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.
References
[1]
Liang H, Zheng W, Xu H, Lei J, Song Z, et al. (2012) No evidence of association between the LINGO4 gene and essential tremor in Chinese Han patients. Parkinsonism Relat Disord 18: 303–305.
[2]
Shill HA, Adler CH, Beach TG (2012) Pathology in essential tremor. Parkinsonism Relat Disord 18 Suppl 1S135–137.
Raethjen J, Deuschl G (2012) The oscillating central network of Essential tremor. Clin Neurophysiol 123: 61–64.
[5]
Louis ED, Faust PL, Vonsattel JP (2011) Purkinje cell loss is a characteristic of essential tremor. Parkinsonism Relat Disord 17: 406–409.
[6]
Louis ED, Faust PL, Vonsattel J-PG, Honig LS, Henchcliffe C, et al. (2009) Older onset essential tremor: More rapid progression and more degenerative pathology. Movement Disorders 24: 1606–1612.
[7]
Louis ED, Vonsattel JP (2008) The emerging neuropathology of essential tremor. Mov Disord 23: 174–182.
[8]
Rajput AH, Adler CH, Shill HA, Rajput A (2012) Essential tremor is not a neurodegenerative disease. Neurodegener Dis Manag 2: 259–268.
[9]
Rajput AH, Robinson CA, Rajput ML, Rajput A (2011) Cerebellar Purkinje cell loss is not pathognomonic of essential tremor. Parkinsonism Relat Disord 17: 16–21.
[10]
Rajput AH, Robinson CA, Rajput ML, Robinson SL, Rajput A (2012) Essential tremor is not dependent upon cerebellar Purkinje cell loss. Parkinsonism Relat Disord 18: 626–628.
[11]
Bagepally BS, Bhatt MD, Chandran V, Saini J, Bharath RD, et al. (2012) Decrease in Cerebral and Cerebellar Gray Matter in Essential Tremor: A Voxel-Based Morphometric Analysis under 3T MRI. J Neuroimaging 22: 275–278.
[12]
Benito-Leon J, Alvarez-Linera J, Hernandez-Tamames JA, Alonso-Navarro H, Jimenez-Jimenez FJ, et al. (2009) Brain structural changes in essential tremor: voxel-based morphometry at 3-Tesla. J Neurol Sci 287: 138–142.
[13]
Cerasa A, Messina D, Nicoletti G, Novellino F, Lanza P, et al. (2009) Cerebellar atrophy in essential tremor using an automated segmentation method. AJNR Am J Neuroradiol 30: 1240–1243.
[14]
Daniels C, Peller M, Wolff S, Alfke K, Witt K, et al. (2006) Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor. Neurology 67: 1452–1456.
[15]
Quattrone A, Cerasa A, Messina D, Nicoletti G, Hagberg G, et al. (2008) Essential head tremor is associated with cerebellar vermis atrophy: a volumetric and voxel-based morphometry MR imaging study. American Journal of Neuroradiology 29: 1692–1697.
[16]
Buijink AW, Caan MW, Tijssen MA, Hoogduin JM, Maurits NM, et al. (2013) Decreased Cerebellar Fiber Density in Cortical Myoclonic Tremor but Not in Essential Tremor. The Cerebellum 12: 199–204.
[17]
Klein JC, Lorenz B, Kang JS, Baudrexel S, Seifried C, et al. (2011) Diffusion tensor imaging of white matter involvement in essential tremor. Hum Brain Mapp 32: 896–904.
[18]
Nicoletti G, Manners D, Novellino F, Condino F, Malucelli E, et al. (2010) Diffusion tensor MRI changes in cerebellar structures of patients with familial essential tremor. Neurology 74: 988–994.
[19]
Saini J, Bagepally BS, Bhatt MD, Chandran V, Bharath RD, et al. (2012) Diffusion tensor imaging: Tract based spatial statistics study in essential tremor. Parkinsonism Relat Disord 18: 477–482.
[20]
Boecker H, Brooks DJ (1998) Functional imaging of tremor. Movement Disorders 13: 64–72.
[21]
Bucher SF, Seelos KC, Dodel RC, Reiser M, Oertel WH (1997) Activation mapping in essential tremor with functional magnetic resonance imaging. Ann Neurol 41: 32–40.
[22]
Passamonti L, Novellino F, Cerasa A, Chiriaco C, Rocca F, et al. (2011) Altered cortical-cerebellar circuits during verbal working memory in essential tremor. Brain 134: 2274–2286.
[23]
Cerasa A, Passamonti L, Novellino F, Salsone M, Gioia MC, et al. (2010) Fronto-parietal overactivation in patients with essential tremor during Stroop task. Neuroreport 21: 148–151.
[24]
Fox MD, Greicius M (2010) Clinical applications of resting state functional connectivity. Frontiers in systems neuroscience 4: 19–26.
[25]
Biswal B, Yetkin FZ, Haughton VM, Hyde JS (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34: 537–541.
[26]
Biswal BB (2012) Resting state fMRI: a personal history. Neuroimage 62: 938–944.
[27]
Hacker C, Perlmutter J, Criswell S, Ances B, Snyder A (2012) Resting state functional connectivity of the striatum in Parkinson’s disease. Brain 135: 3699–3711.
[28]
Baudrexel S, Witte T, Seifried C, von Wegner F, Beissner F, et al. (2011) Resting state fMRI reveals increased subthalamic nucleus-motor cortex connectivity in Parkinson’s disease. Neuroimage 55: 1728–1738.
[29]
Douaud G, Filippini N, Knight S, Talbot K, Turner MR (2011) Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis. Brain 134: 3470–3479.
[30]
Zarei M, Beckmann CF, Binnewijzend MA, Schoonheim MM, Oghabian MA, et al. (2012) Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer’s disease. Neuroimage 66: 28–35.
[31]
Xie C, Bai F, Yu H, Shi Y, Yuan Y, et al. (2012) Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment. Neuroimage 63: 320–327.
[32]
Wang L, Zang Y, He Y, Liang M, Zhang X, et al. (2006) Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: evidence from resting state fMRI. Neuroimage 31: 496–504.
[33]
Popa T, Russo M, Vidailhet M, Roze E, Lehericy S, et al. (2013) Cerebellar rTMS stimulation may induce prolonged clinical benefits in essential tremor, and subjacent changes in functional connectivity: An open label trial. Brain Stimul 6: 175–179.
[34]
Shukla DK, Keehn B, Müller RA (2010) Regional homogeneity of fMRI time series in autism spectrum disorders. Neuroscience letters 476: 46–51.
[35]
Zang Y, Jiang T, Lu Y, He Y, Tian L (2004) Regional homogeneity approach to fMRI data analysis. Neuroimage 22: 394–400.
[36]
Zuo XN, Xu T, Jiang L, Yang Z, Cao XY, et al. (2012) Toward reliable characterization of functional homogeneity in the human brain: Preprocessing, scan duration, imaging resolution and computational space. Neuroimage 65: 374–386.
[37]
You H, Wang J, Wang H, Zang YF, Zheng FL, et al. (2011) Altered regional homogeneity in motor cortices in patients with multiple system atrophy. Neuroscience letters 502: 18–23.
[38]
Wu T, Long X, Zang Y, Wang L, Hallett M, et al. (2009) Regional homogeneity changes in patients with Parkinson’s disease. Hum Brain Mapp 30: 1502–1510.
[39]
Zhang Z, Liu Y, Jiang T, Zhou B, An N, et al. (2012) Altered spontaneous activity in Alzheimer’s disease and mild cognitive impairment revealed by Regional Homogeneity. Neuroimage 59: 1429–1440.
[40]
He Y, Wang L, Zang Y, Tian L, Zhang X, et al. (2007) Regional coherence changes in the early stages of Alzheimer’s disease: a combined structural and resting-state functional MRI study. Neuroimage 35: 488–500.
[41]
Louis ED, Ford B, Lee H, Andrews H, Cameron G (1998) Diagnostic criteria for essential tremor: a population perspective. Arch Neurol 55: 823–828.
[42]
Tessitore A, Esposito F, Vitale C, Santangelo G, Amboni M, et al. (2012) Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease. Neurology 79: 2226–2232.
[43]
Louis ED (2005) Essential tremor. Lancet Neurol 4: 100–110.
[44]
Chao-Gan Y, Yu-Feng Z (2010) DPARSF: A MATLAB Toolbox for “Pipeline” Data Analysis of Resting-State fMRI. Front Syst Neurosci 4: 13–16.
[45]
Song XW, Dong ZY, Long XY, Li SF, Zuo XN, et al. (2011) REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One 6: e25031.
[46]
Tian L, Ren J, Zang Y (2012) Regional homogeneity of resting state fMRI signals predicts Stop signal task performance. Neuroimage 60: 539–544.
[47]
Hellwig B, Haussler S, Schelter B, Lauk M, Guschlbauer B, et al. (2001) Tremor-correlated cortical activity in essential tremor. Lancet 357: 519–523.
[48]
Louis ED (2009) Essential tremors: a family of neurodegenerative disorders? Arch Neurol 66: 1202–1208.
[49]
Louis ED (2010) Essential tremor: evolving clinicopathological concepts in an era of intensive post-mortem enquiry. Lancet Neurol 9: 613–622.
[50]
Santangelo G, Trojano L, Barone P, Errico D, Improta I, et al. (2013) Cognitive and affective theory of mind in patients with essential tremor. J Neurol 260: 513–520.
[51]
Ozen Barut B, Gunal DI, Turkmen C, Mollahasanoglu A, Ankarali H (2012) Clinical and cognitive profiles of patients with both Parkinson’s disease and essential tremor. Acta Neurol Belg. DOI:10.1007/s13760-012-0124-z.
[52]
Hoskovcova M, Ulmanova O, Sprdlik O, Sieger T, Novakova J, et al. (2013) Disorders of Balance and Gait in Essential Tremor Are Associated with Midline Tremor and Age. The Cerebellum 12: 27–34.
[53]
Chandran V, Pal PK (2012) Essential tremor: beyond the motor features. Parkinsonism Relat Disord 18: 407–413.
[54]
Fasano A, Herzog J, Raethjen J, Rose FEM, Muthuraman M, et al. (2010) Gait ataxia in essential tremor is differentially modulated by thalamic stimulation. Brain 133: 3635–3648.
[55]
Boecker H, Weindl A, Brooks DJ, Ceballos-Baumann AO, Liedtke C, et al. (2010) GABAergic dysfunction in essential tremor: an 11C-flumazenil PET study. Journal of Nuclear Medicine 51: 1030–1035.
[56]
Breit S, Reimold M, Reischl G, Klockgether T, Wullner U (2006) [(11)C]d-threo-methylphenidate PET in patients with Parkinson’s disease and essential tremor. J Neural Transm 113: 187–193.
[57]
Stoodley CJ, Schmahmann JD (2009) Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage 44: 489–501.
[58]
Stoodley CJ, Valera EM, Schmahmann JD (2012) Functional topography of the cerebellum for motor and cognitive tasks: An fMRI study. Neuroimage 59: 1560–1570.
[59]
Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G (2001) The gait disorder of advanced essential tremor. Brain 124: 2278–2286.
[60]
Kronenbuerger M, Gerwig M, Brol B, Block F, Timmann D (2007) Eyeblink conditioning is impaired in subjects with essential tremor. Brain 130: 1538–1551.
[61]
K？ster B, Deuschl G, Lauk M, Timmer J, Guschlbauer B, et al. (2002) Essential tremor and cerebellar dysfunction: abnormal ballistic movements. Journal of Neurology, Neurosurgery & Psychiatry 73: 400–405.
[62]
Avanzino L, Bove M, Tacchino A, Ruggeri P, Giannini A, et al. (2009) Cerebellar involvement in timing accuracy of rhythmic finger movements in essential tremor. European Journal of Neuroscience 30: 1971–1979.
[63]
Perlmutter JS, Mink JW, Bastian AJ, Zackowski K, Hershey T, et al. (2002) Blood flow responses to deep brain stimulation of thalamus. Neurology 58: 1388–1394.
[64]
Louis ED, Shungu DC, Mao X, Chan S, Jurewicz EC (2004) Cerebellar metabolic symmetry in essential tremor studied with 1H magnetic resonance spectroscopic imaging: implications for disease pathology. Mov Disord 19: 672–677.
[65]
Helmich RC, Janssen MJ, Oyen WJ, Bloem BR, Toni I (2011) Pallidal dysfunction drives a cerebellothalamic circuit into Parkinson tremor. Ann Neurol 69: 269–281.
[66]
Sheline YI, Price JL, Yan Z, Mintun MA (2010) Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci U S A 107: 11020–11025.
[67]
Coste CP, Sadaghiani S, Friston KJ, Kleinschmidt A (2011) Ongoing brain activity fluctuations directly account for intertrial and indirectly for intersubject variability in Stroop task performance. Cereb Cortex 21: 2612–2619.
[68]
Sheline YI, Raichle ME (2013) Resting State Functional Connectivity in Preclinical Alzheimer’s Disease. Biol Psychiatry. DOI:10.1016/j.biopsych.2012.11.028.
[69]
Bermejo-Pareja F, Louis ED, Benito-Leon J (2007) Risk of incident dementia in essential tremor: a population-based study. Mov Disord 22: 1573–1580.
[70]
Galvin JE, Price JL, Yan Z, Morris JC, Sheline YI (2011) Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease. Neurology 76: 1797–1803.
[71]
Molnar GF, Pilliar A, Lozano AM, Dostrovsky JO (2005) Differences in neuronal firing rates in pallidal and cerebellar receiving areas of thalamus in patients with Parkinson’s disease, essential tremor, and pain. Journal of neurophysiology 93: 3094–3101.
[72]
Lenglet C, Abosch A, Yacoub E, De Martino F, Sapiro G, et al. (2012) Comprehensive in vivo mapping of the human basal ganglia and thalamic connectome in individuals using 7T MRI. PLoS One 7: e29153.
[73]
Shibasaki H (2012) Cortical activities associated with voluntary movements and involuntary movements. Clin Neurophysiol 123: 229–243.
[74]
Hellwig B, Schelter B, Guschlbauer B, Timmer J, Lucking CH (2003) Dynamic synchronisation of central oscillators in essential tremor. Clin Neurophysiol 114: 1462–1467.
[75]
Muthuraman M, Heute U, Arning K, Anwar AR, Elble R, et al. (2012) Oscillating central motor networks in pathological tremors and voluntary movements. What makes the difference? Neuroimage 60: 1331–1339.
[76]
Shehzad Z, Kelly AM, Reiss PT, Gee DG, Gotimer K, et al. (2009) The resting brain: unconstrained yet reliable. Cereb Cortex 19: 2209–2229.
[77]
Zuo XN, Kelly C, Adelstein JS, Klein DF, Castellanos FX, et al. (2010) Reliable intrinsic connectivity networks: test-retest evaluation using ICA and dual regression approach. Neuroimage 49: 2163–2177.
[78]
Zuo XN, Di Martino A, Kelly C, Shehzad ZE, Gee DG, et al. (2010) The oscillating brain: complex and reliable. Neuroimage 49: 1432–1445.
[79]
Satterthwaite TD, Elliott MA, Gerraty RT, Ruparel K, Loughead J, et al. (2013) An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data. Neuroimage 64: 240–256.
[80]
Van Dijk KR, Sabuncu MR, Buckner RL (2012) The influence of head motion on intrinsic functional connectivity MRI. Neuroimage 59: 431–438.
[81]
Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 59: 2142–2154.
[82]
Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE (2013) Steps toward optimizing motion artifact removal in functional connectivity MRI; a reply to Carp. Neuroimage 76: 439–441.
