Factors to consider when reviewing and reconciling research findings: Methodological, statistical and theoretical.

Neuroscience is a rapidly evolving interdisciplinary field that is changing the way research is conducted and theories are developed. However, variability between studies and apparently discrepant findings may contribute to difficulties identifying commonalities that can help inform and enhance clinical practice. This article presents a framework to consider when reviewing neuropsychological studies, such that apparent discrepancies in findings may be considered in unison to provide informed theoretical understanding. For illustrative purposes, the article considers the studies of Vargha-Khadem, Salmond, Friston, Gadian, and Mishkin ( 2003 ) and Beauchamp et al. ( 2008 ), which report contrasting memory deficits during development in association with apparently similar bilateral hippocampal damage. The importance of reflecting on participant characteristics, methodological approaches, statistical analysis, and the interpretative value placed on selective test findings are discussed. Factors such as functional brain development, relationships between apparently "typical" functioning and underlying neural structures and networks, the limits of plasticity on the developing cognitive system and clinical implications are also considered. Thus, this article provides a structure that can be applied when reviewing neuropsychological studies and evaluating research inconsistencies, with consideration of the need for greater collaboration between neuroscientists and clinicians to support the development of translational research with real life implications.

Semantic knowledge fractionations: verbal propositions vs. perceptual input? Evidence from a child with Klinefelter syndrome.

This paper addresses the relative independence of different types of lexical- and factually-based semantic knowledge in JM, a 9-year-old boy with Klinefelter syndrome (KS). JM was matched to typically developing (TD) controls on the basis of chronological age. Lexical-semantic knowledge was investigated for common noun (CN) and mathematical vocabulary items (MV). Factually-based semantic knowledge was investigated for general and number facts. For CN items, JM's lexical stores were of a normal size but the volume of correct 'sensory feature' semantic knowledge he generated within verbal item descriptions was significantly reduced. He was also significantly impaired at naming item descriptions and pictures, particularly for fruit and vegetables. There was also weak object decision for fruit and vegetables. In contrast, for MV items, JM's lexical stores were elevated, with no significant difference in the amount and type of correct semantic knowledge generated within verbal item descriptions and normal naming. JM's fact retrieval accuracy was normal for all types of factual knowledge. JM's performance indicated a dissociation between the representation of CN and MV vocabulary items during development. JM's preserved semantic knowledge of facts in the face of impaired semantic knowledge of vocabulary also suggests that factually-based semantic knowledge representation is not dependent on normal lexical-semantic knowledge during development. These findings are discussed in relation to the emergence of distinct semantic knowledge representations during development, due to differing degrees of dependency upon the acquisition and representation of semantic knowledge from verbal propositions and perceptual input.

Dissociations in mathematical knowledge: case studies in Down's syndrome and Williams syndrome.

A study is reported of mathematical vocabulary and factual mathematical knowledge in PQ, a 22 year old with Down's syndrome (DS) who has a verbal mental age (MA) of 9 years 2 months and ST, a 15 year old with Williams syndrome (WS) who has a verbal MA of 9 years 6 months, matched to typically developing controls. The number of mathematical words contained within PQ's lexical stores was significantly reduced as reflected by performance on lexical decision. PQ was also impaired at both naming from descriptions and describing mathematical words. These results contrast with normal lexical decision and item descriptions for concrete words reported recently for PQ (Robinson and Temple, 2010). PQ's recall of mathematical facts was also impaired, whilst his recall of general knowledge facts was normal. This performance in DS indicates a deficit in both lexical representation and semantic knowledge for mathematical words and mathematical facts. In contrast, ST, the teenager with WS had good accuracy on lexical decision, naming and generating definitions for mathematical words. This contrasted with the atypical performance with concrete words recently reported for ST (Robinson and Temple, 2009). Knowledge of addition facts and general knowledge facts was also unimpaired for ST, though knowledge of multiplication facts was weak. Together the cases form a double dissociation and provide support for the distinct representation of mathematical and concrete items within the lexical-semantic system during development. The dissociations between mathematical and general factual knowledge also indicate that different types of factual knowledge may be selectively impaired during development. There is further support for a modular structure within which mathematical vocabulary and mathematical knowledge have distinct representations. This supports the case for the independent representation of factual and language-based knowledge within the semantic system during development.

Childhood epilepsy and autism spectrum disorders: psychiatric problems, phenotypic expression, and anticonvulsants.

Epilepsy and autism spectrum disorders (ASDs) frequently co-occur during childhood, however, the characteristics of psychiatric or behavioural problems in these children remains largely unknown. This article contributes to these discussions by reporting on the prevalence and presentation of psychiatric or behavioural problems in children with epilepsy and ASDs, as well as on the use of anticonvulsants in these children. The current evidence suggests that children with epilepsy and ASDs may present with a distinct clinical profile, with a greater number of developmental difficulties, and a more severe expression of the ASD phenotype that can not solely be accounted for by level of intellectual functioning. Positive effects of anticonvulsants on behavioural symptoms associated with ASDs were also reported, though pharmacoresistance and a lack of clear treatment guidelines may contribute to an elevated risk of adverse side effects. In relation to clinical presentation and management there is a need for careful consideration of potential interaction effects between disorder specific factors (e.g., age of seizure onset/ASD diagnosis), cognitive characteristics (e.g., intellectual functioning, memory), and psychosocial variables (e.g., coping strategies). Ultimately however, many conclusions are tentative and this review highlights the need for more empirically validated research on children with epilepsy and ASDs.

Atypical semantic knowledge and autobiographical memory disorder in a young adult with Downs syndrome.

A study of lexical semantic knowledge and autobiographical memory is described in PQ, a 22-year-old male with Downs syndrome. Performance is compared with younger typically developing verbal mental age controls. PQ's lexical stores contained a normal number of items, however, he was impaired at naming both pictures and item descriptions. PQ's own descriptions of items contained a normal volume of information, but the pattern of information differed from normal as he produced less 'sensory' and more 'thematic' and 'functional' information. PQ has an autobiographical memory deficit. His ability to recall 'specific' memories was significantly impoverished. It is suggested that both PQ's naming difficulties and his autobiographical memory disorder may reflect atypical knowledge specification with absence of distinctive featural knowledge and increased conceptual overlap and looser networks pervasive across both semantic and autobiographical memory systems.

The representation of semantic knowledge in a child with Williams syndrome.

This study investigated whether there are distinct types of semantic knowledge with distinct representational bases during development. The representation of semantic knowledge in a teenage child (S.T.) with Williams syndrome was explored for the categories of animals, fruit, and vegetables, manipulable objects, and nonmanipulable objects. S.T.'s lexical stores were of a normal size but the volume of "sensory feature" semantic knowledge she generated in oral descriptions was reduced. In visual recognition decisions, S.T. made more false positives to nonitems than did controls. Although overall naming of pictures was unimpaired, S.T. exhibited a category-specific anomia for nonmanipulable objects and impaired naming of visual-feature descriptions of animals. S.T.'s performance was interpreted as reflecting the impaired integration of distinctive features from perceptual input, which may impact upon nonmanipulable objects to a greater extent than the other knowledge categories. Performance was used to inform adult-based models of semantic representation, with category structure proposed to emerge due to differing degrees of dependency upon underlying knowledge types, feature correlations, and the acquisition of information from modality-specific processing modules.

Protection induced by Plasmodium falciparum MSP1(42) is strain-specific, antigen and adjuvant dependent, and correlates with antibody responses.

Vaccination with Plasmodium falciparum MSP1(42)/complete Freund's adjuvant (FA) followed by MSP1(42)/incomplete FA is the only known regimen that protects Aotus nancymaae monkeys against infection by erythrocytic stage malaria parasites. The role of adjuvant is not defined; however complete FA cannot be used in humans. In rodent models, immunity is strain-specific. We vaccinated Aotus monkeys with the FVO or 3D7 alleles of MSP1(42) expressed in Escherichia coli or with the FVO allele expressed in baculovirus (bv) combined with complete and incomplete FA, Montanide ISA-720 (ISA-720) or AS02A. Challenge with FVO strain P. falciparum showed that suppression of cumulative day 11 parasitemia was strain-specific and could be induced by E. coli expressed MSP1(42) in combination with FA or ISA-720 but not with AS02A. The coli42-FVO antigen induced a stronger protective effect than the bv42-FVO antigen, and FA induced a stronger protective effect than ISA-720. ELISA antibody (Ab) responses at day of challenge (DOC) were strain-specific and correlated inversely with c-day 11 parasitemia (r = -0.843). ELISA Ab levels at DOC meeting a titer of at least 115,000 ELISA Ab units identified the vaccinees not requiring treatment (noTx) with a true positive rate of 83.3% and false positive rate of 14.3 %. Correlation between functional growth inhibitory Ab levels (GIA) and cumulative day 11 parasitemia was weaker (r = -0.511), and was not as predictive for a response of noTx. The lowest false positive rate for GIA was 30% when requiring a true positive rate of 83.3%. These inhibition results along with those showing that antigen/FA combinations induced a stronger protective immunity than antigen/ISA-720 or antigen/AS02 combinations are consistent with protection as ascribed to MSP1-specific cytophilic antibodies. Development of an effective MSP1(42) vaccine against erythrocytic stage P. falciparum infection will depend not only on antigen quality, but also upon the selection of an optimal adjuvant component.