Toshitaka Nakamura

Patterns of regional brain activation associated with different forms of motor learning

To examine the variations in regional cerebral blood flow during execution and learning of reaching movements, we employed a family of kinematically and dynamically controlled motor tasks in which cognitive, mnemonic and executive features of performance were differentiated and characterized quantitatively. During 15O-labeled water positron emission tomography (PET) scans, twelve right-handed subjects moved their dominant hand on a digitizing tablet from a central location to equidistant targets displayed with a cursor on a computer screen in synchrony with a tone. In the preceding week, all subjects practiced three motor tasks: 1) movements to a predictable sequence of targets; 2) learning of new visuomotor transformations in which screen cursor motion was rotated by 30 degrees -60 degrees; 3) learning new target sequences by trial and error, by using previously acquired routines in a task placing heavy load on spatial working memory. The control condition was observing screen and audio displays. Subtraction images were analyzed with Statistical Parametric Mapping to identify significant brain activation foci. Execution of predictable sequences was characterized by a modest decrease in movement time and spatial error. The underlying pattern of activation involved primary motor and sensory areas, cerebellum, basal ganglia. Adaptation to a rotated reference frame, a form of procedural learning, was associated with decrease in the imposed directional bias. This task was associated with activation in the right posterior parietal cortex. New sequences were learned explicitly. Significant activation was found in dorsolateral prefrontal and anterior cingulate cortices. In this study, we have introduced a series of flexible motor tasks with similar kinematic characteristics and different spatial attributes. These tasks can be used to assess specific aspects of motor learning with imaging in health and disease.

Functional networks in motor sequence learning: abnormal topographies in Parkinson's disease.

We examined the neural circuitry underlying the explicit learning of motor sequences in normal subjects and patients with early stage Parkinsons disease (PD) using 15O‐water (H215O) positron emission tomography (PET) and network analysis. All subjects were scanned while learning motor sequences in a task emphasizing explicit learning, and during a kinematically controlled motor execution reference task. Because different brain networks are thought to subserve target acquisition and retrieval during motor sequence learning, we used separate behavioral indices to quantify these aspects of learning during the PET experiments. In the normal cohort, network analysis of the PET data revealed a significant covariance pattern associated with acquisition performance. This topography was characterized by activations in the left dorsolateral prefrontal cortex (PFdl), rostral supplementary motor area (preSMA), anterior cingulate cortex, and in the left caudate/putamen. A second independent covariance pattern was associated with retrieval performance. This topography was characterized by bilateral activations in the premotor cortex (PMC), and in the right precuneus and posterior parietal cortex. The normal learning‐related topographies failed to predict acquisition performance in PD patients and predicted retrieval performance less accurately in the controls. A separate network analysis was performed to identify discrete learning‐related topographies in the PD cohort. In PD patients, acquisition performance was associated with a covariance pattern characterized by activations in the left PFdl, ventral prefrontal, and rostral premotor regions, but not in the striatum. Retrieval performance in PD patients was associated with a covariance pattern characterized by activations in the right PFdl, and bilaterally in the PMC, posterior parietal cortex, and precuneus. These results suggest that in early stage PD sequence learning networks are associated with additional cortical activation compensating for abnormalities in basal ganglia function. Hum. Brain Mapping 12:42–60, 2001.

Blinded positron emission tomography study of dopamine cell implantation for Parkinson's disease

We assessed nigrostriatal dopaminergic function in Parkinsons disease (PD) patients undergoing a double‐blind, placebo‐controlled surgical trial of embryonic dopamine cell implantation. Forty PD patients underwent positron emission tomography (PET) imaging with [18F]fluorodopa (FDOPA) prior to randomization to transplantation or placebo surgery. The 39 surviving patients were rescanned 1 year following surgery. Images were quantified by investigators blinded to treatment status and clinical outcome. Following unblinding, we determined the effects of treatment status and age on the interval changes in FDOPA/PET signal. Blinded observers detected a significant increase in FDOPA uptake in the putamen of the group receiving implants compared to the placebo surgery patients (40.3%). Increases in putamen FDOPA uptake were similar in both younger (age ≤60 years) and older (age >60 years) transplant recipients. Significant decrements in putamen uptake were evident in younger placebo‐operated patients (–6.5% ) but not in their older counterparts. Correlations between the PET changes and clinical outcome were significant only in the younger patient subgroup (r = 0.58). The findings suggest that patient age does not influence graft viability or development in the first postoperative year. However, host age may influence the time course of the downstream functional changes that are needed for clinical benefit to occur.

Changing treatment strategy from clipping to radial artery graft bypass and parent artery sacrifice in patients with ruptured blister-like internal carotid artery aneurysms.

BACKGROUND: Blood blister-like aneurysms (BBAs) are aneurysms with ill-defined fragile necks arising from an internal carotid artery (ICA) and associated with high mortality. OBJECTIVE: To describe strategies and outcomes in patients in whom radial artery (RA) graft bypass with ICA sacrifice was considered as the primary treatment during the acute phase of subarachnoid hemorrhage. METHODS: The authors analyzed the clinical records of 20 patients who were treated between 2004 and 2011 at their hospital and affiliate institutions. RESULTS: A majority of the patients were treated during the acute phase (<24 hours, n = 15). A favorable outcome was achieved in 18 (90%) patients. The treatment strategies used were as follows: (1) ICA trapping/external carotid artery (ECA)-RA-middle cerebral artery (MCA) bypass (n = 13), (2) ICA trapping/superficial temporal artery-MCA bypass (n = 2), (3) aneurysm clipping with RA-MCA temporary bypass (n = 3), (3) aneurysm clipping with proximal ICA ligation and ECA-RA-MCA bypass (n = 1), and (4) direct clipping (n = 1). Postoperative infarction was observed in 6 patients and was ascribed to vasospasm (n = 1), retrograde thrombosis associated with trapping (n = 2), and reasons unrelated to the surgical procedures (n = 3). CONCLUSION: Trapping with RA graft bypass demonstrated favorable results in patients with internal carotid BBAs. Although trapping/RA graft bypass is a definitive treatment for BBAs located proximal to the origin of the posterior communicating artery, some distal BBAs preclude ICA trapping to spare the perforating arteries. ABBREVIATIONS: BBA, blister-like aneurysm DCI, delayed cerebral ischemia ECA, external carotid artery ICA, internal carotid artery MCA, middle cerebral artery mRS, modified Rankin scale Pcom, posterior communicating RA, radial artery SAH, subarachnoid hemorrhage; STA, superficial temporal artery

Intraoperative Dual Monitoring During Carotid Endarterectomy Using Motor Evoked Potentials and Near-Infrared Spectroscopy

BACKGROUND Carotid endarterectomy (CEA) is a useful procedure to prevent subsequent ischemic stroke in patients with severe stenosis of internal carotid artery. However, lowering of morbidity is still essential to keep its clinical significance. This study aimed to evaluate the validity of dual monitoring using transcranial motor evoked potential (MEP) and near-infrared spectroscopy (NIRS) during CEA. METHODS Transcranial MEP and NIRS monitoring were conducted in 20 consecutive CEAs. MEP was recorded in the contralateral extremities. Regional cerebral saturation of oxygen (rSO(2)) was continuously measured in the ipsilateral forehead. The changes of MEP amplitudes and rSO(2) during cross-clamping of carotid artery were compared in each case. RESULTS The amplitudes of MEP significantly decreased when rSO(2) reduced to more than 20% during carotid clamping. There was a significant correlation between the changes of MEP amplitude and rSO(2) during carotid clamping in a quadratic manner (P < .001, r = 0.821). However, NIRS could not detect critical cerebral ischemia in 1 patient with cerebral infarction in the ipsilateral frontal lobe. On the other hand, MEP could not identify it in 1 patient with severe motor deficit. No perioperative complication occurred. CONCLUSIONS These findings strongly suggest that both MEP and NIRS can detect critical cerebral ischemia during CEA in most patients. Dual MEP and NIRS monitoring may further increase the sensitivity to identify it, being valuable to prevent perioperative complications due to cerebral ischemia during CEA.

Surgical Outcomes for Cervical Carotid Artery Stenosis: Treatment Strategy for Bilateral Cervical Carotid Artery Stenosis

BACKGROUND Carotid endarterectomy (CEA) and carotid stenting (CAS) are beneficial procedures for patients with high-grade cervical carotid stenosis. However, it is sometimes difficult to manage patients with bilateral carotid stenosis. To decide the treatment strategy, one of the most important questions is whether contralateral stenosis increases the risk of patients undergoing CEA. METHODS This retrospective study included 201 patients with carotid stenosis who underwent a total of 219 consecutive procedures (CEA 189/CAS 30). We retrospectively analyzed outcomes in patients with carotid stenosis who were treated with either CEA or CAS and evaluated whether or not contralateral lesions increases the risk of patients undergoing CEA or CAS. Furthermore, we retrospectively verified our treatment strategy for bilateral carotid stenosis. RESULTS The incidences of perioperative complications were 5.3% in the CEA patients and 6.7% in the CAS patients, respectively. There was no significant difference between these 2 groups. The existences of contralateral occlusion and/or contralateral stenosis were not associated with perioperative complications in both the groups. There were 32 patients with bilateral severe carotid stenosis (>50%). Of those, 13 patients underwent bilateral revascularizations; CEA followed by CEA in 8, CEA followed by CAS in 3, CAS followed by CEA + coronary artery bpass grafting in 1, and CAS followed by CAS in 1. CONCLUSIONS Our date showed that the existence of contralateral carotid lesion was not associated with perioperative complications, and most of our cases with bilateral carotid stenosis initially underwent CEA.