Todd B. Parrish

Relationship of MRI Delayed Contrast Enhancement to Irreversible Injury, Infarct Age, and Contractile Function

BACKGROUND Contrast MRI enhancement patterns in several pathophysiologies resulting from ischemic myocardial injury are controversial or have not been investigated. We compared contrast enhancement in acute infarction (AI), after severe but reversible ischemic injury (RII), and in chronic infarction. METHODS AND RESULTS In dogs, a large coronary artery was occluded to study AI and/or chronic infarction (n = 18), and a second coronary artery was chronically instrumented with a reversible hydraulic occluder and Doppler flowmeter to study RII (n = 8). At 3 days after surgery, cine MRI revealed reduced wall thickening in AI (5+/-6% versus 33+/-6% in normal, P<0.001). In RII, wall thickening before, during, and after inflation of the occluder for 15 minutes was 35+/-5%, 1+/-8%, and 21+/-10% and Doppler flow was 19.8+/-5.3, 0.2+/-0.5, and 56.3+/-17.7 (peak hyperemia) cm/s, respectively, confirming occlusion, transient ischemia, and reperfusion. Gd-DTPA-enhanced MR images acquired 30 minutes after contrast revealed hyperenhancement of AI (294+/-96% of normal, P<0.001) but not of RII (98+/-6% of normal, P = NS). Eight weeks later, the chronically infarcted region again hyperenhanced (253+/-54% of normal, n = 8, P<0.001). High-resolution (0.5 x 0.5 x 0.5 mm) ex vivo MRI demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis with and without reperfusion at 1 day (R = 0.99, P<0.001) and 3 days (R = 0.99, P<0.001) and collagenous scar at 8 weeks (R = 0.97, P<0.001). CONCLUSIONS In the pathophysiologies investigated, contrast MRI distinguishes between reversible and irreversible ischemic injury independent of wall motion and infarct age.

Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density

The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain (CBP) patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. CBP patients were divided into neuropathic, exhibiting pain because of sciatic nerve damage, and non-neuropathic groups. Pain-related characteristics were correlated to morphometric measures. Neocortical gray matter volume was compared after skull normalization. Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10-20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm3 loss of gray matter for every year of chronic pain. Regional gray matter density in 17 CBP patients was compared with matched controls using voxel-based morphometry and nonparametric statistics. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic CBP. Our results imply that CBP is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.

Dissociation of Neural Representation of Intensity and Affective Valuation in Human Gustation

We used a 2 x 2 factorial design to dissociate regions responding to taste intensity and taste affective valence. Two intensities each of a pleasant and unpleasant taste were presented to subjects during event-related fMRI scanning. The cerebellum, pons, middle insula, and amygdala responded to intensity irrespective of valence. In contrast, valence-specific responses were observed in anterior insula/operculum extending into the orbitofrontal cortex (OFC). The right caudolateral OFC responded preferentially to pleasant compared to unpleasant taste, irrespective of intensity, and the left dorsal anterior insula/operculuar region responded preferentially to unpleasant compared to pleasant tastes equated for intensity. Responses best characterized as an interaction between intensity and pleasantness were also observed in several limbic regions. These findings demonstrate a functional segregation within the human gustatory system. They also show that amygdala activity may be driven by stimulus intensity irrespective of valence, casting doubt upon the notion that the amygdala responds preferentially to negative stimuli.

Chronic pain and the emotional brain : Specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain

Living with unrelenting pain (chronic pain) is maladaptive and is thought to be associated with physiological and psychological modifications, yet there is a lack of knowledge regarding brain elements involved in such conditions. Here, we identify brain regions involved in spontaneous pain of chronic back pain (CBP) in two separate groups of patients (n = 13 and n = 11), and contrast brain activity between spontaneous pain and thermal pain (CBP and healthy subjects, n = 11 each). Continuous ratings of fluctuations of spontaneous pain during functional magnetic resonance imaging were separated into two components: high sustained pain and increasing pain. Sustained high pain of CBP resulted in increased activity in the medial prefrontal cortex (mPFC; including rostral anterior cingulate). This mPFC activity was strongly related to intensity of CBP, and the region is known to be involved in negative emotions, response conflict, and detection of unfavorable outcomes, especially in relation to the self. In contrast, the increasing phase of CBP transiently activated brain regions commonly observed for acute pain, best exemplified by the insula, which tightly reflected duration of CBP. When spontaneous pain of CBP was contrasted to thermal stimulation, we observe a double-dissociation between mPFC and insula with the former correlating only to intensity of spontaneous pain and the latter correlating only to pain intensity for thermal stimulation. These findings suggest that subjective spontaneous pain of CBP involves specific spatiotemporal neuronal mechanisms, distinct from those observed for acute experimental pain, implicating a salient role for emotional brain concerning the self.

Hunger selectively modulates corticolimbic activation to food stimuli in humans.

Functional magnetic resonance imaging (fMRI) was used to determine whether visual responses to food in the human amygdala and related corticolimbic structures would be selectively altered by changes in states of hunger. Participants viewed images of motivationally relevant (food) and motivationally irrelevant (tool) objects while undergoing fMRI in alternately hungry and satiated conditions. Food-related visual stimuli elicited greater responses in the amygdala, parahippocampal gyrus. and anterior fusiform gyrus when participants were in a hungry state relative to a satiated state. The state-dependent activation of these brain structures did not generalize to the motivationally irrelevant objects. These results support the hypothesis that the amygdala and associated inferotemporal regions are involved in the integration of subjective interoceptive states with relevant sensory cues processed along the ventral visual stream.

The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions

Chronic complex regional pain syndrome (CRPS) is a debilitating pain condition accompanied by autonomic abnormalities. We investigated gray matter morphometry and white matter anisotropy in CRPS patients and matched controls. Patients exhibited a disrupted relationship between white matter anisotropy and whole-brain gray matter volume; gray matter atrophy in a single cluster encompassing right insula, right ventromedial prefrontal cortex (VMPFC), and right nucleus accumbens; and a decrease in fractional anisotropy in the left cingulum-callosal bundle. Reorganization of white matter connectivity in these regions was characterized by branching pattern alterations, as well as increased (VMPFC to insula) and decreased (VMPFC to basal ganglion) connectivity. While regional atrophy differentially related to pain intensity and duration, the strength of connectivity between specific atrophied regions related to anxiety. These abnormalities encompass emotional, autonomic, and pain perception regions, implying that they likely play a critical role in the global clinical picture of CRPS.

The large-scale neural network for spatial attention displays multifunctional overlap but differential asymmetry.

Functional magnetic resonance imaging (fMRI) was used to determine the brain regions activated by two types of covert visuospatial attentional shifts: one based on exogenous spatial priming and the other on foveally presented cues which endogenously regulated the direction of spatial expectancy. Activations were seen in the cortical and subcortical components of a previously characterized attentional network, namely, the frontal eye fields, posterior parietal cortex, the cingulate gyrus, the putamen, and the thalamus. Additional activations occurred in the anterior insula, dorsolateral prefrontal cortex, temporo-occipital cortex in the middle and inferior temporal gyri, the supplementary motor area, and the cerebellum. Direct comparisons showed a nearly complete overlap in the location of activations resulting from the two tasks. However, the spatial priming task displayed a more pronounced rightward asymmetry of parietal activation, and a conjunction analysis showed that the area of posterior parietal cortex jointly activated by both tasks was more extensive in the right hemisphere. Furthermore, the posterior parietal and temporo-occipital activations were more pronounced in the task of endogenous attentional shifts. The results show that both exogenous (based on spatial priming) and endogenous (based on expectancy cueing) shifts of attention are subserved by a common network of cortical and subcortical regions. However, the differences between the two tasks, especially in the degree of rightward asymmetry, suggests that the pattern of activation within this network may show variations that reflect the specific attributes of the attentional task.

Functional Anatomy of Intra- and Cross-Modal Lexical Tasks

Functional magnetic resonance imaging (fMRI) was used to examine lexical processing in normal adults (20-35 years). Two tasks required only intramodal processing (spelling judgments with visual input and rhyming judgments with auditory input) and two tasks required cross-modal processing between phonologic and orthographic representations (spelling judgments with auditory input and rhyming judgments with visual input). Each task led to greater activation in the unimodal association area concordant with the modality of input, namely fusiform gyrus (BA 19, 37) for written words and superior temporal gyrus (BA 22, 42) for spoken words. Cross-modal tasks generated greater activation in posterior heteromodal regions including the supramarginal and angular gyri (BA 40, 39). Cross-modal tasks generated additional activation in unimodal areas representing the target of conversion, superior temporal gyrus for visual rhyming and fusiform gyrus for auditory spelling. Our findings suggest that the fusiform gyrus processes orthographic word forms, the superior temporal gyrus processes phonologic word forms, and posterior heteromodal regions are involved in the conversion between orthography and phonology.

The posterior cingulate and medial prefrontal cortex mediate the anticipatory allocation of spatial attention.

The purpose of this study was to identify brain regions underlying internally generated anticipatory biases toward locations where significant events are expected to occur. Subjects fixated centrally and responded to peripheral targets preceded by a spatially valid (predictive), invalid (misleading), or neutral central cue while undergoing fMRI scanning. In some validly cued trials, reaction time was significantly shorter than in trials with neutral cues, indicating that the cue had successfully induced a spatial redistribution of motivational valence, manifested as expectancy. The largest cue benefits led to selectively greater activations within the posterior cingulate and medial prefrontal cortex. These two areas thus appear to establish a neural interface between attention and motivation. An inverse relationship to cue benefit was seen in the parietal cortex, suggesting that spatial expectancy may entail the inhibition of attention-related areas to reduce distractibility by events at irrelevant locations.

Neural development of selective attention and response inhibition

Brain activation differences between 12 children (9- to 12-year-olds) and 12 adults (20- to 30-year-olds) were examined on two cognitive tasks during functional magnetic resonance imaging (fMRI). Spatial selective attention was measured with the visual search for a conjunction target (red triangle) in a field of distracters and response inhibition was measured with a go no-go task. There were small developmental differences in the selective attention task, with children showing greater activation than adults in the anterior cingulate and thalamus. There were large developmental differences in the response inhibition task, with children showing greater activation than adults in a fronto-striatal network including middle cingulate, medial frontal gyrus, medial aspects of bilateral superior frontal gyrus, and the caudate nucleus on the left. Children also showed greater bilateral activation for the response inhibition task in posterior cingulate, thalamus and the hippocampo-amygdaloid region. The extensive developmental differences on the response inhibition task are consistent with the prolonged maturation of the fronto-striatal network.