P300 in response to the subject's own name

The P300 component is influenced by task relevance which is typically achieved by employing an active task involving the evoking stimulus. This study explored the possibility of making use of the subject's name, which is innately relevant to the subject, to achieve stimulus relevance.Dependence of P300 amplitude on auditory presentation of the subject's name was assessed in two experiments in which no response was required: (1) a passive 2-word “oddball” paradigm where the low probability word was the subject's first name; (2) a passive 3-word “oddball” paradigm consisting of two low probability words, one of which was the subject's name, and a third, high probability word.In the first experiment, a typical active 2-word “oddball” paradigm, which did not include the subject's name, was compared with the passive paradigm.P300 amplitude was larger in response to the subject's name compared to the other word in the two-word paradigm, indicating that the name can be used to evoke P300 in a passive paradigm. It was also larger than either of the other two words in the 3-word paradigm, suggesting that stimulus relevance has an additional effect on P300 amplitude beyond rarity.     

Prolonged P300 latency in children with the D2 dopamine receptor A1 allele.

Previous studies have indicated the presence of a hereditary component in the generation of the P300, or P3, a late positive component of the event-related potential. Moreover, the dopaminergic system has been implicated in the P3. In the present study, 98 healthy Caucasian boys, mean age of 12.5 years and of above-average intelligence, were studied. The sample was composed of 32 sons of active alcoholic (SAA) fathers, 36 sons of recovering alcoholic (SRA) fathers, and 30 sons of social drinker (SSD) fathers, with none of them having yet begun to consume alcohol or other drugs. TaqI A D2 dopamine receptor alleles (A1 and A2) were determined. A significant difference in the frequency of the A1 allele was found among these three groups of boys, with the SAA group having the highest A1 allele frequency (.313), followed by the SRA (.139) and the SSD (.133) groups. The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between boys with the A1 and A2 allele. However, P3 latency was significantly longer in the total sample of boys with the A1 allele compared with those carrying the A2 allele. These findings suggest that polymorphism of the D2 dopamine receptor gene is an important determinant of P3 latency.     

Heart rate variability and methylphenidate in children with ADHD

Although an extensive number of studies support the efficacy and tolerability of stimulants in the treatment of attention deficit/hyperactivity disorder (ADHD), in recent years, increasing concerns have been raised about their cardiovascular safety. We investigated whether a time domain analysis of heart rate variability (HRV) recordings in 24-h ECG under medication with stimulants yielded new information about therapy control in ADHD. We analysed the HRV parameter standard deviation of all normal sinus RR intervals over 24 h (SDNN), percentage of successive normal sinus RR intervals > 50 ms (pNN50) and root-mean-square of the successive normal sinus RR interval difference (rMSSD) from 23 children diagnosed by ADHD (19 boys and 4 girls), aged 10.5 ± 2.2 years, who were consecutively referred to our outpatient clinic for paediatric cardiology. Eleven children received medication with methylphenidate (MPH), while twelve children were initially examined without medication. Of these, eight probands were re-examined after therapy with MPH was established. Controls comprised 19 children (10 boys, 9 girls) from our Holter ECG data base without any cardiac or circulatory disease. Compared to healthy controls, the ADHD children with and without MPH treatment showed significantly higher mean heart rates (ADHD without MPH: 94.3 ± 2.2; ADHD with MPH: 90.5 ± 1.8, controls: 84.7 ± 1.8). pNN50 (ADHD without MPH: 6.5 ± 2.7; ADHD with MPH: 14.2 ± 6.9, controls: 21.5 ± 9.0) and rMSSD (ADHD without MPH: 26.1 ± 4.1; ADHD with MPH: 36.7 ± 8.3, controls: 44.5 ± 10.1) were lowest in ADHD children without MPH, middle in ADHD children with MPH and highest in controls. SDNN values were not significantly different. The hourly analysis shows highly significant reduced pNN50 and rMSSD values in untreated ADHD children between 5:00 pm and 6:00 am while the pattern approaches to levels of controls during MPH treatment. Data of this pilot study indicate a decreased vagal tone with significantly diminished HRV and higher heart rates in unmedicated ADHD children. These parameters of autonomic activation are ameliorated by MPH treatment. No evidence for negative impact of MPH on HRV was detected. Further studies will clarify a potential cardio-protective effect of MPH in ADHD.     

Dipole source analysis of auditory P300 response in depressive and anxiety disorders

This paper is to study auditory event-related potential P300 in patients with anxiety and depressive disorders using dipole source analysis. Auditory P300 using 2-stimulus oddball paradigm was collected from 35 patients with anxiety disorder, 32 patients with depressive disorder, and 30 healthy controls. P300 dipole sources and peak amplitude of dipole activities were analyzed. The source analysis resulted in a 4-dipole configuration, where temporal dipoles displayed greater P300 amplitude than that of frontal dipoles. In addition, a right-greater-than-left hemispheric asymmetry of dipole magnitude was found in patients with anxiety disorder, whereas a left-greater-than-right hemispheric asymmetry of dipole magnitude was observed in depressed patients. Results indicated that the asymmetry was more prominent over the temporal dipole than that of frontal dipoles in patients. Patients with anxiety disorder may increase their efforts to enhance temporal dipole activity to compensate for a deficit in frontal cortex processing, while depressed patients show dominating reduction of right temporal activity. The opposite nature of results observed with hemispheric asymmetry in depressive and anxiety disorders could serve to be valuable information for psychiatric studies.     

Both inflammatory and regulatory cytokine responses to malaria are blunted with increasing age in highly exposed children

Background

Young children are at greatest risk for malaria-associated morbidity and mortality. The immune response of young children differs in fundamental ways from that of adults, and these differences likely contribute to the increased susceptibility of children to severe malaria and to their delayed development of immunity. Elevated levels of pro-inflammatory cytokines and chemokines in the peripheral blood during acute infection contribute to the control of parasitaemia, but are also responsible for much of the immunopathology seen during symptomatic disease. Clinical immunity to malaria may depend upon the ability to regulate these pro-inflammatory responses, possibly through mechanisms of immunologic tolerance. In order to explore the effect of age on the immune response to malaria and the development of clinical immunity, cytokines and chemokines were measured in the plasma of children at day 0 of an acute malaria episode and during convalescence.

Results

Younger children presenting with acute malaria exhibited much higher levels of TNF, IL2, and IL6, as well as increased Th1 associated chemokines IP10, MIG, and MCP1, compared to older children with acute malaria. Additionally, the regulatory cytokines IL10 and TNFRI were dramatically elevated in younger children compared to older children during acute infection, indicating that regulatory as well as pro-inflammatory cytokine responses are dampened in later childhood.

Conclusions

Together these data suggest that there is a profound blunting of the cytokine and chemokine response to malaria among older children residing in endemic settings, which may be due to repeated malaria exposure, intrinsic age-based differences in the immune response, or both.

     

Latency of auditory P300 response is related with cognitive deficits in Obstructive Sleep Apnea Syndrome

Sleep and Biological Rhythms - Obstructive Sleep Apnea Syndrome (OSAS) is characterized by desaturation in blood oxygen level and sleep fragmentation because of repeated upper airway obstruction....     

ATP inhibition competes with activating cations in modulating the NAD(P)(+)-malic enzyme activity in the mitochondrial matrix of Xenopus laevis oocytes

1. ATP inhibits NAD(P)(+)-dependent malic enzyme activity by competing with the essential activators Mn2+ and Mg2+. 2. The kinetics fit an equation of co-operative kind with Ki of 26 microM and KA of 11.3 microM for ATP/Mn2+ competition; with Ki of 1.1 mM and KA of 0.96 mM for ATP/Mg2+ competition. 3. In the absence of the inhibitor, the co-operativity index increases from 1.77 to greater than 4 in the presence of ATP, in the case of ATP/Mn2+ competition, while it increases from 1.88 to greater than 9 for ATP/Mg2+ competition.     

Cortisol responses in children and adults with attention deficit hyperactivity disorder (ADHD): a possible marker of inhibition deficits

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disease whose neurobiological background is not completely understood. It has been proposed that deficits of the inhibitory function with an underactive behavioral inhibition system (BIS) may be in the core of ADHD. In this regard, this review summarizes all studies that examine the involvement of cortisol in ADHD. Differences in cortisol responses from different ADHD subtypes, hyperactive/impulsive, inattentive, and combined, are analyzed. In addition, we examine the role of comorbidities as confounding factors in the study of cortisol in ADHD, including comorbid disruptive behavioral disorder (DBD), as well as anxiety and depressive disorders. Because ADHD is a neurodevelopmental condition and approximately half of the children enter adulthood with the disorder, we review cortisol studies in adults and children separately. Two diverse patterns of cortisol have been reported both in children and adults with ADHD. Blunted cortisol responses to stress are associated with comorbid DBD, whereas high cortisol responses are associated to comorbid anxiety disorders. Nevertheless, the inhibitory deficits in ADHD do not appear to be related directly to cortisol deficits in either children or adults. This review increases our understanding of the heterogeneity of ADHD and could help in determining new strategies for the treatment of these patients. Future studies including gender and a more systematic methodology to study the cortisol response are needed.     

Brain fingerprinting field studies comparing P300-MERMER and P300 brainwave responses in the detection of concealed information

Brain fingerprinting detects concealed information stored in the brain by measuring brainwave responses. We compared P300 and P300-MERMER event-related brain potentials for error rate/accuracy and statistical confidence in four field/real-life studies. 76 tests detected presence or absence of information regarding (1) real-life events including felony crimes; (2) real crimes with substantial consequences (either a judicial outcome, i.e., evidence admitted in court, or a $100,000 reward for beating the test); (3) knowledge unique to FBI agents; and (4) knowledge unique to explosives (EOD/IED) experts. With both P300 and P300-MERMER, error rate was 0 %: determinations were 100 % accurate, no false negatives or false positives; also no indeterminates. Countermeasures had no effect. Median statistical confidence for determinations was 99.9 % with P300-MERMER and 99.6 % with P300. Brain fingerprinting methods and scientific standards for laboratory and field applications are discussed. Major differences in methods that produce different results are identified. Markedly different methods in other studies have produced over 10 times higher error rates and markedly lower statistical confidences than those of these, our previous studies, and independent replications. Data support the hypothesis that accuracy, reliability, and validity depend on following the brain fingerprinting scientific standards outlined herein.     

The P300 event-related potentials in dementia of the Alzheimer type. Correlations between P300 and monoamine metabolites

We studied auditory event-related potentials (ERPs) in 40 patients with dementia of the Alzheimer type (DAT). Peak latencies and amplitudes of N100, P200 and P300 components were measured. To study the possible relationships between the ERPs and monoaminergic neurotransmitter functions, CSF neurotransmitter metabolites were also analyzed. In patients with DAT, the P300 amplitude was significantly reduced and the P300 latency was prolonged. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were decreased. The P300 amplitude was significantly correlated with the 5-HIAA concentration. There were no correlations between the P300 components and the HVA concentration. These findings suggest that the serotonergic system modulates the P300 component of ERPs in patients with DAT.     

Self-regulation strategies support children with ADHD to overcome symptom-related behavior in the classroom

Children with attention deficit hyperactivity disorder (ADHD) suffer from self-regulation deficits that cause inattention, impulsivity, and hyperactivity. Self-regulation interventions may address these deficits, but to date, only few empirical studies have examined their benefits for children with ADHD in everyday life. The present study investigated three classroom interventions to promote self-regulation and tested their benefit on self-regulatory competencies (assessed with an ADHD questionnaire) in children with ADHD. Students of a special education school for children with ADHD participated in the intervention study that included three sessions (Session 1: Goal Intention or Goal Intention + If–Then Plan; Session 2: Goal Intention + If–Then Plan; Session 3: Goal Intention + If–Then Plan + Self-Monitoring). Teacher-rated self-regulatory competencies were assessed both before and after the intervention sessions. Children with ADHD had better self-regulatory competencies after their first Goal Intention + If–Then Plan Session, but lasting intervention effects were found only when children started with a mere goal intention session.     

用P300评价连续工作记忆能力差异的研究

目的：评价长时间连续工作记忆的行为学表现与事件相关电位（Event-related potential,ERP）的关系。方法：对16位健康男性青年（平均年龄21.4岁）,连续进行1h的3-back数字倒背实验,记录ERP。结果：受试者的行为学表现明显差异,记录的ERP的P300波幅存在显著性差异（P〈0.01）。结论：ERP的P300成分可以客观评价行为学上的差异。     

Causality in the association between P300 and alpha event-related desynchronization

Recent findings indicated that both P300 and alpha event-related desynchronization (α-ERD) were associated, and similarly involved in cognitive brain functioning, e.g., attention allocation and memory updating. However, an explicit causal influence between the neural generators of P300 and α-ERD has not yet been investigated. In the present study, using an oddball task paradigm, we assessed the task effect (target vs. non-target) on P300 and α-ERD elicited by stimuli of four sensory modalities, i.e., audition, vision, somatosensory, and pain, estimated their respective neural generators, and investigated the information flow among their neural generators using time-varying effective connectivity in the target condition. Across sensory modalities, the scalp topographies of P300 and α-ERD were similar and respectively maximal at parietal and occipital regions in the target condition. Source analysis revealed that P300 and α-ERD were mainly generated from posterior cingulate cortex and occipital lobe respectively. As revealed by time-varying effective connectivity, the cortical information was consistently flowed from α-ERD sources to P300 sources in the target condition for all four sensory modalities. All these findings showed that P300 in the target condition is modulated by the changes of α-ERD, which would be useful to explore neural mechanism of cognitive information processing in the human brain.     

APP and APLP1 are degraded through autophagy in response to proteasome inhibition in neuronal cells

Amyloid beta (Aβ) precursor protein (APP) is a key protein in the pathogenesis of Alzheimer’s disease (AD). Both APP and its paralogue APLP1 (amyloid beta precursor-like protein 1) have multiple functions in cell adhesion and proliferation. Previously it was thought that autophagy is a novel beta-amyloid peptide (Aβ)-generating pathway activated in AD. However, the protein proteolysis of APLP1 is still largely unknown. The present study shows that APLP1 is rapidly degraded in neuronal cells in response to stresses, such as proteasome inhibition. Activation of the endoplasmic reticulum (ER) stress by proteasome inhibitors induces autophagy, causing reduction of mature APLP1/APP. Blocking autophagy or JNK stress kinase rescues the protein expression for both APP and APLP1. Therefore, our results suggest that APP/APLP1 is degraded through autophagy and the APLP1 proteolysis is mainly mediated by autophagy-lysosome pathway.     

Prepotent response inhibition and reaction times in children with attention deficit/hyperactivity disorder from a Caribbean community

Impairment in inhibitory control has been postulated as an underlying hallmark of attention deficit/hyperactivity disorder (ADHD), which can be utilized as a quantitative trait for genetic studies. Here, we evaluate whether inhibitory control, measured by simple automatized prepotent response (PR) inhibition variables, is a robust discriminant function for the diagnosis of ADHD in children and can be used as an endophenotype for future genetic studies. One hundred fifty-two school children (30.9% female, 67.8% with ADHD) were recruited. The ADHD checklist was used as the screening tool, whilst the DSM-IV Mini International Neuropsychiatry Interview, neurologic interview and neurologic examination, and the WISC III FSIQ test were administered as the gold standard procedure to assert ADHD diagnosis. A Go/No-Go task using a naturalistic and automatized visual signal was administered. A linear multifactor model (MANOVA) was fitted to compare groups including ADHD status, age, and gender as multiple independent factors. Linear discriminant analysis and the receiver operating characteristic curve were used to assess the predictive performance of PR inhibition variables for ADHD diagnosis. We found that four variables of prepotent response reaction time- and prepotent response inhibition established statistically significant differences between children with and without ADHD. Furthermore, these variables generated a strong discriminant function with a total classification capability of 73, 84% specificity, 68% sensitivity, and 90% positive predictive value for ADHD diagnosis, which support reaction times as a candidate endophenotype that could potentially be used in future ADHD genetic research.     

ADHD symptoms in healthy adults are associated with stressful life events and negative memory bias

Stressful life events, especially Childhood Trauma, predict ADHD symptoms. Childhood Trauma and negatively biased memory are risk factors for affective disorders. The association of life events and bias with ADHD symptoms may inform about the etiology of ADHD. Memory bias was tested using a computer task in N = 675 healthy adults. Life events and ADHD symptoms were assessed using questionnaires. The mediation of the association between life events and ADHD symptoms by memory bias was examined. We explored the roles of different types of life events and of ADHD symptom clusters. Life events and memory bias were associated with overall ADHD symptoms as well as inattention and hyperactivity/impulsivity symptom clusters. Memory bias mediated the association of Lifetime Life Events, specifically Childhood Trauma, with ADHD symptoms. Negatively biased memory may be a cognitive marker of the effects of Childhood Trauma on the development and/or persistence of ADHD symptoms.