Wolfgang Staffen

The visual word form area and the frequency with which words are encountered: evidence from a parametric fMRI study.

Cohen and Dehaene et al. proposed that the Visual Word Form Area (VWFA) in the left midfusiform gyrus, contrary to its name, is limited to the extraction of an abstract letter string and not involved in proper visual word recognition. We examined this prelexical function of the VWFA by a parametric block design with five levels of written word frequency. The lowest level was represented by pseudowords and the highest level by words of very high frequency. Contrary to the assumed prelexical function of the VWFA, increasing frequency was associated with decreasing brain activation in a large posterior cluster of the left hemisphere including middle and posterior fusiform regions. The same negative relation between frequency and activation was found in several left frontal clusters. The relation of increasing frequency and decreasing activation in occipitotemporal regions corresponds to a similar relation in the same brain regions found by studies which experimentally manipulated object or face familiarity. This convergence suggests that fusiform regions are specialized for extracting and storing abstract patterns when processing visual objects and these patterns serve as recognition units in subsequent encounters with the same objects.

Thinking of mental and other representations: The roles of left and right temporo-parietal junction

Abstract Adopting new versions of the false belief and “false” photo vignettes used by Saxe & Kanwisher (2003) we were able to show activation in all five areas previously reported. Activations by added false sign and temporal change control vignettes in these areas showed that the right temporo-parietal junction (TPJ-R) is specifically associated with processing mental states like belief. In contrast, TPJ-L was also activated by false signs suggesting an association with processing perspective differences for mental and non-mental objects in line with work on visual perspective tasks. A similar, but less clearly interpretable pattern of activations was also found in the middle temporal gyrus, precuneus and in the MPFC. These results are discussed in relation to findings in normal development where false belief and false sign tasks associate more strongly with each other than does each of them with the “false” photo task.

Temporo-parietal junction activity in theory-of-mind tasks: Falseness, beliefs, or attention

By combining the false belief (FB) and photo (PH) vignettes to identify theory-of-mind areas with the false sign (FS) vignettes, we re-establish the functional asymmetry between the left and right temporo-parietal junction (TPJ). The right TPJ (TPJ-R) is specially sensitive to processing belief information, whereas the left TPJ (TPJ-L) is equally responsible for FBs as well as FSs. Measuring BOLD at two time points in each vignette, at the time the FB-inducing information (or lack of information) is presented and at the time the test question is processed, made clear that the FB is processed spontaneously as soon as the relevant information is presented and not on demand for answering the question in contrast to extant behavioral data. Finally, a fourth, true belief vignette (TB) required teleological reasoning, that is, prediction of a rational action without any doubts being raised about the adequacy of the actors information about reality. Activation by this vignette supported claims that the TPJ-R is activated by TBs as well as FBs.

Developmental dyslexia: Gray matter abnormalities in the occipitotemporal cortex

Functional neuroimaging studies have consistently demonstrated less activation of the left occipitotemporal cortex in dyslexic readers. This region is considered critical for skilled reading and damage to it in adult readers leads to severe deficits in reading ability. In contrast to these findings, structural abnormalities in the occipitotemporal cortex were not consistently found to date. We used optimized Voxel Based Morphometry with T1 weighted MR images to investigate gray matter volume in 13 dyslexic and 15 nonimpaired reading adolescents (age 14–16). Less gray matter volume for dyslexic readers was found in the left and right fusiform gyrus, the bilateral anterior cerebellum and in the right supramarginal gyrus. Decreased gray matter volume in the left and right fusiform gyrus of dyslexic readers highlights the importance of this brain region for developmental dyslexia. The structural abnormalities in the right occipitotemporal cortex suggest that dyslexia may be such a persistent disorder because an occipitotemporal reading area, critical for skilled reading, cannot develop in any hemisphere. The extended areas of reduced gray matter volume in dyslexic readers in the cerebellum suggest that structural abnormalities in the cerebellum are also strongly associated with dyslexia and warrant further investigation. Hum Brain Mapp, 2008.

Taxi vs. Taksi: On Orthographic Word Recognition in the Left Ventral Occipitotemporal Cortex

The importance of the left occipitotemporal cortex for visual word processing is highlighted by numerous functional neuroimaging studies, but the precise function of the visual word form area (VWFA) in this brain region is still under debate. The present functional magnetic resonance imaging study varied orthographic familiarity independent from phonological-semantic familiarity by presenting orthographically familiar and orthographically unfamiliar forms (pseudohomophones) of the same words in a phonological lexical decision task. Consistent with orthographic word recognition in the VWFA, we found lower activation for familiar compared with unfamiliar forms, but no difference between pseudohomophones and pseudowords. This orthographic familiarity effect in the VWFA differed from the phonological familiarity effect in left frontal regions, where phonologically unfamiliar pseudowords led to higher activation than phonologically familiar pseudohomophones. We suggest that the VWFA not only computes letter string representations but also hosts word-specific orthographic representations. These representations function as recognition units with the effect that letter strings that readily match with stored representations lead to less activation than letter strings that do not.

O-(2-18F-fluoroethyl)-L-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma.

The objective of this study was to compare MRI response assessment with metabolic O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG). Methods: Eleven patients with rHGG were treated biweekly with bevacizumab–irinotecan. MR images and 18F-FET PET scans were obtained at baseline and at follow-up 8–12 wk after treatment onset. MRI treatment response was evaluated by T1/T2 volumetry according to response assessment in neurooncology (RANO) criteria. For 18F-FET PET evaluation, an uptake reduction of more than 45% calculated with a standardized uptake value of more than 1.6 was defined as a metabolic response (receiver-operating-characteristic curve analysis). MRI and 18F-FET PET volumetry results and response assessment were compared with each other and in relation to progression-free survival (PFS) and overall survival (OS). Results: At follow-up, MR images showed partial response in 7 of 11 patients (64%), stable disease in 2 of 11 patients (18%), and tumor progression in 2 of 11 patients (18%). In contrast, 18F-FET PET revealed 5 of 11 metabolic responders (46%) and 6 of 11 nonresponders (54%). MRI and 18F-FET PET showed that responders survived significantly longer than did nonresponders (10.24 vs. 4.1 mo, P = 0.025, and 7.9 vs. 2.3 mo, P = 0.015, respectively). In 4 patients (36.4%), diagnosis according to RANO criteria and 18F-FET PET was discordant. In these cases, PET was able to detect tumor progression earlier than was MRI. Conclusion: In rHGG patients undergoing antiangiogenic treatment, 18F-FET PET seems to be predictive for treatment failure in that it contributes important information to response assessment based solely on MRI and RANO criteria.

Evidence for a dysfunction of left posterior reading areas in German dyslexic readers.

The brain activity during a sentence reading task and a visual control task was examined with fMRI in 13 German dyslexic readers and 15 age-matched fluent readers (age: 14-16 years). These participants came from a longitudinal study and the dyslexic readers exhibited a persistent reading fluency deficit from early on. For the first time with German dyslexic readers, and in correspondence with the majority of functional imaging studies, we found reduced dyslexic activation in the left occipitotemporal cortex and in a small region of the left supramarginal gyrus. Enhanced activation was found in left inferior frontal and subcortical regions.

Comparison of disulfiram and placebo in treatment of alcohol dependence of adolescents

About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that disulfiram may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term disulfiram treatment in alcohol dependence of adolescents. In this double-blind, placebo-controlled study we recruited 26 adolescents, aged 16-19 years, with chronic or episodic alcohol dependence. Patients were allocated treatment randomly with disulfiram (200 mg daily) or placebo for 90 days. Patients were assessed on the day treatment started and on days 30 and 90 by interview, self-report, questionnaire and laboratory screening. Patients were classified as abstinent, relapsing or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. The disulfiram (n=13) and placebo (n=13) groups were well matched in terms of baseline demographic and alcohol-related variables. Thirteen disulfiram-treated and 13 placebo-treated patients completed the treatment phase; seven (1 vs. 6) relapsed, five (3 vs. 2) refused to continue treatment, three (1 vs. 2) had concurrent illness and two (1 vs. 1) had adverse side effects. At the end of treatment, seven disulfiram-treated and two placebo-treated patients had been abstinent continuously (p=0.0063). Mean cumulative abstinence duration was significantly greater in the disulfiram group than in the placebo group [68.5 (SD 37.5) vs. 29.7 (19.0) days; p=0.012]. Apart from occasional diarrhoea, there was no difference in side effects between groups. In some cases, disulfiram may be an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of adolescent alcohol-dependent patients.

On the functional neuroanatomy of visual word processing: Effects of case and letter deviance

This functional magnetic resonance imaging study contrasted case-deviant and letter-deviant forms with familiar forms of the same phonological words (e.g., TaXi and Taksi vs. Taxi) and found that both types of deviance led to increased activation in a left occipito-temporal region, corresponding to the visual word form area (VWFA). The sensitivity of the VWFA to both types of deviance may suggest that this region represents well-known visual words not only as sequences of abstract letter identities but also includes information on the typical case-format pattern of visual words. Case-deviant items, in addition, led to increased activation in a right occipito-temporal region and in a left occipital and a left posterior occipito-temporal region, which may reflect increased demands on letter processing posed by the case-deviant forms.

RETRACTED ARTICLE: Acamprosate and its efficacy in treating alcohol dependent adolescents

Abstract.Background: About 50 % of adult alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence of adolescents. Methods: In this, double-blind, placebo-controlled study, we recruited 26 patients, aged 16–19 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1332 mg daily) or placebo for 90 days. Patients were assessed on the day treatment started and on days 30, and 90 by interview, self report, questionnaire, and laboratory screening. Findings: 13 acamprosate-treated and 13 placebo-treated patients completed the treatment phase: of those withdrawn, 11 (1 vs 6) relapsed, 5 (3 vs 2) refused to continue treatment, 3 (1 vs 2) had concurrent illness, and 2 (1 vs 1) had adverse side-effects. At the end of treatment, 7 acamprosate treated and 2 placebo-treated patients had been continuously abstinent (p = 0.0076). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (79.8 [SD 37.5] vs 32.8 [19.0] days; p = 0.012). Interpretation: Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial treatment programmes.