A transdiagnostic evaluation of contrast avoidance across generalized anxiety disorder,major depressive disorder,and social anxiety disorder

BackgroundThe contrast avoidance model (CAM) proposes that persons with generalized anxiety disorder (GAD) are sensitive to sharp increases in negative emotion or decreases in positive emotion (i.e., negative emotional contrasts; NEC) and use worry to avoid NEC. Sensitivity to and avoidance of NEC could also be a shared feature of major depressive disorder (MDD) and social anxiety disorder (SAD).MethodsIn a large college sample (N = 1409), we used receiver operating characteristics analysis to examine the accuracy of a measure of emotional contrast avoidance in detecting probable GAD, MDD, and SAD.ResultsParticipants with probable GAD, MDD, and SAD all reported higher levels of contrast avoidance than participants without the disorder (Cohen’s d = 1.32, 1.62 and 1.53, respectively). Area under the curve, a measure of predictive accuracy, was .81, .87, and .83 for predicting probable GAD, MDD, and SAD, respectively. A cutoff score of 48.5 optimized predictive accuracy for probable GAD and SAD, and 50.5 optimized accuracy for probable MDD.ConclusionA measure of emotional contrast avoidance demonstrated excellent ability to predict probable GAD, MDD, and SAD. Sensitivity to and avoidance of NEC appears to be a transdiagnostic feature of these disorders.     

The transdiagnostic use of worry and rumination to avoid negative emotional contrasts following negative events: A momentary assessment study

The contrast avoidance model (CAM) suggests that individuals with generalized anxiety disorder (GAD) are sensitive to a sharp increase in negative and/or decrease in positive affect. They thus worry to increase negative emotion to avoid negative emotional contrasts (NECs). However, no prior naturalistic study has examined reactivity to negative events, or ongoing sensitivity to NECs, or the application of CAM to rumination. We used ecological momentary assessment to examine effects of worry and rumination on negative and positive emotion before and after negative events and intentional use of repetitive thinking to avoid NECs. Individuals with major depressive disorder (MDD) and/or GAD (N = 36) or without psychopathology (N = 27) received 8 prompts/day for 8 days and rated items on negative events, emotions, and repetitive thoughts. Regardless of group, higher worry/rumination before negative events was associated with less increased anxiety and sadness, and less decreased happiness from before to after the events. Participants with MDD/GAD (vs. controls) reported higher ratings on focusing on the negative to avoid NECs and greater vulnerability to NECs when feeling positive. Results support the transdiagnostic ecological validity for CAM extending to rumination and intentional engagement in repetitive thinking to avoid NECs among individuals with MDD/GAD.     

Comparison of clinical outcomes with two Transcranial Magnetic Stimulation treatment protocols for major depressive disorder

BackgroundTranscranial magnetic stimulation (TMS) is an effective treatment for major depressive disorder (MDD). The rest time between pulse trains is the inter-train interval (ITI). Since 2016, some TMS clinicians have adopted a stimulation protocol with shorter ITIs than were used in regulatory clinical trials.ObjectiveTo contrast treatment outcomes with the Standard TMS protocol (38.5 min per session) and the “Dash” protocol, which, at the shortest ITI, has a session duration of 18.75 min.MethodsRegistry data were collected at 103 practice sites. Of 7759 participants, 5010 were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the PHQ-9 before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. Within the ITT sample, 613 patients were treated with the Standard NeuroStar 38-min protocol and 1493 patients with the new Dash protocol. CGI-S ratings were obtained in smaller samples. Treatment outcomes were also examined in subgroups considered Completers, as well as the subgroups who met criteria for Full Adherence to the Standard or Dash protocol parameters.ResultsIn the ITT, Completer, and Fully Adherent samples, response (58–72%) and remission (28–53%) rates were notably high across PHQ-9 and CGI-S ratings. The Standard and Dash protocols did not differ in number of treatment sessions, and both manifested strong antidepressant effects.ConclusionsThe Standard and Dash protocols did not meaningfully differ in efficacy.     

Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES)

ObjectiveTo investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants.MethodsDetailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES.ResultsNeurodevelopment in infancy was normal in two patients, delayed in three. Epilepsy onset (age range: 2–6 years) was associated with appearance or aggravation of cognitive impairment, language regression and/or behavioral disorders. Worsening of epilepsy and of cognitive/behavioral disturbances paralleled by enhancement of non-rapid eye movement (NREM) sleep-related, frontally predominant, EEG epileptic discharges [spike-wave-index (SWI): range 60–96%] was consistent with ESES. In three patients, episodes of absence status epilepticus or aggravation of atypical absences occurred, in this latter case associated with striking increment of awake SWI. Speech/oro-motor dyspraxia was diagnosed in four patients. In two patients, long-term follow-up showed epilepsy remission and persistence of mild/moderate cognitive disorders and behavioral disturbances into adulthood.ConclusionsNovel findings of our study are occurrence also in females, normal neurodevelopment before epilepsy onset, epilepsy aggravation associated with enhanced awake SWI, mild/moderate evolution in adulthood and language disorder due to speech/oro-motor dyspraxia.SignificanceOur findings expand the phenotypic spectrum of CNKSR2-related ESES.     

Resting state oscillations suggest a motor component of Parkinson’s Impulse Control Disorders

ObjectivesImpulse control disorders (ICDs) in Parkinson’s disease (PD) have been associated with cognitive impulsivity and dopaminergic dysfunction and treatment. The present study tests the neglected hypothesis that the neurofunctional networks involved in motor impulsivity might also be dysfunctional in PD-ICDs.MethodsWe performed blind spectral analyses of resting state electroencephalographic (EEG) data in PD patients with and without ICDs to probe the functional integrity of all cortical networks. Analyses were performed directly at the source level after blind source separation. Discrete differences between groups were tested by comparing patients with and without ICDs. Gradual dysfunctions were assessed by means of correlations between power changes and clinical scores reflecting ICD severity (QUIP score).ResultsSpectral signatures of ICDs were found in the medial prefrontal cortex, the dorsal anterior cingulate and the supplementary motor area, in the beta and gamma bands. Beta power changes in the supplementary motor area were found to predict ICDs severity.ConclusionICDs are associated with abnormal activity within frequency bands and cortical circuits supporting the control of motor response inhibition.SignificanceThese results bring to the forefront the need to consider, in addition to the classical interpretation based on aberrant mesocorticolimbic reward processing, the issue of motor impulsivity in PD-ICDs and its potential implications for PD therapy.     

D-cycloserine normalizes long-term motor plasticity after transcranial magnetic intermittent theta-burst stimulation in major depressive disorder

ObjectivesMajor Depressive Disorder (MDD) is associated with glutamatergic alterations, including the N-methyl-D-aspartate receptor (NMDA-R). The NMDA-R plays an important role in synaptic plasticity, and individuals with MDD have been shown to have impairments in repetitive Transcranial Magnetic Stimulation (rTMS) motor plasticity. Here, we test whether D-cycloserine, a NMDA-R partial agonist, can rescue TMS motor plasticity in MDD.MethodsWe conducted randomized double-blind placebo-controlled crossover studies in healthy (n = 12) and MDD (n = 12) participants. We stimulated motor cortex using TMS intermittent theta burst stimulation (iTBS) with placebo or D-cycloserine (100 mg). Motor evoked potentials (MEPs) were sampled before and after iTBS. Stimulus response curves (SRC) were characterized at baseline, +90 minutes, and the following day.ResultsAcute iTBS MEP facilitation is reduced in MDD and is not rescued by D-cycloserine. After iTBS, SRCs shift to indicate sustained decrease in excitability in healthy participants, yet increased in excitability in MDD participants. D-cycloserine normalized SRC changes from baseline to the following day in MDD participants. In both healthy and MDD participants, D-cycloserine stabilized changes in SRC.ConclusionMDD is associated with alterations in motor plasticity that are rescued and stabilized by NMDA-R agonism.SignificanceAgonism of NMDA receptors rescues iTBS motor plasticity in MDD.     

α and θ oscillations in the subthalamic nucleus are potential biomarkers for Parkinson's disease with depressive symptoms

IntroductionAbnormal α oscillations in the bed nucleus of stria terminalis and subgenual cingulate of patients with depression correlate with symptom severity. Some Parkinson's disease (PD) patients also have abnormal θ-α oscillations in the subthalamic nucleus (STN). However, the relationship between abnormal θ-α oscillations and depressive symptoms in PD patients has not been determined. This study explored the correlation between α and θ oscillations of the STN and depressive symptoms in PD patients.MethodsWe conducted a retrospective case-control study on 36 PD patients with (dPD group) or without depressive symptoms (nPD group), analyzing the difference in the average power spectral density (PSD) of α and θ oscillations of the local field potential (LFP) recorded in the STN during deep brain stimulation (DBS), and their correlation with the Hamilton depression rating scale (HAMD) of PD patients during the same period.ResultsThe dPD group had a higher PSD of α oscillations and a lower PSD of θ oscillations in the left ventral STN. The PSD of α oscillations of the left ventral STN were positively correlated with the severity of depressive symptoms, whereas the PSD of θ oscillations of this location was negatively correlated with severity of depressive symptoms. The PSD of α and θ oscillations did not correlate with motor symptoms, sleep quality, or quality of life score.ConclusionAbnormal α and θ oscillations of the left ventral STN could be used as biomarkers of PD with depressive symptoms, which might guide STN-DBS treatment.     

Longitudinal bidirectional association between sleep and behavior problems at age 6 and 11 years

BackgroundAlthough a growing number of longitudinal studies have found that sleep problems precede behavior problems, few have examined potential bidirectional relationships longitudinally. The present study examined prospective associations between sleep problems and internalizing, externalizing, and attention problems over the course of childhood.MethodsParticipants included 775 children from the China Jintan Cohort Study. Sleep problems were rated by mothers at ages six and 11.5, as well as self-reported by children at age 11.5. Behavior problems were rated by mothers and teachers at ages six and 11.5, and self-reported by children at age 11.5.ResultsAt age six, 15.0% of children were reported to have sleep problems as rated by mothers. At age 11, this prevalence was 12% as rated by mothers and 20% as rated by youth. Bidirectional relationships between sleep problems and behavior problems were observed. Mother-reported sleep problems at age six were predictive of self-reported internalizing and attention problems at age 11.5, even after controlling for baseline behavioral problems. At age six, teacher-reported externalizing, internalizing, and attention problems, and mother-rated internalizing and externalizing problems were all related to sleep problems at age 11.5, even after controlling for baseline sleep problems. Other sociodemographic covariates including child sex, age, and parental education were controlled for.ConclusionsFindings provide further support for the reciprocal relationship between sleep problems and behavior problems. Early interventions that target both types of problems may be especially effective in preventing this aggravating health–behavior cycle.     

Prediction of motor Unified Parkinson's Disease Rating Scale scores in patients with Parkinson’s disease using surface electromyography

ObjectiveParkinson's disease (PD) is a chronic neurodegenerative disorder with increasing prevalence in the elderly. Especially patients with advanced PD often require complex medication regimens due to fluctuations, that is abrupt transitions from ON to OFF or vice versa. Current gold standard to quantify PD-patients’ motor symptoms is the assessment of the Unified Parkinson's Disease Rating Scale (UPDRS), which, however, is cumbersome and may depend upon investigators. This work aimed at developing a mobile, objective and unobtrusive measurement of motor symptoms in PD.MethodsData from 45 PD-patients was recorded using surface electromyography (sEMG) electrodes attached to a wristband. The motor paradigm consisted of a tapping task performed with and without dopaminergic medication. Our aim was to predict UPDRS scores from the sEMG characteristics with distinct regression models and machine learning techniques.ResultsA random forest regression model outnumbered other regression models resulting in a correlation of 0.739 between true and predicted UPDRS values.ConclusionsPD-patients’ motor affection can be extrapolated from sEMG data during a simple tapping task. In the future, such records could help determine the need for medication changes in telemedicine applications.SignificanceOur findings support the utility of wearables to detect Parkinson's symptoms and could help in developing tailored therapies in the future.     

Longitudinal study of striatal aromatic l-amino acid decarboxylase activity in patients with idiopathic rapid eye movement sleep behavior disorder

Study objectivesTo determine if nigrostriatal dopaminergic system function, evaluated by aromatic l-amino acid decarboxylase (AADC) activity using 6-[¹⁸F]fluoro-meta-tyrosine brain positron emission tomography (FMT-PET) can accurately and efficiently identify idiopathic rapid-eye-movement behavior disorder (IRBD) individuals at risk for conversion to a clinical diagnosis of Parkinson's disease (PD) or dementia with Lewy bodies (DLB).MethodsWe assessed prospectively striatal aromatic l-amino acid decarboxylase activity using FMT brain PET imaging in IRBD patients who were followed systematically every 1–3 months for 1–10 years. IRBD patients (n = 27) were enrolled in this prospective cohort study starting in 2009. Those who underwent follow-up scans between January 2011 and September 2014 (n = 24) were analyzed in the present study.ResultsOf the 24 IRBD patients with baseline and follow-up FMT-PET scans, 11 (45.8%) developed PD (n = 6) or DLB (n = 5). Compared to IRBD patients who were still disease-free, those who developed PD (n = 5) or DLB with parkinsonism (n = 1) had significantly reduced bilateral putaminal FMT uptake during the follow-up. Furthermore, the rate of FMT decline between baseline and follow-up scans was higher in all converted patients, even for those with DLB without parkinsonism, than in IRBD patients who remained disease-free.ConclusionsFMT-PET, which represents a dynamic change in AADC activity over time, may also be a useful predictor for the risk of conversion to PD or DLB over short-term clinical follow-up periods, or when testing neuroprotective and restorative strategies in the prodromal phases of PD or DLB.     

Prevalence and evolution of snoring and the associated factors in two-year-old children

ObjectivesTo evaluate the prevalence and persistence of snoring during the first two years of life in two Finnish birth cohorts and to assess the associated factors.Study designThe study population comprised 947 children from the CHILD-SLEEP (CS) and 1393 children from the FinnBrain (FB) birth cohorts. Questionnaires were provided to both parents when the child was 24 months of age. The questionnaire consisted of parts concerning the child's sleep and environmental factors.ResultsThe combined prevalence of habitual snoring in the two birth cohorts at the age of 24 months was 2.3% (95% CI 1.5–3.1), which is markedly lower than reported previously.Children suffering from recurrent infections (CS odds ratio (OR) 3.9, 95% CI 1.2–12.5) or asthma (FB OR 4.3, 1.4–13.5) snored habitually more often. Both the mother's (CS OR 3.2, 1.2–9.0) and father's (CS OR 3.4, 1.4–8.0) snoring every night added to the risk of the child snoring. In the multivariate models, parental snoring (CS adjusted odds ratio (OR_a) 2.8, 1.1–6.8), the mother's lower level of education (CS OR_a 2.9, 1.2–7.5, FB OR_a 2.1, 1.0–4.5), and the mother's lower monthly income (FB OR_a 2.9, 1.3–6.3) associated with the child's habitual snoring.ConclusionsThe prevalence of habitual snoring in two Finnish birth cohorts is lower than reported previously. The independent risk factors for habitual snoring at the age of two years were the parents' snoring and the mother's low income and low education.     

No enhanced (p-) α-synuclein deposition in gastrointestinal tissue of Parkinson's disease patients

BackgroundNeuronal alpha-synuclein (α-Syn) aggregation in the brain is believed to be a central component of the pathogenesis of Parkinson's disease (PD). α-Syn aggregates in the gastrointestinal tract have been suggested as a potential biomarker of PD that may even signal an early event of the Parkinsonian molecular pathology. However, studies further investigating this hypothesis have produced mixed results.ObjectiveTo determine whether the prevalence of α-Syn- and serine 129-phosphorylated α-Syn (Ser129p-α-Syn) depositions detected in intestine from PD patients differed from that of non-Parkinsonian controls.MethodsIn this retrospective study, we examined post-mortem small and large intestine samples of 25 PD patients and 20 age- and sex-matched controls without PD. Specimens were taken from archived paraffin-embedded tissue blocks. Immunohistochemical techniques were applied to detect α-Syn and Ser129p-α-Syn aggregates in situ. Immunoreactivity was quantified by a new approach that employed the detailed assessment of α-Syn- and Ser129p-α-Syn-positive morphological structures of the enteric nervous system (i.e., nerve fibers, myenteric and submucous plexus as well as ganglion cells).Resultsα-Syn immunoreactivity was a common finding in intestinal tissues from PD patients and controls. Importantly, α-Syn and Ser129p-α-Syn immunoreactivity were significantly reduced in PD patients compared to controls in each of the morphological structures examined.ConclusionsImmunohistochemical detection of intestinal α-Syn and Ser129p-α-Syn seems to be a frequent and potentially normal finding. Neither α-Syn nor Ser129p-α-Syn immunoreactivity may, therefore, be regarded as a molecular intestinal biomarker of PD pathology. Reduced intestinal α-Syn and Ser129p-α-Syn immunoreactivity in PD patients rather reflect PD-related neuronal degeneration.     

Subthalamic dynamic neural states correlate with motor symptoms in Parkinson’s Disease

ObjectiveThis study aims to discriminate the dynamic synchronization states from the subthalamic local field potentials and investigate their correlations with the motor symptoms in Parkinson’s Disease (PD).MethodsThe resting-state local field potentials of 10 patients with PD were recorded from the subthalamic nucleus. The dynamic neural states of multiple oscillations were discriminated and analyzed. The Spearman correlation was used to investigate the correlations between occurrence rate or duration of dynamic neural states and the severity of motor symptoms.ResultsThe proportion of long low-beta and theta synchronized state was significantly correlated with the general motor symptom and tremor, respectively. The duration of combined low/high-beta state was significantly correlated with rigidity, and the duration of combined alpha/high-beta state was significantly correlated with bradykinesia.ConclusionsThis study provides evidence that motor symptoms are associated with the neural states coded with multiple oscillations in PD.SignificanceThis study may advance the understanding of the neurophysiological mechanisms of the motor symptoms and provide potential biomarkers for closed-loop deep brain stimulation in PD.     

Real-time feedback on mobile application use for emergency management affects the door-to-needle time and functional outcomes in acute ischemic stroke

ObjectivesTime from onset to reperfusion affects mortality and favorable outcomes in patients with acute ischemic stroke (AIS). To evaluate effects of a real-time feedback mobile application on critical time intervals and functional outcomes in stroke emergency management.MethodsWe recruited patients with clinically suspected acute stroke from December 1st, 2020 until July 30st, 2022. All Patients had a non-contrast computed tomography (CT) and were included only if they had AIS. We divided the patients into two groups based on the date of availability on mobile application: pre-APP group and post-APP group. Onset to Door time (ODT), Door to Imaging Time (DIT), Door to Needle Time (DNT), Door to Puncture Time (DPT), Door to Recanalization Time (DRT), National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were compared between two groups.ResultsWe retrospectively enrolled 312 AIS patients who were assigned into the pre-APP group (n = 159) and post-APP group (n = 153). The median ODT time and median admission NIHSS score were not significantly different between the two groups at baseline assessment. The median (IQR) DIT [44 (30-60) min vs 28 (20-36) min, P < 0.01] and DNT [44 (36.25-52) min vs 39 (29-45) min, P = 0.02] both decreased significantly in two groups. However, median DPT and DRT time showed no significant differences. The proportion of mRS score of 0 to 2 at day 90 was significantly higher in the post-App group than in the pre-App group, at 82.4% and 71.7%, respectively (dominance ratio OR=1.84, 95% CI: 1.07 to 3.16, P = 0.03).ConclusionThe present findings indicate that the real-time feedback of stroke emergency management used by a mobile application have potential for shortening the DIT and DNT time and improve the prognosis of stroke patients.     

Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6

ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β_indirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: β_indirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β_indirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.     

Long-term health and socioeconomic consequences of childhood and adolescent-onset of narcolepsy

ObjectivesThere is limited information about the long-term consequences of childhood- and adolescent-onset narcolepsy on educational and social factors. Here, we estimate the long-term socioeconomic consequences and health care costs of narcolepsy.MethodsThe prospective cohort study included Danish individuals with narcolepsy onset in childhood or adolescence, diagnosed between 1994 and 2015. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. One hundred seventy-one patients were compared with 680 controls (mean index age, 15.2 years; SD, 3.4 years) matched for age, gender, and other sociodemographic characteristics.ResultsComparing the narcolepsy patient and control groups at age 20 years we found: (1) no differences in parental educational level; (2) patients had a significantly lower educational level than controls; (3) patients had significantly lower grade-point averages; (4) patients had a lower employment rate and lower-income, even when transfer payments were considered; and (5) patients' initial health care costs were higher. Patients had a higher mortality rate than controls, although the difference was not statistically significant.ConclusionNarcolepsy is associated with a significant influence on educational level, grading, social outcome, and welfare consequences. The development of narcolepsy is independent of parental social level.     

Intermuscular coherence as biomarker for pallidal deep brain stimulation efficacy in dystonia

ObjectiveFinding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients.MethodsEEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4–12 Hz) and beta band (13–30 Hz) peak coherences were studied.ResultsDystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3–10), TWSTRS: 22%, median 6.8 (IQR 4–9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit.ConclusionsPeak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity.SignificanceIMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice.     

Auditory neurophysiological development in early childhood: A growth curve modeling approach

ObjectiveDuring early childhood, the development of communication skills, such as language and speech perception, relies in part on auditory system maturation. Because auditory behavioral tests engage cognition, mapping auditory maturation in the absence of cognitive influence remains a challenge. Furthermore, longitudinal investigations that capture auditory maturation within and between individuals in this age group are scarce. The goal of this study is to longitudinally measure auditory system maturation in early childhood using an objective approach.MethodsWe collected frequency-following responses (FFR) to speech in 175 children, ages 3–8 years, annually for up to five years. The FFR is an objective measure of sound encoding that predominantly reflects auditory midbrain activity. Eliciting FFRs to speech provides rich details of various aspects of sound processing, namely, neural timing, spectral coding, and response stability. We used growth curve modeling to answer three questions: 1) does sound encoding change across childhood? 2) are there individual differences in sound encoding? and 3) are there individual differences in the development of sound encoding?ResultsSubcortical auditory maturation develops linearly from 3-8 years. With age, FFRs became faster, more robust, and more consistent. Individual differences were evident in each aspect of sound processing, while individual differences in rates of change were observed for spectral coding alone.ConclusionsBy using an objective measure and a longitudinal approach, these results suggest subcortical auditory development continues throughout childhood, and that different facets of auditory processing follow distinct developmental trajectories.SignificanceThe present findings improve our understanding of auditory system development in typically-developing children, opening the door for future investigations of disordered sound processing in clinical populations.     

Long-term health and socioeconomic outcome of obstructive sleep apnea in children and adolescents

BackgroundThere is limited information about the long-term outcome of obstructive sleep apnea (OSA) diagnosed in children and adolescents for educational and social factors. Here, we estimate the long-term socioeconomic outcome and health care costs of OSA.MethodsThe historical case-control cohort study included Danish individuals with OSA diagnosed in childhood or adolescence between 1994 and 2015. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. A total of 5419 were diagnosed during this period; of these we traced 1004 patients who we compared with 4085 controls (mean index age, 10.2 years; Standard Deviation (SD), 5.6 years) until the age of 20 years. Controls were matched for age, gender, and residency.ResultsComparing the OSA patient and control groups at age 20 years we found: 1) lower parental educational level; 2) significantly lower educational level also after adjustment for parental educational level; 3) lower school grade-point averages; 4) lower employment rate and lower income, which was not fully compensated when transfer payments were considered; and 5) patients' initial health care costs were higher due to higher morbidity. Patients showed higher mortality rates than controls (Hazard Ratio (HR) = 7.63, 95% CI = 4.87–11.95, P < 0.001).ConclusionsOSA in children and adolescent is associated with a significant influence on morbidity, mortality, educational level, grading, social outcome, and welfare consequences.     

Changes in the treatment of pediatric acute encephalopathy in Japan between 2015 and 2021: A national questionnaire-based survey

BackgroundAlthough acute encephalopathy (AE) is the most serious disorder associated with a viral infection in childhood and often causes death or neurological sequelae, standard treatments have not been established. In 2016, the Japanese Society of Child Neurology published the “Guidelines for the Diagnosis and Treatment of Acute Encephalopathy in Childhood 2016” (AE GL 2016). We conducted a questionnaire survey to evaluate the status of the treatment of pediatric AE in 2021 and the changes in treatment before and after the publication of the AE GL 2016.MethodsIn October 2021, questionnaires were mailed via the web to members of two mailing lists who were involved in the practice of pediatric neurological disorders.ResultsMost Japanese physicians (98 %) engaged in the treatment of pediatric AE used the AE GL 2016 as a clinical reference. From 2015 to 2021, the number of institutions that implemented targeted temperature management (TTM), vitamin administration, and continuous electroencephalographic monitoring increased significantly. Regarding the targeted temperature for TTM, the proportion of patients who were treated with normothermia (36.0–37.0 °C) increased from 2015 (55 %) to 2021 (79 %). The use of corticosteroids in patients with AE caused by a cytokine storm, which is recommended in the AE GL 2016, had already been implemented in most institutions by 2015.ConclusionThe AE GL 2016 could be used to disseminate the knowledge accumulated to date. Evidence of the efficacy and proper indication criteria for the treatment of AE is insufficient and must be further accumulated.