Activation of the amygdala to emotionally valenced stimuli, and particularly to fearful faces, has been widely demonstrated in healthy young adults. However, recent studies assessing amygdala responses to fearful emotional faces in the normal elderly have not shown similar results. The reason for this is uncertain, but it may relate to life-span developmental changes in processing emotional stimuli or structural alterations in the amygdala with aging. In order to examine whether the amygdala could be activated in the elderly, we developed a paradigm designed to engage the amygdala on several levels. Based on recent imaging work indicating that novelty and stimulus change activates the amygdala, we assessed amygdala responses in young and elderly adults to novel fearful faces (versus familiar neutral ones). We demonstrate a robust activation in both groups, indicating that the amygdala remains responsive in aging. This activation did not differ between the two groups when we examined regions of interest in the amygdala based on functional or structural criteria. However, there were significantly greater activations in the inferior temporal cortex in the young versus elderly subjects.

Habituation is a highly adaptive property of the nervous system, which allows for the allocation of attention and other cognitive resources to more imperative environmental events. The amygdala is an important site of habituation in humans, but no studies to date have examined the effects of aging on amygdala habituation. Given the amygdala's role in evaluating the salience of a stimulus and initiating behavioral responses, the potential importance of amygdala habituation in aging may be far-reaching. Therefore, we assessed for differences in habituation in the amygdalae of healthy young and elderly adults during repeated presentations of neutral human faces using functional magnetic resonance imaging (fMRI). In addition, we evaluated the relationship between amygdala volume and habituation, to examine the effects of atrophy. Eighteen healthy young controls and 18 healthy elderly subjects were scanned with fMRI during viewing of repeatedly presented neutral human face stimuli. Significant fMRI signal decrement was observed across all subjects for early versus late face presentations. Analysis of group, condition, and hemisphere revealed a significant three-way interaction, with right greater than left habituation in the young, but left greater than right amygdala habituation in the elderly. Volumetric and correlational analyses demonstrated that amygdala volume is associated with habituation in the right, but not left, hemisphere. We conclude that, in healthy elderly adults, the amygdala retains its adaptive habituation response, but speculate that intrinsic changes in amygdala anatomy during aging may modulate its laterality.

Functional magnetic resonance imaging (fMRI) was used to study age-related differences in the neural circuitry involved in perception of negative facial affect. During scanning, 24 younger and 22 older adults viewed blocks of angry and neutral faces. The fMRI data analysis of the angry versus neutral faces contrast demonstrated greater activation in younger versus older individuals in the right amygdala/hippocampus region, whereas older adults demonstrated greater activation in the right anterior-ventral insula cortex. Hence, normal aging seems to affect specific nodes in the neural network involved in processing negative emotional face information. This age-related change from more subcortical to more cortical involvement could reflect functional compensation within the neural system involved in perception of facial affect, or the fact that older adults process emotional information in a different manner than do young adults.

A balance of inhibitory and facilitatory mechanisms is essential for efficient and goal-directed behaviors. These mechanisms may go awry in several neuropsychiatric disorders characterized by uncontrolled, repetitive behaviors. The visuospatial priming paradigm is a well-established probe of inhibition and facilitation that has been used to demonstrate behavioral deficits in patients with Tourette syndrome and obsessive–compulsive disorder. However, the brain correlates of this visuospatial priming paradigm are not yet well established. In the present study, we used a visuospatial priming paradigm and event-related functional MRI, to probe inhibitory and facilitatory brain mechanisms in healthy adult women. When subjects performed the negative priming (i.e., inhibitory) task, several regions of the prefrontal cortex were selectively activated relative to the neutral condition. Non-overlapping regions of the prefrontal cortex were deactivated in the positive priming condition. These results support the notion that the prefrontal cortex is involved in both inhibitory and facilitatory processing and demonstrate that this visuospatial priming task shares brain correlates with other positive and negative priming tasks. In conjunction with functional MRI, this visuospatial priming task may be useful for studying the pathophysiology of neuropsychiatric disorders in which deficient inhibitory processing or excessive facilitation is a feature.

Inhibitory mechanisms that begin to develop in childhood are essential for efficient and goal-directed behaviors. These inhibitory mechanisms may go awry in several childhood-onset neuropsychiatric disorders, such as Tourette syndrome, obsessive-compulsive disorder and attention deficit hyperactivity disorder. Negative visuospatial priming is a well-established behavioral probe of inhibition that has been used to demonstrate deficits in children with neuropsychiatric disorders of inhibition, but the brain correlates of negative visuospatial priming have not previously been well delineated. In the present study, we use a visuospatial priming paradigm and event-related functional magnetic resonance imaging (fMRI) to probe inhibitory brain mechanisms in healthy children. When subjects performed the control (i.e. neutral) motor task, a network of cortical and subcortical sensorimotor regions was activated. In contrast, during performance of the negative priming (i.e. inhibitory) task, several regions of the prefrontal cortex were selectively engaged. These results support the notion that the prefrontal cortex is involved in inhibitory processing in healthy children and demonstrate that negative visuospatial priming shares brain correlates with other inhibitory tasks. In conjunction with fMRI, the visuospatial priming task described in the current study may be useful for studying the pathophysiology of childhood-onset neuropsychiatric disorders characterized by deficient inhibitory processing.

Background In healthy individuals, the activity of the medial temporal lobe habituates rapidly with the repeated presentation of a stimulus. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that habituation of the medial temporal lobe is reduced in schizophrenia. Methods During fMRI scanning, fearful and happy faces were presented repeatedly to healthy control subjects (n =16) and patients with schizophrenia (n =18). Habituation of medial temporal lobe structures was measured by comparing the hemodynamic response occurring during the early and late portions of the presentation of each face. Results Control subjects demonstrated significant medial temporal lobe habituation to fearful but not to happy faces. In contrast, patients with schizophrenia did not demonstrate medial temporal lobe habituation in response to fearful or happy faces. In a direct, between-group comparison, right hippocampal habituation to fearful faces was significantly greater in control subjects than in the schizophrenia patients. Also, there were no significant differences between the patients and control subjects in the early medial temporal lobe response to fearful faces, suggesting that attenuated hippocampal habituation in schizophrenia is not associated with a reduction in initial activation. Conclusions These findings suggest that there is abnormal modulation of hippocampal responses to fearful faces in schizophrenia.

Background Despite the high prevalence of specific phobia (SP), its neural substrates remain undetermined. Although an initial series of functional neuroimaging studies have implicated paralimbic and sensory cortical regions in the pathophysiology of SP, to date contemporary morphometric neuroimaging methods have not been applied to test specific hypotheses regarding structural abnormalities. Methods Morphometric magnetic resonance imaging (MRI) methods were used to measure regional cortical thickness in 10 subjects with SP (animal type) and 20 healthy comparison (HC) subjects. Results Consistent with a priori hypotheses, between-group differences in cortical thickness were found within paralimbic and sensory cortical regions. Specifically, in comparison with the HC group, the SP group exhibited increased cortical thickness in bilateral insular, bilateral pregenual anterior cingulate, and bilateral posterior cingulate cortex as well as left visual cortical regions. Conclusions Taken together, these structural findings parallel results from initial functional imaging studies that implicate paralimbic and sensory cortical regions in the mediating anatomy of SP symptoms. Further research will be necessary to replicate these findings and to determine their specificity as well as their pathophysiologic significance.

BACKGROUND:To assess the amygdala response to emotional faces in obsessive-compulsive disorder (OCD) using functional magnetic resonance imaging (fMRI).METHODS:Ten subjects with current OCD and 10 healthy control subjects underwent fMRI, during which they viewed pictures of fearful, happy, and neutral human faces, as well as a fixation cross.RESULTS:Across both groups, there was significant activation in left and right amygdala for the fearful versus neutral faces contrast. Data extracted from these functionally defined regions of interest indicated that OCD subjects exhibited a weaker response than control subjects bilaterally across all face conditions versus fixation. No group-by-face condition interactions were observed.CONCLUSIONS:Contrary to findings in other anxiety disorders, there was no observed increase in amygdala responsivity to fearful versus neutral human faces in OCD as compared with healthy control subjects. Moreover, across all face conditions, amygdala responsivity was attenuated in OCD subjects relative to control subjects. Therefore, the present findings are consistent with abnormal amygdala function in OCD and are of a character that may distinguish OCD from other anxiety disorders.

Sex-discriminating facial features are examples of visual information involved in guiding social behavior. We used functional magnetic resonance imaging (fMRI) to assess brain responses in face-relevant brain areas in men and women during exposure to neutral male and female faces. An increased fMRI signal was found in the left amygdala and adjacent anterior temporal regions in men, but not in women, during exposure to faces of the opposite versus the same sex. These data indicate that the relationship between the sex of the subject and the sex of the face affects activity in the inferior temporal lobe. The sex-differential nature of this activation pattern may reflect sex differences in cognitive style and attentional processes when confronting faces of the opposite sex.