Surprise signals in the supplementary eye field: rectified prediction errors drive exploration-exploitation transitions.

Visual search is coordinated adaptively by monitoring and predicting the environment. The supplementary eye field (SEF) plays a role in oculomotor control and outcome evaluation. However, it is not clear whether the SEF is involved in adjusting behavioral modes based on preceding feedback. We hypothesized that the SEF drives exploration-exploitation transitions by generating "surprise signals" or rectified prediction errors, which reflect differences between predicted and actual outcomes. To test this hypothesis, we introduced an oculomotor two-target search task in which monkeys were required to find two valid targets among four identical stimuli. After they detected the valid targets, they exploited their knowledge of target locations to obtain a reward by choosing the two valid targets alternately. Behavioral analysis revealed two distinct types of oculomotor search patterns: exploration and exploitation. We found that two types of SEF neurons represented the surprise signals. The error-surprise neurons showed enhanced activity when the monkey received the first error feedback after the target pair change, and this activity was followed by an exploratory oculomotor search pattern. The correct-surprise neurons showed enhanced activity when the monkey received the first correct feedback after an error trial, and this increased activity was followed by an exploitative, fixed-type search pattern. Our findings suggest that error-surprise neurons are involved in the transition from exploitation to exploration and that correct-surprise neurons are involved in the transition from exploration to exploitation.

Pure amnestic seizure: A clinico-intracranial EEG study.

OBJECTIVE: Enduring anterograde amnesia is caused by lesions in bilateral mesial temporal lobes. However, whether transient dysfunction of bilateral mesial temporal regions induces reversible amnesia has not been proven. We investigated this association in patients with epilepsy and analyzed the electroclinical correlation during pure amnestic seizures (PAS). PAS are defined as seizures with anterograde amnesia as the only ictal manifestation, accompanied by preserved responsiveness and other cognitive functions. METHODS: We retrospectively searched our intracranial EEG database to find PAS. Pure ictal amnesia was confirmed by immediate and comprehensive ictal examinations. RESULTS: Among 401 patients who underwent intracranial EEG recording, three patients with temporal lobe epilepsy (TLE) manifesting PAS were identified. The patients talked and behaved normally during seizure but did not remember the episodes afterwards. Ictal discharges were confined to bilateral mesial temporal regions, with no or mild involvement of surrounding structures. Spread of low-voltage fast activities to bilateral mesial temporal regions corresponded to onset of ictal anterograde amnesia. Two patients underwent unilateral mesial temporal resection and became seizure-free with improvement in cognitive functions. SIGNIFICANCE: PAS is a rare ictal semiology in TLE. Bilateral mesial temporal regions that play a critical role in memory encoding are presumably the symptomatogenic zones for PAS.

Status of epilepsy care delivery and referral in clinics, hospitals, and epilepsy centers in Japan: A nationwide survey.

OBJECTIVE: Collaboration among medical facilities is crucial to deliver comprehensive epilepsy care to a diverse and large population of people with epilepsy. We conducted a survey among medical facilities of various sizes throughout Japan to investigate the status of epilepsy care delivery, functioning, and referral. METHODS: With the cooperation of the Japan Neurological Society (1428 facilities), Japanese Neurosurgical Society (3489 specialists), and Epilepsy Care Network (948 facilities), a questionnaire was mailed to 5865 locations that provide epilepsy care in Japan. The facilities were classified into clinics (19 beds or less), small hospitals (SH, 20-199 beds), large hospitals (LH, 200 beds or more), and epilepsy centers (EC). The status of epilepsy care delivery, functioning, and referral was compared among the four groups. RESULTS: Responses were received from 1014 facilities (17.3% response rate). After excluding duplicate responses, 957 facilities were analyzed (394 clinics, 149 SH, 388 LH, 26 EC). EC responded "manageable" in more items of epilepsy care functions in general, especially those related to epilepsy surgery, compared to LH with similar facility size. However, EC responded being less manageable in psychiatric service (61.5%), dietary therapy (46.2%), rehabilitation (53.8%), and patient employment support (61.5%). The percentage of facilities that responded "always able to refer" was highest in clinics (67.6%) and the lowest in EC (40%). Referral difficulties were more commonly encountered in EC, and less common in clinics. In EC, the most common reason for inability to refer was patient or family refusal (64%). SIGNIFICANCE: We have clarified the epilepsy care delivery, functioning, and referral in facilities of various sizes in Japan. This study highlights the issues of downward referral and patient stagnation in EC, which have not received much attention. PLAIN LANGUAGE SUMMARY: A nationwide survey of healthcare facilities ranging in size from small clinics to large hospitals in Japan examined medical care delivery and patient referrals related to epilepsy. Compared to other facilities, epilepsy centers provided a variety of medical services to people with epilepsy but were inadequate in addressing psychiatric symptoms, providing dietary therapy, rehabilitation, and patient employment support. Referrals from epilepsy centers to other medical facilities were often refused by patients and their families. This results in patient crowding at epilepsy centers.

[Diagnosis and Classification of Epilepsy: Clinical Reasoning].

Epilepsy is defined as a chronic disorder that presents with recurrent episodes of unprovoked seizures. Epileptic seizures are caused by excessive excitation of cortical neurons. The condition has various etiologies and comorbidities. Here, we introduce the definition of epilepsy and classify it based on the newly proposed ILAE (International League Against Epilepsy) classification. In addition, we explain the process of diagnosing epilepsy and delineating the epileptic focus by presenting a case description. Transient functional alterations occur in an epileptic focus only during seizures. Thus, epileptologists are required to record a detailed history and examine its semiology to determine the epileptic focus based on knowledge in neuroscience and epileptology.

Periictal water drinking revisited: Occurrence and lateralizing value in surgically confirmed patients with focal epilepsy.

OBJECTIVE: Periictal water drinking (PIWD), which is a rare seizure-related autonomic behavior, has been reported in temporal lobe epilepsy (TLE) but only rarely in extra-TLE. Additionally, the lateralizing value of PIWD is controversial. We aimed to clarify the occurrence and lateralizing value of PIWD in patients with focal epilepsy. METHODS: This retrospective study included 240 focal epilepsy patients aged >10 years with a favorable postoperative seizure outcome (Engel class I). PIWD was defined as water drinking behavior during a seizure or within 2 min in the postictal phase. The occurrence of PIWD documented on video-electroencephalogram monitoring was assessed. The lateralizing value of PIWD was analyzed among patients whose language dominant hemisphere was identified. RESULTS: Twenty-three (9.5%) patients exhibited PIWD. PIWD occurred more frequently in frontal lobe epilepsy (FLE; eight of 41 patients, 19.5%) than in TLE (15 of 188 patients, 8%). The occurrence of PIWD was significantly different between FLE and extra-FLE (P = 0.035), with a low positive predictive value (34.8%). In FLE with PIWD, all but one patient underwent resective surgery involving the medial frontal lobe. In 194 patients whose language dominant hemisphere was determined, the lateralizing value of PIWD in FLE and TLE showed no statistical significance (P = 0.69 and P = 0.27, respectively). SIGNIFICANCE: Periictal water drinking occurred more often in FLE than TLE. Thus, PIWD might not be a specific periictal symptom in TLE. There was no evidence for the lateralizing value of PIWD in FLE and TLE. These findings can provide useful clinical clues for preoperative evaluations to estimate the epileptogenic zone based on seizure semiology and allow for a better understanding of pathophysiological insights into PIWD.

A Single-center Analysis of Three Japanese Patients with Mahjong-related Seizures.

Mahjong is one of the most popular Chinese tile games played in Japan. Mahjong-related seizures (MRS) are rare praxis-induced seizures. We identified three patients with MRS from February 2000 to February 2021. All cases were men, with a middle-age onset, generalized convulsive seizures, and lack of non-provoked, myoclonic, and absence seizures. All patients had no or non-specific neuroimaging or electroencephalogram abnormalities. They did not have features linked to idiopathic generalized epilepsy. All patients were seizure-free after behavioral adjustments, although one patient required anti-seizure medication and avoided long duration games. These changes may help other patients with MRS continue playing Mahjong.

Bilateral tonic-clonic seizure and focal cortical hyperexcitability in familial Creutzfeldt-Jakob disease with E200K mutation of the prion protein.

Convulsive epileptic seizures are rare in Creutzfeldt-Jakob disease (CJD), and their clinical and EEG features have not been reported in detail. We describe a case of familial CJD with an E200K mutation of the prion protein who presented with bilateral tonic-clonic seizures (BTCS) during long-term video-EEG monitoring. Semiologically, BTCS showed focal clinical signs such as head turning and eye deviation to the left. The ictal EEG started with generalized polyspikes. Interictal EEG showed generalized periodic discharges with right fronto-temporal predominance (larger amplitude and earlier onset compared with other regions). MRI showed high-intensity signals persistently in the right temporo-parietal region on diffusion-weighted images (DWI). Interictal single-photon emission computed tomography (SPECT) showed hyperperfusion in the same region. Brain pathology revealed typical spongiform changes in CJD without other pathological findings of rapidly progressive dementia. Our case demonstrates that CJD can cause BTCS with generalized EEG changes and focal semiological/imaging abnormalities, suggesting that diffuse and inhomogeneous cortical and subcortical epileptic networks may develop in familial CJD.

Mesial temporal lobe epilepsy with amygdalar hamartoma-like lesion: Is it a distinct syndrome?

INTRODUCTION: We examined the clinical, semiological, scalp electroencephalographic (EEG), and neuropsychological features of patients with amygdalar hamartoma-like lesion (AHL) without hippocampal sclerosis (HS). METHODS: This retrospective study included 9 patients with mesial temporal lobe epilepsy (MTLE) who had an amygdalar lesion on preoperative MRI; underwent mesial temporal resection; were diagnosed with amygdalar hamartoma-like lesion (AHL) without hippocampal sclerosis (HS); were followed up for at least 2 years after surgery; and had a favourable postoperative seizure outcome (Engel Class I). There were 5 women and 4 men, and age at surgery ranged from 19 to 54 (mean, 36.6) years. Clinical characteristics, auras, video-recorded seizure semiology, interictal and ictal EEG, and preoperative neuropsychological data were reviewed. Twenty patients with MTLE with HS who had favourable postoperative seizure outcomes (Engel Class I) were selected as controls. RESULTS: Age at seizure onset was significantly higher in patients with AHL without HS than in those with HS. Fear was more frequently seen in patients with AHL (44 %) than in those with HS (5 %) (P = 0.022). There were no significant differences in interictal epileptiform discharges or ictal EEG pattern. Preoperative full-scale IQ score was significantly higher in the AHL group than in the HS group (mean, 92.9 v. 74.8, P = 0.004), as was preoperative memory quotient score (mean 100.7 v. 85.1, P = 0.028). CONCLUSION: We clarified the clinical, semiological, and neuropsychological features of patients with MTLE-AHL. These findings may be useful for preoperative evaluation, especially of patients with suspected MTLE but without apparent HS on preoperative MRI.

Localized focal cortical dysplasia type II: seizure freedom with lesionectomy guided by MRI and FDG-PET.

OBJECTIVE: The authors perform thorough, noninvasive presurgical evaluations for intractable epilepsy at their center and avoid unnecessary intracranial EEG when possible. The purpose of this study was to clarify the appropriateness of their lesion-oriented surgical strategy for localized focal cortical dysplasia (FCD) type II. METHODS: Fifty-one patients with pathologically proven localized FCD type II who were followed for at least 1 year after surgery were included. Patients with FCD type II with lobar or multilobar distribution were excluded. The results of presurgical evaluations, including thin-slice 3-T MRI, FDG-PET, and ictal SPECT, as well as surgical procedures and postoperative seizure and functional outcomes, were examined retrospectively. RESULTS: MRI was positive in 46 (90%) of 51 patients, and FDG-PET revealed localized hypo- or hypermetabolism in 47 (92%) of 51 patients. Ictal SPECT revealed concordant hyperperfusion in 37 of 42 patients examined. Intracranial EEG was used in only 13 patients (25%), including 5 with negative MRI results and 4 with subtle MRI findings. Of the 15 patients with FCD in the vicinity of eloquent (sensorimotor and language) areas, intracranial EEG was used in 4. Lesionectomy was performed in all 51 patients. Intraoperative electrocorticography (ECoG) was performed in 8 patients, but the findings were not used to tailor the extent of resection. Postoperative seizure outcomes were Engel class I in 47 patients (92%) and Ia in 45 (88%). In the 15 patients with FCD in the vicinity of eloquent areas, 13 (87%) achieved a class I outcome. Predictive factors for favorable seizure outcome were complete resection of the MRI lesion (p = 0.006) and frontal lobe surgery (p = 0.012). Postoperative neurological deficits were noted in only 4 (27%) of 15 patients with FCD in the vicinity of eloquent areas. All 5 MRI-negative patients achieved an Engel class I outcome. CONCLUSIONS: In most of the patients with localized FCD type II, MRI and/or FDG-PET detected the localized abnormality. Lesionectomy without intracranial EEG led to seizure freedom in most cases. Even when lesions were in the vicinity of eloquent areas, seizure and functional outcomes were favorable. Intraoperative ECoG may thus be unnecessary. Complete resection of the lesion is essential for favorable seizure outcome in MRI-positive patients. In MRI-negative patients, surgery with intracranial EEG guided by FDG-PET provided seizure-free outcomes.

A case with anti-galactocerebroside antibody-positive Mycoplasma pneumoniae meningoencephalitis presenting secondary hypersomnia.

Galactocerebroside (Gal-C) is a major myelin component in the central nervous system. The anti-Gal-C antibody induced by mycoplasma infection may therefore be involved in the pathogenic mechanisms of mycoplasma-associated encephalitis. Here we report an adult case of mycoplasma encephalitis developing excessive daytime sleepiness. Brain MRI suggested that hypothalamic involvement was compatible with hypersomnia. This finding was corroborated by decreased hypocretin-1 in cerebrospinal fluid (CSF) and the manifestation of diabetes insipidus. Screening for anti-glycolipid antibody profiles showed the selective increase of serum anti-Gal-C antibody. After treatment with minocyclin, the patient's daytime sleepiness was markedly improved and the CSF hypocretin-1 level became almost normal, as well. It is known that CSF hypocretin-1 is decreased in Guillain-Barré syndrome mediated by anti-glycolipid antibody, suggesting a possible mechanistic link between anti-glycolipid antibodies and hypothalamic involvement. The present case further emphasizes the broad spectrum of neurological complications after mycoplasma infection.

Shape and Rule Information Is Reflected in Different Local Field Potential Frequencies and Different Areas of the Primate Lateral Prefrontal Cortex.

The lateral prefrontal cortex (LFPC) plays a crucial role in executive function by adaptively storing behavior-relevant information as working memory. Neural mechanisms associated with local field potentials (LFPs) may underlie the adaptive properties of the LFPC. Here, we analyzed how LFPs recorded from the monkey LFPC are modulated by the crucial factors of a shape manipulation task. In this task, the test shape is transformed by manipulating a lever to match the size and orientation of the sample shape. The subject is required to temporarily memorize the rules such as the arm-movement-manipulation relationship and the sample shape to generate the sequential behavior of operations. In the present study, we focused on task variables about shape and rules, and examined among which aspects distinguish the ventral and dorsal sides of the LFPC. We found that the transformed shape in the sample period strongly affected the theta and delta waves in the delay period on the ventral side, while the arm-manipulation assignment influenced the gamma components on the dorsal side. These findings suggest that area- and frequency-selective LFP modulations are involved in dynamically recruiting different behavior-relevant information in the LFPC.

Reinforcement Learning Model With Dynamic State Space Tested on Target Search Tasks for Monkeys: Extension to Learning Task Events.

Learning is a crucial basis for biological systems to adapt to environments. Environments include various states or episodes, and episode-dependent learning is essential in adaptation to such complex situations. Here, we developed a model for learning a two-target search task used in primate physiological experiments. In the task, the agent is required to gaze one of the four presented light spots. Two neighboring spots are served as the correct target alternately, and the correct target pair is switched after a certain number of consecutive successes. In order for the agent to obtain rewards with a high probability, it is necessary to make decisions based on the actions and results of the previous two trials. Our previous work achieved this by using a dynamic state space. However, to learn a task that includes events such as fixation to the initial central spot, the model framework should be extended. For this purpose, here we propose a "history-in-episode architecture." Specifically, we divide states into episodes and histories, and actions are selected based on the histories within each episode. When we compared the proposed model including the dynamic state space with the conventional SARSA method in the two-target search task, the former performed close to the theoretical optimum, while the latter never achieved target-pair switch because it had to re-learn each correct target each time. The reinforcement learning model including the proposed history-in-episode architecture and dynamic state scape enables episode-dependent learning and provides a basis for highly adaptable learning systems to complex environments.

Electroclinical features of seizures in myelin oligodendrocyte glycoprotein antibody-associated cerebral cortical encephalitis: A case report and literature review.

PURPOSE: Myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs) are associated with various central nervous system demyelinating disorders. Recently, they were detected in cerebral cortical encephalitis (CCE), which often causes seizures. We performed a literature review to elucidate the electroclinical features of CCE. In addition to the published cases, we describe a new, illustrative case of MOG-Ab-associated CCE (MOG-CCE) with multifocal seizures documented by video electroencephalograph (EEG). METHODS: We searched PubMed with the keywords "[MOG] AND [encephalitis]" and reviewed relevant articles. The articles included reports of patients with CCE (as demonstrated by magnetic resonance imaging) and serum MOG Ab positivity. Cases were excluded if no epileptic seizures were reported or if details of the seizures were unavailable. RESULTS: Our literature review identified 34 patients with MOG-CCE. An analysis of these 34 cases and the new case showed that 20 patients were male (57.1%), and the median age at presentation was 23 years (range, 6 to 46 years). Focal to bilateral tonic-clonic seizure was the most common seizure type, followed by focal motor seizure in the face or an arm or leg. EEG findings were available for 26 patients. Interictal epileptiform discharges (IEDs) and ictal EEG patterns were seen in 10 (38.5%) and 5 (19.2%) patients, respectively. Focal EEG abnormalities, including slow waves and IEDs, were observed in the central, parietal, occipital, or posterior temporal region. CONCLUSION: MOG-CCE has distinctive electroclinical features that differ from those of other autoimmune encephalitides. Careful electroclinical analysis of seizures can be helpful for diagnosing MOG-CCE.

Differences in task-phase-dependent time-frequency patterns of local field potentials in the dorsal and ventral regions of the monkey lateral prefrontal cortex.

Although the ventral and dorsal regions of the lateral prefrontal cortex (lPFC) are anatomically distinct, their functional differentiation is still controversial. Local field potentials (LFPs) reflect synaptic input and are widely modulated by information from both the external world and the internal state of the brain. However, functional mapping using LFPs has not been fully tested and is expected to provide new insights into their differences. Thus, the present study analyzed the task-phase-dependent modulations of LFPs recorded from the lPFC of monkeys as they performed a shape manipulation task. Hierarchical cluster analyses of the LFP time-frequency spectra revealed characteristic patterns, especially in the theta and low gamma ranges. In particular, the theta range distinguished the ventral and dorsal parts of the lPFC well. The ventral part exhibited a block of similar LFP patterns whereas the dorsal part showed scattered patterns of small or single sites with different LFP patterns. These results suggest that functional segregation within the lPFC, especially between the ventral and dorsal regions, can be evaluated using task-phase-dependent time-frequency modulations in LFPs.

Extranodal NK/T-cell Lymphoma Mimicking Granulomatous Myositis.

Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract. We encountered an ENKTL patient who presented with generalized muscle weakness with eyelid swelling, diplopia, and facial edema. A muscle biopsy revealed lymphocytic infiltration without significant atypia; some lymphocytes formed granuloma-like structures. Although the initial response to steroids was encouraging, an ulcerative eruption appeared in the thigh, and a skin biopsy revealed lymphocytes with atypia. A re-analysis of the muscle biopsy with additional immunohistochemistry revealed neoplastic NK/T lymphocytes in the granulomatous structures. Our case highlights the significance of re-evaluating muscle biopsy specimens in cases of atypical myositis.

Semiology of hyperkinetic seizures of frontal versus temporal lobe origin.

Hyperkinetic seizures are usually associated with frontal lobe epilepsy. However, some patients have hyperkinetic seizures of temporal lobe origin. The semiological differences in hyperkinetic seizures between frontal and temporal lobe epilepsy have not been well studied. Here, we retrospectively assessed ictal semiology in order to distinguish between hyperkinetic seizures of frontal lobe origin and those of temporal lobe origin. We retrospectively reviewed data on patients who had undergone surgery for hyperkinetic seizures of temporal or frontal lobe origin and achieved favourable seizure outcomes (Engel Class I) with a minimum postoperative follow-up of 24 months. We reviewed seizure histories, imaging reports, video-EEG monitoring data, operative records, and pathological findings. We analysed and compared the hyperkinetic semiology of video-recorded seizures of temporal lobe origin and those of frontal lobe origin. Forty hyperkinetic seizures in eight patients (seven adult patients and one 12-year-old patient) with temporal lobe epilepsy and 45 hyperkinetic seizures in nine patients (eight adult patients and one 16-year-old patient) with frontal lobe epilepsy were analysed. Emotional facial expressions (such as fear, laughing, or anger), bilateral forceful elbow flexion, bilateral forceful grasping, facial flushing, and bilateral facial contraction were observed significantly more frequently in seizures of frontal lobe origin. Oroalimentary automatisms, seizures during wakefulness, salivation, and bilateral drop of the corners of the mouth were observed significantly more frequently in seizures of temporal lobe origin. Observation of a number of signs during hyperkinetic manifestations may help to predict whether a seizure originates from the frontal lobe or the temporal lobe.

[Case of Takayasu arteritis accompanying hypertrophic pachymeningitis].

A 71-year-old woman was referred to our department for evaluation of a right temporal headache. She had been diagnosed with Takayasu arteritis in her twenties but did not receive steroid therapy. A brain MRI scan detected thickened dura mater with abnormal enhancement on the right cerebral hemisphere. She was diagnosed with hypertrophic pachymeningitis, but she refused to be treated with steroids. Three months later, she noticed periorbital pain and blurred vision in her left eye, although the right temporal headache was reduced. A brain MRI scan detected thickened dura mater with abnormal enhancement on the left cerebral hemisphere adjacent to the left orbit and a swelled left superior rectus muscle with abnormal enhancement. However, the MRI results also showed that the thickening of the dura mater on the right cerebral hemisphere had improved. The new symptoms and the abnormalities revealed with imaging were resolved following steroid therapy. Takayasu arteritis mainly affects the large vessels, but can involve small and systemic vessels. This case presents a rare but possible link between hypertrophic pachymeningitis and Takayasu arteritis.

Spatiotemporal patterns of current source density in the prefrontal cortex of a behaving monkey.

One of the fundamental missions of neuroscience is to explore the input and output properties of neuronal networks to reveal their functional significance. However, it is technically difficult to examine synaptic inputs into neuronal circuits in behaving animals. Here, we conducted current source density (CSD) analysis on local field potentials (LFPs) recorded simultaneously using a multi-contact electrode in the prefrontal cortex (PFC) of a behaving monkey. We observed current sink task-dependent spatiotemporal patterns considered to reflect the synaptic input to neurons adjacent to the recording site. Specifically, the inferior convex current sink in the PFC was dominant during the delay period, whereas the current sink was prominent in the principal sulcus during the sample cue and test cue periods. Surprisingly, sulcus current sink patterns were spatially periodic, which corresponds to the columnar structure suggested by previous anatomical studies. The approaches used in the current study will help to elucidate how the PFC network performs executive functions according to its synaptic input.

Recurrent hypogeusia in a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Hypogeusia, a condition with diminished sense of taste, is caused by several conditions, including zinc deficiency and as a side-effect of drugs, but is not common in neurological disorders. A 55-year-old Japanese man with a 30-year history of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) presented with hypogeusia during hospitalization for a recurrence of CIDP. The hypogeusia improved after treatment with high-dose intravenous methylprednisolone (HIMP). Two years later, hypogeusia developed again. A complete taste deficit was revealed by a filter paper test. Brain MRI showed enhancement of the bilateral facial nerve ganglia. Hypogeusia was partially ameliorated after extensive immunosuppressive therapy with repeated HIMP and plasma exchange. Improvement was more prominent in the area innervated by the chorda tympani nerve than that innervated by the glossopharyngeal nerve. To our knowledge, this is the first report of recurrent hypogeusia, which might be caused by cranial nerve injury associated with CIDP.