Cognitive performance is related to cortical grey matter volumes in early stages of schizophrenia: A population-based study of first-episode psychosis

Background: Neuropsychological deficits have been reported in association with first-episode psychosis (FEP). Reductions in grey matter (GM) volumes have been documented in FEP subjects compared to healthy controls. However, the possible inter-relationship between the findings of those two lines of research has been scarcely investigated.

Objective: To investigate the relationship between neuropsychological deficits and GM volume abnormalities in a population-based sample of FEP patients compared to healthy controls from the same geographical area.

Methods: FEP patients (n = 88) and control subjects (n = 86) were evaluated by neuropsychological assessment (Controlled Oral Word Association Test, forward and backward digit span tests) and magnetic resonance imaging using voxel-based morphometry.

Results: Single-group analyses showed that prefrontal and temporo-parietal GM volumes correlated significantly (p < 0.05, corrected) with cognitive performance in FEP patients. A similar pattern of direct correlations between neocortical GM volumes and cognitive impairment was seen in the schizophrenia subgroup (n = 48). In the control group, cognitive performance was directly correlated with GM volume in the right dorsal anterior cingulate cortex and inversely correlated with parahippocampal gyral volumes bilaterally. Interaction analyses with "group status" as a predictor variable showed significantly greater positive correlation within the left inferior prefrontal cortex (BA46) in the FEP group relative to controls, and significantly greater negative correlation within the left parahippocampal gyrus in the control group relative to FEP patients.

Conclusion: Our results indicate that cognitive deficits are directly related to brain volume abnormalities in frontal and temporo-parietal cortices in FEP subjects, most specifically in inferior portions of the dorsolateral prefrontal cortex. (C) 2009 Elsevier B.V. All rights reserved.

Lateralisation of language function in young adults born very preterm

Objective: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm.

Subjects: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls.

Method: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance.

Results: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area.

Conclusions: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.

Episodic memory and learning in patients with chronic schizophrenia

This study explored the pattern of memory functioning in 58 patients with chronic schizophrenia and compared their performance with 53 normal controls. Multiple domains of memory were assessed, including verbal and nonverbal memory span, verbal and non-verbal paired associate learning, verbal and visual long-term memory, spatial and non-spatial conditional associative learning, recognition memory and memory for temporal order. Consistent with previous studies, substantial deficits in long-term memory were observed, with relative preservation of memory span. Memory for temporal order and recognition memory was intact, although significant deficits were observed on the conditional associative learning tasks. There was no evidence of lateralized memory impairment. In these respects, the pattern of memory impairment in schizophrenia is more similar in nature to that found in patients with memory dysfunction following mesiotemporal lobe lesions, rather than that associated with focal frontal lobe damage. (C) 1999 Elsevier Science B.V. All rights reserved.

An enantio-selective chromatographic stationary phase for S-ibuprofen prepared by stoichiometric molecular imprinting

Molecularly Imprinted Polymers (MIPs) against S-ibuprofen were synthesised using a tailor made functional monomer, 2-acrylamido-4-methylpyridine, following extensive pre-polymerisation studies of template-monomer complexation. An apparent association constant of 340 +/- 22 M-1 was calculated that was subsequently corrected to account for dimerisation of ibuprofen (K-dim = 320 +/- 95 M-1) resulting in an intrinsic association constant of 715 +/- 16 M-1, consistent with previously reported values. Using the synthesised imprinted polymer as a stationary phase, complete resolution of a racemic mixture of ibuprofen was achieved in predominantly aqueous mobile phases. An imprinting factor of 10 was observed, and was found to be in agreement with the difference in the average number of binding sites between MIP and blank polymers, calculated by staircase frontal chromatography. The imprinted polymers exhibited enhanced selectivity for the templated drug over structurally related NSAIDs. When applied as sorbents in solid-phase extraction of ibuprofen from commercial tablets, urine and blood serum samples, recoveries up to 92.2% were achieved. © The Royal Society of Chemistry 2012

Electroencephalographic Activity in Response to Procedural Pain in Preterm Infants Born at 28 and 33 Weeks Gestational Age

OBJECTIVES:: Preterm infants undergo frequent painful procedures in the neonatal intensive care unit. Electroencephalography (EEG) changes in reaction to invasive procedures have been reported in preterm and full-term neonates. Frontal EEG asymmetry as an index of emotion during tactile stimulation shows inconsistent findings in full-term infants, and has not been examined in the context of pain in preterm infants. Our aim was to examine whether heel lance for blood collection induces changes in right-left frontal asymmetry, suggesting negative emotional response, in preterm neonates at different gestational age (GA) at birth and different duration of stay in the neonatal intensive care unit. MATERIALS AND METHODS:: Three groups of preterm infants were compared: set 1: group 1 (n=24), born and tested at 28 weeks GA; group 2 (n=22), born at 28 weeks GA and tested at 33 weeks; set 2: group 3 (n=25), born and tested at 33 weeks GA. EEG power was calculated for 30-second artifact-free periods, in standard frequency bandwidths, in 3 phases (baseline, up to 5 min after heel lance, 10 min after heel lance). RESULTS:: No significant differences were found in right-left frontal asymmetry, or in ipsilateral or contralateral somatosensory response, across phases. In contrast, the Behavioral Indicators of Infant Pain scores changed across phase (P

Magnetoencephalography reveals slowing of resting peak oscillatory frequency in children born very preterm

Resting cortical activity is characterized by a distinct spectral peak in the alpha frequency range. Slowing of this oscillatory peak toward the upper theta-band has been associated with a variety of neurological and neuropsychiatric conditions and has been attributed to altered thalamocortical dynamics. Children born very preterm exhibit altered development of thalamocortical systems. To test the hypothesis that peak oscillatory frequency is slowed in children born very preterm, we recorded resting magnetoencephalography (MEG) from school age children born very preterm (= 32 wk gestation) without major intellectual or neurological impairment and age-matched full-term controls. Very preterm children exhibit a slowing of peak frequency toward the theta-band over bilateral frontal cortex, together with reduced alpha-band power over bilateral frontal and temporal cortex, suggesting that mildly dysrhythmic thalamocortical interactions may contribute to altered spontaneous cortical activity in children born very preterm.

Altered Long-Range Phase Synchronization and Cortical Activation in Children Born Very Preterm

Children born very preterm, even with broadly normal IQ, commonly show selective difficulties in visuospatial processing and executive functioning. Very little, however, is known what alterations in cortical processing underlie these deficits. We recorded MEG while eight children born very preterm (=32 weeks gestational age) and eight full-term controls performed a visual short-term memory task at mean age 7.5 years (range 6.4 - 8.4). Previously, we demonstrated increased long-range alpha and beta band phase synchronization between MEG sensors during STM retention in a group of 17 full-term children age 6-10 years. Here we present preliminary evidence that long-range phase synchronization in very preterm children, relative to controls, is reduced in the alpha-band but increased in the theta-band. In addition, we investigated cortical activation during STM retention employing synthetic aperture magnetometry (SAM) beamformer to localize changes in gamma-band power. Preliminary results indicate sequential activation of occipital, parietal and frontal cortex in control children, as well as reduced activation in very preterm children relative to controls. These preliminary results suggest that children born very preterm exhibit altered inter-regional functional connectivity and cortical activation during cognitive processing.

Long-range synchronization and local desynchronization of alpha oscillations during visual short-term memory retention in children

Local alpha-band synchronization has been associated with both cortical idling and active inhibition. Recent evidence, however, suggests that long-range alpha synchronization increases functional coupling between cortical regions. We demonstrate increased long-range alpha and beta band phase synchronization during short-term memory retention in children 6-10 years of age. Furthermore, whereas alpha-band synchronization between posterior cortex and other regions is increased during retention, local alpha-band synchronization over posterior cortex is reduced. This constitutes a functional dissociation for alpha synchronization across local and long-range cortical scales. We interpret long-range synchronization as reflecting functional integration within a network of frontal and visual cortical regions. Local desynchronization of alpha rhythms over posterior cortex, conversely, likely arises because of increased engagement of visual cortex during retention.

Molecularly Imprinted Polymers for Corticosteroids: Impact of polymer format on recognition behaviour

A comparative study of different polymeric formats for the targeting of corticosteroids, focusing on the use of bulk monolith and precipitation polymerisation strategies, was performed and the effect on recognition behaviour was studied. Hydrocortisone-17-butyrate was selected as the template and methacrylic acid as the functional monomer, following 1H NMR investigation of the pre-polymerisation mixture. Three different cross-linkers were tested, ranging from moderate to highly hydrophobic. The synthesised bulk and precipitated imprinted polymers were physically characterised by nitrogen sorption and evaluated by means of HPLC and frontal chromatography against a range of template analogues. While some degree of selectivity for the template was achieved for all tested polymers, the ones based on the tri-functional cross-linking monomer TRIM exhibited the longest retention for all corticosteroids, especially in the precipitated format, which suggested 31 broader group selectivity.

Discriminating Taxonomic Categories and Domains in Mental Simulations of Concepts of Varying Concreteness

Most studies of conceptual knowledge in the brain focus on a narrow range of concrete conceptual categories, rely on the researchers' intuitions about which object belongs to these categories, and assume a broadly taxonomic organization of knowledge. In this fMRI study, we focus on concepts with a variety of concreteness levels; we use a state of the art lexical resource (WordNet 3.1) as the source for a relatively large number of category distinctions and compare a taxonomic style of organization with a domain-based model (associating concepts with scenarios). Participants mentally simulated situations associated with concepts when cued by text stimuli. Using multivariate pattern analysis, we find evidence that all Taxonomic categories and Domains can be distinguished from fMRI data and also observe a clear concreteness effect: Tools and Locations can be reliably predicted for unseen participants, but less concrete categories (e.g., Attributes, Communications, Events, Social Roles) can only be reliably discriminated within participants. A second concreteness effect relates to the interaction of Domain and Taxonomic category membership: Domain (e.g., relation to Law vs. Music) can be better predicted for less concrete categories. We repeated the analysis within anatomical regions, observing discrimination between all/most categories in the left middle occipital and temporal gyri, and more specialized discrimination for concrete categories Tool and Location in the left precentral and fusiform gyri, respectively. Highly concrete/abstract Taxonomic categories and Domain were segregated in frontal regions. We conclude that both Taxonomic and Domain class distinctions are relevant for interpreting neural structuring of concrete and abstract concepts.

Neural correlates of task switching in paternal 15q11-q13 deletion Prader-Willi syndrome

We report a first study of brain activity linked to task switching in individuals with Prader-Willi syndrome (PWS) PWS individuals show a specific cognitive deficit in task switching which may be associated with the display of temper outbursts and repetitive questioning The performance of participants with PWS and typically developing controls was matched in a cued task switching procedure and brain activity was contrasted on switching and non switching blocks using SARI Individuals with PWS did not show the typical frontal-parietal pattern of neural activity associated with switching blocks, with significantly reduced activation in regions of the posterior parietal and ventromedial prefrontal cortices We suggest that this is linked to a difficulty in PWS in setting appropriate attentional weights to enable task set reconfiguration In addition to this, PWS individuals did not show the typical pattern of deactivation, with significantly less deactivation in an anterior region of the ventromedial prefrontal cortex One plausible explanation for this is that individuals with PWS show dysfunction within the default mode network which has been linked to attentional control The data point to functional changes in the neural circuitry supporting task switching in PWS even when behavioural performance is matched to controls and thus highlight neural mechanisms that may be involved in a specific pathway between genes cognition and behaviour (C) 2010 Elsevier B V All rights reserved

The presence of a culturally similar or dissimilar social partner affects neural responses to emotional stimuli

Background: Emotional responding is sensitive to social context; however, little emphasis has been placed on the mechanisms by which social context effects changes in emotional responding.

Objective: We aimed to investigate the effects of social context on neural responses to emotional stimuli to inform on the mechanisms underpinning context-linked changes in emotional responding.

Design: We measured event-related potential (ERP) components known to index specific emotion processes and self-reports of explicit emotion regulation strategies and emotional arousal. Female Chinese university students observed positive, negative, and neutral photographs, whilst alone or accompanied by a culturally similar (Chinese) or dissimilar researcher (British).

Results: There was a reduction in the positive versus neutral differential N1 amplitude (indexing attentional capture by positive stimuli) in the dissimilar relative to alone context. In this context, there was also a corresponding increase in amplitude of a frontal late positive potential (LPP) component (indexing engagement of cognitive control resources). In the similar relative to alone context, these effects on differential N1 and frontal LPP amplitudes were less pronounced, but there was an additional decrease in the amplitude of a parietal LPP component (indexing motivational relevance) in response to positive stimuli. In response to negative stimuli, the differential N1 component was increased in the similar relative to dissimilar and alone (trend) context.

Conclusion: These data suggest that neural processes engaged in response to emotional stimuli are modulated by social context. Possible mechanisms for the social-context-linked changes in attentional capture by emotional stimuli include a context-directed modulation of the focus of attention, or an altered interpretation of the emotional stimuli based on additional information proportioned by the context.

The effects of TMS over dorsolateral prefrontal cortex on trans-saccadic memory of multiple objects

Humans typically make several rapid eye movements (saccades) per second. It is thought that visual working memory can retain and spatially integrate three to four objects or features across each saccade but little is known about this neural mechanism. Previously we showed that transcranial magnetic stimulation (TMS) to the posterior parietal cortex and frontal eye fields degrade trans-saccadic memory of multiple object features (Prime, Vesia, & Crawford, 2008, Journal of Neuroscience, 28(27), 6938-6949; Prime, Vesia, & Crawford, 2010, Cerebral Cortex, 20(4), 759-772.). Here, we used a similar protocol to investigate whether dorsolateral prefrontal cortex (DLPFC), an area involved in spatial working memory, is also involved in trans-saccadic memory. Subjects were required to report changes in stimulus orientation with (saccade task) or without (fixation task) an eye movement in the intervening memory interval. We applied single-pulse TMS to left and right DLPFC during the memory delay, timed at three intervals to arrive approximately 100ms before, 100ms after, or at saccade onset. In the fixation task, left DLPFC TMS produced inconsistent results, whereas right DLPFC TMS disrupted performance at all three intervals (significantly for presaccadic TMS). In contrast, in the saccade task, TMS consistently facilitated performance (significantly for left DLPFC/perisaccadic TMS and right DLPFC/postsaccadic TMS) suggesting a dis-inhibition of trans-saccadic processing. These results are consistent with a neural circuit of trans-saccadic memory that overlaps and interacts with, but is partially separate from the circuit for visual working memory during sustained fixation.

3D Morphable Model Construction for Robust Ear and Face Recognition

Recent work suggests that the human ear varies significantly between different subjects and can be used for identification. In principle, therefore, using ears in addition to the face within a recognition system could improve accuracy and robustness, particularly for non-frontal views. The paper describes work that investigates this hypothesis using an approach based on the construction of a 3D morphable model of the head and ear. One issue with creating a model that includes the ear is that existing training datasets contain noise and partial occlusion. Rather than exclude these regions manually, a classifier has been developed which automates this process. When combined with a robust registration algorithm the resulting system enables full head morphable models to be constructed efficiently using less constrained datasets. The algorithm has been evaluated using registration consistency, model coverage and minimalism metrics, which together demonstrate the accuracy of the approach. To make it easier to build on this work, the source code has been made available online.

Quantitative Measurement of [Na+] and [K+] in Postmortem Human Brain Tissue Indicates Disturbances in Subjects with Alzheimer's Disease and Dementia with Lewy Bodies

Alzheimer’s disease (AD) is associated with significant disturbances in the homeostasis of Na+ and K+ ions as well as reduced levels of Na+/K+ ATPase in the brain. This study used ICP-MS to accurately quantify Na+ and K+ concentrations in human postmortem brain tissue. We analyzed parietal cortex (Brodmann area 7) from 28 cognitively normal age-matched controls, 15 cases of moderate AD, 30 severe AD, and 15 dementia with Lewy bodies (DLB). Associations were investigated between [Na+] and [K+] and a number of variables including diagnosis, age, gender, Braak tangle stage, amyloid-β (Aβ) plaque load, tau load, frontal tissue pH, and APOE genotype. Brains from patients with severe AD had significantly higher (26%; p<0.001) [Na+] (mean 65.43 ± standard error 2.91 mmol/kg) than controls, but the concentration was not significantly altered in moderate AD or DLB. [Na+] correlated positively with Braak stage (r=0.45; p<0.0001), indicating association with disease severity. [K+] in tissue was 10% lower (p<0.05) in moderate AD than controls. However, [K+] in severe AD and DLB (40.97±1.31 mmol/kg) was not significantly different from controls. There was a significant positive correlation between [K+] and Aβ plaque load (r=0.46; p=0.035), and frontal tissue pH (r=0.35; p=0.008). [Na+] was not associated with [K+] across the groups, and neither ion was associated with tau load or APOE genotype. We have demonstrated disturbances of both [Na+] and [K+] in relation to the severity of AD and markers of AD pathology, although it is possible that these relate to late-stage secondary manifestations of the disease pathology.