The Motor Network Reduces Multisensory Illusory Perception.

Observing mouth movements has strikingly effects on the perception of speech. Any mismatch between sound and mouth movements will result in listeners perceiving illusory consonants (McGurk effect), whereas matching mouth movements assist with the correct recognition of speech sounds. Recent neuroimaging studies have yielded evidence that the motor areas are involved in speech processing, yet their contributions to multisensory illusion remain unclear. Using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in an event-related design, we aimed to identify the functional roles of the motor network in the occurrence of multisensory illusion in female and male brains. fMRI showed bilateral activation of the inferior frontal gyrus (IFG) in audiovisually incongruent trials. Activity in the left IFG was negatively correlated with occurrence of the McGurk effect. The effective connectivity between the left IFG and the bilateral precentral gyri was stronger in incongruent than in congruent trials. The McGurk effect was reduced in incongruent trials by applying single-pulse TMS to motor cortex (M1) lip areas, indicating that TMS facilitates the left IFG-precentral motor network to reduce the McGurk effect. TMS of the M1 lip areas was effective in reducing the McGurk effect within the specific temporal range from 100 ms before to 200 ms after the auditory onset, and TMS of the M1 foot area did not influence the McGurk effect, suggesting topographical specificity. These results provide direct evidence that the motor network makes specific temporal and topographical contributions to the processing of multisensory integration of speech to avoid illusion.SIGNIFICANCE STATEMENT The human motor network, including the inferior frontal gyrus and primary motor cortex lip area, appears to be involved in speech perception, but the functional contribution to the McGurk effect is unknown. Functional magnetic resonance imaging revealed that activity in these areas of the motor network increased when the audiovisual stimuli were incongruent, and that the increased activity was negatively correlated with perception of the McGurk effect. Furthermore, applying transcranial magnetic stimulation to the motor areas reduced the McGurk effect. These two observations provide evidence that the motor network contributes to the avoidance of multisensory illusory perception.

Factors correlating to decisions for prescribing pharmacological treatment and referrals in suspected peripheral neuropathy cases in chat consultation-based application.

Introduction: Since the COVID-19 pandemic, there has been increasing use ofchat-based telemedicine, including for patients with neuropathy complaints. It is imperative to learn how to effectively use telemedicine. This study describes the characteristics of patients with neuropathy complaints in chat-based telemedicine services in Indonesia and their influence on treatment decisions and referrals. Methods: This is a retrospective cross-sectional study during the COVID-19 pandemic era (March 2020 to December 2021) using anonymous secondary data from patient chat databases on Indonesian application-based telemedicine services (Halodoc, Alodokter, Good Doctor, and Milvik). We applied bivariate and multivariate analysis. Results: We obtained 1051 patients with suspected peripheral nerve complaints (4 per 10,000) from a total of 2,199,527 user consultations, with the majority being 40-64 years old females and diabetes mellitus was the leading comorbid (90.7%). Most patients received treatment (90.7%) and only 11.4% patients were referred. Multivariate analysis showed that treatment was more likely to be given by a neurologist (p < 0.01). Chronic symptoms (p < 0.01) and previous laboratory/other tests (p = 0.01) decreased the likelihood of medication prescription. Referrals were more likely to be given to chronic onset (p = 0.02), hypertension and heart disease (p < 0.01), and previous laboratory/other tests (p = 0.02). The opposite was true for age≥65 years, female (p = 0.04), and neurologists or other specialists as responders (p < 0.01). Conclusion: We identified several factors that influence the treatment decision such as female patients and onset. Meanwhile, age, sex, chronic symptoms, history of hypertension and heart disease, and previous laboratory/other tests may influence the referral decisions. General practitioners were more likely to refer the patients whereas neurologists or other specialists were more likely to give treatment. Chat-based telemedicine services can still be developed in the future to be better.

Pulmonary Function Assessment in Myasthenia Gravis Patients in a National Referral Hospital in Indonesia.

Purpose: Myasthenia gravis (MG) can cause respiratory muscle weakness and the need of ventilator support. Spirometry as the gold standard for pulmonary function examination has limited availability, especially in our hospital which is only available in outpatient clinic during work hours (not in emergency room or patient room). Furthermore, all primary healthcare in Indonesia do not have spirometry equipment, thus other alternatives are required. This study aimed to analyze the relationship between a single breath counting test (SBCT), peak flow meter (PFM), and spirometry to assess pulmonary function in MG patients in a national referral hospital in Indonesia. Patients and Methods: A single-center, cross-sectional study was conducted and SBCT, PFM, and spirometry examination were performed in MG patients and healthy controls. Results: Seventy patients, aged 47.7 ± 13.4 years old, participated in this study. SBCT, forced vital capacity first second (FVC1), and forced expiratory volume first second (FEV1) value between MG patients and healthy controls showed a significant difference, in which healthy controls have higher SBCT, FVC1, and FEV1 values (p = 0.000, p = 0.000 and p = 0.001 respectively). There was a significant difference between PFM with SBCT and FVC1 value in MG patients. Strong correlation was found between SBCT and FVC1 in MG patients. Conclusion: MG patients had worse pulmonary function compared to healthy controls. SBCT and PFM examination have a significant correlation with FVC1 in MG patients. Therefore, SBCT and PFM can be used as a bedside tool to detect respiratory impairment in MG patients.

Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital.

Objective: Menstrual disorders are more common in women with epilepsy than in those without epilepsy. This study aimed to examine the characteristics of reproductive function in women with epilepsy at an Indonesian national referral hospital. Methods: A case-control study was conducted from March 2020 to March 2021. Women with and without epilepsy aged ≥18 years were enrolled. All women were premenopausal before epilepsy diagnosis. Data on demographic characteristics, menstrual profiles, epileptic syndrome, seizure type, seizure frequency, etiology, localization, and anticonvulsant medication were collected. Hormone levels (follicle stimulating hormone, luteinizing hormone, prolactin, and estradiol) were measured. Results: A total of 72 women with and 50 without epilepsy (controls) were included. Dysmenorrhea was more common in women with epilepsy than in those without (59.7 vs. 20%, p < 0.001; odds ratio: 5.931 [95% confidence interval: 2.566-13.709]). Marriage rates were higher in women without epilepsy (82 vs. 45.8%, p < 0.001). No difference was found in hormone levels between the groups. The frequency of seizures was associated with prolactin and estradiol levels (p < 0.001). Polytherapy with clobazam was associated with menstrual cycle regularity. In women with epilepsy with menstrual disorders, valproic acid was associated with higher estradiol levels (p = 0.001) and lamotrigine with lower follicle stimulating hormone levels (p = 0.008). Significance: Women with epilepsy experienced more dysmenorrhea. A higher frequency of seizures associated with lower prolactin and estradiol levels. Polytherapy with clobazam was associated with irregular menstrual cycles, while valproic acid and lamotrigine was associated with estradiol and follicle stimulating hormone levels.

Enhancement of LTD-like plasticity by associative pairing of quadripulse magnetic stimulation with peripheral nerve stimulation.

OBJECTIVE: Quadripulse magnetic stimulation (QPS) is useful for changing corticospinal excitability, but the long-term depression (LTD)-like effect considerably has low responder rate. To solve this problem, we modified inhibitory QPS (QPSLTD) by pairing it with the application of an electrical stimulus (ES) to peripheral nerves (paired-associative QPS [PA-QPSLTD]), and investigated the effects of PA-QPSLTD on motor-evoked potentials (MEPs). METHODS: The peripheral-nerve ES was applied at two timings with a synchrony to transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). The intrapair interval between ES and TMS was the N20-peak latency plus 2 ms for PALTP-QPSLTD, and N20-peak latency minus 5 ms for PALTD-QPSLTD. MEPs elicited by TMS over the left M1 were recorded from the right abductor pollicis brevis muscle before and after the interventions. The responder rates of PALTD-QPSLTD and QPSLTD was also studied. RESULTS: The PALTD-QPSLTD induced larger LTD-like effect than QPSLTD, and the PALTP-QPSLTD induced smaller aftereffect than QPSLTD. The responder rates were significantly higher for PALTD-QPSLTD than for QPSLTD. CONCLUSIONS: The new protocol, PALTD-QPSLTD, induces powerful and consistent LTD-like aftereffects in the corticospinal tract neurons. SIGNIFICANCE: PALTD-QPSLTD is suitable for use in physiological evaluations and therapeutic approaches in various neurological disorders.

The stigma paradox: Perception of quality-of-life in people with epilepsy among themselves, the family, and the general population in Indonesian urban areas.

OBJECTIVE: To understand quality of life (QoL) perceptions of people with epilepsy (PWE) through knowledge, attitude, and behavior (KAB); PWE; their families (PWEf); and the general population (GPop). METHODS: This descriptive study was conducted in Jakarta and its surrounding cities from January to December 2019. PWE were recruited from outpatient clinics. PWEf were caregivers who lived with PWE. GPop were age matched, randomly selected, and interviewed for public events. The perception of QoL was scaled from 1 to 5 (1 =very poor to 5 =very good). KAB was obtained from open- and closed-ended questionnaires, scaled from 1 to 5 (1 =strongly disagree to 5 =strongly agree). The differences in each group were analyzed using t-tests and analysis of variance. RESULTS: We interviewed 371 participants, predominantly female and senior high school graduates. Unemployment and singlehood were higher in PWEs. QoL perception in PWE was similar to GPop (3.01 [0.75] vs. 3.07 [0.76], p = 0.49), yet lower in PWEf (2.78 [0.76]; p < 0.05). According to PWE and PWEf, not being stigmatized and support from family were essential, while GPop emphasized the medical perspective. Overall, the knowledge section had the lowest score and behavior had the highest. The GPop was uncertain about the cause of epilepsy in K2 (3.73 [1.05]), K4 (3.35 [1.24]), and K7 (2.93 [1.08]); p < 0.001. Despite positive behavior, GPop were unwilling to marry (B4) nor had PWE as their in-laws (B5); (2.83 [0.73] and 2.78 [0.77]; p < 0.001). Moreover, PWEf were still doubtful about GPop's acceptance (B1) (3.86 [0.38] vs 4.00 [0.40]; p < 0.05). CONCLUSION: The perception of QoL in PWE did not seem to be directly associated with KAB. Despite similar knowledge of PWE and PWEf, better perceptions came from PWE and GPop. The reluctance to form deeper bonds between GPop and PWE, along with PWEf's skepticism, could lead to low self-esteem, unemployment, and unmarried rates. Further studies are required to elaborate on these issues.

Altered mental status in moderate-severe traumatic brain injury in Indonesia: the clinical manifestation and EEG features of non-convulsive status epilepticus.

INTRODUCTION: Moderate-to-severe traumatic brain injury (msTBI) can cause non-convulsive status epilepticus (NCSE). Electroencephalography (EEG) is employed as a diagnostic tool due to the non-specificity of clinical symptoms. This study aimed to identify clinical and EEG features related to NCSE in patients with msTBI. METHODS: This was a cross-sectional study. Suspected NCSE in msTBI was examined using EEG data collected in consecutive patients from January 2017 to December 2019 at Dr. Cipto Mangunkusumo Hospital, Jakarta. Diagnoses of NCSE were made based on clinical manifestations and EEG features using the modified Salzburg Consensus Criteria for NCSE (mSCNC). RESULTS: Of the 39 msTBI patients, 19 were diagnosed with NCSE; only two fulfilled the definitive criteria, and the remaining were possible NCSE. Delirium and perceptual impairment were only found in NCSE, while psychomotor agitation was higher (12.8% vs. 5.1% in NCSE vs. non-NCSE). The most common EEG feature was rhythmic activity (>0.5 Hz) without fluctuation, which improved with anti-epileptic drug administration. The Glasgow Coma Scale (GCS) score at onset and at hospitalisation discharge was significantly lower in patients with NCSE. The lesions in NCSE mostly originated from the temporal lobe. Injury to the temporal lobe had a significant relationship with NCSE occurrence (p = 0.036, odds ratio 11.45 [95% confidence interval 1.17-111.6]). DISCUSSION: Post-traumatic NCSE can manifest as an alteration in mental status that could lead to missed diagnosis. In this study, delirium, perceptual impairment, and psychomotor agitation were confirmed as NCSE using EEG. The most common discharge originated from the injured temporal lobe, and this site was a significant factor associated with NCSE in patients with msTBI. CONCLUSION: NCSE can be found in msTBI cases with clinical manifestations of altered mental status, psychomotor agitation, and hallucination. An injured temporal lobe was a susceptible site for the development of NCSE.

Event-Related Potentials During Decision-Making in a Mixed-Strategy Game.

The decisions we make are sometimes influenced by interactions with other agents. Previous studies have suggested that the prefrontal cortex plays an important role in decision-making and that the dopamine system underlies processes of motivation, motor preparation, and reinforcement learning. However, the physiological mechanisms underlying how the prefrontal cortex and the dopaminergic system are involved in decision-making remain largely unclear. The present study aimed to determine how decision strategies influence event-related potentials (ERPs). We also tested the effect of levodopa, a dopamine precursor, on decision-making and ERPs in a randomized double-blind placebo-controlled investigation. The subjects performed a matching-pennies task against an opposing virtual computer player by choosing between right and left targets while their ERPs were recorded. According to the rules of the matching-pennies task, the subject won the trial when they chose the same side as the opponent, and lost otherwise. We set three different task rules: (1) with the alternation (ALT) rule, the computer opponent made alternating choices of right and left in sequential trials; (2) with the random (RAND) rule, the opponent randomly chose between right and left; and (3) with the GAME rule, the opponent analyzed the subject's past choices to predict the subject's next choice, and then chose the opposite side. A sustained medial ERP became more negative toward the time of the subject's target choice. A biphasic potential appeared when the opponent's choice was revealed after the subject's response. The ERPs around the subject's choice were greater in RAND and GAME than in ALT, and the negative peak was enhanced by levodopa. In addition to these medial ERPs, we observed lateral frontal ERPs tuned to the choice direction. The signals emerged around the choice period selectively in RAND and GAME when levodopa was administered. These results suggest that decision processes are modulated by the dopamine system when a complex and strategic decision is required, which may reflect decision updating with dopaminergic prediction error signals.

Nonconvulsive Status Epilepticus in Metabolic Encephalopathy in Indonesia Referral Hospital.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is often underdiagnosed in patients with metabolic encephalopathy (ME). The diagnosis of ME should be made specifically to recognize the underlying etiology. Delay in seizure identification and making a diagnosis of NCSE contributed to the poor outcome. OBJECTIVE: This study aimed to find the incidence and outcome of NCSE in patients with ME. METHODS AND MATERIAL: This was an observational prospective cross-sectional study in patients with ME in emergency and critical care units in Cipto Mangunkusumo General Hospital. The diagnosis of NCSE was based on EEG using Salzburg Criteria for Nonconvulsive Status Epilepticus (SCNC). The outcome was assessed within 30 days after the NCSE diagnosis has been made. RESULTS: A total of 50 patients with ME were involved in this study. NCSE was confirmed in 32 subjects (64%). The most common etiology of ME was sepsis (58%). The mortality rate in the NCSE and non-NCSE group was 40.6% vs 44.4%. Multiple aetiologies were risk factors to poor outcome in the NCSE group. CONCLUSIONS: The incidence of NCSE among patients with ME at our hospital was high. Despite the anti-epileptic treatment of the NCSE group, the underlying cause of ME is still the main factor that affected the outcome. Therefore, aggressive treatment of anti-epileptic drug (AED) should be very carefully considered knowing the possible side-effect that might worsen the outcome of patients with ME.

Case series: COVID-19 in patients with mild to moderate myasthenia gravis in a National Referral Hospital in Indonesia.

BACKGROUND: During the COVID-19 pandemic, patients with myasthenia gravis (MG) are most likely to be affected by this situation. Corticosteroids and immunosuppressant agents increase the risk of severe infection. Furthermore, viral infection and some medications in COVID-19 may exacerbate MG symptoms. CASE DESCRIPTION: We presented three patients with MG who contracted COVID-19. All of the patients had a favourable outcome. Only one patient who was not treated with corticosteroids or immunosuppressant therapy experienced deterioration of MG symptoms, while the other patients who received immunosuppressant therapy did not develop MG exacerbation. Surprisingly, azithromycin did not provoke myasthenic crisis (MC) in patients with normal MGFA classification. CONCLUSION: Using immunosuppressant agents may not lead to MG deterioration and may not be related to unfavourable outcomes.

Direct comparison of efficacy of the motor cortical plasticity induction and the interindividual variability between TBS and QPS.

BACKGROUND: Theta burst stimulation (TBS) and quadripulse stimulation (QPS) are known to induce synaptic plasticity in humans. There have been no head-to-head comparisons of the efficacy and variability between TBS and QPS. OBJECTIVE: To compare the efficacy and interindividual variability between the original TBS and QPS protocols. We hypothesized that QPS would be more effective and less variable than TBS. METHODS: Forty-six healthy subjects participated in this study. Thirty subjects participated in the main comparison experiment, and the other sixteen subjects participated in the experiment to obtain natural variation in motor-evoked potentials. The facilitatory effects were compared between intermittent TBS (iTBS) and QPS5, and the inhibitory effects were compared between continuous TBS (cTBS) and QPS50. The motor-evoked potential amplitudes elicited by transcranial magnetic stimulation over the primary motor cortex were measured before the intervention and every 5 min after the intervention for 1 h. To investigate the interindividual variability, the responder/nonresponder/opposite-responder rates were also analyzed. RESULTS: The facilitatory effects of QPS5 were greater than those of iTBS, and the inhibitory effects of QPS50 were much stronger than those of cTBS. The responder rate of QPS was significantly higher than that of TBS. QPS had a smaller number of opposite responders than TBS. CONCLUSION: QPS is more effective and stable for synaptic plasticity induction than TBS.

Assessment of Cognitive and Motor Skills in Parkinson's Disease by a Robotic Object Hitting Game.

Parkinson's disease (PD) patients experience various symptoms including extrapyramidal motor disturbances and cognitive impairments, which cause difficulties in daily life. However, PD patients have rarely been studied under realistic task situations that require high-level interaction of cognitive and motor skills. The aim of this study was to investigate the contribution of cognitive and motor factors to the performance of PD patients under high cognitive and kinematic loads. Twenty-six PD patients and 14 control subjects participated in the study. The PD patients performed a task involving hitting targets and avoiding distractors in levodopa On and Off states. A robotic manipulandum device recorded the numbers of target and distractor hits and hand kinematics, including movement area and speed. Performance on standard cognitive batteries and the Movement Disorder Society - Unified Parkinson's Disease Rating Scale motor scores were examined. The results indicated that the PD patients hit significantly fewer targets and more distractors than did the controls (p < 0.05). In PD patients, the average hand speed was slower and the area of hand movement was smaller than those of the control subjects (p < 0.001). Levodopa significantly increased the average hand speed and movement area (p < 0.01), but levodopa had an insignificant effect on the number of correct targets hit and erroneous distractor hits. The scores of cognitive batteries predicted the performance with regard to both targets hit and distractor avoidance. Our results were indicative of a dynamic interaction between cognitive and kinematic skills while the PD patients performed a virtual reality game. Single-dose levodopa enhanced kinematic capacity, and the global intelligence level predicted game performance.

Variability in Response to Quadripulse Stimulation of the Motor Cortex.

BACKGROUND: Responses to plasticity-inducing brain stimulation protocols are highly variable. However, no data are available concerning the variability of responses to quadripulse stimulation (QPS). OBJECTIVE: We assessed the QPS parameters of motor cortical plasticity induction in a systematic manner, and later investigated the variability of QPS using optimal parameters. METHODS: First, two different interburst intervals (IBI) with the same total number of pulses were compared. Next we investigated three different IBIs with a different total number of pulses but with same duration of intervention. We also compared the after-effects of monophasic and biphasic QPS. Finally, variability of QPS was tested in 35 healthy subjects. Twenty motor evoked potentials (MEPs) were measured every 5-10 min for up to one hour after intervention. RESULTS: QPS at an IBI of 5 s produced MEPs changes that are dependent on the interstimulus interval of the four magnetic pulses, consistent with previous reports. Unexpectedly, QPS at an IBI of 2.5 s did not induce any plasticity, even with the same total number of pulses, that is, 1440. QPS at an IBI of 7.5 s produced a variable response but was likely to be comparable to conventional QPS. Biphasic QPS had shorter lasting after-effects compared with monophasic QPS. Finally, the after-effects of QPS were relatively consistent across subjects: more than 80% of subjects responded as expected in the excitatory QPS at an IBI of 5 s. CONCLUSIONS: The IBI, total duration of the procedure and pulse waveform strongly affected the magnitude or duration of the plasticity induced by QPS. In this cohort, 80% of subjects responded to excitatory QPS as expected.