Cortico-limbic responsiveness to high-calorie food images predicts weight status among women.

OBJECTIVES: Excessive weight gain and obesity are currently among the world's major threats to health. Women show significantly higher rates of obesity and eating disorders relative to men, but the factors contributing to these gender differences remain uncertain. We examined the correlations between regional brain responses to images of high-calorie versus low-calorie foods and self-reported motivational status, including ratings of general appetite, overeating propensity, state hunger and desire for specific foods. SUBJECTS: Thirty-eight healthy right-handed adults (22 male; 16 female) ages 18-45 participated. There were no differences between males and females with regard to age or body mass index (BMI). RESULTS: Overall, motivational status correlated significantly with activation within the amygdala, insula and orbitofrontal cortex. Regional activation was then used to predict BMI, an indicator of long-term food consumption and energy expenditure. The combined model was significant, accounting for 76% of the variance in BMI for women, whereas the same regions were not predictive of weight status among men. CONCLUSIONS: Findings suggest that long-term weight status is related to visual responsiveness to calorie-dense food imagery among women.

Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder.

BACKGROUND: Neuroimaging research has demonstrated medial prefrontal cortex (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few studies have examined brain responses to the recollection of stressful, but trauma-unrelated, personal events in PTSD. In the current study, we sought to determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and amygdala in PTSD could be observed during the recollection of trauma-unrelated stressful personal events. METHOD: Participants were 35 right-handed male combat veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven male, 10 female) with current military-related PTSD and 18 (nine male, nine female) with no current or lifetime PTSD. We used positron emission tomography (PET) and script-driven imagery to study rCBF during the recollection of trauma-unrelated stressful versus neutral and traumatic events. RESULTS: Voxelwise tests revealed significant between-group differences for the trauma-unrelated stressful versus neutral comparison in mPFC, specifically in the anterior cingulate cortex (ACC). Functional region of interest (ROI) analyses demonstrated that this interaction in mPFC represented greater rCBF decreases in the PTSD group during trauma-unrelated stressful imagery relative to neutral imagery compared to the non-PTSD group. No differential amygdala activation was observed between groups or in either group separately. CONCLUSIONS: Veterans with PTSD, compared to those without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma-unrelated stressful personal experiences. Functional neuroanatomical models of PTSD must account for diminished mPFC responses that extend to emotional stimuli, including stressful personal experiences that are not directly related to PTSD.

Probing striato-thalamic function in obsessive-compulsive disorder and Tourette syndrome using neuroimaging methods.

In summary, contemporary pathophysiological models of OCD and related disorders implicate CSTC circuitry. In this chapter, we have reviewed relevant concepts related to implicit learning and more specifically, the use of an implicit sequence learning paradigm as a probe of striato-thalamic function. An initial PET investigation of patients with OCD confirmed a priori hypotheses of failure to recruit right striatum, despite the absence of a performance deficit (22). A modified version of the SRT was studied in conjunction with fMRI and yielded reliable right-lateralized striatal activation in a cohort of 10 male subjects, with clear spatial dissociation of caudate and putamen activation foci (119). Subsequent studies in our laboratory suggest that this paradigm also yields a reliable temporal window of thalamic deactivation, and hence a means for assessing thalamic gating in human subjects (120). Finally, as presented in this chapter, preliminary data from the fMRI-SRT in patients with OCD and TS as well as normal control subjects appear to replicate and extend the findings from our original PET-SRT study in OCD. Future investigations in our laboratory will seek to elaborate upon these preliminary results. In particular, we intend to study psychiatric comparison groups to establish the generalizability and/or specificity of these findings across disorders. Within OCD, we hope to explore the relationship between abnormal brain-activation patterns and symptom dimensions (34). Further, by studying subjects with remitted OCD who have been successfully treated, we hope to determine whether the observed brain-activation abnormalities represent state or trait markers. Finally, we have already begun to test a hypothesis of parallel processing deficiency in OCD by using a dual-task version of the SRT that makes simultaneous demands on implicit and explicit information processing systems (128). It is our hope that this program of research will yield new insights about OCD and related disorders, including TS. Most importantly, as other teams of investigators pursue complementary lines of inquiry, it is our wish that collective efforts in this field will lead to improved diagnosis and treatment, if not cure or prevention, for those who are afflicted with these illnesses.

Deficits in visual cognition and attention following bilateral anterior cingulotomy.

A series of eight tests of visual cognitive abilities was used to examine pre- to post-operative performance changes in a patient receiving bilateral anterior cingulotomy. Compared with a set of eight matched control participants, post-operatively, the patient exhibited deficits in (a) the ability to sequence novel cognitive operations required to generate multipart images or rotate perceptual stimuli; (b) the ability to search for, select, and compare images of objects when the instructions did not specify precisely which objects should be visualized; and, (c) the ability to select a controlled and unpracticed response over an automatic one. Other imagery and cognitive tasks were not affected. Results are consistent with the hypothesis that anterior cingulate cortex is a component of an executive control system. One of the anterior cingulate's roles may be to monitor on-line processing and signal the motivational significance of current actions or cognitions.

Prefrontal regions supporting spontaneous and directed application of verbal learning strategies: evidence from PET.

The prefrontal cortex has been implicated in strategic memory processes, including the ability to use semantic organizational strategies to facilitate episodic learning. An important feature of these strategies is the way they are applied in novel or ambiguous situations-failure to initiate effective strategies spontaneously in unstructured settings is a central cognitive deficit in patients with frontal lobe disorders. The current study examined strategic memory with PET and a verbal encoding paradigm that manipulated semantic organization in three encoding conditions: spontaneous, directed and unrelated. During the spontaneous condition, subjects heard 24 words that were related in four categories but presented in mixed order, and they were not informed of this structure beforehand. Any semantic reorganization was, therefore, initiated spontaneously by the subject. In the directed condition, subjects were given a different list of 24 related words and explicitly instructed to notice relationships and mentally group related words together to improve memory. The unrelated list consisted of 24 unrelated words. Behavioural measures included semantic clustering, which assessed active regrouping of words into semantic categories during free recall. In graded PET contrasts (directed > spontaneous > unrelated), two distinct activations were found in left inferior prefrontal cortex (inferior frontal gyrus) and left dorsolateral prefrontal cortex (middle frontal gyrus), corresponding to levels of semantic clustering observed in the behavioural data. Additional covariate analyses in the first spontaneous condition indicated that blood flow in orbitofrontal cortex (OFC) was strongly correlated with semantic clustering scores during immediate free recall. Thus, blood flow in OFC during encoding predicted which subjects would spontaneously initiate effective strategies during free recall. Our findings indicate that OFC performs an important, and previously unappreciated, role in strategic memory by supporting the early mobilization of effective behavioural strategies in novel or ambiguous situations. Once initiated, lateral regions of left prefrontal cortex control verbal semantic organization.

The cognitive-affective neuroscience of obsessive-compulsive disorder.

There is substantial evidence that obsessive-compulsive disorder (OCD) is mediated by specific cortico-striatal- thalamic-cortical (CTSC) circuits. Here we discuss very recent publications that address the following questions: How does damage to CSTC circuitry come about?; What are the neurochemical systems involved in mediating this circuitry?; and What are the implications of such damage for understanding the pathogenesis and management of OCD? A cognitive-affective neuroscience perspective is helpful in advancing our understanding of the role of these circuits in OCD and the dysfunctional procedural strategies that appear to characterize this disorder. Furthermore, this model is becoming integrated with a range of data including brain imaging, genetic, immunologic, and neurochemical findings.

Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study.

OBJECT: The goal of this study was to test hypotheses regarding changes in volume in subcortical structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance (MR) imaging methods were used to assess volume reductions in subcortical regions following anterior cingulate lesioning in nine patients. Magnetic resonance imaging data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected to segmentation and subcortical parcellation. Significant volume reductions were predicted and found bilaterally within the caudate nucleus, but not in the amygdala, thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed that the volume reduction in the caudate nucleus was principally referrable to the body, rather than the head. Furthermore, the magnitude of volume reduction in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS: Taken together, these findings implicate significant connectivity between a region of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate body. This unique data set complements published findings in nonhuman primates, and advances our knowledge regarding patterns of cortical-subcortical connectivity involving the ACC in humans. Moreover, these findings indicate changes distant from the site of anterior cingulotomy lesions that may play a role in the clinical response to this neurosurgical procedure.

Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia.

BACKGROUND: Many patients with schizophrenia demonstrate memory deficits. We studied patterns of brain activity during episodic recognition of new and previously seen three-dimensional objects. METHODS: We used (15)O positron emission tomography to study regional cerebral blood flow in eight normal subjects and nine patients with schizophrenia during a visual object recognition task. RESULTS: In comparison with control subjects, patients with schizophrenia showed less regional cerebral blood flow increases in the pulvinar region of the right thalamus and the right prefrontal cortex during the recognition of new objects and significantly greater left prefrontal cortex regional cerebral blood flow increases during the recognition of previously seen objects. Patients with schizophrenia exhibited alarm rates to new objects similar to those of control subjects, but significantly lower recognition rates for previously seen objects. CONCLUSIONS: Schizophrenia is associated with attenuated right thalamic and right prefrontal activation during the recognition of novel visual stimuli and with increased left prefrontal cortical activation during impaired episodic recognition of previously seen visual stimuli. This study provides further evidence for abnormal thalamic and prefrontal cortex function in schizophrenia.

Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance.

BACKGROUND: Working memory (WM) deficits in schizophrenia have been associated with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic versus normal subjects during WM performance (Manoach et al 1999b). We now have investigated whether schizophrenic subjects recruit different brain regions, particularly the basal ganglia and thalamus, components of frontostriatal circuitry thought to mediate WM. METHODS: We examined regional brain activation in nine normal and nine schizophrenic subjects during WM performance using functional magnetic resonance imaging. Subjects performed a modified version of the Sternberg Item Recognition Paradigm that included a monetary reward for correct responses. We compared high and low WM load conditions to each other and to a non-WM baseline condition. We examined activation in both individual subjects and averaged group data. RESULTS: Relative to normal subjects, schizophrenic subjects exhibited deficient WM performance, at least an equal magnitude of right DLPFC activation, significantly greater left DLPFC activation, and increased spatial heterogeneity of DLPFC activation. Furthermore, only the schizophrenic group activated the basal ganglia and thalamus, even when matched for task performance with the normal group. CONCLUSIONS: Aberrant WM performance and brain activation in schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves WM. Future studies will elucidate the contribution of the anatomical components of this circuitry to WM deficits.

Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation.

OBJECTIVE: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). METHOD: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. RESULTS: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. CONCLUSIONS: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.

Thalamic deactivation during early implicit sequence learning: a functional MRI study.

Previous research has implicated the striatum in implicit sequence learning. However, imaging findings have been inconsistent with regard to activity within the thalamus during performance of such tasks. Contemporary models of cortico-striato-thalamic circuitry suggest opposing influences on thalamic activity; suppression of thalamic activity is mediated by the indirect pathway and enhancement is mediated by the direct pathway. Using functional magnetic resonance imaging, we studied activity within human thalamus during early and late phases of an implicit sequence learning task known to reliably recruit the striatum. Significant deactivation (decreased signal relative to a baseline condition) was observed within the thalamus during early implicit learning. This finding is consistent with models of cortico-striato-thalamic function and specifically supports a profile of early 'thalamic gating' via the indirect pathway.

Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation.

BACKGROUND: Relative regional cerebral blood flow (rCBF) changes were measured in Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) during exposure to combat-related stimuli. METHODS: Positron emission tomography was used to measure rCBF in 7 combat veterans with PTSD (PTSD group) and 7 healthy combat veterans (control group) who viewed and generated visual mental images of neutral, negative, and combat-related pictures. RESULTS: Unlike control subjects, subjects with PTSD had increased rCBF in ventral anterior cingulate gyrus and right amygdala when generating mental images of combat-related pictures; when viewing combat pictures, subjects with PTSD showed decreased rCBF in Broca's area. CONCLUSIONS: Results suggest that ventral anterior cingulate gyrus and right amygdala play a role in the response of combat veterans with PTSD to mental images of combat-related scenes. Reexperiencing phenomena of PTSD, which often involve emotional visual mental imagery, may be likewise associated with increased rCBF in these regions.

A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery.

BACKGROUND: Previous studies have used symptom provocation and positron emission tomography to delineate the brain systems that mediate various anxiety states. Using an analogous approach, the goal of this study was to measure regional cerebral blood flow changes associated with posttraumatic stress disorder (PTSD) symptoms. METHODS: Eight patients with PTSD, screened as physiologically responsive to a script-driven imagery symptom provocation paradigm, were exposed sequentially to audiotaped traumatic and neutral scripts in conjunction with positron emission tomography. Heart rate and subjective measures of emotional state were obtained for each condition. Statistical mapping techniques were used to determine locations of significant brain activation. RESULTS: Increases in normalized blood flow were found for the traumatic as compared with control conditions in right-sided limbic, paralimbic, and visual areas; decreases were found in left inferior frontal and middle temporal cortex. CONCLUSIONS: The results suggest that emotions associated with the PTSD symptomatic state are mediated by the limbic and paralimbic systems within the right hemisphere. Activation of visual cortex may correspond to the visual component of PTSD reexperiencing phenomena.

Neurosurgical treatment of Tourette's syndrome: a critical review.

Some patients with Tourette's syndrome (TS) remain disabled despite conventional treatment. Recently, neurosurgical procedures have been reported to be potentially effective interventions for such intractable cases. Clinicians are now being asked to make recommendations to patients about these candidate operations. This review explores the reported experience with neurosurgical treatment of TS to assess critically the evidence regarding risks and benefits. Toward that end, the rationale for the various procedures and the relevant neuroanatomy are outlined and recommendations for patient selection and management of future cases are discussed. We reviewed all available published reports on this subject and two unpublished cases, totaling 36 patients. Although a variety of operations have been used to treat TS, there is limited evidence pertaining to the risks or benefits of any surgical procedure. Neurosurgical treatment of TS remains experimental, since there is only anecdotal experience with these operations. Furthermore, there is no compelling evidence that any neurosurgical procedure is superior to all others. If these experimental neurosurgeries are to continue, guidelines should be developed regarding patient and operation selection, and interdisciplinary assessment committees should implement such guidelines at institutions where these operations are performed. Moreover, future cases should be prospectively studied using contemporary technologies to assess lesion placement and size and validated clinical instruments to characterize patients and assess outcome, including adverse effects.

A positron emission tomographic study of simple phobic symptom provocation.

BACKGROUND: The goal of this study was to determine the mediating neuroanatomy of simple phobic symptoms. METHODS: Positron emission tomography and oxygen 15 were used to measure normalized regional cerebral blood flow in seven subjects with simple phobia during control and provoked states. Stereotactic transformation and statistical parametric mapping techniques were employed to determine the locations of significant activation. RESULTS: Statistical parametric maps demonstrated significant increases in normalized regional blood flow for the symptomatic state compared with the control state in the anterior cingulate cortex, the insular cortex, the anterior temporal cortex, the somatosensory cortex, the posterior medial orbitofrontal cortex, and the thalamus. CONCLUSIONS: The results suggest that anxiety associated with the simple phobic symptomatic state is mediated by paralimbic structures. Moreover, activation of somatosensory cortex may reflect tactile imagery as one component of the phobic symptomatic condition.

Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography.

BACKGROUND: The study was designed to determine the mediating neuroanatomy of obsessive-compulsive disorder (OCD). METHODS: The short half-life tracer oxygen 15-labeled carbon dioxide was used to allow for repeated positron emission tomographic determinations of regional cerebral blood flow on each of eight patients with OCD during a resting and a provoked (symptomatic) state. RESULTS: Individually tailored provocative stimuli were successful in provoking OCD symptoms, in comparison with paired innocuous stimuli, as measured by self-report on OCD analogue scales (P = .002). Omnibus subtraction images demonstrated a statistically significant increase in relative regional cerebral blood flow during the OCD symptomatic state vs the resting state in right caudate nucleus (P < .006), left anterior cingulate cortex (P < .045), and bilateral orbitofrontal cortex (P < .008); increases in the left thalamus approached but did not reach statistical significance (P = .07). CONCLUSIONS: These findings are consistent with results of previous functional neuroimaging studies and contemporary neurocircuitry models of OCD. The data further implicate orbitofrontal cortex, caudate nucleus, and anterior cingulate cortex in the pathophysiology of OCD and in mediating OCD symptoms.

Visual Mental Imagery Activates Topographically Organized Visual Cortex: PET Investigations.

Abstract 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.