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Biomedical subjects

Gregory G Brown

Publications and source records attributed to Gregory G Brown.

At least 37 records · Page 2Linked to original sources
PubMed2004

Abnormal brain response of chronic schizophrenia patients despite normal performance during a visual vigilance task.

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.

Adult↗
PubMed2004

fMRI BOLD response to alcohol stimuli in alcohol dependent young women.

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.

Adolescent↗
PubMed2004

Functional brain asymmetries during visuomotor tracking.

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.

Adult↗
PubMed2004

Blood oxygen level dependent response and spatial working memory in adolescents with alcohol use disorders.

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.

Adolescent↗
PubMed2004

A functional magnetic resonance imaging study of cortical asymmetry in bipolar disorder.

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.

Adult↗
PubMed2003

An fMRI study of affective state and medication on cortical and subcortical brain regions during motor performance in bipolar disorder.

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.

Affect↗
PubMed2003

Brain regions involved in simple and complex grammatical transformations.

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.

Adult↗
PubMed2003

Error-rate-related caudate and parietal cortex activation during decision making.

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.

Adult↗
PubMed2003

Functional abnormalities of medial temporal cortex during novel picture learning among patients with chronic schizophrenia.

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.

Chronic Disease↗
PubMed2003

Decision making by methamphetamine-dependent subjects is associated with error-rate-independent decrease in prefrontal and parietal activation.

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."

Adult↗
PubMed2003

Neural response to alcohol stimuli in adolescents with alcohol use disorder.

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.

Adolescent↗
PubMed2003

The radish Rfo restorer gene of Ogura cytoplasmic male sterility encodes a protein with multiple pentatricopeptide repeats.

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.

Amino Acid Sequence↗
PubMed2003

BOLD and perfusion response to finger-thumb apposition after acetazolamide administration: differential relationship to global perfusion.

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.

Acetazolamide↗
PubMed2003

Effects of alcoholism and gender on brain metabolism.

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.

Adult↗
PubMed2002

Schizophrenia subjects show intact success-related neural activation but impaired uncertainty processing during decision-making.

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.

Adult↗
PubMed2002

Habituation of attentional networks during emotion processing.

Dysfunctional emotion processing is a key aspect of many neuropsychiatric disorders. This dysfunction may be due to an abnormal magnitude of neural substrate activation during emotion processing or due to an altered time course of the neural substrate response. To better understand the temporal characteristics of the neural substrate activation underlying implicit emotion processing, nine healthy female controls were repeatedly exposed to pictures of affective faces while performing a gender identification task in an fMRI. As the salience of the stimuli decreased with repeated exposure, brain areas implicated in a right hemispheric spatial attention network (including the posterior parietal cortex (BA 40) and the frontal eye fields (BA 6)) habituated while brain areas lateralized to the left hemisphere (including the angular gyrus (BA 39), posterior superior temporal gyrus (BA 39) and insula (BA 13)) sensitized. These results provide strong evidence that the time course of activation is a critical component when assessing the function of neural substrates underlying emotion processing (specifically whether habituation is altered) in neuro-psychiatric patients.

Adult↗
PubMed2002

Parietal dysfunction is associated with increased outcome-related decision-making in schizophrenia patients.

BACKGROUND: Decision-making is a complex process and depends on a network of fronto-parietal and cingulate areas. Decision-making dysfunctions in schizophrenia patients are characterized by an alternation between stereotypic and unpredictable responses. This study tested the hypothesis that schizophrenia patients show less decision-making-related activation in the prefrontal and parietal cortex. METHODS: Fifteen schizophrenia patients were matched with fifteen normal comparison subjects. During functional magnetic resonance imaging (fMRI) scanning, subjects were tested on the two-choice prediction task (predicting the location of a randomly presented stimulus) and the two-choice response task (responding according to the location of the stimulus). RESULTS: Schizophrenia patients relative to comparison subjects generated more outcome-dependent responses. Schizophrenia patients and normal comparison subjects showed decision-making-related activation in right prefrontal cortex, insula, anterior cingulate, and bilateral precuneus. Schizophrenia patients showed less activation in inferior, medial prefrontal, and right superior temporal cortex and more activation in the postcentral and inferior parietal cortex. Decision-making-related activation in both right prefrontal and bilateral parietal cortex was higher in medicated compared to unmedicated schizophrenia patients. CONCLUSIONS: These results support the hypothesis that the interaction between prefrontal and parietal cortex during decision-making by schizophrenia patients is dysregulated, which results in an increased outcome-dependent response selection.

Adult↗