Biomedical subjects

Jean A King

Publications and source records attributed to Jean A King.

11 recordsLinked to original sources

PubMed2006

Imaging the neural substrates involved in the genesis of pentylenetetrazol-induced seizures.

PURPOSE: Functional imaging of animal models makes it possible to map the functional neuroanatomy contributing to the genesis of seizures. Pentylenetetrazol (PTZ)-induced seizure in rats, a relevant model of human absence and of generalized tonic-clonic epilepsy, was used to stimulate seizure activity within 30 s of administration while collecting continuous, high-resolution, multislice images at subsecond intervals. METHODS: Pilot studies were conducted to establish a quick and effective PTZ model for the imaging experiments. PTZ was then used to stimulate seizure activity in rats while collecting multislice functional MRI (fMRI) images from the entire forebrain at 4.7 Tesla. Ethosuximide (ESM) also was used to block seizure activity. RESULTS: Within 2-4 s of PTZ administration, a rapid increase in blood oxygen level-dependent (BOLD) signal intensity was noted in the thalamus, especially the anterior thalamic nuclei. Activity in the anterior thalamus peaked approximately 15 s before seizure onset and was more than twofold greater than that in all other thalamic areas. The retrosplenial cortex showed a twofold greater increase in activity as compared with other cortical areas, also peaking at approximately 15 s. The dentate gyrus was twice as active as other hippocampal areas but peaked just before seizure onset. Treatment with ESM blocked seizures, decreasing PTZ-induced activation in most forebrain areas. The anterior thalamus and retrosplenial cortex were essentially blocked by pretreatment with ESM. CONCLUSIONS: The anterior thalamus, retrosplenial cortex, and dentate gyrus show the greatest increases in BOLD signal activity before seizure onset. Neurons in these areas may contribute to the neural network controlling the initiation of generalized tonic-clonic seizure.

Animals↗

PubMed2005

Procedure for minimizing stress for fMRI studies in conscious rats.

Functional magnetic resonance imaging (fMRI) in conscious animals is evolving as a critical tool for neuroscientists. The present study explored the effectiveness of an acclimation procedure in minimizing the stress experienced by the animal as assessed by alterations in physiological parameters including heart rate, respiratory rate, and serum corticosterone levels. Results confirm that as the stress of the protocol is minimized, there is a significant decrease in head movements and enhancement in data quality. The feasibility of improving the quality of fMRI data acquired in alert rats by utilizing a relatively simple technique is presented.

Acclimatization↗

PubMed2005

Association of stress, hostility and plasma testosterone levels.

OBJECTIVES: Many studies assessing the role of sex hormones, like testosterone, on stress and hostility factors have been primarily conducted in selected atypical populations such as violent criminals as well as androgen users and abusers. Therefore, the main aim of the current study was to investigate the association between testosterone levels and two psychosocial variables: stress and hostility in a cohort of healthy individuals who were members of a health maintenance organization (HMO). METHODS: At five quarterly visits, psychosocial scales and blood draws were collected. Psychological stress was measured by using several scales that assessed different types of stress, including daily hassles, major life events and perceived stress. Similarly, different aspects of hostility were measured, among them cynicism, hostile affect and aggressive responding. Plasma collected from each visit was used for testosterone level determinations. RESULTS: Testosterone levels were significantly associated with stress in both males and females. However, whereas this association exhibited a "threshold effect" in males, it demonstrated a direct and continuous linear relationship between these variables in females. Hostility was not correlated with testosterone levels in neither males nor females. CONCLUSIONS: These results suggest that testosterone levels in normal males and females may be more reflective of an intricate balance between physiological responding and emotional coping to stressors than the hostility profile of the individual.

Adaptation, Psychological↗

PubMed2004

Deficits in testosterone facilitate enhanced fear response.

Testosterone has been implicated in many behaviors related to sexual and reproductive function, but its role in fear responses is unclear. Studies in both humans and animals have linked altered testosterone concentrations to externalizing behaviors like aggression and violence, but less to more internalizing behaviors like fear. Therefore, the current study was designed to investigate the effects of testosterone on innate fear response in male rats. TMT (2,5-dihydo-2,4,5-trimethylthiazoline), a chemical extracted from fox feces, was used to elicit a fear response in the male rats with normal and diminished levels of testosterone. Behavioral indices such as in freezing response, and fear-induced analgesia were monitored in response to TMT. The results demonstrate that deficits in testosterone resulted in a significant increase in the freezing time and fear-induced analgesia. These studies suggest that testosterone decline may have a significant effect on increasing innate fear response and fear-induced enhancement of analgesia in male rats.

Animals↗

PubMed2004

Activation of neural pathways associated with sexual arousal in non-human primates.

PURPOSE: To evaluate brain activity associated with sexual arousal, fully conscious male marmoset monkeys were imaged during presentation of odors that naturally elicit high levels of sexual activity and sexual motivation. MATERIAL AND METHODS: Male monkeys were lightly anesthetized, secured in a head and body restrainer with a built-in birdcage resonator and positioned in a 9.4-Tesla spectrometer. When fully conscious, monkeys were presented with the odors of a novel receptive female or an ovariectomized monkey. Both odors were presented during an imaging trial and the presentation of odors was counterbalanced. Significant changes in both positive and negative BOLD signal were mapped and averaged. RESULTS: Periovulatory odors significantly increased positive BOLD signal in several cortical areas: the striatum, hippocampus, septum, periaqueductal gray, and cerebellum, in comparison with odors from ovariectomized monkeys. Conversely, negative BOLD signal was significantly increased in the temporal cortex, cingulate cortex, putamen, hippocampus, substantia nigra, medial preoptic area, and cerebellum with presentation of odors from ovariectomized marmosets as compared to periovulatory odors. A common neural circuit comprising the temporal and cingulate cortices, putamen, hippocampus, medial preoptic area, and cerebellum shared both the positive BOLD response to periovulatory odors and the negative BOLD response to odors of ovariectomized females. CONCLUSION: These data suggest the odor-driven enhancement and suppression of sexual arousal affect neuronal activity in many of the same general brain areas. These areas included not only those associated with sexual activity, but also areas involved in emotional processing and reward.

Animals↗

PubMed2004

fMRI of generalized absence status epilepticus in conscious marmoset monkeys reveals corticothalamic activation.

PURPOSE: A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (fMRI) experiments to elucidate the brain mechanisms underlying this disorder. METHODS: Adult male marmoset monkeys (Callithrix jacchus) were treated with gamma-butyrolactone (GBL) to induce prolonged absence seizures, and the resulting spike-wave discharges (SWDs) were analyzed to determine the similarity to the 3-Hz SWDs that characterize the disorder. In addition, blood-oxygenation-level-dependent (BOLD) fMRI was measured at 4.7 Tesla after absence seizure induction with GBL. RESULTS: Electroencephalographic recordings during imaging showed 3-Hz SWDs typical of human absence seizures. This synchronized EEG pattern started within 15 to 20 min of drug administration and persisted for >60 min. In addition, pretreatment with the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG changes caused by GBL. Changes in BOLD signal intensity in the thalamus and sensorimotor cortex correlated with the onset of 3-Hz SWDs. The change in BOLD signal intensity was bilateral but heterogeneous, affecting some brain areas more than others. No significant negative BOLD changes were seen. CONCLUSIONS: The BOLD fMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex.

4-Butyrolactone↗

PubMed2004

FMRI of brain activation in a genetic rat model of absence seizures.

PURPOSE: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions. METHODS: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level-dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images. RESULTS: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area. CONCLUSIONS: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure.

Animals↗

PubMed2003

Corticothalamic modulation during absence seizures in rats: a functional MRI assessment.

PURPOSE: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. METHODS: Blood-oxygenation-level-dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using gamma-butyrolactone (GBL; 200 mg/kg, intraperitoneal). RESULTS: The corticothalamic circuitry, critical for spike-wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. CONCLUSIONS: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents.

Anesthesia↗

PubMed2003

Regional cerebral blood flow and BOLD responses in conscious and anesthetized rats under basal and hypercapnic conditions: implications for functional MRI studies.

Anesthetics, widely used in magnetic resonance imaging (MRI) studies to avoid movement artifacts, could have profound effects on cerebral blood flow (CBF) and cerebrovascular coupling relative to the awake condition. Quantitative CBF and tissue oxygenation (blood oxygen level-dependent [BOLD]) were measured, using the continuous arterial-spin-labeling technique with echo-planar-imaging acquisition, in awake and anesthetized (2% isoflurane) rats under basal and hypercapnic conditions. All basal blood gases were within physiologic ranges. Blood pressure, respiration, and heart rates were within physiologic ranges in the awake condition but were depressed under anesthesia (P < 0.05). Regional CBF was heterogeneous with whole-brain CBF values of 0.86 +/- 0.25 and 1.27 +/- 0.29 mL. g-1. min-1 under awake and anesthetized conditions, respectively. Surprisingly, CBF was markedly higher (20% to 70% across different brain conditions) under isoflurane-anesthetized condition compared with the awake state (P < 0.01). Hypercapnia decreased pH, and increased Pco(2) and Po(2). During 5% CO(2) challenge, under awake and anesthetized conditions, respectively, CBF increased 51 +/- 11% and 25 +/- 4%, and BOLD increased 7.3 +/- 0.7% and 5.4 +/- 0.4%. During 10% CO(2) challenge, CBF increased 158 +/- 28% and 47 +/- 11%, and BOLD increased 12.5 +/- 0.9% and 7.2 +/- 0.5%. Since CBF and BOLD responses were substantially higher under awake condition whereas blood gases were not statistically different, it was concluded that cerebrovascular reactivity was suppressed by anesthetics. This study also shows that perfusion and perfusion-based functional MRI can be performed in awake animals.

Anesthesia↗

PubMed2003

Neural substrates underlying impulsivity.

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder whose three main symptoms are impulsiveness, inattention, and hyperactivity. Although ADHD is an early developmental disorder, it may persist into adulthood, resulting in deficits associated with poor academic performance, frequent job changes, poor and unstable marriages, and increases in motor vehicle accidents. Of the three primary symptoms of ADHD, deficits in impulse control are the most challenging to the social network and the judicial system. While the etiology of ADHD remains unknown, recent work suggests that the central deficits in ADHD may be due to poor response inhibition that is linked to monoamine and prefrontal lobe deficiencies. In the past, preclinical studies designed to understand the lack of impulse control have generally been relegated to studies linked to aggression and drug abuse. With the use of innovative noninvasive techniques, like anatomical and functional magnetic resonance imaging, selective neurochemical and behavioral paradigms have converged with preclinical reports and lend support to the premise that monoaminergic neurotransmitter systems and the cortico-striatal circuitry are essential to impulse control. Furthermore, new emerging data on neural substrates underlying impulsivity have incorporated brain regions involved in reinforcement, reward, and decision making such as the nucleus accumbens, cerebellum, and amygdala. As noninvasive brain imaging, neurochemical, and behavioral approaches are combined, our knowledge of the neural networks underlying impulsivity will hopefully give rise to therapeutic approaches aimed at alleviating this disorder.

Animals↗

PubMed2002

Seed finding in golden hamsters: a potential animal model for screening anxiolytic drugs.

Fasting hamsters overnight, followed by temporary isolation in a novel environment are stressful conditions that hamper their ability or motivation to find hidden sunflower seeds when returned to their home environment. Studies were done to test whether treatment with antianxiety drugs would reduce stress and shorten the latency to find the hidden seeds. Prior to testing, the animals were fasted for 18-20 h. Ninety minutes after intraperitoneal injection of test drugs (fluoxetine, buspirone, chlordiazepoxide, clozapine, desipramine, yohimbine), the animals were taken from their home cage and placed into a novel holding cage for 2 min. During their absence, 6 sunflower seeds were buried under the bedding in one corner of their home cage. The animals were placed back into their home cage and timed for their latency to find the seeds in a 5-min observation period. Treatment with anxiolytics caused a dose-dependent reduction in the latency to find the sunflower seed, while treatment with other psychotherapeutics were ineffective. Seed finding is an extremely sensitive bioassay, responding to anxiolytics given in doses as low as 1 microg/kg. These data provide evidence that seed finding in hamsters may serve as an animal model for screening potential anxiolytic drugs.

Adrenergic alpha-Agonists↗