Yuki Sakai | ATR - Academia.edu (original) (raw)
Papers by Yuki Sakai
Cell Reports, Aug 30, 2022
We may view most of our daily activities as rational action selections; however, we sometimes rei... more We may view most of our daily activities as rational action selections; however, we sometimes reinforce maladaptive behaviors despite having explicit environmental knowledge. In this study, we model obsessive-compulsive disorder (OCD) symptoms as implicitly learned maladaptive behaviors. Simulations in the reinforcement learning framework show that agents implicitly learn to respond to intrusive thoughts when the memory trace signal for past actions decays differently for positive and negative prediction errors. Moreover, this model extends our understanding of therapeutic effects of behavioral therapy in OCD. Using empirical data, we confirm that patients with OCD show extremely imbalanced traces, which are normalized by serotonin enhancers. We find that healthy participants also vary in their obsessive-compulsive tendencies, consistent with the degree of imbalanced traces. These behavioral characteristics can be generalized to variations in the healthy population beyond the spectrum of clinical phenotypes.
Journal of Neurosurgery, 2021
OBJECTIVE Deep brain stimulation (DBS) of the centromedian thalamic nucleus has been reportedly ... more OBJECTIVE
Deep brain stimulation (DBS) of the centromedian thalamic nucleus has been reportedly used to treat severe Tourette syndrome, yielding promising outcomes. However, it remains unclear how DBS electrode position and stimulation parameters modulate the specific area and related networks. The authors aimed to evaluate the relationships between the anatomical location of stimulation fields and clinical responses, including therapeutic and side effects.
METHODS
The authors collected data from 8 patients with Tourette syndrome who were treated with DBS. The authors selected the active contact following threshold tests of acute side effects and gradually increased the stimulation intensity within the therapeutic window such that acute and chronic side effects could be avoided at each programming session. The patients were carefully interviewed, and stimulation-induced side effects were recorded. Clinical outcomes were evaluated using the Yale Global Tic Severity Scale, the Yale-Brown Obsessive-Compulsive Scale, and the Hamilton Depression Rating Scale. The DBS lead location was evaluated in the normalized brain space by using a 3D atlas. The volume of tissue activated was determined, and the associated normative connective analyses were performed to link the stimulation field with the therapeutic and side effects.
RESULTS
The mean follow-up period was 10.9 ± 3.9 months. All clinical scales showed significant improvement. Whereas the volume of tissue activated associated with therapeutic effects covers the centromedian and ventrolateral nuclei and showed an association with motor networks, those associated with paresthesia and dizziness were associated with stimulation of the ventralis caudalis and red nucleus, respectively. Depressed mood was associated with the spread of stimulation current to the mediodorsal nucleus and showed an association with limbic networks.
CONCLUSIONS
This study addresses the importance of accurate implantation of DBS electrodes for obtaining standardized clinical outcomes and suggests that meticulous programming with careful monitoring of clinical symptoms may improve outcomes.
European Psychiatry, 2011
The basal ganglia represents a key component of the pathophysiological model for obsessive-compul... more The basal ganglia represents a key component of the pathophysiological model for obsessive-compulsive disorder (OCD). This brain region is part of several neural circuits, including the orbitofronto-striatal circuit and dorsolateral prefronto-striatal circuit. There are, however, no published studies investigating those circuits at a network level in non-medicated patients with OCD. Resting state functional magnetic resonance imaging scans were obtained from 20 non-medicated patients with OCD and 23 matched healthy volunteers. Voxelwise statistical parametric maps testing strength of functional connectivity of three striatal seed regions of interest (ROIs) with remaining brain regions were calculated and compared between groups. We performed additional correlation analyses between strength of connectivity and the severity scores for obsessive-compulsive symptoms, depression, and anxiety in the OCD group. Positive functional connectivity with the ventral striatum was significantly increased (P(corrected) < .05) in the orbitofrontal cortex, ventral medial prefrontal cortex and dorsal lateral prefrontal cortex of subjects with OCD. There was no significant correlation between measures of symptom severity and the strength of connectivity (P(uncorrected) < .001). This is the first study to investigate the corticostriatal connectivity in non-medicated patients with OCD. These findings provide the first direct evidence supporting a pathophysiological model involving basal ganglia circuitry in OCD.
Frontiers in Human Neuroscience, 2021
Introduction: The clinical efficacy of deep brain stimulation (DBS) for midline tremor has been h... more Introduction: The clinical efficacy of deep brain stimulation (DBS) for midline tremor has been heterogenous. Here, we present an atypical case with facial and palatal tremor treated with DBS. We aimed to show the difference between the fibers affected by stimulation of the two targets [globus pallidus interna (GPi) and ventral intermediate (Vim) thalamic nucleus] using a normative connectome analysis.
Case Report: A 76-year-old woman with a 4-year history of severe facial and palatal tremor due to craniofacial dystonia. Following a failed bilateral Vim DBS, explantation of preexisting leads and implantation of bilateral GPi leads resulted in the resolution of tremor symptoms following a failed bilateral Vim DBS. We performed a normative connectome analysis using the volume of tissue activated (VTA) as a region of interest. The results revealed that the fiber tracts associated with VTA of GPi DBS had connections with the facial area of the motor cortex while the Vim DBS did not.
Conclusion: This case study suggests the possibility that GPi DBS may be considered for midline tremor, and that the normative connectome analysis may possibly offer clues as to the structures underpinning a positive response. We may refine targets for some of the more difficult to control symptoms such as the midline tremor in this case.
Scientific Reports, 2017
Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence o... more Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3%. Recently, brain activity in the resting state is gathering attention for exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated the neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, our machine learning algorithm identified an OCD biomarker that achieves high accuracy for an internal dataset (AUC = 0.81; N = 108) and demonstrates generalizability to an external dataset (AUC = 0.70; N = 28). Our biomarker was unaffected by medication status, and the functional networks contributing to the biomarker were distributed widely, including the frontoparietal and default mode networks. Our biomarker has the potential to deepen our understanding of OCD and to be applied clinically.
Journal of Psychiatric Research, 2011
There is increasing evidence of white matter abnormalities in patients with obsessive-compulsive ... more There is increasing evidence of white matter abnormalities in patients with obsessive-compulsive disorder (OCD). The results of previous diffusion tensor imaging (DTI) studies, however, are inconsistent. Reasons for this inconsistency may include methodological issues such as misregistration, the differences in smoothing voxel-based morphometry style analysis or both. To date there are no DTI studies with tract-based spatial statistics (TBSS) which overcome these issues. In addition, previous studies had few drug-free patients, thus potentially reducing their power and obscuring their findings. Therefore, the aim of present study was to investigate white matter abnormalities using DTI and TBSS analysis in a large sample of drug-free patients with OCD. Thirty drug-free patients with OCD and 30 healthy controls underwent DTI. Fourteen of 30 patients were drug naïve. Voxel-wise group comparison of white matter fractional anisotropy (FA) was performed using TBSS. Compared to healthy volunteers, OCD patients had statistically less FA in the anterior body of corpus callosum (CC) (p < .05, corrected). They also had a trend for a lower FA in the large portion of CC, the right cingulum, and the left anterior limb of internal capsule (ALIC). There were no areas of the brain with significantly higher FA. This is the first study that has investigated white matter abnormalities in non-medicated patients with OCD using DTI and TBSS analyses. Microstructural white matter abnormalities in the CC, the cingulum, and the ALIC might be involved in the pathophysiology of OCD.
Cell Reports, Aug 30, 2022
We may view most of our daily activities as rational action selections; however, we sometimes rei... more We may view most of our daily activities as rational action selections; however, we sometimes reinforce maladaptive behaviors despite having explicit environmental knowledge. In this study, we model obsessive-compulsive disorder (OCD) symptoms as implicitly learned maladaptive behaviors. Simulations in the reinforcement learning framework show that agents implicitly learn to respond to intrusive thoughts when the memory trace signal for past actions decays differently for positive and negative prediction errors. Moreover, this model extends our understanding of therapeutic effects of behavioral therapy in OCD. Using empirical data, we confirm that patients with OCD show extremely imbalanced traces, which are normalized by serotonin enhancers. We find that healthy participants also vary in their obsessive-compulsive tendencies, consistent with the degree of imbalanced traces. These behavioral characteristics can be generalized to variations in the healthy population beyond the spectrum of clinical phenotypes.
Journal of Neurosurgery, 2021
OBJECTIVE Deep brain stimulation (DBS) of the centromedian thalamic nucleus has been reportedly ... more OBJECTIVE
Deep brain stimulation (DBS) of the centromedian thalamic nucleus has been reportedly used to treat severe Tourette syndrome, yielding promising outcomes. However, it remains unclear how DBS electrode position and stimulation parameters modulate the specific area and related networks. The authors aimed to evaluate the relationships between the anatomical location of stimulation fields and clinical responses, including therapeutic and side effects.
METHODS
The authors collected data from 8 patients with Tourette syndrome who were treated with DBS. The authors selected the active contact following threshold tests of acute side effects and gradually increased the stimulation intensity within the therapeutic window such that acute and chronic side effects could be avoided at each programming session. The patients were carefully interviewed, and stimulation-induced side effects were recorded. Clinical outcomes were evaluated using the Yale Global Tic Severity Scale, the Yale-Brown Obsessive-Compulsive Scale, and the Hamilton Depression Rating Scale. The DBS lead location was evaluated in the normalized brain space by using a 3D atlas. The volume of tissue activated was determined, and the associated normative connective analyses were performed to link the stimulation field with the therapeutic and side effects.
RESULTS
The mean follow-up period was 10.9 ± 3.9 months. All clinical scales showed significant improvement. Whereas the volume of tissue activated associated with therapeutic effects covers the centromedian and ventrolateral nuclei and showed an association with motor networks, those associated with paresthesia and dizziness were associated with stimulation of the ventralis caudalis and red nucleus, respectively. Depressed mood was associated with the spread of stimulation current to the mediodorsal nucleus and showed an association with limbic networks.
CONCLUSIONS
This study addresses the importance of accurate implantation of DBS electrodes for obtaining standardized clinical outcomes and suggests that meticulous programming with careful monitoring of clinical symptoms may improve outcomes.
European Psychiatry, 2011
The basal ganglia represents a key component of the pathophysiological model for obsessive-compul... more The basal ganglia represents a key component of the pathophysiological model for obsessive-compulsive disorder (OCD). This brain region is part of several neural circuits, including the orbitofronto-striatal circuit and dorsolateral prefronto-striatal circuit. There are, however, no published studies investigating those circuits at a network level in non-medicated patients with OCD. Resting state functional magnetic resonance imaging scans were obtained from 20 non-medicated patients with OCD and 23 matched healthy volunteers. Voxelwise statistical parametric maps testing strength of functional connectivity of three striatal seed regions of interest (ROIs) with remaining brain regions were calculated and compared between groups. We performed additional correlation analyses between strength of connectivity and the severity scores for obsessive-compulsive symptoms, depression, and anxiety in the OCD group. Positive functional connectivity with the ventral striatum was significantly increased (P(corrected) < .05) in the orbitofrontal cortex, ventral medial prefrontal cortex and dorsal lateral prefrontal cortex of subjects with OCD. There was no significant correlation between measures of symptom severity and the strength of connectivity (P(uncorrected) < .001). This is the first study to investigate the corticostriatal connectivity in non-medicated patients with OCD. These findings provide the first direct evidence supporting a pathophysiological model involving basal ganglia circuitry in OCD.
Frontiers in Human Neuroscience, 2021
Introduction: The clinical efficacy of deep brain stimulation (DBS) for midline tremor has been h... more Introduction: The clinical efficacy of deep brain stimulation (DBS) for midline tremor has been heterogenous. Here, we present an atypical case with facial and palatal tremor treated with DBS. We aimed to show the difference between the fibers affected by stimulation of the two targets [globus pallidus interna (GPi) and ventral intermediate (Vim) thalamic nucleus] using a normative connectome analysis.
Case Report: A 76-year-old woman with a 4-year history of severe facial and palatal tremor due to craniofacial dystonia. Following a failed bilateral Vim DBS, explantation of preexisting leads and implantation of bilateral GPi leads resulted in the resolution of tremor symptoms following a failed bilateral Vim DBS. We performed a normative connectome analysis using the volume of tissue activated (VTA) as a region of interest. The results revealed that the fiber tracts associated with VTA of GPi DBS had connections with the facial area of the motor cortex while the Vim DBS did not.
Conclusion: This case study suggests the possibility that GPi DBS may be considered for midline tremor, and that the normative connectome analysis may possibly offer clues as to the structures underpinning a positive response. We may refine targets for some of the more difficult to control symptoms such as the midline tremor in this case.
Scientific Reports, 2017
Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence o... more Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3%. Recently, brain activity in the resting state is gathering attention for exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated the neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, our machine learning algorithm identified an OCD biomarker that achieves high accuracy for an internal dataset (AUC = 0.81; N = 108) and demonstrates generalizability to an external dataset (AUC = 0.70; N = 28). Our biomarker was unaffected by medication status, and the functional networks contributing to the biomarker were distributed widely, including the frontoparietal and default mode networks. Our biomarker has the potential to deepen our understanding of OCD and to be applied clinically.
Journal of Psychiatric Research, 2011
There is increasing evidence of white matter abnormalities in patients with obsessive-compulsive ... more There is increasing evidence of white matter abnormalities in patients with obsessive-compulsive disorder (OCD). The results of previous diffusion tensor imaging (DTI) studies, however, are inconsistent. Reasons for this inconsistency may include methodological issues such as misregistration, the differences in smoothing voxel-based morphometry style analysis or both. To date there are no DTI studies with tract-based spatial statistics (TBSS) which overcome these issues. In addition, previous studies had few drug-free patients, thus potentially reducing their power and obscuring their findings. Therefore, the aim of present study was to investigate white matter abnormalities using DTI and TBSS analysis in a large sample of drug-free patients with OCD. Thirty drug-free patients with OCD and 30 healthy controls underwent DTI. Fourteen of 30 patients were drug naïve. Voxel-wise group comparison of white matter fractional anisotropy (FA) was performed using TBSS. Compared to healthy volunteers, OCD patients had statistically less FA in the anterior body of corpus callosum (CC) (p < .05, corrected). They also had a trend for a lower FA in the large portion of CC, the right cingulum, and the left anterior limb of internal capsule (ALIC). There were no areas of the brain with significantly higher FA. This is the first study that has investigated white matter abnormalities in non-medicated patients with OCD using DTI and TBSS analyses. Microstructural white matter abnormalities in the CC, the cingulum, and the ALIC might be involved in the pathophysiology of OCD.