Keisuke Wakusawa

The neural basis of agency: an fMRI study.

Agency, a feeling that the self is the cause of action, has a strong relationship to the processing of discrepancies between the predicted multi-sensory feedback from ones intended action and its actual outcome (hereafter, agency error). Although previous studies have explored the neural basis of agency by assessing the brains response to agency error, the effects found are confounded by two types of error irrelevant to agency: a mismatch between different sensory inputs in general (sensory mismatch, SM error) and a basic response to any type of prediction error (oddball error). In this functional magnetic resonance imaging study, we identified the neural response specific to agency error by dissociating it from responses to SM and oddball errors. Subjects played a game in which they controlled an on-screen character. Neural responses to rare events of violated control and congruency between types of audio-visual feedback were compared to dissociate agency from SM error. In a separate session, subjects viewed repetitive motions of the character, and neural responses to rare events of unpredictable change in movement were identified as related to oddball error. Agency-error-specific activation was observed in the supplementary motor area (SMA), left cerebellum, right posterior parietal cortex (PPC), and right extrastriate body area (EBA). Oddball errors also activated areas near the PPC and EBA peaks. SM errors activated the pre-SMA and the right posterior superior temporal sulcus. Our results suggest that the SMA, cerebellum, and some parts of the PPC and EBA serve as the neural bases of agency.

Self-face recognition in social context

The concept of “social self” is often described as a representation of the self‐reflected in the eyes or minds of others. Although the appearance of ones own face has substantial social significance for humans, neuroimaging studies have failed to link self‐face recognition and the likely neural substrate of the social self, the medial prefrontal cortex (MPFC). We assumed that the social self is recruited during self‐face recognition under a rich social context where multiple other faces are available for comparison of social values. Using functional magnetic resonance imaging (fMRI), we examined the modulation of neural responses to the faces of the self and of a close friend in a social context. We identified an enhanced response in the ventral MPFC and right occipitoparietal sulcus in the social context specifically for the self‐face. Neural response in the right lateral parietal and inferior temporal cortices, previously claimed as self‐face‐specific, was unaffected for the self‐face but unexpectedly enhanced for the friends face in the social context. Self‐face‐specific activation in the pars triangularis of the inferior frontal gyrus, and self‐face‐specific reduction of activation in the left middle temporal gyrus and the right supramarginal gyrus, replicating a previous finding, were not subject to such modulation. Our results thus demonstrated the recruitment of a social self during self‐face recognition in the social context. At least three brain networks for self‐face‐specific activation may be dissociated by different patterns of response‐modulation in the social context, suggesting multiple dynamic self‐other representations in the human brain. Hum Brain Mapp, 2011.

Acute encephalopathy with a truncation mutation in the SCN1A gene: A case report

A girl aged 1 year 9 months had recurrent episodes of febrile status epilepticus. She recovered completely after the first three episodes. However, at 9 months she developed acute encephalopathy resulting in severe neurologic sequelae. Diffusion‐weighted magnetic resonance imaging revealed diffuse high‐intensity signals over the cortex and subcortical white matter in the acute phase and severe diffuse cerebral atrophy in the chronic phase. Mutations were detected in the neuronal voltage‐gated sodium channel alpha subunit type 1 (SCN1A) gene. SCN1A sequence analysis revealed a truncation mutation: ex1‐c.126Adel (D43fs). Our patient was likely afflicted by severe myoclonic epilepsy in infancy, and the fourth episode of status epilepticus was similar to acute encephalopathy. This report provides further insight into the molecular pathophysiology underlying acute encephalopathy.

Learning second language vocabulary: Neural dissociation of situation-based learning and text-based learning

Second language (L2) acquisition necessitates learning and retrieving new words in different modes. In this study, we attempted to investigate the cortical representation of an L2 vocabulary acquired in different learning modes and in cross-modal transfer between learning and retrieval. Healthy participants learned new L2 words either by written translations (text-based learning) or in real-life situations (situation-based learning). Brain activity was then measured during subsequent retrieval of these words. The right supramarginal gyrus and left middle frontal gyrus were involved in situation-based learning and text-based learning, respectively, whereas the left inferior frontal gyrus was activated when learners used L2 knowledge in a mode different from the learning mode. Our findings indicate that the brain regions that mediate L2 memory differ according to how L2 words are learned and used.

Brain magnetic resonance imaging and motor and intellectual functioning in 86 patients born at term with spastic diplegia.

Aim  To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients born at term with spastic diplegia.

Utility of subtraction ictal SPECT images in detecting focal leading activity and understanding the pathophysiology of spasms in patients with West syndrome

PURPOSES The aims of the study were to evaluate the detectability of focal leading activity in three cases of West syndrome having focal abnormal activity on EEG by comparing subtraction ictal images and raw ictal images, and to interpret the results in 16 cases. METHODS Subtraction images were constructed using iNeurostat (revision 2). RESULTS In three cases with focal abnormal activity on EEG, subtraction ictal images reflected the EEG findings; in contrast, raw ictal images did not. Diverse degrees of cortical hyperperfusion, ranging from zero to 10 sites, seen in the other 13 cases seemed to reflect spasm pathophysiology and rapid spasm propagation. Subtraction ictal images also allowed the ready detection of hyperperfusion of subcortical structures and of a tight cortico-subcortical relationship in a subset of cases. CONCLUSIONS We showed the superiority of subtraction ictal images in detecting the focal epileptic region and in showing propagation pathways from the cortex to subcortical structures. A subset of spasms in WS may be focal cortical-onset secondarily generalized seizures. We believe that subtraction analysis is valuable in patients with complex WS who have partial seizures and spasms simultaneously along with focal epileptic EEG activity, as they will likely be candidates for epilepsy surgery.

Efficacy of sumatriptan in two pediatric cases with abdominal pain-related functional gastrointestinal disorders: does the mechanism overlap that of migraine?

We successfully treated 2 pediatric cases of abdominal pain-related functional gastrointestinal disorder with sumatriptan. When 9 years old, patient 1 developed periodic abdominal pain that was intractable to medication and remitted spontaneously. She was diagnosed with abdominal migraine, categorized as H2c in the Rome III criteria for functional gastrointestinal disorders. At age 12, intranasal sumatriptan relieved her pain, and her attacks halted 2 years later. Patient 2 was a 9-year-old girl diagnosed with attention-deficit hyperactivity disorder (ADHD), who began to have intermittent abdominal pain of variable severity, which sometimes restricted daily activity. She was diagnosed with childhood functional abdominal pain syndrome, categorized as H2d1 using the Rome III criteria. Intranasal sumatriptan also relieved her pain. These cases suggest that the mechanism of pain in abdominal pain-related functional gastrointestinal disorders is similar to that of migraine, with probable central hypersensitivity, at least in a subset of cases.

Schinzel–Giedion syndrome: A further cause of early myoclonic encephalopathy and vacuolating myelinopathy

Here, we report a male child with Schinzel-Giedion syndrome associated with intramyelinic edema detected on brain magnetic resonance imaging (MRI) and persistent suppression-burst pattern on electroencephalography (EEG) with erratic myoclonus of the extremities and face. Similar to nonketotic hyperglycinemia, Schinzel-Giedion syndrome may be recognized as another causative genetic disease of early myoclonic encephalopathy and vacuolating myelinopathy.

Successful treatment of a 2-year-old girl with intractable myasthenia gravis using tacrolimus

We used tacrolimus to successfully treat a patient with childhood-onset oropharyngeal myasthenia gravis (MG). A girl (2 years, 5 months old) with oropharyngeal MG responded partially to treatment including pyridostigmine bromide, intravenous immunoglobulin, and prednisolone (2 mg/kg/day) for 7 weeks, but this resulted in worsening of her eye symptoms. By contrast, tacrolimus at 2 mg/day resulted in complete remission of the MG, which made it possible to reduce the dose of prednisolone. This is a rare report of the use of tacrolimus as an effective treatment for patients with intractable childhood-onset MG.

Extraction of Situational Meaning by Integrating Multiple Meanings in a Complex Environment: A Functional MRI Study

Humans extract behaviorally significant meaning from a situation by integrating meanings from multiple components of a complex daily environment. To determine the neural underpinnings of this ability, the authors performed functional magnetic resonance imaging of healthy subjects while the latter viewed naturalistic scenes of two people and an object, including a threatening situation of a person being attacked by an offender with an object. The authors used a two‐factorial design: the object was either aversive or nonaversive, and the offenders action was either directed to the person or elsewhere. This allowed the authors to examine the neural response to object aversiveness and person‐directed intention separately. A task unrelated to threat was also used to address incidental (i.e., subconscious or unintentional) detection. Assuming individual differences in incidental threat detection, the authors used a functional connectivity analysis using principal components analysis of intersubject variability. The left lateral orbitofrontal cortex and medial prefrontal cortex (MPFC) were specifically activated in response to a threatening situation. The threat‐related component of intersubject variability was extracted from these data and showed a significant correlation with personality scores. There was also a correlation between threat‐related intersubject variability and activation for object aversiveness in the left temporal pole and lateral orbitofrontal cortex; person‐directed intention in the left superior frontal gyrus; threatening situations in the left MPFC; and independently for both factors in the right MPFC. Results demonstrate independent processing of object aversiveness and person‐directed intention in the left temporal‐orbitofrontal and superior frontal networks, respectively, and their integration into situational meaning in the MPFC. Hum Brain Mapp, 2009.