A characteristic pattern of behavioral and physiological effects is produced by marijuana and its principal psychoactive component, THC, in humans. However, THC’s sites of action in the human brain and their relationships to the drug’s actions are not well described. We have now studied in frequent marijuana users, the effects of two doses of THC (1 and 3 mg iv over 1 min) that produce effects similar to those seen with marijuana use in a social situation, on regional brain activity using BOLD fMRI. The subjects reported that the intensity of the “high” produced by the 3 mg dose was twice that of the lower dose (8/10 vs. 4.5/10). A modest dose-related tachycardia was also observed.Both increases and decreases in brain activity as measured by BOLD fMRI were seen in discrete brain regions. The 3 mg dose of THC produced time-related decreases in fMRI signal in the cerebellum including the region of the dentate nucleus, the middle temporal gyrus and the orbitofrontal region. Decreases were also seen in several...

Obstructive sleep apnea (OSA) is precipitated by atonia of the upper airway muscles and is characterized by extreme loading of airflow, marked diaphragmatic efforts, excessive thoracic and upper airway negative pressures, and significant changes in blood pressure and heart rate. In addition to anatomical factors that enhance obstruction, neural mechanisms that maintain upper airway patency appear defective in the syndrome. We examined the time course of signal changes in neural sites recruited during a challenge approximating the extreme constriction of the airway in OSA, i.e., marked inspiratory loading. A series of 20 image slices (25 repetitions, Echo Planar technique) through the entire brain of 12 male OSA patients (29-59 yrs) and 8 control subjects (29-62 yrs) was collected during 1 min baseline and 1.5 min inspiratory loading challenges in a GE 1.5T Signa scanner. Images collected during baseline and challenge conditions were subjected to a fixed effects analysis using the SPM imaging package. Regio...

The insular cortex receives direct connections from primary olfactory structures such as the piriform cortex, anterior olfactory nucleus and primary olfactory bulb. Based upon these connections an olfactory related function within the insular cortex would be expected, yet such a relationship has not been clearly characterized. Using whole brain fMRI, we have identified a discrete region of the human posterior insular cortex which responds to different olfactory stimuli over successive exposures both within and between experimental sessions. Further, this activity appears highly dependent upon the number of odorant exposures and the length of time between odorant exposures, possibly reflecting habituation at a hemodynamic and presumably neural level. We propose that this olfactory-responsive region of the posterior insular cortex performs a previously unrealized role in olfaction and the insular cortex may be a key player in olfactory related sensation. This work was supported by the Cornell/Rockefeller/Slo...

Prefrontal anomalies in psychiatric disorders are often preceded early in life by disruptions in parental care. Genetic risk factors may play an equally influential role as revealed by the human twin-study approach. To test for genetic and social effects on prefrontal cortical volumes in squirrel monkeys, this study combined a paternal half-sibling analysis with three postnatal conditions that altered aspects of early maternal care. In one condition, offspring were periodically removed from natal groups between 13-21 weeks of age. Differences in maternal availability were produced in two other conditions by manipulating the effort required to find food. Whole brain T1-weighted 3D-FSPGR images were obtained 3-5 years later from all 39 young adults. Significantly larger right than left prefrontal volumes were discerned, although left and right cerebral hemispheric measures did not differ. Both genetic and postnatal rearing related differences were evident in the right but not left prefrontal cortex. Asymmetr...

Constraints from functional magnetic resonance imaging (fMRI) were used to identify the sources of the visual P300 event-related potential (ERP). Healthy subjects performed a visual three-stimulus oddball paradigm with a difficult discrimination task while fMRI and high-density ERP data were acquired in separate sessions. This paradigm allowed us to differentiate the P3b component of the P300, which has been implicated in the detection of rare events in general (target and distractor), from the P3a component, which is mainly evoked by distractor events. The fMRI-constrained source model explained >99% of the variance of the scalp ERP for both components. The P3b was mainly produced by parietal and inferior temporal areas, whereas frontal areas and the insula contributed mainly to the P3a. This source model reveals that both higher visual and supramodal association areas contribute to the visual P3b and that the P3a has a strong frontal contribution, which is compatible with its more anterior distribution o...

Brain-imaging studies have shown that visually-cued, voluntary swallowing activates a distributed network of cortical regions including the precentral and postcentral gyri, anterior cingulate cortex (ACC), insula, frontoparietal operculum, cuneus and precuneus. To elucidate the functional contributions of these discrete activation foci for swallowing, a “Go, No-Go” functional magnetic resonance imaging (fMRI) paradigm was designed. Brain activation associated with visually-cued swallowing was compared with brain activation evoked by a comparable visual cue instructing the subject not to swallow. Region-of-interest analyses performed on data from 8 healthy subjects showed a significantly greater number of activated voxels within the precentral gyrus, postcentral gyrus, and ACC during the “Go” condition compared to the “No-Go” condition. This finding suggests that the precentral gyrus, postcentral gyrus, and ACC contribute primarily to the act of swallowing. In contrast, the numbers of activated voxels withi...

Pitch, one of the primary auditory percepts, is related to the temporal regularity or periodicity of a sound. Previous functional brain imaging work in humans has shown that the level of population neural activity in centers throughout the auditory system is related to the temporal regularity of a sound, suggesting a possible relationship to pitch. In the current study, functional magnetic resonance imaging was used to measure activation in response to harmonic tone complexes whose temporal regularity was identical, but whose pitch salience (or perceptual pitch strength) differed, across conditions. Cochlear nucleus, inferior colliculus, and primary auditory cortex did not show significant differences in activation level between conditions. Instead, a correlate of pitch salience was found in the neural activity levels of a small, spatially localized region of nonprimary auditory cortex, overlapping the anterolateral end of Heschl's gyrus. The present data contribute to converging evidence that anterior are...

Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was th...