Ryoichi Okiyama

Effects of cueing on visuospatial processing in unilateral spatial neglect

Patients with typical left unilateral spatial neglect bisected lines after cueing to the left end-point, the fixation point being monitored with an eye camera. They persisted with the point of initial fixation made after cueing and placed the mark there without searching leftwards again. The rightward shift of fixation to the initial point of fixation thus determined the location of the subjective midpoint. We consider that rightward attentional bias increased the amplitude of this shift that was planned on the basis of the perception of the whole line while cueing. This hypothesis may explain smaller but obvious rightward bisection errors found in the cueing condition.

Mechanisms of unilateral STN-DBS in patients with Parkinson's disease

Bilateral symptoms and signs of Parkinson’s disease (PD) are often improved by unilateral subthalamic nucleus deep brain stimulation (STN-DBS). However, the mechanism for such bilateral effects is unknown. This study was intended to examine effects of unilateral STN-DBS using positron emission computed tomography (PET) and to elucidate mechanisms for bilateral improvement achieved by unilateral stimulation.We conducted 18F-fluorodeoxyglucose (18FDG) and 18F-fluorodopa (18F-DOPA ) PET scans in PD patients whose bilateral limb symptoms and axial symptoms were improved by unilateral DBS. Two scans were performed in each PET study: when DBS was on and off. We compared those images using statistic parametric mapping (SPM) 99.The significant clinical improvement obtained by unilateral DBS was shown as improvements in bilateral motor limb, axial, and gait subscores of the Unified PD Rating Scale (UPDRS). Moreover, 18FDG PET revealed significant metabolic increases in the ipsilateral ventrolateral thalamic areas and metabolic decrease at the contralateral globus pallidus interna (GPi). In contrast, 18F-DOPA PET showed no significant differences between DBS on and off.Ipsilateral thalamic activation might induce ipsilateral motor cortical activation, which explains the improvement of contralateral limb symptoms. Furthermore, deactivation of the contralateral GPi might disinhibit the thalamus and contralateral motor cortex, which explains reduction of ipsilateral limb symptoms. These results suggest the mechanisms for bilateral improvement achieved by unilateral DBS.

Microelectrode findings and topographic reorganisation of kinaesthetic cells after gamma knife thalamotomy.

SummaryA 64-year-old woman with Parkinson is disease had a severe resting tremor that was not completely relieved by right-sided gamma knife thalamotomy (GKT). We performed bilateral staged thalamic deep brain stimulation (DBS) and compared the right and left ventral intermediate nucleus (Vim) of the thalamus including the frequency of single units recorded with microelectrodes, and also the somatotopical distribution of kinaesthetic cells (Ki). The average frequency of units for the presumed left Vim exceeded that of the right (22.6 ± 19.2 Hz vs. 14.3 ± 8.8 Hz). Regarding the somatotopic distribution of Ki, the receptive field for the leg, which is usually situated in the dorsolateral Vim, was more widely scattered in the right Vim than the non-lesioned left side. Our findings raise the possibility that the specific properties of the neurons changed due to partial coagulation by GKT within both the coagulated and the surrounding thalamic lesions.

Frequency-Specific Synchronization in the Bilateral Subthalamic Nuclei Depending on Voluntary Muscle Contraction and Relaxation in Patients with Parkinson's Disease.

The volitional control of muscle contraction and relaxation is a fundamental component of human motor activity, but how the processing of the subcortical networks, including the subthalamic nucleus (STN), is involved in voluntary muscle contraction (VMC) and voluntary muscle relaxation (VMR) remains unclear. In this study, local field potentials (LFPs) of bilateral STNs were recorded in patients with Parkinson’s disease (PD) while performing externally paced VMC and VMR tasks of the unilateral wrist extensor muscle. The VMC- or VMR-related oscillatory activities and their functional couplings were investigated over the theta (4–7 Hz), alpha (8–13 Hz), beta (14–35 Hz), and gamma (40–100 Hz) frequency bands. Alpha and beta desynchronizations were observed in bilateral STNs at the onset of both VMC and VMR tasks. On the other hand, theta and gamma synchronizations were prominent in bilateral STNs specifically at the onset of the VMC task. In particular, just after VMC, theta functional coupling between the bilateral STNs increased, and the theta phase became coupled to the gamma amplitude within the contralateral STN in a phase-amplitude cross-frequency coupled manner. On the other hand, the prominent beta-gamma cross-frequency couplings observed in the bilateral STNs at rest were reduced by the VMC and VMR tasks. These results suggest that STNs are bilaterally involved in the different performances of muscle contraction and relaxation through the theta-gamma and beta-gamma networks between bilateral STNs in patients with PD.

Effect of Deep Brain Stimulation on Tremor

Our clinical observations by surface electromyography show that the effects of Vim DBS and STN DBS on tremor are different. It might be postulated that Vim DBS inhibits the current rising tremor, whereas STN DBS modulates the tremor circuit. This investigation is preliminary and it is as yet very difficult to speculate the mechanisms underlying the modulation of the tremor circuit and the mechanisms of Vim and STN. Further clinical investigations should be carried out.

Resting-State Pallidal-Cortical Oscillatory Couplings in Patients With Predominant Phasic and Tonic Dystonia

Pallidal deep brain stimulation (DBS) improves the symptoms of dystonia. The improvement processes of dystonic movements (phasic symptoms) and tonic symptoms differ. Phasic symptoms improve rapidly after starting DBS treatment, but tonic symptoms improve gradually. This difference implies distinct neuronal mechanisms for phasic and tonic symptoms in the underlying cortico-basal ganglia neuronal network. Phasic symptoms are related to the pallido–thalamo–cortical pathway. The pathway related to tonic symptoms has been assumed to be different from that for phasic symptoms. In the present study, local field potentials of the globus pallidus internus (GPi) and globus pallidus externus (GPe) and electroencephalograms from the motor cortex (MCx) were recorded in 19 dystonia patients to analyze the differences between the two types of symptoms. The 19 patients were divided into two groups, 10 with predominant phasic symptoms (phasic patients) and 9 with predominant tonic symptoms (tonic patients). To investigate the distinct features of oscillations and functional couplings across the GPi, GPe, and MCx by clinical phenotype, power and coherence were calculated over the delta (2–4 Hz), theta (5–7 Hz), alpha (8–13 Hz), and beta (14–35 Hz) frequencies. In phasic patients, the alpha spectral peaks emerged in the GPi oscillatory activities, and alpha GPi coherence with the GPe and MCx was higher than in tonic patients. On the other hand, delta GPi oscillatory activities were prominent, and delta GPi–GPe coherence was significantly higher in tonic than in phasic patients. However, there was no significant delta coherence between the GPi/GPe and MCx in tonic patients. These results suggest that different pathophysiological cortico-pallidal oscillations are related to tonic and phasic symptoms.

8. Effects of STN DBS on saccade latency – Analysis using probability distribution

Background: Reciprocals of saccade latencies show a Gaussian distribution (Carpenter, 1981). This model (LATER model) allows us to investigate the rate of information processing and amount of total information by plotting the reciprocal of latency against the cumulative probability of latency distribution (reciprobit plot). Objectives: To investigate effects of subthalamic stimulation (STN DBS) on saccade latencies using a probability distribution in Parkinson’s disease (PD) patients. Methods: Thirty-two PD patients (HY II-IV, age 58.3 ± 7.9, 15 men, 17 women) with STN DBS performed visually (VGS) and memory (MGS) guided saccade tasks when DBS was on and off. Results: STN DBS significantly shortened the latencies of VGS, but did not change that of MGS. The distribution of VGS latencies showed a parallel leftward shift in the reciprobit plot by STN DBS. However, plots for MGS latencies showed a complete overlap on and off DBS. Discussion: Parallel shift of distribution curves for VGS suggested an increase in information required for decision making, whereas there was no change in information processing for decision making in MGS. STN DBS is considered to accelerate the processing of visual information, and shift the distribution curve of saccade latencies more in VGS than MGS.