Amygdala response to both positively and negatively valenced stimuli.

Human lesion and functional imaging data suggest a central role for the amygdala in the processing of negative stimuli. To determine whether the amygdala's role in affective processing extends beyond negative stimuli, subjects viewed pictures that varied in emotional content (positive vs negative valence) and arousal level (high vs low) while undergoing functional magnetic resonance imaging. Amygdala activation, relative to a low arousal and neutral valence picture baseline, was significantly increased for both positively and negatively valenced stimuli and did not differ for the two valences. There were no laterality effects. Whereas arousal level appeared to modulate the amygdala response for negative stimuli, all positively valenced pictures (both high and low in arousal) produced significant amygdala responses. These results clearly demonstrate a role for the amygdala in processing emotional stimuli that extends beyond negative and fearful stimuli.

Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli.

OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.

Effects of methylphenidate on functional MRI blood-oxygen-level-dependent contrast.

OBJECTIVE: The authors' goal was to determine potential hemodynamic consequences of methylphenidate on functional magnetic resonance imaging (MRI) blood-oxygen-level-dependent (BOLD) contrast. METHOD: BOLD and perfusion changes were recorded from the motor cortex of six healthy subjects while they performed flexion-extension movements of the right index finger (finger tapping) at varying rates before and after oral methylphenidate administration. RESULTS: Functional MRI signals increased monotonically with faster movement rates. Subjects' heart rates increased modestly after methylphenidate administration, but no changes in finger tapping performance or functional MRI signals were observed. CONCLUSIONS: Methylphenidate does not alter BOLD neural-hemodynamic coupling. Consequently, functional MRI can be used to map neural systems that subserve cognitive operations (e.g., attention and executive processes) in subjects taking methylphenidate.

Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI.

Functional magnetic resonance imaging (fMRI) was conducted to observe the effects of cocaine administration on the physiological fluctuations of fMRI signal in two brain regions. Seven long-term cocaine users with an average age of 32 years and 8 years of cocaine use history were recruited for the study. A T2*-weighted fast echo-planar imaging (EPI) pulse sequence was employed at 1.5 T to acquire three sets of brain images for each subject under three conditions (at rest, after saline injection, and after cocaine injection [0.57 mg/kg]). Cross-correlation maps were constructed using the synchronous, low frequency signal from voxel time courses after filtering respiratory, cardiac, and other physiological noise. A quantitative evaluation of the changes in functional connectivity was made using spatial correlation coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region of primary visual cortex and 43% reduction in SCC values in the region of primary motor cortex were observed after cocaine administration. This significant reduction in SCC values in these cortical regions is a reflection of changes in neuronal activity. It is suggested that the observed changes in low frequency components after acute cocaine administration during a resting, no-task situation may be used as a baseline reference source when assessing the effects of cocaine on task-driven activation or on mesolimbic dopamine pathways.

Responses to alpha 2-adrenoceptor blockade by idazoxan in healthy male and female volunteers.

Seven male and five female volunteers underwent double-blind infusions of the alpha 2-adrenoceptor antagonist idazoxan (100 and 200 micrograms/mg) and placebo in random order. Blood pressure, plasma norepinephrine, growth hormone and subjective responses were measured. The higher dose of idazoxan produced increases in blood pressure, norepinephrine and growth hormone and slight increases in anxiety. Both subject age and sex appeared to influence the magnitude of responses.

The rhythms of human premolar eruption: a study using continuous observation.

New optical technology now allows for precise observation of erupting human premolars. Continuous overnight tracking of an erupting tooth with a video microscope system shows that eruption occurs almost exclusively during the early evening. During the day, slight intrusion is likely to occur. When Moiré magnification is used to provide extremely high resolution (0.05 micrometer), slight movements of the erupting tooth in concert with the arterial pulse can be observed, and a previously unknown cyclic movement with a period of 20 to 50 seconds is seen consistently. Rhythms in skeletal growth and tooth eruption suggest that treatment to influence jaw growth and move teeth may be most effective at specific times of the day.

Continuous overnight observation of human premolar eruption.

Such observation was made possible by transmitting the image of a mobile ceramic ruling on the erupting maxillary second premolar to a video-microscope via a coaxial fibreoptic cable. The cable was inserted into a reference bar secured to the adjacent first molar and first premolar. The image of the ruling was superimposed with the image from a surveillance camera focused on the patient and continuously recorded on video-tape along with the participant's blood pressure, pulse rate, electromyographic activity and occlusal contact sounds. Overnight data from 12 individuals clearly revealed a circadian rhythm in eruption during the prefunctional spurt. On average, the maxillary second premolar erupted 41 microns during an 11-h overnight observation, with almost all the eruption occurring in the late evening from 8 p.m. to 1 a.m. After 1 a.m., eruption typically ceased, with a tendency for intrusion to occur until 7 a.m. Sleep increased the rate of eruption during the late evening, but did not influence the eruption rate during the early morning. Haemodynamic changes, including blood pressure and pulse rate, did not have a significant impact on the rhythm of eruption. The observed eruption rhythm is most probably caused by changing hormone levels and their effect on the periodontal ligament. The late-evening eruption of human premolars coincides with the late-evening secretion of growth hormone and thyroid hormone typically found in humans.

Extraversion: a "hidden" personality factor in coping?

Recent evidence suggests a larger role for personality determinants of the coping response than has been traditionally held. In the two studies presented here, we examined the influence of personality on the use of social support and other coping strategies in samples of undergraduate students. The first study surveyed a range of coping responses to naturally occurring stressors and found that Extraversion was related to social support seeking, optimism (identified as germane to coping in prior research) was related to problem solving, and both dispositions were negatively related to avoidance. The second study used an experimental approach and multiple personality measures to correct for possible methodological problems in the first. Extraversion again proved to be associated with help seeking; moreover, this relationship accounted for that of another disposition, self-esteem--a construct considered crucial in the literature. The utility of personality variables, particularly Extraversion, in predicting and explaining the choice of a coping strategy is discussed.

Regional brain glucose metabolism after acute alpha 2-blockade by idazoxan.

BACKGROUND: Several classes of antidepressant drugs act on alpha 2-adrenergic receptors. Studies of patients with disorders responsive to treatment with these drugs report group differences in ex vivo measures of alpha 2-binding and in vivo responses mediated by alpha 2-receptors. Measurement of regional brain metabolic response to an alpha 2-antagonist may be a useful method for further definition of the role alpha 2-receptor regulation plays in the treatment of neuropsychiatric disorders. METHODS: Regional brain glucose metabolism was measured before and after infusion with 200 micrograms/kg idazoxan with use of 18F-fluoro-2-deoxyglucose positron emission tomography in 13 healthy men. Arterial drug concentration, behavioral responses, and cardiovascular responses were also measured. RESULTS: The absolute and normalized glucose metabolic rate significantly increased in primary visual cortex. Significant increases and decreases occurred in normalized metabolic rates in prefrontal cortical regions. Measurement of metabolic effects occurred during the peak cardiovascular response. CONCLUSIONS: Our findings are consistent with regionally specific effects of alpha 2-blockade. This method may be useful for the study of alpha 2-receptor function in humans.

Anomalous transverse relaxation in 1H spectroscopy in human brain at 4 Tesla.

Longitudinal (T1) and apparent transverse relaxation times (T2) of choline-containing compounds (Cho), creatine/phosphocreatine (Cr/PCr), and N-acetyl aspartate (NAA) were measured in vivo in human brain at 4 Tesla. Measurements were performed using a water suppressed stimulated echo pulse sequence with complete outside volume presaturation to improve volume localization at short echo times. T1-values of Cho (1.2 +/- 0.1 s), Cr (1.6 +/- 0.3 s), and NAA (1.6 +/- 0.2 s) at 4 Tesla in occipital brain were only slightly larger than those reported in the literature at 1.5 Tesla. Thus, TR will not adversely affect the expected enhancement of signal-to-noise at 4 Tesla. Surprisingly, apparent T2-values of Cho (142 +/- 34 ms), Cr (140 +/- 13 ms), and NAA (185 +/- 24 ms) at 4 Tesla were significantly smaller than those at 1.5 Tesla and further decreased when increasing the mixing interval TM. Potential contributing factors, such as diffusion in local susceptibility related gradients, dipolar relaxation due to intracellular paramagnetic substances and motion effects are discussed. The results suggest that short echo time spectroscopy is advantageous to maintain signal to noise at 4 Tesla.

High speed 1H spectroscopic imaging in human brain by echo planar spatial-spectral encoding.

We introduce a fast and robust spatial-spectral encoding method, which enables acquisition of high resolution short echo time (13 ms) proton spectroscopic images from human brain with acquisition times as short as 64 s when using surface coils. The encoding scheme, which was implemented on a clinical 1.5 Tesla whole body scanner, is a modification of an echo-planar spectroscopic imaging method originally proposed by Mansfield Magn. Reson. Med. 1, 370-386 (1984), and utilizes a series of read-out gradients to simultaneously encode spatial and spectral information. Superficial lipid signals are suppressed by a novel double outer volume suppression along the contours of the brain. The spectral resolution and the signal-to-noise per unit time and unit volume from resonances such as N-acetyl aspartate, choline, creatine, and inositol are comparable with those obtained with conventional methods. The short encoding time of this technique enhances the flexibility of in vivo spectroscopic imaging by reducing motion artifacts and allowing acquisition of multiple data sets with different parameter settings.

The effects of prolonged lithium exposure on the immune system of normal control subjects: serial serum soluble interleukin-2 receptor and antithyroid antibody measurements.

The purpose of this study was to begin evaluating the effects of lithium carbonate on in vivo immune function in normal controls. We postulated that lithium carbonate would stimulate lymphocytes but would not affect the production of antithyroid antibodies. Twenty-seven normal controls had blood samples drawn for measurements of serum soluble interleukin-2 receptors (SIL-2Rs), antithyroglobulin antibodies, and antimicrosomal antibodies prior to and after approximately 1 and 4 weeks of treatment with lithium carbonate at therapeutic blood levels. Subjects had a small but statistically significant increase in serum SIL-2Rs after 4 weeks of lithium treatment (446.3 +/- 177.2 U/ml versus 497.6 +/- 232.3 U/ml, p = 0.033). There was no increase in the prevalence of antithyroglobulin or antimicrosomal antibodies with lithium treatment nor did lithium act as an adjuvant to increase the titers in subjects with preexisting antithyroid antibodies.

Identification of a gamma subunit associated with the adenylyl cyclase regulatory proteins Ns and Ni.

The subunit composition of the Ns and Ni, the human erythrocyte stimulatory and inhibitory regulatory proteins of adenylyl cyclase, respectively, were analyzed by a sodium dodecyl sulfate-containing discontinuous urea and polyacrylamide gradient gel electrophoresis system designed for the study of low molecular weight polypeptides. This system disclosed that these proteins, in addition to their known alpha and beta subunits, contain an additional small peptide of apparent molecular weight of 5,000 (5K). This "5K peptide" is also present in preparations of another protein which we termed "40K protein" on the basis of its hydrodynamic behavior and whose primary protein constituent is the Mr 35,000 beta subunit of the above regulatory proteins. Analyzing Ni, the 5K peptide was functionally related to the protein by showing that its apparent Stokes radius changes from 5.9 to 5.1 nm after treatment with guanyl-5'-yl imidodiphosphate and magnesium in parallel with the alpha and beta subunits. These data are interpreted as evidence for the existence of a third subunit associated with the regulatory proteins of adenylyl cyclase. We call this subunit gamma and propose a minimum subunit structure for these proteins of the alpha beta gamma type.