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Biomedical subjects

G Bush

Publications and source records attributed to G Bush.

At least 19 recordsLinked to original sources
PubMed2003

The Multi-Source Interference Task: validation study with fMRI in individual subjects.

Dorsal anterior cingulate cortex (dACC) plays critical roles in cognitive processing, but group-averaging techniques have generally been required to obtain significant dACC activation in functional neuroimaging studies. Development of a task that reliably and robustly activates dACC within individuals is needed to improve imaging studies of neuropsychiatric disorders and localization of dACC in normal volunteers. By combining sources of cognitive interference (Stroop, Eriksen and Simon) with factors known to increase dACC activity, the Multi-Source Interference Task (MSIT) maximally taxes dACC, making it possible to reliably activate dACC within individuals using functional magnetic resonance imaging (fMRI). In this study, eight normal adult volunteers performed the MSIT during fMRI. We compared fMRI responses and performance data between interference and control trials. Significant dACC activation (P < 1.7 x 10(-4)) was observed in all eight individuals and in the group-averaged fMRI data. In addition to dACC activation, group data also showed activation of presumably networked regions including dorsolateral prefrontal, premotor, and parietal cortices. The MSIT's reaction time interference effect (overall mean 312 +/- 61 ms) was up to 10 times greater than that of its component predecessors and temporally stable over hundreds of trials. The robustness, reliability and stability of the neuroimaging and performance data should make the MSIT a useful task with which to study normal human cognition and psychiatric pathophysiology.

Adult↗
PubMed2001

An fMRI study of anterior cingulate function in posttraumatic stress disorder.

BACKGROUND: Several recent neuroimaging studies have provided data consistent with functional abnormalities in anterior cingulate cortex in posttraumatic stress disorder (PTSD). In our study, we implemented a cognitive activation paradigm to test the functional integrity of anterior cingulate cortex in PTSD. METHODS: Eight Vietnam combat veterans with PTSD (PTSD Group) and eight Vietnam combat veterans without PTSD (non-PTSD Group) underwent functional magnetic resonance imaging (fMRI) while performing the Emotional Counting Stroop. In separate conditions, subjects counted the number of combat-related (Combat), generally negative (General Negative), and neutral (Neutral) words presented on a screen and pressed a button indicating their response. RESULTS: In the Combat versus General Negative comparison, the non-PTSD group exhibited significant fMRI blood oxygenation level-dependent signal increases in rostral anterior cingulate cortex, but the PTSD group did not. CONCLUSIONS: These findings suggest a diminished response in rostral anterior cingulate cortex in the presence of emotionally relevant stimuli in PTSD. We speculate that diminished recruitment of this region in PTSD may, in part, mediate symptoms such as distress and arousal upon exposure to reminders of trauma.

Case-Control Studies↗
PubMed2001

Ligand-induced signaling in the absence of furin processing of Notch1.

Notch is a conserved cell surface receptor that is activated through direct contact with neighboring ligand-expressing cells. The primary 300-kDa translation product of the Notch1 gene (p300) is cleaved by a furin-like convertase to generate a heterodimeric, cell-surface receptor composed of 180- (p180) and 120- (p120) kDa polypeptides. Heterodimeric Notch is thought to be the only form of the receptor which is both present on the cell surface and able to generate an intracellular signal in response to ligand. Consistent with previous reports, we found that disruption of furin processing of Notch1, either by coexpression of a furin inhibitor or by mutation of furin target sequences within Notch1 itself, perturbed ligand-dependent signaling through the well-characterized mediator of Notch signal transduction, CSL (CBF1, Su(H), and LAG-1). Yet contrary to these reports, we could detect the full-length p300 Notch1 product on the cell surface. Moreover, this uncleaved form of Notch1 could suppress the differentiation of C2C12 myoblasts in response to ligand. Taken together, these data support our previous studies characterizing a CSL-independent Notch signaling pathway and identify this uncleaved isoform of Notch as a potential mediator of this pathway. Our results suggest a novel paradigm in signal transduction, one in which two isoforms of the same cell-surface receptor could mediate two distinct signaling pathways in response to ligand.

Animals↗
PubMed2000

Functional brain mapping of the relaxation response and meditation.

Meditation is a conscious mental process that induces a set of integrated physiologic changes termed the relaxation response. Functional magnetic resonance imaging (fMRI) was used to identify and characterize the brain regions that are active during a simple form of meditation. Significant (p<10(-7)) signal increases were observed in the group-averaged data in the dorsolateral prefrontal and parietal cortices, hippocampus/parahippocampus, temporal lobe, pregenual anterior cingulate cortex, striatum, and pre- and post-central gyri during meditation. Global fMRI signal decreases were also noted, although these were probably secondary to cardiorespiratory changes that often accompany meditation. The results indicate that the practice of meditation activates neural structures involved in attention and control of the autonomic nervous system.

Adult↗
PubMed2000

Cognitive and emotional influences in anterior cingulate cortex.

Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.

Journal Article↗
PubMed1999

Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.

BACKGROUND: The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e., focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-deficit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recruit the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. METHODS: Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI. RESULTS: While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network, indicating ACcd hypoactivity was not caused by globally poor neuronal responsiveness. CONCLUSIONS: The data support a hypothesized dysfunction of the ACcd in ADHD.

Adolescent↗
PubMed1999

Activation of distinct motor cortex regions during ipsilateral and contralateral finger movements.

Previous studies have shown that unilateral finger movements are normally accompanied by a small activation in ipsilateral motor cortex. The magnitude of this activation has been shown to be altered in a number of conditions, particularly in association with stroke recovery. The site of this activation, however, has received limited attention. To address this question, functional magnetic resonance imaging (MRI) was used to study precentral gyrus activation in six control and three stroke patients during right index finger tapping, then during left index finger tapping. In each hemisphere, the most significantly activated site (P < 0.001 required) was identified during ipsilateral and during contralateral finger tapping. In the motor cortex of each hemisphere, the site activated during use of the ipsilateral hand differed from that found during use of the contralateral hand. Among the 11 control hemispheres showing significant activation during both motor tasks, the site for ipsilateral hand representation (relative to contralateral hand site in the same hemisphere) was significantly shifted ventrally in all 11 hemispheres (mean, 11 mm), laterally in 10/11 hemispheres (mean, 12 mm), and anteriorly in 8/11 hemispheres (mean, 10 mm). In 6 of 11 hemispheres, tapping of the contralateral finger simultaneously activated both the ipsilateral and the contralateral finger sites, suggesting bilateral motor control by the ipsilateral finger site. The sites activated during ipsilateral and contralateral hand movement showed similar differences in the unaffected hemisphere of stroke patients. The region of motor cortex activated during ipsilateral hand movements is spatially distinct from that identified during contralateral hand movements.

Brain Mapping↗
PubMed1998

The emotional counting Stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division.

BACKGROUND: The emotional counting Stroop (ecStroop) functional magnetic resonance imaging (fMRI) activation paradigm was designed to recruit the anterior cingulate affective division (ACad). METHODS: Nine normal, healthy male and female subjects (mean age 24.2 years) reported via button press the number of neutral and negative words that appeared on a screen while reaction time and fMRI data were acquired. RESULTS: We observed a) greater ACad activation for negative versus neutral words during initial presentation blocks; b) lower overall ACad signal intensity during task performance (i.e., both negative and neutral words) compared to the baseline fixation condition; and c) no reaction time increase to negative versus neutral words. CONCLUSIONS: In a companion study of a cognitive version of the counting Stroop (Bush et al 1998), these same 9 subjects a) activated the more dorsal anterior cingulate cognitive division; b) also showed the overall decrease in ACad signal intensity; and c) demonstrated a reliable reaction time effect. Taken together, these data offer a within-group spatial dissociation of AC function based upon information content (i.e., cognitive vs. emotional) and/or presence of behavioral interference. We propose that the ecStroop will be a useful fMRI probe of ACad function in anxiety disorders.

Adult↗
PubMed1998

An automatic device for the assessment of cardiovascular autonomic function.

Autonomic neuropathy is a common complication of diabetes mellitus and is associated with significant morbidity and possibly an increase in mortality. Despite this, however, autonomic dysfunction is not usually sought in the routine assessment of diabetic patients. We report the development and testing of a small, portable and reliable device that allows the routine testing of cardiac autonomic function in the outpatient setting with minimal inconvenience to the patient. This should facilitate the accurate assessment both of patients with symptoms suggestive of autonomic dysfunction and of autonomic function in research.

Arrhythmias, Cardiac↗
PubMed1998

Notch receptor activation inhibits oligodendrocyte differentiation.

In this study, we show that oligodendrocyte differentiation is powerfully inhibited by activation of the Notch pathway. Oligodendrocytes and their precursors in the developing rat optic nerve express Notch1 receptors and, at the same time, retinal ganglion cells express Jagged1, a ligand of the Notch1 receptor, along their axons. Jagged1 expression is developmentally regulated, decreasing with a time course that parallels myelination in the optic nerve. These results suggest that the timing of oligodendrocyte differentiation and myelination is controlled by the Notch pathway and raise the question of whether localization of myelination is controlled by this pathway.

Animals↗
PubMed1998

The counting Stroop: an interference task specialized for functional neuroimaging--validation study with functional MRI.

The anterior cingulate cortex has been activated by color Stroop tasks, supporting the hypothesis that it is recruited to mediate response selection or allocate attentional resources when confronted with competing information-processing streams. The current study used the newly developed "Counting Stroop" to identify the mediating neural substrate of cognitive interference. The Counting Stroop, a Stroop variant allowing on-line response time measurements while obviating speech, was created because speaking produces head movements that can exceed those tolerated by functional magnetic resonance imaging (fMRI), preventing the collection of vital performance data. During this task, subjects report by button-press the number of words (1-4) on the screen, regardless of word meaning. Interference trials contain number words that are incongruent with the correct response (e.g., "two" written three times), while neutral trials contain single semantic category common animals (e.g., "bird"). Nine normal right-handed adult volunteers underwent fMRI while performing the Counting Stroop. Group fMRI data revealed significant (P < or = 10(-4) activity in the cognitive division of anterior cingulate cortex when contrasting the interference vs. neutral conditions. On-line performance data showed 1) longer reaction times for interference blocks than for neutral ones, and 2) decreasing reaction times with practice during interference trials (diminished interference effects), indicating that learning occurred. The performance data proved to be a useful guide in analyzing the image data. The relative difference in anterior cingulate activity between the interference and neutral conditions decreased as subjects learned the task. These findings have ramifications for attentional, cognitive interference, learning, and motor control mechanism theories.

Adult↗
PubMed1997

Catatonia and other motor syndromes in a chronically hospitalized psychiatric population.

BACKGROUND: To determine the motor characteristics of chronic catatonia, catatonia and other motor disorders were systematically rated in a long-term hospitalized sample. METHOD: Chronically hospitalized psychiatric inpatients (N = 42) with a clinical diagnosis of catatonic schizophrenia (295.2X) were rated for catatonia with a novel 23-item catatonia rating scale, and for parkinsonism, dyskinesia and akathisia using standard rating scales with scale-based criteria for case definition. RESULTS: Catatonia was the sole motor syndrome in nine cases (21%), co-existed with parkinsonism in five (12%), tardive dyskinesia in four (10%), and both parkinsonism and tardive dyskinesia in 10 (24%). There was no correlation between total scores across the four rating scales. 'Rigidity' was the sole catatonic sign which overlapped with other scales. The symptom profile of catatonia in this chronic sample was similar to previous reports based on acutely ill patients. CONCLUSION: Catatonia is distinguishable from other motor disorders in chronic psychiatric patients using the 23-item catatonia rating scale. The features of chronic catatonia are described, and the distribution of catatonic signs is similar for chronic and acute catatonia.

Adult↗
PubMed1997

Synergism of lorazepam and electroconvulsive therapy in the treatment of catatonia.

Electroconvulsive therapy (ECT) and lorazepam are effective treatments for catatonia. ECT combined with benzodiazepines has been associated with reduced efficacy and efficiency and therefore is not recommended in the routine practice of ECT. We report 5 prospectively identified cases of catatonia treated either sequentially or concurrently with lorazepam and ECT. In each case, the combination of lorazepam with ECT was superior to monotherapy. This apparent synergism, its possible mechanisms, and its implications for treating catatonia are discussed.

Adolescent↗
PubMed1997

Striatal recruitment during an implicit sequence learning task as measured by functional magnetic resonance imaging.

Prior research has repeatedly implicated the striatum in implicit sequence learning; however, imaging findings have been inconclusive with respect to the sub-territories and laterality involved. Using functional magnetic resonance imaging (fMRI), we studied brain activation profiles associated with performance of the serial reaction time task (SRT) in 10 normal right-handed males. Behavioral results indicate that significant implicit learning occurred, uncontaminated by significant explicit knowledge. Concatenated fMRI data from the entire cohort revealed significant right-lateralized activation in both the caudate and putamen. Analysis of fMRI data from individual subjects showed inter-individual variability as to the precise territories involved, including right as well as left caudate and putamen. Interestingly, all seven subjects who manifested robust learning effects exhibited significant activation within the putamen. Moreover, among those seven subjects, the magnitude of signal intensity change within the putamen correlated significantly with the magnitude of reaction time advantage achieved. These findings demonstrate right-sided striatal activation across subjects during implicit sequence learning, but also highlight interindividual variability with respect to the laterality and striatal subterritories involved. In particular, results from individual subjects suggest that, during the SRT, the reaction time advantage garnered via implicit sequence learning might be predominantly associated with activity within the putamen.

Adult↗
PubMed1996

Catatonia. I. Rating scale and standardized examination.

To facilitate the systematic description of catatonic signs, we developed a catatonia rating examination, rating scale and screening instrument. We constructed a 23-item rating scale and a truncated 14-item screening instrument using operationalized definitions of signs ascribed to catatonia in published sources. Inter-rater reliability was tested in 44 simultaneous ratings of 28 cases defined by the presence of > or = 2 signs on the 14-item screen. Inter-rater reliability for total score on the rating scale was 0.93, and mean agreement of items was 88.2% (SD 9.9). Inter-rater reliability for total score on the screening instrument was 0.95, and mean agreement of items was 92.7% (SD 4.9). Diagnostic agreement was high based on criteria for catatonia put forth by other authors. Seven per cent (15/215) of consecutively admitted patients to an academic psychiatric in-patient facility met criteria for catatonia. It is concluded that catatonia is a distinct, moderately prevalent neuropsychiatric syndrome. The rating scale and screening instrument are reliable and valid. Their use facilitates diagnosis, treatment protocols, and cross-study comparisons.

Catatonia↗
PubMed1996

Catatonia. II. Treatment with lorazepam and electroconvulsive therapy.

Case material and retrospective studies support the use of both lorazepam and ECT in treating catatonia, but few prospective investigations exist and none employ quantitative monitoring of response. In this study we test their efficacy in an open, prospective protocol, and define a "lorazepam test' with predictive value for treatment. Twenty-eight patients with catatonia were treated systematically with parenteral and/or oral lorazepam for up to 5 days, and with ECT if lorazepam failed. Outcome was monitored quantitatively during the treatment phase with the Bush-Francis Catatonia Rating Scale (BFCRS). In 16 of 21 patients (76%) who received a complete trial of lorazepam (11 with initial intravenous challenge), catatonic signs resolved. A positive response to an initial parenteral challenge predicted final lorazepam response, as did length of catatonic symptoms prior to treatment. Neither demographic variables nor severity of catatonia predicted response to lorazepam. Four patients failing lorazepam responded promptly to ECT. It is concluded that lorazepam and ECT are effective treatments for catatonia. The rating scale has predictive value and displays sensitivity to change in clinical status.

Adult↗