Novel Functional MRI Task for Studying the Neural Correlates of Upper Limb Tremor (original) (raw)
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Quantification and Modulation of Tremor in Rapid Upper Limb Movements
IFMBE Proceedings, 2014
Tremor is a manifestation of a variety of human neurodegenerative diseases, notably Parkinson's disease (PD), a chronic disease that affects one in 100 people over age 60 years. Recent research indicates that more than five million worldwide have PD. This disease is primarily caused by a progressive loss of dopamine neurons in the nigrostriatal system that leads to widespread motor symptoms such as bradykinesia, rigidity, tremor and postural instability. Although the diagnosis of PD remains clinical, advances in functional and structural imaging have improved the ability to differentiate between PD and Essential Tremor (ET), as well as between different akinetic-rigid syndromes. No definitive test or biomarker is available for PD, so the rate of misdiagnosis is relatively high. It is therefore crucial to be able to characterize tremor in PD and ET as it is a very common feature at the onset of both diseases. This is made possible with a combination of a neuroscientific and methodological multi-modal imaging approaches, namely kinetic recording methods using accelerometers to quantify tremor amplitude and frequency and functional magnetic resonance imaging (fMRI). These allow the identification of the neural underpinnings of tremor in both PD and ET patients, which in fact have been surprisingly difficult to decipher. In this work we aim to find which tasks involving upper limb movements are suitable to modulate both PD and ET tremor. The same tasks are considered with and without added loading. The resulting analysis will allow designing an efficient fMRI protocol aiming at the identification of the cortical circuits responsible for the modulation of tremor.
2012
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.
Scientific Reports
The pathophysiology of essential tremor (ET) is controversial and might be further elucidated by advanced neuroimaging. Focusing on homogenous ET patients diagnosed according to the 2018 consensus criteria, this study aimed to: (1) investigate whether task functional MRI (fMRI) can identify networks of activated and deactivated brain areas, (2) characterize morphometric and functional modulations, relative to healthy controls (HC). Ten ET patients and ten HC underwent fMRI while performing two motor tasks with their upper limb: (1) maintaining a posture (both groups); (2) simulating tremor (HC only). Activations/deactivations were obtained from General Linear Model and compared across groups/tasks. Voxel-based morphometry and linear regressions between clinical and fMRI data were also performed. Few cerebellar clusters of gray matter loss were found in ET. Conversely, widespread fMRI alterations were shown. Tremor in ET (task 1) was associated with extensive deactivations mainly inv...
PLoS ONE, 2013
Essential tremor (ET) is one of the most common movement disorders in human adults. It can be characterized as a progressive neurological disorder of which the most recognizable feature is a tremor of the arms or hands that is apparent during voluntary movements such as eating and writing. The pathology of ET remains unclear. Resting-state fMRI (RS-fMRI), as a non-invasive imaging technique, was employed to investigate abnormalities of functional connectivity in ET in the brain. Regional homogeneity (ReHo) was used as a metric of RS-fMRI to assess the local functional connectivity abnormality in ET with 20 ET patients and 20 age-and gender-matched healthy controls (HC). The ET group showed decreased ReHo in the anterior and posterior bilateral cerebellar lobes, the bilateral thalamus and the insular lobe, and increased ReHo in the bilateral prefrontal and parietal cortices, the left primary motor cortex and left supplementary motor area. The abnormal ReHo value of ET patients in the bilateral anterior cerebellar lobes and the right posterior cerebellar lobe were negatively correlated with the tremor severity score, while positively correlated with that in the left primary motor cortex. These findings suggest that the abnormality in cerebello-thalamo-cortical motor pathway is involved in tremor generation and propagation, which may be related to motor-related symptoms in ET patients. Meanwhile, the abnormality in the prefrontal and parietal regions may be associated with non-motor symptoms in ET. These findings suggest that the ReHo could be utilized for investigations of functional-pathological mechanism of ET.
Resting state functional MRI reveals abnormal network connectivity in orthostatic tremor
Medicine, 2016
Very little is known about the pathogenesis of orthostatic tremor (OT). We have observed that OT patients might have deficits in specific aspects of neuropsychological function, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests a possible involvement of frontocerebellar circuits. We examined whether resting-state functional magnetic resonance imaging (fMRI) might provide further insights into the pathogenesis on OT. Resting-state fMRI data in 13 OT patients (11 women and 2 men) and 13 matched healthy controls were analyzed using independent component analysis, in combination with a "dual-regression" technique, to identify group differences in several resting-state networks (RSNs). All participants also underwent neuropsychological testing during the same session. Relative to healthy controls, OT patients showed increased connectivity in RSNs involved in cognitive processes (default mode network [DMN] and frontoparietal networks), and decreased connectivity in the cerebellum and sensorimotor networks. Changes in network integrity were associated not only with duration (DMN and medial visual network), but also with cognitive function. Moreover, in at least 2 networks (DMN and medial visual network), increased connectivity was associated with worse performance on different cognitive domains (attention, executive function, visuospatial ability, visual memory, and language). In this exploratory study, we observed selective impairments of RSNs in OT patients. This and other future resting-state fMRI studies might provide a novel method to understand the pathophysiological mechanisms of motor and nonmotor features of OT.
of a thesis at the University of Miami. Thesis supervised by Dr. Akmal Younis and Dr. Fatta Basil Nahab. No. of pages in text. (65) Essential Tremor (ET) is the most common neurological movement disorder, with slowly progressive symptoms that impact the patient's quality of life and ability to perform activities of daily living. Tremors in ET occur during kinetic, with two subtypes: postural tremors and kinetic tremors. Postural tremors appear when the arms are topically maintained in a position against gravity, whereas kinetic tremors appear during sustained voluntary movements such as writing or drawing. The underlying mechanisms of either tremor type are not known, and further work is needed to determine whether they are two manifestations of the same brain dysfunction, or consequences of different underlying causes. To further understand these disease manifestations, we employed functional magnetic resonance imaging (fMRI) in conjunction with quantitative tremor measures (accelerometry and spirography). iii iii Dedicated to my parents for their forever support; to love and patience my Mom gave me and to my dad who is the best teacher of my life. Also to my friend and brother (arman) for being with me to overcome dificulties. iv Acknowledgement I would like to first give my great appreciation to Dr. Akmal Younis who is not among us today. Although I worked under his supervision for a short time and could not graduate with the Ph.D. degree, he taught me how to have a scientific problem-solving mind which was what I needed at the time. God bless his soul. I would like to thank Dr. Fatta Nahab who introduced me to the beautiful word of functional MRI. He kindly found the unimproved parts of my academic and personal characteristics and in a friendly manner guided me to this point in my academic development. Working with him has effectively changed my career experience.
Functional Brain Activity Relates to 0–3 and 3–8 Hz Force Oscillations in Essential Tremor
It is well-established that during goal-directed motor tasks, patients with essential tremor have increased oscillations in the 0-3 and 3-8 Hz bands. It remains unclear if these increased oscillations relate to activity in specific brain regions. This study used task-based functional magnetic resonance imaging to compare the brain activity associated with oscillations in grip force output between patients with essential tremor, patients with Parkinson's disease who had clinically evident tremor, and healthy controls. The findings demonstrate that patients with essential tremor have increased brain activity in the motor cortex and supplementary motor area compared with controls, and this activity correlated positively with 3-8 Hz force oscillations. Brain activity in cerebellar lobules I-V was reduced in essential tremor compared with controls and correlated negatively with 0-3 Hz force oscillations. Widespread differences in brain activity were observed between essential tremor and Parkinson's disease. Using functional connectivity analyses during the task evidenced reduced cerebellar-cortical functional connectivity in patients with essential tremor compared with controls and Parkinson's disease. This study provides new evidence that in essential tremor 3-8 Hz force oscillations relate to hyperactivity in motor cortex, 0-3 Hz force oscillations relate to the hypoactivity in the cerebellum, and cerebellar-cortical functional connectivity is impaired.
Magnetic Resonance Imaging, 2016
Over 0.9% of the population suffers from a movement disorder. The pathophysiology of most movement disorders remains unknown, thereby impairing effective diagnosis and consequently effective treatment. Abnormal activity of the cerebellum (CBL) and basal ganglia (BG) has been implicated in many movement disorders, including Parkinsonian tremor and dystonia. Selectively activating these brain regions may help identify pathological changes and expedite diagnosis. Dedicated pairs of isometric wrist flexion tasks with and without visual feedback of the exerted torque were devised to selectively activate the CBL and BG in healthy subjects (N=5), while ensuring safety and keeping artifacts to a minimum. Increased activity in CBL and BG (putamen) was found during a constant torque task with visual feedback compared to a constant torque task without visual feedback. Increased BG (caudate nucleus) activity was found when comparing a torque task with visual feedback where flexion and rest were rapidly alternated, to the same task without visual feedback. Increased activity in the CBL was found during a constant torque task with visual feedback with an added visual error compared to a constant torque task with normal visual feedback. This study shows that specific pairs of motor tasks using the wrist and simple MRcompatible equipment allow for targeted activation of CBL and BG and paves the way for more extensive research and eventually improved diagnosis of patients.
NeuroImage, 2010
Multicentre MRI studies offer great potential to increase study power and flexibility, but it is not yet clear how reproducible the results from multiple centres may be. Here we present results from the multicentre study 'CaliBrain', examining the reproducibility of fMRI data within and between three sites. Fourteen subjects were scanned twice on three 1.5 T GE scanners using an identical scanning protocol. We present data from a motor task with three conditions, sequential and random finger tapping and rest. Similar activation maps were obtained for each site and visit; brain areas consistently activated during the task included the premotor, primary motor and supplementary motor areas, the striatum and cerebellum. Reproducibility was evaluated within and between sites by comparing the extent and spatial agreement of activation maps at both the subject and group levels. The results were within the range previously reported for similar tasks on single scanners and both mea...