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Biomedical subjects

Mark A Mandelkern

Publications and source records attributed to Mark A Mandelkern.

23 records · Page 2Linked to original sources

Brain responses to visceral and somatic stimuli in patients with irritable bowel syndrome with and without fibromyalgia.

OBJECTIVE: Symptoms of irritable bowel syndrome (IBS) and fibromyalgia (FM) commonly coexist. We hypothesized that one of the mechanisms underlying this comorbidity is increased activation of brain regions concerned with the processing and modulation of visceral and somatic afferent information, in particular subregions of the anterior cingulate cortex (ACC). METHODS: Regional cerebral blood flow (rCBF) was assessed in age-matched female IBS (n = 10) and IBS + FM (n = 10) subjects using H(2)(15)O positron emission tomography during noxious visceral (rectal) and somatic pressure stimuli. RESULTS: GI symptom severity was significantly higher in the IBS patients compared with the IBS + FM patients (p < 0.05). In addition, IBS + FM patients rated somatic pain as more intense than their abdominal pain (p < 0.05). Whereas the somatic stimulus was less unpleasant than the visceral stimulus for IBS patients without FM, the somatic and visceral stimuli were equally unpleasant in the IBS + FM group. Group differences in regional brain activation were entirely within the middle subregion of the ACC. There was a greater rCBF increase in response to noxious visceral stimuli in IBS patients and to somatic stimuli in IBS + FM patients. CONCLUSION: Chronic stimulus-specific enhancement of ACC responses to sensory stimuli in both syndromes may be associated with cognitive enhancement of either visceral (IBS) or somatic (IBS + FM) sensory input and may play a key pathophysiologic role in these chronic pain syndromes.

Adult↗

Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer's disease.

OBJECTIVE: Delusional thoughts are common in patients with Alzheimer's disease and contribute prominently to morbidity. The pathophysiologic underpinnings for delusions in Alzheimer's disease are not well understood. In this study the authors examined the relationship between delusional thoughts and regional cortical metabolism in patients with Alzheimer's disease. METHOD: Twenty-five patients with probable Alzheimer's disease were included. None was taking psychotropic medication. Severity of delusions and other neuropsychiatric symptoms was assessed by using a semistructured interview and the Neurobehavioral Rating Scale just before the imaging procedure. [(18)F]Fluorodeoxyglucose positron emission tomography was used to measure resting cerebral glucose metabolic rates in the cortical lobes and in anatomically defined subregions of the frontal and temporal cortexes. RESULTS: A linear regression model, controlling for the effects of cognitive deficits, revealed a significant relationship between severity of delusional thought and the metabolic rates in three frontal regions: the right superior dorsolateral frontal cortex (Brodmann's area 8), the right inferior frontal pole (Brodmann's area 10), and the right lateral orbitofrontal region (Brodmann's area 47). Bivariate partial correlation analysis indicated that severity of delusions was associated with hypometabolism in additional prefrontal and anterior cingulate regions. Robust relationships with metabolism in regions of the temporal cortex were not apparent. CONCLUSIONS: Dysmetabolism in specific regions of the right prefrontal cortex may be associated with delusional thought in Alzheimer's disease. Delusions appear to reflect the pathophysiologic state of particular cortical regions. Activity across distributed neuronal networks and the specific content of delusional thoughts may modulate these relationships.

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Brain metabolic changes during cigarette craving.

BACKGROUND: In functional brain imaging studies, exposure to cues related to cocaine, opiates, and alcohol in dependent individuals is associated with activation of the anterior cingulate gyrus, amygdala, orbitofrontal cortex, and dorsolateral prefrontal cortex. Craving for these substances positively correlates with activity in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula. The objective of this study was to determine changes in regional cerebral glucose metabolism and correlations between craving and regional metabolism in heavy cigarette smokers exposed to cigarette-related cues. METHODS: Twenty heavy smokers (who smoked > or =20 cigarettes per day) and 20 nonsmoking control subjects underwent 2 fluorine 18-fluorodeoxyglucose positron emission tomography scans 10 days apart in randomized order: one while watching a videotape that presented cigarette-related cues and handling a cigarette, and the other while watching an educational (nature) videotape and handling a neutral object (pen). RESULTS: From the neutral to the cigarette cue scan, heavy smokers had greater increases than nonsmoking controls in relative glucose metabolism in the perigenual anterior cingulate gyrus spanning the midline. Significant positive correlations were found between intensity of craving and metabolism in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula bilaterally. An unexpected positive association was found between craving and metabolism in the right sensorimotor cortex. CONCLUSIONS: Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances.

Adult↗

The use of 2-deoxy-2-[18F]fluoro-D-glucose (FDG-PET) positron emission tomography in the routine diagnosis of epilepsy.

PURPOSE: Positron emission tomography with 2-deoxy fluoroglucose positron emission tomography (18-FDG-PET) is widely used in the pre-surgical evaluation of subjects with epilepsy, but little is known of its usefulness in a non-surgical population. PROCEDURES: We analyzed the sensitivity of PET as a diagnostic tool in a large unselected population of epilepsy subjects. Pre-surgical and non-surgical portions of this population were individually assessed as well. The relationship of PET abnormalities to other neurodiagnostic tests was examined. Statistical assessment relied primarily on contingency tables (chi-square tests), with ANOVA or non-parametric assessment used as necessary. RESULTS: While PET was more likely to identify areas of decreased metabolism in the surgical population than in the non-surgical populations, it nevertheless found a significant number of abnormalities in the total population and in the non-surgical group alone. Even in groups in which the clinical diagnosis was unknown, abnormalities were found 40% of the time. PET was useful as an exclusionary diagnostic tool for non-epileptic seizures (NES) and primary generalized epilepsies (PGE) with sensitivity, specificity, and accuracy > 90%. The PET was somewhat more sensitive than magnetic resonance imaging (MRI) in finding abnormalities in the total population, but was less sensitive than electroencephalography (EEG). CONCLUSION: PET may be a useful diagnostic tool in the general epilepsy population even when a definitive clinical diagnosis is not suggested by other modalities.

Journal Article↗

Subcortical hyperintensities in Alzheimer's disease: associated clinical and metabolic findings.

The authors measured subcortical hyperintensities (SH) on magnetic resonance images (MRI) in 18 patients with probable Alzheimer's disease and examined the relationships of SH severity with cortical metabolic function and clinical symptoms. Severity of SH was not correlated with absolute metabolic rates in cortical lobes. However, anterior SH severity was inversely correlated with frontal/ parietal metabolic ratios after covarying for cognitive impairment. SH severity in some areas was associated with the severity of global neuropsychiatric symptoms, but marked effects on individual symptoms were not apparent. The small sample size and multiple variables limit conclusions that can be drawn. These preliminary findings indicate that subcortical MRI hyperintensities may play a role in the pathophysiology and clinical expression of Alzheimer's disease.

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