THE BRITISH NEUROPSYCHOLOGICAL



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SNN Annual Meeting

Theme: Executive Function

Friday 10 December 2004

Walton Conference Centre, Southern General Hospital, Glasgow

09.30 SNN Annual General Meeting (SNN members only)

10.00 Registration and coffee

10.30 Executive dysfunction and word retrieval deficits in motor neurone disease

Sharon Abrahams (University of Edinburgh)

11.00 Speed of decision-making and set-switching: subtle executive deficits in children with

treated phenylketonuria

Peter Griffiths, Peter Robinson, Karen Livingstone and Stephanie Plews (University of Stirling; Royal Hospital for Sick Children, Glasgow)

11.30 Spinocerebellar Ataxia Type 8: Cognitive features in 11 unrelated cases

Lorna Torrens, Adam Zeman, Elaine Burns, Jon Stone, Mary Porteous and Helen Wright (Royal Edinburgh Hospital; Western General Hospital,Edinburgh)

12.00 Combining neuropsychology and genetics in the study of mood disorders

Daniel Smith (Southern General Hospital, Glasgow)

12.30 Lunch

01.30 The DivA: an ecologically valid test of divided attention and dual-tasking

Jonathan J. Evans, Eve Greenfield, Barbara A. Wilson and Tom Manly (University of Glasgow; Oliver Zangwill Centre, Ely; MRC Cognition and Brain SciencesUnit, Cambridge)

02.00 Executive control of personality: affect regulation and behaviour regulation

M.C. Obonsawin, S. Jefferis, R. Lowe, J.R. Crawford, J. Fernandes, L. Holland,

K. Woldt, E. Worthington, and G. Bowie (University of Strathclyde; University of Aberdeen)

02.30 Coffee

03.00 Invited speaker: Professor Ian Robertson (Trinity College Dublin)

Vigilant attention, arousal and error processing: Lessons from TBI, ADHD and the plain absent-minded

04.00 Close

Details at .uk

Abstracts

Executive dysfunction and word retrieval deficits in motor neurone disease

Sharon Abrahams (University of Edinburgh)

Objectives. The cognitive impairment revealed in some non-demented motor neurone disease patients is characterized by executive dysfunction with verbal fluency deficits. Conflicting evidence exists of an impairment on other word retrieval tasks, which do not place heavy demands on executive processes. Our previous research demonstrated intact confrontation naming in the presence of verbal fluency deficits. In this investigation functional magnetic resonance imaging (fMRI) was employed to explore whether word retrieval deficits and underlying cerebral abnormalities were specific to letter fluency, more likely to indicate executive dysfunction, or were also present in confrontation naming indicating language dysfunction.

Methods. Twenty-eight non-demented MND patients were compared with 18 healthy controls. Two compressed sequence overt fMRI activation paradigms were employed, letter fluency and confrontation naming.

Results. The letter fluency fMRI task revealed significantly impaired activation in the middle and inferior frontal gyri and anterior cingulate gyrus, in addition to regions of the parietal and temporal lobes in MND patients.

The confrontation naming fMRI task also revealed impaired activation in less extensive prefrontal regions, (inferior frontal gyrus) and regions of the temporal, parietal and occipital lobes. These changes were present despite matched performance between patients and controls during scanning.

Conclusions. The pattern of dysfunction corresponded to the presence of cognitive deficits on both letter fluency and confrontation naming in the MND group. This study provides evidence of cerebral abnormalities in MND in the network of regions involved in language and executive functions. Moreover the findings further illustrate the heterogeneity of cognitive and cerebral change in MND.

s.abrahams@ed.ac.uk

Speed of decision-making and set-switching:

subtle executive deficits in children with treated phenylketonuria

Peter Griffiths, Peter Robinson, Karen Livingstone and Stephanie Plews (University of Stirling; Royal Hospital for Sick Children, Glasgow)

Objectives. Dopamine is thought to underlie efficient executive functioning. However, dopamine may be in short supply as a neurotransmitter in the prefrontal cortex of treated children with phenylketonuria (PKU). Dopamine is a downstream metabolite of dietary phenylalanine, whose conversion in PKU is impaired by hepatic enzyme deficiency of genetic origin. Consequently, executive functions such as attentional and memory control may be compromised. We investigated the dopamine depletion hypothesis indirectly by studying executive function in childhood PKU.

Methods. Using a matched-samples design, we compared the performance of early and continuously treated PKU children (classical type) with healthy controls (n = 22 per group) on the Test of Everyday Attention for Children (TEA-Ch), a standardised profiling measure of executive function containing tasks of selection, sustainment and switching of attention; and rapid response inhibition and set management. Matching variables were age, sex, social class and IQ.

Results. Relative to the controls, we found the PKU children were not inaccurate on the TEA-Ch subtests. However, they did significantly badly on subtests in which speed contributed to the overall score or in which time was quantifiable separately. Thus, they were slow at figure-ground scanning (Sky Search, P < 0.01) and set-switching (Creature Counting, P < 0.001; Opposite Worlds, P < 0.01); and especially deficient at rapid response inhibition (Walk/Don’t Walk, P < 0.001). We did not find significant TEA-Ch correlations with either lifetime or test-concurrent phenylalanine concentrations.

Conclusions. Our findings add to a growing body of evidence that speed of information processing and decision-making are subtly impaired in PKU, but how they translate into daily adaptation has yet to be established. Dopamine depletion in prefrontal neurotransmission is a likely factor on biochemical grounds. Speeded strategic and choice-reaction (stop-go) tests may be particularly sensitive tools for exploring executive dysfunction in the clinic and laboratory.

p.v.griffiths@stir.ac.uk

Spinocerebellar Ataxia Type 8: Cognitive features in 11 unrelated cases

Lorna Torrens, Adam Zeman, Elaine Burns, Jon Stone, Mary Porteous and Helen Wright (Royal Edinburgh Hospital; Western General Hospital,Edinburgh)

Objectives. Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders characterised by gait, limb and speech incoordination. SCA 8 has been recognised only fairly recently (Koob et al 1999, Zeman et al 2004). Neuropsychiatric features, including "dementia", have been reported in some individuals with the SCA 8 expansion. Stone et al (2001) described a family in which the condition was associated with dysexecutive syndrome. Our objective was to establish whether the DNA expansion linked to SCA 8 is associated with characteristic cognitive deficits, in particular impairment of executive function.

Methods. 11 individuals with the SCA 8 extension underwent neurological, radiological, neuropsychiatric and comprehensive cognitive assessment.

Results. Results suggested that the SCA 8 syndrome is associated with subtle impairments in executive function, independent of concurrent mood disorder.

Conclusions. Individuals with the SCA 8 expansion exhibit a specific pattern of cognitive deficit, notably, subtle deficits in executive function. It is not entirely clear whether these deficits reflect cerebellar dysfunction, along the lines of the "Cerebellar Cognitive Affective Syndrome" (Schmahmann & Sherman 1998) or more widespread cerebral involvement.

Lorna.Torrens@lpct.scot.nhs.uk

Combining neuropsychology and genetics in the study of mood disorders

Daniel Smith (Southern General Hospital, Glasgow)

(1) Neuropsychological impairments in young adults with recurrent, early-onset depression.

Background. Many neuropsychological studies in depression are complicated by the state effect of depressive symptoms during testing and by clinical and genetic heterogeneity within the samples of patients studied. Despite this, some reports have identified global-diffuse impairments as well as specific impairments of selective attention and working memory. These findings are consistent with abnormal functioning of the frontal lobes and hippocampus, and are supported by imaging and preclinical research. In the present study, we use a case-control design to examine neuropsychological functioning in clinically-well (euthymic) young adults who have a history of recurrent, early-onset major depressive disorder (RE-MDD). RE-MDD, defined as two or more episodes of DSM-IV major depressive disorder before age 25, is recognised as a strongly heritable and genetically homogeneous sub-type of mood disorder. As a result, any differences in cognitive functioning detected between patients and controls might be considered trait neurobiological abnormalities of recurrent depression in young adults.

Methods. 53 euthymic young adults with a history of RE-MDD were compared to 38 well-matched controls on a neuropsychological battery. An estimate of premorbid intelligence was obtained using number of years in full-time education, the NART, and the Block Design subtest of the WAIS-R. Testing also included the California Verbal Learning Test (CVLT), the Brixton Spatial Anticipation Test (BSAT), the Trail-making Test (TMT) and The Stroop Colour Word Test.

Results. Patients and controls were well-matched in terms of age, gender distribution, social class, ethnicity and premorbid estimates of intelligence. Significant differences between patients and controls were detected on CVLT scores, the TMT and the Stroop test, suggesting that RE-MDD is associated with specific impairments in verbal memory and frontal executive function.

Conclusions. These findings are consistent with previous work on the neuropsychology of depression but have the advantage of having been carried out in a carefully selected sample of euthymic young patients who suffer from a genetically homogenous sub-type of depression. Impairments in verbal memory and frontal executive function may represent endophenotypic markers of depressive disorder.

(2) Neurocognitive function in euthymic young adults with recurrent depression: a case-control comparison of major depressive disorder and bipolar-spectrum disorder.

Objectives. In response to evidence that DSM-IV tends to over-diagnose recurrent major depressive disorder (MDD) at the expense of bipolar affective disorder (BPAD), Ghaemi and colleagues have proposed diagnostic criteria for bipolar-spectrum disorder (BSD) [Can J Psychiatry 2002; 47(2):125-134]. The current study tested the validity of the proposed BSD criteria by using cognitive function as an endophenotypic measure. Three diagnostic groups were compared on tests of verbal memory, attention and executive function: i) euthymic young adults with recurrent MDD; ii) euthymic young adults with BSD; and iii) euthymic controls. It was hypothesized that BSD patients would perform less well than ‘pure MDD’ patients and controls.

Methods. A neuropsychological battery was administered to 42 euthymic MDD patients, 21 euthymic BSD patients, and 33 controls. The test battery consisted of the NART; the Block Design subtest of the WAIS-R; the California Verbal Learning Test (CVLT); the Brixton Spatial Anticipation Test (BSAT); the Trail-making Test (TMT); and the Stroop Colour Word Test.

Results. Patients and controls were well matched in terms of age, gender ratio, ethnicity, social class, levels of depressive symptoms, and estimates of current intellectual functioning. BSD patients and MDD patients were also matched in terms of current medication. BSD patients performed worse than MDD patients on the CVLT short delay recall (p ................
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