Hans C. Breiter

Response and Habituation of the Human Amygdala during Visual Processing of Facial Expression

We measured amygdala activity in human volunteers during rapid visual presentations of fearful, happy, and neutral faces using functional magnetic resonance imaging (fMRI). The first experiment involved a fixed order of conditions both within and across runs, while the second one used a fully counterbalanced order in addition to a low level baseline of simple visual stimuli. In both experiments, the amygdala was preferentially activated in response to fearful versus neutral faces. In the counterbalanced experiment, the amygdala also responded preferentially to happy versus neutral faces, suggesting a possible generalized response to emotionally valenced stimuli. Rapid habituation effects were prominent in both experiments. Thus, the human amygdala responds preferentially to emotionally valenced faces and rapidly habituates to them.

Acute Effects of Cocaine on Human Brain Activity and Emotion

We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, ventral tegmentum, and pons and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pons, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.

Beautiful faces have variable reward value: fMRI and behavioral evidence.

The brain circuitry processing rewarding and aversive stimuli is hypothesized to be at the core of motivated behavior. In this study, discrete categories of beautiful faces are shown to have differing reward values and to differentially activate reward circuitry in human subjects. In particular, young heterosexual males rate pictures of beautiful males and females as attractive, but exert effort via a keypress procedure only to view pictures of attractive females. Functional magnetic resonance imaging at 3 T shows that passive viewing of beautiful female faces activates reward circuitry, in particular the nucleus accumbens. An extended set of subcortical and paralimbic reward regions also appear to follow aspects of the keypress rather than the rating procedures, suggesting that reward circuitry function does not include aesthetic assessment.

Reward circuitry activation by noxious thermal stimuli.

Using functional magnetic resonance imaging (fMRI), we observed that noxious thermal stimuli (46 degrees C) produce significant signal change in putative reward circuitry as well as in classic pain circuitry. Increases in signal were observed in the sublenticular extended amygdala of the basal forebrain (SLEA) and the ventral tegmentum/periaqueductal gray (VT/PAG), while foci of increased signal and decreased signal were observed in the ventral striatum and nucleus accumbens (NAc). Early and late phases were observed for signals in most brain regions, with early activation in reward related regions such as the SLEA, VT/PAG, and ventral striatum. In contrast, structures associated with somatosensory perception, including SI somatosensory cortex, thalamus, and insula, showed delayed activation. These data support the notion that there may be a shared neural system for evaluation of aversive and rewarding stimuli.

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. Hum. Brain Mapping 5:124–132, 1997.

Human brain activation under controlled thermal stimulation and habituation to noxious heat: An fMRI study

Brain activity was studied with functional magnetic resonance imaging (fMRI) following thermal stimulation. Two groups (n = 6/group) of human male volunteers were given up to four noxious (46°C) and four non‐noxious (41°C) stimuli. In the 46°C experiment, positive signal changes were found in the frontal gyri, anterior and posterior cingulate gyrus, thalamus, motor cortex, somatosensory cortex (SI and SII), supplementary motor area, insula, and cerebellum. Low‐level negative signal changes appeared in the amygdala and hypothalamus. All regions activated by 46°C were also activated by 41°C. However, except for SI and thalamus, significantly more activation was observed for the 46°C stimulus. A significant attenuation of the signal change was observed by the third stimulus for the 46°C, but not for 41°C experiment. Similar findings were replicated in the second group. These fMRI findings specify differences between somatosensory and pain sensation and suggest a number of rich avenues for future research. Magn Reson Med 41:1044–1057, 1999.

Functional magnetic resonance imaging of brain reward circuitry in the human.

ABSTRACT: To produce behavior, motivational states necessitate at least three fundamental operations, including (1) selection of objectives focused on goal‐objects, (2) compilation of goal‐object information, and (3) determination of physical plans for securing goal‐objects. The second of these general operations has been theorized to involve three subprocesses: (a) feature detection and other perceptual processing of putative goal‐object “rewards,” (b) valuation of goal‐object worth in the context of potential hedonic deficit states, and (c) extraction of incidence and temporal data regarding the goal‐object. A number of subcortical brain regions appear to be involved in these three informational subprocesses, in particular, the amygdala, sublenticular extended amygdala (SLEA) of the basal forebrain, and nucleus accumbens/subcallosal cortex (NAc/SCC). Components of the amygdala, SLEA, and NAc/SCC together constitute the larger anatomic structure of the extended amygdala. Functional magnetic resonance imaging (fMRI) studies of humans have recently begun to localize these subcortical regions within the extended amygdala during specific experimental conditions. In this manuscript, two human cocaine‐ infusion studies and one cognitive psychology experiment are reviewed in relation to their pattern of fMRI activation within regions of the extended amygdala. Activation in the NAc/SCC, in particular, is evaluated in relation to a hypothesis that one function of the NAc/SCC and associated brain regions is the evaluation of goal‐object incidence data for the computation of conditional probabilities regarding goal‐object availability. Further work is warranted to test hypothesized functions for all regions within the extended amygdala and integrate them toward an understanding of motivated behavior.

Acute plasticity in the human somatosensory cortex following amputation.

WE studied a patient after amputation of an arm and found that in less than 24 h stimuli applied on the ipsilateral face were referred in a precise, topographically organized, modality-specific manner to distinct points on the phantom. Functional magnetic resonance imaging (fMRI) performed one month later showed that brush-evoked activity in the brain demonstrates objective signal changes which correlate with perceptual changes in the phantom hand. This finding in humans corresponds to the observations of immediate plasticity in cortical pathways described in animals, including primates. The results suggest that reorganization of sensory pathways occurs very soon after amputation in humans, potentially due to the unmasking of ordinarily silent inputs rather than sprouting of new axon terminals.

A Proposal for a Coordinated Effort for the Determination of Brainwide Neuroanatomical Connectivity in Model Organisms at a Mesoscopic Scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brainwide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brainwide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open-access data repository; compatibility with existing resources; and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.

Amygdala Volume Associated With Alcohol Abuse Relapse and Craving

OBJECTIVE Amygdala volume has been associated with drug craving in cocaine addicts, and amygdala volume reduction is observed in some alcohol-dependent subjects. This study sought an association in alcohol-dependent subjects between volumes of reward-related brain regions, alcohol craving, and the risk of relapse. METHOD Besides alcohol craving, the authors assessed amygdala, hippocampus, and ventral striatum volumes in 51 alcohol-dependent subjects and 52 age- and education-matched healthy comparison subjects after detoxification. After imaging and clinical assessment, patients were followed for 6 months and alcohol intake was recorded. RESULTS Alcohol-dependent subjects showed reduced amygdala, hippocampus, and ventral striatum volumes and reported stronger craving in relation to healthy comparison subjects. However, only amygdala volume and craving differentiated between subsequent relapsers and abstainers. A significant decrease of amygdala volume in alcohol-dependent subjects was associated with increased alcohol craving before imaging and an increased alcohol intake during the 6-month follow-up period. CONCLUSIONS These findings suggest a relationship between amygdala volume reduction, alcohol craving, and prospective relapse into alcohol consumption.