Mismatch Negativity and P3a in Unaffected Siblings of Individuals with Autism Spectrum Disorder and the Exploration on the Neurocognitive Implications.

Evidence suggests different mismatch negativity (MMN) and P3a responses in individuals with autism spectrum disorder (ASD). Since unaffected siblings shared aberrant neurocognition and brain connectivity with ASD probands, this study investigated MMN and P3a responses in unaffected siblings and explored its neurocognitive implications and effects modifiers. We assessed 43 unaffected siblings of ASD probands and 64 non-autistic comparisons (NTC) using MMN and P3a on both frequency and duration oddball paradigms. The amplitude and latency of MMN and P3a were compared between unaffected siblings and NTC, and validated in 67 ASD probands. In addition, the neurocognitive correlates of MMN and P3a parameters were explored in attention performance, spatial working memory (SWM), and visual research via the tasks of the Conners' Continuous Performance Test and the Cambridge Neuropsychological Test Automated Battery. Compared to NTC, unaffected siblings and ASD probands presented a shorter MMN latency. The P3a amplitude of the duration paradigm (dP3a) was correlated with fewer commission errors, fewer SWM total errors, higher detectability, and more correct responses on visual search tasks. In addition, the dP3a amplitude significantly interacted with sibship, age, and full-scale IQ to predict attention performance, SWM total errors, and total correct response on visual search. Findings suggest that unaffected siblings of ASD may have earlier brain responses upon novelty discrimination. P3a amplitude may correlate with better neurocognitive performance, but the effect was moderated by sibship, age, and intelligence.

Electrophysiological responses to digit stimulation in a tactile oddball paradigm.

Sensory memory traces are assessed via oddball paradigms in which deviant (infrequent) stimuli are interspersed into a string of standard (frequent) stimuli. Once a memory trace for the standard is established, the deviant spurs a change detection response measured via the resulting event related potential (ERP). Response magnitude is sensitive to the differences in stimuli properties or categories and influenced by individual experience. The goal of the present study was to use ERPs to test the relation between individual digits in the somatosensory cortex and the extent to which digit representations are influenced by individual differences in experience such as independent mobility and playing video games. The present study of 60 undergraduates utilized a passive tactile oddball paradigm, stimulating the thumb, middle, and little fingers. The oddball paradigm was fully matched with each digit serving as the standard and deviant. A temporal principal component analysis (tPCA) identified factors that matched three a priori ERP components: N80, somatosensory mismatch negativity (sMMN), and P300. Analyses confirmed the anticipated differences between standards and deviants and provided some support for prior ERP work suggesting the thumb is in a different functional category than the other digits. Independent control of individual digits (such as the little finger) was positively related to only one aspect of the ERP (P3a) while video game experience was not associated with ERP differences. Cumulatively, these results provide a more nuanced examination of tactile oddball paradigms and how ERP methods can shed light on the relations between different digits.

Tracking the habituation of the event-related EEG potential in automatic change detection using an auditory two-tone oddball paradigm.

The mismatch negativity and the P3a of the event-related EEG potential reflect the electrocortical response to a deviant stimulus in a series of stimuli. Although both components have been investigated in various paradigms, these paradigms usually incorporate many repetitions of the same deviant, thus leaving open whether both components vary as a function of the deviant's position in a series of deviant stimuli-i.e. whether they are subject to qualitative/quantitative habituation from one instantiation of a deviant to the next. This is so because the detection of mismatch negativity/P3a in the event-related EEG potential requires an averaging over dozens or hundreds of stimuli, i.e. over many instantiations of the deviant per participant. The present study addresses this research gap. We used a two-tone oddball paradigm implementing only a small number of (deviant) stimuli per participant, but applying it to a large number of participants (n > 230). Our data show that the mismatch negativity amplitude exhibits no decrease as a function of the deviant's position in a series of (standard and) deviant stimuli. Importantly, only after the very first deviant stimulus, a distinct P3a could be detected, indicative of an orienting reaction and an attention shift, and thus documenting a dissociation of mismatch negativity and P3a.

Effort expenditure modulates feedback evaluations involving self-other agreement: evidence from brain potentials and neural oscillations.

The influence of effort expenditure on the subjective value in feedback involving material reward has been the focus of previous research. However, little is known about the impact of effort expenditure on subjective value evaluations when feedback involves reward that is produced in the context of social interaction (e.g. self-other agreement). Moreover, how effort expenditure influences confidence (second-order subjective value) in feedback evaluations remains unclear. Using electroencephalography, this study aimed to address these questions. Event-related potentials showed that, after exerting high effort, participants exhibited increased reward positivity difference in response to self-other (dis)agreement feedback. After exerting low effort, participants reported high confidence, and the self-other disagreement feedback evoked a larger P3a. Time-frequency analysis showed that the high-effort task evoked increased frontal midline theta power. In the low (vs. high)-effort task, the frontal midline delta power for self-other disagreement feedback was enhanced. These findings suggest that, at the early feedback evaluation stage, after exerting high effort, individuals exhibit an increased sensitivity of subjective value evaluation in response to self-other agreement feedback. At the later feedback evaluation stage, after completing the low-effort task, the self-other disagreement feedback violates the individuals'high confidence and leads to a metacognitive mismatch.

Comparing auditory distance perception in real and virtual environments and the role of the loudness cue: A study based on event-related potentials.

The perception of the distance to a sound source is relevant in many everyday situations, not only in real spaces, but also in virtual reality (VR) environments. Where real rooms often reach their limits, VR offers far-reaching possibilities to simulate a wide range of acoustic scenarios. However, in virtual room acoustics a plausible reproduction of distance-related cues can be challenging. In the present study, we compared the detection of changes of the distance to a sound source and its neurocognitive correlates in a real and a virtual reverberant environment, using an active auditory oddball paradigm and EEG measures. The main goal was to test whether the experiments in the virtual and real environments produced equivalent behavioral and EEG results. Three loudspeakers were placed at ego-centric distances of 2 m (near), 4 m (center), and 8 m (far) in front of the participants (N = 20), each 66 cm below their ear level. Sequences of 500 ms noise stimuli were presented either from the center position (standards, 80 % of trials) or from the near or far position (targets, 10 % each). The participants had to indicate a target position via a joystick response ("near" or "far"). Sounds were emitted either by real loudspeakers in the real environment or rendered and played back for the corresponding positions via headphones in the virtual environment. In addition, within both environments, loudness of the auditory stimuli was either unaltered (natural loudness) or the loudness cue was manipulated, so that all three loudspeakers were perceived equally loud at the listener's position (matched loudness). The EEG analysis focused on the mismatch negativity (MMN), P3a, and P3b as correlates of deviance detection, attentional orientation, and context-updating/stimulus evaluation, respectively. Overall, behavioral data showed that detection of the target positions was reduced within the virtual environment, and especially when loudness was matched. Except for slight latency shifts in the virtual environment, EEG analysis indicated comparable patterns within both environments and independent of loudness settings. Thus, while the neurocognitive processing of changes in distance appears to be similar in virtual and real spaces, a proper representation of loudness appears to be crucial to achieve a good task performance in virtual acoustic environments.

Reduced duration mismatch negativity elicited by the multi-feature 'optimal' paradigm in early-phase psychosis.

BACKGROUND: MMN and P3a are EEG-derived event related potentials that are thought to be prospective biomarkers for schizophrenia and, potentially, early-phase psychosis (EPP). METHODS: EPP (n = 12) and healthy control (HC; n = 35) participants listened to a multi-feature optimal paradigm with five deviant types (gap, duration, location, intensity, and frequency). RESULTS: There was a significant amplitude difference between the EPP and HC group with duration MMN (p = .02). No significant amplitude differences between groups were found for the P3a waveform. There were several correlations for the EPP group with the BNSS, SOFAS, and PANSS-general questionnaires. Length of illness was not associated with MMN or P3a. CONCLUSIONS: The optimal paradigm is suitable for eliciting multiple deviant types within a short amount of time in both clinical and healthy populations. This study confirms duration MMN deficits within an EPP group and that MMN is related to functional outcomes and positive and negative symptomology.

Age-related changes to electroencephalographic markers of visuomotor error processing and learning in prism adaptation.

Aging is associated with changes in cognitive function, including declines in learning, memory, and executive function. Prism adaptation (PA) is a useful paradigm to measure changes in explicit and implicit mechanisms of visuo-motor learning with age, but the neural correlates are not well understood. In the present study, we used PA to investigate visuo-motor learning and error processing in older adults. Twenty older adults (56-85 yrs) and 20 younger adults (18-33 yrs) underwent a goal-oriented reaching task while wearing prism goggles as continuous EEG was recorded to examine neural correlates of error detection. We examined behavioural measures of PA, as well as ERP components previously found associated with the early and late phases of adaptation to visual distortion caused by the prism goggles. Our results indicate important age-related behavioural and neurophysiological differences. Older adults reached more slowly than younger adults but showed the same accuracy throughout the prism exposure. Older adults also displayed larger aftereffects, indicating preserved visuomotor adaptation. EEG results indicated similar initial error processing in older and younger adults, as measured by the feedback error related negativity (FRN). As seen previously in young adults, the P3a and P3b declined over the prism exposure phase in both groups. Older adults displayed reduced P3a amplitude compared to the younger group in the early phase of adaptation, however, suggesting reduced attentional orienting. Finally, the older group exhibited a greater P3b amplitude compared to the younger group in the later phases of adaptation, potentially a marker of enhanced context updating underlying spatial realignment, leading to their larger aftereffect. Implications for age-related learning differences and clinical applications are discussed.

Identification and Functional Analyses of Host Proteins Interacting with the P3a Protein of Brassica Yellows Virus.

Viruses are obligate parasites that only undergo genomic replication in their host organisms. ORF3a, a newly identified non-AUG-initiated ORF encoded by members of the genus Polerovirus, is required for long-distance movement in plants. However, its interactions with host proteins still remain unclear. Here, we used Brassica yellows virus (BrYV)-P3a as bait to screen a plant split-ubiquitin-based membrane yeast two-hybrid (MYTH) cDNA library to explain the functional role of P3a in viral infections. In total, 138 genes with annotations were obtained. Bioinformatics analyses revealed that the genes from carbon fixation in photosynthetic, photosynthesis pathways, and MAPK signaling were affected. Furthermore, Arabidopsis thaliana purine permease 14 (AtPUP14), glucosinolate transporter 1 (AtGTR1), and nitrate transporter 1.7 (AtNRT1.7) were verified to interact with P3a in vivo. P3a and these three interacting proteins mainly co-localized in the cytoplasm. Expression levels of AtPUP14, AtGTR1, and AtNRT1.7 were significantly reduced in response to BrYV during the late stages of viral infection. In addition, we characterized the roles of AtPUP14, AtGTR1, and AtNRT1.7 in BrYV infection in A. thaliana using T-DNA insertion mutants, and the pup14, gtr1, and nrt1.7 mutants influenced BrYV infection to different degrees.

Auditory P3a response to native and foreign speech in children with or without attentional deficit.

The aim of this study was to investigate the attentional mechanism in speech processing of native and foreign language in children with and without attentional deficit. For this purpose, the P3a component, cognitive neuromarker of the attentional processes, was investigated in a two-sequence two-deviant oddball paradigm using Finnish and English speech items via event-related potentials (ERP) technique. The difference waves reflected the temporal brain dynamics of the P3a response in native and foreign language contexts. Cluster-based permutation tests evaluated the group differences over the P3a time window. A correlation analysis was conducted between the P3a response and the attention score (ATTEX) to evaluate whether the behavioral assessment reflected the neural activity. The source reconstruction method (CLARA) was used to investigate the neural origins of the attentional differences between groups and conditions. The ERP results showed a larger P3a response in the group of children with attentional problems (AP) compared to controls (CTR). The P3a response differed statistically between the two groups in the native language processing, but not in the foreign language. The ATTEX score correlated with the P3a amplitude in the native language contrasts. The correlation analyses hint at some hemispheric brain activity difference in the frontal area. The group-level CLARA reconstruction showed activation in the speech perception and attention networks over the frontal, parietal, and temporal areas. Differences in activations of these networks were found between the groups and conditions, with the AP group showing higher activity in the source level, being the origin of the ERP enhancement observed on the scalp level.

A novel phenotype of AChR-deficiency syndrome with predominant facial and distal weakness resulting from the inclusion of an evolutionary alternatively-spliced exon in CHRNA1.

Primary acetylcholine receptor deficiency is the most common subtype of congenital myasthenic syndrome, resulting in reduced amount of acetylcholine receptors expressed at the muscle endplate and impaired neuromuscular transmission. AChR deficiency is caused mainly by pathogenic variants in the ε-subunit of the acetylcholine receptor encoded by CHRNE, although pathogenic variants in other subunits are also seen. We report the clinical and molecular features of 13 patients from nine unrelated kinships with acetylcholine receptor deficiency harbouring the CHRNA1 variant NM_001039523.3:c.257G>A (p.Arg86His) in homozygosity or compound heterozygosity. This variant results in the inclusion of an alternatively-spliced evolutionary exon (P3A) that causes expression of a non-functional acetylcholine receptor α-subunit. We compare the clinical findings of this group to the other cases of acetylcholine receptor deficiency within our cohort. We report differences in phenotype, highlighting a predominant pattern of facial and distal weakness in adulthood, predominantly in the upper limbs, which is unusual for acetylcholine receptor deficiency syndromes, and more in keeping with slow-channel syndrome or distal myopathy. Finally, we stress the importance of including alternative exons in variant analysis to increase the probability of achieving a molecular diagnosis.

Temporal and Spectral Properties of the Auditory Mismatch Negativity and P3a Responses in Schizophrenia.

The mismatch negativity (MMN) event-related potential (ERP) indexes relatively automatic detection of changes in sensory stimuli and is typically attenuated in individuals with schizophrenia. However, contributions of different frequencies of electroencephalographic (EEG) activity to the MMN and the later P3a attentional orienting response in schizophrenia are poorly understood and were the focus of the present study. Participants with a schizophrenia-spectrum disorder (n = 85) and non-psychiatric control participants (n = 74) completed a passive auditory oddball task containing 10% 50 ms "deviant" tones and 90% 100 ms "standard" tones. EEG data were analyzed using spatial principal component analysis (PCA) applied to wavelet-based time-frequency analysis and MMN and P3a ERPs. The schizophrenia group compared to the control group had smaller MMN amplitudes and lower deviant-minus-standard theta but not alpha event-related spectral perturbation (ERSP) after accounting for participant age and sex. Larger MMN and P3a amplitudes but not latencies were correlated with greater theta and alpha time-frequency activity. Multiple linear regression analyses revealed that control participants showed robust relationships between larger MMN amplitudes and greater deviant-minus-standard theta inter-trial coherence (ITC) and between larger P3a amplitudes and greater deviant-minus-standard theta ERSP, whereas these dynamic neural processes were less tightly coupled in participants with a schizophrenia-spectrum disorder. Study results help clarify frequency-based contributions of time-domain (ie, ERP) responses and indicate a potential disturbance in the neural dynamics of detecting change in sensory stimuli in schizophrenia. Overall, findings add to the growing body of evidence that psychotic illness is associated with widespread neural dysfunction in the theta frequency band.

Attentional impairment in Parkinson's disease is modulated by side of onset: Neurophysiological evidence.

OBJECTIVE: Neurophysiological studies exploring involuntary attention have reported that electroencephalographic (EEG) measures can indicate impaired neural processing from initial stages of Parkinson's disease (PD). Since involuntary attention is regulated by right hemisphere networks and PD generally initiates its motor symptomatology unilaterally, whether involuntary attention is impaired depending on the onset side of PD remains unknown. METHODS: We compared the neurophysiological correlates of involuntary attention among a PD group with left-side onset (L-PD), a PD group with right-side onset (R-PD) symptomatology, and a healthy control group (HC). All participants performed an auditory involuntary attention task while a digital EEG was recorded. RESULTS: Our main finding was a reduction both in the P3a amplitude and evoked delta-theta phase alignment in the L-PD group compared to the HC. Further, there was a significant correlation between P3a amplitude and disease duration in the R-PD, but not in the L-PD group. Behaviorally, both clinical groups, and in particular L-PD, showed reduced orientation towards novel stimuli, and no reduction of distraction effects during the experiment. CONCLUSIONS: Our results indicate that involuntary attention is differentially impaired in patients with left side onset of symptoms. Involuntary attention impairment might be present from initial stages of left onset PD and become progressively compromised in patients with right onset PD. SIGNIFICANCE: The onset side of symptomatology should be considered for attentional impairment in PD.

Auditory event-related potentials, neurocognition, and global functioning in drug naïve first-episode schizophrenia and bipolar disorder.

BACKGROUND: Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning. METHODS: Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm. RESULTS: Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = -0.31). In BPD, MMN was significantly correlated with DMS (r = -0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD. CONCLUSIONS: The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.

Top-down auditory attention modulates neural responses more strongly in neurotypical than ADHD young adults.

Human cognitive abilities naturally vary along a spectrum, even among those we call "neurotypical". Individuals differ in their ability to selectively attend to goal-relevant auditory stimuli. We sought to characterize this variability in a cohort of people with diverse attentional functioning. We recruited both neurotypical (N = 20) and ADHD (N = 25) young adults, all with normal hearing. Participants listened to one of three concurrent, spatially separated speech streams and reported the order of the syllables in that stream while we recorded electroencephalography (EEG). We tested both the ability to sustain attentional focus on a single "Target" stream and the ability to monitor the Target but flexibly either ignore or switch attention to an unpredictable "Interrupter" stream from another direction that sometimes appeared. Although differences in both stimulus structure and task demands affected behavioral performance, ADHD status did not. In both groups, the Interrupter evoked larger neural responses when it was to be attended compared to when it was irrelevant, including for the P3a "reorienting" response previously described as involuntary. This attentional modulation was weaker in ADHD listeners, even though their behavioral performance was the same. Across the entire cohort, individual performance correlated with the degree of top-down modulation of neural responses. These results demonstrate that listeners differ in their ability to modulate neural representations of sound based on task goals, while suggesting that adults with ADHD may have weaker volitional control of attentional processes than their neurotypical counterparts.

Electrophysiological Markers of Aberrant Cue-Specific Exploration in Hazardous Drinkers.

Background: Hazardous drinking is associated with maladaptive alcohol-related decision-making. Existing studies have often focused on how participants learn to exploit familiar cues based on prior reinforcement, but little is known about the mechanisms that drive hazardous drinkers to explore novel alcohol cues when their value is not known. Methods: We investigated exploration of novel alcohol and non-alcohol cues in hazardous drinkers (N = 27) and control participants (N = 26) during electroencephalography (EEG). A normative computational model with two free parameters was fit to estimate participants' weighting of the future value of exploration and immediate value of exploitation. Results: Hazardous drinkers demonstrated increased exploration of novel alcohol cues, and conversely, increased probability of exploiting familiar alternatives instead of exploring novel non-alcohol cues. The motivation to explore novel alcohol stimuli in hazardous drinkers was driven by an elevated relative future valuation of uncertain alcohol cues. P3a predicted more exploratory decision policies driven by an enhanced relative future valuation of novel alcohol cues. P3b did not predict choice behavior, but computational parameter estimates suggested that hazardous drinkers with enhanced P3b to alcohol cues were likely to learn to exploit their immediate expected value. Conclusions: Hazardous drinkers did not display atypical choice behavior, different P3a/P3b amplitudes, or computational estimates to novel non-alcohol cues-diverging from previous studies in addiction showing atypical generalized explore-exploit decisions with non-drug-related cues. These findings reveal that cue-specific neural computations may drive aberrant alcohol-related decision-making in hazardous drinkers-highlighting the importance of drug-relevant cues in studies of decision-making in addiction.

The development of cortical processing of speech differs between children with cochlear implants and normal hearing and changes with parental singing.

Objective: The aim of the present study was to investigate speech processing development in children with normal hearing (NH) and cochlear implants (CI) groups using a multifeature event-related potential (ERP) paradigm. Singing is associated to enhanced attention and speech perception. Therefore, its connection to ERPs was investigated in the CI group. Methods: The paradigm included five change types in a pseudoword: two easy- (duration, gap) and three difficult-to-detect (vowel, pitch, intensity) with CIs. The positive mismatch responses (pMMR), mismatch negativity (MMN), P3a and late differentiating negativity (LDN) responses of preschoolers (below 6 years 9 months) and schoolchildren (above 6 years 9 months) with NH or CIs at two time points (T1, T2) were investigated with Linear Mixed Modeling (LMM). For the CI group, the association of singing at home and ERP development was modeled with LMM. Results: Overall, responses elicited by the easy- and difficult to detect changes differed between the CI and NH groups. Compared to the NH group, the CI group had smaller MMNs to vowel duration changes and gaps, larger P3a responses to gaps, and larger pMMRs and smaller LDNs to vowel identity changes. Preschoolers had smaller P3a responses and larger LDNs to gaps, and larger pMMRs to vowel identity changes than schoolchildren. In addition, the pMMRs to gaps increased from T1 to T2 in preschoolers. More parental singing in the CI group was associated with increasing pMMR and less parental singing with decreasing P3a amplitudes from T1 to T2. Conclusion: The multifeature paradigm is suitable for assessing cortical speech processing development in children. In children with CIs, cortical discrimination is often reflected in pMMR and P3a responses, and in MMN and LDN responses in children with NH. Moreover, the cortical speech discrimination of children with CIs develops late, and over time and age, their speech sound change processing changes as does the processing of children with NH. Importantly, multisensory activities such as parental singing can lead to improvement in the discrimination and attention shifting toward speech changes in children with CIs. These novel results should be taken into account in future research and rehabilitation.

Children's inhibition skills are associated with their P3a latency-results from an exploratory study.

BACKGROUND: The P3a response is thought to reflect involuntary orienting to an unexpected stimulus and has been connected with set-shifting and inhibition in some studies. In our exploratory study, we investigated if the amplitude and the latency of the P3a response were associated with the performance in a modified flanker task measuring inhibition and set-shifting in 10-year-old children (N = 42). Children participated in electroencephalography (EEG) measurement with an auditory multifeature paradigm including standard, deviating, and novel sounds. In addition, they performed a separate flanker task requiring inhibition and set-shifting skills. RESULTS: The P3a latencies for deviant sounds were associated with the reaction time reflecting inhibition: the shorter the response latencies were, the faster the reaction time was. The P3a latencies for novel sounds were not linked to the reaction times reflecting either inhibition or set-shifting. In addition, the magnitude of the P3a response was not associated with the performance in the flanker task. CONCLUSIONS: Our results suggest that P3a response latency and reaction speed reflecting inhibitory skills are based on shared neural mechanism. Thus, the present study brings new insight to the field investigating the associations between behavior and its neural indices.

MMN and P3a Elicited by a Novelty Oddball Paradigm Are Not Reduced in Early-Phase Psychosis.

INTRODUCTION: The present study compared the mismatch negativity (MMN) and P3a waveforms among early-phase psychosis (EPP; n = 13) individuals and healthy controls (n = 30) to contribute to the research on these waveforms as potential biomarkers for schizophrenia. METHODS: MMN and P3a were elicited with a novelty paradigm using complex stimuli with electrophysiological technology. RESULTS: No significant group differences of amplitude were observed with either waveform. Increased asociality and blunted affect were associated with a reduction in both MMN and P3a waveforms indicating a relationship between these negative symptoms and cognitive deficits. Good social and occupational functioning correlated with improved MMN and P3a waveforms in the EPP group. CONCLUSIONS: This study suggests that MMN and P3a may be more appropriately used as an indicator of illness progression and symptomology rather than a biomarker in the early phase of the illness.

Timing characteristics of reactive and proactive emotion regulation.

The dual mechanisms of control (DMC) framework is important for portraying two temporally distinct modes of cognitive control. In parallel with this model, understanding emotion regulation (ER) from a dual-mechanism perspective becomes plausible since cognitive control is a crucial element of ER. The present study characterized reactive and proactive ER based on a dual mechanisms framework to identify their distinct temporal dynamics using electroencephalography (EEG) recordings. The reappraisal cue, compared with the watch-cue and no-cue conditions, evoked a larger fronto-central P3a magnitude, suggesting that participants could adaptively distribute their attention resources to prepare for strategy use. To track the cognitive effort that supports the ER process, we measured the frontal late positive potential (LPP). The results indicated that the reactive group, compared with the proactive group, used more effort to complete the reappraisal task when participants were subjected to decreased negative-emotional experiences to the same degree. Furthermore, decoding analysis showed that proactive ER starts earlier than reactive ER. These findings highlight the advantages of proactive ER. Further understanding of the modes of ER will help elucidate the control mechanisms underlying ER, which can then be applied to a variety of conditions, such as alcoholism, gambling, and drug addiction, to avert self-regulation failures caused by negative emotions.

Influence of trazodone on the pharmacodynamics and pharmacokinetics of pioglitazone.

BACKGROUND: These days, poly pharmacy is very common for the treatment of multiple diseases and majority of drugs were metabolized with CYP 450 enzymes. Diabetes mellitus is such a disorder, which requires continuous therapy for the control of blood glucose concentration. Depression was quite common in diabetic patients. Therefore, multiple drugs required to treat diabetes mellitus and depression. Simultaneous administration of these drugs leads to drug interaction. Pioglitazone and trazodone metabolized by CYP3A4 enzymes which may lead to potential drug interaction. OBJECTIVES: This study aimed to find the influence of trazodone on the pharmacokinetics & pharmacodynamics of pioglitazone in normal & diabetic rats, also on rabbits and subsequently effectiveness and safety of the combination was evaluated. METHODS AND MATERIAL: Blood glucose concentration was determined by Glucose oxidase/peroxidase method in normal and diabetic rats. Diabetes was induced with Streptozotocin at a dose of 55 mg/kg body weight. Serum pioglitazone concentration was estimated by high performance liquid chromatography method for pharmacokinetic data. The values were expressed as Mean ± Standard Error Mean (SEM), GraphPad Prism 3.0 (San Diego, California, USA) software was used to express the data. Student's paired 't' test was used to determine the significance. RESULTS: Pioglitazone produces hypoglycaemia in normal rats with a maximum decrease of 36.78 % ± 0.81 at 3 hours interval and anti-hyperglycaemic activity in diabetic rats with maximum reduction of 45.13 % ± 1.52 at 2 hours interval. Trazodone altered the pharmacokinetics of pioglitazone and improved the pioglitazone hypoglycaemic effect. CONCLUSION: Trazodone apparently produced pharmacokinetic interaction with pioglitazone which might be by attenuating the metabolism of pioglitazone. Therefore, care should be taken in simultaneous therapy with pioglitazone and trazodone.