Improvement of medical judgments by numerical training in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: People with multiple sclerosis (MS) have to face important decisions with regard to their medical treatment. The aim of this study was to evaluate whether a targeted cognitive training reduces framing effects and thus improves medical judgments. METHODS: This was a randomized, double-blind, cross-over study enrolling patients with relapsing-remitting MS and healthy controls (HCs). Participants were randomly assigned to training order A (first week, numerical training; second week, control training) or B (reverse order). The primary endpoint was changed in a framing task score (framing effect). In the framing task, participants evaluated the success of fictive medications on a 7-point scale. Medications were described in either positive or negative terms. RESULTS: A total of 37 patients and 73 HCs performed either training order A (n = 56) or B (n = 54). The framing effect decreased after the numerical training regardless of training order. No such decrease was found after the control training. Mean change in framing effect was -0.3 ± 0.8 after the numerical training and 0.03 ± 0.6 after the control training. This specific effect of training type was comparable between groups. CONCLUSION: Judgments of medical information improve in both patients with relapsing-remitting MS and HCs after a targeted numerical training. Thus, a specific cognitive intervention may help patients making informed decisions.

The neuropsychiatric phenotype in CACNA1A mutations: a retrospective single center study and review of the literature.

BACKGROUND AND PURPOSE: CACNA1A encodes the α1 subunit of the neuronal calcium channel P/Q. CACNA1A mutations underlie three allelic disorders: familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). A clear-cut genotype-phenotype correlation is often lacking since clinical manifestations may overlap. Several case reports have described cognitive and behavioral features in CACNA1A disorders, but studies in larger case series are lacking. METHODS: Genetically confirmed CACNA1A cases were retrieved from the database of the ataxia outpatient clinic of the Department of Neurology at Innsbruck Medical University. Clinical charts and neuropsychological test results were retrospectively analyzed. In addition, a review of the literature including only genetically confirmed cases was performed. RESULTS: Forty-four CACNA1A cases were identified in our database. Delayed psychomotor milestones and poor school performance were described in seven (four FHM1, three EA2) and eight (three FHM1, five EA2) patients, respectively. Psychiatric comorbidities were diagnosed in eight patients (two FHM1, six EA2). Neuropsychological testing was available for 23 patients (11 FHM1, 10 EA2, two SCA6). Various cognitive deficits were documented in 21 cases (all patients except one SCA6). Impairments were predominantly seen in figural memory, visuoconstructive abilities and verbal fluency. In the literature, an early psychomotor delay is described in several children with EA2 and FHM1, whilst reports of cognitive and psychiatric findings from adult cases are scarce. CONCLUSIONS: Neuropsychiatric manifestations are common in episodic CACNA1A disorders. In the case of otherwise unexplained developmental delay and a positive family history, CACNA1A mutations should be considered in the differential diagnosis.

A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type.

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.

[Consensus statement "Dementia 2010" of the Austrian Alzheimer Society]. / Konsensusstatement "Demenz 2010" der Osterreichischen Alzheimer Gesellschaft.

The Austrian Alzheimer Society developed evidence-based guidelines based on a systematic literature search and criteria-guided assessment with subsequent transparent determination of grades of clinical recommendation. The authors evaluated currently available therapeutic approaches for the most common forms of dementia and focused on diagnosis and pharmacological intervention, taking into consideration the situation in Austria. The purpose of these guidelines is the rational and cost-effective use of diagnostic and therapeutic measures in dementing illnesses. Users are physicians and all other providers of care for patients with dementia in Austria.

Numerical deficits in a single case of basal ganglia dysfunction.

The present investigation assesses specific numerical difficulties in a patient (SJ) with basal ganglia (BG) dysfunction. While previous studies on number processing in BG disorders typically tested arithmetic facts by production tasks, the present study uses production, recognition (verification, multiple-choice) and indirect (number-matching) arithmetic tasks. Patient SJ was severely impaired in production and to a lesser extent in verification and multiple-choice tasks. In number-matching, an abnormal latency pattern was found. This study extends previous research by indicating that BG dysfunction may not only affect production processes and sequencing, as was found in previous investigations, but may lead to a breakdown of semantic relationships of arithmetic facts.

Impact of ambiguity and risk on decision making in mild Alzheimer's disease.

Decisions under ambiguity and decisions under risk are crucial types of decision making in daily living at any age. This is the first study assessing these two types of decisions in patients with mild dementia of Alzheimer's type (DAT) by means of the Iowa Gambling Task (IGT) and a newly developed, Probability-Associated Gambling (PAG) task. While rules for gains and losses are implicit in the IGT, in the PAG task rules are explicit and winning probabilities, which change from trial to trial, can be estimated. Results of the IGT indicated that DAT patients made more disadvantageous decisions than healthy controls. Patients also shifted more frequently among decks, i.e. under ambiguity decisions were taken randomly and no advantageous strategy was established over time by DAT patients. Thus, not only actual choices but also development of advantageous strategies may be revealing about decision making in the IGT. Compared to controls, patients demonstrated less advantageous choices in the PAG task as well. They gambled more often in the low winning probabilities and less frequently in the high probabilities than healthy participants. Patients' performance on both tasks correlated with measures of executive functions. Findings of the present investigation are consistent with the early pathological cerebral changes and related (cognitive, emotional) deficits reported for DAT. As suggested by our study, decisions under ambiguity as well as decisions under risk are impaired in mild DAT. It may thus be expected that patients with mild DAT have difficulties in taking decisions in every-day life situations, both in cases of ambiguity (information on probability is missing or conflicting, and the expected utility of the different options is incalculable) and in cases of risk (outcomes can be predicted by well-defined or estimable probabilities).

Decision-making with explicit and stable rules in mild Alzheimer's disease.

Decision-making in mild dementia of Alzheimer's type (DAT) was assessed in a gambling task with stable and explicit rules [Game of Dice Task; Brand, M., Labudda, K., Kalbe, E., Hilker, R., Emmans, D., Fuchs, G., et al. (2004). Decision-making impairments in patients with Parkinson's disease. Behavioural Neurology, 15, 77-85]. DAT patients in an early stage of the disease chose safe alternatives as frequently as healthy elderly persons and did not show risky behaviour as has been reported for other neurological patient groups. However, a more detailed analysis disclosed important differences between DAT and healthy elderly. Compared to healthy controls, DAT patients shifted more frequently between safe and risky alternatives and showed less consistent response patterns. Frequent changes between strategies indicate that decisions were taken randomly, that no advantageous strategy was established and that no consistent response pattern was developed over time. As regards performance changes over the task, healthy participants had a stronger tendency towards safe and advantageous responses than DAT patients. While healthy controls showed learning as the task proceeded, DAT patients did not adapt their strategies. The proportion of "consistently safe responders" was significantly higher in the control group than in the DAT group. Analysis of reaction times indicated that differences in response behaviour were not due to fast and impulsive decision taking in the DAT group. DAT patients' response pattern may be attributed to deficits in learning and in executive functions. The frequency of changes between safe and risky choices proved to be a fair predictor for the distinction between mild DAT and healthy aging.

Effects of age and mild cognitive impairment on direct and indirect access to arithmetic knowledge.

The present study aimed at investigating age-related changes and mild cognitive impairment (MCI) related effects in simple arithmetic. To pursue this goal, MCI patients, healthy old adults and young adults performed three computerised tasks. The production (e.g., 3 x 4=?) and the verification task (3 x 4 12?) evaluated direct access to multiplication knowledge, the number-matching task (3 x 4 34?, 'do 3 x 4 and 34 have the same digits?') tested indirect access. In verification and number-matching, interference from related distractors (e.g., 3 x 4 followed by 16) relative to unrelated distractors (17) reflects access to stored fact representations as well as efficiency of inhibition processes. Results indicated that, compared to young adults, MCI and healthy old adults were slower in responding across tasks. In production and verification, analyses of individual latency regression slopes and intercepts suggested that these age effects were related to differences at peripheral processing stages (e.g., encoding) rather than at the central (arithmetic retrieval) stage. Differences between MCI and healthy elderly emerged only in the number-matching task. While in verification effects were comparable between groups, in number-matching MCI patients were more susceptible to interference from irrelevant information than healthy old participants. Overall, the present findings indicate that aging has a general effect on peripheral processing speed, but not on arithmetic memory retrieval. Parietal cortico-subcortical circuits mediating arithmetic fact retrieval (Dehaene, S., & Cohen, L. (1995). Towards an anatomical and functional model of number processing. Mathematical Cognition, 1, 83-120; Dehaene, S., & Cohen, L. (1997). Cerebral pathways for calculation: Double dissociation between rote verbal and quantitative knowledge of arithmetic. Cortex, 33, 219-250) thus seem to be preserved in normal aging and MCI. In contrast, MCI patients show enhanced interference in number-matching. This task-specific lack of inhibition may point to dysfunctional frontal cortico-subcortical networks in MCI.

Number processing in posterior cortical atrophy--a neuropsycholgical case study.

Posterior cortical atrophy (PCA) is an uncommon syndrome of dementia with early onset, characterised by disorders of higher visual function, variable symptoms of Balint's syndrome, visual agnosia, alexia, agraphia, finger agnosia, right-left disorientation and dyscalculia [Benson D. F., Davis R. J., & Snyder B. D. (1988). Posterior cortical atrophy. Archives of Neurology, 45, 789-793]. In a single case study specific numerical deficits were observed which may be predicted by parietal neurodegeneration (more pronounced on the right side; verified by SPECT). Besides impairments in all tasks involving visuo-spatial abilities (e.g., dot counting, analog number scale task), deficits appeared in tasks requiring access to an internal representation of numbers such as mental number bisection, approximation, estimation and semantic facts. In number comparison an increased distance effect was found. In simple arithmetic, a striking dissociation between operations was found-multiplication and addition facts being preserved at a superficial level, subtraction and division being severely impaired. The study confirms the close relation between spatial and numerical processing and highlights the modular organisation of the semantic system (number semantics impaired). Moreover, the study adds evidence about the clinical manifestation of the particular degenerative syndrome.

Knowing 7 x 8, but not the meaning of 'elephant': evidence for the dissociation between numerical and non-numerical semantic knowledge.

Patients affected by semantic dementia (SD) and other severe cognitive deficits may show preserved numerical skills, including the retrieval of multiplication facts from long-term memory. No studies so far specifically investigated the network of arithmetic facts in semantic dementia. Thus, it is unknown whether preserved multiplication in SD truly reflects intact semantic knowledge or preserved retrieval of verbal sequences (just as the recitation of rhymes or poems). In the present study a patient (SG) with SD underwent an extensive assessment of number processing and calculation abilities. In particular, multiplication knowledge was investigated through a series of computerised tasks (production task, multiple-choice task, number bisection task with multiplicative triplets, number-matching task). SG demonstrated excellent performance in all number processing and calculation tasks. In computerised tasks tapping multiplication fact knowledge, SG was as accurate and fast as healthy controls. Analyses on individual regression slopes indicated that SG's reaction time effects (problem-size effect, problem-difficulty effect, interference effects, and facilitation effect) were comparable to those found in controls in each task. These results add new evidence to the independence of numerical knowledge from other semantic information and provide further insight into the organisation of stored arithmetic knowledge.

Priming arithmetic facts in amnesic patients.

In this study, amnesic patients showed significant repetition priming effects in arithmetic fact retrieval tasks. The results indicate that repetition priming effects in arithmetic depend not on explicit recognition, but on the activation of specific long-term representations of arithmetic facts. Processing dissociations between easy and difficult items suggest that the priming effects results from the stage of fact retrieval and not from peripheral activation. This claim is also supported by encoding and naming tasks, which showed only slight priming effects as compared to the priming found in calculation tasks. Significant priming was found for identical (5 x 6 and 5 x 6) and complement problems (5 x 6 and 6 x 5), the latter showing a smaller magnitude of priming.

Anomia for people names in DAT--evidence for semantic and post-semantic impairments.

Proper name anomia is a frequent finding among patients in the early stages of Alzheimer's disease. The present study investigates naming of famous persons in a group of DAT patients, a group of persons with mild cognitive impairment (MCI) and healthy controls. The study is aimed at distinguishing the relative contributions of semantic and post-semantic factors to difficulties in proper name retrieval. As shown by a significantly lower score in answering semantic questions, DAT patients retrieve less biographical knowledge related to famous persons than healthy elderly subjects and persons with mild cognitive impairment. This finding is in line with the frequent observation of semantic deficits in early and moderate DAT. The high number of Tip-of-the-Tongue (TOT) answers in DAT found in relation to few spontaneously named items shows that post-semantic deficits are as important as semantic deficits in determining anomia for people names in DAT. Moreover, DAT patients were less sensitive to phonological cueing than healthy persons or persons with mild cognitive impairment. These findings suggest that proper name anomia in DAT is not only due to semantic deficits, but also to problems in accessing the phonological representation, as well as to a degradation of phonological representations. Thus, naming deficits in DAT differ not only quantitatively, but also qualitatively from the difficulties of healthy elderly persons. No significant differences were found between persons with mild cognitive impairment and healthy controls in proper name retrieval.

When writing 0 (zero) is easier than writing O (o): a neuropsychological case study of agraphia.

Though a few case studies reported a dissociation between intact writing of Arabic and impaired writing of alphabetical script, a detailed experimental analysis of such a dissociation is still lacking. We report a follow-up study of a patient with a parieto-occipital lesion who is affected by severe peripheral agraphia for letters, but not for Arabic digits. While letters in writing to dictation are frequently illegible, distorted, or consist in meaningless strokes, Arabic digits are well-formed and fluently produced. In a series of tasks, including copying of letters with tachistoscopic presentation and handwriting on a digitizing tablet, several processing levels are assessed in order to localize JS' functional writing impairment and to determine different processing routes for letters and for numbers. Overall, the results of the experimental investigation suggest a notation specific deficit in the activation of graphomotor patterns for letters, but not for digits. The study thus adds evidence to the so far reported dissociations between Arabic and alphabetical scripts.

Anomia for people's names.

The case of an anomia for people's names is reported. The study of this dissociation helps to clarify the difference in processing between proper and common names. Associated deficits in this and previously described cases provide support for the idea that an inability to retrieve arbitrary relations is the basis of the naming difficulty. This would confirm the role of proper names as purely referring expressions.

Learning complex arithmetic--an fMRI study.

Aim of the present functional magnet resonance imaging (fMRI) study was to detect modifications of cerebral activation patterns related to learning arithmetic. Thirteen right-handed subjects were extensively trained on a set of 18 complex multiplication problems. In the following fMRI session, trained and untrained problems (closely matched for difficulty) were presented in blocked order alternating with a number matching task and a fact retrieval task. Importantly, left hemispheric activations were dominant in the two contrasts between untrained and trained condition, suggesting that learning processes in arithmetic are predominantly supported by the left hemisphere. Contrasting untrained versus trained condition, the left intraparietal sulcus showed significant activations, as well as the inferior parietal lobule. A further significant activation was found in the left inferior frontal gyrus. This activation may be accounted for by higher working memory demands in the untrained as compared to the trained condition. Contrasting trained versus untrained condition a significant focus of activation was found in the left angular gyrus. Following the triple-code model [Science 284 (1999) 970], the shift of activation within the parietal lobe from the intraparietal sulcus to the left angular gyrus suggests a modification from quantity-based processing to more automatic retrieval. The present study shows that the left angular gyrus is not only involved in arithmetic tasks requiring simple fact retrieval, but may show significant activations as a result of relatively short training of complex calculation.

Sex differences in brain activation pattern during a visuospatial cognitive task: a functional magnetic resonance imaging study in healthy volunteers.

Sex differences in mental rotation tasks, favoring men, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. Regions of activation were detected after performance of a mental rotation task inside the scanner. In contrast to previous studies, confounding factors such as performance differences between genders or high error rates were excluded. Men showed significantly stronger parietal activation, while women showed significantly greater right frontal activation. Our results point to gender specific differences in the neuropsychological processes involved in mental rotation tasks.

Brain activation pattern during a verbal fluency test in healthy male and female volunteers: a functional magnetic resonance imaging study.

Sex differences in executive speech tasks, favoring women, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. All subjects were selected on the basis of high performance on the verbal fluency task. Regions of activation were detected after performance of a covert lexical verbal fluency task inside the scanner. Men and women who did not differ significantly in verbal fluency task performance showed a very similar pattern of brain activation. Our data argue against genuine between-sex differences in cerebral activation patterns during lexical verbal fluency activities when confounding factors like performance differences are excluded.

Subtraction bugs in an acalculic patient.

We report a patient, MT, who presented a specific, though not isolated, deficit in written calculation. Despite a preserved knowledge of simple arithmetic - single-digit addition and subtraction - he failed systematically in multi-digit subtraction. The nature of errors was consistent across problems and reflected the application of a disturbed underlying algorithm. Moreover, the pattern of error observed mimies a very common finding in developmental studies on arithmetical procedure acquisition (Fuson, 1990, 1992, Young and O'Shea, 1981; VanLehn, 1986, 1990). The data suggest that, within calculation skills, syntax may exist as a system of stable, but inappropriate, rules which are independent of any underlying conceptual knowledge.

Arithmetic facts without meaning.

The paper presents a single-case study of patient J.G. showing severe calculation problems (and also agraphia, finger agnosia, right-left disorientation and apraxia) after the surgery of a left parietal tumor. Although the patient completely lost conceptual knowledge of arithmetic, she preserved part of memorised fact knowledge (multiplications and some additions and subtractions). The study indicates that arithmetic facts can be represented at a superficial level without understanding of the operation performed. The study completes a valid double dissociation between two types of knowledge involved in calculation (memorised facts and conceptual knowledge).

Arithmetic reasoning and implicit memory: a neuropsychological study on amnesia.

The present study investigates implicit memory and arithmetic reasoning in a group of severely amnesic patients. Priming effects have been observed in the retrieval of arithmetic facts in amnesic patients (Delazer, Ewen and Benke, 1997), but no studies have so far investigated the effect of previous experience in a pure reasoning task. Findings indicate that answering to a first numerical series (e.g, 1 3 5 7, answer "9") facilitates answering to a second numerical series (2 4 6 8, answer "10") including different numbers but sharing the same underlying algorithm (+ 2). Within the model of Langdon and Warrington (1997) priming effects are attributed to the stage of abstract formula generation.