Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small cell lung cancer reduces hippocampal atrophy compared to conventional PCI.

BACKGROUND: Reducing radiation dose to the hippocampus with hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is proposed to prevent cognitive decline. It has, however, not been investigated whether hippocampal atrophy is actually mitigated by this approach. Here, we determined whether HA-PCI reduces hippocampal atrophy. Additionally, we evaluated neurotoxicity of (HA-)PCI to other brain regions. Finally, we evaluated associations of hippocampal atrophy and brain neurotoxicity with memory decline. METHODS: High-quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated for 4 months (57 HA-PCI patients and 46 PCI patients) and 12 months (28 HA-PCI patients and 27 PCI patients) after (HA-)PCI. We additionally studied multimodal indices of brain injury. Memory was assessed with the Hopkins Verbal Learning Test-Revised (HVLT-R). RESULTS: HA-PCI reduced hippocampal atrophy at 4 months (1.8% for HA-PCI and 3.0% for PCI) and at 12 months (3.0% for HA-PCI and 5.8% for PCI). Both HA-PCI and PCI were associated with considerable reductions in gray matter and normal-appearing white matter, increases in white matter hyperintensities, and brain aging. There were no significant associations between hippocampal atrophy and memory. CONCLUSIONS: HA-PCI reduces hippocampal atrophy at 4 and 12 months compared to regular PCI. Both types of radiotherapy are associated with considerable brain injury. We did not find evidence for excessive brain injury after HA-PCI relative to PCI. Hippocampal atrophy was not associated with memory decline in this population as measured with HVLT-R. The usefulness of HA-PCI is still subject to debate.

Outcome Prediction and Inter-Rater Comparison of Four Brain Magnetic Resonance Imaging Scoring Systems of Infants with Perinatal Asphyxia and Therapeutic Hypothermia.

INTRODUCTION: The brain magnetic resonance imaging (MRI) result is a major predictor for the outcome of term infants with perinatal asphyxia who underwent therapeutic hypothermia. In daily practice, no uniform method is used to assess these images. PURPOSE: The aim of this study was to determine which MRI-score best predicts adverse outcome at 24 months of age and has the highest inter-rater reliability. METHODS: Four MRI scoring systems for term infants with perinatal asphyxia were selected: Rutherford score, Trivedi score, Weeke score, and NICHD NRN score. Experienced blinded raters retrospectively evaluated the brain MR Images of 161 infants using all four scoring systems. Long-term outcome (the composite outcome death or adverse outcome, and its separate components) were routinely assessed by standardized testing at the age of 24 months. The predictive accuracy was assessed by logistic regression analyses and expressed as area under the ROC curve (AUC). The inter-rater reliability of the scores was calculated by the weighted Kappa or intraclass correlation. A sensitivity analysis using only high-quality MRI scans was performed. RESULTS: All four MRI scoring systems demonstrated an AUC of >0.66 for the prediction of adverse outcome and ≥0.80 for the prediction of death. The inter-rater reliability analyses demonstrated the highest reliability for the Weeke and Trivedi scores. When only assessing the high-quality scans, the AUC increased further. CONCLUSION: All four MRI brain scores proved reliable predictors for an adverse outcome at 24 months of age. The Weeke and Trivedi score demonstrated the highest inter-rater reliability. The use of high-quality MRI further improved prediction.

Dynamic magnetic resonance measurements of calf muscle oxygenation and energy metabolism in peripheral artery disease.

BACKGROUND: Clinical assessments of peripheral artery disease (PAD) severity are insensitive to pathophysiological changes in muscle tissue oxygenation and energy metabolism distal to the affected artery. PURPOSE: To quantify the blood oxygenation level-dependent (BOLD) response and phosphocreatine (PCr) recovery kinetics on a clinical MR system during a single exercise-recovery session in PAD patients. STUDY TYPE: Case-control study. SUBJECTS: Fifteen Fontaine stage II patients, and 18 healthy control subjects FIELD STRENGTH/SEQUENCE: Interleaved dynamic multiecho gradient-echo 1 H T2 * mapping and adiabatic pulse-acquire 31 P-MR spectroscopy at 3T. ASSESSMENT: Blood pressure in the arms and ankles were measured to determine the ankle-brachial index (ABI). Subjects performed a plantar flexion exercise-recovery protocol. The gastrocnemius and soleus muscle BOLD responses were characterized using the T2 * maps. High-energy phosphate metabolite concentrations were quantified by fitting the series of 31 P-MR spectra. The PCr recovery time constant (τPCr ) was derived as a measure of in vivo mitochondrial oxidative capacity. STATISTICAL TESTS: Comparisons between groups were performed using two-sided Mann-Whitney U-tests. Relations between variables were assessed by Pearson's r correlation coefficients. RESULTS: The amplitude of the functional hyperemic BOLD response in the gastrocnemius muscle was higher in PAD patients compared with healthy subjects (-3.8 ± 1.4% vs. -1.4 ± 0.3%; P < 0.001), and correlated with the ABI (r = 0.79; P < 0.001). PCr recovery was slower in PAD patients (τPCr = 52.0 ± 13.5 vs. 30.3 ± 9.7 sec; P < 0.0001), and correlated with the ABI (r = -0.64; P < 0.001). Moreover, τPCr correlated with the hyperemic BOLD response in the gastrocnemius muscle (r = -0.66; P < 0.01). DATA CONCLUSION: MR readouts of calf muscle tissue oxygenation and high-energy phosphate metabolism were acquired essentially simultaneously during a single exercise-recovery session. A pronounced hypoxia-triggered vasodilation in PAD is associated with a reduced mitochondrial oxidative capacity. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:98-107.

Impaired reward-related learning signals in remitted unmedicated patients with recurrent depression.

One of the core symptoms of major depressive disorder is anhedonia, an inability to experience pleasure. In patients with major depressive disorder, a dysfunctional reward-system may exist, with blunted temporal difference reward-related learning signals in the ventral striatum and increased temporal difference-related (dopaminergic) activation in the ventral tegmental area. Anhedonia often remains as residual symptom during remission; however, it remains largely unknown whether the abovementioned reward systems are still dysfunctional when patients are in remission. We used a Pavlovian classical conditioning functional MRI task to explore the relationship between anhedonia and the temporal difference-related response of the ventral tegmental area and ventral striatum in medication-free remitted recurrent depression patients (n = 36) versus healthy control subjects (n = 27). Computational modelling was used to obtain the expected temporal difference errors during this task. Patients, compared to healthy controls, showed significantly increased temporal difference reward learning activation in the ventral tegmental area (PFWE,SVC = 0.028). No differences were observed between groups for ventral striatum activity. A group × anhedonia interaction [t(57) = -2.29, P = 0.026] indicated that in patients, higher anhedonia was associated with lower temporal difference activation in the ventral tegmental area, while in healthy controls higher anhedonia was associated with higher ventral tegmental area activation. These findings suggest impaired reward-related learning signals in the ventral tegmental area during remission in patients with depression. This merits further investigation to identify impaired reward-related learning as an endophenotype for recurrent depression. Moreover, the inverse association between reinforcement learning and anhedonia in patients implies an additional disturbing influence of anhedonia on reward-related learning or vice versa, suggesting that the level of anhedonia should be considered in behavioural treatments.

Prolonged time between intravenous contrast administration and image acquisition results in increased synovial thickness at magnetic resonance imaging in patients with juvenile idiopathic arthritis.

BACKGROUND: Post-contrast synovial thickness measurement is necessary for scoring disease activity in juvenile idiopathic arthritis (JIA). However, the timing of post-contrast sequences varies widely among institutions. This variation in timing could influence thickness measurements. OBJECTIVE: To measure thickness of the synovial membrane on early and late post-contrast knee magnetic resonance (MR) images of patients with JIA. MATERIALS AND METHODS: Dynamic contrast-enhanced T1-weighted knee MR images of 53 children with JIA with current or past knee arthritis were used to study synovial thickness at time point 1 (about 1 min) and time point 2 (about 5 min after contrast administration). Two experienced readers, who were blinded for the time point, independently measured synovial thickness at a predefined, marked location in the patellofemoral compartment on randomized images. Synovial thickness at the two time points was compared using the Wilcoxon signed rank test. Repeatibility of the synovial thickness measurements was studied using intraclass correlation coefficients and Bland-Altman plots. RESULTS: Median synovial thickness of the 53 patients (median age: 13.5 years, 59% female) increased with prolonged post-contrast interval with a synovial thickness of 1.4 mm at time point 1 and a synovial thickness of 1.5 mm at time point 2 (P<0.001). Repeated synovial thickness measurements showed an intraclass correlation coefficient (ICC) of 0.75, P<0.05 for time point 1 and an ICC of 0.91, P<0.05 for time point 2. CONCLUSION: Post-contrast synovial membrane thickness measurements are time-dependent. Therefore, standardization of post-contrast image acquisition timing is important to achieve consistent grading of synovial inflammation.

Distinctive tics suppression network in Gilles de la Tourette syndrome distinguished from suppression of natural urges using multimodal imaging.

BACKGROUND AND OBJECTIVES: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by tics. A hallmark of GTS is the ability to voluntarily suppress tics. Our aim was to distinguish the neural circuits involved in the voluntary suppression of ocular tics in GTS patients from blink suppression in healthy subjects. METHODS: Fifteen GTS patients and 22 healthy control subjects were included in a multimodal study using eye-tracker recordings during functional MRI (fMRI). The ability to suppress tics/blinks was compared both on subjective (self-rating) and objective (eye-tracker) performance. For fMRI analysis we used a novel designed performance-adapted block design analysis of tic/blink suppression and release based on eye-tracker monitoring. RESULTS: We found that the subjective self-reported ability to suppress tics or blinks showed no significant correlation with objective task performance. In GTS during successful suppression of tics, the dorsal anterior cingulate cortex and associated limbic areas showed increased activation. During successful suppression of eye blinks in healthy subjects, the right ventrolateral prefrontal cortex and supplementary and cingulate motor areas showed increased activation. CONCLUSIONS: These findings demonstrate that GTS patients use a characteristic limbic suppression strategy. In contrast, control subjects use the voluntary sensorimotor circuits and the classical 'stop' network to suppress natural urges. The employment of different neural suppression networks provides support for cognitive behavioral therapy in GTS.

Comparison of arterial spin labeling registration strategies in the multi-center GENetic frontotemporal dementia initiative (GENFI).

PURPOSE: To compare registration strategies to align arterial spin labeling (ASL) with 3D T1-weighted (T1w) images, with the goal of reducing the between-subject variability of cerebral blood flow (CBF) images. MATERIALS AND METHODS: Multi-center 3T ASL data were collected at eight sites with four different sequences in the multi-center GENetic Frontotemporal dementia Initiative (GENFI) study. In a total of 48 healthy controls, we compared the following image registration options: (I) which images to use for registration (perfusion-weighted images [PWI] to the segmented gray matter (GM) probability map (pGM) (CBF-pGM) or M0 to T1w (M0-T1w); (II) which transformation to use (rigid-body or non-rigid); and (III) whether to mask or not (no masking, M0-based FMRIB software library Brain Extraction Tool [BET] masking). In addition to visual comparison, we quantified image similarity using the Pearson correlation coefficient (CC), and used the Mann-Whitney U rank sum test. RESULTS: CBF-pGM outperformed M0-T1w (CC improvement 47.2% ± 22.0%; P < 0.001), and the non-rigid transformation outperformed rigid-body (20.6% ± 5.3%; P < 0.001). Masking only improved the M0-T1w rigid-body registration (14.5% ± 15.5%; P = 0.007). CONCLUSION: The choice of image registration strategy impacts ASL group analyses. The non-rigid transformation is promising but requires validation. CBF-pGM rigid-body registration without masking can be used as a default strategy. In patients with expansive perfusion deficits, M0-T1w may outperform CBF-pGM in sequences with high effective spatial resolution. BET-masking only improves M0-T1w registration when the M0 image has sufficient contrast. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:131-140.

Neural response to alcohol taste cues in youth: effects of the OPRM1 gene.

Genetic variations in the mu-opioid receptor (OPRM1) gene have been related to high sensitivity to rewarding effects of alcohol. The current study focuses on the neural circuitry underlying this phenomenon using an alcohol versus water taste-cue reactivity paradigm in a young sample at relatively early stages of alcohol use, thus limiting the confound of variations in duration of alcohol use. Drinkers (17-21 years old) were selected on genotype carrying the AA-(n = 20) or the AG-(n = 16) variant of the A118G single nucleotide polymorphism (SNP) of the OPRM1 gene (rs1799971), and underwent functional magnetic resonance imaging (fMRI). Magnitude of the neural activity and frontostriatal functional connectivity in response to alcohol versus water were investigated. The AG-group demonstrated reduced activation in prefrontal and parietal regions, including the inferior and middle frontal gyrus, superior and inferior parietal lobule, compared with the AA-group. No activation differences were observed in the mesolimbic pathway. Connectivity from the ventral-striatum to frontal regions for alcohol > water trials was higher in the AG than the AA group. For the dorsal-striatum seed region, the AG group showed increased connectivity to non-PFC regions. These results indicate that adolescents carrying the G-allele may be more vulnerable for the alcohol to hijack the reward system in the absence of frontal control to regulate craving. This implies that findings of hyperactivation in the mesolimbic structures of G-allele carriers in earlier studies might result from both genetic susceptibility and heavy drinking.

Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study.

OBJECTIVE: Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac autonomic nervous system (ANS) levels during a standardized stressful situation, and whether these associations are symptom-specific. METHODS: We examined 715 adolescents (16.1 years, 51.3% girls) from the Dutch cohort study Tracking Adolescents' Individual Lives Sample during the Groningen Social Stress Test (GSST). FSS were assessed by the Youth Self-Report, and clustered into a cluster of overtiredness, dizziness and musculoskeletal pain and a cluster of headache and gastrointestinal symptoms. Perceived stress levels (i.e. unpleasantness and arousal) were assessed by the Self-Assessment Manikin, and cardiac ANS activity by assessing heart rate variability (HRV-HF) and pre-ejection period (PEP). Perceived stress and cardiac ANS levels before, during, and after the GSST were studied as well as cardiac ANS reactivity. Linear regression analyses were used to examine the associations. RESULTS: Perceived arousal levels during (beta = 0.09, p = 0.04) and after (beta = 0.07, p = 0.047) the GSST, and perceived unpleasantness levels before (beta = 0.07, p = 0.048) and during (beta = 0.12, p = 0.001) the GSST were related to FSS during the past couple of months. The association between perceived stress and FSS was stronger for the FSS cluster of overtiredness, dizziness and musculoskeletal pain than for the cluster of headache and gastrointestinal symptoms. Neither ANS activity levels before, during, and after the GSST, nor maximal HF-HRV and PEP reactivity were related to FSS. CONCLUSIONS: This study suggests that perceived stress levels during social stress are related to FSS, whereas cardiac ANS activity and reactivity are not related to FSS.

Targeted brain activation using an MR-compatible wrist torque measurement device and isometric motor tasks during functional magnetic resonance imaging.

Dedicated pairs of isometric wrist flexion tasks, with and without visual feedback of the exerted torque, were designed to target activation of the CBL and BG in healthy subjects during functional magnetic resonance imaging (fMRI). Selective activation of the cerebellum (CBL) and basal ganglia (BG), often implicated in movement disorders such as tremor and dystonia, may help identify pathological changes and expedite diagnosis. A prototyped MR-compatible wrist torque measurement device, free of magnetic and conductive materials, allowed safe execution of tasks during fMRI without causing artifacts. A significant increase of activity in CBL and BG was found in healthy volunteers during a constant torque task with visual feedback compared to a constant torque task without visual feedback. This study shows that specific pairs of motor tasks using MR-compatible equipment at the wrist allow for targeted activation of CBL and BG, paving a new way for research into the pathophysiology of movement disorders.

Bilateral cerebellar activation in unilaterally challenged essential tremor.

BACKGROUND: Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities. OBJECTIVE: In this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging (EMG-fMRI) to study a group of ET patients selected according to strict criteria to achieve maximal homogeneity. With this approach we expected to improve upon the localization of the bilateral cerebellar abnormalities found in earlier fMRI studies. METHODS: We included 21 propranolol sensitive patients, who were not using other tremor medication, with a definite diagnosis of ET defined by the Tremor Investigation Group. Simultaneous EMG-fMRI recordings were performed while patients were off tremor medication. Patients performed unilateral right hand and arm extension, inducing tremor, alternated with relaxation (rest). Twenty-one healthy, age- and sex-matched participants mimicked tremor during right arm extension. EMG power variability at the individual tremor frequency as a measure of tremor intensity variability was used as a regressor, mathematically independent of the block regressor, in the general linear model used for fMRI analysis, to find specific tremor-related activations. RESULTS: Block-related activations were found in the classical upper-limb motor network, both for ET patients and healthy participants in motor, premotor and supplementary motor areas. In ET patients, we found tremor-related activations bilaterally in the cerebellum: in left lobules V, VI, VIIb and IX and in right lobules V, VI, VIIIa and b, and in the brainstem. In healthy controls we found simulated tremor-related activations in right cerebellar lobule V. CONCLUSIONS: Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.

Endogenous GLP1 and GLP1 analogue alter CNS responses to palatable food consumption.

Glucagon-like peptide-1 (GLP1) affects appetite, supposedly mediated via the central nervous system (CNS). In this study, we investigate whether modulation of CNS responses to palatable food consumption may be a mechanism by which GLP1 contributes to the central regulation of feeding. Using functional MRI, we determined the effects of endogenous GLP1 and treatment with the GLP1 analogue liraglutide on CNS activation to chocolate milk receipt. Study 1 included 20 healthy lean individuals and 20 obese patients with type 2 diabetes (T2DM). Scans were performed on two occasions: during infusion of the GLP1 receptor antagonist exendin 9-39 (blocking actions of endogenous GLP1) and during placebo infusion. Study 2 was a randomised, cross-over intervention study carried out in 20 T2DM patients, comparing treatment with liraglutide to insulin, after 10 days and 12 weeks. Compared with lean individuals, T2DM patients showed reduced activation to chocolate milk in right insula (P = 0.04). In lean individuals, blockade of endogenous GLP1 effects inhibited activation in bilateral insula (P ≤ 0.03). Treatment in T2DM with liraglutide, vs insulin, increased activation to chocolate milk in right insula and caudate nucleus after 10 days (P ≤ 0.03); however, these effects ceased to be significant after 12 weeks. Our findings in healthy lean individuals indicate that endogenous GLP1 is involved in the central regulation of feeding by affecting central responsiveness to palatable food consumption. In obese T2DM, treatment with liraglutide may improve the observed deficit in responsiveness to palatable food, which may contribute to the induction of weight loss observed during treatment. However, no long-term effects of liraglutide were observed.

Motor network disruption in essential tremor: a functional and effective connectivity study.

Although involvement of the cerebello-thalamo-cortical network has often been suggested in essential tremor, the source of oscillatory activity remains largely unknown. To elucidate mechanisms of tremor generation, it is of crucial importance to study the dynamics within the cerebello-thalamo-cortical network. Using a combination of electromyography and functional magnetic resonance imaging, it is possible to record the peripheral manifestation of tremor simultaneously with brain activity related to tremor generation. Our first aim was to study the intrinsic activity of regions within the cerebello-thalamo-cortical network using dynamic causal modelling to estimate effective connectivity driven by the concurrently recorded tremor signal. Our second aim was to objectify how the functional integrity of the cerebello-thalamo-cortical network is affected in essential tremor. We investigated the functional connectivity between cerebellar and cortical motor regions showing activations during a motor task. Twenty-two essential tremor patients and 22 healthy controls were analysed. For the effective connectivity analysis, a network of tremor-signal related regions was constructed, consisting of the left primary motor cortex, premotor cortex, supplementary motor area, left thalamus, and right cerebellar motor regions lobule V and lobule VIII. A measure of variation in tremor severity over time, derived from the electromyogram, was included as modulatory input on intrinsic connections and on the extrinsic cerebello-thalamic connections, giving a total of 128 models. Bayesian model selection and random effects Bayesian model averaging were used. Separate seed-based functional connectivity analyses for the left primary motor cortex, left supplementary motor area and right cerebellar lobules IV, V, VI and VIII were performed. We report two novel findings that support an important role for the cerebellar system in the pathophysiology of essential tremor. First, in the effective connectivity analysis, tremor variation during the motor task has an excitatory effect on both the extrinsic connection from cerebellar lobule V to the thalamus, and the intrinsic activity of cerebellar lobule V and thalamus. Second, the functional integrity of the motor network is affected in essential tremor, with a decrease in functional connectivity between cortical and cerebellar motor regions. This decrease in functional connectivity, related to the motor task, correlates with an increase in clinical tremor severity. Interestingly, increased functional connectivity between right cerebellar lobules I-IV and the left thalamus correlates with an increase in clinical tremor severity. In conclusion, our findings suggest that cerebello-dentato-thalamic activity and cerebello-cortical connectivity is disturbed in essential tremor, supporting previous evidence of functional cerebellar changes in essential tremor.

Prefrontal involvement related to cognitive impairment in progressive muscular atrophy.

OBJECTIVE: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). METHODS: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in 18 patients with PMA, 21 patients with ALS, and 17 healthy control subjects, matched for age and education. fMRI results are reported at p<0.05, family-wise error (FWE)-corrected for multiple comparisons. We analyzed effects of performance, age-related white matter changes (ARWMC), and regional brain volumes; all participants underwent neuropsychological investigation. RESULTS: Disease duration of patients with PMA (mean 26.0 months, SD 13.6) and ALS (22.2 months, SD 11.4) was comparable. Patients with PMA and ALS had mild to moderate disease severity and showed impaired letter fluency compared with controls. Between-group analysis showed a main effect of group in the left inferior frontal gyrus (IFG, Brodmann area 45) during letter fluency, which was unaffected by performance, ARWMC, and IFG volume: patients with PMA showed lower activation than controls but higher than that of patients with ALS (ALS

MR elastography of the liver: defining thresholds for detecting viscoelastic changes.

PURPOSE: To define thresholds for detecting significant change in liver viscoelasticity with magnetic resonance (MR) elastography, both for whole-liver measurements and for voxel-wise measurements in relation to spatial resolution. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and all participants provided written informed consent. Thirty participants (16 volunteers and 14 patients with hepatitis B or C; 18 men; median age, 30.4 years; age range, 18.9-58.6 years) underwent imaging twice while in the same position (intraimage reproducibility), after repositioning (within-day reproducibility), and 1-4 weeks later (between-weeks reproducibility). MR elastography parameters comprised elasticity, viscosity, attenuation parameter α, and propagation parameter ß. Bland-Altman analysis was used to calculate repeatability indexes for each parameter. Analyses were performed in a region-of-interest and a voxel-by-voxel level. Voxel-wise results were calculated in relation to spatial resolution by applying Gaussian filtering to establish the optimal trade-off point between resolution and reproducibility. RESULTS: For elasticity, α, and ß, within-day and between-weeks results were significantly lower than intraimage results (P ≤ .018 for all). Within-day and between-weeks results did not differ significantly. Over-time changes of more than 22.2% for elasticity, 26.3% for viscosity, 26.8% for α, and 10.1% for ß represented thresholds for significant change. The optimal trade-off between spatial resolution and reproducibility was found at a filter size of 8-mm full width at half maximum (FWHM) for elasticity and propagation parameter ß and at 16-mm FWHM for viscosity and attenuation parameter α. CONCLUSION: Repositioning causes a significant decrease in the reproducibility of MR elastography. The propagation parameter ß is the most reliable parameter, with an over-time threshold for significant change of 10.1% and the ability to reproduce viscoelasticity up to a resolution of 8-mm FWHM. Online supplemental material is available for this article.

Symptom validity testing in memory clinics: Hippocampal-memory associations and relevance for diagnosing mild cognitive impairment.

Patients with mild cognitive impairment (MCI) do not always convert to dementia. In such cases, abnormal neuropsychological test results may not validly reflect cognitive symptoms due to brain disease, and the usual brain-behavior relationships may be absent. This study examined symptom validity in a memory clinic sample and its effect on the associations between hippocampal volume and memory performance. Eleven of 170 consecutive patients (6.5%; 13% of patients younger than 65 years) referred to memory clinics showed noncredible performance on symptom validity tests (SVTs, viz. Word Memory Test and Test of Memory Malingering). They were compared to a demographically matched group (n = 57) selected from the remaining patients. Hippocampal volume, measured by an automated volumetric method (Freesurfer), was correlated with scores on six verbal memory tests. The median correlation was r = .49 in the matched group. However, the relation was absent (median r = -.11) in patients who failed SVTs. Memory clinic samples may include patients who show noncredible performance, which invalidates their MCI diagnosis. This underscores the importance of applying SVTs in evaluating patients with cognitive complaints that may signify a predementia stage, especially when these patients are relatively young.

Is there a role for combined EMG-fMRI in exploring the pathophysiology of essential tremor and improving functional neurosurgery?

BACKGROUND: Functional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting. OBJECTIVE: Aim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery. METHODS: Simultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor. RESULTS: Analysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius. CONCLUSION: EMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery.

Validation of the thoracic impedance derived respiratory signal using multilevel analysis.

The purpose of the current study was to validate the change in thoracic impedance (dZ) derived respiratory signal obtained from four spot electrodes against incidental spirometry. Additionally, a similar validation was performed for a dual respiratory belts signal to compare the relative merit of both methods. Participants were 38 healthy adult subjects (half male, half female). Cross-method comparisons were performed at three (paced) respiration frequencies in sitting, supine and standing postures. Multilevel regression was used to examine the within- and between-subjects structure of the relationship between spirometric volume and the respiratory amplitude signals obtained from either dZ or respiratory belts. Both dZ derived respiratory rate and dual belts derived respiratory rate accurately reflected the pacing frequencies. For both methods, fixed factors indicated acceptable but posture-specific regression on spirometric volume. However, random factors indicated large individual differences, which was supported by variability of gain analyses. It was concluded that both the dZ and dual belts methods can be used for measurement of respiratory rate and within-subjects, posture-specific, changes in respiratory volume. The need for frequent subject-specific and posture-specific calibration combined with relatively large measurement errors may strongly limit the usefulness of both methods to assess absolute tidal volume and minute ventilation in ambulatory designs.

Effects of variation in posture and respiration on RSA and pre-ejection period.

The extent to which variation in posture and respiration can confound pre-ejection period and respiratory sinus arrhythmia (RSA) as indices of cardiac sympatho-vagal activity was examined. Within-subjects changes in these measures were assessed in 36 subjects during different postures and (paced) respiratory frequencies. Changes from supine to sitting to standing led to reduced RSA values and longer pre-ejection periods, reflecting the known decrease in vagal but not the increase of sympathetic activity. Multilevel path analysis showed that within-subjects changes in sympatho-vagal balance were faithfully reflected by changes in interbeat interval, but imperfectly by changes in RSA and pre-ejection period. It was concluded that pre-ejection period should be stratified for posture and RSA for respiratory frequency to reliably index changes in sympatho-vagal balance when these factors are prone to change (e.g., during 24-h ambulatory recording).

Large-scale ensemble averaging of ambulatory impedance cardiograms.

Impedance cardiography has been used increasingly to measure human physiological responses to emotional and mentally engaging stimuli. The validity of large-scale ensemble averaging of ambulatory impedance cardiograms was evaluated for preejection period (PEP), interbeat interval, and dZ/dt(min) amplitude. We tested whether the average of "classical" 60-sec ensemble averages across periods with fixed activity, posture, physical load, social situation, and location could be accurately estimated from a single large-scale ensemble average spanning these entire periods. Impedance and electrocardiograms were recorded for about 24-h from 21 subjects. Recordings were scored by seven raters, using both methods for each subject. Good agreement (average intraclass correlation coefficient was .91) between both ensemble averaging methods was found for all three cardiac function measures. The results indicate that for unambiguous ambulatory impedance cardiograms, large-scale ensemble averaging is valid, which makes measuring prolonged changes in cardiac sympathetic activity by measuring ambulatory PEP feasible even in large epidemiological samples.