***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In a prior study of 54 relatives of patients with schizophrenia and 72 control participants , 3 neuropsychological functions met the criteria for risk indicators of the schizophrenia genotype : executive functioning , memory , and auditory attention . In an assessment of the stability of these findings , the sample was reexamined 4 years after the initial assessment . Three test scores were found to differ between groups ( Immediate Verbal Memory , Delayed Verbal Memory , and Dichotic Listening Digits Detected ) or to show a significant Group x Gender interaction ( immediate and delayed verbal and visual memories ) . None of the test scores showed Group x Time interactions , suggesting that the discriminating power of the tests was stable over time . Evidence for deficits in working memory and rule learning on the object alternation test was also found . These results support the idea that neuropsychological dysfunction among relatives of patients with schizophrenia is a stable trait caused by the familial predisposition to schizophrenia Imaging genetics provides an enormous amount of functional-structural data on gene effects in living brain , but the sheer quantity of potential phenotypes raises concerns about false discovery . Here , we provide the first empirical results on false positive rates in imaging genetics . We analyzed 720 frequent coding SNPs without significant association with schizophrenia and a subset of 492 of these without association with cognitive function . Effects on brain structure ( using voxel-based morphometry , VBM ) and brain function , using two archival imaging tasks , the n-back working memory task and an emotional face matching task , were studied in whole brain and regions of interest and corrected for multiple comparisons using st and ard neuroimaging procedures . Since these variants are unlikely to impact relevant brain function , positives obtained provide an upper empirical estimate of the false positive association rate . In a separate analysis , we r and omly permuted genotype labels across subjects , removing any true genotype-phenotype association in the data , to derive a lower empirical estimate . At a set correction level of 0.05 , in each region of interest and data set used , the rate of positive findings was well below 5 % ( 0.2 - 4.1 % ) . There was no relationship between the region of interest and the false positive rate . Permutation results were in the same range as empirically derived rates . The observed low rates of positives provide empirical evidence that the type I error rate is well controlled by current commonly used correction procedures in imaging genetics , at least in the context of the imaging paradigms we have used . In fact , our observations indicate that these statistical thresholds are conservative Rationale First generation antipsychotics induce extrapyramidal motor symptoms ( EPS ) , presumably through dopamine D2 receptor blockade at the dorsal striatum . This may also produce impairment of cognitive processes , such as procedural learning , that are dependent on this region . Haloperidol and , to a lesser extent , risperidone , are active in the dorsal striatum and may induce EPS and impairment of procedural learning . In contrast , the prototypical second-generation antipsychotic , clozapine , is less active in the dorsal striatum and does not induce EPS or impair procedural learning .  Olanzapine is pharmacologically similar to clozapine and has a low incidence of EPS induction . Objectives To assess the hypothesis that olanzapine would not have a deleterious effect on procedural learning . Methods Thirty-nine subjects with early phase schizophrenia were r and omly assigned to double blind treatment with haloperidol , risperidone , or olanzapine . They were administered the Tower of Toronto test at an unmedicated baseline and again following 6 weeks and 6 months of treatment . Results Procedural learning , defined as the improvement observed between two blocks of five trials of the Tower of Toronto , was preserved after 6 weeks of all three treatments but showed a substantial decline after 6 months of treatment with haloperidol or risperidone . Conclusions These data are consistent with the differential activity of the three medications in dorsal striatum structures and suggest that the advantages of olanzapine over haloperidol and risperidone in relation to extrapyramidal syndromes may also generalize to procedural learning . The results also suggest that the procedural learning disadvantages of haloperidol and risperidone accrue slowly but are apparent after 6 months of treatment The striatum is known to play a primary role in procedural learning . In this study , the authors simultaneously assessed the effects of two antipsychotic drugs on procedural learning and on striatal dopamine ( D2 ) receptor occupancy . Twenty-seven patients receiving either olanzapine or haloperidol as antipsychotic medication were assessed with the Computed Visual Tracking Task ( CVTT ) and Single Photon Emission Computed Tomography ( SPECT ) following the administration of Iodine 123-IBZM ( 123I-IBZM ) , a radiolig and with a high affinity and specificity for the D2 receptors . The results showed poorer procedural learning in the haloperidol-treated patients than in normal control subjects , while no difference could be found between olanzapine-treated patients and normal control subjects . In the haloperidol but not the olanzapine group , significant correlations were found between procedural learning deficits and striatal D2 receptor occupancy . However , there was no significant difference in D2 receptor occupancy between olanzapine- and haloperidol-treated patients , and this may be related to the high doses of olanzapine and low doses of haloperidol administered . The authors concluded that : 1 ) striatal D2 receptor blockade may alter procedural learning in humans ; and 2 ) olanzapine may have a protective effect on procedural learning , even at doses that produce striatal D2 receptor occupancy as high as that found with haloperidol . This protective effect of olanzapine may be related to its atypical pharmacological properties BACKGROUND Prospect i ve studies of young individuals at high risk of schizophrenia allow the investigation of whether neural abnormalities pre date development of illness and , if present , have the potential to identify those who may become ill . METHODS We studied young individuals with at least two relatives with the disorder . At baseline functional magnetic resonance imaging ( fMRI ) scan , none met criteria for any psychiatric disorder , but four subjects subsequently developed schizophrenia . We report the baseline functional imaging findings in these subjects performing a sentence completion task compared with  normal control subjects ( n = 21 ) and those at high risk with ( n = 21 ) and without ( n = 41 ) psychotic symptoms who have not developed the disorder . RESULTS High-risk subjects who became ill demonstrated increased activation of the parietal lobe , decreased activation of the anterior cingulate , and smaller increases in activation with increasing task difficulty in the right lingual gyrus and bilateral temporal regions . The hypothesized predictive power of parietal activation was supported only in combination with lingual gyrus activity , which gave a positive predictive value in this sample of .80 . CONCLUSIONS Although these findings should be considered cautiously , as only four subjects who had an fMRI scan subsequently became ill , they suggest functional abnormalities are present in high-risk subjects who later became ill , which distinguish them not only from normal control subjects but also those at high risk who had not developed the disorder . These differences are detectable with fMRI and may have clinical utility BACKGROUND First-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness and show deficits on high-load information processing tasks . We used functional magnetic resonance imaging ( fMRI ) to test whether nonpsychotic relatives show altered functional activation in the prefrontal cortex ( PFC ) , thalamus , hippocampus , and anterior cingulate during a working memory task requiring interference resolution . METHODS Twelve nonpsychotic relatives of persons with schizophrenia and 12 healthy control subjects were administered an auditory , verbal working memory version of the Continuous Performance Test during fMRI . An asymmetric , spin-echo , T2 * -weighted sequence ( 15 contiguous , 7-mm axial slices ) was acquired on a full-body MR scanner . Data were analyzed by Statistical Parametric Mapping ( SPM ) . RESULTS Compared with control subjects , relatives showed greater task-elicited activation in the PFC and the anterior and dorsomedial thalamus . When task performance was controlled , relatives showed significantly greater activation in the anterior cingulate . When effects of other potentially confounding variables were controlled , relatives generally showed significantly greater activation in the dorsomedial thalamus and anterior cingulate . CONCLUSIONS This pilot study suggests that relatives of persons with schizophrenia have subtle differences in brain function in the absence of psychosis . These differences add to the growing literature identifying neurobiological vulnerabilities to schizophrenia Studies of high-risk offspring ( HR ) of schizophrenic patients have found abnormalities in attention , working memory and executive functions , suggesting impaired integrity of the prefrontal cortex and related brain regions . The authors conducted a preliminary high-field ( 3 T ) functional magnetic resonance imaging ( fMRI ) study to assess performance and activation during a  memory-guided saccade ( MGS ) task  , which measures spatial working memory .  HR subjects showed significant decreases in fMRI-measured activation in the dorsolateral prefrontal cortex ( Brodmann 's areas 8 and 9/46 ) and the inferior parietal cortex ( Brodmann 's area 40 ) compared to age- and sex-matched healthy controls ( HC ) . Abnormal functional integrity of prefrontal and parietal regions of the heteromodal association cortical ( HAC ) regions in subjects at genetic risk for schizophrenia is consistent with findings observed in adults with the illness [ Callicott et al. , Cereb . Cortex 10 ( 2000 ) 1078 ; Manoach et al. , Biol . Psychiatry 48 ( 2000 ) 99 . ] . These abnormalities need to be prospect ively investigated in nonpsychotic individuals at risk for schizophrenia in order to determine their predictive value for eventual emergence of schizophrenia or related disorders 
    Output:
    
The most consistent increases in activation within hemisphere were found in right ventral prefrontal cortex ( PFC ) and right parietal cortex .
The diversity of findings in studies of patients ' relatives may derive from differences between the cognitive dem and s across studies .