Familial Mortality Risks in Patients With Ischemic Stroke: A Swedish Sibling Study.

BACKGROUND: The influence of familial factors on the prognosis of ischemic stroke (IS) is unknown. This nationwide follow-up study evaluated familial mortality risks of IS among Swedish sibling pairs hospitalized for IS. METHODS: We linked Swedish nationwide registers for the identification of 1380 Swedish born sibling pairs (2760 cases), where both siblings were hospitalized for first-time IS between 1991 and 2010. Median age was 62 years (range, 26-78 years). Sibling pairs with cancer were excluded. Familial hazard ratios (FHRs) for mortality after first IS hospitalization were determined with Cox regression. The influence of proband survival after IS was categorized as short sibling survival (<1, 2, 3, 4, or 5 years) or long sibling survival (≥1, 2, 3, 4, or 5 years) after IS. FHRs were adjusted for age at onset, sex, education, county, year of diagnosis, days of hospitalization, and comorbidities. RESULTS: Short sibling survival (ie, <3 or <4 years) after IS was associated with an adjusted FHR of 1.29 (95% CI, 1.05-1.58) and 1.24 (95% CI, 1.02-1.51), respectively, for overall mortality after IS. Stratified analysis showed that short sibling survival (ie, <2-<5 years) was stronger and significant only among younger individuals (<62 years) and males. Highest FHR for short sibling survival (ie, <4 years) was 1.42 (95% CI, 1.08-1.88) for younger individuals and 1.50 (95% CI, 1.21-1.87) for males. For young male subjects, FHR was 1.80 (95% CI, 1.33-2.46). In the adjusted model, mortality was also associated with sex, education, age at onset, year of diagnosis, days of hospitalization, coronary heart disease, diabetes, dementia, heart failure, obesity, alcoholism, and hyperlipidemia. CONCLUSIONS: Our results suggest that family history of short survival in siblings after IS is associated with mortality after IS for younger male subjects. Additional studies are needed to characterize possible genetic and nongenetic familial environmental causes of this association.

Cognitive dysfunction and quality of life during pollen season in children with seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis often gives rise to impaired quality of life and is believed to also affect cognitive function. We aimed to examine whether cognitive functions were impaired during grass pollen season in symptomatic allergic children and to relate the degree of impairment to quality of life and biomarkers related to stress and inflammation. METHODS: Forty-three grass pollen-allergic children (age 8-17 years) with non-satisfactory effect of medication (antihistamines and nasal steroids daily) during previous seasons were included. In addition, 26 matched non-allergic children were included as controls. Both groups performed cognitive tests (CANTAB) and completed Quality of Life questionnaires outside and during the pollen season. Blood samples were collected and analyzed for stress and inflammatory biomarkers. Pollen level was measured daily. RESULTS: Impaired cognitive function was found in spatial working memory, where the allergic group made more errors compared to the non-allergic group during pollen season, but not off-season. No significant differences could be seen between the allergic group and the controls in the other tests investigating visual memory or attention. Quality of health questionnaires revealed more symptoms and impaired quality of life in allergic compared to non-allergic children, and increased symptoms in allergic children were associated with longer reaction time for simple movement during pollen season. No differences in stress or inflammatory biomarkers could be found between the groups. CONCLUSION: Cognitive function was affected during pollen season in pollen-allergic children, and the more symptoms the allergic children had, the longer the reaction time in the cognitive tests.

Using a multi-feature paradigm to measure mismatch responses to minimal sound contrasts in children with cochlear implants and hearing aids.

Our aim was to explore whether a multi-feature paradigm (Optimum-1) for eliciting mismatch negativity (MMN) would objectively capture difficulties in perceiving small sound contrasts in children with hearing impairment (HI) listening through their hearing aids (HAs) and/or cochlear implants (CIs). Children aged 5-7 years with HAs, CIs and children with normal hearing (NH) were tested in a free-field setting using a multi-feature paradigm with deviations in pitch, intensity, gap, duration, and location. There were significant mismatch responses across all subjects that were positive (p-MMR) for the gap and pitch deviants (F(1,43) = 5.17, p = 0.028 and F(1,43) = 6.56, p = 0.014, respectively) and negative (MMN) for the duration deviant (F(1,43) = 4.74, p = 0.035). Only the intensity deviant showed a significant group interaction with MMN in the HA group and p-MMR in the CI group (F(2,43) = 3.40, p = 0.043). The p-MMR correlated negatively with age, with the strongest correlation in the NH subjects. In the CI group, the late discriminative negativity (LDN) was replaced by a late positivity with a significant group interaction for the location deviant. Children with severe HI can be assessed through their hearing device with a fast multi-feature paradigm. For further studies a multi-feature paradigm including more complex speech sounds may better capture variation in auditory processing in these children.

Segmental and suprasegmental properties in nonword repetition--an explorative study of the associations with nonword decoding in children with normal hearing and children with bilateral cochlear implants.

This study explored nonword repetition (NWR) and nonword decoding in normal-hearing (NH) children and in children with bilateral cochlear implants (CI). Participants were 11 children, with CI, 5:0-7:11 years (M = 6.5 years), and 11 NH children, individually age-matched to the children with CI. This study fills an important gap in research, since it thoroughly describes detailed aspects of NWR and nonword decoding and their possible associations. All children were assessed after having practiced with a computer-assisted reading intervention with a phonics approach during four weeks. Results showed that NH children outperformed children with CI on the majority of aspects of NWR. The analysis of syllable number in NWR revealed that children with CI made more syllable omissions than did the NH children, and predominantly in prestressed positions. In addition, the consonant cluster analysis in NWR showed significantly more consonant omissions and substitutions in children with CI suggesting that reaching fine-grained levels of phonological processing was particularly difficult for these children. No significant difference was found for nonword-decoding accuracy between the groups, as measured by whole words correct and phonemes correct, but differences were observed regarding error patterns. In children with CI phoneme, deletions occurred significantly more often than in children with NH. The correlation analysis revealed that the ability to repeat consonant clusters in NWR had the strongest associations to nonword decoding in both groups. The absence of as frequent significant associations between NWR and nonword decoding in children with CI compared to children with NH suggest that these children partly use other decoding strategies to compensate for less precise phonological knowledge, for example, lexicalizations in nonword decoding, specifically, making a real word of a nonword.

Impact of orbitofrontal lesions on electrophysiological signals in a stop signal task.

Behavioral inhibition and performance monitoring are critical cognitive functions supported by distributed neural networks including the pFC. We examined neurophysiological correlates of motor response inhibition and action monitoring in patients with focal orbitofrontal (OFC) lesions (n = 12) after resection of a primary intracranial tumor or contusion because of traumatic brain injury. Healthy participants served as controls (n = 14). Participants performed a visual stop signal task. We analyzed behavioral performance as well as event-related brain potentials and oscillations. Inhibition difficulty was adjusted individually to yield an equal amount of successful inhibitions across participants. RTs of patients and controls did not differ significantly in go trials or in failed stop trials, and no differences were observed in estimated stop signal RT. However, electrophysiological response patterns during task performance distinguished the groups. Patients with OFC lesions had enhanced P3 amplitudes to congruent condition go signals and to stop signals. In stop trials, patients had attenuated N2 and error-related negativity, but enhanced error positivity. Patients also showed enhanced and prolonged post-error beta band increases for stop errors. This effect was particularly evident in patients whose lesion extended to the subgenual cingulate cortex. In summary, although response inhibition was not impaired, the diminished stop N2 and ERN support a critical role of the OFC in action monitoring. Moreover, the increased stop P3, error positivity, and post-error beta response indicate that OFC injury affected action outcome evaluation and support the notion that the OFC is relevant for the processing of abstract reinforcers such as performing correctly in the task.

Computer-assisted reading intervention with a phonics approach for children using cochlear implants or hearing aids.

The present study examined computer-assisted reading intervention with a phonics approach for deaf and hard of hearing (DHH) children in Sweden using cochlear implants or hearing aids, or a combination of both. The study included 48 children, 5, 6 and 7 years of age. Sixteen children with normal hearing (NH) served as a reference group. The first purpose of the study was to compare NH and DHH children's reading ability at pre and post-intervention. The second purpose was to investigate effects of the intervention. Cognitive and demographic factors were analyzed in relation to reading improvement. Results showed no statistically significant difference for reading ability at the group level, although NH children showed overall higher reading scores at both test points. Age comparisons revealed a statistically significant higher reading ability in the NH 7-year-olds compared to the DHH 7-year-olds. The intervention proved successful for word decoding accuracy, passage comprehension and as a reduction of nonword decoding errors in both NH and DHH children. Reading improvement was associated with complex working memory and phonological processing skills in NH children. Correspondent associations were observed with visual working memory and letter knowledge in the DHH children. Age was the only demographic factor that was significantly correlated with reading improvement. The results suggest that DHH children's beginning reading may be influenced by visual strategies that might explain the reading delay in the older children.

Associative learning measured with ERP predicts deferred imitation using a strict observation only design in 14 to 15 month old children.

Deferred imitation (DI) is an established procedure for behavioral measurement of early declarative-like memories in infancy and previous work has indicated a link between this type of memory and brain potentials in infants. The present study compared infants' memory performance in this paradigm with electrophysiological indices of associative learning. Thirty children (M = 14.5 months) participated, of which 15 (8 boys) had acceptable event-related potentials (ERP) recordings that could be included in the final analysis. Deferred imitation was measured with an observation-only procedure using three actions and a 30 min delay. ERP was recorded with a high-density electrode net (128 electrodes) during associative learning. Change scores based on Nc, a middle latency component associated with attentional processes, predicted deferred imitation performance. Thus, associative learning measured with ERP predicts deferred imitation using a strict observation only design in 14 to 15 month old children.

Contribution of subregions of human frontal cortex to novelty processing.

Novelty processing was studied in patients with lesions centered in either OFC or lateral pFC (LPFC). An auditory novelty oddball ERP paradigm was applied with environmental sounds serving as task irrelevant novel stimuli. Lesions to the LPFC as well as the OFC resulted in a reduction of the frontal Novelty P3 response, supporting a key role of both frontal subdivisions in novelty processing. The posterior P3b to target sounds was unaffected in patients with frontal lobe lesions in either location, indicating intact posterior cortical target detection mechanisms. LPFC patients displayed an enhanced sustained negative slow wave (NSW) to novel sounds not observed in OFC patients, indicating prolonged resource allocation to task-irrelevant stimuli after LPFC damage. Both patient groups displayed an enhanced NSW to targets relative to controls. However, there was no difference in behavior between patients and controls suggesting that the enhanced NSW to targets may index an increased resource allocation to response requirements enabling comparable performance in the frontal lesioned patients. The current findings indicate that the LPFC and OFC have partly shared and partly differential contributions to the cognitive subcomponents of novelty processing.

Growth of language-related brain areas after foreign language learning.

The influence of adult foreign-language acquisition on human brain organization is poorly understood. We studied cortical thickness and hippocampal volumes of conscript interpreters before and after three months of intense language studies. Results revealed increases in hippocampus volume and in cortical thickness of the left middle frontal gyrus, inferior frontal gyrus, and superior temporal gyrus for interpreters relative to controls. The right hippocampus and the left superior temporal gyrus were structurally more malleable in interpreters acquiring higher proficiency in the foreign language. Interpreters struggling relatively more to master the language displayed larger gray matter increases in the middle frontal gyrus. These findings confirm structural changes in brain regions known to serve language functions during foreign-language acquisition.

Activating without inhibiting: left-edge boundary tones and syntactic processing.

Right-edge boundary tones have earlier been found to restrict syntactic processing by closing a clause for further integration of incoming words. The role of left-edge intonation, however, has received little attention to date. We show that Swedish left-edge boundary tones selectively facilitate the on-line processing of main clauses, the syntactic structure they are associated with. In spoken Swedish, main clauses are produced with a left-edge boundary tone, which is absent in subordinate clauses. Main and subordinate clauses are further distinguished syntactically by word order when containing sentence adverbs. The effects of tone and word order on the processing of embedded main, subordinate, and neutral clauses (lacking sentence adverbs) were measured using ERPs. A posterior P600 in embedded main clauses and a smaller P600 in subordinate clauses indicated that embedded clauses with sentence adverbs were structurally less expected than neutral clauses and thus were reanalyzed. The tone functioned as a cue for main clause word order, selectively reducing the P600 in embedded main clauses, without affecting the processing of subordinate or neutral clauses. Its perception was reflected in a right frontal P200 effect. The left-edge boundary tone thus seems to activate a main clause structure, albeit without suppressing alternative structures. The P600 was also preceded by a short positive effect in cases where a left-edge boundary tone was absent.

Dissociated control as a signature of typological variability in high hypnotic suggestibility.

This study tested the prediction that dissociative tendencies modulate the impact of a hypnotic induction on cognitive control in different subtypes of highly suggestible individuals. Low suggestible (LS), low dissociative highly suggestible (LDHS), and high dissociative highly suggestible (HDHS) participants completed the Stroop color-naming task in control and hypnosis conditions. The magnitude of conflict adaptation (faster response times on incongruent trials preceded by an incongruent trial than those preceded by a congruent trial) was used as a measure of cognitive control. LS and LDHS participants displayed marginally superior up-regulation of cognitive control following a hypnotic induction, whereas HDHS participants' performance declined. These findings indicate that dissociative tendencies modulate the influence of a hypnotic induction on cognitive control in high hypnotic suggestibility and suggest that HS individuals are comprised of distinct subtypes with dissimilar cognitive profiles.

Dissociative tendencies and individual differences in high hypnotic suggestibility.

INTRODUCTION: Inconsistencies in the relationship between dissociation and hypnosis may result from heterogeneity among highly suggestible individuals, in particular the existence of distinct highly suggestible subtypes that are of relevance to models of psychopathology and the consequences of trauma. This study contrasted highly suggestible subtypes high or low in dissociation on measures of hypnotic responding, cognitive functioning, and psychopathology. METHODS: Twenty-one low suggestible (LS), 19 low dissociative highly suggestible (LDHS), and 11 high dissociative highly suggestible (HDHS) participants were administered hypnotic suggestibility scales and completed measures of free recall, working memory capacity, imagery, fantasy-proneness, psychopathology, and exposure to stressful life events. RESULTS: HDHS participants were more responsive to positive and negative hallucination suggestions and experienced greater involuntariness during hypnotic responding. They also exhibited impaired working memory capacity, elevated pathological fantasy and dissociative symptomatology, and a greater incidence of exposure to stressful life events. In contrast, LDHS participants displayed superior object visual imagery. CONCLUSIONS: These results provide further evidence for two highly suggestible subtypes: a dissociative subtype characterised by deficits in executive functioning and a predisposition to psychopathology, and a subtype that exhibits superior imagery and no observable deficits in functioning.

Oh, it's you again: memory interference from irrelevant emotional and neutral faces.

In two experiments, repeated runs of a continuous recognition task were employed to assess healthy participants' ability to handle interference from irrelevant emotional and neutral memories. Presumably, such interference can be due to salience from either emotional or mnemonic processing. In both experiments, participants made more false alarms to emotional faces that were familiar from preceding runs (i.e., emotion-induced temporal-context confusion). Participants performed well for neutral faces in the first experiment including only two runs. However, increasing the number of runs to four in the second experiment induced temporal context confusion also for neutral faces. The findings suggest that memory interference can be induced when the salience of irrelevant information is erroneously considered diagnostic for memory judgements.

Auditory event-related potentials and mismatch negativity in children with hearing loss using hearing aids or cochlear implants - A three-year follow-up study.

OBJECTIVES: The primary aim was to examine how event-related potentials (ERPs) and mismatch negativity (MMN) change and develop over time among children with hearing loss (HL) using hearing aids (HAs) or cochlear implants (CIs). Children with normal hearing (NH) were tested as a reference group. METHODS: This three-year follow-up study included 13 children with sensorineural HL (SNHL); 7 children using bilateral HAs and 6 children using CIs; and 10 children with NH as a reference group. ERPs were recorded at baseline and after three years. At time for the original study the children were approximately 5-8 years old and at the follow-up study 8-11 years old. ERP recordings and data processing were identical in both sessions. A standard stimulus alternated with five different deviants (gap, intensity, pitch, location and duration), presented in a pseudorandom sequence, thus following the multi-feature paradigm, Optimum-1. MMN was calculated from the average ERP of each deviant minus the standard stimuli. Repeated measures ANOVA was used for the statistical analyses and the results were based on samples within a specific time interval; 80-224 ms. RESULTS: There was a statistically significant difference in the obligatory responses between the NH and HA groups at baseline, but this difference disappeared after three years in our follow-up study. The children with HA also showed a significant difference in mean ERP at baseline compared to follow-up, and significant differences between the deviants at follow-up but not at baseline. This suggests an improvement over time among the children with HAs. On the other hand, the children with CIs did not differ from the NH children at baseline, but after three years their mean ERP was significantly lower compared to both the children with HA and NH, indicating a reduced development of the central auditory system in this age span among the children with CIs. Regarding MMN, there was an interaction between the duration deviant and time for the children with HA, also indicating a possible improvement over time among the HA children. CONCLUSIONS: This three-year follow-up study shows neurophysiological differences between children with HL and children with NH. The results suggest a delay in the central auditory processing among the HA children compared to children with NH, but a possible catch-up, over time, and this potential may be worth to be utilized. Regarding the CI children, similar improvement in this age span is missing, meaning there are differences between the subgroups of children with HL, i.e. the children with HAs vs. CIs. The results highlight the importance of distinguishing between subgroups of children with HL in further research.

Endurance exercise training-responsive miR-19b-3p improves skeletal muscle glucose metabolism.

Skeletal muscle is a highly adaptable tissue and remodels in response to exercise training. Using short RNA sequencing, we determine the miRNA profile of skeletal muscle from healthy male volunteers before and after a 14-day aerobic exercise training regime. Among the exercise training-responsive miRNAs identified, miR-19b-3p was selected for further validation. Overexpression of miR-19b-3p in human skeletal muscle cells increases insulin signaling, glucose uptake, and maximal oxygen consumption, recapitulating the adaptive response to aerobic exercise training. Overexpression of miR-19b-3p in mouse flexor digitorum brevis muscle enhances contraction-induced glucose uptake, indicating that miR-19b-3p exerts control on exercise training-induced adaptations in skeletal muscle. Potential targets of miR-19b-3p that are reduced after aerobic exercise training include KIF13A, MAPK6, RNF11, and VPS37A. Amongst these, RNF11 silencing potentiates glucose uptake in human skeletal muscle cells. Collectively, we identify miR-19b-3p as an aerobic exercise training-induced miRNA that regulates skeletal muscle glucose metabolism.

ERP correlates of target-distracter differentiation in repeated runs of a continuous recognition task with emotional and neutral faces.

The emotional salience of faces has previously been shown to induce memory distortions in recognition memory tasks. This event-related potential (ERP) study used repeated runs of a continuous recognition task with emotional and neutral faces to investigate emotion-induced memory distortions. In the second and third runs, participants made more false alarms to distracters (repeated from previous runs). Emotion did not modulate the amount of errors, but the extent to which recollection was employed to maximise performance as reflected in the putative ERP correlate of recollection; the parietal old-new effect. Targets from all stimulus classes (positive, negative, neutral) were associated with parietal ERP memory effects, but this was also the case for correctly rejected negative distracters. This suggests that recollection was strategically used to correctly reject negative distracters (recall-to-reject). This finding is consistent with the view that facilitated recollection of negative stimuli may be used to decrease the susceptibility to memory errors induced by emotional salience.

Mortality risks associated with sibling heart failure.

BACKGROUND: The mortality in individuals with a family history of heart failure (HF) has not been determined. This nationwide sib-pair study aimed to determine mortality in individuals with a sibling affected with HF. METHODS: Sib-pairs were linked using the Swedish Multi-Generation Register, the Hospital Discharge Register and the Cause of Death Register for the period 1987-2012. Families with cardiomyopathy or congenital heart disease were excluded. Mortality hazard ratios (HRs) were calculated for siblings of individuals who had been diagnosed with HF compared with siblings of individuals unaffected by HF as the reference group. Similar analyses were made for spouses. HRs were determined for overall mortality, cardiovascular mortality, and death of unknown cause. RESULTS: Among siblings, the adjusted HR for overall mortality was 1.21 (95% CI 1.18-1.25). This risk remained (HR = 1.19, 95% CI 1.15-1.23) also among subjects without HF themselves. The adjusted HRs for cardiovascular mortality and death of unknown cause were 1.39 (95% CI 1.32-1.45) and 1.58 (95% CI 1.29-1.95), respectively. The mortality risk associations with spousal HF were all minimal, with an overall mortality HR of 1.02 (1.01-1.02). Early sibling age of onset of HF < 50 years was associated with higher HRs for overall mortality, cardiovascular mortality, and death of unknown cause, 1.33 (1.27-1.41), 1.54 (1.40-1.68) and 1.84 (1.27-2.67), respectively. CONCLUSIONS: Sibling HF, especially early-onset HF, is associated with increased mortality. The low risk in spouses suggests genetic factors might be of importance. Screening for HF, and cardiovascular disease in general, in these individuals may be warranted.

Computer-assisted reading intervention for children with hearing impairment using cochlear implants: Effects on auditory event-related potentials and mismatch negativity.

OBJECTIVES: The primary aim was to find out whether a computer-assisted reading intervention program with a phonic approach can affect event-related (ERPs) and mismatch negativity (MMN) in hearing impaired (HI) children using cochlear implants (CIs). METHODS: This study involved a test group of 15 HI children with CIs and a control group of 14 normal hearing (NH) children. The children were 4 years and 10 months to 8 years and 1 month old. ERPs were recorded immediately before and after 4 weeks of training with a computer-assisted reading intervention, GraphoGame. A multi-feature paradigm, Optimum-1, was used, i.e. a standard stimulus alternated with five different deviants: gap intensity, pitch, location and duration. MMN was calculated from the mean amplitude ERP of each deviant minus the standard stimulus response in a specific time interval, 80 - 224 ms. Repeated measures ANOVA was used for the statistical analysis. RESULTS: The results did not show any significant changes with the computerassisted training in the ERPs and MMNs among the HI children with CIs. The presence of both MMN and a positive mismatch response (pMMR), which might reflect an immaturity, complicates interpreting the results in this age group. Individually, there was a mix of MMNs and pMMRs among all participants, pre and post training, and the change of each deviant after intervention was not predictable. CONCLUSIONS: There are no significant changes in ERP or MMN after intervention, however lack of significances must be interpreted with caution. Besides the presence of both MMNs and pMMRs, only modest changes are to be expected on an individual basis and small samples hinder making statistical conclusions regarding the training's effects. The study contributes to some more descriptive pieces of ERPs and MMNs among the HI children with CIs. The issues of MMN and pMMR are highlighted.

Electrophysiological and behavioral measures of some speech contrasts in varied attention and noise.

This paper investigates the salience of speech contrasts in noise, in relation to how listening attention affects scalp-recorded cortical responses. The contrasts that were examined with consonant-vowel syllables, were place of articulation, vowel length and voice-onset time (VOT) and our analysis focuses on the correspondence between the effect of attention on the electrophysiology and the decrement in behavioral results when noise was added to the stimuli. Normal-hearing subjects (n = 20) performed closed-set syllable identification in no noise, 0, 4 and 8 dB signal-noise ratio (SNR). Identification in noise decreased markedly for place of articulation, moderately for vowel length and marginally for VOT. The same syllables were used in two electrophysiology conditions, where subjects attended to the stimuli, and also while their attention was diverted to a visual discrimination task. Differences in global field power between the attention conditions from each contrast showed that that the effect of attention was negligible for place of articulation. They implied offset encoding of vowel length and were early (starting at 117 ms), and of high amplitude (>3 µV) for VOT. There were significant correlations between the difference in syllable identification in no noise and 0 dB SNR and the electrophysiology results between attention conditions for the VOT contrast. Comparison of the two attention conditions with microstate analysis showed a significant difference in the duration of microstate class D. These results show differential integration of attention and syllable processing according to speech contrast and they suggest that there is correspondence between the salience of a contrast in noise and the effect of attention on the evoked electrical response.

Brain Measures of Toddlers' Shape Recognition Predict Language and Cognitive Skills at 6-7 Years.

While a number of studies have found that an improvement in object shape recognition is associated with language growth in infants and toddlers, no published studies have investigated the longitudinal relation between early shape recognition, and language abilities in later childhood. An electrophysiological measure of semantic processing (the N400) was used to assess shape recognition and general object recognition in a naming context in 20-month-olds. The measures of shape recognition strongly predicted language and cognitive abilities at 6-7 years even after controlling for toddler vocabulary size. The electrophysiological measures of general object recognition were not related to future language or cognitive abilities. These results suggest that early shape recognition abilities may play a role in language acquisition and influence even long-term language outcomes.