Clinical Functional Magnetic Resonance Imaging Research Articles

Abnormal baseline brain activity in Parkinson's disease with and without REM sleep behavior disorder: A resting-state functional MRI study.

To investigate the differences in spontaneous brain activity between Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD), PD patients without RBD, and normal controls, which may shed new light on the neural mechanism of RBD. Eighteen PD patients with RBD, 16 patients without RBD, and 19 age- and gender-matched normal controls underwent clinical assessment and functional magnetic resonance imaging (fMRI) with a 3.0T scanner. Resting-state fMRI scans were collected using an echo planar imaging sequence. Amplitude of low-frequency fluctuations (ALFF) were calculated to measure spontaneous brain activity in each subject. Compared with PD patients without RBD, patients with RBD exhibited significantly decreased ALFF values (P < 0.001, cluster level) in primary motor cortex extending to premotor cortex. Compared with normal controls, PD patients exhibited decreased ALFF values (P < 0.001, cluster level) in caudate and putamen (P < 0.001, cluster level), and increased ALFF values (P = 0.03, cluster level) in prefrontal cortex. The altered spontaneous brain activity in motor cortex may contribute to the pathogenesis of RBD in PD patients, which further supports the idea that the pathophysiology of RBD involves not only midbrain dysfunction but also cerebral cortex abnormalities. Our findings provide additional insight into the neural mechanism of RBD and may drive future research to develop better treatment. 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:697-703.

PC3 - 191 Assessment of Preoperative Functional MRI Measurement of Language Lateralisation in Brain Tumour Patients

This study aims to evaluate reliability of clinical functional magnetic resonance imaging (fMRI) in identifying language lateralisation index (LI), verified with Edinburgh handedness inventory (EHI), in brain tumour patients. Methods In this retrospective study, 31 of a single surgeon’s brain tumour patients over a 12 year period have been selected. Lesion type varied, 12 (39 percent) were high grade gliomas, 10 (32 percent) low grade gliomas, 3 (10 percent) meningiomas, and 6 (19 percent) other types. Patients underwent language fMRI paradigms for preoperative assessment, and a neuroimaging analyst was able to identify an LI value for at least one Brodmann area (BA). For each paradigm, a neuroimaging analyst attempted to calculate LI for Wernicke’s area (BA 22) and Broca’s area (BA 44 and 45). Results Of 113 total LI values, 66 (58 percent) were concordant to EHI-predicted hemispheric dominance. Reliability of language LI appears dependent upon the type of language task performed. Verb generation correctly identified Broca’s area in 18 patients (64 percent) and Wernicke’s area in 11 patients (61 percent), sentence completion correctly identified Broca’s area in 18 patients (72 percent) and Wernicke’s area in 9 patients (60 percent), and naming correctly identified Broca’s area in 7 patients (47 percent) and Wernicke’s area in 3 patients (27 percent). Conclusions Results show limited correlation between language LI determined by fMRI and EHI. The main limitation of this study is that language LI is being compared to EHI, rather than gold standard measure of hemispheric dominance (e.g. Wada).

Neurofeedback Training Effects on Inhibitory Brain Activation in ADHD: A Matter of Learning?

Neurofeedback training (NF) is a promising non-pharmacological treatment for ADHD that has been associated with improvement of attention-deficit/hyperactivity disorder (ADHD)-related symptoms as well as changes in electrophysiological measures. However, the functional localization of neural changes following NF compared to an active control condition, and of successful learning during training (considered to be the critical mechanism for improvement), remains largely unstudied. Children with ADHD (N=16, mean age: 11.81, SD: 1.47) were randomly assigned to either slow cortical potential (SCP, n=8) based NF or biofeedback control training (electromyogram feedback, n=8) and performed a combined Flanker/NoGo task pre- and post-training. Effects of NF, compared to the active control, and of learning in transfer trials (approximating successful transfer to everyday life) were examined with respect to clinical outcome and functional magnetic resonance imaging (fMRI) changes during inhibitory control. After 20 sessions of training, children in the NF group presented reduced ADHD symptoms and increased activation in areas associated with inhibitory control compared to baseline. Subjects who were successful learners (n=9) also showed increased activation in an extensive inhibitory network irrespective of the type of training. Activation increased in an extensive inhibitory network following NF training, and following successful learning through NF and control biofeedback. Although this study was only powered to detect large effects and clearly requires replication in larger samples, the results suggest a crucial role for learning effects in biofeedback trainings.

Altered neural activation pattern during teeth clenching in temporomandibular disorders.

The aim was to explore the neural activations during teeth clenching in TMDs patients pre- and post-treatment. Thirty TMDs patients and 20 controls underwent clinical evaluations and functional magnetic resonance imaging with a teeth clenching task. Eleven patients received repeat evaluation and imaging after wearing a stabilization splint for 3months. During teeth clench, the TMDs patients showed decreased positive activity in the left precentral gyrus, right and left inferior temporal gyrus, and left cerebellum and increased negative activations in the right medial prefrontal cortex (P<0.05 after AlphaSim correction). The 11 TMDs patients after treatment showed a return to normal neural activity in these areas. No brain areas in TMDs patients showed differences in activation after treatment compared with the controls, except for an increase in activation in the right cerebellum in the 11 TMDs patients (P<0.05 after AlphaSim correction). Decreased activations in cerebral areas associated with motor and cognitive functions in TMDs patients during teeth clenching were observed. Normalized activations of these areas happened in patients after routine treatment. These findings may facilitate the understanding of TMDs pathogenesis and the therapeutic mechanisms of the stabilization splint.

Functional versus Nonfunctional Rehabilitation in Chronic Ischemic Stroke: Evidences from a Randomized Functional MRI Study.

Motor rehabilitation of stroke survivors may include functional and/or nonfunctional strategy. The present study aimed to compare the effect of these two rehabilitation strategies by means of clinical scales and functional Magnetic Resonance Imaging (fMRI). Twelve hemiparetic chronic stroke patients were selected. Patients were randomly assigned a nonfunctional (NFS) or functional (FS) rehabilitation scheme. Clinical scales (Fugl-Meyer, ARA test, and modified Barthel) and fMRI were applied at four moments: before rehabilitation (P1) and immediately after (P2), 1 month after (P3), and three months after (P4) the end of rehabilitation. The NFS group improved significantly and exclusively their Fugl-Meyer scores at P2, P3, and P4, when compared to P1. On the other hand, the FS group increased significantly in Fugl-Meyer at P2, when compared to P1, and also in their ARA and Barthel scores. fMRI inspection at the individual level revealed that both rehabilitation schemes most often led to decreased activation sparseness, decreased activity of contralesional M1, increased asymmetry of M1 activity to the ipsilesional side, decreased perilesional activity, and decreased SMA activity. Increased M1 asymmetry with rehabilitation was also confirmed by Lateralization Indexes. Our clinical analysis revealed subtle differences between FS and NFS.

Presurgical functional magnetic resonance imaging in patients with brain tumors.

Clinical functional magnetic resonance imaging (fMRI) is still an upcoming diagnostic tool because it is time-consuming to perform the post-scan calculations and interpretations. A standardized and easily used method for the clinical assessment of fMRI scans could decrease the workload and make fMRI more attractive for clinical use. To evaluate a standardized clinical approach for distance measurement between benign brain tumors and eloquent cortex in terms of the ability to predict pre- and postoperative neurological deficits after intraoperative neuronavigation-assisted surgery. A retrospective study of 34 patients. The fMRI data were reanalyzed using a standardized distance measurement procedure combining data from both fMRI and three-dimensional T1 MRI scans. The pre- and postoperative neurological status of each patient was obtained from hospital records. Data analysis was performed using logistic regression analysis to determine whether the distance measured between the tumor margin and fMRI activity could serve as a predictor for neurological deficits. An odds ratio of 0.89 mm(-1) (P = 0.03) was found between the risk of preoperative neurological motor deficits and the tumor-fMRI distance. An odds ratio of 0.82 mm(-1) (P = 0.04) was found between the risk of additional postoperative neurological motor deficits and the tumor-fMRI distance. The tumor was radically removed in 10 cases; five patients experienced additional postoperative motor deficits (tumor-fMRI distance <18 mm) and five did not (tumor-fMRI distance >18 mm) (P = 0.008). This study indicates that the distance measured between the tumor margin and fMRI activation could serve as a valuable predictor of neurological motor deficits.

The economics of functional magnetic resonance imaging: clinical and research.

It is difficult to justify maintaining a clinical functional magnetic resonance imaging (fMRI) program based solely on revenue generation. The use of fMRI is, therefore, based mostly in patient care considerations, leading to better outcomes. The high costs of the top-of-the-line equipment, hardware, and software needed for state-of-the-art fMRI and the time commitment by multiple professionals are not adequately reimbursed at a representative rate by current payor schemes for the Current Procedure Terminology codes assigned.

Merging clinical neuropsychology and functional neuroimaging to evaluate the construct validity and neural network engagement of the n-back task.

The n-back task is a widely used neuroimaging paradigm for studying the neural basis of working memory (WM); however, its neuropsychometric properties have received little empirical investigation. The present study merged clinical neuropsychology and functional magnetic resonance imaging (fMRI) to explore the construct validity of the letter variant of the n-back task (LNB) and to further identify the task-evoked networks involved in WM. Construct validity of the LNB task was investigated using a bootstrapping approach to correlate LNB task performance across clinically validated neuropsychological measures of WM to establish convergent validity, as well as measures of related but distinct cognitive constructs (i.e., attention and short-term memory) to establish discriminant validity. Independent component analysis (ICA) identified brain networks active during the LNB task in 34 healthy control participants, and general linear modeling determined task-relatedness of these networks. Bootstrap correlation analyses revealed moderate to high correlations among measures expected to converge with LNB (|ρ|≥ 0.37) and weak correlations among measures expected to discriminate (|ρ|≤ 0.29), controlling for age and education. ICA identified 35 independent networks, 17 of which demonstrated engagement significantly related to task condition, controlling for reaction time variability. Of these, the bilateral frontoparietal networks, bilateral dorsolateral prefrontal cortices, bilateral superior parietal lobules including precuneus, and frontoinsular network were preferentially recruited by the 2-back condition compared to 0-back control condition, indicating WM involvement. These results support the use of the LNB as a measure of WM and confirm its use in probing the network-level neural correlates of WM processing.

The reporting of observational clinical functional magnetic resonance imaging studies: a systematic review.

IntroductionComplete reporting assists readers in confirming the methodological rigor and validity of findings and allows replication. The reporting quality of observational functional magnetic resonance imaging (fMRI) studies involving clinical participants is unclear.ObjectivesWe sought to determine the quality of reporting in observational fMRI studies involving clinical participants.MethodsWe searched OVID MEDLINE for fMRI studies in six leading journals between January 2010 and December 2011.Three independent reviewers abstracted data from articles using an 83-item checklist adapted from the guidelines proposed by Poldrack et al. (Neuroimage 2008; 40: 409–14). We calculated the percentage of articles reporting each item of the checklist and the percentage of reported items per article.ResultsA random sample of 100 eligible articles was included in the study. Thirty-one items were reported by fewer than 50% of the articles and 13 items were reported by fewer than 20% of the articles. The median percentage of reported items per article was 51% (ranging from 30% to 78%). Although most articles reported statistical methods for within-subject modeling (92%) and for between-subject group modeling (97%), none of the articles reported observed effect sizes for any negative finding (0%). Few articles reported justifications for fixed-effect inferences used for group modeling (3%) and temporal autocorrelations used to account for within-subject variances and correlations (18%). Other under-reported areas included whether and how the task design was optimized for efficiency (22%) and distributions of inter-trial intervals (23%).ConclusionsThis study indicates that substantial improvement in the reporting of observational clinical fMRI studies is required. Poldrack et al.'s guidelines provide a means of improving overall reporting quality. Nonetheless, these guidelines are lengthy and may be at odds with strict word limits for publication; creation of a shortened-version of Poldrack's checklist that contains the most relevant items may be useful in this regard.

Variability of Clinical Functional MR Imaging Results: A Multicenter Study

To investigate intersite variability of clinical functional magnetic resonance (MR) imaging, including influence of task standardization on variability and use of various parameters to inform the clinician whether the reliability of a given functional localization is high or low. Local ethics committees approved the study; all participants gave written informed consent. Eight women and seven men (mean age, 40 years) were prospectively investigated at three experienced functional MR sites with 1.5- (two sites) or 3-T (one site) MR. Nonstandardized motor and highly standardized somatosensory versions of a frequently requested clinical task (localization of the primary sensorimotor cortex) were used. Perirolandic functional MR variability was assessed (peak activation variability, center of mass [COM] variability, intraclass correlation values, overlap ratio [OR], activation size ratio). Data quality measures for functional MR images included percentage signal change (PSC), contrast-to-noise ratio (CNR), and head motion parameters. Data were analyzed with analysis of variance and a correlation analysis. Localization of perirolandic functional MR activity differed by 8 mm (peak activity) and 6 mm (COM activity) among sites. Peak activation varied up to 16.5 mm (COM range, 0.4-16.5 mm) and 45.5 mm (peak activity range, 1.8-45.5 mm). Signal strength (PSC, CNR) was significantly lower for the somatosensory task (mean PSC, 1.0% ± 0.5 [standard deviation]; mean CNR, 1.2 ± 0.4) than for the motor task (mean PSC, 2.4% ± 0.8; mean CNR, 2.9 ± 0.9) (P < .001, both). Intersite variability was larger with low signal strength (negative correlations between signal strength and peak activation variability) even if the task was highly standardized (mean OR, 22.0% ± 18.9 [somatosensory task] and 50.1% ± 18.8 [motor task]). Clinical practice and clinical functional MR biomarker studies should consider that the center of task-specific brain activation may vary up to 16.5 mm, with the investigating site, and should maximize functional MR signal strength and evaluate reliability of local results with PSC and CNR.

Clinical Functional MRI of the kidneys

In functional renal magnetic resonance imaging (MRI), advanced techniques are applied to obtain information on a functional and molecular level from the kidney tissue beyond pure morphology. Techniques such as diffusion-weighted and diffusion tensor imaging, arterial spin labelling, and blood oxygenation level-dependent imaging provide potential biomarkers of organ function. Moreover, dynamic contrast-enhanced techniques after the intra-venous injection of gadolinium-chelates may be used to assess glomerular filtration and urinary excretion. This review summarizes recent developments of contrast- and non-contrast-enhanced MRI techniques for assessment of renal function in a clinical setting. The physiological background and the sequence techniques are described in detail. Potential clinical applications of the different techniques are discussed regarding their potential usefulness in the assessment of parenchymal diseases, urinary tract anomalies, transplant kidney function, and renal masses.

Identification of Successful Clinical fMRI Sessions in Children: An Objective Approach

The term clinical functional magnetic resonance imaging (fMRI) describes an examination with direct clinical impact on the patient. Interpretation of clinical fMRI especially in children, however, is often difficult due to suboptimal data quality. The current gold standard is standardized visual evaluation. To evaluate such data in an automated and objective way, we developed an approach to identify successful sessions. Average activation inside a predefined, task-specific region of interest (ROI) is compared with average activation in the rest of the brain, and their ratio (classification factor [Fc]) is determined for different statistical thresholds (T). The approach was tested and validated using 239 clinical pediatric fMRI sessions (sensorimotor, perceptive /productive language). Performance was assessed in terms of sensitivity, specificity, and positive likelihood ratio. Best performance was found for Fc ≥ 2 and T ≥ 2.5, achieving a sensitivity of 0.87 and specificity of 0.94. Comparing the different domains, sensitivity was lowest for language production tasks, mainly due to atypical activation foci. We demonstrate that an objective, automated framework for the classification of clinical pediatric fMRI sessions may provide important additional information, supporting visual evaluation, especially from sensorimotor and language perception domains. In the current form, atypical or strong network activation is not easily captured.

Auditory orienting and inhibition of return in schizophrenia: A functional magnetic resonance imaging study

Patients with schizophrenia (SP) exhibit deficits in both attentional reorienting and inhibition of return (IOR) during visual tasks. However, it is currently unknown whether these deficits are supramodal in nature and how these deficits relate to other domains of cognitive dysfunction. In addition, the neuronal correlates of this pathological orienting response have not been investigated in either the visual or auditory modality. Therefore, 30 SP and 30 healthy controls (HC) were evaluated with an extensive clinical protocol and functional magnetic resonance imaging (fMRI) during an auditory cuing paradigm. SP exhibited both increased costs and delayed IOR during auditory orienting, suggesting a prolonged interval for attentional disengagement from cued locations. Moreover, a delay in the development of IOR was associated with cognitive deficits on formal neuropsychological testing in the domains of attention/inhibition and working memory. Event-related fMRI showed the characteristic activation of a frontoparietal network (invalid trials>valid trials), but there were no differences in functional activation between patients and HC during either attentional reorienting or IOR. Current results suggest that orienting deficits are supramodal in nature in SP, and are related to higher-order cognitive deficits that directly interfere with day-to-day functioning.

Methodische Probleme klinischer funktioneller MRT-Untersuchungen

During presurgical diagnostics clinical functional magnetic resonance imaging is increasingly being performed to improve the management of epilepsy and tumor patients. Rapid technical developments in fMRI technology continuously further new diagnostic applications. Safe clinical application requires a profound and critical handling of the various methodological problems inherent with this complex technique. This article reviews relevant problems and solutions for patient investigations up to the preparation of an individual clinical fMRI report.

Clinical Functional Magnetic Resonance Imaging for Pre-surgical Planning – the Singapore General Hospital Experience with the First 30 Patients

Functional magnetic resonance imaging (fMRI) is a neuroradiological technique for the localisation of cortical function. FMRI made its debut in cognitive neuroscience and then eventually to other clinical applications. We report our experience with pre-surgical fMRI on a high field scanner, based purely on a clinical platform. The protocols included motor, auditory, visual and language fMRI. The choice of protocols was dependant on clinical request and lesion locale. Retrospective analysis and audit of the fi rst 30 consecutive patients over a 12-month period revealed that about 85% of patients had a successful examination. In a pictorial essay, we demonstrate that patients with weakness in performing a motor task showed abnormal activations of the pre-motor and supplementary motor areas. FMRI data greatly enhances the pre-surgical planning process and the conduct of surgery when it is incorporated into the surgical navigation system in the operating theatre.

A longitudinal study of functional magnetic resonance imaging in upper-limb hemiplegia after stroke treated with constraint-induced movement therapy

Primary objective: To investigate the correlation of cerebral function reorganization and functional recovery by using functional magnetic resonance imaging (fMRI) with constraint-induced movement therapy (CIMT) for chronic upper-limb hemiparesis in one subject with stroke.Research design: The patient was treated with 2 weeks of CIMT and the unaffected upper-limb was restricted by a splint for 2 weeks. Clinical measures and functional magnetic resonance imaging (fMRI) tests were performed 1 day before the treatment, the day of after the treatment and 2 weeks after the treatment.Main outcomes: Compared with the baseline, Upper Extremity Function Test (UEFT) of the patient's upper limb increased by 29.1% and Simple Test for Evaluating Hand Function (STEF) increased by 18.4%. Before, after and 2 weeks after the treatment, changes of activation in brain by using fMRI were found during the movement of the affected and unaffected hand.Conclusion: CIMT could significantly improve the upper limb movement function of stroke patients and fMRI proved that this kind of change was related with the plasticity change of the cerebrum. The motor function of the unaffected limb could not be affected when it was restricted and the change of the cerebrum excitation area was a transient change.

Evidence of Deviant Emotional Processing in Psychopathy: A fMRI Case Study

In this case–report we describe a prototypical criminal psychopath by clinical characteristics and functional magnetic resonance imaging (fMRI). To study emotional disability in psychopathy we compared fMRI-BOLD (blood oxygen level dependent) responses to healthy controls. In a block-design subjects were exposed to drawings of facial expressions alternated with scrambled drawings. Exposure to facial expressions activated brain regions of older origin in the psychopath, whereas all activated regions in controls were neocortical. Our findings support the notion that the processing of emotional stimuli in psychopathy is atypical.

The Influence of Hand Dominance on the Response to a Constraint-Induced Therapy Program Following Stroke

Background. Following stroke it is common to exhibit deficits in mobility of the upper extremity. Constraint-induced therapy (CIT) is a rehabilitation technique used to promote use of the more affected hand via constraint of the less affected hand. One factor that could impact the outcome following CIT is hand dominance. Years of preferred use of one hand may give individuals with the dominant hand affected by stroke an advantage in improving the mobility of the more affected hand compared to those individuals with the nondominant hand affected by stroke. In addition, the diminished use of the less affected hand during CIT may also create changes. Objective. Our goal was to better understand how hand dominance may influence the response to a CIT program both cortically and behaviorally in both the more affected hand and less affected constrained hand. Methods. A repeated measures design with a double baseline was used to assess changes in clinical tests and functional magnetic resonance imaging (fMRI) in individuals with their dominant or nondominant hand affected by stroke involved in a CIT program. Results. No significant differences were found between groups in their responses to CIT. Overall subjects demonstrated behavioral and cortical changes with the more affected hand and the less affected constrained hand did not significantly change. Conclusion. CIT promotes improvement of the more affected hand particularly on complex tests without decrements to the less affected constrained hand. Cortically, statistically significant changes in activation were noted after the intervention for the more affected hand; no changes were noted with the less affected constrained hand.

Clinical Functional Magnetic Resonance Imaging (fMRI)

The clinical application of functional magnetic resonance imaging (fMRI) makes the implementation of dedicated imaging protocols mandatory that measure specific functions of the human brain validly in short scanning times. Clinical fMRI requires – in contrast to research applications – the analysis of data from individual patients to achieve an fMRI diagnosis. To this end, the paradigms need to be applicable also in patients with neurologic, linguistic or other cognitive deficits. Clinical fMRI protocols typically consist of a set of different paradigms to better assess complex brain functions (e.g., language, memory) and/or to enhance the validity of the fMRI results through reproduction. In this paper, optimized clinical fMRI protocols for motor, somatosensory and language function are proposed.

Clinical Functional Magnetic Resonance Imaging

To describe a new series of evaluation/procedural codes that were approved by the American Medical Association (AMA) CPT Editorial Panel for use in billing for these procedures by physicians or licensed clinical psychologists. As of January of 2007, 3 distinct CPT codes for billing related to the functional magnetic resonance imaging (fMRI) procedure are available for use. Description of CPT codes. CPT code 70554: MRI, brain, fMRI; including test selection and administration of repetitive body part movement and/or visual stimulation, not requiring physician or psychologist administration. CPT code 70555: MRI, brain, fMRI; requiring physician or psychologist administration. This is to be always reported with CPT code 96020: neurofunctional testing selection and administration during noninvasive imaging functional brain mapping, with test administered entirely by a physician or psychologist, with review of test results and report. These CPT codes will allow for billing of both the neurofunctional and imaging components of fMRI. Functional brain mapping will now be available as an activation study to aid in localizing neurofunctional abilities.