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Painful diabetic peripheral neuropathy (DPN) is difficult to manage, as treatment response is often varied. The primary aim of this study was to examine differences in pain phenotypes between responders and nonresponders to intravenous lidocaine treatment using quantitative sensory testing. The secondary aim was to explore differences in brain structure and functional connectivity with treatment response. Forty-five consecutive patients who received intravenous lidocaine treatment for painful DPN were screened. Twenty-nine patients who met the eligibility criteria (responders, n = 14, and nonresponders, n = 15) and 26 healthy control subjects underwent detailed sensory profiling. Subjects also underwent multimodal brain MRI. A greater proportion of patients with the irritable (IR) nociceptor phenotype were responders to intravenous lidocaine treatment compared with nonresponders. The odds ratio of responding to intravenous lidocaine was 8.67 times greater (95% CI 1.4–53.8) for the IR nociceptor phenotype. Responders to intravenous lidocaine also had significantly greater mean primary somatosensory cortex cortical volume and functional connectivity between the insula cortex and the corticolimbic circuitry. This study provides preliminary evidence for a mechanism-based approach for individualizing therapy in patients with painful DPN.

Background Clinical phenotypic heterogeneity represents a major barrier to trials in motor neuron disease (MND) and objective surrogate outcome measures are required, especially for slowly progressive patients. We assessed responsiveness of clinical, electrophysiological and radiological muscle-based assessments to detect MND-related progression. Materials and methods A prospective, longitudinal cohort study of 29 MND patients and 22 healthy controls was performed. Clinical measures, electrophysiological motor unit number index/size (MUNIX/MUSIX) and relative T2- and diffusion-weighted whole-body muscle magnetic resonance (MR) were assessed three times over 12 months. Multi-variable regression models assessed between-group differences, clinico-electrophysiological associations, and longitudinal changes. Standardized response means (SRMs) assessed sensitivity to change over 12 months. Results MND patients exhibited 18% higher whole-body mean muscle relative T2-signal than controls (95% CI 7–29%, p p p Conclusion MUNIX and relative T2-weighted MR represent objective surrogate markers of progressive denervation in MND. Radiological changes were maximal in leg muscles, irrespective of clinical onset-site.

One of the fundamental challenges when dealing with medical imaging datasets is class imbalance. Class imbalance happens where an instance in the class of interest is relatively low, when compared to the rest of the data. This study aims to apply oversampling strategies in an attempt to balance the classes and improve classification performance. We evaluated four different classifiers from k-nearest neighbors (k-NN), support vector machine (SVM), multilayer perceptron (MLP) and decision trees (DT) with 73 oversampling strategies. In this work, we used imbalanced learning oversampling techniques to improve classification in datasets that are distinctively sparser and clustered. This work reports the best oversampling and classifier combinations and concludes that the usage of oversampling methods always outperforms no oversampling strategies hence improving the classification results.

Cognitive impairments are commonly observed in patients with multiple sclerosis and are associated with lower levels of quality of life. No consensus has been reached on how to tackle effectively cognitive decline in this clinical population non-pharmacologically. This exploratory case-control study aims to investigate the effectiveness of a hypothesis-based cognitive training designed to target multiple domains by promoting the synchronous co-activation of different brain areas and thereby improve cognition and induce changes in functional connectivity in patients with relapsing-remitting multiple sclerosis. Forty-five patients (36 females and 9 males, mean age 44.62 +/- 8.80 years) with clinically stable relapsing-remitting multiple sclerosis were assigned to either a standard cognitive training or to control groups (sham training and non-active control). The standard training included twenty sessions of computerized exercises involving various cognitive functions supported by distinct brain networks. The sham training was a modified version of the standard training that comprised the same exercises and number of sessions but with increased processing speed load. The non-active control group received no cognitive training. All patients underwent comprehensive neuropsychological and magnetic resonance imaging assessments at baseline and after 5 weeks. Cognitive and resting-state magnetic resonance imaging data were analyzed using repeated measures models. At reassessment, the standard training group showed significant cognitive improvements compared to both control groups in memory tasks not specifically targeted by the training: the Buschke Selective Reminding Test and the Semantic Fluency test. The standard training group showed reductions in functional connectivity of the salience network, in the anterior cingulate cortex, associated with improvements on the Buschke Selective Reminding Test. No changes were observed in the sham training group. These findings suggest that multi-domain training that stimulates multiple brain areas synchronously may improve cognition in people with relapsing-remitting multiple sclerosis if sufficient time to process training material is allowed. The associated reduction in functional connectivity of the salience network suggests that training-induced neuroplastic functional reorganization may be the mechanism supporting performance gains. This study was approved by the Regional Ethics Committee of Yorkshire and Humber (approval No. 12/YH/0474) on November 20, 2013.

Aims/hypothesis The aim of this work was to investigate whether different clinical pain phenotypes of diabetic polyneuropathy (DPN) are distinguished by functional connectivity at rest. Methods This was an observational, cohort study of 43 individuals with painful DPN, divided into irritable (IR, n = 10) and non-irritable (NIR, n = 33) nociceptor phenotypes using the German Research Network of Neuropathic Pain quantitative sensory testing protocol. In-situ brain MRI included 3D T1-weighted anatomical and 6 min resting-state functional MRI scans. Subgroup differences in resting-state functional connectivity in brain regions involved with somatic (thalamus, primary somatosensory cortex, motor cortex) and non-somatic (insular and anterior cingulate cortices) pain processing were examined. Multidimensional reduction of MRI datasets was performed using a machine-learning approach to classify individuals into each clinical pain phenotype. Results Individuals with the IR nociceptor phenotype had significantly greater thalamic–insular cortex (p false discovery rate [FDR] = 0.03) and reduced thalamus–somatosensory cortex functional connectivity (p-FDR = 0.03). We observed a double dissociation such that self-reported neuropathic pain score was more associated with greater thalamus–insular cortex functional connectivity (r = 0.41; p = 0.01) whereas more severe nerve function deficits were more related to lower thalamus–somatosensory cortex functional connectivity (r = −0.35; p = 0.03). Machine-learning group classification performance to identify individuals with the NIR nociceptor phenotype achieved an accuracy of 0.92 (95% CI 0.08) and sensitivity of 90%. Conclusions/interpretation This study demonstrates differences in functional connectivity in nociceptive processing brain regions between IR and NIR phenotypes in painful DPN. We also establish proof of concept for the utility of multimodal MRI as a biomarker for painful DPN by using a machine-learning approach to classify individuals into sensory phenotypes. Graphical abstract

IntroductionThere are no disease-modifying treatments for Parkinson’s disease (PD). We undertook the first drug screen in PD patient tissue and idntified ursodeoxycholic acid (UDCA) as a promising mitochondrial rescue agent. The aims of this trial are to determine safety and tolerability of UDCA in PD at 30 mg/kg, confirm the target engagement of UDCA, apply a novel motion sensor-based approach to quantify disease progression objectively, and estimate the mean effect size and its variance on the change in motor severity.Methods and analysisThis is a phase II, two-centre, double-blind, randomised, placebo-controlled trial of UDCA at a dose of 30 mg/kg in 30 participants with early PD. Treatment duration is 48 weeks, followed by an 8-week washout phase. Randomisation is 2:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48 and 56. The primary outcome is safety and tolerability. Secondary outcomes will compare the change between baseline and week 48 using the following three approaches: the Movement Disorders Society Unified Parkinson’s Disease Rating Scale Part 3 in the practically defined ‘OFF’ medication state; confirmation of target engagement, applying 31Phosphorus MR Spectroscopy to assess the levels of ATP and relevant metabolites in the brain; and objective quantification of motor impairment, using a validated, motion sensor-based approach. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups. For each secondary outcome, the change from baseline will be summarised within treatment groups using summary statistics and appropriate statistical tests assessing for significant differences. All outcomes will use an intention-to-treat analysis population.Ethics and disseminationThis trial has been approved by the East of England – Cambridgeshire and Hertfordshire Research Ethics committee. Results will be disseminated in peer-reviewed journals, presentations at scientific meetings and to patients in a lay-summary format.Trial registration numberNCT03840005.

Diabetic distal symmetrical peripheral polyneuropathy (DSP) results in decreased somatosensory cortical gray matter volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has examined whether changes in brain volume alter the functional organization of the somatosensory cortex and how this relates to the various painful DSP clinical phenotypes. In this case-controlled, multimodal brain MRI study of 44 carefully phenotyped subjects, we found significant anatomical and functional changes in the somatosensory cortex. Subjects with painful DSP insensate have the lowest somatosensory cortical thickness, with expansion of the area representing pain in the lower limb to include face and lip regions. Furthermore, there was a significant relationship between anatomical and functional changes within the somatosensory cortex and severity of the peripheral neuropathy. These data suggest a dynamic plasticity of the brain in DSP driven by the neuropathic process. It demonstrates, for the first time in our knowledge, a pathophysiological relationship between a clinically painful DSP phenotype and alterations in the somatosensory cortex.

Mitochondrial dysfunction is postulated to be central to amyotrophic lateral sclerosis pathophysiology. Evidence comes primarily from disease models and conclusive data to support bioenergetic dysfunction in vivo in patients is currently lacking. This study is the first to assess mitochondrial dysfunction in brain and muscle in people living with amyotrophic lateral sclerosis using phosphorus-31 magnetic resonance spectroscopy, the modality of choice to assess energy metabolism in vivo. We recruited twenty patients and 10 healthy age and gender-matched controls in this cross-sectional clinico-radiological study. Phosphorus-31 magnetic resonance spectroscopy was acquired from cerebral motor regions and from tibialis anterior during rest and exercise. Bioenergetic parameter estimates were derived including: adenosine triphosphate, phosphocreatine, inorganic phosphate, adenosine diphosphate, Gibbs free energy of adenosine triphosphate hydrolysis, phosphomonoesters, phosphodiesters, pH, free magnesium concentration, and muscle dynamic recovery constants. Linear regression was used to test for associations between brain data and clinical parameters (revised amyotrophic functional rating scale, slow vital capacity, and upper motor neuron score) and between muscle data and clinico-neurophysiological measures (motor unit number and size indices, force of contraction, and speed of walking). Evidence for primary dysfunction of mitochondrial oxidative phosphorylation was detected in brainstem where Gibbs free energy of adenosine triphosphate hydrolysis and phosphocreatine were reduced. Alterations were also detected in skeletal muscle in patients where resting inorganic phosphate, pH, and phosphomonoesters were increased, whereas resting Gibbs free energy of adenosine triphosphate hydrolysis, magnesium, and dynamic phosphocreatine to inorganic phosphate recovery were decreased. Phosphocreatine in brainstem correlated with respiratory dysfunction and disability; in muscle, energy metabolites correlated with motor unit number index, muscle power, and speed of walking. This study provides in vivo evidence for bioenergetic dysfunction in amyotrophic lateral sclerosis in brain and skeletal muscle, which appears clinically and electrophysiologically relevant. Phosphorus-31 magnetic resonance spectroscopy represents a promising technique to assess the pathophysiology of mitochondrial function in vivo in amyotrophic lateral sclerosis and a potential tool for future clinical trials targeting bioenergetic dysfunction.

ObjectiveTo assess clinical, electrophysiological and whole-body muscle MRI measurements of progression in patients with motor neuron disease (MND), as tools for future clinical trials, and to probe pathophysiological mechanisms in vivo.MethodsA prospective, longitudinal, observational, clinicoelectrophysiological and radiological cohort study was performed. Twenty-nine patients with MND and 22 age-matched and gender-matched healthy controls were assessed with clinical measures, electrophysiological motor unit number index (MUNIX) and T2-weighted whole-body muscle MRI, at first clinical presentation and 4 months later. Between-group differences and associations were assessed using age-adjusted and gender-adjusted multivariable regression models. Within-subject longitudinal changes were assessed using paired t-tests. Patterns of disease spread were modelled using mixed-effects multivariable regression, assessing associations between muscle relative T2 signal and anatomical adjacency to site of clinical onset.ResultsPatients with MND had 30% higher relative T2 muscle signal than controls at baseline (all regions mean, 95% CI 15% to 45%, pConclusionsWhole-body muscle MRI offers a new approach to objective assessment of denervation over short timescales in MND and enables investigation of patterns of disease spread in vivo. Muscles inaccessible to conventional clinical and electrophysiological assessment may be investigated using this methodology.

Using advanced MR neuroimaging we have demonstrated altered brain structure and functional connectivity that could serve as a potential Central Pain Signature (CPS) for painful diabetic neuropathy (DN). However, the key challenge is how to apply this potential biomarker for routine diagnostic purposes. The aim of this study was to examine if the CPS can accurately classify painful DN patients based on a patient’s pain severity. Methods: 53 painful DN patients underwent detailed clinical and neurophysiological assessments. The NTSS-6, a validated questionnaire that measures both the frequency and the intensity of neuropathic pain was used to assess pain severity. Patients were divided into high pain (NTSS-6 score >7) and low pain ( Results: There was no age or gender difference (p > 0.05) between the high and low pain groups. The CPS classified painful DN patients based on their pain intensity with 94% accuracy (AUC 0.98). The positive and negative predictive values were 0.80 and 1.00 respectively. The F1 scores for predicting high pain and low pain were 0.89 and 0.96 respectively. Brain regions identified as the best classifier were the left and right postcentral gyri, thalami, and anterior and posterior cingulate cortices. Conclusions: This novel study demonstrates that a simple, 15-minute MR brain scan can accurately classify painful DN patients according to pain intensities with high accuracy. This assessment tool has a great potential as a biomarker of diabetic neuropathic pain and may serve as a target for future trials of analgesic compounds for painful DN. Disclosure D. Selvarajah: None. K. Teh: None. G.P. Sloan: None. P. Shillo: None. I.D. Wilkinson: None. S. Tesfaye: Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation, WÖRWAG Pharma. Speaker's Bureau; Self; AstraZeneca, Merck & Co., Inc., NAPP Pharmaceuticals Limited, Neurometrix, Novo Nordisk Inc., Pfizer Inc. Other Relationship; Self; Impeto Medical. Funding European Foundation for the Study of Diabetes

Background\ud \ud A common symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM). Various brain abnormalities have been observed in patients with ME/CFS, especially in insular and limbic areas, but their link with ME/CFS symptoms is still unclear. This pilot study aimed at investigating the association between PEM in ME/CFS and changes in functional connectivity (FC) of two main networks: the salience network (SN) and the default-mode network (DMN).\ud \ud \ud Methods\ud \ud A total of 16 women, 6 with and 10 without ME/CFS, underwent clinical and MRI assessment before and after cognitive exertion. Resting-state FC maps of 7 seeds (3 for the SN and 4 for the DMN) and clinical measures of fatigue, pain and cognition were analysed with repeated-measure models. FC-symptom change associations were also investigated.\ud \ud \ud Results\ud \ud Exertion induced increases in fatigue and pain in patients with ME/CFS compared to the control group, while no changes were found in cognitive performance. At baseline, patients showed altered FC between some DMN seeds and frontal areas and stronger FC between all SN seeds and left temporal areas and the medulla. Significantly higher FC increases in patients than in controls were found only between the right insular seed and frontal and subcortical areas; these increases correlated with worsening of symptoms.\ud \ud \ud Conclusions\ud \ud Cognitive exertion can induce worsening of ME/CFS-related symptoms. These changes were here associated with strengthening of FC of the right insula with areas involved in reward processing and cognitive control.

Diabetic peripheral neuropathy (DPN) affects up to 50% of patients with diabetes and is a major cause of morbidity and increased mortality. Its clinical manifestations include distressing painful neuropathic symptoms and insensitivity to trauma that result in foot ulcerations and amputations. Several recent studies have implicated poor glycemic control, duration of diabetes, hyperlipidemia (particularly hypertryglyceridaemia), elevated albumin excretion rates, and obesity as risk factors for the development of DPN. However, similar data are not available for painful DPN. Moreover, although there is now strong evidence for the importance of peripheral nerve microvascular disease in the pathogenesis of DPN, peripheral structural biomarkers of painful DPN are lacking. However, there is now emerging evidence for the involvement of the central nervous system in both painful and painless DPN afforded by magnetic resonance imaging. This review will focus on this emerging evidence for central changes in DPN, hitherto considered a peripheral nerve disease only.

Aims: Diabetic neuropathy (DN) is a serious complication which was hitherto considered a disease of the peripheral nervous system. In this study we sought to investigate in detail changes in brain morphometry in DN. The aim of this study was to identify regional brain volume changes that were specific to DN (painful and painless DN) Methods: 102 patients with diabetes (34 No-DN, 34 Painless DN and 34 Painful DN) and 34 healthy volunteers underwent detailed clinical and neurophysiological assessments. All subjects underwent 3-dimensional T1-weighted brain MRI (3.0T, Philips). Brain volume analysis was performed using SIENAX (www.fmrib.ox.ac.uk/fsl) and Freesurfer (http://surfer.nmr.mgh.harvard.edu/). Results: Groups were matched for age and gender. Total brain volume was significantly lower painful DN [1401.7 (10.7)ml] and painless DN [1393.5 (69.6)ml]) compared to HV [1457.2(79.2)ml] and No DN [1437.2(60.9)ml]; ANOVA p= Conclusion: This is the largest cohort study of brain volume changes in subjects with DN examined to date. We have demonstrated significant reduction in grey matter volume in painful and painless DN subjects. In painful DN this is localised within the somatomotor cortex and insula. These findings highlight significant CNS involvement in DN that provides clues to the pathogenesis of this condition. Disclosure D. Selvarajah: None. F. Heiberg-Gibbons: None. I.D. Wilkinson: None. R. Gandhi: None. S. Tesfaye: Speaker's Bureau; Self; Pfizer Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Wörwag Pharma GmbH & Co. KG.

Aim: Mild Cognitive Impairment (MCI) is thought to be a chronic sequelae of type 2 diabetes (T2DM). Cerebral atrophy is known to be associated with cognitive decline, particularly in dementia. Cerebral tissue volumes, in areas associated with cognitive function, were examined in matched patients with T2DM subjects and early cognitive decline. The aim of this study was to compare T2DM patients with and without MCI to identify regional brain volume changes that were specific to MCI. Method: Seventy-six age and gender matched subjects [30, T2DM+normal cognition (T2DM); 17, T2DM+MCI (T2DM/MCI) and 29, healthy volunteers (HV)] were recruited. All subjects underwent clinical and questionnaire (Addenbrooke’s Cognitive Assessment [ACE-R]) assessments and high-resolution, 3D T1-weighted Magnetic Resonance Imaging (MRI, 3T Philips Ingenia). Cerebral volumes were analysed using voxel based morphometry (VBM, FSL, Oxford). Results: Demographic data revealed aged-matched participants between all three groups (mean age 69.3-71.5 years, ANOVA, p = 0.164). Mean age of last education was significantly lower in the T2DM/MCI group (mean±SD;15.1 ±0.9 when compared to the other groups (HV 19.3±5.6, T2DM 17.1±2.9) Kruskal-Wallis, p = 0.003. T2DM/MCI ACE-R score (mean±SD; 83±4) was significantly lower compared to other groups (HV=96±2, T2DM=94±3; ANOVA, p Conclusion: This study demonstrates significantly lower cortical differences in areas associated with cognition in patients with T2DM and early cognitive impairment. Further investigation of both anatomical and functional cerebral involvement is required to examine the pathological mechanisms underlying the increased cognitive impairment risk associated with T2DM. Disclosure L. Hunt: None. D. Selvarajah: None. S. Tesfaye: Speaker's Bureau; Self; Pfizer Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Wörwag Pharma GmbH & Co. KG. I.D. Wilkinson: None.

PURPOSE: As Quantitative Susceptibility Mapping (QSM) is maturing, more clinical applications are being explored. With this comes the question whether QSM is sufficiently robust and reproducible to be directly used in a clinical setting where patients are possibly not cooperative and/or unable to suppress involuntary movements sufficiently. Subjects and Methods: Twenty-nine patients with Alzheimer's Disease (AD), 31 patients with Mild Cognitive Impairment (MCI) and 41 healthy controls (HC) were scanned on a 3T scanner, including a multi-echo gradient-echo sequence for QSM and an inversion-prepared segmented gradient-echo sequence (T1-TFE, MPRAGE). The severity of motion artifacts (excessive/strong /noticeable/invisible) was categorized via visual inspection by two independent raters. Quantitative susceptibility was reconstructed using "Joint background-field removal and segmentation-Enhanced Dipole Inversion" (JEDI), based on segmented subcortical gray-matter regions, as well as using "Morphology Enabled Dipole Inversion" (MEDI). Statistical analysis of the susceptibility maps was performed per region. Results: A large fraction of the data showed motion artifacts, visible in both magnitude images and susceptibility maps. No statistically significant susceptibility differences were found between groups including motion-affected data. Considering only subjects without visible motion, a significant susceptibility differences were observed in caudate nucleus as well as in putamen. Conclusion: Motion-effects can obscure statistically significant differences in QSM between patients and controls. Additional measures to restrict and/or compensate for subject motion should be taken for QSM in standard clinical settings to avoid risk of false findings.&#13.

Self-deception and impression-management comprise two types of deceptive, but generally socially acceptable behaviours, which are common in everyday life as well as being present in a number of psychiatric disorders. We sought to establish and dissociate the 'normal' brain substrates of self-deception and impression-management. Twenty healthy participants underwent fMRI scanning at 3T whilst completing the 'Balanced Inventory of Desirable Responding' test under two conditions: 'fake good', giving the most desirable impression possible and 'fake bad' giving an undesirable impression. Impression-management scores were more malleable to manipulation via 'faking' than self-deception scores. Response times to self-deception questions and 'fake bad' instructions were significantly longer than to impression-management questions and 'fake good' instructions respectively. Self-deception and impression-management manipulation and 'faking bad' were associated with activation of medial prefrontal cortex (mPFC) and left ventrolateral prefrontal cortex (vlPFC). Impression-management manipulation was additionally associated with activation of left dorsolateral prefrontal cortex and left posterior middle temporal gyrus. 'Faking bad' was additionally associated with activation of right vlPFC, left temporo-parietal junction and right cerebellum. There were no supra-threshold activations associated with 'faking good'. Our neuroimaging data suggest that manipulating self-deception and impression-management and more specifically 'faking bad' engages a common network comprising mPFC and left vlPFC. Shorter response times and lack of dissociable neural activations suggests that 'faking good', particularly when it comes to impression-management, may be our most practiced 'default' mode.

Gravitational forces may lead to local changes in subarachnoid cerebrospinal fluid (CSF) layer thickness, which has important implications for neurophysiological modulation and recording techniques. This study examines the effect of gravitational pull associated with different head positions on the distribution of subarachnoid CSF using structural magnetic resonance imaging. Images of seven subjects in three different positions (supine, left lateral and prone) were statistically compared. Results suggest that subarachnoid CSF volume decreases on the side of the head closest to the ground, due to downward brain movement with gravity. These findings warrant future research into currently unexplored gravitation-induced changes in regional subarachnoid CSF thickness.

MR elastography (MRE) of the brain is being explored as a biomarker of neurodegenerative disease such as dementia. However, MRE measures for healthy brain have varied widely. Differing wave delivery methodologies may have influenced this, hence finite element-based simulations were performed to explore this possibility.The natural frequencies of a series of cranial models were calculated, and MRE-associated vibration was simulated for different wave delivery methods at varying frequency, using simple isotropic viscoelastic material models for the brain. Displacement fields and the corresponding brain constitutive properties estimated by standard inversion techniques were compared across delivery methods and frequencies.The delivery methods produced widely different MRE displacement fields and inversions. Furthermore, resonances at natural frequencies influenced the displacement patterns. Consequently, some delivery methods led to lower inversion errors than others, and the error on the storage modulus varied by up to 11% between methods.Wave delivery has a considerable impact on brain MRE reliability. Assuming small variations in brain biomechanics, as recently reported to accompany neurodegenerative disease (e.g., 7% for Alzheimer's disease), the effect of wave delivery is important. Hence, a consensus should be established on a consistent methodology to ensure diagnostic and prognostic consistency. Magn Reson Med 78:341-356, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

To examine the extent of brain abnormality in patients with coeliac disease referred for neurological opinion and evaluate MR imaging sequences as biomarkers for neurological dysfunction, given the lack of readily available serological markers of neurological disease in this cohort.Retrospective examination of a consecutive cohort of patients (n = 33, mean age = 44 ± 13 years (range 19-64)) with biopsy proven coeliac disease referred for neurological opinion. Patients were divided into subgroups based on their primary neurological complaint (balance disturbance, headache and sensory loss). 3T MR was used to evaluate differences in brain grey matter density, cerebellar volume, cerebellar neurochemistry and white matter abnormalities (WMAs) between subjects and controls.Cerebellar volume was significantly less in the patient group than in controls (6.9 ± 0.7% vs 7.4 ± 0.9% of total intracranial volume, p0.05). Significantly less grey matter density was found in multiple brain regions, both above and below the tentorium cerebelli, than in controls (p0.05). 12 (36%) patients demonstrated WMAs unexpected for the patient's age, with the highest incidence occurring in the headache subgroup. This subgroup averaged almost twice the number of WMAs per MR imaging than the subgroup with balance disturbance and six times more than the subgroup with sensory loss.Patients with established coeliac disease referred for neurological opinion show significant brain abnormality on MR imaging. MR imaging may provide valuable biomarkers of disease in this patient cohort.

Although there is evidence that exact calculation recruits left hemisphere perisylvian language systems, recent work has shown that exact calculation can be retained despite severe damage to these networks. In this study, we sought to identify a "core" network for calculation and hence to determine the extent to which left hemisphere language areas are part of this network. We examined performance on addition and subtraction problems in two modalities: one using conventional two-digit problems that can be easily encoded into language; the other using novel shape representations. With regard to numerical problems, our results revealed increased left fronto-temporal activity in addition, and increased parietal activity in subtraction, potentially reflecting retrieval of linguistically encoded information during addition. The shape problems elicited activations of occipital, parietal and dorsal temporal regions, reflecting visual reasoning processes. A core activation common to both calculation types involved the superior parietal lobule bilaterally, right temporal sub-gyral area, and left lateralized activations in inferior parietal (BA 40), frontal (BA 6/8/32) and occipital (BA 18) regions. The large bilateral parietal activation could be attributed to visuo-spatial processing in calculation. The inferior parietal region, and particularly the left angular gyrus, was part of the core calculation network. However, given its activation in both shape and number tasks, its role is unlikely to reflect linguistic processing per se. A possibility is that it serves to integrate right hemisphere visuo-spatial and left hemisphere linguistic and executive processing in calculation.

Introduction\ud Current methods of identifying axillary node metastases in breast cancer patients are highly accurate, but are associated with several adverse events. This review evaluates the diagnostic accuracy of magnetic resonance imaging (MRI) techniques for identification of axillary metastases in early stage newly diagnosed breast cancer patients.\ud \ud Methods\ud Comprehensive searches were conducted in April 2009. Study quality was assessed. Sensitivity and specificity were meta-analysed using a bivariate random effects approach, utilising pathological diagnosis via node biopsy as the comparative gold standard.\ud \ud Results\ud Based on the highest sensitivity and specificity reported in each of the nine studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78–96%; range 65–100%) and mean specificity 90% (95% CI: 75–96%; range 54–100%). Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61–100%) and mean specificity 96% (95% CI: 72–100%). Across three studies of gadolinium-enhanced MRI (n = 187), mean sensitivity was 88% (95% CI: 78–94%) and mean specificity 73% (95% CI: 63–81%). In the single study of in-vivo proton MR spectroscopy (n = 27), sensitivity was 65% (95% CI: 38–86%) and specificity 100% (95% CI: 69–100%).\ud \ud Conclusions\ud USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity and may make a useful addition to the current diagnostic pathway. Additional larger studies with standardised methods and standardised criteria for classifying a node as positive are needed. Current estimates of sensitivity and specificity do not support replacement of SLNB with any current MRI technology in this patient group.

Diabetic neuropathy is a chronic and often disabling condition that affects a significant number of individuals with diabetes. Long considered a disease of the peripheral nervous system, there is now increasing evidence of central nervous system involvement. Recent advances in neuroimaging methods detailed in this review have led to a better understanding and refinement of how diabetic neuropathy affects the central nervous system. Recognition that diabetic neuropathy is, in part, a disease that affects the whole nervous system is resulting in a critical rethinking of this disorder, opening a new direction for further research.

The clock drawing (CD) task involves visual integration skills associated with parietal lobe function. Seven mild Alzheimer's Disease (AD) patients and 11 healthy elderly controls (EC) underwent functional magnetic resonance imaging (fMRI) scanning while viewing a radial motion (RM) task. This RM task in EC activated the bilateral secondary visual cortex and parietal regions, whereas AD patients activated only the right-sided secondary visual cortex. The magnitude of the fMRI signal in the left superior parietal lobe was positively correlated with performance on the CD task in AD patients. These findings suggest that complex visuospatial processing impairments reflect the underlying AD neuropathology in parietal regions.

Background: In vitro studies have shown that the 3-Tesla (T) magnetic resonance (MR) characteristics of high- and standard-molar gadolinium-based contrast agents differ. Such differences may indicate that high-molar (1.0 M) agents offer advantages for perfusion-weighted imaging (PWI) at 3T, as has been previously reported at 1.5T. Purpose: To investigate possible intraindividual differences of high- versus low-molar contrast agents on PWI at 3T in patients with intracranial space-occupying lesions. Material and Methods: Six patients with intraaxial and five patients with extraaxial tumors underwent two MR examinations at 3T, separated by at least 48 hours. On each occasion, an exogenous contrast-based, T2*-weighted, gradient-recalled echo-planar imaging (EPI) technique was used to determine the intracranial perfusion characteristics using one of two intravenous contrast agents: either 5 ml of 1.0 M gadobutrol or 10 ml of 0.5 M gadopentetate dimeglumine. The primary PWI outcome measure was region-of-interest maximal signal change (Cmax). Results: The difference in Cmax for gray and white matter (ΔCmax) was significantly higher for gadobutrol compared to gadopentetate dimeglumine ( Pmax between gray and white matter (rCmax = CmaxGray/CmaxWhite) was also significantly higher (median 24.6%, range 13.7–36.5%) for gadobutrol ( Pmax between the whole tumor and whole normal side hemisphere was higher in five out of the six intraaxial tumor cases. A significantly higher ratio (ΔCmax/Cmax) in the difference between Cmax of gray and white matter (from hemisphere without brain lesion) compared to Cmax for the hemisphere containing the neoplasm (hemisphere with brain lesion) was demonstrated for gadobutrol in intraaxial tumors ( P Conclusion: Higher-concentration 1.0 M gadobutrol can offer advantages over standard 0.5 M gadopentetate dimeglumine, particularly with respect to delineation between gray and white matter and for the demarcation of highly vascularized tumor tissue on brain PWI performed at 3T.

Dehydration can affect brain structure which has important implications for human health. In this study, we measured regional changes in brain structure following acute dehydration. Healthy volunteers received a structural MRI scan before and after an intensive 90‐min thermal‐exercise dehydration protocol. We used two techniques to determine changes in brain structure: a manual point counting technique using MEASURE, and a fully automated voxelwise analysis using SIENA. After the exercise regime, participants lost (2.2% ± 0.5%) of their body mass. Using SIENA, we detected expansion of the ventricular system with the largest change occurring in the left lateral ventricle (P = 0.001 corrected for multiple comparisons) but no change in total brain volume (P = 0.13). Using manual point counting, we could not detect any change in ventricular or brain volume, but there was a significant correlation between loss in body mass and third ventricular volume increase (r = 0.79, P = 0.03). These results show ventricular expansion occurs following acute dehydration, and suggest that automated longitudinal voxelwise analysis methods such as SIENA are more sensitive to regional changes in brain volume over time compared with a manual point counting technique. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.

‘Munchausen's syndrome by proxy’ characteristically describes women alleged to have fabricated or induced illnesses in children under their care, purportedly to attract attention. Where conclusive evidence exists the condition's aetiology remains speculative, where such evidence is lacking diagnosis hinges upon denial of wrong-doing (conduct also compatible with innocence). How might investigators obtain objective evidence of guilt or innocence? Here, we examine the case of a woman convicted of poisoning a child. She served a prison sentence but continues to profess her innocence. Using a modified fMRI protocol (previously published in 2001) we scanned the subject while she affirmed her account of events and that of her accusers. We hypothesized that she would exhibit longer response times in association with greater activation of ventrolateral prefrontal and anterior cingulate cortices when endorsing those statements she believed to be false (i.e., when she ‘lied’). The subject was scanned 4 times at 3 Tesla. Results revealed significantly longer response times and relatively greater activation of ventrolateral prefrontal and anterior cingulate cortices when she endorsed her accusers' version of events. Hence, while we have not ‘proven’ that this subject is innocent, we demonstrate that her behavioural and functional anatomical parameters behave as if she were.

Objective quantification of brain structure can aid diagnosis and therapeutic monitoring in several neuropsychiatric disorders. In this study, we aimed to compare direct and indirect quantification approaches for hippocampal formation changes in patients with mild cognitive impairment and Alzheimer's disease (AD).Twenty-one healthy volunteers (mean age: 66.2), 21 patients with mild cognitive impairment (mean age: 66.6), and 10 patients with AD (mean age: 65.1) were enrolled. All subjects underwent extensive neuropsychological testing and were imaged at 1.5T (Vision, Siemens, Germany; T1w coronal TR=4 ms, Flip=13 degrees , FOV=250 mm, Matrix=256 x 256, 128 contiguous slices, 1.8mm). Direct measurement of the hippocampal formation was performed on coronal slices using a standardized protocol, while indirect temporal horn volume (THV) was calculated using a watershed algorithm-based software package (MeVis, Germany). Manual tracing took about 30 min, semi-automated measurement less than 3 min time.Successful direct and indirect quantification was performed in all subjects. A significant volume difference was found between controls and AD patients (p0.001) with both the manual and the semi-automated approach. Group analysis showed a slight but not significant decrease of hippocampal volume and increase in temporal horn volume (THV) for subjects with mild cognitive impairment compared to volunteers (p0.07). A significant correlation (p0.001) of direct and indirect measurement was found.The presented indirect approach for hippocampus volumetry is equivalent to the direct approach and offers the advantages of observer independency, time reduction and thus usefulness for clinical routine.

Behavioural and functional anatomical responses exhibited by humans support the hypothesis that deception involves the prefrontal executive. Functional neuroimaging studies have demonstrated that ventrolateral prefrontal cortex (among other areas) is activated during lying, compared with telling the truth. However, despite some consistencies discernible across studies, problems remain concerning experimental validity, e.g., the expediencies of experimenter-sanctioned cued-deception (i.e., subjects being told when to lie); such 'lies' may not have comprised adequate proxies for 'real-life' deception. In this experiment, we attempted to address such confounding issues by designing an fMRI paradigm in which subjects chose when to lie (thereby minimising cue-dependency), using spoken words, concerning intimate material, which they regarded as 'embarrassing'; and where further control conditions required them to 'comply' with their examiners or to 'defy' them (by withholding pre-specified responses). The main effect of lying revealed significant activation of ventrolateral prefrontal cortices. These results replicate and extend our previous findings to those circumstances under which subjects are allowed to choose when to deceive.

Familiarity with a speaker’s voice has been shown to enhance its auditory processing, implicating physiological eiects at the level of the auditory cortex, although auditory cortical involvement has not previously been demonstrated.Eleven healthy right-handed male participants performed two tasks during blood oxygenation level-dependant functional MRI at 1.5 T. Both tasks used the same vocal stimuli. In task 1, they classi¢ed speakers as familiar or unfamiliar. In task 2, they judged stimuli as being in the right or left auditory ¢eld. Our analysis showed an area of auditory cortex on the lower bank of the superior temporal sulcus that was preferentially activated by familiar voices in both tasks. Familiar voices may elicit access to detailed sensory expectations, allowing enhanced auditory cortical processing. NeuroReport 00:000^ 000 � c 2007 Lippincott Williams & Wilkins.

Background: Understanding hemodynamic environment in vessels is important for realizing the mechanisms leading to vascular pathologies.\ud \ud \ud \ud Objectives: Three-dimensional velocity vector field in carotid bifurcation is visualized using TR 3D phase-contrast magnetic resonance imaging (TR 3D PC MRI) and computational fluid dynamics (CFD). This study aimed to present a qualitative and quantitative comparison of the velocity vector field obtained by each technique.\ud \ud \ud \ud Subjects and Methods: MR imaging was performed on a 30-year old male normal subject. TR 3D PC MRI was performed on a 3 T scanner to measure velocity in carotid bifurcation. 3D anatomical model for CFD was created using images obtained from time-of-flight MR angiography. Velocity vector field in carotid bifurcation was predicted using CFD and PC MRI techniques. A statistical analysis was performed to assess the agreement between the two methods.\ud \ud \ud \ud Results: Although the main flow patterns were the same for the both techniques, CFD showed a greater resolution in mapping the secondary and circulating flows. Overall root mean square (RMS) errors for all the corresponding data points in PC MRI and CFD were 14.27% in peak systole and 12.91% in end diastole relative to maximum velocity measured at each cardiac phase. Bland-Altman plots showed a very good agreement between the two techniques. However, this study was not aimed to validate any of methods, instead, the consistency was assessed to accentuate the similarities and differences between Time-resolved PC MRI and CFD.\ud \ud \ud \ud Conclusion: Both techniques provided quantitatively consistent results of in vivo velocity vector fields in right internal carotid artery (RCA). PC MRI represented a good estimation of main flow patterns inside the vasculature, which seems to be acceptable for clinical use. However, limitations of each technique should be considered while interpreting results.

That auditory hallucinations are voices heard in the absence of external stimuli implies the existence of endogenous neural activity within the auditory cortex responsible for their perception. Further, auditory hallucinations occur across a range of healthy and disease states that include reduced arousal, hypnosis, drug intoxication, delirium, and psychosis. This suggests that, even in health, the auditory cortex has a propensity to spontaneously “activate” during silence. Here we report the findings of a functional MRI study, designed to examine baseline activity in speech-sensitive auditory regions. During silence, we show that functionally defined speech-sensitive auditory cortex is characterized by intermittent episodes of significantly increased activity in a large proportion (in some cases >30%) of its volume. Bilateral increases in activity are associated with foci of spontaneous activation in the left primary and association auditory cortices and anterior cingulate cortex. We suggest that, within auditory regions, endogenous activity is modulated by anterior cingulate cortex, resulting in spontaneous activation during silence. Hence, an aspect of the brain's “default mode” resembles a (preprepared) substrate for the development of auditory hallucinations. These observations may help explain why such hallucinations are ubiquitous.

The purpose of this study is to describe our initial experience of imaging adults with localisation-related epilepsy using MR imaging at 3.0T. We discuss the findings in the context of the recently released NICE guidelines that provide detailed advice on imaging people with epilepsy in the UK. 120 consecutive people over the age of 16 years with localisation-related epilepsy were referred for clinical MR examinations from a regional neuroscience centre in England. None of the people had had MR examinations prior to the present study. High resolution MR imaging was performed taking advantage of the high field strength and high performance gradients of the system. Two experienced neuroradiologists reported on the examinations independently and the presence and type of pathology was recorded. There was complete agreement between the two reporters in all 120 cases. The overall frequency of abnormalities shown by MR was 31/120 (26%) and the commonest abnormality shown was mesial temporal sclerosis found in 10/120 (8%). Tumours were shown in 4/120, all of which appeared low grade as judged by imaging criteria. Epilepsy is the commonest neurological condition and demands a significant resource in order to provide good care for sufferers. Recent guidelines published in the UK have suggested that the majority of people with epilepsy should receive brain MR as part of their routine assessment. Our work shows that using the most sophisticated MR imaging in a highly selected population there is a modest pick-up rate of brain abnormalities. If a widespread epilepsy-imaging programme is started the detection rate is likely to be much lower. Although MR is acknowledged to be a reliable way of detecting pathology in people with epilepsy there is a dearth of information studying the health economics of imaging epilepsy in relation to patient management and outcomes.

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

MRI imaging has significantly improved the detection of brain lesions over the past few decades. It has high sensitivity to intracranial pathology but confident preoperative tissue diagnosis is relatively unusual. MR spectroscopy provides in-vivo biochemical information and has been used to improve the low specificity of tumour diagnosis. During the last decade there have been a number of reports making the case that proton spectroscopy can distinguish different grades of glial tumours and in some situations provide information on histological type. We report four children who presented with neurological symptoms and focal masses on MRI. MRS in each of them gave results consistent with textbook descriptions of malignancy, but in all four cases the abnormalities were subsequently shown to be due to demyelination. We reiterate that spectroscopic appearances are nonspecific and spectroscopic data should be evaluated in the light of concurrent imaging features and the clinical presentation.

AIMS: To corroborate the findings of in utero magnetic resonance imaging (MRI) with autopsy and post-mortem MRI in cases of known or suspected central nervous system (CNS) abnormalities on ultrasound and to compare the diagnostic accuracy of ante-natal ultrasound and in utero MRI. METHODS: Twelve pregnant women, whose foetuses had suspected central nervous system abnormalities underwent in utero MRI. The foetuses were imaged using MRi before autopsy. The data were used to evaluate the diagnostic accuracy of in utero MRI when compared with a reference standard of autopsy and post-mortem MRI in 10 cases and post-mortem MRI alone in two cases. RESULTS: The diagnostic accuracy of antenatal ultrasound and in utero MRI in correctly characterizing brain and spine abnormalities were 42 and 100%, respectively. CONCLUSION: In utero MRI provides a useful adjuvant to antenatal ultrasound when assessing CNS abnormalities by providing more accurate anatomical information. Post-mortem MRI assists the diagnosis of macroscopic structural abnormalities.

Objective To compare the diagnostic accuracy of the current reference standard-ultrasound with in utero magnetic resonance imaging, in a selected group of patients. Design Prospective study. Setting Five fetal maternal tertiary referral centres and an academic radiology unit. Sample One hundred cases of fetuses with central nervous system abnormalities where there has been diagnostic difficulties on ultrasound. In 48 cases the women were less than 24 weeks of gestation and in 52 cases later in pregnancy. Methods All women were imaged on a 1.5 T clinical system using a single shot fast spin echo technique. The results of antenatal ultrasound and in utero magnetic rosenance were compared. Main outcome measures The definitive diagnosis was made either at autopsy or by postmortem magnetic resonance imaging, in cases that went to termination of pregnancy, or a combination of postnatal imaging and clinical follow up in the others. Results In 52 of cases, ultrasound and magnetic resonance gave identical results and in a further 12, magnetic resonance provided extra information that was judged not to have had direct effects on management. In 35 of cases, magnetic resonance either changed the diagnosis (29) or gave extra information that could have altered management (6). In 11 of the 30 cases where magnetic resonance changed the diagnosis, the brain was described as normal on magnetic resonance. Conclusions In utero magnetic resonance imaging is a powerful tool in investigating fetal brain abnormalities. Our results suggest that in selected cases of brain abnormalitites, detected by ultrasound, antenatal magnetic resonance may provide additional, clinically useful information that may alter management.

Purpose: To evaluate post mortem magnetic resonance imaging of the fetus to provide data on the rate of growth of the cerebellum, bony posterior fossa, supratentorial bony compartment and cerebrum. Material and Methods: Twenty fetuses subsequently shown to have normal brain and spines on autopsy were studied using MRI post mortem. MRI from 20 normal pediatric brain examinations in children aged 6 years or younger were studied for comparison. Post mortem MRI was performed using a high‐resolution fast spin echo technique providing T2 weighted images. The area of the cerebellar vermis, posterior fossa, supratentorial skull cavity and cerebral hemispheres was measured in the sagittal plane in all cases. These measurements were compared over the age ranges studied. Results: We have shown that there are differences in the rate of growth and the apparent commencement of growth between the structures under study. The cerebellum appeared to start its significant growth at 16.5 weeks with a rate of 16 mm2/week throughout pregnancy, while the cerebral hemisphere appeared to commence significant growth at 13 weeks at a rate of 184 mm2/week throughout pregnancy. This is in contrast to the bony posterior fossa, whose growth paralleled the supratentorial bony compartment at all ages studied. Conclusion: We interpret our findings as showing relatively late commencement of cerebellar growth compared to the cerebral hemispheres, whereas the growth of the bony posterior fossa appears to be in advance and independent of cerebellar growth. Our results support the hypothesis that posterior fossa development depends on raised hydrostatic pressure in the CSF containing structures of the posterior fossa. When this mechanism fails, as in some cases of myelomeningocoele, a small posterior fossa is formed which characterizes the Chiari 2 malformation.

The stereological method of cross-counting based on the Cavalieri principle is widely used in neuroimaging to estimate the volume of cerebral structures. Although superficially simple, the stereological technique is validated by arcane mathematical proofs, so the cross size is determined by most investigators on a pragmatic basis with the assumption that the volume calculated is independent of the cross size used. We used three cross sizes (8x8, 5x5 and 3x3 voxels) to estimate the brain volume of six healthy control subjects. The volume estimate using a cross size of 3x3 was 9% larger than with a cross size of 5x5 and the latter was 15% larger than with a cross size of 8x8. We conclude that cross size significantly affects whole brain volume estimates and this result is presumably applicable to other structures whose cross-sectional areas form complex shapes. Investigators should be aware of this fact, especially when trying to make direct comparisons between volume estimates derived from the stereological method using different cross sizes.

The first generation of digital subtraction MR angiography using thick-slab contrast-enhanced 2D projection techniques has confirmed the potential of MRI to produce noninvasive subsecond angiograms of the craniocervical circulation. As time-resolved techniques become more sophisticated and 3D acquisitions can be obtained with high isotropic spatial resolution we may start to see the demise of catheter angiography as a diagnostic procedure.

This paper introduces the concept of imaging with stepped magnetic fields within the main B 0 field. The resonance frequency within each step is separated from the next by an amount greater than the imaging bandwidth. Each step thus gives rise to a separate imaging region enabling simultaneous imaging over multiple slices without aliasing. The auxiliary magnetic field regions are produced by coil inserts. The principle is illustrated using simple coil designs which introduce up to two steps into the main B 0 field. Phantoms placed in each uniform region were successfully imaged simultaneously with no aliasing.

The combination of an in-plane B(1) sensitivity encoding (SENSE) technique with a simultaneous multiple-slice B(0) field step technique (multiple-acquisition micro B(0) array (MAMBA)) has produced high scan time reduction factors (R < or = 8). In this study, two slices were acquired simultaneously in combination with x2 and x4 SENSE in-plane encoding using a MAMBA stepped B(0) field coil inside a four-channel phased-array coil system. Experiments were performed on a 1.5 T Infinion system (Philips Medical Systems, Cleveland, OH). The signal-to-noise ratio (SNR) was reduced with higher R factors, as was expected from the reduced number of acquisitions used to create the unaliased images. The combination of SENSE and MAMBA offers great promise for reducing scan times through parallel acquisition while at the same time reducing the number of RF channels required by a factor equal to the number of field steps employed. The B(1) array combined with MAMBA (B(1)AC-MAMBA) technique is applicable when the length of an object is much greater than its diameter, as in scanning limbs or in whole-body screening for disease.

AIM: To study the proton MR spectroscopic findings in Creutzfeldt--Jakob disease (CJD) (sporadic and variant). MATERIALS AND METHODS: MR imaging and proton MR spectra were acquired in two patients with sporadic CJD (biopsy proven) and one patient with variant CJD. RESULTS: The two patients with sporadic CJD demonstrated MR signal change within the basal ganglia and thalami and reduced N-acetylaspartate (NAA):creatine ratios. The patient with variant CJD showed characteristic signal change within the pulvinar of the thalami and a markedly reduced N-acetylaspartate:creatine ratio. CONCLUSION: All three patients with CJD demonstrated evidence of reduced N-acetylaspartate: creatine ratios on MR spectroscopy. These changes imply that neuronal loss and/or dysfunction is a consistent finding in established CJD. Pandya H. G., et al (2003) Clinical Radiology58, 148--153

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency.

Healthy human brain diffusion anisotropy maps derived from standard spin echo diffusion tensor imaging (DTI) were compared with those using fluid-attenuated inversion recovery (FLAIR) preparation prior to DTI to null the signal from cerebrospinal fluid (CSF). Consistent comparisons entailed development of DTI postprocessing methods, image masking based on fitting quality, and an objective region-of-interest-based method for assessment of white matter extent. FLAIR DTI achieved an extended delineation of major white-matter tracts (genu, splenium, and body of the corpus callosum) close to large CSF-filled spaces (lateral ventricles), but did not affect representation of tracts remote from CSF (internal and external capsules and coronal radiation). This result, which was detectable qualitatively (visual inspection), was verified quantitatively by analyses of the relative anisotropy (RA) distribution over white matter structures for 11 subjects. FLAIR DTI thus suppresses the CSF signal that otherwise masks underlying anisotropic parenchymal tissue through partial volume averaging.

We introduce two independent component analysis (ICA) methods, spatiotemporal ICA (stICA) and skew-ICA, and demonstrate the utility of these methods in analyzing synthetic and event-related fMRI data. First, stICA simultaneously maximizes statistical independence over both time and space. This contrasts with conventional ICA methods, which maximize independence either over time only or over space only; these methods often yield physically improbable solutions. Second, skew-ICA is based on the assumption that images have skewed probability density functions (pdfs), an assumption consistent with spatially localized regions of activity. In contrast, conventional ICA is based on the physiologically unrealistic assumption that images have symmetric pdfs. We combine stICA and skew-ICA, to form skew-stICA, and use it to analyze synthetic data and data from an event-related, left-right visual hemifield fMRI experiment. Results obtained with skew-stICA are superior to those of principal component analysis, spatial ICA (sICA), temporal ICA, stICA, and skew-sICA. We argue that skew-stICA works because it is based on physically realistic assumptions and that the potential of ICA can only be realized if such prior knowledge is incorporated into ICA methods.

A method of image guidance for neurosurgery using the surgeon's binocular depth perception is described. Magnetic resonance volume acquisitions and surface rendering software were used to produce stereoscopic pairs of images of the surface of the heads of patients with brain tumours. Stereoscopic pairs of the surface rendering of the tumour were also produced. The two pairs of images were colour-coded and combined into one pair of 35-mm slides. A stereoscopic viewer was constructed to allow simultaneous viewing of the pair of slides and the patient's head. Registration was achieved by moving the stereoscope in space until the virtual images of the rendered surface of the head coincided with the real head. The stereoscope was then locked in position and the virtual image of the tumour was projected 'into' the patient's head to allow the surgeon to locate the tumour. The instrument was used in six cases. A lateral accuracy of 10-15 mm was achieved and a depth accuracy of 5-10 mm.

Efficient storage and retrieval of digital data is the focus of much commercial and academic attention. With personal computers, there are two main ways to retrieve files: hierarchical navigation and query-based search. In navigation, users move down their virtual folder hierarchy until they reach the folder in which the target item is stored. When searching, users first generate a query specifying some property of the target file (e.g., a word it contains) and then select the relevant file when the search engine returns a set of results. Despite advances in search technology, users prefer retrieving files using virtual folder navigation, rather than the more flexible query-based search. Using fMRI we provide an explanation for this phenomenon by demonstrating that folder navigation results in activation of the posterior limbic (including the retrosplenial cortex) and parahippocampal regions similar to that previously observed during real-world navigation in both animals and humans. In contrast, search activates the left inferior frontal gyrus, commonly observed in linguistic processing. We suggest that the preference for navigation may be due to the triggering of automatic object finding routines and lower dependence on linguistic processing. We conclude with suggestions for future computer systems design.

Self-harm, such as self-cutting, self-poisoning or jumping from height, regardless of intentions, is common among people with schizophrenia. We wished to investigate brain activations relating to self-harm, in order to test whether these activations could differentiate between schizophrenia patients with self-harm and those without. We used event-related functional MRI with a go/no-go response inhibition paradigm. Fourteen schizophrenia patients with a history of self-harm were compared with 14 schizophrenia patients without a history of self-harm and 17 healthy control participants. In addition, we used standard clinical measures and neuropsychological tests to assess risk factors associated with self-harm. The right dorsolateral prefrontal cortex (DLPFC) and the left posterior cingulate cortex differentiated all three groups; brain activation in these regions being greatest in the control group, and the self-harm patient group being greater than in the non-self-harm patient group. In the self-harm patient group, right DLPFC activity was positively correlated with severity of suicidal thinking. In addition, both patient groups showed less activation in the right orbitofrontal cortex, left ventral anterior cingulate cortex and right thalamus. This is the first study to report right DLPFC activation in association with self-harm and suicidal thinking in patients with schizophrenia. This area could be a target for future neuromodulation studies to treat suicidal thinking and self-harm behaviors in patients with schizophrenia.

OBJECTIVE Diabetic peripheral neuropathy (DPN) has hitherto been considered a disease of the peripheral nervous system only, with central nervous system (CNS) involvement largely overlooked. The aim of this study was to investigate any differences in brain structure in subjects with DPN. RESEARCH DESIGN AND METHODS Thirty-six subjects with type 1 diabetes (No DPN [n = 18], Painful DPN [n = 9], Painless DPN [n = 9]) underwent neurophysiological assessment to quantify the severity of DPN. All subjects, including 18 healthy volunteers (HVs), underwent volumetric brain magnetic resonance imaging at 3 Tesla. RESULTS Adjusted peripheral gray matter volume was statistically significantly lower in subjects with painless and painful DPN (mean 599.6 mL [SEM 9.8 mL] and 585.4 mL [10.0 mL], respectively) compared with those with No DPN (626.5 mL [5.7 mL]) and HVs (639.9 mL [7.2 mL]; ANCOVA, P = 0.001). The difference in adjusted peripheral gray matter volume between subjects with No DPN and HVs and those with Painful DPN and Painless DPN was not statistically significant (P = 0.16 and 0.30, respectively). Voxel-based morphometry analyses revealed greater localized volume loss in the primary somatosensory cortex, supramarginal gyrus, and cingulate cortex (corrected P < 0.05) in DPN subjects. CONCLUSIONS This is the first study to focus on structural changes in the brain associated with DPN. Our findings suggest increased peripheral gray matter volume loss, localized to regions involved with somatosensory perception in subjects with DPN. This may have important implications for the long-term prognosis of DPN.