Nathaniel M. Alpert

Regional Cerebral Blood Flow in the Amygdala and Medial Prefrontal Cortex During Traumatic Imagery in Male and Female Vietnam Veterans With PTSD

CONTEXT Theoretical neuroanatomic models of posttraumatic stress disorder (PTSD) and the results of previous neuroimaging studies of PTSD highlight the potential importance of the amygdala and medial prefrontal regions in this disorder. However, the functional relationship between these brain regions in PTSD has not been directly examined. OBJECTIVE To examine the relationship between the amygdala and medial prefrontal regions during symptom provocation in male combat veterans (MCVs) and female nurse veterans (FNVs) with PTSD. DESIGN Case-control study. SETTING Academic medical center. PARTICIPANTS Volunteer sample of 17 (7 men and 10 women) Vietnam veterans with PTSD (PTSD group) and 19 (9 men and 10 women) Vietnam veterans without PTSD (control group). MAIN OUTCOME MEASURES We used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the recollection of personal traumatic and neutral events. Psychophysiologic and emotional self-report data also were obtained to confirm the intended effects of script-driven imagery. RESULTS The PTSD group exhibited rCBF decreases in medial frontal gyrus in the traumatic vs neutral comparison. When this comparison was conducted separately by subgroup, MCVs and FNVs with PTSD exhibited these medial frontal gyrus decreases. Only MCVs exhibited rCBF increases in the left amygdala. However, for both subgroups with PTSD, rCBF changes in medial frontal gyrus were inversely correlated with rCBF changes in the left amygdala and the right amygdala/periamygdaloid cortex. Furthermore, in the traumatic condition, for both subgroups with PTSD, symptom severity was positively related to rCBF in the right amygdala and negatively related to rCBF in medial frontal gyrus. CONCLUSIONS These results suggest a reciprocal relationship between medial prefrontal cortex and amygdala function in PTSD and opposing associations between activity in these regions and symptom severity consistent with current functional neuroanatomic models of this disorder.

Impaired recruitment of the hippocampus during conscious recollection in schizophrenia

Poor attention and impaired memory are enduring and core features of schizophrenia. These impairments have been attributed either to global cortical dysfunction or to perturbations of specific components associated with the dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used positron emission tomography (PET) to dissociate activations in DLPFC and hippocampus during verbal episodic memory retrieval. We found reduced hippocampal activation during conscious recollection of studied words, but robust activation of the DLPFC during the effort to retrieve poorly encoded material in schizophrenic patients. This finding provides the first evidence of hippocampal dysfunction during episodic memory retrieval in schizophrenia.

Visual mental imagery activates topographically organized visual cortex: Pet investigations

Cerebral blood flow was measured using positron emission tomography (PET) in three experiments while subjects performed mental imagery or analogous perceptual tasks. In Experiment 1, the subjects either visualized letters in grids and decided whether an X mark would have fallen on each letter if it were actually in the grid, or they saw letters in grids and decided whether an X mark fell on each letter. A region identified as part of area 17 by the Talairach and Tournoux (1988) atlas, in addition to other areas involved in vision, was activated more in the mental imagery task than in the perception task. In Experiment 2, the identical stimuli were presented in imagery and baseline conditions, but subjects were asked to form images only in the imagery condition; the portion of area 17 that was more active in the imagery condition of Experiment 1 was also more activated in imagery than in the baseline condition, as was part of area 18. Subjects also were tested with degraded perceptual stimuli, which caused visual cortex to be activated to the same degree in imagery and perception. In both Experiments 1 and 2, however, imagery selectively activated the extreme anterior part of what was identified as area 17, which is inconsistent with the relatively small size of the imaged stimuli. These results, then, suggest that imagery may have activated another region just anterior to area 17. In Experiment 3, subjects were instructed to close their eyes and evaluate visual mental images of upper case letters that were formed at a small size or large size. The small mental images engendered more activation in the posterior portion of visual cortex, and the large mental images engendered more activation in anterior portions of visual cortex. This finding is strong evidence that imagery activates topographically mapped cortex. The activated regions were also consistent with their being localized in area 17. Finally, additional results were consistent with the existence of two types of imagery, one that rests on allocating attention to form a pattern and one that rests on activating stored visual memories.

Mental rotation of objects versus hands: Neural mechanisms revealed by positron emission tomography

Twelve right-handed men participated in two mental rotation tasks as their regional cerebral blood flow (rCBF) was monitored using positron emission tomography. In one task, participants mentally rotated and compared figures composed of angular branching forms; in the other task, participants mentally rotated and compared drawings of human hands. In both cases, rCBF was compared with a baseline condition that used identical stimuli and required the same comparison, but in which rotation was not required. Mental rotation of branching objects engendered activation in the parietal lobe and Area 19. In contrast, mental rotation of hands engendered activation in the precentral gyrus (M1), superior and inferior parietal lobes, primary visual cortex, insula, and frontal Areas 6 and 9. The results suggest that at least two different mechanisms can be used in mental rotation, one mechanism that recruits processes that prepare motor movements and another mechanism that does not.

Effects of Syntactic Structure and Propositional Number on Patterns of Regional Cerebral Blood Flow

Positron emission tomography (PET) was used to determine regional cerebral blood flow (rCBF) as a function of the syntactic form and propositional density of sentences. rCBF increased in the left pars opercularis, part of Brocas area, when subjects processed syntactically more complex sentences. There were no differences in rCBF in the perisylvian association cortex traditionally associated with language processing when subjects made plausibility judgments about sentences with two propositions as compared to sentences with one proposition, but rCBF increased in infero-posterior brain regions. These results suggest that there is a specialization of neural tissue in Brocas area for constructing aspects of the syntactic form of sentences to determine sentence meaning. They also suggest that this specialization is separate from the brain systems that are involved in utilizing the meaning of a sentence that has been understood to accomplish a task.

The functional neuroanatomy of anxiety: a study of three disorders using positron emission tomography and symptom provocation

Previous neuroimaging research has contributed insights regarding the neural substrates of specific psychiatric disorders. The purpose of this study was to determine the shared mediating neuroanatomy of anxiety symptoms across three different anxiety disorders. Data were pooled from 23 right-handed adult outpatients meeting criteria for obsessive-compulsive disorder, simple phobia, or posttraumatic stress disorder. Relative regional cerebral blood flow (rCBF) was measured using positron emission tomography in the context of symptom provocation paradigms. Symptom severity was measured via self-reports. The analysis of pooled imaging data indicated activation in right inferior frontal cortex, right posterior medial orbitofrontal cortex, bilateral insular cortex, bilateral lenticulate nuclei, and bilateral brain stem foci during the symptomatic versus control conditions. A positive correlation was found between rCBF at one brain stem locus and subjective anxiety scores (r = .744, p < .001). These findings suggest that elements of the paralimbic belt together with right inferior frontal cortex and subcortical nuclei mediate symptoms across different anxiety disorders. In addition, activation at one brain stem locus appears to be associated with the subjective severity of anxiety. Further studies are warranted to determine whether these same brain systems mediate normal anxiety states as well.

Activation of Broca's area by syntactic processing under conditions of concurrent articulation.

Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) when 11 subjects made plausibility judgments about written sentences that varied in their syntactic complexity. While making their judgments, subjects uttered the word “double” aloud at a rate of one utterance per second to inhibit their ability to rehearse the sentences. Blood flow increased in Brocas area when subjects made judgments about the more complex sentences. This result replicates and extends previous findings that blood flow increases in this region when subjects process complex syntax under no interference conditions. The results of this experiment provide strong evidence that the increase in blood flow seen in Brocas area in association with processing syntactically complex structures is not due to subvocal rehearsal of those structures, but rather results from processing syntactic forms themselves. Hum. Brain Mapping 9:65–71, 2000.

Neural Systems Shared by Visual Imagery and Visual Perception: A Positron Emission Tomography Study

Subjects participated in perceptual and imagery tasks while their brains were scanned using positron emission tomography. In the perceptual conditions, subjects judged whether names were appropriate for pictures. In one condition, the objects were pictured from canonical perspectives and could be recognized at first glance; in the other, the objects were pictured from noncanonical perspectives and were not immediately recognizable. In this second condition, we assume that top-down processing is used to evaluate the names. In the imagery conditions, subjects saw a grid with a single X mark; a lowercase letter was presented before the grid. In the baseline condition, they simply responded when they saw the stimulus, whereas in the imagery condition they visualized the corresponding block letter in the grid and decided whether it would have covered the X if it were physically present. Fourteen areas were activated in common by both tasks, only 1 of which may not be involved in visual processing (the precentral gyrus); in addition, 2 were activated in perception but not imagery, and 5 were activated in imagery but not perception. Thus, two-thirds of the activated areas were activated in common.

Anger in healthy men: a PET study using script-driven imagery.

BACKGROUND An understanding of the neurobiological basis of normal emotional processing is useful in formulating hypotheses regarding the pathophysiology of psychiatric illnesses. METHODS This study examined the mediating functional neuroanatomy of anger in eight healthy men. Narrative scripts were developed from autobiographical information to induce anger and neutral states. The subjects imagined the content of the narrative scripts to induce anger during positron emission tomography to measure normalized regional cerebral blood flow (rCBF). Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Statistical parametric maps were constructed to reflect the Anger versus Neutral state contrast. RESULTS Anger was associated with activation of the left orbitofrontal cortex, right anterior cingulate cortex affective division, and bilateral anterior temporal poles. CONCLUSIONS These results suggest that the subjective experience of anger is associated with rCBF increases in anterior paralimbic regions of the brain.

PET studies of syntactic processing with auditory sentence presentation.

Sixteen subjects made plausibility judgments regarding auditorily presented cleft object and cleft subject sentences (It was the actress that the award thrilled; It was the award that thrilled the actress). rCBF increased in Brocas area, pars triangularis, when subjects processed the syntactically more complex cleft object sentences. The results are consistent with previous experiments using written materials and suggest that an increase in rCBF in Brocas area is associated with processing syntactically more complex sentences.