Biomedical subjects

G G Brown

Publications and source records attributed to G G Brown.

At least 19 recordsLinked to original sources

PubMed2001

Prefrontal, parietal, and temporal cortex networks underlie decision-making in the presence of uncertainty.

Decision-making in the presence of uncertainty, i.e., selecting a sequence of responses in an uncertain environment according to a self-generated plan of action, is a complex activity that involves both cognitive and noncognitive processes. Using functional magnetic resonance imaging, the neural substrates of decision-making in the presence of uncertainty are examined. Normal control subjects show a significant activation of a frontoparietal and limbic neural system during a two-choice prediction task relative to a two-choice response task. The most prevalent response strategy during the two-choice prediction task was "win-stay/lose-shift," where subjects will repeat the previous response if it successfully predicted the stimulus and switch to the alternative response otherwise. Increased frequency of responses that are consistent with this strategy is associated with activation in the superior temporal gyrus. In comparison, increased frequency of response inconsistent with win-stay/lose-shift is associated with parietal cortex activation. These results support the hypothesis that subjects use a frontoparietal neural system to establish a contingency based decision-making strategy even in the presence of random reinforcement.

Adult↗

PubMed2001

Sleep deprivation, EEG, and functional MRI in depression: preliminary results.

One night of total or partial sleep deprivation (SD) produces temporary remissions in 40-60% of patients with major depression. Two unmedicated patients with major depression and a matched control received quantitative perfusion MR images at baseline and after one night of partial SD (PSD). A reduction > or =30% in the 17-item Hamilton Depression Rating Scale (omitting sleep and weight loss items) defined antidepressant response. Theory, techniques, strengths and weaknesses of quantitative perfusion MRI are described in detail. At baseline, the responder exhibited elevated perfusion covering ventral anterior cingulate/medial frontal cortex; the control's maximal perfusion area was markedly smaller. The nonresponder's perfusion was lowest of all, particularly ventrally. PSD decreased perfusion over much of the responder's hyperperfused area but did not change the nonresponder's scan. These preliminary findings are consistent with previous SD studies using PET and SPECT.

Depressive Disorder↗

PubMed2001

The effects of total sleep deprivation on cerebral responses to cognitive performance.

We review the findings from a study utilizing functional magnetic resonance imaging (FMRI) to examine the effects of total sleep deprivation (TSD) on verbal learning, arithmetic, and divided attention. For verbal learning and divided attention, TSD was associated with increased activation in the bilateral prefrontal cortex and parietal lobes. Increased sleepiness after TSD and lower levels of memory impairment were correlated with increased activation in specific regions of the prefrontal cortex and parietal lobes, respectively. The arithmetic task led to significantly decreased activation in the bilateral prefrontal cortex and parietal lobes. Based on this and other data, we hypothesize an adaptive cerebral response during cognitive performance following TSD with the specific pattern of adaptation depending on the specific cognitive processes performed. We discuss the need to test the hypothesis in a variety of ways.

Adaptation, Physiological↗

PubMed2001

Increased cerebral response during a divided attention task following sleep deprivation.

We recently reported that the brain showed greater responsiveness to some cognitive demands following total sleep deprivation (TSD). Specifically, verbal learning led to increased cerebral activation following TSD while arithmetic resulted in decreased activation. Here we report data from a divided attention task that combined verbal learning and arithmetic. Thirteen normal control subjects performed the task while undergoing functional magnetic resonance imaging (FMRI) scans after a normal night of sleep and following 35 h TSD. Behaviourally, subjects showed only modest impairments following TSD. With respect to cerebral activation, the results showed (a) increased activation in the prefrontal cortex and parietal lobes, particularly in the right hemisphere, following TSD, (b) activation in left inferior frontal gyrus correlated with increased subjective sleepiness after TSD, and (c) activation in bilateral parietal lobes correlated with the extent of intact memory performance after TSD. Many of the brain regions showing a greater response after TSD compared with normal sleep are thought to be involved in control of attention. These data imply that the divided attention task required more attentional resources (specifically, performance monitoring and sustained attention) following TSD than after normal sleep. Other neuroimaging results may relate to the verbal learning and/or arithmetic demands of the task. This is the first study to examine divided attention performance after TSD with neuroimaging and supports our previous suggestion that the brain may be more plastic during cognitive performance following TSD than previously thought.

Adult↗

PubMed2001

fMRI measurement of brain dysfunction in alcohol-dependent young women.

BACKGROUND: Studies of brain functioning in alcohol-dependent adults have produced varied results but generally suggest that alcohol affects brain functioning and that relatively short durations of heavy drinking may adversely affect women. It remains unclear when in the course of alcohol dependency and at which developmental stage these brain changes emerge. Our neuropsychological studies have indicated that drinking-related neurocognitive effects occur as early as adolescence (Brown et al., 2000; Tapert & Brown, 1999). This study seeks to characterize brain regions that subserve the affected neurocognitive functions. METHODS: Alcohol-dependent young women (n = 10) were recruited from a longitudinal study of alcohol- and drug-abusing youth, all of whom met criteria for alcohol dependence. Control participants (n = 10) had no history of alcohol or drug problems and were comparable with alcohol-dependent participants on age (18-25 years), family history of alcohol use disorders, and education. After a minimum of 72 hr of abstinence, functional magnetic resonance imaging, neuropsychological, alcohol/drug involvement, and mood data were collected. Participants performed spatial working memory and vigilance tasks during functional magnetic resonance imaging acquisition to probe brain response. RESULTS: Alcohol-dependent women demonstrated significantly less blood oxygen level-dependent response than controls during the spatial working memory task in the right superior and inferior parietal, right middle frontal, right postcentral, and left superior frontal cortex, after controlling for the baseline vigilance response. CONCLUSIONS: Working memory produces a larger neuronal response in some cortical regions than vigilance. Alcohol-dependent women showed less differential response to working memory than controls in frontal and parietal regions, especially in the right hemisphere. Heavy, chronic drinking appears to produce adverse neural effects that are detectable by functional magnetic resonance imaging.

Adolescent↗

PubMed2001

Chemical pathology in brain white matter of recently detoxified alcoholics: a 1H magnetic resonance spectroscopy investigation of alcohol-associated frontal lobe injury.

BACKGROUND: Investigations have suggested that frontal lobe abnormalities are a prominent feature of the alcoholic brain, indicated by impaired neuropsychological performance on tests of frontal lobe function and by reduced frontal lobe volume in neuroimaging and neuropathological examinations. White matter compartment volume loss may underlie observed brain shrinkage and cognitive deficits associated with the frontal lobes, although the nature of this change has not been well-characterized. METHOD: To investigate the susceptibility of frontal lobe white matter to alcohol-associated metabolic change and to understand the nature of alcohol-related white matter injury, 1H magnetic resonance spectroscopy (MRS) was used to measure concentrations of metabolites in frontal white matter (FWM) and parietal white matter (PWM) of recently detoxified alcoholics (RDA) and nonalcoholic controls (CON). Concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were measured in 37 RDA (mean age, 40.4 years; mean length of abstinence, 27.9 days) and 15 CON (mean age, 38.0 years). RESULTS: Analysis of variance (ANOVA) revealed a group by region of interest interaction for concentrations of NAA. Simple effects analysis revealed a significant 14.7% reduction in FWM NAA, while NAA levels in PWM were similar in RDA and CON. In addition, RDA had an 11.8% increase (averaged across both regions of interest) in brain white matter Ins relative to CON. Reductions in FWM NAA were associated with a longer drinking history in the RDA group, but this result was not found when both age and drinking history were used to predict the level of FWM NAA. CONCLUSIONS: Alcohol-associated reductions in FWM NAA may be the result of neuronal loss or dysfunction in the metabolism of NAA. While alcohol-induced oxidative stress may cause global brain impairments in the metabolism and subsequent reduction of NAA, the frontal lobes are particularly rich in excitatory amino acid pathways, and axonal damage or destruction secondary to glutamate-mediated excitotoxicity during alcohol withdrawal may cause frontal lobe-specific reductions in NAA. Elevations in brain white matter Ins may reflect astrocyte proliferation as well as an osmotic response to cell shrinkage.

Adult↗

PubMed2000

Altered brain response to verbal learning following sleep deprivation.

The effects of sleep deprivation on the neural substrates of cognition are poorly understood. Here we used functional magnetic resonance imaging to measure the effects of 35 hours of sleep deprivation on cerebral activation during verbal learning in normal young volunteers. On the basis of a previous hypothesis, we predicted that the prefrontal cortex (PFC) would be less responsive to cognitive demands following sleep deprivation. Contrary to our expectations, however, the PFC was more responsive after one night of sleep deprivation than after normal sleep. Increased subjective sleepiness in sleep-deprived subjects correlated significantly with activation of the PFC. The temporal lobe was activated after normal sleep but not after sleep deprivation; in contrast, the parietal lobes were not activated after normal sleep but were activated after sleep deprivation. Although sleep deprivation significantly impaired free recall compared with the rested state, better free recall in sleep-deprived subjects was associated with greater parietal lobe activation. These findings show that there are dynamic, compensatory changes in cerebral activation during verbal learning after sleep deprivation and implicate the PFC and parietal lobes in this compensation.

Adult↗

PubMed2000

Executive functions and P300 latency in elderly depressed patients and control subjects.

The authors asked whether impaired executive functioning and long P300 latency are related dysfunctions and whether they are associated with geriatric depression. A group of 25 elderly depressed patients without dementia and 20 control subjects were assessed on tasks of fluency, initiation and perseveration, the Stroop task, the Wisconsin Card Sorting Test (WCST) perseverative error score, and P300 latency. The groups' performance differed significantly on these tasks and in P300 latency. Longer latency was associated with poorer performance in both groups on all measures except WCST perseverative errors. Regardless of patients' depression status, increased P300 latency predicts poorer performance on executive function tasks requiring speeded performance.

Aged↗

PubMed1999

Sleep deprivation-induced reduction in cortical functional response to serial subtraction.

Thirteen normal volunteers were studied with fMRI during arithmetic performance after a normal night of sleep and following sleep deprivation (SD). Aims included determining whether the prefrontal cortex (PFC) and the parietal lobe arithmetic areas are vulnerable to the effects of SD. After a normal night of sleep, activation localized to the bilateral PFC, parietal lobes and premotor areas. Following SD, activity in these regions decreased markedly, especially in the PFC. Performance also dropped. Data from the serial subtraction task are consistent with Horne's PFC vulnerability hypothesis but, based on this and other studies, we suggest the localized, functional effects of SD in the brain may vary, in part, with the specific cognitive task.

Adult↗

PubMed1999

CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans.

Mutations in the clk-1 gene of the nematode Caenorhabditis elegans result in an average slowing of a variety of developmental and physiological processes, including the cell cycle, embryogenesis, post-embryonic growth, rhythmic behaviors and aging. In yeast, a CLK-1 homologue is absolutely required for ubiquinone biosynthesis and thus respiration. Here we show that CLK-1 is fully active when fused to green fluorescent protein and is found in the mitochondria of all somatic cells. The activity of mutant mitochondria, however, is only very slightly impaired, as measured in vivo by a dye-uptake assay, and in vitro by the activity of succinate cytochrome c reductase. Overexpression of CLK-1 activity in wild-type worms can increase mitochondrial activity, accelerate behavioral rates during aging and shorten life span, indicating that clk-1 regulates and controls these processes. These observations also provide strong genetic evidence that mitochondria are causally involved in aging. Furthermore, the reduced respiration of the long-lived clk-1 mutants suggests that longevity is promoted by the age-dependent decrease in mitochondrial function that is observed in most species.

Aging↗

PubMed1999

Brain activation and pupil response during covert performance of the Stroop Color Word task.

Patterns of brain activation associated with covert performance of the Stroop Color-Word task were studied in young, healthy, adult volunteers using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Comparisons of the incongruous Stroop condition were made with both color naming and word reading baselines. Areas of the left and right anterior cingulate, the right precuneus, and the left pars opercularis displayed larger BOLD signal responses during the incongruous Stroop condition than during baseline conditions. Activation of BOLD signals in these areas was highly repeatable. In a second experiment, pupil diameter was used to assess cognitive load in 7 individuals studied during overt and covert performance of both Stroop and color naming conditions. Cognitive load was similar in overt and covert response conditions. Results from the BOLD study indicate that brain regions participating in selective visual attention and in the selection of motor programs involved in speech were activated more by the Stroop task than by the baseline tasks. The neural substrate involved in the resolution of the perceptual and motor conflicts elicited by the Stroop Color-Word task does not appear to be a single brain region. Rather, a network of brain regions is implicated, with separate regions within this system supporting distinct functions.

Adult↗

PubMed1999

Post-transcriptional and developmental regulation of a CMS-associated mitochondrial gene region by a nuclear restorer gene.

Transcripts of the mitochondrial gene region orf224/atp6, which is associated with the Polima or pol cytoplasmic male sterility (CMS) of Brassica napus, differ among fertile, sterile and nuclear-restored plants. We show here that the effects of the restorer gene Rfp on orf224/atp6 transcripts varies among different floral organs. Relative to monocistronic atp6 transcripts, levels of the dicistronic transcripts spanning orf224 and atp6 are dramatically reduced in petals, stamens and carpels, but not sepals, of restored flowers. In pol CMS plants, the relative levels of different orf224/atp6 transcripts are similar among the floral organs. Analysis of guanylyltransferase-labeled mtRNA indicates that only the dicistronic 2.2 and 1.9 kb orf224/atp6 transcripts carry an initiator 5' terminus; hence the 1.4 and 1.3 kb transcripts of restored plants, as well as the 1.1 kb atp6 transcript common to all genotypes, are generated by RNA processing and not de novo initiation. Although steady-state levels of dicistronic transcripts in flower buds are lower in restored than in sterile plants, run-on transcription experiments show that these transcripts are synthesized at the same rate in both types of flowers. These findings imply that the restorer gene acts by conditioning the removal of sequences from the 5' end of dicistronic transcripts in a developmentally regulated manner. Run-on transcription experiments indicate that the single 1.1 kb atp6 transcript of nap cytoplasm is also generated by removal of sequences from the 5' end of a precursor. We suggest that specific endonucleolytic cleavage of a precursor RNA, followed by non-specific 3' to 5' exonuclease action, may represent a common mechanism for tailoring transcripts in plant mitochondria.

Base Sequence↗

PubMed1999

Lexical priming on Neely's (1977) paradigm in Parkinson's disease: where do we stand?

In two published studies, we used a variant of Neely's (1977) lexical decision paradigm to study shifts of attention and automatic lexical activation in nondemented individuals with Parkinson's disease (McDonald, Brown, & Gorell, 1996; Spicer, Brown, & Gorell, 1994). Arnott and Chenery (in press) noticed differences between Neely's results and the results we observed in our control group that raise questions about some of the conclusions presented in the McDonald et al. (1996) and Spicer et al. (1994) papers. Even when considering the important differences between Neely's (1977) results and those in our control groups, we argue that our results support the conclusions of normal automatic semantic activation and deficient set-shifting in Parkinson's disease. We also introduce the notion of generalized priming to account for some of the priming effects observed in our studies.

Adult↗

PubMed1999

Validity of the Dementia Rating Scale in assessing cognitive function in Parkinson's disease.

Two studies examined the validity of the Dementia Rating Scale (DRS) as a measure of cognitive functioning among patients with Parkinson's disease (PD). The DRS accounted for more variation in the level of cognitive functioning of PD patients than either the Mini-Mental Status Examination or a battery of tests selected to assess specific cognitive deficits associated with PD. Further, DRS subtests displayed strong convergent and discriminant validity with a comprehensive Criterion Neuropsychology Battery. The DRS subtests appear to be valid measures of attention, perseveration, conceptualization, and memory among PD patients. However, the DRS-Construction subtest should be supplemented with additional visuoconstructional items to provide a thorough screen of cognitive functioning in PD. Although about three-quarters of nondemented PD patients did not appear to have any specific cognitive deficits on the DRS, the remaining patients were impaired on the Construction or Initiation/Perseveration subtests of the DRS. In summary, the DRS is a valid mental status screening test of cognitive functioning for individuals with PD.

Aged↗

PubMed1998

Restorer genes for different forms of Brassica cytoplasmic male sterility map to a single nuclear locus that modifies transcripts of several mitochondrial genes.

The oilseed rape plant, Brassica napus, possesses two endogenous male sterile cytoplasms, nap and pol. Previous studies have shown that nuclear restoration of pol cytoplasmic male sterility (CMS) is conditioned by a gene, Rfp, that is also involved in modifying transcripts of the pol CMS-associated orf224/atp6 mtDNA region. We now find that the nap nuclear restorer gene Rfn apparently is identical to Mmt, a gene that conditions the modification of transcripts from several different mtDNA regions, including one that is associated with nap CMS and contains orf222, a chimeric gene related to orf224. Mmt, in turn, is found to be allelic to Rfp, suggesting that restorer genes for the two cytoplasms represent different alleles or haplotypes of a single nuclear locus. This view is supported by restriction fragment length polymorphism mapping studies that indicate that Rfn and Rfp map to the same chromosomal position. Thus, in contrast to CMS in other species, different forms of Brassica CMS are restored by alleles of a single nuclear locus, and the restoration properties of these alleles reflect their involvement in the modification of transcripts of corresponding CMS-associated mtDNA regions. A survey of 51 varieties from 8 Brassica and Sinapis species failed to find evidence of Rfn(Mmt) in other than fertility-restored, nap cytoplasm B. napus. This suggests that Rfn(Mmt) arose in Brassica with nap cytoplasm and that the necessity for fertility restoration may have provided the selective pressure for its origin and maintenance.

Journal Article↗

PubMed1998

P300 latency in geriatric depression.

OBJECTIVE: The purpose of this study was to determine if P300 latency is prolonged in geriatric depression and if longer P300 latency and deficits in initiation and errors of perseveration in depressed elderly patients are related to risk factors for vascular disease. METHOD: Geriatric patients with unipolar depression (N = 43) and elderly comparison subjects (N = 24) were assessed for depressive symptoms, cognitive functions, risk factors for vascular disease, and P300 latency. RESULTS: Depressed elderly patients had longer P300 latency than normal elderly subjects. In the depressed patients, P300 latency was related to deficits in initiation and errors in perseveration. Risk factors for vascular disease were associated not only with P300 latency but also with deficits in initiation and errors in perseveration. CONCLUSIONS: Functional impairment of the cortico-striato-pallido-thalamo-cortical pathways from vascular disease, implicated in late-life depressive disorders, may explain not only deficits in initiation and errors in perseveration but also longer P300 latency in depressed elderly patients. These results are preliminary and need further examination with brain imaging and more sensitive neuropsychological measures.

Aged↗

PubMed1998

Analysis of fMRI data by blind separation into independent spatial components.

Current analytical techniques applied to functional magnetic resonance imaging (fMRI) data require a priori knowledge or specific assumptions about the time courses of processes contributing to the measured signals. Here we describe a new method for analyzing fMRI data based on the independent component analysis (ICA) algorithm of Bell and Sejnowski ([1995]: Neural Comput 7:1129-1159). We decomposed eight fMRI data sets from 4 normal subjects performing Stroop color-naming, the Brown and Peterson work/number task, and control tasks into spatially independent components. Each component consisted of voxel values at fixed three-dimensional locations (a component "map"), and a unique associated time course of activation. Given data from 144 time points collected during a 6-min trial, ICA extracted an equal number of spatially independent components. In all eight trials, ICA derived one and only one component with a time course closely matching the time course of 40-sec alternations between experimental and control tasks. The regions of maximum activity in these consistently task-related components generally overlapped active regions detected by standard correlational analysis, but included frontal regions not detected by correlation. Time courses of other ICA components were transiently task-related, quasiperiodic, or slowly varying. By utilizing higher-order statistics to enforce successively stricter criteria for spatial independence between component maps, both the ICA algorithm and a related fourth-order decomposition technique (Comon [1994]: Signal Processing 36:11-20) were superior to principal component analysis (PCA) in determining the spatial and temporal extent of task-related activation. For each subject, the time courses and active regions of the task-related ICA components were consistent across trials and were robust to the addition of simulated noise. Simulated movement artifact and simulated task-related activations added to actual fMRI data were clearly separated by the algorithm. ICA can be used to distinguish between nontask-related signal components, movements, and other artifacts, as well as consistently or transiently task-related fMRI activations, based on only weak assumptions about their spatial distributions and without a priori assumptions about their time courses. ICA appears to be a highly promising method for the analysis of fMRI data from normal and clinical populations, especially for uncovering unpredictable transient patterns of brain activity associated with performance of psychomotor tasks.

Algorithms↗

PubMed1997

Review of functional magnetic resonance imaging in schizophrenia.

Functional magnetic resonance imaging (fMRI) holds great promise for assessing temporal changes in brain activity using various challenge paradigms. In this report, we review the 14 studies (eight of them abstracts) that comprise the fMRI literature available to date relating to schizophrenia. Twelve of the 14 investigations examined changes in blood-oxygen-level-dependent (BOLD) contrast: two examined blood volume. Eight of the 12 BOLD studies relied on lower-order cognitive processing to measure activation (involving sensory or motor areas), whereas four used higher-order tasks (word production, auditory processing, and subspan word recall involving multiple brain areas). Although the variability in tasks used, brain regions studied, imaging methods used, patient characteristics reported, and methods of reporting significance precluded a full meta-analysis, we re-analyzed these published data to compute effect sizes. In most studies, resting blood volume and BOLD changes, regardless of the complexity of the cognitive task, appeared to differ between patients with schizophrenia and control subjects.

Brain↗