Risk Factors Associated with Chemotherapy-Induced Nausea and Vomiting Among Women with Breast Cancer Receiving Highly Emetogenic Chemotherapy: Individual Patient-Based Analysis of Three Prospective Antiemetic Trials.

Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated. Results: Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and "no nausea" in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and "no nausea" in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusion: The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

Age-related increases in right hemisphere support for prosodic processing in children.

Language comprehension is a complex process involving an extensive brain network. Brain regions responsible for prosodic processing have been studied in adults; however, much less is known about the neural bases of prosodic processing in children. Using magnetoencephalography (MEG), we mapped regions supporting speech envelope tracking (a marker of prosodic processing) in 80 typically developing children, ages 4-18 years, completing a stories listening paradigm. Neuromagnetic signals coherent with the speech envelope were localized using dynamic imaging of coherent sources (DICS). Across the group, we observed coherence in bilateral perisylvian cortex. We observed age-related increases in coherence to the speech envelope in the right superior temporal gyrus (r = 0.31, df = 78, p = 0.0047) and primary auditory cortex (r = 0.27, df = 78, p = 0.016); age-related decreases in coherence to the speech envelope were observed in the left superior temporal gyrus (r = - 0.25, df = 78, p = 0.026). This pattern may indicate a refinement of the networks responsible for prosodic processing during development, where language areas in the right hemisphere become increasingly specialized for prosodic processing. Altogether, these results reveal a distinct neurodevelopmental trajectory for the processing of prosodic cues, highlighting the presence of supportive language functions in the right hemisphere. Findings from this dataset of typically developing children may serve as a potential reference timeline for assessing children with neurodevelopmental hearing and speech disorders.

Children with autism spectrum disorder who demonstrate normal language scores use a bottom-up semantic processing strategy: Evidence from N400 recordings.

INTRODUCTION: The N400 is an electrophysiological component that reflects lexical access and integration of words with mental representations. METHODS: Thirty-five young children with a range of language capabilities (n = 21 neurotypical controls, 10 males, mean age = 6.3 ± 0.9 years; n = 14 children with autism, 12 males, mean age = 6.4 ± 1.1 years) completed an auditory semantic categorization paradigm to evoke the N400. Electroencephalograph (EEG) data were acquired with a 64-channel electrode cap as children listened via ear inserts to binaurally presented single syllable words and decided whether the words were congruent (in) or incongruent (out) with a pre-specified category. EEG data were filtered, epoched, and averaged referenced, and global field power (GFP) was computed. The amplitude of the N400 peak in the GFP was submitted to a multiple linear regression analysis. RESULTS: N400 amplitude was found to predict language scores only for the children with ASD who have language scores in the normal range (r2  = 0.72). CONCLUSIONS: This finding that N400 amplitude only predicted language scores in children with ASD and normal language scores suggests that these children may rely more on basic semantic processing (as reflected by the N400) and less on anticipating and predicting upcoming words. This suggests preferential utilization of a bottom-up strategy to access higher order language.

Richer than we thought: neurophysiological methods reveal rich-club network development is frequency- and sex-dependent.

A set of highly connected brain regions called the "rich-club" are vital in integrating information across the functional connectome. Although the literature has identified some changes in rich-club organization with age, little is known about potential sex-specific developmental trajectories, and neurophysiologically relevant frequency-dependent changes have not been established. Here we examine the frequency- and sex-dependent development of rich-club organization using magnetoencephalography in a large normative sample (N = 383) over a wide age span (4-39 years). We report strong divergence between males and females across alpha, beta, and gamma frequencies. While males show increased or no change in rich-club organization with age, females show a consistent, non-linear trajectory that increases through childhood, shifting direction in early adolescence. Using neurophysiological modalities for capturing complex inter-relations between oscillatory dynamics, age, and sex, we establish diverging, sex-specific developmental trajectories of the brain's core functional organization, critically important to our understanding of brain health and disease.

Atypical oscillatory dynamics during emotional face processing in paediatric obsessive-compulsive disorder with MEG.

Children and youth with obsessive-compulsive disorder (OCD) demonstrate difficulties with social, emotional and cognitive functions in addition to the core diagnosis of obsessions and compulsions. This is the first magnetoencephalography (MEG) study to examine whole-brain neurophysiological functional connectivity of emotional face processing networks in paediatric OCD. Seventy-two participants (OCD: n = 36; age 8-17 yrs; typically developing controls: n = 36, age 8-17 yrs) completed an implicit emotional face processing task in the MEG. Functional connectivity networks in canonical frequency bands were compared between groups, and within OCD and control groups between emotions (angry vs. happy). Between groups, participants with OCD showed increased functional connectivity in the gamma band to angry faces, suggesting atypical perception of angry faces in OCD. Within groups, the OCD group showed greater engagement of the beta band, suggesting the over-use of top-down processing when perceiving happy versus angry emotions, while controls engaged in bottom-up gamma processing, also greater to happy faces. Over-activation of top-down processing has been linked to difficulties modifying one's cognitive set. Findings establish altered patterns of neurophysiological connectivity in children with OCD, and are striking in their oscillatory specificity. Our results contribute to a greater understanding of the neurobiology of the disorder, and are foundational for the possibility of alternative targets for intervention.

Cerebellar gamma-aminobutyric acid: Investigation of group effects in neurodevelopmental disorders.

Neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are thought to arise in part from the disruption in the excitatory/inhibitory balance of gamma-aminobutyric acid (GABA) and glutamate in the brain. Recent evidence has shown the involvement of the cerebellum in cognition and affect regulation, and cerebellar atypical function or damage is reported frequently in NDDs. Magnetic resonance spectroscopy studies have reported decreases in GABA in cortical brain areas in the NDDs, however, GABA levels in the cerebellum have not been examined. To determine possible group effects, we used a MEGA-PRESS acquisition to investigate GABA+ levels in a cerebellar voxel in 343 individuals (aged 2.5-22 years) with ASD, ADHD, OCD and controls. Using a mixed effects model, we found no significant differences between groups in GABA+ concentration. Our findings suggest that cerebellar GABA+ levels do not differentiate NDD groups.

Characterising the spatial and oscillatory unfolding of Theory of Mind in adults using fMRI and MEG.

Theory of Mind (ToM) is a core social cognitive skill that refers to the ability to attribute mental states to others. ToM involves understanding that others have beliefs, thoughts and desires that may be different from one's own and from reality. ToM is crucial to predict behaviour and navigate social interactions. This study employed the complementary methodological advantages of both functional MRI (fMRI) and magnetoencephalography (MEG) to examine the neural underpinnings of ToM in adults. Twenty healthy adults were first recruited to rate and describe 28 videos (15s long), each containing three moving shapes designed to depict either social interactions or random motion (control condition). The first sample of adults produced consistent narratives for 6 of those social videos and of those, 4 social videos and 4 control videos were chosen to include in the neuroimaging study. Another sample of twenty-five adults were then recruited to complete the neuroimaging in MEG and fMRI. In fMRI, we found increased activation in frontal-parietal regions in the social compared to the control condition corroborating previous fMRI findings. In MEG, we found recruitment of ToM networks in the social condition in theta, beta and gamma bands. The right supramarginal and angular gyri (right temporal parietal junction), right inferior parietal lobe and right temporal pole were recruited in the first 5s of the videos. Frontal regions such as the superior frontal gyrus were recruited in the second time window (5-10s). Brain regions such as the bilateral amygdalae were also recruited (5-10s), indicating that various social processes were integrated in understanding the social videos. Our study is one of the first to combine multi-modal neuroimaging to examine the neural networks underlying social cognitive processes, combining the strengths of the spatial resolution of fMRI and temporal resolution of MEG. Understanding this information from both modalities helped delineate the mechanism by which ToM processing unfolds over time in healthy adults. This allows us to determine a benchmark against which clinical populations can be compared.

Epilepsy disrupts hippocampal phase precision and impairs working memory.

OBJECTIVE: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy. METHODS: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared. RESULTS: Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03). SIGNIFICANCE: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population.

Social-Cognitive Network Connectivity in Preterm Children and Relations With Early Nutrition and Developmental Outcomes.

Infants born very low birth weight (VLBW, < 1,500 g) are at a heightened risk for structural brain abnormalities and social-cognitive deficits, which can impair behavioural functioning. Resting-state fMRI, reflecting a baseline level of brain activity and underlying social-cognitive processes, has also been reported to be altered in children born VLBW. Yet very little is known about the functional networks underlying social cognition using magnetoencephalography (MEG) and how it relates to neonatal factors and developmental outcomes. Thus, we investigated functional connectivity at rest in VLBW children and the associations with early nutrition and IQ and behavioural problems. We collected resting-state MEG recordings and measures of IQ and social-cognitive behaviour, as well as macronutrient/energy intakes during initial hospitalisation in 5-year-old children born VLBW (n = 37) compared to full-term (FT; n = 27) controls. We examined resting-state network differences controlling for sex and age at scan. Functional connectivity was estimated using the weighted phase lag index. Associations between functional connectivity with outcome measures and postnatal nutrition were also assessed using regression analyses. We found increased resting-state functional connectivity in VLBW compared to FT children in the gamma frequency band (65-80 Hz). This hyper-connected network was primarily anchored in frontal regions known to underlie social-cognitive functions such as emotional processing. In VLBW children, increased functional connectivity was related to higher IQ scores, while reduced connectivity was related to increased behavioural problems at 5 years of age. These within-group associations were found in the slower frequency bands of theta (4-7 Hz) and alpha (8-12 Hz), frequently linked to higher-order cognitive functions. We also found significant associations between macronutrient (protein and lipid) and energy intakes during the first postnatal month with functional connectivity at preschool-age, highlighting the long-term impacts of postnatal nutrition on preterm brain development. Our findings demonstrate that at preschool-age, VLBW children show altered resting-state connectivity despite IQ and behaviour being in the average range, possibly reflecting functional reorganisation of networks to support social-cognitive and behavioural functioning. Further, our results highlight an important role of early postnatal nutrition in the development of resting-state networks, which in turn may improve neurodevelopmental outcomes in this vulnerable population.

Shared and Distinct Patterns of Functional Connectivity to Emotional Faces in Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder Children.

Impairments in emotional face processing are demonstrated by individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which is associated with altered emotion processing networks. Despite accumulating evidence of high rates of diagnostic overlap and shared symptoms between ASD and ADHD, functional connectivity underpinning emotion processing across these two neurodevelopmental disorders, compared to typical developing peers, has rarely been examined. The current study used magnetoencephalography to investigate whole-brain functional connectivity during the presentation of happy and angry faces in 258 children (5-19 years), including ASD, ADHD and typically developing (TD) groups to determine possible differences in emotion processing. Data-driven clustering was also applied to determine whether the patterns of connectivity differed among diagnostic groups. We found reduced functional connectivity in the beta band in ASD compared to TD, and a further reduction in the ADHD group compared to the ASD and the TD groups, across emotions. A group-by-emotion interaction in the gamma frequency band was also observed. Greater connectivity to happy compared to angry faces was found in the ADHD and TD groups, while the opposite pattern was seen in ASD. Data-driven subgrouping identified two distinct subgroups: NDD-dominant and TD-dominant; these subgroups demonstrated emotion- and frequency-specific differences in connectivity. Atypicalities in specific brain networks were strongly correlated with the severity of diagnosis-specific symptoms. Functional connectivity strength in the beta network was negatively correlated with difficulties in attention; in the gamma network, functional connectivity strength to happy faces was positively correlated with adaptive behavioural functioning, but in contrast, negatively correlated to angry faces. Our findings establish atypical frequency- and emotion-specific patterns of functional connectivity between NDD and TD children. Data-driven clustering further highlights a high degree of comorbidity and symptom overlap between the ASD and ADHD children.

Dynamic functional brain network connectivity during pseudoword processing relates to children's reading skill.

Learning to read requires children to link print (orthography) with its corresponding speech sounds (phonology). Yet, most EEG studies of reading development focus on emerging functional specialization (e.g., developing increasingly refined orthographic representations), rather than directly measuring the functional connectivity that links orthography and phonology in real time. In this proof-of-concept study we relate children's reading skill to both orthographic specialization for print (via the N170, also called the N1, event related potential, ERP) and orthographic-phonological integration (via dynamic/event-related EEG phase synchronization - an index of functional brain network connectivity). Typically developing English speaking children (n = 24; 4-14 years) and control adults (n = 20; 18-35 years) viewed pseudowords, consonants and unfamiliar false fonts during a 1-back memory task while 64-channel EEG was recorded. Orthographic specialization (larger N170 for pseudowords vs. false fonts) became more left-lateralized with age, but not with reading skill. Conversely, children's reading skill correlated with functional brain network connectivity during pseudoword processing that requires orthography-phonology linking. This was seen during two periods of simultaneous low frequency synchronization/high frequency desynchronization of posterior-occipital brain network activity. Specifically, in stronger readers, left posterior-occipital activity showed more delta (1-3Hz) synchronization around 300-500 ms (simultaneous with gamma 30-80 Hz desynchronization) and more gamma desynchronization around 600-1000 ms (simultaneous with theta 3-7Hz synchronization) during pseudoword vs. false font processing. These effects were significant even when controlling for age (moderate - large effect sizes). Dynamic functional brain network connectivity measures the brain's real-time sound-print linking. It may offer an under-explored, yet sensitive, index of the neural plasticity associated with reading development.

Very preterm brain at rest: longitudinal social-cognitive network connectivity during childhood.

Very preterm (VPT: ≤32 weeks of gestational age) birth poses an increased risk for social and cognitive morbidities that persist throughout life. Resting-state functional network connectivity studies provide information about the intrinsic capacity for cognitive processing. We studied the following four social-cognitive resting-state networks: the default mode, salience, frontal-parietal and language networks. We examined functional connectivity using magnetoencephalography with individual head localization using each participant's MRI at 6 (n = 40) and 8 (n = 40) years of age compared to age- and sex-matched full-term (FT) born children (n = 38 at 6 years and n = 43 at 8 years). VPT children showed increased connectivity compared to FT children in the gamma band (30-80 Hz) at 6 years within the default mode network (DMN), and between the DMN and the salience, frontal-parietal and language networks, pointing to more diffuse, less segregated processing across networks at this age. At 8 years, VPT children had more social and academic difficulties. Increased DMN connectivity at 6 years was associated with social and working memory difficulties at 8 years. Therefore, we suggest that increased DMN connectivity contributes to the observed emerging social and cognitive morbidities in school age.

Quality of Life Associated with Nausea and Vomiting from Anthracycline-Based Chemotherapy: A Pooled Data Analysis from Three Prospective Trials.

BACKGROUND: There is limited work on the impact of chemotherapy-induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin-cyclophosphamide (AC)-treated patients with breast cancer. The objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients' QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC. MATERIALS AND METHODS: This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index-emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included "no significant nausea" (NSN), "significant nausea" (SN), "no vomiting" (NoV), "vomiting" (V), and complete response (CR). RESULTS: Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p < .0001), with lower scores indicating better QoL; the mean scores for the FLIE vomiting domain for patients who experienced NoV versus V were 1.44 versus 19.11, respectively (p < .0001), with similar results across subsequent cycles. Analysis of the effect of the QoL in cycle 1 on the QoL of subsequent cycles revealed the following: for the nausea domain, among patients who had cycle 1 FLIE scores ≥ versus < the mean, the corresponding scores in cycle 2 were 6.87 versus 36.71 (p < .0001); whereas those for cycle 3 were 7.07 versus 36.87 (p < .0001); and those for cycle 4 were 5.92 versus 21.48 (p < .0001). Similar findings were observed for the vomiting domain. Netupitant + palonosetron- or aprepitant/olanzapine-based antiemetics had significantly better QoL outcomes. CONCLUSION: CINV had a significant impact on the QoL of patients with breast cancer treated with AC over multiple cycles. IMPLICATIONS FOR PRACTICE: In this post-hoc analysis of three prospective studies on chemotherapy-induced nausea and vomiting (CINV), quality of life (QoL) using contemporary antiemetic regimens in Chinese breast cancer patients receiving doxorubicin-cyclophosphamide (AC) was evaluated. During the first and subsequent AC cycles, QoL was significantly better for patients who did not experience vomiting or significant nausea. QoL in an earlier cycle affected the QoL in subsequent AC cycles. Furthermore, recent regimens involving olanzapine/aprepitant or netupitant-palonosetron were associated with a positive impact in QoL. Antiemetic guideline-consistent practice and higher clinician awareness of the impact of CINV on QoL can further mitigate the negative effects of CINV on QoL.

Ignore the faces: Neural characterisation of emotional inhibition from childhood to adulthood using MEG.

The ability to effectively and automatically regulate one's response to emotional information is a basic, fundamental skill for social functioning. The neural mechanisms underlying emotion regulation processing have been assessed, however few investigations have leveraged neurophysiological techniques, particularly magnetoencephalography (MEG) to determine the development of this critical ability. The current MEG study is the first to examine developmental changes in the neural mechanisms supporting automatic emotion regulation. We used an emotional go/no-go task with happy and angry faces in a single-site cohort of 97 healthy participants, 4-40 years of age. We found age-related changes as a function of emotion and condition in brain regions key to emotion regulation, including the right inferior frontal gyrus, orbitofrontal cortices and primarily right-lateralized temporal areas. Interaction effects, including an age by emotion and condition, were also found in the left angular gyrus, an area critical in emotion regulation and attention. Findings demonstrate protracted and nonlinear development, due to the adolescent group, of emotion regulation processing from child to adulthood, and highlight that age-related differences in emotion regulation are modulated by emotional face type.

Phase Resetting in the Anterior Cingulate Cortex Subserves Childhood Attention and Is Impaired by Epilepsy.

The neural mechanisms that underlie selective attention in children are poorly understood. By administering a set-shifting task to children with intracranial electrodes stereotactically implanted within anterior cingulate cortex (ACC) for epilepsy monitoring, we demonstrate that selective attention in a set-shifting task is dependent upon theta-band phase resetting immediately following stimulus onset and that the preferred theta phase angle is predictive of reaction time during attentional shift. We also observe selective enhancement of oscillatory coupling between the ACC and the dorsal attention network and decoupling with the default mode network during task performance. When transient focal epileptic activity occurs around the time of stimulus onset, phase resetting is impaired, connectivity changes with attentional and default mode networks are abolished, and reaction times are prolonged. The results of the present work highlight the fundamental mechanistic role of oscillatory phase in ACC in supporting attentional circuitry and present novel opportunities to remediate attention deficits in children with epilepsy.

A review of magnetoencephalography use in pediatric epilepsy: an update on best practice.

Introduction: Magnetoencephalography (MEG) is a noninvasive technique that is used for presurgical evaluation of children with drug-resistant epilepsy (DRE).Areas covered: The contributions of MEG for localizing the epileptogenic zone are discussed, in particular in extra-temporal lobe epilepsy and focal cortical dysplasia, which are common in children, as well as in difficult to localize epilepsy such as operculo-insular epilepsy. Further, the authors review current evidence on MEG for mapping eloquent cortex, its performance, application in clinical practice, and potential challenges.Expert opinion: MEG could change the clinical management of children with DRE by directing placement of intracranial electrodes thereby enhancing their yield. With improved identification of a circumscribed epileptogenic zone, MEG could render more patients as suitable candidates for epilepsy surgery and increase utilization of surgery.

Identification of optimal contemporary antiemetic prophylaxis for doxorubicin-cyclophosphamide chemotherapy in Chinese cancer patients: post-hoc analysis of 3 prospective studies.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) are common with doxorubicin-cyclophosphamide (AC) chemotherapy. Recommended antiemetic regimens incorporate neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5HT3RA), corticosteroid, and dopamine antagonists. This post-hoc analysis compared results of 3 prospective antiemetic studies conducted among Chinese breast cancer patients who received (neo)adjuvant AC, in order to identify optimal antiemetic prophylaxis. METHODS: A total of 304 patients were included: Group 1, ondansetron/dexamethasone (D1); Group 2, aprepitant/ondansetron/dexamethasone (D1); Group 3, aprepitant/ondansetron/dexamethasone (D1-3); Group 4, aprepitant/ondansetron/dexamethasone (D1-3)/olanzapine; and Group 5, netupitant/palonosetron/dexamethasone (D1-3). Antiemetic efficacies of Groups 3, 4, and 5 during cycle 1 of AC were individually compared with Group 1. In addition, emesis outcomes of patients in Groups 3 and 5, and those of Groups 2 and 3, were compared. RESULTS: When comparing efficacies of a historical doublet (5HT3RA/dexamethasone) with triplet antiemetic regimens (NK1RA/5HT3RA/dexamethasone) with/without olanzapine, complete response (CR) percentages and quality of life (QOL) in overall phase of cycle 1 AC were compared between Group 1 and the other groups: Group 1 vs. 3, 41.9% vs. 38.3% (P = 0.6849); Group 1 vs. 4, 41.9% vs. 65.0% (P = 0.0107); and Group 1 vs. 5, 41.9% vs. 60.0% (P = 0.0460). Groups 4 and 5 achieved a better QOL. When comparing netupitant-based (Group 3) with aprepitant-based (Group 5) triplet antiemetics, CR percentages were 38.3% vs. 60.0%, respectively (P = 0.0176); Group 5 achieved a better QOL. When comparing 1 day (Group 2) vs. 3 day (Group 3) dexamethasone, CR percentages were 46.8% and 38.3%, respectively (P = 0.3459); Group 3 had a worse QOL. CONCLUSIONS: Aprepitant-containing triplets were non-superior to doublet antiemetics. Netupitant-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to doublets. Netupitant/palonosetron/dexamethasone was superior to aprepitant/ondansetron/dexamethasone. Protracted administration of dexamethasone provided limited additional benefit.

Atypical spatiotemporal activation of cerebellar lobules during emotional face processing in adolescents with autism.

Autism spectrum disorder (ASD) is characterized by social deficits and atypical facial processing of emotional expressions. The underlying neuropathology of these abnormalities is still unclear. Recent studies implicate cerebellum in emotional processing; other studies show cerebellar abnormalities in ASD. Here, we elucidate the spatiotemporal activation of cerebellar lobules in ASD during emotional processing of happy and angry faces in adolescents with ASD and typically developing (TD) controls. Using magnetoencephalography, we calculated dynamic statistical parametric maps across a period of 500 ms after emotional stimuli onset and determined differences between group activity to happy and angry emotions. Following happy face presentation, adolescents with ASD exhibited only left-hemispheric cerebellar activation in a cluster extending from lobule VI to lobule V (compared to TD controls). Following angry face presentation, adolescents with ASD exhibited only midline cerebellar activation (posterior IX vermis). Our findings indicate an early (125-175 ms) overactivation in cerebellar activity only for happy faces and a later overactivation for both happy (250-450 ms) and angry (250-350 ms) faces in adolescents with ASD. The prioritized hemispheric activity (happy faces) could reflect the promotion of a more flexible and adaptive social behavior, while the latter midline activity (angry faces) may guide conforming behavior.

Brainstem Associated Somatosensory Evoked Potentials and Response to Vagus Nerve Stimulation: An Investigation of the Vagus Afferent Network.

Despite decades of clinical usage, selection of patients with drug resistant epilepsy who are most likely to benefit from vagus nerve stimulation (VNS) remains a challenge. The mechanism of action of VNS is dependent upon afferent brainstem circuitry, which comprises a critical component of the Vagus Afferent Network (VagAN). To evaluate the association between brainstem afferent circuitry and seizure response, we retrospectively collected intraoperative data from sub-cortical recordings of somatosensory evoked potentials (SSEP) in 7 children with focal drug resistant epilepsy who had failed epilepsy surgery and subsequently underwent VNS. Using multivariate linear regression, we demonstrate a robust negative association between SSEP amplitude (p < 0.01), and seizure reduction. There was no association between SSEP latency and seizure outcomes. Our findings provide novel insights into the mechanism of VNS and inform our understanding of the importance of brainstem afferent circuitry within the VagAN for seizure responsiveness following VNS.

EEG phase synchronization during semantic unification relates to individual differences in children's vocabulary skill.

As we listen to speech, our ability to understand what was said requires us to retrieve and bind together individual word meanings into a coherent discourse representation. This so-called semantic unification is a fundamental cognitive skill, and its development relies on the integration of neural activity throughout widely distributed functional brain networks. In this proof-of-concept study, we examine, for the first time, how these functional brain networks develop in children. Twenty-six children (ages 4-17) listened to well-formed sentences and sentences containing a semantic violation, while EEG was recorded. Children with stronger vocabulary showed N400 effects that were more concentrated to centroparietal electrodes and greater EEG phase synchrony (phase lag index; PLI) between right centroparietal and bilateral frontocentral electrodes in the delta frequency band (1-3 Hz) 1.27-1.53 s after listening to well-formed sentences compared to sentences containing a semantic violation. These effects related specifically to individual differences in receptive vocabulary, perhaps pointing to greater recruitment of functional brain networks important for top-down semantic unification with development. Less skilled children showed greater delta phase synchrony for violation sentences 3.41-3.64 s after critical word onset. This later effect was partly driven by individual differences in nonverbal reasoning, perhaps pointing to non-verbal compensatory processing to extract meaning from speech in children with less developed vocabulary. We suggest that functional brain network communication, as measured by momentary changes in the phase synchrony of EEG oscillations, develops throughout the school years to support language comprehension in different ways depending on children's verbal and nonverbal skill levels.