Search PubMed⌕ Search

Biomedical subjects

C S Carter

Publications and source records attributed to C S Carter.

At least 19 recordsLinked to original sources
PubMed2000

Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults.

Administration of mobilized peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy rapidly restores multilineage hematopoiesis, but the ability of such products to restore lymphocyte populations remains unclear. In this report, we evaluated immune reconstitution in a series of patients treated with sequential cycles of high-dose chemotherapy, followed by autologous PBPC infusions (median CD34(+) cell dose 7.2 x 10(6) cells/kg [range 2-29.3]). Although patients experienced rapid reconstitution of B cells and CD8(+) T cells, we observed CD4 depletion and diminished immune responsiveness in all patients for several months after completion of therapy. Mature CD4(+) T cells contained within the grafts did not appear to contribute substantially to immune reconstitution because CD4 counts did not differ between recipients of unmanipulated T-cell replete infusions versus CD34 selected, T-cell-depleted infusions. Rather, at 12 months after therapy, total CD4 count was inversely proportional to age (rho = -0.78, P =.04), but showed no relationship to CD34 cell dose (rho = -0.42, P =.26), suggesting that age-related changes within the host are largely responsible for the limited immune reconstitution observed. These results demonstrate that in the autologous setting, the infusion of large numbers of PBPCs is not sufficient to restore T-cell immune competence and emphasize that specific approaches to enhance immune reconstitution are necessary if immune-based therapy is to be used to eradicate minimal residual disease after autologous PBPC transplantation. (Blood. 2000;96:754-762)

Adolescent↗
PubMed2000

Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control.

Theories of the regulation of cognition suggest a system with two necessary components: one to implement control and another to monitor performance and signal when adjustments in control are needed. Event-related functional magnetic resonance imaging and a task-switching version of the Stroop task were used to examine whether these components of cognitive control have distinct neural bases in the human brain. A double dissociation was found. During task preparation, the left dorsolateral prefrontal cortex (Brodmann's area 9) was more active for color naming than for word reading, consistent with a role in the implementation of control. In contrast, the anterior cingulate cortex (Brodmann's areas 24 and 32) was more active when responding to incongruent stimuli, consistent with a role in performance monitoring.

Adolescent↗
PubMed2000

Parsing executive processes: strategic vs. evaluative functions of the anterior cingulate cortex.

Event-related functional MRI and a version of the Stroop color naming task were used to test two conflicting theories of anterior cingulate cortex (ACC) function during executive processes of cognition. A response-related increase in ACC activity was present when strategic processes were less engaged, and conflict high, but not when strategic processes were engaged and conflict reduced. This is inconsistent with the widely held view that the ACC implements strategic processes to reduce cognitive conflicts, such as response competition. Instead, it suggests that the ACC serves an evaluative function, detecting cognitive states such as response competition, which may lead to poor performance, and representing the knowledge that strategic processes need to be engaged.

Analysis of Variance↗
PubMed2000

Peripheral pulses of oxytocin increase partner preferences in female, but not male, prairie voles.

Centrally administered oxytocin (OT) facilitates social behaviors including the partner preferences that characterize the monogamous social system of prairie voles. In contrast peripherally administered OT generally has been ineffective in influencing central processes including behavior. OT from the posterior pituitary gland is released in pulses into the peripheral circulation. We hypothesized that peripherally administered OT, if delivered in repeated injections mimicking these pulses, would influence behavior. Male and female prairie voles received three subcutaneous injections of OT, a single injection of OT, or isotonic saline. Animals then were placed with an adult member of the opposite sex, designated as a "partner," for a 1-h period of cohabitation, and subsequently tested for preference for the familiar partner versus a comparable stranger. Females treated with pulses of peripheral OT (1, 5, or 20 microg) displayed a significant preference for the partner compared to control females, while females receiving a lower dose of OT (0.1 microg) or a single injection (20 microg) did not. There was also a significant within-group effect as pulsed OT-treated females spent more time with the partner when compared to the stranger, while control females spent equal amounts of time with the partner and stranger. Peripheral pulses of OT were no longer effective in inducing partner preferences when females were pretreated with a selective OT receptor antagonist, administered either peripherally or centrally. In contrast to females, peripheral treatment with OT did not facilitate the formation of partner preferences in males.

Animals↗
PubMed1999

Conflict monitoring versus selection-for-action in anterior cingulate cortex.

The anterior cingulate cortex (ACC), on the medial surface of the frontal lobes of the brain, is widely believed to be involved in the regulation of attention. Beyond this, however, its specific contribution to cognition remains uncertain. One influential theory has interpreted activation within the ACC as reflecting 'selection-for-action', a set of processes that guide the selection of environmental objects as triggers of or targets for action. We have proposed an alternative hypothesis, in which the ACC serves not to exert top-down attentional control but instead to detect and signal the occurrence of conflicts in information processing. Here, to test this theory against the selection-for-action theory, we used functional magnetic resonance imaging to measure brain activation during performance of a task where, for a particular subset of trials, the strength of selection-for-action is inversely related to the degree of response conflict. Activity within the ACC was greater during trials featuring high levels of conflict (and weak selection-for-action) than during trials with low levels of conflict (and strong selection-for-action), providing evidence in favour of the conflict-monitoring account of ACC function.

Adult↗
PubMed1999

Developmental exposure to vasopressin increases aggression in adult prairie voles.

Although the biological roots of aggression have been the source of intense debate, the precise physiological mechanisms responsible for aggression remain poorly understood. In most species, aggression is more common in males than females; thus, gonadal hormones have been a focal point for research in this field. Although gonadal hormones have been shown to influence the expression of aggression, in many cases aggression can continue after castration, indicating that testicular steroids are not completely essential for the expression of aggression. Recently, the mammalian neuropeptide arginine vasopressin (AVP) has been implicated in aggression. AVP plays a particularly important role in social behavior in monogamous mammals, such as prairie voles (Microtus ochrogaster). In turn, the effects of social experiences may be mediated by neuropeptides, including AVP. For example, sexually naïve prairie voles are rarely aggressive. However, 24 h after the onset of mating, males of this species become significantly aggressive toward strangers. Likewise, in adult male prairie voles, central (intracerebroventricular) injections of AVP can significantly increase intermale aggression, suggesting a role for AVP in the expression of postcopulatory aggression in adult male prairie voles. In this paper, we demonstrate that early postnatal exposure to AVP can have long-lasting effects on the tendency to show aggression, producing levels of aggression in sexually naïve, adult male prairie voles that are comparable to those levels observed after mating. Females showed less aggression and were less responsive to exogenous AVP, but the capacity of an AVP V(1a) receptor antagonist to block female aggression also implicates AVP in the development of female aggression.

Aggression↗
PubMed1999

Engraftment of hematopoietic progenitor cells transduced with the Fanconi anemia group C gene (FANCC).

Fanconi anemia (FA) is an autosomal recessive disorder that leads to aplastic anemia. Mutations in the FANCC gene account for 10-15% of cases. FA cells are abnormally sensitive to DNA-damaging agents such as mitomycin C (MMC). Transfection of normal FANCC into mutant cells corrects this hypersensitivity and improves their viability in vitro. Four FA patients, representing the three major FANCC mutation subgroups, were entered into a clinical trial of gene transduction aimed at correction of the hematopoietic defect. Three patients received three or four cycles of gene transfer, each consisting of one or two infusions of autologous hematopoietic progenitor cells that had been transduced ex vivo with a retroviral vector carrying the normal FANCC gene. Prior to infusion, the FANCC transgene was demonstrated in transduced CD34-enriched progenitor cells. After infusion, FANCC was also present transiently in peripheral blood (PB) and bone marrow (BM) cells. Function of the normal FANCC transgene was suggested by a marked increase in hematopoietic colonies measured by in vitro cultures, including colonies grown in the presence of MMC, after successive gene therapy cycles in all patients. Transient improvement in BM cellularity coincided with this expansion of hematopoietic progenitors. A fourth patient, who received a single infusion of transduced CD34-enriched BM cells, was given radiation therapy for a concurrent gynecologic malignancy. The FANCC transgene was detected in her PB and BM cells only after recovery from radiation-induced aplasia, suggesting that FANCC gene transduction confers a selective engraftment advantage. These experiments highlight both the potential and difficulties in applying gene therapy to FA.

Adolescent↗
PubMed1999

Increased stroop facilitation effects in schizophrenia are not due to increased automatic spreading activation.

Studies using the single trial Stroop task consistently reveal increased reaction time (RT) facilitation effects among schizophrenia patients. One possible mechanism underlying this effect is increased automatic spreading activation in semantic networks. The current study was designed to test this hypothesis. We administered the Stroop task and two semantic priming tasks to the same subjects. Patients showed greater Stroop RT facilitation than controls, no evidence of increased semantic priming at short stimulus onset asynchronies (SOAs), and reduced semantic priming at long SOAs. In addition, abnormal Stroop performance was related to the severity of Disorganization symptoms. These results are inconsistent with the spreading activation hypothesis. Alternative hypotheses regarding the source of Stroop task performance deficits in schizophrenia are discussed.

Adult↗
PubMed1999

A study of injected dose for brain mapping on the ECAT HR+: activation maps for a parametric verbal working memory task.

The success of the 15O-water PET technique to localize statistically significant changes in regional cerebral blood flow is dependent on factors such as the activity level injected and the magnitude of the flow change. Undetectable changes may occur if insufficient activity is injected leading to high levels of statistical noise or the task performed results in only small changes in blood flow. To explore the relationship between injected activity and statistical significance, we performed a series of studies with the ECAT EXACT HR+, a high resolution PET tomograph. A parametric verbal working memory task (the N-back task) was selected to examine the relationship between regional cerebral blood flow and working memory load across a range of injected doses of 15O-water. At each activity level the volunteers were required to perform four different levels of the N-back task, a task in which a letter displayed on a monitor is matched with the letter displayed N letters previously. With increasing N, this task places increased load on working memory. For this study, 5, 10, and 15 mCi of 15O-water were injected into nine normal volunteers. The complete sequence of four tasks (N = 0, 1, 2, and 3) at three activity levels was repeated twice, for a total of 24 injections of 15O-water. We show that the peak count rate performance for the HR+ is approached at injected activity levels of 15O-water around 15 mCi. For this particular choice of N-back task, robust activation maps can nevertheless be obtained with as little as 5 mCi injected dose.

Adult↗
PubMed1999

Overt verbal responding during fMRI scanning: empirical investigations of problems and potential solutions.

This paper presents a pair of studies designed to empirically explore the severity of potential artifacts associated with overt verbal responding during fMRI scanning and to examine several different solutions to these artifacts. In Study One, we compared susceptibility artifacts, signal-to-noise ratios, and activation patterns when overt versus covert verbal responses were elicited during fMRI scanning, using both individual and group analyses. The results indicated that different patterns of brain activation were elicited during covert as compared to overt verbal responses. This suggests that covert responses cannot be used as a simple substitute for overt verbal responses. Further, the results suggested that the use of overt verbal responses during fMRI scanning can produce interpretable results if: (1) the primary comparison is between two conditions that both use overt verbal responses, and (2) analyses are conducted on pooled group data rather than individual participant data. In Study Two, we evaluated the feasibility and validity of a method for acquiring participants' overt responses during fMRI scanning. The results indicated that our method was very accurate in acquiring the content of participant's responses. Further, inspection of the responses demonstrated that participants do not always comply with task instructions and highlighted the importance of obtaining behavioral performance measures during fMRI scanning.

Adult↗
PubMed1999

The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster).

This study compared the effects of centrally administered oxytocin (OT) and arginine vasopressin (AVP) on partner preference formation and social contact in male and female prairie voles (Microtus ochrogaster). After 1 hr of cohabitation and pretreatment with either AVP or OT, both males and females exhibited increased social contact and significant preference for the familiar partner. After pretreatment with either an OT receptor antagonist (OTA) or an AVP (V1a) receptor antagonist (AVPA), neither OT nor AVP induced a partner preference. In addition, treatment with OT+OTA or AVP+AVPA was associated with low levels of social contact in both sexes. Either AVP or OT is sufficient to facilitate social contact if either the OT or AVP receptor is available. However, the formation of partner preferences may require access to both AVP and OT receptors.

Animals↗
PubMed1999

Prior exposure To oxytocin mimics the effects Of social contact and facilitates sexual behaviour In females.

The purpose of this study was to determine whether pretreatment with oxytocin could mimic the effects of social contact and enhance sexual receptivity in female prairie voles. Female prairie voles require prolonged exposure to males to become sexually active and oxytocin has been shown to play a major role in the establishment of social bonds between males and females. Therefore, we hypothesized that prior exposure to exogenous oxytocin, in the absence of males, would enhance sexual activity in females. Two experiments were conducted to test this hypothesis. Experiment 1 examined the capacity of oxytocin to enhance sexual behaviour in females undergoing natural oestrus. Sexually naive female prairie voles received a daily subcutaneous injection of 20 microg oxytocin or isotonic saline for 5 days before being placed with a sexually experienced male for 48 h. Females treated with oxytocin were significantly more likely to mate during this period than saline-treated females. In experiment 2 the ability of oxytocin to increase subsequent sensitivity of sexually naive females to oestradiol was tested. Females that received oxytocin pretreatment, as in experiment 1, followed by oestradiol displayed a significant increase in sexual receptivity when compared to females treated with saline and oestradiol or oestradiol only. The results supported the hypothesis that prior exposure to oxytocin can mimic the effects of social contact, and can facilitate sexual receptivity by increasing the sensitivity of females to very low doses of oestradiol.

Animals↗
PubMed1999

The "benefits" of distractibility: mechanisms underlying increased Stroop effects in schizophrenia.

Recent studies of selective attention in schizophrenia patients suggest a particular pattern of single-trial Stroop performance: increased facilitation but not interference in reaction times (RTs), combined with increased error interference. Our Stroop task analysis suggests that this pattern can be explained by a selective attention deficit if one accounts for (1) performance in the congruent condition; (2) the nature of the neutral stimulus; (3) the relationship between accuracy and RT; and (4) response set effects. To test these hypotheses, we examined Stroop performance in 40 DSM-IV schizophrenia patients and 20 healthy control subjects, using a range of neutral stimuli (color patches, noncolor words, color words not in the response set). The findings confirmed several of our predictions and the results were consistent with the hypothesis that abnormal Stroop performance in schizophrenia reflects a failure to adequately attend to the task-appropriate stimulus dimension (color). This inattention affects both the congruent and incongruent conditions and multiple points in the information processing pathway.

Adult↗
PubMed1999

The contribution of the anterior cingulate cortex to executive processes in cognition.

The anterior cingulate cortex (ACC), on the medial surface of the frontal lobes, has frequently been hypothesized to make critical contributions to the function of neural systems involved in the executive control of cognition. Three principal theories have been developed to account for this role. The first, 'motivated attention', emphasizes the limbic identity of the ACC and the effects of lesions to this area of the brain. The second, 'attention allocation', emphasizes the fact that during functional neuroimaging studies activation of the ACC is seen during tasks that elicit incompatible response tendencies that must be resolved for correct performance. The third theory, 'error detection', reflects the observation of a negative scalp potential occurring during incorrect responses which appears to have a medial frontal generator. The first and last theories suggest evaluative functions by the ACC in the service of control, while attention allocation suggests a strategic function. We have proposed that the data supporting all three theories can be reconciled if the ACC were detecting conflicting processes during task performance that might be associated with errors. In support of this hypothesis we describe results using event-related fMRI which confirm that the ACC does show error related activity but that the same region of the brain also shows increased response related activity during correct responses associated with response competition. This suggests a re-conceptualization of the contribution of the ACC to executive processes that support an evaluative role, specifically the on-line detection of processing conflicts that may be associated with deteriorating performance. Unresolved questions related to the contribution of this region to executive processes and potential future directions for research on the function of this region of the brain are discussed.

Animals↗
PubMed1999

Effectiveness of antipsychotic therapy in a naturalistic setting: a comparison between risperidone, perphenazine, and haloperidol.

BACKGROUND: Therapeutic ineffectiveness and noncompliance with antipsychotic agents are major contributors to rehospitalization in patients with psychotic disorders. It is unknown whether risperidone's favorable side effect profile compared with that of the conventional antipsychotics results in improved compliance and reduced hospitalizations in a naturalistic setting. The purpose of this study was to test the hypothesis that treatment with risperidone reduces readmission rates and associated costs when compared with treatment with perphenazine or haloperidol. METHOD: Inpatients prescribed either risperidone, perphenazine, or haloperidol between January 1, 1995, and December 31, 1995, as a single oral antipsychotic at discharge were retrospectively identified. Data were collected for that index hospitalization and for a 1-year follow-up period. Primary outcome measures included re-admission rates, changes in antipsychotic therapy, anticholinergic drug use, and costs. RESULTS: There were 202 evaluable patients (81 treated with risperidone, 78 with perphenazine, and 43 with haloperidol). Baseline demographics were similar between groups except that more patients in the risperidone group had a primary diagnosis of psychotic disorder or had been hospitalized in the year prior to study. The percentage of patients readmitted during the 1-year follow-up period was similar among drug groups (41% risperidone, 26% perphenazine, and 35% haloperidol) when controlled for baseline differences in diagnosis and hospitalization history (p = .32). Anticholinergic drug use was more common in the haloperidol group (p = .004). Mean yearly cost (drug + hospitalization) in the risperidone group was $20,317, nearly double that in the other treatment groups (p < .001). CONCLUSION: The results from this naturalistic study indicate that the high cost of risperidone is not offset by a reduction in readmission rates when compared with conventional antipsychotics.

Adolescent↗
PubMed1998

Selective attention in schizophrenia: relationship to verbal working memory.

In previous work using the Stroop task to examine cognitive function in schizophrenia, we have suggested that reaction time (RT) facilitation and error interference should be more sensitive measures of cognitive function than RT interference. We examined this hypothesis in 36 DSM-IV schizophrenia and schizoaffective patients, who performed both the Stroop and the Speaking Span, a measure of verbal working memory. The results supported our hypotheses, demonstrating that RT facilitation and error interference were associated more strongly with working memory performance than RT interference. The robust correlations between these measures of selective attention and Speaking Span performance has implications for understanding the nature and selectivity of cognitive dysfunction in schizophrenia. We present several different hypotheses that may explain this relationship, including: (1) a generalized deficit; (2) a common cognitive disturbance; and (3) a common neurobiological dysfunction.

Adult↗
PubMed1998

Dopamine and the mechanisms of cognition: Part I. A neural network model predicting dopamine effects on selective attention.

BACKGROUND: Dopamine affects neural information processing, cognition, and behavior; however, the mechanisms through which these three levels of function are affected have remained unspecified. We present a parallel-distributed processing model of dopamine effects on neural ensembles that accounts for effects on human performance in a selective attention task. METHODS: Task performance is stimulated using principles and mechanisms that capture salient aspects of information processing in neural ensembles. Dopamine effects are simulated as a change in gain of neural assemblies in the area of release. RESULTS: The model leads to different predictions as a function of the hypothesized location of dopamine effects. Motor system effects are simulated as a change in gain over the response layer of the model. This induces speeding of reaction times but an impairment of accuracy. Cognitive attentional effects are simulated as a change in gain over the attention layer. This induces a speeding of reaction times and an improvement of accuracy, especially at very fast reaction times and when processing of the stimulus requires selective attention. CONCLUSIONS: A computer simulation using widely accepted principles of processing in neural ensembles can account for reaction time distributions and time-accuracy curves in a selective attention task. The simulation can be used to generate predictions about the effects of dopamine agonists on performance. An empirical study evaluating these predictions is described in a companion paper.

Attention↗