Efficient behavioral functioning requires early perceptual inhibition of irrelevant stimuli and later motor inhibition of inappropriate responses. The Perceptual and Motor Conflict Tasks were developed to differentially assess perceptual and motor inhibition, and to determine whether these processes utilize separate or shared cognitive resources. The computerized tasks include six subtests involving a box or an arrow appearing in various locations. Subjects respond by pressing a key on the left or right side of a keyboard. In different subtests, arrow direction or stimulus location determines correct responses. Perceptual inhibition assessment requires the subject to respond to a conflicting arrow direction while ignoring stimulus location. Motor inhibition assessment involves the subject responding in the direction opposite to that indicated by a centrally located arrow. In a neurologically normal sample (N 5 44), reaction time analyses yielded significant Perceptual and Motor Conflict main effects, with slower performance under conflict conditions, but no significant Perceptual 3 Motor interaction. The lack of a significant Perceptual 3 Motor interaction, according to the additive factor model, indicates that these two processes utilize distinct cognitive resources. Nevertheless, performance on the two conflict tasks was significantly correlated with each other, and Perceptual Conflict performance was significantly correlated with Stroop interference. (JINS, 2003, 9, 25-30.)

Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research.

Traditional case-control genetic association studies utilizing unrelated probands are often used interchangeably with family-based designs to detect genes for complex psychiatric disorders. This strategy may be limited, however, if significant phenotypic variation exists between probands enrolled in these two types of studies. The present study compared 37 probands enrolled in a case-control study of schizophrenia with 37 age-, sex-, and ethnically matched probands enrolled in a family-based study of schizophrenia. Age of onset of illness was compared as well as performance on a battery of cognitive tests assessing attention, working memory, executive function, and verbal memory. Results revealed no significant differences in age of onset between the two groups or on any measure of cognitive performance. These data do not support reports of significant phenotypic variation between probands in case-control and family-based studies, and suggest that studies utilizing family-based approaches may be used to replicate reports of association made with case-control designs in schizophrenia.

We were pleased by Dr. Bruyer's opinion that our paper is likely to become "influential shortly" and welcome this opportunity to respond to his thoughtful comments and cautions regarding the manuscript. We certainly agree with his view that novel manuscripts and approaches must be examined carefully and appreciate his careful examination of our manuscript. Dr. Bruyer raises three qualifications related to our analyses and interpretation of the data.The first relates to the potential for over-interpretation of the meaning of finding the null when examining the Perceptual 3 Motor conflict interaction. We agree that nonsignificant results must be viewed with extreme caution, and that additional research and replication is warranted. Dr. Bruyer's suggestion for a control task in which the interaction is predicted and observed is quite clever and would have been a useful addition to the study, but unfortunately we did not administer such a task. Nevertheless, in this case, we have reasonable confidence that the lack of a significant interaction is not an artifact of measurement issues such as ceiling and floor effects, or limited power as suggested by Dr. Bruyer. Unlike error scores, where ceiling and floor effects frequently occur, the use of reaction time as the primary dependent measure in this paradigm virtually precludes ceiling and floor effects. In addition, as discussed in the manuscript, other methodological concerns that might impact upon the findings such as a speedaccuracy tradeoff or overall intellectual ability do not appear to impact upon the findings. With regard to power, the interaction did not "fall just short of significance," but rather was virtually null (F 5 0.08). To emphasize this point, we indicated in the manuscript that the p value was not just ..10, but rather ..50. Thus, it is unlikely that this nonsignificant finding for the interaction is spurious.The second point raised by Dr. Bruyer was somewhat less clear to us. He indicates that traditional statistical approaches for examining main effects and interactions are not convincing in this case and that the effect of each conflict should be assessed purely, in the absence of the other conflict. This certainly seems to make sense. His commentary indicates that we did not report the mean reaction times for the four critical subconditions. However, those means are depicted in Figure 2 in the manuscript; the precise means (SD) are indicated in the Using these numbers, the calculated impact of perceptual conflict in the absence of motor conflict is 175 ms (538 2 363); the magnitude of the motor conflict effect is 119 ms (482 2 363), and the combined effect is 285 ms (648 2 363). This is clearly an additive effect (175 1 119 5 294 vs. 285 ms). It is not clear to us how he generated his estimates which led to an underadditive effect, but we suspect that he erroneously used marginal rather than cell means to calculate them.Dr. Bruyer's third point relates to the use of absolute scores rather than proportional differences to determine the magnitud...