Metabolic brain networks in translational neurology: Concepts and applications

Over the past 2 decades, functional imaging techniques have become commonplace in the study of brain disease. Nevertheless, very few validated analytical methods have been developed specifically to identify and measure systems‐level abnormalities in living patients. Network approaches are particularly relevant for translational research in the neurodegenerative disorders, which often involve stereotyped abnormalities in brain organization. In recent years, spatial covariance mapping, a multivariate analytical tool applied mainly to metabolic images acquired in the resting state, has provided a useful means of objectively assessing brain disorders at the network level. By quantifying network activity in individual subjects on a scan‐by‐scan basis, this technique makes it possible to objectively assess disease progression and the response to treatment on a system‐wide basis. To illustrate the utility of network imaging in neurological research, we review recent applications of this approach in the study of Parkinson disease and related movement disorders. Novel uses of the technique are discussed, including the prediction of cognitive responses to dopaminergic therapy, evaluation of the effects of placebo treatment on network activity, assessment of preclinical disease progression, and the use of automated pattern‐based algorithms to enhance diagnostic accuracy. ANN NEUROL 2012;72:635–647

[1]  M. Ghilardi,et al.  Dopaminergic Suppression of Brain Deactivation Responses during Sequence Learning , 2008, The Journal of Neuroscience.

[2]  D. Eidelberg,et al.  Abnormal metabolic networks in atypical parkinsonism , 2008, Movement disorders : official journal of the Movement Disorder Society.

[3]  Y Ben-Shlomo,et al.  Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study , 1999, The Lancet.

[4]  P. Holgate Lognormal Distributions: Theory and Applications , 1989 .

[5]  Richard Watts,et al.  Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease. , 2011, Brain : a journal of neurology.

[6]  M. McKeown,et al.  Imaging of compensatory mechanisms in Parkinson's disease. , 2010, Current opinion in neurology.

[7]  M. Hallett,et al.  Regional homogeneity changes in patients with Parkinson's disease , 2009, Human brain mapping.

[8]  Anna Barnes,et al.  Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease , 2006, NeuroImage.

[9]  Chris C. Tang,et al.  Abnormalities in Metabolic Network Activity Precede the Onset of Motor Symptoms in Parkinson's Disease , 2010, The Journal of Neuroscience.

[10]  Chris C. Tang,et al.  Network correlates of disease severity in multiple system atrophy , 2012, Neurology.

[11]  T. Ishikawa,et al.  The Metabolic Topography of Parkinsonism , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  Yaakov Stern,et al.  Multivariate and Univariate Analysis of Continuous Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  Thomas Wichmann,et al.  Circuits and circuit disorders of the basal ganglia. , 2007, Archives of neurology.

[14]  M. Arias-Rodríguez,et al.  [Diagnosis of Parkinson's disease]. , 2009, Revista de neurología (Ed. impresa).

[15]  Angelo Antonini,et al.  Tc‐99m ethylene cysteinate dimer SPECT in the differential diagnosis of parkinsonism , 2002, Movement disorders : official journal of the Movement Disorder Society.

[16]  David Eidelberg,et al.  Functional brain networks and abnormal connectivity in the movement disorders , 2012, NeuroImage.

[17]  R. Postuma,et al.  REM sleep behavior disorder: From dreams to neurodegeneration , 2012, Neurobiology of Disease.

[18]  Yaakov Stern,et al.  Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease , 2008, NeuroImage.

[19]  Jean-Claude Baron,et al.  Executive processes in Parkinson's disease: FDG‐PET and network analysis , 2004, Human brain mapping.

[20]  J R Moeller,et al.  Metabolic correlates of pallidal neuronal activity in Parkinson's disease. , 1997, Brain : a journal of neurology.

[21]  V. Dhawan,et al.  Metabolic correlates of levodopa response in Parkinson’s disease , 2001, Neurology.

[22]  W D Heiss,et al.  STN-DBS activates the target area in Parkinson disease , 2008, Neurology.

[23]  J R Moeller,et al.  Metabolic changes following subthalamotomy for advanced Parkinson's disease , 2001, Annals of neurology.

[24]  David Eidelberg,et al.  Functional Imaging of Cerebral Blood Flow and Glucose Metabolism in Parkinson’s Disease and Huntington’s Disease , 2007, Molecular Imaging and Biology.

[25]  Tao Wu,et al.  Effective connectivity of brain networks during self-initiated movement in Parkinson's disease , 2011, NeuroImage.

[26]  D. Eidelberg Metabolic brain networks in neurodegenerative disorders: a functional imaging approach , 2009, Trends in Neurosciences.

[27]  J. Nyengaard,et al.  Endothelial Proliferation and Increased Blood–Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydroxyphenyl-l-Alanine-Induced Dyskinesia , 2006, The Journal of Neuroscience.

[28]  David Eidelberg,et al.  Assessment of the progression of Parkinson's disease: a metabolic network approach , 2007, The Lancet Neurology.

[29]  T. Ishikawa,et al.  Assessment of disease severity in parkinsonism with fluorine-18-fluorodeoxyglucose and PET. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  V. Dhawan,et al.  Network correlates of the cognitive response to levodopa in Parkinson disease , 2011, Neurology.

[31]  V. Dhawan,et al.  Changes in network activity with the progression of Parkinson's disease. , 2007, Brain : a journal of neurology.

[32]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[33]  David Eidelberg,et al.  Dissociation of Metabolic and Neurovascular Responses to Levodopa in the Treatment of Parkinson's Disease , 2008, The Journal of Neuroscience.

[34]  D. Eidelberg,et al.  Hereditary dystonia as a neurodevelopmental circuit disorder: Evidence from neuroimaging , 2011, Neurobiology of Disease.

[35]  V. Dhawan,et al.  The metabolic anatomy of tremor in Parkinson's disease , 1998, Neurology.

[36]  Chris C. Tang,et al.  Using imaging to identify psychogenic parkinsonism before deep brain stimulation surgery. Report of 2 cases. , 2012, Journal of neurosurgery.

[37]  Andreea C. Bostan,et al.  The basal ganglia communicate with the cerebellum , 2010, Proceedings of the National Academy of Sciences.

[38]  Chris C. Tang,et al.  Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis , 2010, The Lancet Neurology.

[39]  Erwan Bezard,et al.  Presymptomatic compensation in Parkinson's disease is not dopamine-mediated , 2003, Trends in Neurosciences.

[40]  Fair M. Vassoler,et al.  Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia. , 2011, Brain : a journal of neurology.

[41]  Angelo Antonini,et al.  Parkinson's disease tremor-related metabolic network: Characterization, progression, and treatment effects , 2011, NeuroImage.

[42]  David Eidelberg,et al.  Scaled subprofile modeling of resting state imaging data in Parkinson's disease: Methodological issues , 2011, NeuroImage.

[43]  A. Rezai,et al.  AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial , 2011, The Lancet Neurology.

[44]  Mark W. Woolrich,et al.  Network modelling methods for FMRI , 2011, NeuroImage.

[45]  V. Dhawan,et al.  Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[46]  Y. Guan,et al.  Modulation of metabolic brain function by bilateral subthalamic nucleus stimulation in the treatment of Parkinson’s disease , 2008, Journal of Neurology.

[47]  J R Moeller,et al.  A Regional Covariance Approach to the Analysis of Functional Patterns in Positron Emission Tomographic Data , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[48]  David Eidelberg,et al.  Differential diagnosis of parkinsonian syndromes using PCA-based functional imaging features , 2009, NeuroImage.

[49]  V. Dhawan,et al.  Network modulation in the treatment of Parkinson's disease. , 2006, Brain : a journal of neurology.

[50]  V. Sossi,et al.  Abnormal Metabolic Brain Networks in a Nonhuman Primate Model of Parkinsonism , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[51]  W. Oertel,et al.  Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. , 2004, Brain : a journal of neurology.

[52]  Hagai Bergman,et al.  Akineto-rigid vs. tremor syndromes in Parkinsonism , 2009, Current opinion in neurology.

[53]  D. Alsop,et al.  Parkinson's Disease Spatial Covariance Pattern: Noninvasive Quantification with Perfusion MRI , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[54]  Yaakov Stern,et al.  A New Approach to Spatial Covariance Modeling of Functional Brain Imaging Data: Ordinal Trend Analysis , 2005, Neural Computation.

[55]  K. Elisabet Ohlin,et al.  Impact of L-DOPA treatment on regional cerebral blood flow and metabolism in the basal ganglia in a rat model of Parkinson's disease , 2012, NeuroImage.

[56]  S. Aalto,et al.  Impaired cognitive performance in Parkinson's disease is related to caudate dopaminergic hypofunction and hippocampal atrophy. , 2009, Parkinsonism & related disorders.

[57]  Chris C. Tang,et al.  Abnormal metabolic brain networks in Tourette syndrome , 2011, Neurology.

[58]  Yaakov Stern,et al.  Multivariate Data Analysis for Neuroimaging Data: Overview and Application to Alzheimer’s Disease , 2010, Cell Biochemistry and Biophysics.

[59]  David Eidelberg,et al.  Metabolic correlates of subthalamic nucleus activity in Parkinson's disease. , 2008, Brain : a journal of neurology.

[60]  Jane S. Paulsen,et al.  Thalamic metabolism and symptom onset in preclinical Huntington's disease. , 2007, Brain : a journal of neurology.

[61]  W. Oyen,et al.  Pallidal dysfunction drives a cerebellothalamic circuit into Parkinson tremor , 2011, Annals of neurology.

[62]  L. Hazrati,et al.  Functional anatomy of the basal ganglia , 1995 .

[63]  Michael Pourfar,et al.  Assessing the microlesion effect of subthalamic deep brain stimulation surgery with FDG PET. , 2009, Journal of neurosurgery.

[64]  D. Aarsland,et al.  The epidemiology of dementia associated with Parkinson disease , 2010, Journal of the Neurological Sciences.

[65]  D. Surmeier,et al.  Brain networks in Huntington disease. , 2011, The Journal of clinical investigation.

[66]  D. Eidelberg,et al.  Imaging essential tremor , 2010, Movement disorders : official journal of the Movement Disorder Society.

[67]  S. Pappatà,et al.  Mild cognitive impairment in drug-naive patients with PD is associated with cerebral hypometabolism , 2011, Neurology.

[68]  Valtteri Kaasinen,et al.  Striatal FDOPA uptake and cognition in advanced non-demented Parkinson's disease: a clinical and FDOPA-PET study. , 2008, Parkinsonism & related disorders.

[69]  M. Cenci,et al.  The “motor complication syndrome” in rats with 6-OHDA lesions treated chronically with l-DOPA: Relation to dose and route of administration , 2007, Behavioural Brain Research.

[70]  R. Chervin,et al.  Decreased striatal dopaminergic innervation in REM sleep behavior disorder , 2000, Neurology.

[71]  P. Strick,et al.  The cerebellum communicates with the basal ganglia , 2005, Nature Neuroscience.

[72]  Y. Itoyama,et al.  Distinct patterns of regional cerebral glucose metabolism in Parkinson's disease with and without mild cognitive impairment , 2009, Movement disorders : official journal of the Movement Disorder Society.

[73]  J R Moeller,et al.  Divergent expression of regional metabolic topographies in Parkinson's disease and normal ageing. , 1997, Brain : a journal of neurology.

[74]  G. Maassen The standard error in the Jacobson and Truax Reliable Change Index: The classical approach to the assessment of reliable change , 2004, Journal of the International Neuropsychological Society.

[75]  V. Dhawan,et al.  Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease , 2007, Proceedings of the National Academy of Sciences.

[76]  Anna Barnes,et al.  Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism , 2004, NeuroImage.

[77]  V. Dhawan,et al.  Reproducibility of regional metabolic covariance patterns: comparison of four populations. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[78]  V. Dhawan,et al.  Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease , 2008, Neurology.

[79]  Koen Van Laere,et al.  Quantification of Parkinson’s disease-related network expression with ECD SPECT , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[80]  David Eidelberg,et al.  Metabolic brain networks associated with cognitive function in Parkinson's disease , 2007, NeuroImage.

[81]  C. Tanner,et al.  Levodopa and the progression of Parkinson's disease. , 2004, The New England journal of medicine.