Sensorimotor network segregation declines with age and is linked to GABA and to sensorimotor performance.

Aging is typically associated with declines in sensorimotor performance. Previous studies have linked some age-related behavioral declines to reductions in network segregation. For example, compared to young adults, older adults typically exhibit weaker functional connectivity within the same functional network but stronger functional connectivity between different networks. Based on previous animal studies, we hypothesized that such reductions of network segregation are linked to age-related reductions in the brain's major inhibitory transmitter, gamma aminobutyric acid (GABA). To investigate this hypothesis, we conducted graph theoretical analyses of resting state functional MRI data to measure sensorimotor network segregation in both young and old adults. We also used magnetic resonance spectroscopy to measure GABA levels in the sensorimotor cortex and collected a battery of sensorimotor behavioral measures. We report four main findings. First, relative to young adults, old adults exhibit both less segregated sensorimotor brain networks and reduced sensorimotor GABA levels. Second, less segregated networks are associated with lower GABA levels. Third, less segregated networks and lower GABA levels are associated with worse sensorimotor performance. Fourth, network segregation mediates the relationship between GABA and performance. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. More broadly, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks.

Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation.

BACKGROUND: Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). METHODS: The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. DISCUSSION: By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. TRIAL REGISTRATION: This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .

Speckle tracking as a method to measure hemidiaphragm excursion.

INTRODUCTION: Diaphragm excursion measured via ultrasound may be an important imaging outcome measure of respiratory function. We developed a new method for measuring diaphragm movement and compared it to the more traditional M-mode method. METHODS: Ultrasound images of the right and left hemidiaphragms were collected to compare speckle tracking and M-mode measurements of diaphragm excursion. Speckle tracking was performed using EchoInsight (Epsilon Imaging, Ann Arbor, Michigan). RESULTS: Six healthy subjects without a history of pulmonary diseases were included in this proof-of-concept study. Speckle tracking of the diaphragm is technically possible. Unlike M-mode, speckle tracking carries the advantage of reliable visualization and measurement of the left hemidiaphragm. CONCLUSIONS: Speckle tracking accounted for diaphragm movement simultaneously in the cephalocaudad and mediolateral directions, unlike M-mode, which is 1-dimensional. Diaphragm speckle tracking may represent a novel, more robust method for measuring diaphragm excursion, especially for the left hemidiaphragm. Muscle Nerve 55: 125-127, 2017.

Vision Loss After Central Retinal Artery Occlusion Secondary to Orbital Sarcoid Mass.

The authors describe the first report in the literature of central retinal artery occlusion as the presenting manifestation of sarcoidosis. A 33-year-old man with asthma, headache, and 6 days of intermittent, transient vision loss in the OS presented with persistent vision loss in the OS. Ophthalmic examination was consistent with diagnosis of central retinal artery occlusion in the OS. Vascular imaging with CT angiography revealed an incidental finding of an intraconal mass surrounding the left optic nerve and hilar lymphadenopathy. Broncho scopic lymph node biopsy demonstrated noncaseating granulomas consistent with sarcoidosis. This case proffers a unique mechanism of vision loss in sarcoidosis and highlights that atypical causes of central retinal artery occlusion must be considered in patients without typical risk factors.

Amyloid deposition in Parkinson's disease and cognitive impairment: a systematic review.

BACKGROUND: Varying degrees of cortical amyloid deposition are reported in the setting of Parkinsonism with cognitive impairment. We performed a systematic review to estimate the prevalence of Alzheimer disease (AD) range cortical amyloid deposition among patients with Parkinson's disease with dementia (PDD), Parkinson's disease with mild cognitive impairment (PD-MCI) and dementia with Lewy bodies (DLB). We included amyloid positron emission tomography (PET) imaging studies using Pittsburgh Compound B (PiB). METHODS: We searched the databases Ovid MEDLINE, PubMed, Embase, Scopus, and Web of Science for articles pertaining to amyloid imaging in Parkinsonism and impaired cognition. We identified 11 articles using PiB imaging to quantify cortical amyloid. We used the metan module in Stata, version 11.0, to calculate point prevalence estimates of patients with "PiB-positive" studies, that is, patients showing AD range cortical Aß-amyloid deposition. Heterogeneity was assessed. A scatterplot was used to assess publication bias. RESULTS: Overall pooled prevalence of "PiB-positive" studies across all three entities along the spectrum of Parkinson's disease and impaired cognition (specifically PDD, PD-MCI, and DLB) was 0.41 (95% confidence interval [CI], 0.24-0.57). Prevalence of "PiB-positive" studies was 0.68 (95% CI, 0.55-0.82) in the DLB group, 0.34 (95% CI, 0.13-0.56) in the PDD group, and 0.05 (95% CI, -0.07-0.17) in the PD-MCI group. CONCLUSIONS: Substantial variability occurs in the prevalence of "PiB-positive" studies in subjects with Parkinsonism and cognitive impairment. Higher prevalence of PiB-positive studies was encountered among subjects with DLB as opposed to subjects with PDD. The PD-MCI subjects showed overall lower prevalence of PiB-positive studies than reported findings in non-PD-related MCI. © 2015 International Parkinson and Movement Disorder Society.

Macrocerebellum, epilepsy, intellectual disability, and gut malrotation in a child with a 16q24.1-q24.2 contiguous gene deletion.

Macrocerebellum is a rare condition characterized by enlargement of the cerebellum with conservation of the overall shape and cytoarchitecture. Here, we report on a child with a distinctive constellation of clinical features including macrocerebellum, epilepsy, apparent intellectual disability, dysautonomia, gut malrotation, and poor gut motility. Oligonucleotide chromosome microarray analysis identified a 16q24.1-q24.2 deletion that included four OMIM genes (FBXO31, MAP1LC3B, JPH3, and SLC7A5). Review of prior studies describing individuals with similar or overlapping16q24.1-q24.2 deletions identified no other reports of macrocerebellum. These observations highlight a potential genetic cause of this rare disorder and raise the possibility that one or more gene(s) in the 16q24.1-q24.2 interval regulate cerebellar development.

Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients.

BACKGROUND: Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. METHODS: To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia. RESULTS: The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = -0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo. CONCLUSIONS: The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of central-acting analgesics.

Reduced insular γ-aminobutyric acid in fibromyalgia.

OBJECTIVE: Recent scientific findings have reinvigorated interest in examining the role of γ-aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressure-pain thresholds. METHODS: Sixteen FM patients and 17 age- and sex-matched healthy controls underwent pressure-pain testing and a 3T proton magnetic resonance spectroscopy session in which the right anterior insula, right posterior insula, anterior cingulate, and occipital cortex were examined in subjects at rest. RESULTS: GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls (mean ± SD 1.17 ± 0.24 arbitrary institutional units versus 1.42 ± 0.32 arbitrary institutional units; P = 0.016). There was a trend toward increased GABA levels in the anterior cingulate of FM patients compared with healthy controls (P = 0.06). No significant differences between groups were detected in the posterior insula or occipital cortex (P > 0.05 for all comparisons). Within the right posterior insula, higher levels of GABA were positively correlated with pressure-pain thresholds in the FM patients (Spearman's rho = 0.63; P = 0.02). CONCLUSION: Diminished inhibitory neurotransmission resulting from lower concentrations of GABA within the right anterior insula may play a role in the pathophysiology of FM and other central pain syndromes.

Neuroimaging evaluation of non-accidental head trauma with correlation to clinical outcomes: a review of 57 cases.

OBJECTIVE: To review the clinical presentation and neuroimaging findings in patients with high clinical suspicion for non-accidental trauma (NAT) of the head, to investigate associations between imaging findings and long-term neurologic outcome in abused children. STUDY DESIGN: A retrospective review of 57 cases of NAT of the head from a single institution was performed. Neuroimaging studies (computed tomography [CT] and magnetic resonance imaging [MRI]) were reviewed by a senior neuroradiologist, a neuroradiology fellow, and a radiology resident. Clinical history and physical findings, including retinal examination, imaging, and follow-up assessment, were reviewed. RESULTS: The mean time between the patient's arrival at the hospital and CT and MRI imaging was 2.9 hours and 40.6 hours, respectively. The most common clinical presentation was mental status changes, seen in 47% of patients. The most common neuroimaging finding was subdural hematoma, seen in 86% of patients. In the 47 patients who underwent both MRI and CT, 1 case of suspected NAT was missed on head CT. CT detected signs of global ischemia in all 11 patients who died (mean time after arrival at the hospital until undergoing CT, 1.1 hours). MRI detected additional signs of injury in patients who developed mild to moderate developmental delay. CONCLUSION: CT was able to detect evidence of NAT of the head in 56 of 57 abused children included in our cohort and predicted severe neurologic injury and mortality. MRI was useful in detecting additional evidence of trauma, which can be helpful in risk stratification for neurologic outcomes as well in providing confirming evidence of repeated injury.

Age-Related Declines in Occipital GABA are Associated with Reduced Fluid Processing Ability.

RATIONALE AND OBJECTIVES: Healthy aging is associated with pervasive declines in cognitive, motor, and sensory functioning. There are, however, substantial individual differences in behavioral performance among older adults. Several lines of animal research link age-related reductions of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, to age-related cognitive, motor, and sensory decline. Our study used proton magnetic resonance spectroscopy (MRS) at 3T to explore whether occipital GABA declines with age in humans and whether individual differences in occipital GABA are linked to individual differences in fluid processing ability. MATERIALS AND METHODS: We used a MEGA-PRESS sequence that combines frequency spectral editing with a point-resolved spectroscopy sequence to quantify GABA. Spectra were obtained from a 30 × 30 × 25 mm voxel placed in the occipital cortex of 20 young adults (mean age 20.7 years) and 18 older adults (mean age 76.5 years). Participants also performed 11 fluid processing tasks outside the scanner, the results of which were z-scored and averaged to calculate a summary measure of fluid processing ability. Regression analysis was employed to determine the relationship between GABA concentrations in the occipital cortex and a summary measure of fluid processing ability. RESULTS: Occipital GABA was significantly lower in older participants compared to the younger participants. We also observed a significant positive relationship between occipital GABA and fluid processing ability. In fact, higher GABA was associated with better task performance in 10 of the 11 tasks. CONCLUSION: These findings suggest that GABA levels decline with age in humans and are associated with declines in fluid processing ability.

Building Imaging Institutes of Patient Care Outcomes: Imaging as a Nidus for Innovation in Clinical Care, Research, and Education.

Traditionally, radiologists have been responsible for the protocol of imaging studies, imaging acquisition, supervision of imaging technologists, and interpretation and reporting of imaging findings. In this article, we outline how radiology needs to change and adapt to a role of providing value-based, integrated health-care delivery. We believe that the way to best serve our specialty and our patients is to undertake a fundamental paradigm shift in how we practice. We describe the need for imaging institutes centered on disease entities (eg, lung cancer, multiple sclerosis) to not only optimize clinical care and patient outcomes, but also spur the development of a new educational focus, which will increase opportunities for medical trainees and other health professionals. These institutes will also serve as unique environments for testing and implementing new technologies and for generating new ideas for research and health-care delivery. We propose that the imaging institutes focus on how imaging practices-including new innovations-improve patient care outcomes within a specific disease framework. These institutes will allow our specialty to lead patient care, provide the necessary infrastructure for state-of-the art-education of trainees, and stimulate innovative and clinically relevant research.

How to Perform a Systematic Review and Meta-analysis of Diagnostic Imaging Studies.

A systematic review is a comprehensive search, critical evaluation, and synthesis of all the relevant studies on a specific (clinical) topic that can be applied to the evaluation of diagnostic and screening imaging studies. It can be a qualitative or a quantitative (meta-analysis) review of available literature. A meta-analysis uses statistical methods to combine and summarize the results of several studies. In this review, a 12-step approach to performing a systematic review (and meta-analysis) is outlined under the four domains: (1) Problem Formulation and Data Acquisition, (2) Quality Appraisal of Eligible Studies, (3) Statistical Analysis of Quantitative Data, and (4) Clinical Interpretation of the Evidence. This review is specifically geared toward the performance of a systematic review and meta-analysis of diagnostic test accuracy (imaging) studies.

Added utility of gadolinium in the magnetic resonance imaging (MRI) workup of seizures in children younger than 2 years.

The purpose of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging (MRI) workup of seizures in children younger than 2 years. A computerized retrospective search of the radiology information system identified all brain MRI examinations performed at the authors' institution from 1995 to 2002 for children younger than 2 years. Review of the clinical records revealed that 437 of a total 1466 brain magnetic resonance examinations performed on this subset of the pediatric population were performed as part of an initial seizure workup. Magnetic resonance reports and clinical notes were reviewed. MRI studies with enhancing lesions as well as those with equivocal findings were also reviewed in a consensus fashion by 2 senior neuro-radiologists and 2 radiology residents. Contrast administration was rated as essential, helpful, or not helpful for each study. Administration of contrast medium was felt to be essential in formulating a diagnosis in a total of 8 (1.8%) studies, all of which involved documented or highly suspected cases of infection. In an additional 26 cases (5.9%), which included 4 cases of neoplasm, contrast was felt to be useful but not essential in reaching a diagnosis. Contrast was judged not helpful in making the diagnosis in the other 403 studies (92.3%).

Manually adjusted versus vendor-preset definition of metabolite boundaries impact on proton metabolite ratios.

RATIONALE AND OBJECTIVES: Metabolite peak boundary definition is an important postprocessing step in proton magnetic resonance spectroscopy (1H-MRS). We compare metabolite ratios calculated using three different postprocessing strategies: software-rendered default peak boundaries, manually adjusted peak boundaries and a curve-fitting program. The first two of these methods are commercially available. MATERIALS AND METHODS: A total of 42 spectra acquired on a 1.5-T MR unit using two-dimensional chemical shift proton MR spectroscopy (TR/TE = 1500/144 ms) were analyzed. Choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) relative concentrations were derived and the following metabolite ratios were calculated: Cho/Cr, Cho/NAA, and NAA/Cr. Metabolite concentrations/ratios were calculated using (a) default peak boundaries rendered by commercially available, postprocessing software (Functool 2000, version 2.6.0); (b) manually adjusted peak boundaries by an experienced spectroscopist, using an option offered by the same commercially available software; and (c) an offline in-house curve-fitting program. Measurements obtained with method (c) were considered as the "gold standard." Paired t-tests comparing default and adjusted metabolite ratios, as well as default and adjusted ratios with their respective curve-fit values were used for statistical analysis. RESULTS: Significant differences between default and manually adjusted values were found for Cho/Cr ratios <1.5 and for all Cho/NAA ratios. For Cho/Cr ratios <1.5, significant differences between default and curve-fit values were present; this was not the case when comparing manually adjusted and curve-fit values. Default and manually adjusted Cho/NAA ratios were significantly higher than corresponding curve-fit ratios. Manually adjusted values were, however, closer to the curve-fit values. No significant differences were noted between default and adjusted NAA/Cr values; default and manually adjusted ratios were significantly lower than curve-fit ratios. CONCLUSION: There can be significant differences in metabolite ratios calculated using default and manually adjusted peak limits in proton MR spectroscopy. Furthermore, Cho/Cr and NAA/Cho adjusted metabolite ratios are closer to curve-fit values, which are considered the most accurate of the three.

Microstructural mechanisms of analgesia in percutaneous cervical cordotomy revealed by diffusion tensor imaging.

The purpose of this study is to demonstrate the potential of diffusion tensor imaging (DTI) to reveal structural mechanisms underlying spinal ablative procedures, including percutaneous radiofrequency cordotomy (PRFC). PRFC is a surgical procedure that produces analgesia through focal ablation of the lateral spinothalamic tract (STT), thereby interrupting the flow of pain information from the periphery to the brain. To date, studies regarding mechanisms of analgesia after PRFC have been limited to postmortem cadaveric dissection and histology. However, with recent advances in DTI, the opportunity has arisen to study the STT non-invasively in vivo. In this technical note, an individual with successful pain relief following unilateral STT PRFC was examined using DTI, with the contralateral STT serving as an internal control. PRFC substantially reduced rostrocaudal directional DTI signal in the STT from the lesion in the cervical spinal cord through the pons and mesencephalon. Our findings confirm that focal ablation and anterograde degeneration accompany the analgesic effects of PRFC. In vivo imaging of the STT with DTI may contribute to surgical targeting for PRFC procedures, better understanding of the therapeutic and untoward effects of PRFC, and a deeper understanding of spinothalamic contributions to nociception.

A Simplified Approach to Encephalitis and Its Mimics: Key Clinical Decision Points in the Setting of Specific Imaging Abnormalities.

RATIONALE AND OBJECTIVES: Infectious encephalitis is a relatively common cause of morbidity and mortality. Treatment of infectious encephalitis with antiviral medication can be highly effective when administered promptly. Clinical mimics of encephalitis arise from a broad range of pathologic processes, including toxic, metabolic, neoplastic, autoimmune, and cardiovascular etiologies. These mimics need to be rapidly differentiated from infectious encephalitis to appropriately manage the correct etiology; however, the many overlapping signs of these various entities present a challenge to accurate diagnosis. A systematic approach that considers both the clinical manifestations and the imaging findings of infectious encephalitis and its mimics can contribute to more accurate and timely diagnosis. MATERIALS AND METHODS: Following an institutional review board approval, a health insurance portability and accountability act (HIPAA)-compliant search of our institutional imaging database (teaching files) was conducted to generate a list of adult and pediatric patients who presented between January 1, 1995 and October 10, 2013 for imaging to evaluate possible cases of encephalitis. Pertinent medical records, including clinical notes as well as surgical and pathology reports, were reviewed and correlated with imaging findings. Clinical and imaging findings were combined to generate useful flowcharts designed to assist in distinguishing infectious encephalitis from its mimics. Key imaging features were reviewed and were placed in the context of the provided flowcharts. RESULTS: Four flowcharts were presented based on the primary anatomic site of imaging abnormality: group 1: temporal lobe; group 2: cerebral cortex; group 3: deep gray matter; and group 4: white matter. An approach that combines features on clinical presentation was then detailed. Imaging examples were used to demonstrate similarities and key differences. CONCLUSIONS: Early recognition of infectious encephalitis is critical, but can be quite complex due to diverse pathologies and overlapping features. Synthesis of both the clinical and imaging features of infectious encephalitis and its mimics is critical to a timely and accurate diagnosis. The use of the flowcharts presented in this article can further enable both clinicians and radiologists to more confidently differentiate encephalitis from its mimics and improve patient care.

Effect of Template Reporting of Brain MRIs for Multiple Sclerosis on Report Thoroughness and Neurologist-Rated Quality: Results of a Prospective Quality Improvement Project.

PURPOSE: To assess the impact of structured reporting templates on the objective and subjective quality of radiology reports for brain MRIs in patients with multiple sclerosis (MS). METHODS: A HIPAA-compliant prospective quality improvement initiative was undertaken to develop and implement a 12-item structured reporting template for brain MRI examinations in patients with known or suspected MS based on published guidelines. Reports created 1 year before implementing the template served as the baseline. A random sample of 10 template and 10 non-template reports was sent to five neurologists outside the study institution with MS expertise, who reviewed the reports for comprehensiveness and quality. The number of MS-relevant elements in template and non-template reports were compared with unpaired t tests. Proportions were compared with χ2 and Fisher exact tests. RESULTS: There were 63 reports in the pre-template period and 93 reports in the post-template period. Use of the template increased over time in the post-template period (P = .04). All 12 MS-relevant findings were addressed more often and with less variability in template reports: (11.1 ± 0.7 findings versus 5.8 ± 2.2 findings in non-template reports, P < .001). Neurologists were more likely to give the template reports the highest positive rating (56% [107/190] versus 28% [56/199], P < .001) and less likely to give the template reports a lower rating (7% [13/190] versus 15% [29/199], P = .01) compared with the non-template reports. CONCLUSION: Template reporting of brain MRI examinations increases the rate at which MS-relevant findings are included in the report. Standardized reports are preferred by neurologists with MS expertise.

Value of gadolinium in brain MRI examinations for developmental delay.

The aim of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging evaluation of developmental delay in children less than 2 years of age. A computerized retrospective study identified all brain magnetic resonance imaging examinations using gadolinium performed at our institution from 1995-2002 for children under the age of 2 years. Review of the clinical records and magnetic resonance imaging reports identified 170 brain magnetic resonance imaging examinations that were performed for developmental delay. Magnetic resonance imaging studies with enhancing lesions were reviewed by two staff neuroradiologists and two radiology residents. Contrast administration was rated as essential, helpful, or not helpful for each study. In the 107 patients in whom developmental delay was the primary concern, there were no cases in which the findings would have been missed without gadolinium administration. In the 63 patients in whom developmental delay was a secondary concern, there were several cases (11%) where contrast was helpful but not essential in reaching a radiologic diagnosis. In conclusion, intravenous gadolinium has an extremely low yield in children under the age of 2 where developmental delay is the primary concern. In young children for whom developmental delay is a secondary concern, we advocate the use of gadolinium particularly where tumor or infection is clinically suspected.

Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients.

BACKGROUND: Fibromyalgia (FM) is a chronic, centralized pain condition characterized by alterations in the functional, chemical, and structural brain networks responsible for sensory and mood processing. Transcranial direct current stimulation (tDCS) has emerged as a potential treatment for FM. tDCS can alter functional connectivity (FC) in brain regions underneath and distant to the stimulating electrode, although the analgesic mechanisms of repetitive tDCS remain unknown. The aim of this study was to investigate how a clinically relevant schedule of tDCS sessions alters resting state FC and how these changes might relate to clinical pain. METHODS: Resting state functional magnetic resonance imaging data were collected from 12 patients with FM at baseline, after 5 days of sham treatment, and after 5 days of real tDCS with the anode over the left primary motor cortex (M1) and the cathode over the right supraorbital cortex. Seed to whole-brain FC analyses were performed with seed regions placed in bilateral M1, primary somatosensory cortices (S1), ventral lateral (VL) and ventral posterolateral (VPL) thalami, and periaqueductal gray (PAG). RESULTS: Stronger baseline FC between M1-VL thalamus, S1-anterior insula, and VL thalamus-PAG predicted greater analgesia after sham and real tDCS. Sham treatment (compared with baseline) reduced FC between the VPL thalamus, S1, and the amygdala. Real tDCS (compared with sham treatment) reduced FC between the VL thalamus, medial prefrontal, and supplementary motor cortices. Interestingly, decreased FC between the VL/VPL thalamus and posterior insula, M1, and S1 correlated with reductions in clinical pain after both sham and active treatments. CONCLUSIONS: These results suggest that while there may be a placebo response common to both sham and real tDCS, repetitive M1 tDCS causes distinct changes in FC that last beyond the stimulation period and may produce analgesia by altering thalamic connectivity.

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of upper and lower motor neurons, with variable involvement of extramotor brain regions. Currently, there are no established objective markers of upper motor neuron and extramotor involvement in ALS. Here, we review the potential diagnostic value of advanced neuroimaging techniques that are increasingly being used to study the brain in ALS. First, we discuss the role of different imaging modalities in our increasing understanding of ALS pathogenesis, and their potential to contribute to objective upper motor neuron biomarkers for the disease. Second, we discuss the challenges to be overcome and the required phases of diagnostic test development to translate imaging technology to clinical care. We also present examples of multidimensional imaging approaches to achieve high levels of diagnostic accuracy. Last, we address the role of neuroimaging in clinical therapeutic trials. Advanced neuroimaging techniques will continue to develop and offer significant opportunities to facilitate the development of new effective treatments for ALS.