Age matters in the prevalence and clinical significance of ultra‐high‐risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS‐kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high‐risk symptoms in children and adolescents as compared to adults. We examined ultra‐high‐risk (UHR) symptoms and criteria in a sample of individuals aged 8‐40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non‐perceptive APS were differentiated. Psychosocial functioning and current non‐psychotic DSM‐IV axis I disorders were also surveyed. Well‐trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8‐15‐year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non‐perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non‐perceptive APS, and their interaction with age, also in terms of conversion to psychosis.     

Reading and Visual Search: A Developmental Study in Normal Children

Studies dealing with developmental aspects of binocular eye movement behaviour during reading are scarce. In this study we have explored binocular strategies during reading and during visual search tasks in a large population of normal young readers. Binocular eye movements were recorded using an infrared video-oculography system in sixty-nine children (aged 6 to 15) and in a group of 10 adults (aged 24 to 39). The main findings are (i) in both tasks the number of progressive saccades (to the right) and regressive saccades (to the left) decreases with age; (ii) the amplitude of progressive saccades increases with age in the reading task only; (iii) in both tasks, the duration of fixations as well as the total duration of the task decreases with age; (iv) in both tasks, the amplitude of disconjugacy recorded during and after the saccades decreases with age; (v) children are significantly more accurate in reading than in visual search after 10 years of age. Data reported here confirms and expands previous studies on children''s reading. The new finding is that younger children show poorer coordination than adults, both while reading and while performing a visual search task. Both reading skills and binocular saccades coordination improve with age and children reach a similar level to adults after the age of 10. This finding is most likely related to the fact that learning mechanisms responsible for saccade yoking develop during childhood until adolescence.     

Efficiency of use of physical exercises for management of the functional state of 6-8 year-old anxious children

In the research directed on optimisation of a functional state (FS) of disturbing children of 6-8 years, complex application of physical activities of mainly aerobic character, relaxation training is shown, that, respiratory exercises and functional music in long-term aspect selective use of considered means possesses more efficiency. At selective influence the expressed influence on FS disturbing children of 6-8 years in the conditions of intense information loading is rendered only by physical exercises. Application of other ways of optimisation FS is less effective. High effectiveness of use of physical exercises is caused by adaptable changes of mechanisms of regulation FS of disturbing children. Apparently, long-term adaptation to adequate muscular activity provides improvement of functioning and perfection of interaction activating and nonactivating structures of modulating system of the brain, localised on different levels the central nervous system (CNS) and, in particular, frontal departments of a bark. It is underlined, that features of influence of various receptions of regulation FS on an organism of disturbing children of younger school age are substantially caused by immaturity frontocortical-thalamic regulating system and specificity of the functional organisation limbic brain structures.     

Maturation of Cognitive Control: Delineating Response Inhibition and Interference Suppression

Cognitive control is integral to the ability to attend to a relevant task whilst suppressing distracting information or inhibiting prepotent responses. The current study examined the development of these two subprocesses by examining electrophysiological indices elicited during each process. Thirteen 18 year-old adults and thirteen children aged 8–11 years (mean = 9.77 years) completed a hybrid Go/Nogo flanker task while continuous EEG data were recorded. The N2 topography for both response inhibition and interference suppression changed with increasing age. The neural activation associated with response inhibition became increasingly frontally distributed with age, and showed decreases of both amplitude and peak latency from childhood to adulthood, possibly due to reduced cognitive demands and myelination respectively occurring during this period. Interestingly, a significant N2 effect was apparent in adults, but not observed in children during trials requiring interference suppression. This could be due to more diffuse activation in children, which would require smaller levels of activation over a larger region of the brain than is reported in adults. Overall, these results provide evidence of distinct maturational processes occurring throughout late childhood and adolescence, highlighting the separability of response inhibition and interference suppression.     

Effectiveness of physical exercises for regulation of the functional state of six- to eight-year-old anxious children

The study aimed at optimizing the functional state (FS) of anxious six- to eight-year-old children showed that integrated use of physical exercises of a mainly aerobic character, relaxation training, respiratory exercises, and functional music is more effective in the long-term aspect than selective use of these means. Only physical exercises exert a marked influence in the FS of six- to eight-year-old anxious children under a stressful informational load. The use of other means of optimizing the FS appears to be less effective. The high effectiveness of physical exercises is determined by adaptive changes in the mechanisms of FS regulation in anxious children. Apparently, long-term adaptation to an adequate muscular activity ensures improved functioning of, and a better interaction between, the activating and inactivating structures of the modulating brain system located at different levels of the CNS, in particular, in the frontal cortical areas. It is emphasized that the peculiarities of the influence of different means of regulation of the FS on the body of anxious elementary school children are, largely determined by the immaturity of the frontothalamic regulatory system and the specifics of the functional organization of the limbic brain structures.     

The Congruency Effect in the Posterior Medial Frontal Cortex Is More Consistent with Time on Task than with Response Conflict

The posterior medial frontal cortex (pMFC) is thought to play a pivotal role in enabling the control of attention during periods of distraction. In line with this view, pMFC activity is ubiquitously greater in incongruent trials of response-interference (e.g., Stroop) tasks than in congruent trials. Nonetheless, the process underlying this congruency effect remains highly controversial. We therefore sought to distinguish between two competing accounts of the congruency effect. The conflict monitoring account posits the effect indexes a process that detects conflict between competing response alternatives, which is indexed by trial-specific reaction time (RT). The time on task account posits the effect indexes a process whose recruitment increases with time on task independent of response conflict (e.g., sustained attention, arousal, effort, etc.). To distinguish between these accounts, we used functional MRI to record brain activity in twenty-four healthy adults while they performed two tasks: a response-interference task and a simple RT task with only one possible response. We reasoned that demands on a process that detects response conflict should increase with RT in the response-interference task but not in the simple RT task. In contrast, demands on a process whose recruitment increases with time on task independent of response conflict should increase with RT in both tasks. Trial-by-trial analyses revealed that pMFC activity increased with RT in both tasks. Moreover, pMFC activity increased with RT in the simple RT task enough to fully account for the congruency effect in the response-interference task. These findings appear more consistent with the time on task account of the congruency effect than with the conflict monitoring account.     

Increased brain signal variability accompanies lower behavioral variability in development

As the brain matures, its responses become optimized. Behavioral measures show this through improved accuracy and decreased trial-to-trial variability. The question remains whether the supporting brain dynamics show a similar decrease in variability. We examined the relation between variability in single trial evoked electrical activity of the brain (measured with EEG) and performance of a face memory task in children (8–15 y) and young adults (20–33 y). Behaviorally, children showed slower, more variable response times (RT), and less accurate recognition than adults. However, brain signal variability increased with age, and showed strong negative correlations with intrasubject RT variability and positive correlations with accuracy. Thus, maturation appears to lead to a brain with greater functional variability, which is indicative of enhanced neural complexity. This variability may reflect a broader repertoire of metastable brain states and more fluid transitions among them that enable optimum responses. Our results suggest that the moment-to-moment variability in brain activity may be a critical index of the cognitive capacity of the brain.     

Developmental changes of prefrontal activation in humans: a near-infrared spectroscopy study of preschool children and adults

Previous morphological studies indicated that development of the human prefrontal cortex (PFC) appears to continue into late adolescence. Although functional brain imaging studies have sought to determine the time course of functional development of the PFC, it is unclear whether the developmental change occurs after adolescence to adulthood and when it achieves a peak because of the narrow or discontinuous range in the participant's age. Moreover, previous functional studies have not focused on the anterior frontal region, that is, the frontopolar regions (BA9/10). Thus, the present study investigated the developmental change in frontopolar PFC activation associated with letter fluency task by using near-infrared spectroscopy (NIRS), in subjects from preschool children to adults. We analyzed the relative concentration of hemoglobin (ΔHb) in the prefrontal cortex measured during the activation task in 48 typically-developing children and adolescents and 22 healthy adults. Consistent with prior morphological studies, we found developmental change with age in the children/adolescents. Moreover, the average Δoxy-Hb in adult males was significantly larger than that in child/adolescent males, but was not true for females. These data suggested that functional development of the PFC continues into late adolescence. Although the developmental change of the frontopolar PFC was independent of gender from childhood to adolescence, in adulthood a gender difference was shown.     

Electrophysiological analysis of the perceptive activities of children with normal and retarded mental development

Visual EPs of the occipital, parieto-temporal-occipital, parietal and central areas of the left and right hemispheres in response to unilaterally presented stimuli (figures) were analyzed in normal and developmentally backward children. In tasks of detection and recognition of the signal, developmentally backward children manifested a lowered reactivity of associative cerebral structures, especially of the left hemisphere, during perceptive activity, and a changed, in comparison with normal, interhemispheric interaction in processing of sensory information. It is suggested that properties of brain system organization during perceptive activity reflect to a certain extent neurophysiological mechanisms of disturbance of cognitive processes in developmentally backward children.     

Age-related alterations of extracellular signal-regulated kinase 2 mRNA expression in the rat brain

Brain glutathione system (Glut-Syst) exhibits functional changes with age as well as during neurodegenerative diseases. After NGF treatment, cognitive functions and Glut-Syst activity are favorably modified in aged rats. also, the environmental enrichment (E-E) activates molecular mechanisms linked to cognition and sensorimotor coordination. We evaluate the functional repercussion of the combination of both factors. Old cognitively impaired rats received intracerebroventricular infusion of NGF (ICV, 22 mg/mL) or intraparenquimal (IP-nbM, 5.5 mg/mL) during 14 days using ALZET osmotic minipumps. Simultaneously, these animals received a passive training in an E-E during 4 weeks. A control group received training + saline infusion. Animals were assessed in the water maze task, avoidance passive test, open field test and transverse bridges test. At the end of the week 4, glutathione content and Choline Acetyltransferase (ChAT) activity were measured in brain areas of interest. E-E or NGF treatments, particularly the IP route, improve the rat's overall behavioral performance but a synergic effect was observed when NGF and E-E were applied simultaneously. A trend to hyperactivity was detected in the ICV group. Glutathione content and ChAT activity exhibited significant changes according to the group and brain area. It's well known that activity/levels of antioxidant enzymes and ChAT activity are related to age, brain region and neurotrophins activity. Results point out the possibilities of neurotrophic therapy if an adequate route of delivery is used as well as the benefit of combining a neurorehabilitation program on both, behavioural and protection from oxidative stress.     

Poster Sessions CP02: Aging. Combination of NGF treatment and enrichment environment in old rats: biochemical and behavioral consequences

Brain glutathione system (Glut‐Syst) exhibits functional changes with age as well as during neurodegenerative diseases. After NGF treatment, cognitive functions and Glut‐Syst activity are favorably modified in aged rats. also, the environmental enrichment (E‐E) activates molecular mechanisms linked to cognition and sensorimotor coordination. We evaluate the functional repercussion of the combination of both factors. Old cognitively impaired rats received intracerebroventricular infusion of NGF (ICV, 22 mg/mL) or intraparenquimal (IP‐nbM, 5.5 mg/mL) during 14 days using ALZET osmotic minipumps. Simultaneously, these animals received a passive training in an E‐E during 4 weeks. A control group received training + saline infusion. Animals were assessed in the water maze task, avoidance passive test, open field test and transverse bridges test. At the end of the week 4, glutathione content and Choline Acetyltransferase (ChAT) activity were measured in brain areas of interest. E‐E or NGF treatments, particularly the IP route, improve the rat's overall behavioral performance but a synergic effect was observed when NGF and E‐E were applied simultaneously. A trend to hyperactivity was detected in the ICV group. Glutathione content and ChAT activity exhibited significant changes according to the group and brain area. It's well known that activity/levels of antioxidant enzymes and ChAT activity are related to age, brain region and neurotrophins activity. Results point out the possibilities of neurotrophic therapy if an adequate route of delivery is used as well as the benefit of combining a neurorehabilitation program on both, behavioural and protection from oxidative stress.     

Functional maturation of the brain and formation of the neurophysiological mechanisms of selective voluntary attention in young schoolchildren

A particular role was demonstrated for functional maturation of the frontothalamic system (FTS) of the brain in forming the cerebral organization of selective voluntary attention in ontogeny. Analysis of the coherence of the rhythmic components of the EEG α range in adults and seven-to eight-and nine-to ten-year-old children showed that, if the functional state of the control structures corresponds to the age, the formation of the neurophysiological mechanisms selectively modulating cortical activity and supporting selective tuning of the cerebral structures to the cognitive task is completed by the age of seven or eight years. Unlike adults, children demonstrated no interhemispheric features of the intercenter integration of cortical zones in the prestimulus period of voluntary attention. Children with a functionally immature FTS lacked selective specific integration of cortical zones in the pretuning period. The deficit of selective modulation of cortical activity in children with a functionally immature FTS is considered as the neurophysiological factor that delays the formation of voluntary attention and voluntary control of activity and, finally, leads to learning difficulties.     

Working memory in attention deficit/hyperactivity disorder is characterized by a lack of specialization of brain function

Working memory impairments are frequent in Attention Deficit/Hyperactivity Disorder (ADHD) and create problems along numerous functional dimensions. The present study utilized the Visual Serial Addition Task (VSAT) and functional magnetic resonance imaging (fMRI) to explore working memory processes in thirteen typically developing (TD) control and thirteen children with ADHD, Combined type. Analysis of Variance (ANOVA) was used to examine both main effects and interactions. Working memory-specific activity was found in TD children in the bilateral prefrontal cortex. In contrast the within-group map in ADHD did not reveal any working-memory specific regions. Main effects of condition suggested that the right middle frontal gyrus (BA6) and the right precuneus were engaged by both groups during working memory processing. Group differences were driven by significantly greater, non-working memory-specific, activation in the ADHD relative to TD group in the bilateral insula extending into basal ganglia and the medial prefrontal cortex. A region of interest analysis revealed a region in left middle frontal gyrus that was more active during working memory in TD controls. Thus, only the TD group appeared to display working memory-modulated brain activation. In conclusion, children with ADHD demonstrated reduced working memory task specific brain activation in comparison to their peers. These data suggest inefficiency in functional recruitment by individuals with ADHD represented by a poor match between task demands and appropriate levels of brain activity.     

Age-Related Changes in Task Related Functional Network Connectivity

Aging has a multi-faceted impact on brain structure, brain function and cognitive task performance, but the interaction of these different age-related changes is largely unexplored. We hypothesize that age-related structural changes alter the functional connectivity within the brain, resulting in altered task performance during cognitive challenges. In this neuroimaging study, we used independent components analysis to identify spatial patterns of coordinated functional activity involved in the performance of a verbal delayed item recognition task from 75 healthy young and 37 healthy old adults. Strength of functional connectivity between spatial components was assessed for age group differences and related to speeded task performance. We then assessed whether age-related differences in global brain volume were associated with age-related differences in functional network connectivity. Both age groups used a series of spatial components during the verbal working memory task and the strength and distribution of functional network connectivity between these components differed across the age groups. Poorer task performance, i.e. slower speed with increasing memory load, in the old adults was associated with decreases in functional network connectivity between components comprised of the supplementary motor area and the middle cingulate and between the precuneus and the middle/superior frontal cortex. Advancing age also led to decreased brain volume; however, there was no evidence to support the hypothesis that age-related alterations in functional network connectivity were the result of global brain volume changes. These results suggest that age-related differences in the coordination of neural activity between brain regions partially underlie differences in cognitive performance.     

Influence of cognitive load on the body functional state in children aged 9 to 12 years during early stages of puberty

This article analyzes heart rate variability (HRV), the glucocorticoid function of adrenal glands, and brain electrical activity (EA) in children aged 9 to 12 years to study their functional state during early stages of puberty. The cognitive load (mental arithmetic) caused low-frequency waves in the heart rate spectrum in all subjects, regardless of the puberty stage and gender. With respect to the age range under study, the hormonal response to the arithmetic test, expressed in a decrease in the level of cortisol, was observed in boys only at the third stage of puberty. The visual analysis of the background electrical encephalogram showed frequent generalized bilateral and synchronous changes in the electrical activity (EA) in the form of diencephalic signs in children. The features of the relationship between the autonomic nervous system and the hypothalamic pituitary-adrenal system have been revealed in children aged 9 to 12 years during cognitive load. The closest correlations between HRV indices and cortisol levels have been found in girls at the first stage and boys at the third stage of puberty.     

Cognitive mechanisms of nicotine on visual attention

Understanding nicotine's neurobiological and cognitive mechanisms may help explain both its addictive properties and potential therapeutic applications. As such, functional MRI was used to determine the neural substrates of nicotine's effects on a sustained attention (rapid visual information-processing) task. Performance was associated with activation in a fronto-parietal-thalamic network in both smokers and nonsmokers. Along with subtle behavioral deficits, mildly abstinent smokers showed less task-induced brain activation in the parietal cortex and caudate than did nonsmokers. Transdermal nicotine replacement improved task performance in smokers and increased task-induced brain activation in the parietal cortex, thalamus, and caudate, while nicotine induced a generalized increase in occipital cortex activity. These data suggest that nicotine improves attention in smokers by enhancing activation in areas traditionally associated with visual attention, arousal, and motor activation.     

The role of the temporal neocortex in the origin of convulsive activity]

Experiments on cats with cooling capsules implanted over different areas of the neocortex have shown that cooling of different intensity applied to the temporal neocortex may result in both stimulation and switching off effects. Cold stimulation (temperature dropping to 27-33 degrees C) manifested in generalized epileptiform brain electrical activity and paroxysmal states. The functional switching off the temporal area observed during its deeper cooling (20-21 degrees C) discontinues the paroxysmal state already developed and prevents the appearance of seizures, regrardless of the localization of the epileptogenic focus. The paroxysmal state weakens and ceases after repeated cooling of the temporal neocortex. The temporal neocortex, involved in the integrated activating brain system, plays a decisive role in the emergence of paroxysmal states.     

Developmental Changes in Task‐Induced Brain Deactivation in Humans Revealed by a Motor Task

Performing tasks activates relevant brain regions in adults while deactivating task‐irrelevant regions. Here, using a well‐controlled motor task, we explored how deactivation is shaped during typical human development and whether deactivation is related to task performance. Healthy right‐handed children (8–11 years), adolescents (12–15 years), and young adults (20–24 years; 20 per group) underwent functional magnetic resonance imaging with their eyes closed while performing a repetitive button‐press task with their right index finger in synchronization with a 1‐Hz sound. Deactivation in the ipsilateral sensorimotor cortex (SM1), bilateral visual and auditory (cross‐modal) areas, and bilateral default mode network (DMN) progressed with development. Specifically, ipsilateral SM1 and lateral occipital deactivation progressed prominently between childhood and adolescence, while medial occipital (including primary visual) and DMN deactivation progressed from adolescence to adulthood. In adults, greater cross‐modal deactivation in the bilateral primary visual cortices was associated with higher button‐press timing accuracy relative to the sound. The region‐specific deactivation progression in a developmental period may underlie the gradual promotion of sensorimotor function segregation required in the task. Task‐induced deactivation might have physiological significance regarding suppressed activity in task‐irrelevant regions. Furthermore, cross‐modal deactivation develops to benefit some aspects of task performance in adults.     

The Maturation of Interference Suppression and Response Inhibition: ERP Analysis of a Cued Go/Nogo Task

Inhibitory control is a core function that allows us to resist interference from our surroundings and to stop an ongoing action. To date, it is not clear whether inhibitory control is a single process or whether it is composed of different processes. Further, whether these processes are separate or clustered in childhood is under debate. In this study, we investigated the existence and development of two hypothesized component processes of inhibitory control–interference suppression and response inhibition–using a single task and event related potential components. Twenty 8-year-old children and seventeen adults performed a spatially cued Go/Nogo task while their brain activity was recorded using electroencephalography. Mean N2 amplitudes confirmed the expected pattern for response inhibition with both the children and the adults showing more negative N2 for Nogo vs. Go trials. The interference suppression N2 effect was only present in adults and appeared as a more negative N2 in response to Go trials with a congruent cue than Go trials with an incongruent cue. Contrary to previous findings, there was no evidence that the interference suppression N2 effect was later occurring than the response inhibition N2 effect. Overall, response inhibition was present in both the children and the adults whereas interference suppression was only present in the adults. These results provide evidence of distinct maturational processes for both component processes of inhibitory control, with interference suppression probably continuing to develop into late childhood.