWI had significantly higher contrast compared with HPH-SWI and SVD-SWI (P < 0.001, Friedman nonparametric test). Residual background fields and phase wraps in HPH-SWI and SVD-SWI corrupted the vessel signal and/or generated vessel-mimicking artifact. Optimized implementation of the IEV-SWI pipeline processed a six-echo 16-channel dataset in under 10 min., Conclusion: IEV-SWI benefits from channel-by-channel processing of phase data and results in high contrast images with an optimal balance between contrast and background noise removal, thereby presenting evidence of importance of the order in which postprocessing techniques are applied for multi-channel SWI generation., Level of Evidence: 2 J. Magn. Reson. Imaging 2017;45:1113-1124., (© 2016 International Society for Magnetic Resonance in Medicine.)

Using resting state functional magnetic resonance imaging (MRI), we aim to understand the neurologic basis of improved function in children with hemiplegic cerebral palsy treated with constraint-induced movement therapy. Eleven children including 4 untreated comparison subjects diagnosed with hemiplegic cerebral palsy were recruited from 3 clinical centers. MRI and clinical data were gathered at baseline and 1 month for both groups, and 6 months later for the case group only. After constraint therapy, the sensorimotor resting state network became more bilateral, with balanced contributions from each hemisphere, which was sustained 6 months later. Sensorimotor resting state network reorganization after therapy was correlated with a change in the Quality of Upper Extremity Skills Test score at 1 month (r = 0.79, P = .06), and Canadian Occupational Performance Measure scores at 6 months (r = 0.82, P = .05). This clinically correlated resting state network reorganization provides further evidence of the neuroplastic mechanisms underlying constraint-induced movement therapy., (© The Author(s) 2015.)

The aim was to identify neuroimaging predictors of clinical improvements following constraint-induced movement therapy. Resting state functional magnetic resonance and diffusion tensor imaging data was acquired in 7 children with hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data were acquired at baseline and 1 month later following a 3-week constraint therapy regimen. A more negative baseline laterality index characterizing an atypical unilateral sensorimotor resting state network significantly correlated with an improvement in the Canadian Occupational Performance Measure score (r = -0.81, P = .03). A more unilateral network with decreased activity in the affected hemisphere was associated with greater improvements in clinical scores. Higher mean diffusivity in the posterior limb of the internal capsule of the affect tract correlated significantly with improvements in the Jebsen-Taylor score (r = -0.83, P = .02). Children with more compromised networks and tracts improved the most following constraint therapy., (© The Author(s) 2015.)

Purpose: To develop and evaluate a local frequency shift (LFS) mapping method specifically designed for multi-echo acquisitions and multi-channel receive coils., Methods: The proposed method uses the pixel-by-pixel inter-echo variance (IEV) as a weighting factor during channel-combination. Five healthy volunteers were scanned at 7 T. The IEV-weighted method was quantitatively compared to established (adaptive and Hermitian product) channel-combination methods with respect to IEV of LFS over the entire brain., Results: In all experiments, the IEV-weighted method generated LFS maps free of artifacts caused by unwrapping errors. Based on measurements of the inter-echo frequency variance throughout the whole brain, the IEV-weighted method produced the lowest variation and the best contrast at the edge of the brain., Conclusion: The primary finding of the present study is that accurate LFS maps are achievable if the data from each channel is processed independently prior to combination followed by a weighted combination using IEV as the weighting term. The software is freely available to the scientific community., (© 2014 Wiley Periodicals, Inc.)

Despite their widespread use, the effect of anesthetic agents on the brain's functional architecture remains poorly understood. This is particularly true of alterations that occur beyond the point of induced unconsciousness. Here, we examined the distributed intrinsic connectivity of macaques across six isoflurane levels using resting-state functional MRI (fMRI) following the loss of consciousness. The results from multiple analysis strategies showed stable functional connectivity (FC) patterns between 1.00% and 1.50% suggesting this as a suitable range for anesthetized nonhuman primate resting-state investigations. Dose-dependent effects were evident at moderate to high dosages showing substantial alteration of the functional topology and a decrease or complete loss of interhemispheric cortical FC strength including that of contralateral homologues. The assessment of dynamic FC patterns revealed that the functional repertoire of brain states is related to anesthesia depth and most strikingly, that the number of state transitions linearly decreases with increased isoflurane dosage. Taken together, the results indicate dose-specific spatial and temporal alterations of FC that occur beyond the typically defined endpoint of consciousness. Future work will be necessary to determine how these findings generalize across anesthetic types and extend to the transition between consciousness and unconsciousness., (© 2014 Wiley Periodicals, Inc.)

Resting-state functional MRI (RS-fMRI) is a widely used method for inferring connectivity between brain regions or nodes. As with task-based fMRI, the spatial specificity of the connectivity maps can be distorted by the strong biasing effect of the BOLD signal in macroscopic veins. In RS-fMRI this effect is exacerbated by the temporal coherences of physiological origin between large veins that are widely distributed in the brain. In gradient echo based EPI, used for the vast majority of RS-fMRI, macroscopic veins that carry BOLD-related changes exhibit a strong phase response. This allows for post-processing identification and removal of venous signals using a phase regressor technique. Here, we employ this approach to suppress macrovascular venous contributions in high-field whole-brain RS-fMRI data sets, resulting in significant changes to both the spatial localization of the networks and the correlations between the network nodes. These effects were observed at both the individual and group analysis level, suggesting that venous contamination is a confounding factor for RS-fMRI studies even at relatively low image resolutions. Suppression of the macrovascular signal using the phase regression approach may therefore help to better identify, delineate, and interpret the true structure of large-scale brain networks., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the potential of quantitative susceptibility (QS) and R2* mapping as surrogate biomarkers of clinically relevant, age-adjusted demyelination and iron deposition in multiple sclerosis (MS)., Materials and Methods: All study participants gave written informed consent, and the study was approved by the institutional review board. Quantitative maps of the magnetic resonance imaging susceptibility parameters (R2* and QS) were computed for 25 patients with either clinically isolated syndrome (CIS) or relapsing-remitting MS, as well as for 15 age- and sex-matched control subjects imaged at 7 T. The candidate MR imaging biomarkers were correlated with Extended Disability Status Scale (EDSS), time since CIS diagnosis, time since MS diagnosis, and age., Results: QS maps aided identification of significant, voxel-level increases in iron deposition in subcortical gray matter (GM) of patients with MS compared with control subjects. These voxel-level increases were not observed on R2* maps. Region-of-interest analysis of mean R2* and QS in subcortical GM demonstrated that R2* (R ≥ 0.39, P < .01) and QS (R ≥ 0.44, P < .01) were strongly correlated with EDSS. In white matter (WM), the volume of total WM damage (defined by a z score of less than -2.0 criterion, indicating demyelination) on QS maps correlated significantly with EDSS (R = 0.46, P = .02). Voxelwise QS also supported a significant contribution of age to demyelination in patients with MS, suggesting that age-adjusted clinical scores may provide more robust measures of MS disease severity compared with non-age-adjusted scores., Conclusion: Using QS and R2* mapping, evidence of both significant increases in iron deposition in subcortical GM and myelin degeneration along the WM skeleton of patients with MS was identified. Both effects correlated strongly with EDSS.

The complex network dynamics that arise from the interaction of the brain's structural and functional architectures give rise to mental function. Theoretical models demonstrate that the structure-function relation is maximal when the global network dynamics operate at a critical point of state transition. In the present work, we used a dynamic mean-field neural model to fit empirical structural connectivity (SC) and functional connectivity (FC) data acquired in humans and macaques and developed a new iterative-fitting algorithm to optimize the SC matrix based on the FC matrix. A dramatic improvement of the fitting of the matrices was obtained with the addition of a small number of anatomical links, particularly cross-hemispheric connections, and reweighting of existing connections. We suggest that the notion of a critical working point, where the structure-function interplay is maximal, may provide a new way to link behavior and cognition, and a new perspective to understand recovery of function in clinical conditions., (Copyright © 2014 the authors 0270-6474/14/347910-07$15.00/0.)

Estimates of the apparent transverse relaxation rate (R2*) can be used to quantify important properties of biological tissue. Surprisingly, the mechanism of R2* dependence on tissue orientation is not well understood. The primary goal of this paper was to characterize orientation dependence of R2* in gray and white matter and relate it to independent measurements of two other susceptibility based parameters: the local Larmor frequency shift (fL) and quantitative volume magnetic susceptibility (Δχ). Through this comparative analysis we calculated scaling relations quantifying R2' (reversible contribution to the transverse relaxation rate from local field inhomogeneities) in a voxel given measurements of the local Larmor frequency shift. R2' is a measure of both perturber geometry and density and is related to tissue microstructure. Additionally, two methods (the Generalized Lorentzian model and iterative dipole inversion) for calculating Δχ were compared in gray and white matter. The value of Δχ derived from fitting the Generalized Lorentzian model was then connected to the observed R2* orientation dependence using image-registered optical density measurements from histochemical staining. Our results demonstrate that the R2* and fL of white and cortical gray matter are well described by a sinusoidal dependence on the orientation of the tissue and a linear dependence on the volume fraction of myelin in the tissue. In deep brain gray matter structures, where there is no obvious symmetry axis, R2* and fL have no orientation dependence but retain a linear dependence on tissue iron concentration and hence Δχ.

Characterization of large-scale brain networks using blood-oxygenation-level-dependent functional magnetic resonance imaging is typically based on the assumption of network stationarity across the duration of scan. Recent studies in humans have questioned this assumption by showing that within-network functional connectivity fluctuates on the order of seconds to minutes. Time-varying profiles of resting-state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are thus mechanistically of particular importance. However, because these studies acquired data from awake subjects, the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. Here, we characterize RSN dynamics of anesthetized macaques that control for these accounts, and compare them to awake human subjects. We find that functional connectivity among nodes comprising the "oculomotor (OCM) network" strongly fluctuated over time during awake as well as anaesthetized states. For time dependent analysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticorrelations that were missed when assessed with longer time windows. Similarly, the analysis identified network nodes that transiently link to the OCM network and did not emerge in average RSN analysis. Furthermore, time-dependent analysis reliably revealed transient states of large-scale synchronization that spanned all seeds. The results illustrate that resting-state functional connectivity is not static and that RSNs can exhibit nonstationary, spontaneous relationships irrespective of conscious, cognitive processing. The findings imply that mechanistically important network information can be missed when using average functional connectivity as the single network measure., (Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.)

Parallel transmission has been used to reduce the inevitable inhomogeneous radiofrequency fields produced in human high-field MRI greater than 3 T. Further improvements in the transmit homogeneity and efficiency are possible by leveraging the additional degree of freedom permitted by multislice acquisitions. Compared to simple scaling of the flip angle to compensate for B1+ falloff along the radiofrequency coil, calculation of B1+ shim solutions on a slice-by-slice basis can markedly improve homogeneity and/or reduce transmitted power and global SAR. Performance measures were acquired at 7 T with a 15-channel head-only transceive array featuring elements distributed over all three logical axes, facilitating B1+ shimming over arbitrary orientations. Compared to a circularly polarized volume mode of the same coil, shimming to maximize excitation efficiency on a slice-by-slice basis yielded improvements in mean B1+ by 12.8±2.4% and a reduction in standard deviation of B1+ of 16.3±6.8%, while reducing relative SAR by 6.2±3.1%. When shimming for greater uniformity, the mean and standard deviation of B1+ were further improved by 15.9±2.6% and 26.2±10.4%, respectively, at the expense of a 135±8% increase in global SAR. Robust multislice-shim solutions are demonstrated that can be quickly calculated, applied in real time, and reliably improve on volume coil modes., (Copyright © 2011 Wiley Periodicals, Inc.)

The first few years of fMRI were dominated by block design tasks that were essentially adapted from the PET literature. In 1995 the concept of acquiring single trials that took better advantage of fMRI's strengths was introduced. Single trials opened up the possibility of regressing fMRI timing extracted from hemodynamic responses with behavioral measures that were also acquired on a trial-by-trial basis. Utilizing the enhanced sensitivity of higher field MRI scanners, a number of us started to exploit this paradigm design to explore the temporal nature of processing in the human brain using fMRI of one to a few slices. I try to trace back the various events by which these studies came about and outline why the field stalled for almost a decade. With modern volumetric EPI techniques, there should be renewed interest in these types of studies for the study of whole brain temporal processing., (Copyright © 2011 Elsevier Inc. All rights reserved.)

From the earliest fMRI experiments, it was quickly appreciated by those working with BOLD at high field that the signal change originated from visible veins whose spatial localization was relatively coarse ("the macrovasculature"), and smaller vessels ("the microvasculature") that were not individually visible in BOLD images. It was expected that a functional brain imaging technique that was predominantly sensitive to the macrovasculature would not have the same effective resolution as one sensitive to the microvasculature. Elimination of the venous signal and enhancement of the microvascular one offered the tantalizing ability to image columnar and lamellar structures in the brain and distinguished fMRI from its predecessor techniques. This article reviews a brief history of how these signal sources were first identified and separated and some of the controversy associated with the "brain versus vein" debate., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A 15-channel transmit-receive (transceive) radiofrequency (RF) coil was developed to image the human brain at 7 T. A hybrid decoupling scheme was implemented that used both capacitive decoupling and the partial geometric overlapping of adjacent coil elements. The decoupling scheme allowed coil elements to be arrayed along all three Cartesian axes; this facilitated shimming of the transmit field, B₁⁺, and parallel imaging acceleration along the longitudinal direction in addition to the standard transverse directions. Each channel was independently controlled during imaging using a 16-channel console and a 16 × 1-kW RF amplifier-matrix. The mean isolation between all combinations of coil elements was 18 ± 7 dB. After B₁⁺ shimming, the standard deviation of the transmit field uniformity was 11% in an axial plane and 32% over the entire brain superior to the mid-cerebellum. Transmit uniformity was sufficient to acquire fast spin echo images of this region of the brain with a single B₁⁺ shim solution. Signal-to-noise ratio (SNR) maps showed higher SNR in the periphery vs center of the brain, and higher SNR in the occipital and temporal lobes vs the frontal lobe. Parallel imaging acceleration in a rostral-caudal oblique plane was demonstrated. The implication of the number of channels in a transmit-receive coil was discussed: it was determined that improvements in SNR and B₁⁺ shimming can be expected when using more than 15 independently controlled transmit-receive channels., (Copyright © 2010 John Wiley & Sons, Ltd.)

Assessment of brain connectivity has revealed that the structure and dynamics of large-scale network organization are altered in multiple disease states suggesting their use as diagnostic or prognostic indicators. Further investigation into the underlying mechanisms, organization, and alteration of large-scale brain networks requires a homologous animal model that would allow neurophysiological recordings and experimental manipulations. The current study presents a comprehensive assessment of macaque resting-state networks based on evaluation of intrinsic low-frequency fluctuations of the blood oxygen-level-dependent signal using group independent component analysis. Networks were found underlying multiple levels of sensory, motor, and cognitive processing. The results demonstrate that macaques share remarkable homologous network organization with humans, thereby providing strong support for their use as an animal model in the study of normal and abnormal brain connectivity as well as aiding the interpretation of electrophysiological recordings within the context of large-scale brain networks., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Parallel imaging (PI) techniques employ the use of multiple radiofrequency (RF) channels to transmit and/or receive the NMR signal. In the current study we use a finite difference time domain (FDTD) method to simulate the electromagnetic fields of a RF coil array operating in transmit-receive (transceive) mode and receive-only mode. Optimization of these configurations for PI is studied as well. Our results suggest that a coil array can effectively be used for transceive or receive-only PI techniques. For a head coil configuration, the sensitivity encoding (SENSE) optimized coil array gap size and PI acceleration factor for MRI are shown to be a function of the physiological-to-intrinsic-noise ratio (PhINR) with a much stronger dependence on acceleration factor than gap size. The results provide a means to optimize any PI sequence by varying the acceleration factor based on the measured PhINR. In addition, an example design for an eight-element transceive coil array for heads at 4 T is given., (Copyright (c) 2006 Wiley-Liss, Inc.)

Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of "pure" estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a (31)P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.

Objective: To use functional magnetic resonance imaging (fMRI) to investigate functional connectivity, and hence, underlying neural networks, in never-treated, first-episode patients with schizophrenia using a word fluency paradigm known to activate prefrontal, anterior cingulate, and thalamic regions. Abnormal connectivity between the prefrontal cortex (PFC) and other brain regions has been demonstrated in chronic, medicated patients in previous positron emission tomography (PET) studies, but has not to our knowledge, previously been demonstrated using both first-episode, drug-naïve patients and fMRI technology., Methods: A 4.0-Tesla (T) fMRI was used to examine activation and functional connectivity [psychophysiological interactions (PPIs)] during a word fluency task compared to silent reading in 10 never-treated, first-episode patients with schizophrenia and 10 healthy volunteers of comparable age, sex, handedness, and parental education., Results: Compared to healthy volunteers, the schizophrenia patient group exhibited less activation during the word fluency task, mostly in the right anterior cingulate and prefrontal regions. Psychophysiological interactions between right anterior cingulate and other parts of the brain revealed a localized interaction with the left temporal lobe in healthy volunteers during the task and a widespread unfocussed interaction in patients., Conclusion: These findings suggest anterior cingulate involvement in the neuronal circuitry underlying schizophrenia.

Single-voxel STEAM-localized spectroscopy studies of neuropsychiatric patients yield high-quality data at short echo times, but are often limited to only a few regions of interest due to the linear increase of acquisition time with the number of regions examined. A multivoxel STEAM approach increases the number of regions of interest examined with a less than linear increase in acquisition time. Several implementation issues were considered, especially the signal contribution of outer voxel stimulated echoes (OVSE), which can lead to systematic errors in the quantification of relative metabolite concentrations. The relative signal contribution of OVSEs was found to be as great as 30% in phantoms. Gradient polarity switching completely canceled the contribution of OVSEs. A two-voxel STEAM approach produces phantom and in vivo data quality comparable to single-voxel STEAM in practically half the time. Quantification precision and accuracy are preserved in phantoms and in vivo., ((c) 2005 Wiley-Liss, Inc.)

The unique ability to learn transformed or altered visuo-motor relationships during motor learning (visuo-motor transformation learning) has engaged researchers for over a century. Compared to other forms of motor learning (e.g., sequence learning), little is known about plasticity in the cortical and/or subcortical systems involved. We used fMRI to isolate region-specific activation changes during the learning of a visuo-motor (joystick) task under a simple transformation (90 degree rotation of visual feedback). Distributed brain systems were engaged in the learning process. In particular, we found evidence of a learning-dependent transition from early activation of the posterior parietal cortex to later distributed cortico-subcortical-cerebellar responses (in the temporal and occipital cortices, basal ganglia, cerebellum and thalamus). The role of the posterior parietal cortex may relate specifically to the acquisition of the transformation, while that of the fusiform and superior temporal gyri may reflect higher level visual and visuo-spatial processing underlying consolidation. Learning-related increases in cerebellar responses are consistent with its proposed role in the acquisition of internal models of the motor apparatus. These learning-related changes suggest a role for interacting neural systems involving the co-operation of cortico-cortico, cortico-cerebellar and cortico-basal ganglia loops during visuo-motor transformation learning.

This study used high-field magnetic resonance spectroscopy to examine the correlation of 1H and 31P metabolite levels in patients with schizophrenia and normal controls. 1H and 31P in vivo spectra were acquired successively from the left anterior cingulate and left thalamus of nine chronic schizophrenic patients and eight comparable healthy controls. A significant positive correlation between glutamine (Gln) and phosphoethanolamine (PEtn) was found in the left anterior cingulate of patients. In the left thalamus of patients, a significant negative correlation between N-acetylaspartate (NAA) and glycerophosphocholine (GroPCho) was found. No significant correlations were found in controls. The correlation between glutamine and phosphoethanolamine may reflect a link between neurotransmission alterations and membrane phospholipid metabolism alterations. The negative correlation between N-acetylaspartate and glycerophosphocholine may reflect the presence of neurodegeneration.

Although multiple regions of the cerebral cortex have been implicated in swallowing, the functional contributions of each brain area remain unclear. The present study sought to clarify the roles of these cortical foci in swallowing by comparing brain activation associated with voluntary saliva swallowing and voluntary tongue elevation. Fourteen healthy right-handed subjects were examined with single-event-related functional magnetic resonance imaging (fMRI) while laryngeal movements associated with swallowing and tongue movement were simultaneously recorded. Both swallowing and tongue elevation activated 1) the left lateral pericentral and anterior parietal cortex, and 2) the anterior cingulate cortex (ACC) and adjacent supplementary motor area (SMA), suggesting that these brain regions mediate processes shared by swallowing and tongue movement. Tongue elevation activated a larger total volume of cortex than swallowing, with significantly greater activation within the ACC, SMA, right precentral and postcentral gyri, premotor cortex, right putamen, and thalamus. Although a contrast analysis failed to identify activation foci specific to swallowing, superimposed activation maps suggested that the most lateral extent of the left pericentral and anterior parietal cortex, rostral ACC, precuneus, and right parietal operculum/insula were preferentially activated by swallowing. This finding suggests that these brain areas may mediate processes specific to swallowing. Approximately 60% of the subjects showed a strong functional lateralization of the postcentral gyrus toward the left hemisphere for swallowing, whereas 40% showed a similar activation bias for the tongue elevation task. This finding supports the view that the oral sensorimotor cortices within the left and right hemispheres are functionally nonequivalent.

Signal intensity in 23Na images is altered in pathologic conditions such as ischemia and may provide information regarding tissue viability complementary to MR diffusion and perfusion imaging. However, the multicomponent transverse relaxation of 23Na (spin 3/2) complicates the determination of tissue sodium concentration from 23Na images with nonzero echo-time. The purpose of this study was to measure the long component time constant of tissue sodium T*2 relaxation in the healthy human brain at 4 T. Multiecho gradient-echo 23Na images (10 echo-times ranging from 3.8-68.7 ms) were acquired in five healthy human volunteers. T*2 was quantified on a pixel-by-pixel basis using a nonnegative least squares fitting routine using 100 equally spaced bins between 0.5-99.5 ms and parametric maps were produced representing components between 0.5-3, 3.1-50, 50.1-98, and 98.1-99.5 ms. The long T*2 component of tissue sodium (average +/- standard deviation) varied between cortex (occipital = 22.0 +/- 2.4 ms), white matter (parietal = 18.2 +/- 1.9 ms), and subcortical gray matter (thalamus = 16.9 +/- 2.4 ms). These results demonstrate considerable regional variability and establish a foundation for future characterization of 23Na T*2 in conditions such as cerebral ischemia and cancer.

Background: Membrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy ((31)P-MRS) have been reported in patients with schizophrenia in several brain regions., Aims: Using improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T (31)P-MRS., Method: Brain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm(3) effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex., Results: People with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group., Conclusions: The increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.

Objective: This study used functional connectivity analyses to assess interregional brain activity correlations during the recall of traumatic memories in traumatized subjects with and without posttraumatic stress disorder (PTSD)., Method: Both 4-T functional magnetic resonance imaging (fMRI) and functional connectivity analyses were used to assess interregional brain activity correlations during script-driven symptom provocation in traumatized subjects with (N=11) and without (N=13) PTSD. Functional connectivity analyses were carried out by using data for brain regions activated in both the PTSD group and the comparison group. The use of functional connectivity analyses in addition to subtraction analyses allowed assessment of specific brain regions involved in the recall of traumatic events and of the neuronal networks underlying the recall of such events., Results: Significant between-group differences in functional connectivity were found. Comparison of connectivity maps at coordinates x=2, y=20, z=36 (right anterior cingulate gyrus) for the two groups showed that the subjects without PTSD had greater correlation than the PTSD subjects in the left superior frontal gyrus (Brodmann's area 9), left anterior cingulate gyrus (Brodmann's area 32), left striatum (caudate), left parietal lobe (Brodmann's areas 40 and 43), and left insula (Brodmann's area 13). In contrast, the PTSD subjects showed greater correlation than the subjects without PTSD in the right posterior cingulate gyrus (Brodmann's area 29), right caudate, right parietal lobe (Brodmann's areas 7 and 40), and right occipital lobe (Brodmann's area 19)., Conclusions: The differences in brain connectivity between PTSD and comparison subjects may account for the nonverbal nature of traumatic memory recall in PTSD subjects, compared to a more verbal pattern of traumatic memory recall in comparison subjects.

Background: The goal of this study was to examine the neuronal circuitry underlying different emotional states (neutral, sad, anxious, and traumatic) in posttraumatic stress disorder (PTSD) in traumatized subjects versus traumatized subjects without PTSD., Methods: Traumatized subjects with (n = 10) and without (n = 10) PTSD were studied using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging (fMRI) at a 4 Tesla field strength., Results: Compared to the trauma-exposed comparison group, PTSD subjects showed significantly less activation of the thalamus and the anterior cingulate gyrus (area 32) in all three emotional states (sad, anxious, and traumatic)., Conclusion: These findings suggest thalamic and anterior cingulate dysfunction in the recollection of traumatic as well as other negative events. Thalamic and anterior cingulate dysfunction may underlie emotion dysregulation often observed clinically in PTSD.