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Designs for a broadband chirped pulse Fourier transform microwave (CP-FTMW) spectrometer are presented. The spectrometer is capable of measuring the 7-18 GHz region of a rotational spectrum in a single data acquisition. One design uses a 4.2 Gsampless arbitrary waveform generator (AWG) to produce a 1 mus duration chirped pulse with a linear frequency sweep of 1.375 GHz. This pulse is sent through a microwave circuit to multiply the bandwidth of the pulse by a factor of 8 and upconvert it to the 7.5-18.5 GHz range. The chirped pulse is amplified by a traveling wave tube amplifier and broadcast inside the spectrometer by using a double ridge standard gain horn antenna. The broadband molecular free induction decay (FID) is received by a second horn antenna, downconverted, and digitized by a 40 Gsampless (12 GHz hardware bandwidth) digital oscilloscope. The second design uses a simplified pulse generation and FID detection scheme, employing current state-of-the-art high-speed digital electronics. In this spectrometer, a chirped pulse with 12 GHz of bandwidth is directly generated by using a 20 Gsampless AWG and upconverted in a single step with an ultrabroadband mixer. The amplified molecular emission is directly detected by using a 50 Gsampless digital oscilloscope with 18 GHz bandwidth. In both designs, fast Fourier transform of the FID produces the frequency domain rotational spectrum in the 7-18 GHz range. The performance of the CP-FTMW spectrometer is compared to a Balle-Flygare-type cavity-FTMW spectrometer. The CP-FTMW spectrometer produces an equal sensitivity spectrum with a factor of 40 reduction in measurement time and a reduction in sample consumption by a factor of 20. The CP-FTMW spectrometer also displays good intensity accuracy for both sample number density and rotational transition moment. Strategies to reduce the CP-FTMW measurement time by another factor of 90 while simultaneously reducing the sample consumption by a factor of 30 are demonstrated.

Patients with schizophrenia often show verbal learning deficits that have been linked to the pathophysiology of the disorder and result in functional impairment. This study examined the biological basis of these deficits by comparing the brain response of patients with schizophrenia (n=17) to that of healthy comparison participants (n=14) during a verbal paired-associates learning task using functional magnetic resonance imaging (fMRI). Brain response during new word learning was examined within and between groups in two a priori regions of interest, the inferior frontal gyrus and hippocampus, and across the whole brain. In regions of group difference, we also examined the relationship of brain response during learning to later recall of the word pairs. Despite successful matching of levels of word-pair recall, patients' brain response during new learning was abnormal in bilateral regions within the inferior frontal gyrus, a small region in left posterior hippocampus, and other areas within the frontal, parietal and temporal cortex compared with healthy individuals. In some regions, but not in the hippocampus, patients with the most normal brain response also remembered the most word pairs following scanning. Thus, verbal learning deficits found among patients with schizophrenia appear to be related to hypofunction of distributed brain networks.

Working memory (WM) was studied in 82 healthy volunteers, 43 schizophrenia patients, and 81 bipolar patients. Schizophrenia patients were impaired on verbal and figural WM tasks that possessed similar test discriminating power. Bipolar patients performed similarly to healthy volunteers. A mathematical model of WM performance revealed a primary role for reduced WM span in accounting for the impaired verbal WM of schizophrenia patients and a primary role for diminished attention in accounting for impaired figural WM. Although WM impairment in schizophrenia is due neither to the general effects of severe mental illness nor to the specific type of material studied, the microarchitecture of abnormal WM in schizophrenia may depend on the stimulus material presented., ((c) 2007 APA)

The current investigation examined changes in working memory (WM) component processes following total sleep deprivation (TSD) in a sample of healthy young persons. Forty subjects were administered a verbal form of a continuous recognition test (CRT) before and after 42 hr of TSD. Parameters of a computational model of the CRT reflecting attention, WM span, and rate of episodic memory encoding were estimated for each individual. Subjects made more errors on the test following sleep deprivation. Analysis of model parameters revealed statistically independent declines in both the attention and WM span parameters, with a larger effect observed for the decline in WM span. Examination of individual profiles suggested that the effects of TSD on verbal WM component processes vary from person to person. Declines in global verbal WM functioning appear to be primarily driven by reduced WM span and attention; however, these effects may be individual-specific. Further applications of the computational model for examining WM component processes with sleep deprivation and other clinical populations are discussed., (PsycINFO Database Record (c) 2007 APA, all rights reserved.)

Due to the increasing need for subject privacy, the ability to deidentify structural MR images so that they do not provide full facial detail is desirable. A program was developed that uses models of nonbrain structures for removing potentially identifying facial features. When a novel image is presented, the optimal linear transform is computed for the input volume (Fischl et al. [2002]: Neuron 33:341-355; Fischl et al. [2004]: Neuroimage 23 (Suppl 1):S69-S84). A brain mask is constructed by forming the union of all voxels with nonzero probability of being brain and then morphologically dilated. All voxels outside the mask with a nonzero probability of being a facial feature are set to 0. The algorithm was applied to 342 datasets that included two different T1-weighted pulse sequences and four different diagnoses (depressed, Alzheimer's, and elderly and young control groups). Visual inspection showed none had brain tissue removed. In a detailed analysis of the impact of defacing on skull-stripping, 16 datasets were bias corrected with N3 (Sled et al. [1998]: IEEE Trans Med Imaging 17:87-97), defaced, and then skull-stripped using either a hybrid watershed algorithm (Ségonne et al. [2004]: Neuroimage 22:1060-1075, in FreeSurfer) or Brain Surface Extractor (Sandor and Leahy [1997]: IEEE Trans Med Imaging 16:41-54; Shattuck et al. [2001]: Neuroimage 13:856-876); defacing did not appreciably influence the outcome of skull-stripping. Results suggested that the automatic defacing algorithm is robust, efficiently removes nonbrain tissue, and does not unduly influence the outcome of the processing methods utilized; in some cases, skull-stripping was improved. Analyses support this algorithm as a viable method to allow data sharing with minimal data alteration within large-scale multisite projects., ((c) 2007 Wiley-Liss, Inc.)

In this manuscript, basic principles of functional magnetic resonance imaging (fMRI) are reviewed. In the first section, two intrinsic mechanisms of magnetic resonance image contrast related to the longitudinal and transverse components of relaxing spins and their relaxation rates, T(1) and T(2), are described. In the second section, the biophysical mechanisms that alter the apparent transverse relaxation time, T(2*), in blood oxygenation level dependent (BOLD) studies and the creation of BOLD activation maps are discussed. The physiological complexity of the BOLD signal is emphasized. In the third section, arterial spin labeling (ASL) measures of cerebral blood flow are presented. Arterial spin labeling inverts or saturates the magnetization of flowing spins to measure the rate of delivery of blood to capillaries. In the fourth section, calibrated fMRI, which uses BOLD and ASL to infer alterations of oxygen utilization during behavioral activation, is reviewed. The discussion concludes with challenges confronting studies of individual cases.

Background: The pentatricopeptide repeat (PPR) is a degenerate 35 amino acid motif that occurs in multiple tandem copies in members of a recently recognized eukaryotic gene family. Most analyzed eukaryotic genomes contain only a small number of PPR genes, but in plants the family is greatly expanded. The factors that underlie the expansion of this gene family in plants are not as yet understood., Results: We show that the location of PPR genes is highly variable in comparisons between orthologous, closely related, and otherwise co-linear chromosomal regions of the Brassica rapa or radish and Arabidopsis thaliana. This observation also pertains to paralogous duplicated segments of the genomes of Arabidopsis thaliana and Brassica rapa. In addition, we show that PPR genes that seem closely linearly aligned in these comparisons are not generally found to be closely related to one another at the nucleotide and amino acid sequence level. We observe a relatively high level of non-synonomous vs synonomous changes among a group tandemly repeated radish PPR genes, suggesting that these, and possibly other PPR genes, are subject to diversifying selection. We also show that a duplicated region of the Arabidopsis genome possesses a relatively high density of PPR genes showing high similarity to restorers of fertility of cytoplasmic male sterile (CMS) systems of petunia, radish and rice. The PPR genes in these regions, together with the restorer genes, are more highly similar to one another, in sequence as well as in structure, than to other PPR genes, even within the same sub-family., Conclusion: Our results suggest are consistent with a model in which at least some PPR genes undergo a "birth and death" process that involves transposition to unrelated chromosomal sites. PPR genes hold certain features in common with disease resistance genes (R genes), and their "nomadic" character suggests that their evolutionary expansion in plants may have involved novel molecular processes and selective pressures.

Arterial spin labeling (ASL) uses magnetic resonance imaging methods to measure cerebral blood flow (CBF) non-invasively. ASL CBF validly localizes brain function and may be especially useful for studies where the time frame of behavioral change is more than a few minutes, such as in longitudinal and treatment studies. ASL measures of cerebral perfusion are highly accurate in detecting lesion laterality in temporal lobe epilepsy, stenotic-occlusive disease, and brain tumors. Among lesioned patients, ASL CBF has excellent concurrent validity when correlated with CBF measured by Positron Emission Tomography or with dynamic susceptibility-weighted magnetic resonance. ASL CBF can predict tumor grading in vivo and can predict six-month response to the surgical treatment of brain tumors. ASL's capability to selectively and non-invasively tag flow in major vessels may refine the monitoring of treatment of cerebrovascular disease and brain tumors. Conclusions about the utility of ASL are limited by the small sample sizes of the studies currently in the literature and by the uncertainty caused by the effect of brain disease on transit times of the magnetic tag. As the method evolves, ASL techniques will likely become more widely used in clinical research and practice.

Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) method that provides a highly repeatable quantitative measure of cerebral blood flow (CBF). As compared to the more commonly used blood oxygenation level dependent (BOLD) contrast-based methods, ASL techniques measure a more biologically specific correlate of neural activity, with the potential for more accurate estimation of the location and magnitude of neural function. Recent advances in acquisition and analysis methods have improved the somewhat limited sensitivity of ASL to perfusion changes associated with neural activity. In addition, ASL perfusion measures are insensitive to the low-frequency fluctuations commonly observed in BOLD experiments and can make use of imaging sequences that are less sensitive than BOLD contrast to signal loss caused by magnetic susceptibility effects. ASL measures of perfusion can aid in the interpretation of the BOLD signal change and, when combined with BOLD, can measure the change in oxygen utilization accompanying changes in behavioral state. Whether used alone to probe neural activity or in combination with BOLD techniques, ASL methods are contributing to the field's understanding of healthy and disordered brain function.

Human immunodeficiency virus (HIV) and methamphetamine (METH) use disorders are associated with cerebral dysfunction. To determine whether these effects were evident on in vivo neuroimaging, quantitative, single voxel magnetic resonance (MR) spectroscopy was used to assess frontal white matter, frontal gray matter, and basal ganglia in 40 HIV+/METH+, 66 HIV+/METH-, 48 HIV-/METH+, and 51 HIV-/METH- participants. HIV was associated with lower N-acetylaspartate (NAA) in frontal white and frontal gray matter but METH was not associated with cerebral metabolite differences in any region. Among HIV+ individuals, lower CD4 counts and higher plasma HIV viral loads were associated with lower NAA in frontal gray matter and basal ganglia. The relationship between detectable plasma HIV viral load and NAA in frontal white matter was significantly stronger in the HIV+/METH+ group, compared to HIV+/METH-. Higher detectable plasma HIV viral load was significantly associated with higher myo-inositol (MI) in frontal white and gray matter for HIV+/METH+, but not HIV+/METH-. For the HIV-/METH+ group, lifetime duration of METH use was associated with higher choline levels in frontal gray matter and higher MI levels in basal ganglia. Our findings are consistent with significant disruption of neuronal integrity in the frontal lobes of HIV-infected individuals. Although METH was not associated with cerebral metabolite levels, other findings suggested that METH use did affect the brain. For example, the relationship between detectable plasma HIV viral load and NAA levels was limited to HIV+/METH+ individuals. This evidence indicates when HIV is poorly suppressed, METH may modify the effects of the virus on neuronal integrity.

The capacity of schizophrenia patients to make decisions regarding research consent relates to neurocognition, but the exact nature of the relationship is unclear. The authors examined the correlation of scores on the MacArthur Competence Assessment Tool for Clinical Research with functional magnetic resonance imaging brain response during a verbal learning task. Understanding of a consent form correlated with activation of the right hippocampus during verbal learning and with brain response in a large area that included the bilateral parahippocampus, cerebellum, and thalamus. Reasoning scores were not significantly related to brain activation. Understanding deficits during informed consent relates to particular brain abnormalities among schizophrenia patients.

Previous studies of episodic memory report a greater extent of blood-oxygenation-level-dependent (BOLD) response in non-demented older adults with the apolipoprotein E epsilon-4 (APOE epsilon4) allele than in those without the allele. We conducted a functional MRI study to investigate whether APOE genotype is related to brain response to verbal paired-associate encoding and consolidation, particularly in the right hemisphere, among non-demented older adults. Structurally segmented volumes and BOLD response were measured in 13 non-epsilon4 and 12 epsilon4 subjects. The epsilon4 group displayed greater activation than the non-epsilon4 group in multiple right hemisphere regions for previously encoded word pairs relative to fixation. Activation within manually outlined hippocampal regions of interest also displayed genotype-specific dissociations consistent with whole brain analyses. Furthermore, this differential BOLD response occurred in the presence of equivalent behavioral and neuropsychological performances as well as comparable hippocampal and overall structural segmentation volumes between groups. Results implicate a widely distributed and interconnected network of right hemisphere brain regions that may be involved in compensating for APOE epsilon4-related deficiencies associated with verbal episodic memory encoding and consolidation.

Background: According to cognitive diathesis-stress theories, a latent cognitive vulnerability to depression is activated by negative affect in individuals at risk for depressive relapse. This vulnerability can manifest as mood-congruent memory during sad mood and may involve amygdala response, which is implicated in memory for emotionally arousing stimuli. This study examined whether amygdala modulates memory for negatively valenced words before and after a sad mood induction in healthy individuals with and without a history of recurrent major depression., Methods: Fourteen unmedicated remitted depressed (RD) and 14 matched never depressed (ND) individuals were scanned using functional magnetic resonance imaging (fMRI) while performing a self-referent encoding/evaluation task (SRET) preceding and following a sad mood challenge. After each SRET, participants' free recall was assessed., Results: Following sad mood induction, bilateral amygdala response during encoding of valenced words predicted increased recall of negative self-referent words for a subset of RD participants. This association was not present before the sad mood induction and was not evident in individuals without a history of depression, regardless of mood state., Conclusions: These results are consistent with cognitive diathesis-stress theories and suggest a role for the amygdala in modulating mood-congruent memory during transient sad mood in individuals who are vulnerable to depression relapse.

Aim: To use the superior spatial resolution of magnetic resonance imaging (MRI) to examine differences in cerebral perfusion between young alcohol dependent and normal women., Methods: Eight alcohol dependent women and 8 controls (all ages 18-25) received single-slice resting perfusion-weighted MRI (directly proportional to brain blood flow), with slices located above the corpus callosum., Results: Alcohol-dependent women had decreased perfusion in prefrontal and left parietal regions., Conclusions: Reduced perfusion has not previously been reported in young, physically healthy alcohol dependent females, yet is consistent with previously reported decreased cerebral activity in alcohol dependence.

Functional magnetic resonance imaging (fMRI) provides a means of identifying neural circuitry associated with startle and its modulation in humans. Twelve subjects who demonstrated eyeblink startle in the laboratory were recruited for an fMRI study in which they were scanned while presented with two identical runs consisting of alternating blocks of no stimuli and startling tactile stimuli. Together, behavioral and imaging data are consistent with a pattern of general cortical and thalamic activation induced by startling stimuli that shows habituation both across and within runs. From Run 1 to Run 2, both the eyeblink amplitude and the fMRI signal decreased. Within Run 1, there was a graded decrease in eyeblink amplitude and whole-brain fMRI signal across blocks of startling stimuli. A similar graded decrease was observed in the thalamus signal, as well. Thus, startling tactile stimuli initially induce widespread cortical and thalamic activity, perhaps mediated by the reticular activating system. The activity then habituates in a graded fashion with repeated presentations of the stimuli.

Previous fMRI research has found altered brain response after total sleep deprivation (TSD), with TSD effects moderated by task difficulty. Specific models of the impact of sleep deprivation and task difficulty on brain response have yet to be developed. Differences in networks of fMRI measured brain response during verbal encoding in sleep deprived and well-rested individuals were examined with structural equation modeling (SEM). During fMRI scanning, 23 healthy volunteers memorized words either easy or difficult to recall, 12 (well-rested) and 36 hours (sleep deprived) after awaking. A priori models that linked specified regions of interest were evaluated, with the focus on the extent to which two left parietal regions interacted with the left inferior frontal gyrus (Model 1) or with the right inferior frontal gyrus (Model 2). Task difficulty, not TSD, determined which model fit the brain response data; Model 2 fit best for hard words before and after TSD, whereas Model 1 fit best for easy words. TSD altered the patterns of interaction within each of the best fitting models: prefrontal interactions with the left inferior parietal lobe were diminished and intra-parietal interactions increased. Sleep deprivation and item difficulty produce different effects on brain networks involved in verbal learning.

The Polima (pol) system of cytoplasmic male sterility (CMS) and its fertility restorer gene Rfp are used in hybrid rapeseed production in Brassica napus. To facilitate map-based cloning of the Rfp gene, we have successfully transferred the pol cytoplasm and Rfp from the amphidiploid B. napus to the diploid species B. rapa and generated a doubled haploid pol cytoplasm B. rapa population that segregates for the Rfp gene. This was achieved through interspecific crosses, in vitro rescue of hybrid embryos, backcrosses, and microspore culture. Male fertility conditioned by Rfp was shown to co-segregate in this population with Rfp-specific mitochondrial transcript modifications and with DNA markers previously shown to be linked to Rfp in B. napus. The selfed-progeny of one doubled haploid plant were confirmed to be characteristic B. rapa diploids by cytogenetic analysis. Clones recovered from a genomic library derived from this plant line using the RFLP probe cRF1 fell into several distinct physical contigs, one of which contained Rfp-linked polymorphic restriction fragments detected by this probe. This indicates that chromosomal DNA segments anchored in the Rfp region can be recovered from this library and that the library may therefore prove to be a useful resource for the eventual isolation of the Rfp gene.

This study used functional magnetic resonance imaging (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: 1) depressed responders' baseline ventral anterior cingulate (AC) perfusion will be greater than that of nonresponders and controls; 2) following partial sleep deprivation (PSD), ventral AC perfusion will significantly decrease in responders only. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD. Talairach-transformed gray matter masks were merged with Talairach Daemon-based region of interest (ROI) templates. Baseline left ventral AC (LVAC) perfusion was greater in responders than nonresponders. There was no difference involving the medial frontal cortex. Responders' LVAC perfusion dropped from baseline to PSD scans compared with nonresponders and controls, as did perfusion in the right dorsal AC. In the patient group as a whole, decrease in LVAC perfusion from baseline to PSD scans correlated directly with the decrease in the modified 17-item Hamilton Depression Rating Scale (HDRS17) between baseline and PSD conditions. These data--the first using fMRI--show greater anatomic specificity than previous findings of SD and depression in linking decreased brain activity in this area with clinical improvement.

Background: Evidence from the neuroimaging literature suggests that the basal ganglia plays an important role in the regulation of affect. This conclusion stems almost exclusively from group comparisons and it remains unclear whether previous findings can be confirmed from a longitudinal study of mood change. The aim of this study was to increase our understanding of the functional role of the basal ganglia and thalamus in relation to change in affect in patients with bipolar disorder., Methods: Ten bipolar disorder subjects participated in a functional MRI study. We used a simple motor reaction time task to probe subcortical regions bilaterally. Subjects were scanned twice, once when their self-reported mood ratings indicated hypomania or euthymia and then again when they were in depressed states., Results: Subjects in their euthymic or hypomanic states exhibited increased caudate activity bilaterally and the globus pallidus of the left hemisphere. Longitudinal analyses revealed a significant association between an increase in severity of depression and a decrease in activity in the external segment of the right globus pallidus., Conclusions: Our findings suggest that the globus pallidus is less responsive during a simple motor task in the depressed compared to the normal or euthymic states in patients with bipolar disorder. These results are consistent with current physiologic models of basal ganglia circuitry in which an increase in caudate activity results in an increase in inhibitory GABAergic outflow to the external globus pallidus and subsequent decrease in thalamocortical excitation and may underlie the clinical manifestations of depression in bipolar disorder., Limitations: The findings of this study need to be interpreted with caution as correlation coefficients may be overestimated in this small study sample.

The amnestic effects of benzodiazepines are well documented on a variety of memory tasks. However, prospective memory (PM), or remembering to execute an action at a future time, has not been studied previously. This study examined the effect of diazepam on word list recall, PM, sustained attention, and subjective ratings of arousal. Forty-eight healthy participants, aged 19-35, received an average of 0.19 mg/kg oral diazepam or placebo in a double-blind manner. Retrospective memory and PM were assessed by free recall of unrelated word lists and by instructing participants to request a hidden belonging at the end of the session, respectively. Sustained attention was measured by multiple trials of a digit cancellation task, and subjective arousal was assessed by self-ratings of drowsiness. Diazepam impaired performance on all measures, including PM. Reduced PM performance was associated with decreased subjective arousal in the diazepam group but was unrelated to sustained attention. This is the first report of the effects of benzodiazepines on prospective remembering, and further supports the view that the arousal/attentional system is composed of partially independent subsystems that have differential relationships to memory.

Performance of automated methods to isolate brain from nonbrain tissues in magnetic resonance (MR) structural images may be influenced by MR signal inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of subjects studied. The present study compared the performance of four methods: Brain Extraction Tool (BET; Smith [2002]: Hum Brain Mapp 17:143-155); 3dIntracranial (Ward [1999] Milwaukee: Biophysics Research Institute, Medical College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al. [2004] Neuroimage 22:1060-1075; in FreeSurfer); and Brain Surface Extractor (BSE, Sandor and Leahy [1997] IEEE Trans Med Imag 16:41-54; Shattuck et al. [2001] Neuroimage 13:856-876) to manually stripped images. The methods were applied to uncorrected and bias-corrected datasets; Legacy and Contemporary T1-weighted image sets; and four diagnostic groups (depressed, Alzheimer's, young and elderly control). To provide a criterion for outcome assessment, two experts manually stripped six sagittal sections for each dataset in locations where brain and nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard similarity coefficients, Hausdorff distances, and an Expectation-Maximization algorithm. Methods tended to perform better on contemporary datasets; bias correction did not significantly improve method performance. Mesial sections were most difficult for all methods. Although AD image sets were most difficult to strip, HWA and BSE were more robust across diagnostic groups compared with 3dIntracranial and BET. With respect to specificity, BSE tended to perform best across all groups, whereas HWA was more sensitive than other methods. The results of this study may direct users towards a method appropriate to their T1-weighted datasets and improve the efficiency of processing for large, multisite neuroimaging studies., (Copyright (c) 2005 Wiley-Liss, Inc.)

This study used functional MRI (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: (1) baseline perfusion in right and left amygdalae will be greater in responders than in nonresponders; (2) following partial sleep deprivation (PSD), perfusion in responders' right and left amygdalae would decrease. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD. Baseline bilateral amygdalar perfusion was greater in responders than nonresponders. Clusters involving both amygdalae decreased from baseline to PSD specifically in responders. Right amygdalar perfusion diverged with PSD, increasing in nonresponders and decreasing in responders. These novel amygdalar findings are consistent with the overarousal hypothesis of SD as well as other functional imaging studies showing increased baseline amygdalar activity in depression and decreased amygdalar activity with remission or antidepressant medications.

Functional magnetic resonance imaging (MRI) is a noninvasive, highly repeatable, and increasingly available method to study disordered brain activity among patients with psychological or neurological disorders. In this chapter the biophysical principles underlying functional MRI are presented, and methodological limitations of the method are discussed. Artifacts related to the biophysical basis of the functional MRI signal or associated with image acquisition methods are presented, as are artifacts related to baseline effects-especially those associated with medication, caffeine, and nicotine use. The difficulties associated with the comparison of groups of subjects differing in performance receive special attention. The limitations of cognitive subtraction designs for functional MRI are also discussed. Functional MRI studies of schizophrenia patients are used to illustrate these points.

This study examined the effects of total sleep deprivation (TSD) on cerebral responses to a verbal learning task with two levels of word difficulty. A total of 32 subjects were studied with functional magnetic resonance imaging (FMRI) after normal sleep and following 36 h of TSD. Cerebral responses to EASY words were identical on both nights, but several brain regions showed increased activation to HARD words following TSD compared with following a normal night of sleep (NORM). These regions included bilateral inferior frontal gyrus, bilateral dorsolateral prefrontal cortex, and bilateral inferior parietal lobe. Better free recall performance on the HARD words after TSD was related to increased cerebral responses within the left inferior and superior parietal lobes and left inferior frontal gyrus. Recall was negatively related to activation within the right inferior frontal gyrus. Overall, the findings support the predictions of the compensatory recruitment hypothesis that task demands influence both the likelihood and location of increased cerebral activation during task performance following TSD, and refine that hypothesis by identifying a specific task demand that plays a role. The performance relationships suggest increased activation may be both beneficial (compensatory) and interfere with task performance, depending on the brain regions involved.

Purpose: To prospectively investigate the factors--including subject, brain hemisphere, study site, field strength, imaging unit vendor, imaging run, and examination visit--affecting the reproducibility of functional magnetic resonance (MR) imaging activations based on a repeated sensory-motor (SM) task., Materials and Methods: The institutional review boards of all participating sites approved this HIPAA-compliant study. All subjects gave informed consent. Functional MR imaging data were repeatedly acquired from five healthy men aged 20-29 years who performed the same SM task at 10 sites. Five 1.5-T MR imaging units, four 3.0-T units, and one 4.0-T unit were used. The subjects performed bilateral finger tapping on button boxes with a 3-Hz audio cue and a reversing checkerboard. In a block design, 15-second epochs of alternating baseline and tasks yielded 85 acquisitions per run. Functional MR images were acquired with block-design echo-planar or spiral gradient-echo sequences. Brain activation maps standardized in a unit-sphere for the left and right hemispheres of each subject were constructed. Areas under the receiver operating characteristic curve, intraclass correlation coefficients, multiple regression analysis, and paired Student t tests were used for statistical analyses., Results: Significant factors were subject (P < .005), k-space (P < .005), and field strength (P = .02) for sensitivity and subject (P = .03) and k-space (P = .05) for specificity. At 1.5-T MR imaging, mean sensitivities ranged from 7% to 32% and mean specificities were higher than 99%. At 3.0 T, mean sensitivities and specificities ranged from 42% to 85% and from 96% to 99%, respectively. At 4.0 T, mean sensitivities and specificities ranged from 41% to 73% and from 95% to 99%, respectively. Mean areas under the receiver operating characteristic curve (+/- their standard errors) were 0.77 +/- 0.05 at 1.5 T, 0.90 +/- 0.09 at 3.0 T, and 0.95 +/- 0.02 at 4.0 T, with significant differences between the 1.5- and 3.0-T examinations and between the 1.5- and 4.0-T examinations (P < .01 for both comparisons). Intraclass correlation coefficients ranged from 0.49 to 0.71., Conclusion: MR imaging at 3.0- and 4.0-T yielded higher reproducibility across sites and significantly better results than 1.5-T imaging. The effects of subject, k-space, and field strength on examination reproducibility were significant., (RSNA, 2005)

Nucleoside reverse transcriptase inhibitors (NRTIs) suppress human immunodeficiency virus (HIV) replication, but are often associated with mitochondrial toxicity. Although well studied outside of the central nervous system, no investigation has examined the effects of these drugs on brain mitochondria of individuals living with HIV. The authors used proton magnetic resonance spectroscopy to evaluate NRTI-related changes in brain mitochondria. N-acetylaspartate (NAA; sensitive to alterations in mitochondrial integrity) was measured in frontal lobe white and gray matter of 18 HIV+ individuals taking didanosine and/or stavudine (two NRTIs likely to cause mitochondrial toxicity), 14 HIV+ individuals taking zidovudine and lamivudine, 16 HIV+ individuals not currently taking antiretrovirals, and 17 HIV- controls. The HIV+ groups were comparable on demographic measures, estimates of illness severity, and estimated length of HIV infection. Those taking didanosine and/or stavudine had a significant 11.4% decrease in concentrations of frontal white matter NAA compared to HIV- controls, whereas NAA levels of the other HIV+ groups were intermediate. Group differences in metabolites were not found in frontal gray matter. Lower levels of frontal white matter NAA were associated with longer periods of didanosine and/or stavudine treatment (r = -.41, P = .06). Levels of NAA were not related to length of zidovudine/lamivudine treatment (r = -.04, P = .44). Furthermore, taking more than one of stavudine, didanosine, and abacavir increased the likelihood of having reduced NAA. The results are consistent with previous studies finding HIV-related changes in neuronal integrity. However, because NRTIs can injure mitochondria, we propose that the observed reductions in NAA in individuals taking didanosine and/or stavudine may be the result of depleted brain mitochondria and/or alterations in cellular respiration. Measurement of brain metabolites sensitive to impairments in energy metabolism, including NAA, may aid in early detection of subclinical NRTI-mediated mitochondrial toxicity.

Alcohol and marijuana use are prevalent in adolescence, yet the neural impact of concomitant use remains unclear. We previously demonstrated functional magnetic resonance imaging (fMRI) response to spatial working memory (SWM) among teens with alcohol use disorders (AUD) compared to controls, and predicted that adolescents with marijuana and alcohol use disorders would show additional abnormalities. Participants were three groups of 15-17-year-olds: 19 non-abusing controls, 15 AUD teens with limited exposure to drugs, and 15 teens with comorbid marijuana and alcohol use disorders (MAUD) and minimal other drug experience. After >2 days' abstinence, participants performed a SWM task during fMRI acquisition. fMRI brain response patterns differed between groups, despite similar performance on the task. MAUD youths showed less activation in inferior frontal and temporal regions than controls, and more response in other prefrontal regions. Compared to AUD teens, MAUD youths also showed less inferior frontal and temporal activation, but more medial frontal response. Overall, MAUD youths showed different brain response abnormalities than teens with AUD alone, despite relatively short histories of substance involvement. This pattern could suggest compensation for marijuana-related attention and working memory deficits. However, relatively recent use and premorbid features may influence results, and should be examined in future studies.

Disenrollment rates from Medicare managed care plans have been reported to the public as an indicator of health plan quality. Previous studies have shown that voluntary disenrollment rates differ among vulnerable subgroups, and that these rates can reflect patient care experiences. We hypothesized that disabled beneficiaries may be affected differently than other beneficiaries by competitive market factors, due to higher expected expenditures and impaired mobility. Findings suggest that disabled beneficiaries are more likely to experience multiple problems with managed care.

Objective: To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults., Methods: Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE epsilon4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions., Results: Nondemented older adults with an APOE epsilon4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched epsilon3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated., Conclusions: The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE epsilon4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding.

Cytoplasmic male sterility (CMS) is a maternally inherited defect in pollen production specified by novel mitochondrial genes. It can be suppressed by nuclear restorer (Rf) genes which normally downregulate expression of a CMS-associated novel mitochondrial gene. Two forms of Brassica napus CMS, nap and pol, are associated with related chimeric genes, orf222 and orf224, respectively. We show that in pol and nap CMS, anther locule development is asynchronous and asymmetric, that one or more locules within each anther may fail to develop entirely and that CMS anthers display polarity in locule development. We show, by in situ hybridization, that orf222 transcripts accumulate in sterile anthers prior to development of morphological differences between CMS and restored stamens, and remain preferentially localized to microsporangia. In fertility-restored anthers, however, orf222 transcript levels remain low throughout development. Some sporogenous and meiotic cells differentiate within CMS anthers and form functional pollen despite retaining high orf222 transcript levels, suggesting that the effect of orf222 expression in blocking pollen development is limited to an early and specific stage. Transcripts of other mitochondrial genes, exemplified by atp6 and cob, and of the nuclear-encoded ATP synthase gamma subunit, accumulate preferentially in the microsporangia of both sterile and fertile anthers. Thus nuclear fertility restoration reduces orf222 transcript levels in a gene and tissue-specific manner. We observe differences between CMS and fertile plants in the timing and patterning of APETALA3 promoter activity that suggest a possible basis for the developmental abnormalities of CMS flowers.

We present the basic principles of dynamic rotational spectroscopy for the highly vibrationally excited symmetric top molecule trifluoropropyne (TFP,CF3CCH). Single molecular eigenstate rotational spectra of TFP were recorded in the region of the first overtone of the nu(1) acetylenic stretching mode at 6550 cm(-1) by infrared-pulsed microwave-Fourier transform microwave triple resonance spectroscopy. The average rotational constant (B) of the highly vibrationally mixed quantum states at 6550 cm(-1) is 2909.33 MHz, a value that is 40 MHz larger than the rotational constant expected for the unperturbed C-H stretch overtone (2869.39 MHz). The average rotational constant and rotational line shape of the molecular eigenstate rotational spectra are compared to the distribution of rotational constants expected for the ensemble of normal-mode vibrational states at 6550 cm(-1) that can interact by intramolecular vibrational energy redistribution (IVR). The normal-mode population distribution at 6550 cm(-1) can be described using a Boltzmann distribution with a microcanonical temperature of 1200 K. At this energy the rotational constant distribution in the normal-mode basis set is peaked at about 2910 MHz with a width of about 230 MHz. The distribution is slightly asymmetric with a tail to the high end. The experimentally measured dynamic rotational spectra are centered at the normal-mode distribution peak; however, the spectral width is significantly narrower (40 MHz) than normal-mode ensemble width (230 MHz). This reduction of the width, along with the Lorentzian shape of the eigenstate rotational spectra when compared to the Gaussian shape of the calculated ensemble distribution, illustrates the narrowing of the spectrum due to IVR exchange. The IVR exchange rate was determined to be 120 ps, about ten times faster than the rate at which energy is redistributed from the v=2 level of the acetylenic stretch.

Background: Previous studies have suggested neural disruption and reorganization in young and older adults with alcohol use disorders (AUD). However, it remains unclear at what age and when in the progression of AUD changes in brain functioning might occur., Methods: Alcohol use disordered (n = 15) and nonabusing (n = 19) boys and girls aged 15 to 17 were recruited from local high schools. Functional magnetic resonance imaging data were collected after a minimum of 5 days' abstinence as participants performed spatial working memory and simple motor tasks., Results: Adolescents with AUD showed greater brain response to the spatial working memory task in bilateral parietal cortices and diminished response in other regions, including the left precentral gyrus and bilateral cerebellar areas (clusters > or =943 microl; p < 0.05), although groups did not differ on behavioral measures of task performance. No brain response differences were observed during a simple finger-tapping task. The degree of abnormality was greater for teens who reported experiencing more withdrawal or hangover symptoms and who consumed more alcohol., Conclusions: Adolescents with AUD show abnormalities in brain response to a spatial working memory task, despite adequate performance, suggesting that subtle neuronal reorganization may occur early in the course of AUD.

Objectives: Individuals with bipolar disorder (BPD) exhibit motor, perceptual, and cognitive disturbances involving predominantly right hemisphere dysfunction. This asymmetry has been used to advance the hypothesis that the pathogenesis of bipolar disorder may be related to disturbances of the right cerebral hemisphere. We employed functional magnetic resonance imaging to examine hemispheric asymmetries in manic and depressed BPD. A secondary goal of the study was to examine effects of psychotropic medications on blood volume changes in the motor cortices., Methods: We studied 18 right-handed BPD and 13 right-handed normal healthy comparison subjects. Blood oxygen level dependent (BOLD) responses in the primary motor area (M1) and supplementary motor area (SMA) of both hemispheres were elicited during reaction time (RT) tasks., Results: Healthy subjects activated the SMA in a reciprocal fashion with significantly greater activity in the left SMA for right hand trials and the right SMA for left hand trials. Depressed BPD subjects failed to show this normal reciprocity indicating a failure to suppress unwanted activity in the ipsilateral right SMA, whereas manic BPD subjects failed to suppress unwanted ipsilateral SMA activity in both hemispheres. Manic and depressed BPD subjects exhibited greater activity in the left primary motor area suggesting increased cortical excitability. BPD subjects treated with antipsychotics or mood-stabilizing medications exhibited longer RTs, lower BOLD responses in M1 and SMA, and a loss of normal hemispheric asymmetry in the SMA than untreated subjects., Conclusions: The presence of a right hemisphere disturbance in BPD is consistent with the hypothesis that the right hemisphere may be dominant in mood regulation. The presence of both left and right hemisphere disturbances in mania may explain the coexisting psychotic and affective symptoms observed in this condition.

Objective: Goldman-Rakic and Selemon (Schizophr. Bull. 23 (1997)) hypothesized that many of the symptoms of schizophrenia can be explained by deficits of working memory (WM) that are, in turn, caused by dysfunction of dorsolateral prefrontal cortex (DLPFC). We examined whether older patients with schizophrenia would show an aberrant neural response in the DLPFC or other brain sites when performing a spatial working memory (WM) task adapted from McCarthy et al. (Proc. Natl. Acad. Sci. U. S. A. 91 (1994))., Method: Middle-aged and older patients with schizophrenia or schizoaffective disorder and healthy volunteers performed a spatial WM task contrasted with two baselines, passive and active viewing (PV and AV, respectively), while blood oxygen level dependent (BOLD) images were acquired in a functional magnetic resonance study., Results: Patients did not perform significantly less well on the spatial tasks compared to the volunteers. Although we found no significant group effects in spatial WM activation of DLPFC, we did observe areas in medial frontal cortex including the left anterior cingulate gyrus, parietal areas of the both hemispheres, multiple sites within the basal ganglia of the left hemisphere, and the left superior temporal gyrus where healthy volunteers showed greater BOLD response to WM. In a second pattern, patients showed a greater BOLD response to WM in left fusiform gyrus [Brodmann's Area (BA) 19], peri-rolandic areas, medial frontal area; right anterior cerebellum (culmen), middle occipital lobe, and postcentral/supramarginal gyri (BA 2/40)., Conclusions: Middle-aged and older patients with schizophrenia display normal or near-normal spatial WM activation of DLPFC when the processing demands of the WM task are within their performance capacity. Nonetheless, even when patients perform nearly normally, they demonstrate an aberrant pattern of brain response.

This study examined brain asymmetries elicited during visuomotor tracking. Thirty-two healthy participants performed a fixed gaze, dynamic, pinch force, visuomotor tracking task during a functional magnetic resonance imaging study. The dynamic task required the subject to press a rubber bulb with the thumb to trace a cosine square wave varying in force amplitude from 0-500 cN and having a frequency of 1.5 Hz. Response hand order and direction of the stimulus presentation (right-to-left or left-to-right) were permuted across participants. Two forms of functional cerebral asymmetry were observed, hemispheric specialization and homologous lateralized response. The superior portion of the right middle frontal gyrus and the left supplementary motor area appeared specialized for VM tracking regardless of response hand used or stimulus movement direction. Lateralized effects appeared in the primary sensorimotor hand area, putamen, parietal operculum/posterior insula, dentate nucleus of the cerebellum, precuneus, and middle occipital gyrus. These lateralized areas of activation surfaced when either response hand or direction of stimulus movement was manipulated. The VM task used in this study activated asymmetrical neural activity in the vertically organized skelotomotor system and in sensory systems involving visual attention or proprioception.

Deficits of attention are common among individuals with schizophrenia (SZ) and are related both to genetic liability to the disorder and to functional outcome among patients. To explore the brain systems underlying these attentional abnormalities, we compared the response of nine patients with chronic SZ or schizoaffective disorder to that of 10 matched healthy individuals performing a simple visual vigilance task during functional magnetic resonance imaging. The two groups performed equivalently on the task. When the blood oxygen level dependent (BOLD) signal during identification of a target letter among similar-looking letters was compared to the response during fixation trials, both groups showed multiple clusters of significant brain response in widespread cortical regions. Compared with healthy participants, SZ patients showed a diminished response in the inferior frontal cortex and an abnormally enhanced response in right postcentral gyrus, right medial temporal lobe and left cerebellum. The results suggest that abnormalities of functional brain response to attentional tasks can be observed among patients with SZ even when behavioral performance is unimpaired, and provide further evidence that brain systems related to attention are likely to be involved in the pathophysiology of the disorder.

Background: Cue reactivity in alcohol dependent adults has revealed autonomic, cognitive, and neural responses to alcohol-related stimuli that differ from those of nonabusers. Cue reactivity and craving responses have not been studied in youth., Method: Alcohol-dependent young women (n=8) and female light social drinkers (n=9) ages 18-24 were administered an alcohol cue reactivity task during functional magnetic resonance imaging (fMRI) to examine brain response to alcohol-related words., Results: Alcohol dependent young women demonstrated significantly more blood oxygen level dependent (BOLD) response than nonabusers during alcohol word presentation trials relative to neutral word trials in subcallosal, anterior cingulate, left prefrontal, and bilateral insular regions (P<.025). However, controls showed greater response to alcohol words in some right hemisphere cortical regions. Increased craving after cue exposure correlated with increased subcallosal cortex BOLD response to alcohol cues (r=.87) among alcohol dependent subjects., Conclusions: This pilot study corroborates previous reports of increased limbic and frontal response to substance cues and extends these findings to young alcohol dependent women. This limbic reaction may underlie the elevated physiological response and altered cognitive reactions to alcohol stimuli that are observed in alcohol dependent individuals.

Structural neuroimaging studies have identified abnormalities in the basal ganglia in patients with bipolar disorder. Findings have been mixed with regard to affective state and have not elaborated on the role of medication on functional brain activity. The aims of the present study were to use functional magnetic resonance imaging (fMRI) to test whether depressed and manic bipolar disorder patients differ in terms of activity in cortical and subcortical brain areas and to examine the effects of psychotropic medication. Twenty-four bipolar disorder subjects and 13 healthy comparison subjects participated in an fMRI study of manual reaction time. Both manic and depressed subjects exhibited abnormally elevated blood oxygen level dependent BOLD responses in cortical and subcortical areas. Manic bipolar subjects had significantly higher BOLD responses in the left globus pallidus and significantly lower BOLD responses in the right globus pallidus compared with depressed bipolar patients. Correlational analyses revealed significant relationships between the severity of mania and activity within the globus pallidus and caudate. Patients off antipsychotic or mood-stabilizing medication exhibited significantly higher BOLD responses throughout the motor cortex, basal ganglia and thalamus compared with patients on these medications. These results suggest that affective state in bipolar disorder may be related to a disturbance of inhibitory regulation within the basal ganglia and that antipsychotics and/or mood stabilizers normalize cortical and subcortical hyperactivity.

The authors studied the effects of altering global cerebral blood flow on both blood oxygen level-dependent (BOLD) response and perfusion response to finger-thumb apposition. A PICORE/QUIPSS II protocol was used to collect interleaved BOLD-weighted and perfusion-weighted images on eight finger-thumb apposition trials. Subjects were studied on a drug-free day and on a day when acetazolamide was administered between the second and third trials. After acetazolamide administration, resting cortical perfusion increased an average of 20% from preadministration levels, whereas the BOLD response to finger-thumb apposition decreased by an average of 35% in the S1M1 hand area. Contrary to predictions from the exhausted cerebrovascular reserve hypothesis and the oxygen limitation model, an effect of acetazolamide on cerebral blood flow response in the S1M1 hand area was not observed. Across the acetazolamide trials, BOLD response was inversely correlated with resting cortical perfusion for individual subject data. These results suggest that resting perfusion affects the magnitude of the BOLD response and is thus an important confounding factor in fMRI studies, and that the physiologic systems that increase cerebral blood flow in response to acetazolamide administration and systems that increase cerebral blood flow in response to altered neural activity appear to have additive effects.

A single radish nuclear gene, Rfo, restores Ogura (ogu) cytoplasmic male sterility (CMS) in Brassica napus. A map-based cloning approach relying on synteny between radish and Arabidopsis was used to clone Rfo. A radish gene encoding a 687-amino-acid protein with a predicted mitochondrial targeting pre-sequence was found to confer male fertility upon transformation into ogu CMS B. napus. This gene, like the recently described Petunia Rf gene, codes for a pentatricopeptide repeat (PPR)-containing protein with multiple, in this case 16, PPR domains. Two similar genes that do not appear to function as Rfo flank this gene. Comparison of the Rfo region with the syntenic Arabidopsis region indicates that a PPR gene is not present at the Rfo-equivalent site in Arabidopsis, although a smaller and related PPR gene is found about 40 kb from this site. The implications of these findings for the evolution of restorer genes and other PPR encoding genes are discussed.

Background: Cue reactivity studies in alcohol-dependent adults have shown atypical physiological, cognitive, and neural responses to alcohol-related stimuli that differ from the responses of light drinkers. Cue reactivity and its neural substrates are unclear in youth. We hypothesized that teens with alcohol use disorder would show greater brain response than nonabusing teens to alcohol images relative to neutral beverage images in limbic and frontal brain regions., Methods: We tested the hypotheses in a cross-sectional functional magnetic resonance imaging study. Adolescents aged 14 to 17 were recruited from local high schools. Teens with alcohol use disorders (n = 15) and demographically similar infrequent drinkers (n = 15) met strict exclusion criteria (no left-handedness or neurological, other psychiatric, or other substance use disorders). Diagnoses were determined by means of structured and semistructured clinical interviews. Subjects were shown pictures of alcoholic and nonalcoholic beverage advertisements during blood oxygen level-dependent functional magnetic resonance imaging. Self-reports of craving were obtained before and after cue exposure., Results: Teens with alcohol use disorders showed substantially greater brain activation to alcoholic beverage pictures than control youths, predominantly in the left anterior, limbic, and visual system areas (P<.05; cluster threshold, 515 microL). The degree of brain response to the alcohol pictures was highest in youths who consumed more drinks per month and reported greater desires to drink., Conclusions: These results confirm previous studies by demonstrating an association between the urge to drink alcohol and blood oxygen use in areas of the brain previously linked to reward, desire, positive affect, and episodic recall. This study extends this relationship to adolescents with relatively brief drinking histories using visual alcohol stimuli, and suggests a neural basis for response to alcohol advertisements in youths with drinking problems.

Grammatical transformation is a verbal reasoning task requiring judging the veracity of statements describing the spatial order of letter sets. We studied 18 adults with FMRI while they performed grammatical transformations of varying complexity levels (2-letter, 3-letter, and 4-letter sentences). Brain regions activated by 2-letter sentences included the visuospatial processing regions of the bilateral parietal lobes and the frontal operculum. A linear increase in sentence complexity engaged dorsolateral and ventrolateral prefrontal cortex as well as significantly increased activation within 2LTR areas. These data provide evidence that grammatical transformation reasoning relies primarily on the posterior visuospatial working memory system and need not necessarily engage the prefrontal cortex. Increasing the complexity of grammatical transformation, though, activates prefrontal cortex.

Objective: Proton magnetic resonance spectroscopy was used to evaluate gender influences on alcohol-associated changes in brain metabolism., Method: Concentrations of N-acetylaspartate, choline-containing compounds, myo-inositol, and creatine plus phosphocreatine in frontal lobe gray matter and white matter were estimated in eight women and 17 men who were recently detoxified from long-term alcoholism. Twelve women and 13 men with no history of alcoholism were used as a comparison group., Results: In male and female alcoholics, frontal lobe white matter concentrations of N-acetylaspartate were significantly lower (-8.8%) than those seen in nonalcoholic comparison subjects. In the frontal lobe gray matter region, a significant alcoholism status-by-gender interaction and follow-up analyses revealed that female alcoholics had significantly lower N-acetylaspartate concentrations (-10.73%) relative to female comparison subjects, while male alcoholics and male comparison subjects had similar levels of this metabolite (<1% difference)., Conclusions: Lower concentrations of white matter N-acetylaspartate, which may indicate neuronal loss or dysfunction, is equally severe in men and women with comparable alcohol abuse histories. However, female alcoholics exhibited significantly less N-acetylaspartate in frontal gray matter relative to female nonalcoholic comparison subjects, which could mean that female alcoholics are more susceptible to gray matter injury than their male counterparts. However, this finding could also be explained by higher-than-expected levels of N-acetylaspartate in the healthy female comparison group.

The role of cortical and subcortical structures in processing success or failure in decision-making situations is unclear. Functional neuroimaging (fMRI) during a two-choice prediction task was used to investigate the relationship between error-rate-related behavioral changes during decision-making and activation patterns in the caudate and parietal cortex. Success-related activation was found in caudate and parietal cortex during a two-choice prediction task. At low error rates, participants utilized success-related behavioral strategies rate by decreasing switching responses and increasing response predictability, which were associated with activation changes in the caudate and parietal cortex. Therefore, less response switching and increased response predictability during decision making can be directly related to the degree of activation in the caudate and posterior parietal cortex.

Decision-making is a complex process that is important for everyday life. This study examined the effect of the degree of success, and outcome uncertainty, on decision-making and associated neural substrate activation in schizophrenia subjects (SZS) and normal comparison subjects (NCS). A total of 15 subjects with a diagnosis of schizophrenia and 15 age- and education-matched NCS participated in this study. These subjects completed the two-choice prediction task during functional magnetic resonance imaging. Decision-making characteristics and activation of neural substrates were obtained at 20, 50, or 80% error rate. Success and uncertainty influenced the behavioral characteristics on the two-choice prediction task, and the task-related activation in SZS and NCS. Neither success nor uncertainty differentially affected the behavioral characteristics of SZS relative to NCS during the two-choice prediction task. Nonetheless, there was a significant interaction between group and error rate in bilateral parietal cortex. The activation in NCS was the highest when the outcome was most uncertain. In contrast, task-related activation in SZS was not modulated by the degree of uncertainty. Thus, SZS failed to utilize the parietal cortex to process decision-making situations with highly uncertain outcomes.

Background: Learning deficits are prominent among patients with chronic schizophrenia and are associated with poor everyday functioning. Little is known, however, about the brain physiology underlying these difficulties with encoding new information., Purpose: The purpose of the current study was to compare the brain response during novel picture encoding between patients with chronic schizophrenia and healthy individuals using functional magnetic resonance imaging (fMRI)., Methods: Nine middle-aged patients with DSM-III-R or DSM-IV schizophrenia and 10 age- and education-comparable healthy individuals were studied. Using fMRI, the blood oxygenation level dependent (BOLD) signal was measured during novel picture encoding (experimental condition) and during presentation of a repeated picture (control condition). Encoding-related brain response was examined in both groups and compared between the patient and comparison groups in each voxel within four bilateral search regions (fusiform gyrus, parahippocampal gyrus, hippocampus, and inferior frontal gyrus)., Results: Despite comparable subsequent ability to recognize the presented pictures, patients with schizophrenia showed abnormal encoding-related brain response in regions of the hippocampus and parahippocampal and fusiform gyrii compared to healthy individuals. In medial temporal regions, patients showed greater BOLD response during the control condition (repeated picture) than during the experimental condition (novel pictures)., Conclusion: Abnormalities of the medial temporal brain systems examined in this study may underlie learning deficits in schizophrenia. Further research is needed to illuminate the role of these brain dysfunctions in poor everyday functioning and their amenability to treatment., (Copyright 2002 Elsevier Science B.V.)

Background: One important aspect in decision making is how success or failure influences the selection of a response. In a previous investigation, methamphetamine-dependent subjects (MD) selected win-stay/lose-shift consistent responses than normal comparison subjects (NC), which may imply that MD are more influenced by success. This study examined whether the degree of success and the degree of predictability differentially affected MD's decision making., Methods: Using functional magnetic resonance imaging, 14 MD were compared with 14 NC while performing the two-choice prediction task at three success rates and the two-choice response task., Results: The increase in win-stay/lose-shift consistent responses by MD relative to NC was independent of success rate. Irrespective of success, MD showed less task-related activation in orbitofrontal cortex (Brodmann's area [BA] 10), dorsolateral prefrontal cortex (BA 9), anterior cingulate (BA 32), and parietal cortex (BA 7). Whereas NC showed success-related patterns of neural activation in the orbitofrontal, dorsolateral prefrontal, and parietal cortex, MD showed activation that was highest when the outcome was most unpredictable., Conclusions: Our results are consistent with the hypothesis of a more rigid stimulus-response relationship during MD's decision making, which may be due to a shift from processing "success" toward processing the degree of stimulus "predictability."