Darren R. Gitelman

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.

Covert Visual Spatial Orienting and Saccades: Overlapping Neural Systems

We used functional magnetic resonance imaging (fMRI) to investigate the functional anatomical relationship between covert orienting of visual spatial attention and execution of saccadic eye movements. Brain areas engaged by shifting spatial attention covertly and by moving the eyes repetitively toward visual targets were compared and contrasted directly within the same subjects. The two tasks activated highly overlapping neural systems and showed that common parietal and frontal regions are more activated during the covert task than the overt oculomotor condition. The possible nature of the relationship between these two operations is discussed.

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 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.

Functional specificity of superior parietal mediation of spatial shifting

Using event-related functional magnetic resonance imaging (fMRI) we determined how brain activity changes when an attended target shifts its location. In the main experiment, a white square could appear at 10 possible eccentricities along the horizontal meridian. It remained on the screen for a variable period of time and then changed location. At any time the stimulus could dim briefly. Subjects had to press a button when the stimulus dimmed. In order to perform this task attention had to be locked onto the target and shift with it. Half of the runs were performed overtly and half covertly. The event of interest consisted of the shift in the location of the attentional target. The state of maintained attention occurring in between the shifts constituted the baseline. The superior parietal gyrus was activated bilaterally in response to attentional shifts. No other area showed a significant response to shifting. On the left side the amplitude of the superior parietal response correlated positively with the distance of the shift. On the right side a significant correlation was present only for overt shifts. In a separate experiment we compared the maintaining of attention at a single spatial location to passive fixation: the frontal eye fields, anterior cingulate, right dorsolateral prefrontal cortex, and inferior parietal lobule were significantly activated, indicating that the absence of a shift-related response in these areas in the main experiment was due to the fact that they were equally activated by maintaining and shifting attention. The response to spatial shifts and the correlation with the distance between the original and the new location points to a specific role of the superior parietal gyrus in shifting the locus of spatial attention.

Modality independence of word comprehension

Functional magnetic resonance imaging (fMRI) was used to examine the functional anatomy of word comprehension in the auditory and visual modalities of presentation. We asked our subjects to determine if word pairs were semantically associated (e.g., table, chair) and compared this to a reference task where they were asked to judge whether word pairs rhymed (e.g., bank, tank). This comparison showed task‐specific and modality‐independent activation for semantic processing in the heteromodal cortices of the left inferior frontal gyrus (BA 46, 47) and left middle temporal gyrus (BA 21). There were also modality‐specific activations in the fusiform gyrus (BA 37) for written words and in the superior temporal gyrus (BA 22) for spoken words. Our findings are consistent with the hypothesis that word form recognition (lexical encoding) occurs in unimodal cortices and that heteromodal brain regions in the anterior as well as posterior components of the language network subserve word comprehension (semantic decoding). Hum. Brain Mapping 16:251–261, 2002.