A mid-central N450 component of the ERP distinguishes trial-by-trial effects of target familiarity and context strength

N400-like components in the ERP are commonly understood as being inversely related to the degree at which contextual factors have prepared the brain for the processing of meaningful stimuli. Here we show independent and systematic effects of familiarity and context on mid-central N450 in a simple visual priming task. Participants selected a target digit defined by color while ignoring a distractor digit. Pairs of two subsequent displays (prime, probe) were considered. Probe target familiarity could be high (prime-probe target repetition), low (novel probe target), or very low (probe target = prime distractor). Context strength depended on history of the probe distractor and could be high (prime-probe distractor repetition), low (novel probe distractor), or very low (probe distractor = prime target). The seven priming conditions showed exactly the predicted order of N450 amplitude, with largest N450 for strong context/low target familiarity and smallest N450 for weak context/high target familiarity. Results significantly broaden the view of N400, as a universal marker of stimulus familiarity and context strength also in basic, non-linguistic settings.     

Electrophysiological evidence of interaction between contextual expectation and semantic integration during the processing of collocations

Despite the potentially infinite creativity of language, many words are patterned in ordered strings called collocations. Final words of these clusters are highly predictable; in addition, their overall meaning can vary on the literality dimension, ranging from (figurative) idiomatic strings to literal strings. These structures thus offer a natural linguistic scenario to contrast ERP correlates of contextual expectation and semantic integration processes during comprehension. In this study, expected endings elicited a positive peak around 300 ms compared to less expected synonyms, suggesting that the earlier recognition of the string leads to the specific pre-activation of the lexical items that conclude the expression. On the other hand, meaning variations of these fixed strings (either a literal or a figurative whole meaning) affected ERPs only around 400 ms, i.e. in the frontal portion of the N400. These findings are discussed within a more general cognitive framework as outlined in Kok's (2001) dual categorization model.     

Apolipoprotein E modulates auditory event-related potentials in healthy aging

42 individuals ranging from 47 to 73 years of age underwent an auditory three-stimulus oddball task while their event-related potentials (ERPs) were recorded. Half were APOE ?3 homozygotes and the remaining participants were either ?3/?4 heterozygotes (n = 13), or ?4 homozygotes (n = 8). Analyses of variance showed that the heterozygotes had lower N1 amplitudes than the ?3 homozygotes, consistent with a previous study of participants with mild cognitive impairment (MCI) [I. Reinvang, T. Espeseth, L. Gjerstad, Cognitive ERPs are related to ApoE allelic variation in mildly cognitively impaired patients, Neuroscience Letters 382 (3) (2005) 346–351]. APOE genotype also significantly modulated N2 latency. ?4 homozygotes had longer N2 latencies, and importantly, longer N2 latencies predicted decline in verbal learning after 3.5 years follow up. These findings indicate a potential clinical significance of individual differences in ERP components N1 and N2.     

Face-to-face versus computer-delivered alcohol interventions for college drinkers: A meta-analytic review, 1998 to 2010

Alcohol misuse occurs commonly on college campuses, necessitating prevention programs to help college drinkers reduce consumption and minimize harmful consequences. Computer-delivered interventions (CDIs) have been widely used due to their low cost and ease of dissemination but whether CDIs are efficacious and whether they produce benefits equivalent to face-to-face interventions (FTFIs) remain unclear. Therefore, we identified controlled trials of both CDIs and FTFIs and used meta-analysis (a) to determine the relative efficacy of these two approaches and (b) to test predictors of intervention efficacy. We included studies examining FTFIs (N = 5237; 56% female; 87% White) and CDIs (N = 32,243; 51% female; 81% White). Independent raters coded participant characteristics, design and methodological features, intervention content, and calculated weighted mean effect sizes using fixed and random-effects models. Analyses indicated that, compared to controls, FTFI participants drank less, drank less frequently, and reported fewer problems at short-term follow-up (d₊s = 0.15–0.19); they continued to consume lower quantities at intermediate (d₊ = 0.23) and long-term (d₊ = 0.14) follow-ups. Compared to controls, CDI participants reported lower quantities, frequency, and peak intoxication at short-term follow-up (d₊s = 0.13–0.29), but these effects were not maintained. Direct comparisons between FTFI and CDIs were infrequent, but these trials favored the FTFIs on both quantity and problem measures (d₊s = 0.12–0.20). Moderator analyses identified participant and intervention characteristics that influence intervention efficacy. Overall, we conclude that FTFIs provide the most effective and enduring effects.     

The efficacy of short-term psychodynamic psychotherapy for depression: A meta-analysis

Objectives

It remains largely unclear, firstly whether short-term psychodynamic psychotherapy (STPP) is an effective treatment for depression, and secondly, which study, participant, or intervention characteristics may moderate treatment effects. The purpose of this study is to assess the efficacy of STPP for depression and to identify treatment moderators.

Results

After a thorough literature search, 23 studies totaling 1365 subjects were included. STPP was found to be significantly more effective than control conditions at post-treatment (d = 0.69). STPP pre-treatment to post-treatment changes in depression level were large (d = 1.34), and these changes were maintained until 1-year follow-up. Compared to other psychotherapies, a small but significant effect size (d = − 0.30) was found, indicating the superiority of other treatments immediately post-treatment, but no significant differences were found at 3-month (d = − 0.05) and 12-month (d = − 0.29) follow-up. Studies employing STPP in groups (d = 0.83) found significantly lower pre-treatment to post-treatment effect sizes than studies using an individual format (d = 1.48). Supportive and expressive STPP modes were found to be equally efficacious (d = 1.36 and d = 1.30, respectively).

Conclusion

We found clear indications that STPP is effective in the treatment of depression in adults. Although more high-quality RCTs are necessary to assess the efficacy of the STPP variants, the current findings add to the evidence-base of STPP for depression.     

The association between perinatal testosterone concentration and early vocabulary development: A prospective cohort study

Prenatal exposure to testosterone is known to affect fetal brain maturation and later neurocognitive function. However, research on the effects of prenatal testosterone exposure has been limited by indirect measures of testosterone and small unrepresentative samples. This study investigated whether bioavailable testosterone (BioT) concentrations in umbilical cord blood are associated with expressive vocabulary development, in a large birth cohort. Cord blood samples were taken immediately after delivery and expressive vocabulary was measured at two years of age using the language development survey (LDS). BioT concentration significantly predicted vocabulary size in males (n = 197), such that higher concentrations were associated with lower LDS scores, indicating smaller vocabulary. This relationship between BioT concentrations and vocabulary at aged 2 years was not observed in girls (n = 176). Higher circulating prenatal testosterone concentrations at birth may be associated with reduced vocabulary in early childhood among boys.     

Effectiveness of the Incredible Years parent training to modify disruptive and prosocial child behavior: A meta-analytic review

The present meta-analytic review examined effectiveness of the Incredible Years parent training (IYPT) regarding disruptive and prosocial child behavior, and aimed to explain variability in intervention outcomes. Fifty studies, in which an intervention group receiving the IYPT was compared to a comparison group immediately after intervention, were included in the analyses. Results showed that the IYPT is an effective intervention. Positive effects for distinct outcomes and distinct informants were found, including a mean effect size of d = .27 concerning disruptive child behavior across informants. For parental report, treatment studies were associated with larger effects (d = .50) than indicated (d = .20) and selective (d = .13) prevention studies. Furthermore, initial severity of child behavior revealed to be the strongest predictor of intervention effects, with larger effects for studies including more severe cases. Findings indicate that the IYPT is successful in improving child behavior in a diverse range of families, and that the parent program may be considered well-established.     

The concentrations of serum, plasma and platelet BDNF are all increased by treadmill VO₂max performance in healthy college men

An important question in healthcare for older patients is whether age-related changes in cortical reorganization can be measured with advancing age. This study investigated the factors behind such age-related changes, using time-frequency analysis of event-related potentials (ERPs). We hypothesized that brain rhythms was affected by age-related changes, which could be reflected in the ERP indices. An oddball task was conducted in two experimental groups, namely young participants (N = 15; mean age 23.7 ± 2.8 years) and older participants (N = 15; mean age 70.1 ± 7.9 years). Two types of stimuli were used: the target (1 kHz frequency) and standard (2 kHz frequency). We scrutinized three ERP indices: event-related spectral power (ERPSP), inter-trial phase-locking (ITPL), and event-related cross-phase coherence (ERPCOH). Both groups performed equally well for correct response rate. However, the results revealed a statistically significant age difference for inter-trial comparison. Compared with the young, the older participants showed the following age-related changes: (a) power activity decreased; however, an increase was found only in the late (P3, 280-450 ms) theta (4-7 Hz) component over the bilateral frontal and temporo-frontal areas; (b) low phase-locking in the early (N1, 80-140 ms) theta band over the parietal/frontal (right) regions appeared; (c) the functional connections decreased in the alpha (7-13 Hz) and beta (13-30 Hz) bands, but no difference emerged in the theta band between the two groups. These results indicate that age-related changes in task-specific brain activity for a normal aging population can be depicted using the three ERP indices.     

Expression of autophagy and ER stress-related proteins in primary salivary adenoid cystic carcinoma

Autophagy is the endogenous cellular pathway that facilitates cellular survival by maintaining energy homeostasis and macromolecular synthesis during cellular stress and nutrient deprivation. Endoplasmic reticulum (ER) stress is the process in which disruption of these physiological functions leads to an accumulation of unfolded proteins and induces the unfolded protein response (UPR). ER stress and autophagy are involved in human cancer. We investigated the expression of autophagic proteins (LC3 and beclin 1) and ER stress-related protein (GRP78) in head and neck adenoid cystic carcinoma tissue. Tissue samples from 79 cases of head and neck adenoid cystic carcinoma tissue were utilized for immunohistochemistry. LC3 expression was significantly correlated with lymph node involvement (P = .016) and TNM (P = .021). Beclin 1 expression was significantly correlated with the histological growth pattern (P = .002), the histological grade (P = .000), and longer survival (P = .000). GRP78 expression was significantly correlated with the histological growth pattern (P = .019), the histological grade (P = .019), and longer survival (P = .001). LC3 expression was positively correlated with beclin 1 expression (P = .000); LC3 and beclin 1 expressions were positively correlated with GRP78 expression respectively (P = .035) (P = .008). Our study describes the expression of LC3, beclin 1, and GRP78 in adenoid cystic carcinoma and its relationship with clinicopathologic factors and overall survival. These results suggest that LC3, beclin 1, and GRP78 may play an important role in the tumorigenesis of adenoid cystic carcinoma, and that beclin 1 and GRP78 may serve as new prognostic indicators for the outcome of patients with adenoid cystic carcinoma.     

Psychotherapy for chronic major depression and dysthymia: A meta-analysis

Although several studies have examined the effects of psychotherapy on chronic depression and dysthymia, no meta-analysis has been conducted to integrate results of these studies. We conducted a meta-analysis of 16 randomized trials examining the effects of psychotherapy on chronic depression and dysthymia. We found that psychotherapy had a small but significant effect (d = 0.23) on depression when compared to control groups. Psychotherapy was significantly less effective than pharmacotherapy in direct comparisons (d = − 0.31), especially SSRIs, but that this finding was wholly attributable to dysthymic patients (the studies examining dysthymia patients were the same studies that examined SSRIs). Combined treatment was more effective than pharmacotherapy alone (d = 0.23) but even more so with respect to psychotherapy alone (d = 0.45), although again this difference may have reflected the greater proportion of dysthymic samples in the latter. No significant differences were found in drop-out rates between psychotherapy and the other conditions. We found indications that at least 18 treatment sessions are needed to realize optimal effects of psychotherapy. We conclude that psychotherapy is effective in the treatment of chronic depression and dysthymia but probably not as effective as pharmacotherapy (particularly the SSRIs).     

Semantic processing in comatose patients with intact temporal lobes as reflected by the N400 event-related potential

The present study aimed at determining whether the N400 effect (an ERP index of semantic processing) for spoken words occurs in comatose patients. The patients, treated in an intensive care unit, scored less than 8 points in the glasgow coma score at the time of the recording. Semantically related and unrelated spoken word pairs were delivered to patients through headphones at a rate of 1/3 s. Patients with an intact temporal lobe exhibited differential N400-like responses for semantically related and unrelated word pairs, which suggests that word semantics can be processed even in the comatose state. In contrast, patients with an injured temporal lobe showed no such effect.     

Evaluation of auditory, visual and olfactory event-related potentials for comparing interspersed- and single-stimulus paradigms

Background

An interspersed-stimulus paradigm (ISP) for event-related potential (ERP) recordings in which different sensory modality stimuli are presented within the same test session was developed to minimize recording time and facilitate modality comparison. The present study compared the ISP with a single-stimulus paradigm (SSP), using auditory, visual, and olfactory stimuli.

Method

Normal participants (n = 16) were assessed on two independent test occasions to obtain data on inter-paradigm and test-retest reliability. Peak amplitude/latency and area measures were obtained for the N1, P2 and P3 peaks for each paradigm.

Results

Except for larger auditory and visual P3 peaks and smaller visual P2 peaks in the ISP, no significant differences in amplitudes or latencies were found between the two paradigms. Correlation coefficients between paradigms were generally fairly high (amplitude mean r = 0.76; latency r = 0.42). Test-retest reliability within paradigms for amplitudes (ISP r = 0.70; SSP r = 0.68) and latencies (ISP r = 0.44; SSP r = 0.42) was similar across paradigms.

Conclusion

The findings suggest that the ISP, compared to the SSP, produces, in general, highly comparable auditory, visual, and olfactory peak amplitudes and latencies, and comparable reliability estimates, even though the ISP takes much less time to record (25 vs. 50 min). The larger auditory and visual P3 peaks and smaller visual P2 peaks in the ISP may be attributable to a less predictable stimulus environment. Thus, this method enables systematic comparisons of ERP peaks across sensory modalities while reducing testing time. Practical implications are discussed.     

Early frontal responses elicited by physical threat words in an emotional Stroop task: Modulation by anxiety sensitivity

High-density brain electrical activity elicited by physical threat, positive and neutral words were recorded in 33 healthy individuals screened for high or low anxiety sensitivity (AS) during a modified emotional Stroop task. The paradigm allowed the separate assessment of block and mixed-trial effects. In the block analysis, a significant emotional RT slowing was observed along with the modulation of a frontocentral negativity (350-400 ms) in the high AS group only. In contrast, the mixed-trial analysis revealed a positive enhancement of the ERP to threat words peaking earlier (200-300 ms) over anterior frontal scalp in the absence of RT slowing. This component was preceded by a very early positive modulation (peaking 50 ms) in the high AS group only. It is concluded that frontal ERPs to physical threat words can distinguish the contribution of emotional conflict and emotional salience, particularly in individuals with high trait-anxiety.     

Birth cohort increases in psychopathology among young Americans, 1938–2007: A cross-temporal meta-analysis of the MMPI

Two cross-temporal meta-analyses find large generational increases in psychopathology among American college students (N = 63,706) between 1938 and 2007 on the MMPI and MMPI-2 and high school students (N = 13,870) between 1951 and 2002 on the MMPI-A. The current generation of young people scores about a standard deviation higher (average d = 1.05) on the clinical scales, including Pd (Psychopathic Deviation), Pa (Paranoia), Ma (Hypomania), and D (Depression). Five times as many now score above common cutoffs for psychopathology, including up to 40% on Ma. The birth cohort effects are still large and significant after controlling for the L and K validity scales, suggesting that the changes are not caused by response bias. The results best fit a model citing cultural shifts toward extrinsic goals, such as materialism and status and away from intrinsic goals, such as community, meaning in life, and affiliation.     

Efficacy of short-term psychotherapy for multiple medically unexplained physical symptoms: a meta-analysis

Multiple medically unexplained physical symptoms (MUPS) are considered to be difficult and costly to treat. The current meta-analysis therefore investigates the efficacy of short-term psychotherapy for MUPS. Based on a multiple-phase literature search, studies were selected according to a-priori defined inclusion criteria. The standardized mean gain was used as the effect size index. Separate data aggregation of between- and within-group contrasts was performed on the basis of a mixed effects model. Outcome variables were physical symptoms, disorder specific emotions, cognitions and behaviors, depressive symptoms, general psychopathology, functional impairment, and health care utilization. Based on 27 included studies, small between-group effect sizes (range: d₊ = 0.06-d₊ = 0.40) and small to large within-group effect sizes (range: d₊ = 0.36-d₊ = 0.80) were found for post-treatment and follow-up assessments for the different outcome variables. Significant moderator variables were identified as the type, mode, and setting of therapy, number of therapy sessions, profession of therapist, age and sex of patients, quality of diagnostic procedure, and the control of concomitant treatments. Implications of the results for clinical practice and future research are discussed.     

A meta-analysis of nonrandomized effectiveness studies on outpatient cognitive behavioral therapy for adult anxiety disorders

Objective

The primary aim of this study was to assess the overall effectiveness of individual and group outpatient cognitive behavioral therapy (CBT) for adults with a primary anxiety disorder in routine clinical practice.

Method

We conducted a random effects meta-analysis of 71 nonrandomized effectiveness studies on outpatient individual and group CBT for adult anxiety disorders. Standardized mean gain effect sizes pre- to posttreatment, and posttreatment to follow-up are reported for disorder-specific symptoms, depression, and general anxiety. The mean dropout from CBT is reported.

Results

Outpatient CBT was effective in reducing disorder-specific symptoms in completer (d = 0.90–1.91) and intention-to-treat samples (d = 0.67–1.45). Moderate to large (d = 0.54–1.09) and small to large effect sizes (d = 0.42–0.97) were found for depressive and general anxiety symptoms posttreatment. Across all anxiety disorders, the weighted mean dropout rate was 15.06%. Posttreatment gains for disorder-specific anxiety were maintained 12 months after completion of therapy.

Conclusions

CBT for adult anxiety disorders is very effective and widely accepted in routine practice settings. However, the methodological and reporting quality of nonrandomized effectiveness studies must be improved.     

Human papillomaviruses 53 and 66: clinical aspects and genetic analysis

Variants of HPV types may have different oncogenic potential. While HPV 16 and 18 variants have been extensively studied, little is known on the less frequent high-risk types such as HPV 53 and 66. Here, we analyzed the genetic variability of HPV 53 and 66 by sequencing the E6, E7, L1 genes and the Long Control Region (LCR) sequences of HPV 53 and HPV 66 from infected women. Fisher's exact-test was performed to correlate viral variants with cervical lesions. Higher-order interactions among identified mutations were analyzed by co-variation and cluster analyses. Antigenic-index alterations following L1 mutations were predicted by Jameson-Wolf algorithm.In HPV53, novel variants were identified in L1 (N = 9) and E6 (N = 1) genes. The novel L1 mutation P432L was statistically associated with L-SIL lesions (P = 0.04) and its development reduced the L1 predicted antigenicity (up to −2.3 for Glu433). HPV 53 E6 and L1 sequences clustered phylogenetically into two main clades.In HPV 66, novel polymorphisms were identified in L1 (N = 4) and E6 (N = 4) genes. The L1 protein mutations S405P and D458N were exclusively found in patients with L-SILs. Seven E7 variants and 10 LCR variants were for the first time analyzed.Novel HPV 53 and 66 variants were identified in this study. Some of these mutations were significantly associated with L-SIL lesions and affected the antigenic index of the L1 protein with possible interesting implications in vaccine design.     

Reversibility in Chinese word formation influences target identification

We recorded event-related brain potentials during the processing of visually presented compound words in Mandarin Chinese. We capitalized on a particular characteristic of Chinese word formation, where two constituents can be combined in two different orders (A + B or B + A), yielding distinct meanings—so-called “reversible words”. By investigating the impact of structural reversibility on the processing of compounds in Chinese during a lexical decision task, the present study revealed a pronounced difference between reversible and non-reversible words. Analyses revealed a more enhanced negativity (N400) for reversible words, reflecting demands during semantic processing, followed by a P300-like deflection for non-reversible words, which we interpret with respect to the ease of target identification due to target discriminability. The findings indicate that both character combinations (A + B, B + A) as well as access to the individual constituent meanings result in interference during the processing of reversible and non-reversible words. They reveal that combinatorial processes are affected by demands arising from competing representations (N400), and more importantly, that this impacts the task-relevant cognitive processes required in the current word/non-word identification task (P300). The observed P300-like potential suggests that the allocation of attentional resources is intertwined with combinatorial operations.