Problem-solving and spatial working memory in patients with schizophrenia and with focal frontal and temporal lobe lesions

Problem-solving ability was investigated in 25 DSM-IIIR schizophrenic (SC) patients using the Tower of Hanoi (TOH) task. Their performance was compared to that of: (1) 22 patients with neurosurgical unilateral prefrontal lesions, 11 left (LF) and 10 right hemisphere (RF); (2) 38 patients with unilateral temporal lobectomies, 19 left (LT) and 19 right (RT); and (3) 44 matched control subjects. Like the RT and LF group, the schizophrenics were significantly impaired on the TOH. The deficit shown by the schizophrenic group was equivalent whether or not the problems to be solved included goal-subgoal conflicts, unlike the LF group who were impaired specifically on these problems. The nature of the SC deficit was also distinct from that of the RT group, in that the problem-solving deficit remained after controlling for the effects of spatial memory performance. This study indicates, therefore, that neither focal frontal nor temporal lobe damage sustained in adult life is a sufficient explanation for the problem-solving deficits found in patients with schizophrenia. (C) 1999 Elsevier Science B.V. All rights reserved.

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.

The role of imitation in video-based interventions for children with autism.

Objective: The aim of this paper is to bridge the gap between the corpus of imitation research and video-based intervention (VBI) research, and consider the impact imitation skills may be having on VBI outcomes and highlight potential areas for improving efficacy.

Method: A review of the imitation literature was conducted focusing on imitation skill deficits in children with autism followed by a critical review of the video modelling literature focusing on pre-intervention assessment of imitation skills and the impact imitation deficits may have on VBI outcomes.

Results: Children with autism have specific imitation deficits, which may impact VBI outcomes. Imitation training or procedural modifications made to videos may accommodate for these deficits.

Conclusions: There are only six studies where VBI researchers have taken pre-intervention imitation assessments using an assortment of imitation measures. More research is required to develop a standardised multi-dimensional imitation assessment battery that can better inform VBI.

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.

Encouraging lifestyle behaviour change in mild cognitive impairment patients:development of appropriate educational material

Objectives: A healthy lifestyle may help maintain cognitive function and reduce the risk of developing dementia. This study employed a focus group approach in order to gain insight into opinions of mild cognitive impairment (MCI) patients, caregivers (CG) and health professionals (HP) regarding lifestyle and its relationship with cognition. The qualitative data were used to design, develop and pilot test educational material (EM) to help encourage lifestyle behaviour change. Method: Data gathering phase: structured interviews were conducted with HP (n = 10), and focus groups with MCI patients (n = 24) and CG (n = 12). EM was developed and pilot tested with a new group of MCI patients (n = 21) and CG (n = 6). Results: HP alluded to the lack of clinical trial evidence for a lifestyle and MCI risk link. Although they felt that lifestyle modifications should be recommended to MCI patients, they appeared hesitant in communicating this information and discussions were often patient-driven. MCI patients lacked awareness of the lifestyle cognition link. Participants preferred EM to be concise, eye-catching and in written format, with personal delivery of information favoured. Most pilot testers approved of the EM but were heterogeneous in terms of lifestyle, willingness to change and support needed to change. Conclusion: MCI patients need to be made more aware of the importance of lifestyle for cognition. EM such as those developed here, which are specifically tailored for this population would be valuable for HP who, currently, appear reticent in initiating lifestyle-related discussions. Following further evaluation, the EM could be used in health promotion activities targeting MCI patients.

Spontaneous and cued gaze-following in autism and Williams syndrome

Background: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and Autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people.

Methods: We used eye tracking to explore how individuals with WS and Autism attended to, and subsequently interpreted, an actor’s eye gaze cue within a social scene. Images were presented for three seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye-gaze in each condition was analyzed by ANOVA and accuracy of identification was compared with t-tests.

Results: Participants with WS allocated more gaze time to face and eyes than their matched controls both with and without being asked to identify the item being looked at; while participants with Autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets, while those with Autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls.

Conclusions: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and Autism are characterised by atypicalities of social attention that impact upon socio-cognitive expertise but importantly the type of atypicality is syndrome-specific.

A long-term follow-up of cognitive, emotional, and behavioural sequelae to Reye syndrome

Eighteen adolescents who had survived Reye syndrome (RS) in early childhood were assessed on cognitive, emotional, and behavioural variables in a second follow-up study tracking this group. Siblings were used as controls. The entire group with RS had survived with no obvious neurological damage at the first follow-up study. Indeed, current findings suggested that long-term cognitive, emotional, and behavioural functioning was comparable to siblings in approximately half of the group with RS. However, two factors were associated with a less favourable outcome. Cognitive, emotional, and behavioural functioning were significantly poorer in the subgroup of survivors whose illness had occurred in the first year of life. In addition, loss of consciousness, although the association with poor outcome was not as noticeable, was also associated with relative deficits on some scales of cognitive ability. Many of these deficits had not been obvious at the first follow-up and the importance of neurodevelopmental factors are considered. Finally, the implications of these findings for research and interventions in RS and other such encephalopathies are discussed.

AßPP over-expressing transgenic rat model of Alzheimer's disease utilizing the Tg2576 mouse protocol.

The current study examined behavioral and histological effects of amyloid-ß (Aß) protein precursor (AßPP) overexpression in transgenic (Tg) rats created using the same gene, mutation, and promoter as the Tg2576 mouse model of Alzheimer's disease (AD). Male Tg+ rats were bred with female wild-type rats to generate litters of hemizygous Tg+ and Tg- offspring. Tg+ rats and Tg- littermates were tested for memory deficits at 4, 8, and 12 months old using a water-maze procedure. There were no significant behavioral differences between Tg+ rats and Tg- littermates at 4 months old but there were significant differences at 8 and 12 months old, and in probe trials at 8 and 12 months old, the Tg+ rats spent significantly less time and covered less distance in the platform zone. Under acquisition of a fixed-consecutive number schedule at 3 months old, Tg- littermates demonstrated a longer latency to learning the response rule than Tg+ rats; while this might seem paradoxical, it is consistent with the role of overexpression of AßPP in learning. Histological analyses revealed activated astrocytes in brains of Tg+ rats but not Tg- littermates at 6 months old, and thioflavin-S positive staining in the hippocampus and cortex of 17-month old Tg+ rats but not Tg- littermates. Quantification of Aß load in the brain at 22 months indicated high levels of Aß38, Aß40, and Aß42 in the Tg+ rats. These data suggest this model might provide a valuable resource for AD research.

Novel 5-aryloxypyrimidine SEN1576 as a candidate for the treatment of Alzheimer's disease

Prefibrillar assembly of amyloid-ß (Aß) is a major event underlying the development of neuropathology and dementia in Alzheimer's disease (AD). This study determined the neuroprotective properties of an orally bioavailable Aß synaptotoxicity inhibitor, SEN1576. Binding of SEN1576 to monomeric Aß 1–42 was measured using surface plasmon resonance. Thioflavin-T and MTT assays determined the ability of SEN1576 to block Aß 1–42-induced aggregation and reduction in cell viability, respectively. In vivo long-term potentiation (LTP) determined effects on synaptic toxicity induced by intracerebroventricular (i.c.v.) injection of cell-derived Aß oligomers. An operant behavioural schedule measured effects of oral administration following i.c.v. injection of Aß oligomers in normal rats. SEN1576 bound to monomeric Aß 1–42, protected neuronal cells exposed to Aß 1–42, reduced deficits in in vivo LTP and behaviour. SEN1576 exhibits the necessary features of a drug candidate for further development as a disease modifying treatment for the early stages of AD-like dementia.

Examining the Neurocognitive Validity of Commercially Available, Smartphone-Based Puzzle Games

Cognitive assessment typically involves assessing a person’s cognitive performance in unfamiliar and ar-guably unnatural clinical surroundings. User-centred approaches to assessment and monitoring, driven by issues such as enjoyability and familiarity, are largely absent. Everyday technologies, for example, smartphones represent an opportunity to obtain an objective assessment of a person’s cognitive capabili-ties in a non-threatening, discreet and familiar way, e.g. by everyday puzzle games undertaken as a leisure activity at home. We examined the strength of relationships that exist between performance on common puzzle games and standard measures of neuropsychological performance. Twenty-nine participants, aged 50 - 65 years, completed a comprehensive neuropsychological test battery and played three smart-phone-based puzzle games in triplicate: a picture puzzle [Matches Plus], a word puzzle [Jumbline] and a number puzzle [Sudoku]. As anticipated, a priori, significant correlations were observed between scores on a picture puzzle and visual memory test (r = 0.49; p = 0.007); a word puzzle and estimated verbal IQ (r = 0.53; p = 0.003) and verbal learning (r = 0.30; p = 0.039) tests; and a number puzzle and reason-ing/problem solving test (r = 0.42; p = 0.023). Further analyses making allowance for multiple compari-sons identified a significant unanticipated correlation (r = 0.49; p = 0.007) between number puzzle scores and a measure of nonverbal working memory. Performance on these smartphone-based games was in-dicative of relative cognitive ability across several cognitive domains at a fixed time point. Smart-phone-based, everyday puzzle games may offer a valid, portable measure of assessing and monitoring cognition in older adults.

Dorsal and ventral stream mediated visual processing in genetic subtypes of Prader-Willi syndrome

Previous work has suggested that there are specific deficits in dorsal stream processing in a variety of developmental disorders. Prader-Willi syndrome (PWS) is associated with two main genetic subtypes, deletion and disomy. Relative strengths in visual processing are shown in PWS, although these strengths may be specific to the deletion subtype. We investigated visual processing in PWS using an adapted Simon task which contrasted location (dorsal stream) and shape identity (ventral stream) tasks. Compared to a group of typically developing children, children with PWS deletion showed a greater degree of impairment in the dorsal stream task than in the ventral stream task, a pattern similar to that shown in a group of boys with Fragile-X syndrome. When matched on a measure of non-verbal ability, children with PWS disomy showed the opposite pattern with better performance in the location compared to the shape task, although these task performance asymmetries may have been linked to executive control processes. It is proposed that children with PWS deletion show a relative strength in visual processing in the ventral stream along with a specific deficit in dorsal stream processing. In contrast, children with PWS disomy show neither effect. (C) 2009 Published by Elsevier Ltd.

Attention-based modulation of tactile stimuli: A comparison between prefrontal lesion patients and healthy age-matched controls

Objectives: To investigate the role of the prefrontal cortex in attention-based modulation of cortical somatosensory processing.

Methods: Six prefrontal stroke patients were compared with eleven neurologically intact older adults during a vibrotactile discrimination task. All subjects attended to stimuli on one digit while ignoring distracter stimuli on a separate digit of the same hand. Subjects were required to report infrequent targets on the attended digit only. Throughout testing electroencephalography was used to measure event-related potentials for both task-relevant and irrelevant stimuli.

Results: Prefrontal patients demonstrated significant changes in cortical somatosensory processing based on attention compared to age-matched controls. This was evident both in early unimodal somatosensory processing (i.e. P100) and in later cortical processing stages (i.e. long-latency positivity). Moreover, there was a tendency towards a tonic loss of inhibition over early somatosensory cortical processing (i.e. P50).

Conclusions: The attention-based modulation noted for neurologically intact older adults was absent in prefrontal lesion patients.

Significance: The present study highlights the important role of prefrontal regions in sustaining inhibition over early sensory cortical processing stages and in modifying somatosensory transmission based on task-relevance. Notably these deficits extend beyond those previously shown to occur as a function of age.

Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia

Deficits in sensitivity to visual stimuli of low spatial frequency and high temporal frequency (so-called frequency-doubled gratings) have been demonstrated both in schizophrenia and in autism spectrum disorder (ASD). Such basic perceptual functions are ideal candidates for molecular genetic study, because the underlying neural mechanisms are well characterized; but they have sometimes been overlooked in favor of cognitive and neurophysiological endophenotypes, for which neural substrates are often unknown. Here, we report a genome-wide association study of a basic visual endophenotype associated with psychological disorder. Sensitivity to frequency-doubled gratings was measured in 1060 healthy young adults, and analyzed for association with genotype using linear regression at 642758 single nucleotide polymorphism (SNP) markers. A significant association (P=7.9×10) was found with the SNP marker rs1797052, situated in the 5′-untranslated region of PDZK1; each additional copy of the minor allele was associated with an increase in sensitivity equivalent to more than half a standard deviation. A permutation procedure, which accounts for multiple testing, showed that the association was significant at the α=0.005 level. The region on chromosome 1q21.1 surrounding PDZK1 is an established susceptibility locus both for schizophrenia and for ASD, mirroring the common association of the visual endophenotype with the two disorders. PDZK1 interacts with N-methyl-d-aspartate receptors and neuroligins, which have been implicated in the etiologies of schizophrenia and ASD. These findings suggest that perceptual abnormalities observed in two different disorders may be linked by common genetic elements. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Impact of abuse and neglect on the health and wellbeing of children:Child sexual abuse

During the past 30 years, the focus on the extent and nature of child abuse and neglect has been coupled with an increasing interest in the impact on children’s development, health and mental wellbeing. Child maltreatment is both a human rights violation and a complex public health issue, likely caused by a myriad of factors that involve the individual, the family, and the community. Child abuse includes any type of maltreatment or harm inflicted upon children and young people in interactions between adults (or older adolescents). Such maltreatment is likely to cause enduring harm to the child.
The different forms of abuse and neglect often occur together in one family and can affect one or more children. These include, in deceasing level of frequency: neglect; physical abuse and non-accidental injury; emotional abuse; and sexual abuse (Cawson et al, 2000; 2002). Recently, bullying and domestic violence have been included as forms of abuse of children.
There is a sizeable body of literature on the relationship between types of child maltreatment and a variety of negative health and mental health consequences. These include biological, psychological, and social deficits (for reviews, see Crittenden, 1998; Kendall-Tackett, 2001; 2003). Aside from the serious physical and health consequences of child maltreatment, several emotional and behavioural consequences for children have been noted in the literature.

'Sorry I meant the patient's left side': impact of distraction on right/left discrimination

Context Medical students can have difficulty in distinguishing left from right. Many infamous medical errors have occurred when a procedure has been performed on the wrong side, such as in the removal of the wrong kidney. Clinicians encounter many distractions during their work. There is limited information on how these affect performance. 
Objectives Using a neuropsychological paradigm, we aim to elucidate the impacts of different types of distraction on left–right (LR) discrimination ability. 
Methods Medical students were recruited to a study with four arms: (i) control arm (no distraction); (ii) auditory distraction arm (continuous ambient ward noise); (iii) cognitive distraction arm (interruptions with clinical cognitive tasks), and (iv) auditory and cognitive distraction arm. Participants’ LR discrimination ability was measured using the validated Bergen Left–Right Discrimination Test (BLRDT). Multivariate analysis of variance was used to analyse the impacts of the different forms of distraction on participants’ performance on the BLRDT. Additional analyses looked at effects of demographics on performance and correlated participants’ self-perceived LR discrimination ability and their actual performance. 
Results A total of 234 students were recruited. Cognitive distraction had a greater negative impact on BLRDT performance than auditory distraction. Combined auditory and cognitive distraction had a negative impact on performance, but only in the most difficult LR task was this negative impact found to be significantly greater than that of cognitive distraction alone. There was a significant medium-sized correlation between perceived LR discrimination ability and actual overall BLRDT performance. 
Conclusions
Distraction has a significant impact on performance and multifaceted approaches are required to reduce LR errors. Educationally, greater emphasis on the linking of theory and clinical application is required to support patient safety and human factor training in medical school curricula. Distraction has the potential to impair an individual's ability to make accurate LR decisions and students should be trained from undergraduate level to be mindful of this.