Frontal FDG-PET activity correlates with cognitive outcome after STN-DBS in Parkinson disease

Background: Inconsistent changes of cognitive functioning have been reported in patients with Parkinson disease (PD) with deep brain stimulation (DBS) of the subthalamic nucleus (STN). To investigate the underlying pathomechanisms, we correlated alterations of cognitive test performance and changes of neuronal energy metabolism in frontal basal ganglia projection areas under bilateral STN stimulation. Methods: We conducted verbal fluency, learning, and memory tests and 18-fluorodeoxyglucose (FDG) PET in nine patients with PD with STN-DBS before and 6 months after surgery. Using coregistered MRI, postoperative changes of the normalized cerebral metabolic rates of glucose (nCMRGlc) in the dorsolateral prefrontal cortex (DLPFC), lateral orbitofrontal cortex (LOFC), ventral and dorsal cingulum (v/dACC), and in Broca area were determined and correlated with alterations of neuropsychological test results. Results: After surgery, highly variable changes of both cognitive test performance and frontal nCMRGlc values were found with significant correlations between verbal fluency and FDG uptake in the left DLPFC (Brodmann area [BA] 9, 46), left Broca area (BA 44/45), and the right dACC (BA 32). A decrease of nCMRGlc in the left OFC (BA 11/47) and dACC (BA 32) correlated with a decline of verbal learning. All patients showed reduced metabolic activity in the right anterior cingulate cortex after DBS. Baseline cognitive abilities did not predict verbal learning or fluency changes after surgery. Conclusions: These data show a significant linear relationship between changes in frontal 18-fluorodeoxyglucose PET activity and changes in cognitive outcome after deep brain stimulation of the subthalamic nucleus (STN) in advanced Parkinson disease. The best correlations were found in the left frontal lobe (dorsolateral prefrontal cortex and Broca area). Baseline performance on cognitive tests did not predict cognitive or metabolic changes after STN electrode implantation.

[1]  Jens Volkmann,et al.  Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position. , 2002, Journal of neurosurgery.

[2]  Paul Krack,et al.  Deep brain stimulation: Neuropsychological and neuropsychiatric issues , 2006, Movement disorders : official journal of the Movement Disorder Society.

[3]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[4]  K Wienhard,et al.  The ECAT EXACT HR: Performance of a New High Resolution Positron Scanner , 1994, Journal of computer assisted tomography.

[5]  Harald Treuer,et al.  Accuracy and conformity of stereotactically guided interstitial brain tumour therapy using I-125 seeds. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[6]  M S Mega,et al.  Frontal-subcortical circuits and neuropsychiatric disorders. , 1994, The Journal of neuropsychiatry and clinical neurosciences.

[7]  U Pietrzyk,et al.  An interactive technique for three-dimensional image registration: validation for PET, SPECT, MRI and CT brain studies. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  Thomas D Parsons,et al.  Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a meta-analysis , 2006, The Lancet Neurology.

[9]  Brian Everitt,et al.  A systematic review and quantitative appraisal of fMRI studies of verbal fluency: Role of the left inferior frontal gyrus , 2006, Human brain mapping.

[10]  P. Remy,et al.  Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT‐PD) , 1999, Movement disorders : official journal of the Movement Disorder Society.

[11]  J D Van Horn,et al.  A comparison of rCBF patterns during letter and semantic fluency. , 2000, Neuropsychology.

[12]  A. Tröster,et al.  Assessing cognitive change in Parkinson's disease: development of practice effect-corrected reliable change indices. , 2007, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[13]  V. Sturm,et al.  Subthalamic Nucleus Stimulation Restores Glucose Metabolism in Associative and Limbic Cortices and in Cerebellum: Evidence from a FDG-PET Study in Advanced Parkinson's Disease , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  Bettina Schrader,et al.  Two‐year follow‐up of subthalamic deep brain stimulation in Parkinson's disease , 2003, Movement disorders : official journal of the Movement Disorder Society.

[15]  E. Hoffman,et al.  TOMOGRAPHIC MEASUREMENT OF LOCAL CEREBRAL GLUCOSE METABOLIC RATE IN HUMANS WITH (F‐18)2‐FLUORO-2‐DEOXY-D‐GLUCOSE: VALIDATION OF METHOD , 1980, Annals of neurology.

[16]  N. Jacobson,et al.  Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. , 1991, Journal of consulting and clinical psychology.

[17]  J. Rothwell,et al.  The impact of deep brain stimulation on executive function in Parkinson's disease. , 2000, Brain : a journal of neurology.

[18]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[19]  A. Benabid,et al.  Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. , 2003, The New England journal of medicine.

[20]  C. Marsden,et al.  The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson's disease. , 1994, Brain : a journal of neurology.

[21]  H. Levin.  A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary , 1993 .

[22]  Ulrike Schroeder,et al.  Subthalamic nucleus stimulation affects a frontotemporal network: A PET study , 2003, Annals of neurology.

[23]  A. C. Pricharp,et al.  A Treatise on Diseases of the Nervous System , 1822, Nature.

[24]  M. Posner,et al.  Attentional networks , 1994, Trends in Neurosciences.

[25]  V. Tronnier,et al.  Subthalamic nucleus stimulation affects striato-anterior cingulate cortex circuit in a response conflict task: a PET study. , 2002, Brain : a journal of neurology.

[26]  O. Selnes.  A Compendium of Neuropsychological Tests , 1991, Neurology.

[27]  Jonathan D. Cohen,et al.  Conflict monitoring versus selection-for-action in anterior cingulate cortex , 1999, Nature.

[28]  A. Benabid,et al.  Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[29]  M Baulac,et al.  Pure psychic akinesia with bilateral lesions of basal ganglia. , 1984, Journal of neurology, neurosurgery, and psychiatry.

[30]  J. Saint-Cyr,et al.  Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. , 2000, Brain : a journal of neurology.

[31]  Yasin Temel,et al.  Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review. , 2006, Parkinsonism & related disorders.

[32]  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.