BackgroundCatechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val158Met polymorphism influences its activity, and multiple neural correlates of this genotype on dopaminergic phenotypes, especially working memory, have been reported. COMT activity can also be regulated pharmacologically by COMT inhibitors. The inverted-U relationship between cortical dopamine signaling and working memory predicts that the effects of COMT inhibition will differ according to COMT genotype.MethodsThirty-four COMT Met158Met (Met-COMT) and 33 COMT Val158Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a randomized, double-blind, between-subjects design. They completed the N-back task of working memory and a gambling task.ResultsIn the placebo group, Met-COMT subjects outperformed Val-COMT subjects on the 2- back, and they were more risk averse. Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance in Met-COMT subjects but enhanced it in Val-COMT subjects. Tolcapone made Met-COMT subjects less risk averse but Val-COMT subjects more so. In both tasks, tolcapone reversed the baseline genotype differences.ConclusionsDepending on genotype, COMT inhibition can enhance or impair working memory and increase or decrease risky decision making. To our knowledge, the data are the clearest demonstration to date that the direction of effect of a drug can be influenced by a polymorphism in its target gene. The results support the inverted-U model of dopamine function. The findings are of translational relevance, because COMT inhibitors are used in the adjunctive treatment of Parkinson's disease and are under evaluation in schizophrenia and other disorders.

The neurological basis of developmental psychopathology in autism is a matter of intense debate. Magnetoencephalography (MEG) was used to study the neuronal responses associated with the processing of faces in 12 able adults with autism spectrum disorders (ASD), performing image categorization and image identification tasks. The neuromagnetic data were analysed using nonparametric time-series analysis and equivalent current dipole estimation. Comparison data were obtained from 22 normally developing adults. In individuals with ASD, the neural responses to images of faces, observed in right extrastriate cortices at approximately 145 ms after stimulus onset, were significantly weaker, less lateralized and less affected by stimulus repetition than in control subjects. Early latency (30-60 ms) responses to face images, over right anterior temporal regions, differed significantly between the two subject groups in the image identification task. No such difference was observed for images of mugs or meaningless geometrical patterns. These findings suggest that, during the course of development in individuals with ASD, the cortical activity associated with the processing of human faces assumes a different-from-normal localization in extrastriate brain regions. This abnormal localization may be associated with unusual, but nevertheless face-specific, fast processing pathways.

Autism is a neurodevelopmental disorder associated with deficits in language and social communication. Behavioural studies indicate abnormal semantic organization in individuals with autism, but little is known about the neural mechanism underlying the processing of language in context. Magnetoencephalography was used to record neural responses in 11 able adults with autism spectrum disorders reading meaningful sentences and sentences ending with a semantically incongruous word (e.g. 'He sent a photo to the trumpet'). Spatially extended evoked signals at 400 ms (N4) and 750 ms (LPC), as well as synchronized gamma-oscillations, provided clear evidence for specific neuronal processes sensitive to sentence context that differed in individuals with autism compared with typically developing individuals (11 healthy volunteers). Amongst other differences, N4 responses following incongruous words were weaker over left temporal cortices, whereas LPC responses to incongruous words and long-latency gamma-oscillations following congruous words were stronger over central and prefrontal regions in individuals with autism compared with the control group. Also, incongruous words elicited long-lasting gamma-oscillations above 40 Hz in the clinical group, but not in typically developing subjects. These findings may indicate unusual strategies for resolving semantic ambiguity in autism. Moreover, the observed gamma-band responses provide evidence for sustained cortical synchronization across segregated areas in individuals with autism, contrary to claims that a general deficit in either temporal binding or long-range connectivity may explain autism.

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In this work, magnetoencephalography was used to study the temporal dynamics of neural responses in 16 subjects (eight women, eight men) choosing among different day-to-day consumer items. At short latencies (< 150 ms), the evoked responses showed striate and extrastriate cortical activation common to the processing of general objects. At about 300 ms, women activated preferentially left posterior cortices, whereas men activated preferentially right temporal cortices. This may reflect sex/gender differences in cognitive strategies, emphasizing category-specific knowledge in women and spatial memories in men. At latencies greater than 500 ms, right parietal cortices were preferentially activated when previously bought or used items were chosen. In contrast, left inferior and right orbital cortices were preferentially activated when selecting less-known items. This may be interpreted as representing the neural correlates of decisions where the outcome is consistent with previous experience, and of choices which are 'difficult' in some sense. Analysis of coherent gamma-oscillations (20-45 Hz) revealed neural activity over left anterior and right dorsolateral cortices at long latency (> 1500 ms) when brand knowledge is low. This is consistent with the late binding of (brand) memories and evaluation of multiple sources of information when a choice is not obvious. gamma-Activity showed that women may activate larger neural networks when preference is high, suggesting that men and women exhibit different patterns of neural activity even though their overt performances are similar.

Electrophysiological responses to previously seen faces reportedly differ from those to novel faces at shorter latencies than generally associated with complex visual analysis. It is unclear, however, whether such observations are unique to faces, and which stages of visual processing they reflect. MEG was used in 21 normal adults to record neural responses to images of faces, other objects and abstract patterns presented individually as part of a classification task and in sequential pairs as part of an image comparison task. The amplitudes of the short latency responses (30-60 ms) to the first image in pairs of faces were significantly greater than the responses to both the second faces and the individual face images. These early responses were recorded over predominantly right hemisphere parietal and occipito-temporal cortical regions including areas that, at longer latencies, have been associated with face specific activity. The differences in the responses within pairs were less for non-face objects and absent for abstract geometrical patterns. No early neuronal activity was observed in the classification task. The results indicate the existence of early latency neural networks that are sensitive to both stimulus type and task and are strongly activated by faces.

Noninvasive brain imaging was used to observe 18 subjects, each making 90 choices of three brands on a virtual (video) supermarket visit. Package height provided a control for the main experiment. Brain activations in brand choice differed from those for height discrimination, and choice times were faster when one brand was more familiar. Brand choice appeared to involve silent vocalization. Decision processes took approximately 1 s and can be seen as two halves. The first period seems to involve problem recognition and here male brain patterns differed from female. The second half concerned the choice itself. No male/female differences were observed but a different pattern was evoked where one brand was familiar and the other two were not. The right parietal cortex was strongly activated in this case. This research pioneers new techniques using relatively few subjects and against a limited theoretical background. As such it must be classified as exploratory. Marketers are fundamentally interested in how consumers make buying decisions and now researchers can virtually look into their minds when they are doing so. Psychology is becoming increasingly anchored

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