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Differential patterns of functional connectivity in tremor dominant Parkinson’s disease and essential tremor plus

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Tremor dominant Parkinson’s disease (TDPD) and essential tremor plus (ETP) syndrome are commonly encountered tremor dominant neurological disorders. Although the basal ganglia thalamocortical (BGTC) and cerebello thalamocortical (CTC) networks are implicated in tremorogenesis, the extent of functional connectivity alterations across disorders is uncertain. This study aims to evaluate functional connectivity of the BGTC and CTC in TDPD and ETP. Resting state functional MRI was acquired for 25 patients with TDPD, ETP and 22 healthy controls (HC). Following pre-processing and denoising, seed-to-voxel based connectivity was carried out at FDR < 0.05 using ROIs belonging to the BGTC and CTC. Fahn-Tolosa-Marin tremor rating scale (FTMRS) was correlated with the average connectivity values at FDR < 0.05. Compared to HC, TDPD showed decreased connectivity between cerebellum and pre, post central gyrus. While, ETP showed decreased connectivity between pallidum and occipital cortex, precuneus, cuneus compared to HC. In comparison to ETP, TDPD showed increased connectivity between precentral gyrus, pallidum, SNc with the default mode network (DMN), and decreased connectivity between cerebellum with superior, middle frontal gyrus was observed. Tremor severity positively correlated with connectivity between SNc and DMN in TDPD, and negatively correlated with pallidal connectivity in ETP. Pattern of BGTC, CTC involvement is differential i.e., higher connectivity of the BGTC nodes in TDPD, and higher connectivity of cerebellar nodes in ETP. The interesting observation of pallidal involvement in ETP suggests the role of BGTC in the pathogenesis of ETP, and indicated similarities in concepts of tremor genesis in TDPD and ETP.

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References

  • Andersson JL, Hutton C, Ashburner J, Turner R, Friston K (2001) Modeling geometric deformations in EPI time series. NeuroImage 13(5):903–919

    Article  CAS  PubMed  Google Scholar 

  • Archer DB, Coombes SA, Chu WT et al (2018) A widespread visually-sensitive functional network relates to symptoms in essential tremor. Brain 141(2):472–485

    Article  PubMed  Google Scholar 

  • Ashburner J, Friston KJ (2005) Unified segmentation. NeuroImage 26(3):839–851

    Article  PubMed  Google Scholar 

  • Basit H, Kahwaji CI (2020) Clonazepam

  • Benabid AL, Pollak P, Gervason C et al (1991) Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 337(8738):403–406

    Article  CAS  PubMed  Google Scholar 

  • Benabid AL, Pollak P, Gao D et al (1996) Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neurosurg 84(2):203–214

    Article  CAS  PubMed  Google Scholar 

  • Benito-León J, Louis ED, Romero JP et al (2015) Altered functional connectivity in essential tremor: a resting-state fMRI study. Medicine. ;94(49)

  • Benito-León J, Sanz‐Morales E, Melero H et al (2019) Graph theory analysis of resting‐state functional magnetic resonance imaging in essential tremor. Hum Brain Mapp

  • Bergman H, Feingold A, Nini A et al (1998) Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates. Trends Neurosci 21(1):32–38

    Article  CAS  PubMed  Google Scholar 

  • Bhatia KP, Bain P, Bajaj N et al (2018) Consensus Statement on the classification of tremors. From the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord 33(1):75–87

    Article  PubMed  Google Scholar 

  • Brittain J-S, Brown P (2013) The many roads to tremor. Exp Neurol 250:104–107

    Article  PubMed  Google Scholar 

  • Bucher SF, Seelos KC, Dodel RC, Reiser M, Oertel WH (1997) Activation mapping in essential tremor with functional magnetic resonance imaging. Annals Neurology: Official J Am Neurol Association Child Neurol Soc 41(1):32–40

    Article  CAS  Google Scholar 

  • Buijink AW, Broersma M, van der Stouwe AM et al (2015) Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor. Parkinsonism Relat Disord 21(4):383–388

    Article  CAS  PubMed  Google Scholar 

  • Cagnan H, Little S, Foltynie T et al (2014) The nature of tremor circuits in parkinsonian and essential tremor. Brain 137(Pt 12):3223–3234

    Article  PubMed  PubMed Central  Google Scholar 

  • Caligiuri ME, Arabia G, Barbagallo G et al (2017) Structural connectivity differences in essential tremor with and without resting tremor. J Neurol 264(9):1865–1874

    Article  CAS  PubMed  Google Scholar 

  • Defer GL, Widner H, Marié RM, Rémy P, Levivier M (1999) Core assessment program for surgical interventional therapies in Parkinson’s disease (CAPSIT-PD). Mov Disord 14(4):572–584

    Article  CAS  PubMed  Google Scholar 

  • Desikan RS, Ségonne F, Fischl B et al (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage 31(3):968–980

    Article  PubMed  Google Scholar 

  • Dirkx MF, den Ouden H, Aarts E et al (2016) The Cerebral Network of Parkinson’s Tremor: an effective connectivity fMRI study. J Neurosci 36(19):5362–5372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dirkx MF, den Ouden HE, Aarts E et al (2017) Dopamine controls Parkinson’s tremor by inhibiting the cerebellar thalamus. Brain 140(3):721–734

    PubMed  Google Scholar 

  • Dupuis MJ, Evrard FL, Jacquerye PG, Picard GR, Lermen OG (2010) Disappearance of essential tremor after stroke. Mov Disord 25(16):2884–2887

    Article  PubMed  Google Scholar 

  • Elble RJ (1996) Central mechanisms of tremor. J Clin Neurophysiol 13(2):133–144

    Article  CAS  PubMed  Google Scholar 

  • Fahn S, Tolosa E, Marín C (1993) Clinical rating scale for tremor. Parkinson’s Disease Mov Disorders Baltimore: Williams Wilkins. :271–280

  • Fang W, Lv F, Luo T et al (2013) Abnormal regional homogeneity in patients with essential tremor revealed by resting-state functional MRI. PLoS ONE 8(7):e69199

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang W, Chen H, Wang H et al (2015) Multiple resting-state networks are Associated with tremors and cognitive features in essential tremor. Mov Disord 30(14):1926–1936

    Article  PubMed  Google Scholar 

  • Fang W, Chen H, Wang H et al (2016) Essential tremor is associated with disruption of functional connectivity in the ventral intermediate nucleus—motor cortex—cerebellum circuit. Hum Brain Mapp 37(1):165–178

    Article  PubMed  Google Scholar 

  • Gallea C, Popa T, García-Lorenzo D et al (2015) Intrinsic signature of essential tremor in the cerebello-frontal network. Brain 138(10):2920–2933

    Article  PubMed  PubMed Central  Google Scholar 

  • Gibson WS, Jo HJ, Testini P et al (2016) Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor. Brain 139(8):2198–2210

    Article  PubMed  PubMed Central  Google Scholar 

  • Grimaldi G, Manto M (2013) Is essential tremor a Purkinjopathy? The role of the cerebellar cortex in its pathogenesis. Mov Disord 28(13):1759–1761

    Article  PubMed  Google Scholar 

  • Helmich RC (2017) The cerebral basis of parkinsonian tremor: a network perspective. Mov Disord

  • Helmich RC, Janssen MJ, Oyen WJ, Bloem BR, Toni I (2011) Pallidal dysfunction drives a cerebellothalamic circuit into Parkinson tremor. Ann Neurol 69(2):269–281

    Article  PubMed  Google Scholar 

  • Helmich RC, Toni I, Deuschl G, Bloem BR (2013) The pathophysiology of essential tremor and Parkinson’s tremor. Curr Neurol Neurosci Rep 13(9):378

    Article  PubMed  Google Scholar 

  • Henson R, Buechel C, Josephs O, Friston K (1999) The slice-timing problem in event-related fMRI. NeuroImage 9:125

    Google Scholar 

  • Hirsch EC, Mouatt A, Faucheux B et al (1992) Dopamine, tremor, and Parkinson’s disease. Lancet 340(8811):125–126

    Article  CAS  PubMed  Google Scholar 

  • Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jang C, Park H-J, Chang WS, Pae C, Chang JW (2016) Immediate and longitudinal alterations of functional networks after thalamotomy in essential tremor. Front Neurol 7:184

    Article  PubMed  PubMed Central  Google Scholar 

  • Jankovic J, McDermott M, Carter J et al (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology 40(10):1529–1534

    Article  CAS  PubMed  Google Scholar 

  • Lenka A, Bhalsing KS, Panda R et al (2017) Role of altered cerebello-thalamo-cortical network in the neurobiology of essential tremor. Neuroradiology 59(2):157–168

    Article  PubMed  Google Scholar 

  • Li J-y, Lu Z-j, Suo X-l et al (2020a) Patterns of intrinsic brain activity in essential tremor with resting tremor and tremor-dominant Parkinson’s disease. Brain Imaging Behav 14:2606–2617

    Article  PubMed  Google Scholar 

  • Li J-y, Lu Z-j, Suo X-l et al (2020b) Patterns of intrinsic brain activity in essential tremor with resting tremor and tremor-dominant Parkinson’s disease. Brain Imaging Behav 14(6):2606–2617

    Article  PubMed  Google Scholar 

  • Li J-y, Suo X-l, Li N-n et al (2021) Altered spontaneous brain activity in essential tremor with and without resting tremor: a resting-state fMRI study. Magn Reson Mater Phys Biol Med 34(2):201–212

    Article  CAS  Google Scholar 

  • Lin CH, Chen CM, Lu MK et al (2013) VBM reveals brain volume differences between Parkinson’s Disease and essential Tremor patients. Front Hum Neurosci 7:247

    Article  PubMed  PubMed Central  Google Scholar 

  • Louis ED, Huey ED, Cosentino S (2021) Features of ET plus correlate with age and tremor duration:ET plus may be a disease stage rather than a subtype of essential tremor. Parkinsonism Relat Disord 91:42–47

    Article  PubMed  Google Scholar 

  • McAuley J, Marsden C (2000) Physiological and pathological tremors and rhythmic central motor control. Brain 123(8):1545–1567

    Article  PubMed  Google Scholar 

  • Middlebrooks EH, Okromelidze L, Wong JK et al (2021) Connectivity correlates to predict essential tremor deep brain stimulation outcome: evidence for a common treatment pathway. NeuroImage: Clin 32:102846

    Article  PubMed  Google Scholar 

  • Mueller K, Jech R, Hoskovcová M et al (2017) General and selective brain connectivity alterations in essential tremor: a resting state fMRI study. NeuroImage: Clin 16:468–476

    Article  PubMed  Google Scholar 

  • Muthuraman M, Heute U, Arning K et al (2012) Oscillating central motor networks in pathological tremors and voluntary movements. What Makes Difference? Neuroimage 60(2):1331–1339

    CAS  PubMed  Google Scholar 

  • Nicoletti V, Cecchi P, Frosini D et al (2015) Morphometric and functional MRI changes in essential tremor with and without resting tremor. J Neurol 262(3):719–728

    Article  PubMed  Google Scholar 

  • Nicoletti V, Cecchi P, Pesaresi I, Frosini D, Cosottini M, Ceravolo R (2020) Cerebello-Thalamo-cortical network is intrinsically altered in essential tremor: evidence from a resting state functional MRI study. Sci Rep 10(1):1–8

    Article  Google Scholar 

  • Nieuwhof F, Toni I, Dirkx MF et al (2022) Cerebello-thalamic activity drives an abnormal motor network into dystonic tremor. NeuroImage: Clin 33:102919

    Article  PubMed  Google Scholar 

  • Novellino F, Nicoletti G, Cherubini A et al (2016) Cerebellar involvement in essential tremor with and without resting tremor: a diffusion Tensor Imaging study. Parkinsonism Relat Disord 27:61–66

    Article  PubMed  Google Scholar 

  • Ohye C, Hirai T, Miyazaki M, Shibazaki T, Nakajima H (1982) Vim thalamotomy for the treatment of various kinds of tremor. Stereotact Funct Neurosurg 45(3):275–280

    Article  CAS  Google Scholar 

  • Passamonti L, Novellino F, Cerasa A et al (2011) Altered cortical-cerebellar circuits during verbal working memory in essential tremor. Brain 134(Pt 8):2274–2286

    Article  PubMed  Google Scholar 

  • Prasad S, Rastogi B, Shah A et al (2018) DTI in essential tremor with and without rest tremor: two sides of the same coin? Mov Disord

  • Raethjen J, Deuschl G (2012) The oscillating central network of essential tremor. Clin Neurophysiol 123(1):61–64

    Article  PubMed  Google Scholar 

  • Safai A, Prasad S, Chougule T, Saini J, Pal PK, Ingalhalikar M (2020) Microstructural abnormalities of substantia nigra in Parkinson’s disease: a neuromelanin sensitive MRI atlas based study. Hum Brain Mapp 41(5):1323–1333

    Article  PubMed  Google Scholar 

  • Saranza G, Lang AE (2021) Levodopa challenge test: indications, protocol, and guide. J Neurol 268(9):3135–3143

    Article  CAS  PubMed  Google Scholar 

  • Schnitzler A, Gross J (2005) Normal and pathological oscillatory communication in the brain. Nat Rev Neurosci 6(4):285–296

    Article  CAS  PubMed  Google Scholar 

  • Schnitzler A, Munks C, Butz M, Timmermann L, Gross J (2009) Synchronized brain network associated with essential tremor as revealed by magnetoencephalography. Mov Disord 24(11):1629–1635

    Article  PubMed  Google Scholar 

  • Shahrokhi M, Gupta V, Propranolol (2020)

  • Tikoo S, Pietracupa S, Tommasin S et al (2020) Functional disconnection of the dentate nucleus in essential tremor. J Neurol. :1–10

  • Timmermann L, Gross J, Dirks M, Volkmann J, Freund HJ, Schnitzler A (2003) The cerebral oscillatory network of parkinsonian resting tremor. Brain 126(Pt 1):199–212

    Article  PubMed  Google Scholar 

  • Tzourio-Mazoyer N, Landeau B, Papathanassiou D et al (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15(1):273–289

    Article  CAS  PubMed  Google Scholar 

  • van den Berg KR, Helmich RC (2021) The role of the Cerebellum in Tremor–evidence from Neuroimaging. Tremor Other Hyperkinetic Movements. ;11

  • Whitfield-Gabrieli S, Nieto-Castanon A (2012) Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect 2(3):125–141

    Article  PubMed  Google Scholar 

  • Yin W, Lin W, Li W, Qian S, Mou X (2016) Resting state fMRI demonstrates a disturbance of the Cerebello-Cortical Circuit in essential tremor. Brain Topogr 29(3):412–418

    Article  PubMed  Google Scholar 

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Acknowledgements

Data was acquired during Shweta Prasad’s PhD which was supported by the India Council of Medical Research (ICMR). Shweta Prasad is currently supported by the DBT/Wellcome Trust India Alliance Early Career Fellowship (IA/CPHE/21/1/505953).

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Department of Biotechnology, India (BT/PR27340/MED/122/130/2018).

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Correspondence to Pramod Kumar Pal.

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Prasad, S., Saini, J., Bharath, R.D. et al. Differential patterns of functional connectivity in tremor dominant Parkinson’s disease and essential tremor plus. J Neural Transm (2024). https://doi.org/10.1007/s00702-024-02761-7

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