Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ (p>.20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain (p=.008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms.

[1]  J. Grace,et al.  Body side of motor symptom onset in Parkinson's disease is associated with memory performance , 2006, Journal of the International Neuropsychological Society.

[2]  R. Leiguarda,et al.  Neuropsychological disturbances in hemiparkinson's disease , 1987, Neurology.

[3]  M. Rundle,et al.  Evaluation of a screening questionnaire for genetic studies of Parkinson's disease. , 1999, American journal of medical genetics.

[4]  John D. E. Gabrieli,et al.  Reduced working memory span in Parkinson's disease: Evidence for the role of frontostriatal system in working and strategic memory. , 1996 .

[5]  R. J. Roberts,et al.  Neuropsychological performance in lateralized parkinsonism. , 1988, Archives of neurology.

[6]  T. Robbins,et al.  Effects of STN lesions on simple vs choice reaction time tasks in the rat: preserved motor readiness, but impaired response selection , 2001, The European journal of neuroscience.

[7]  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.

[8]  G. Siegel,et al.  Analysis of l-dopa induced dyskinesias in 51 patients with Parkinsonism , 1971, Journal of neurology, neurosurgery, and psychiatry.

[9]  C. Marsden,et al.  'Frontal' cognitive function in patients with Parkinson's disease 'on' and 'off' levodopa. , 1988, Brain : a journal of neurology.

[10]  J G Nutt,et al.  Levodopa‐induced dyskinesia , 1990, Neurology.

[11]  D. Gruber,et al.  Subthalamic stimulation differentially modulates declarative and nondeclarative memory , 2004, Neuroreport.

[12]  A L Benabid,et al.  Neuropsychological changes between “off” and “on” STN or GPi stimulation in Parkinson’s disease , 2000, Neurology.

[13]  A. Baddeley Working Memory: The Interface between Memory and Cognition , 1992, Journal of Cognitive Neuroscience.

[14]  L. Wojtecki,et al.  Frequency-dependent reciprocal modulation of verbal fluency and motor functions in subthalamic deep brain stimulation. , 2006, Archives of neurology.

[15]  Maren Carbon,et al.  Functional imaging of cognition in Parkinson's disease , 2003, Current opinion in neurology.

[16]  John D. E. Gabrieli,et al.  Reduced working memory span in Parkinson's disease: Evidence for the role of frontostriatal system in working and strategic memory. , 1996 .

[17]  P. Strick,et al.  Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. , 1994, Science.

[18]  J. Mink,et al.  SAFETY AND EFFICACY OF SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION PERFORMED WITH LIMITED INTRAOPERATIVE MAPPING FOR TREATMENT OF PARKINSON'S DISEASE , 2007, Neurosurgery.

[19]  R. Gur,et al.  Neuropsychological functioning in hemiparkinsonism , 1989, Brain and Cognition.

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

[21]  T. Robbins,et al.  Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson's disease , 2005, Neuropsychologia.

[22]  H. Steinbusch,et al.  The functional role of the subthalamic nucleus in cognitive and limbic circuits , 2005, Progress in Neurobiology.

[23]  P. Goldman-Rakic,et al.  Neocortical memory circuits. , 1990, Cold Spring Harbor symposia on quantitative biology.

[24]  J. Saint-Cyr,et al.  Frontal lobe dysfunction in Parkinson's disease. The cortical focus of neostriatal outflow. , 1986, Brain : a journal of neurology.

[25]  K. Nakano,et al.  Neural circuits and functional organization of the striatum , 2000, Journal of Neurology.

[26]  P. Starr,et al.  Implantation of deep brain stimulators into the subthalamic nucleus: technical approach and magnetic resonance imaging-verified lead locations. , 2002, Journal of neurosurgery.

[27]  T. Robbins,et al.  Functional Disconnection of the Medial Prefrontal Cortex and Subthalamic Nucleus in Attentional Performance: Evidence for Corticosubthalamic Interaction , 2003, The Journal of Neuroscience.

[28]  J. Vitek Mechanisms of deep brain stimulation: Excitation or inhibition , 2002, Movement disorders : official journal of the Movement Disorder Society.

[29]  J B Poline,et al.  The neural system that bridges reward and cognition in humans: An fMRI study , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Mink THE BASAL GANGLIA: FOCUSED SELECTION AND INHIBITION OF COMPETING MOTOR PROGRAMS , 1996, Progress in Neurobiology.

[31]  A L Benabid,et al.  From off-period dystonia to peak-dose chorea. The clinical spectrum of varying subthalamic nucleus activity. , 1999, Brain : a journal of neurology.

[32]  P. Goldman-Rakic,et al.  Activation of human prefrontal cortex during spatial and nonspatial working memory tasks measured by functional MRI. , 1996, Cerebral cortex.

[33]  A. Benabid,et al.  Dyskinesias and the subthalamic nucleus. , 2000, Annals of neurology.

[34]  A. Lozano,et al.  Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation , 1999, Neurology.

[35]  P. Goldman-Rakic,et al.  Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic "scotomas" , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  A L Benabid,et al.  Abnormal involuntary movements induced by subthalamic nucleus stimulation in parkinsonian patients , 1996, Movement disorders : official journal of the Movement Disorder Society.

[37]  R. Depue,et al.  Facilitation of Working Memory in Humans by a D2 Dopamine Receptor Agonist , 1992, Journal of Cognitive Neuroscience.

[38]  Y. Agid,et al.  Improvement of memory guided saccades in parkinsonian patients by high frequency subthalamic nucleus stimulation , 2000, Journal of neurology, neurosurgery, and psychiatry.

[39]  J W Langston,et al.  Quantification of dyskinesia in Parkinson's disease: Validation of a novel instrumental method , 1999, Movement disorders : official journal of the Movement Disorder Society.

[40]  T. Hershey,et al.  Short-term and long-term memory in early temporal lobe dysfunction. , 1998, Neuropsychology.

[41]  T. Hershey,et al.  Stimulation of STN impairs aspects of cognitive control in PD , 2004, Neurology.

[42]  J. Mink,et al.  Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD , 2003, Neurology.

[43]  R. Bornstein,et al.  Asymmetrical cognitive differences associated with hemiparkinsonism. , 1992, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[44]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[45]  G. Deuschl,et al.  Deep brain stimulation of the subthalamic nucleus improves cognitive flexibility but impairs response inhibition in Parkinson disease. , 2004, Archives of neurology.

[46]  Y. Agid,et al.  Subthalamic stimulation in Parkinson disease: intraoperative predictive factors. , 2003, Archives of neurology.