Joan Deus

Cerebral lateralization of language in normal left-handed people studied by functional MRI

Objective: To use functional MRI (fMRI) to further define the occurrence of left-hemisphere, bilateral, and right-hemisphere language in a normal left-handed population. Methods: A total of 100 healthy volunteers, consisting of 50 left-handed subjects and a reference group of 50 right-handed subjects, were studied by fMRI of the frontal cortex during silent word generation. Results: Ninety-six percent of right-handed subjects showed fMRI changes lateralized to the left hemisphere, whereas 4% showed a bilateral activation pattern. In contrast, left-hemisphere lateralization occurred in 76% of left-handers, bilateral activation in 14%, and right-hemisphere lateralization in the remaining 10%. The predominance of right-hemisphere activation, however, was weak in these cases; only a single left-handed subject (2%) showed complete right-hemisphere lateralization. Conclusions: Silent word generation lateralizes to the left cerebral hemisphere in both handedness groups, but right-hemisphere participation is frequent in normal left-handed subjects. Exclusive right-hemisphere activation rarely occurred in the frontal lobe region studied.

Consistency and functional specialization in the default mode brain network.

The notion of a “default mode of brain function” has taken on certain relevance in human neuroimaging studies and in relation to a network of lateral parietal and midline cortical regions that show prominent activity fluctuations during passive imaging states, such as rest. In this study, we perform three fMRI experiments that demonstrate consistency and specialization in the default mode network. Correlated activity fluctuations of default mode network regions are identified during (i) eyes-closed spontaneous rest, (ii) activation by moral dilemma, and (iii) deactivation by Stroop task performance. Across these imaging states, striking uniformity is shown in the basic anatomy of the default mode network, but with both tasks clearly and differentially modulating this activity compared with spontaneous fluctuations of the network at rest. Against rest, moral dilemma is further shown to evoke regionally specific activity increases of hypothesized functional relevance. Mapping spontaneous and task-related brain activity will help to constrain the meaning of the default mode network. These findings are discussed in relation to recent debate on the topic of default modes of brain function.

Anatomical variability of the anterior cingulate gyrus and basic dimensions of human personality.

This study focused on investigating a possible relationship between interindividual variability in the morphology of the cingulate gyrus and behavioral styles. Using magnetic resonance images obtained from 100 healthy young volunteers (50 women and 50 men), we measured the surface area of the anterior cingulate gyrus and related it to the scores on the Temperament and Character Inventory. Anatomical data revealed that hemispheric asymmetry in the anterior cingulate gyrus surface area was very common (83% of cases) and that a prominent right anterior cingulate was more frequent in women than in men. In the correlational analysis, surface measurements of the right anterior cingulate gyrus accounted for a 24% score variance in Harm Avoidance. Both women and men with larger right anterior cingulate described themselves as experiencing greater worry about possible problems, fearfulness in the face of uncertainty, shyness with strangers, and fatigability. Furthermore, women reported overall higher scores in Harm Avoidance than men; these gender differences were largely explained by gender differences in the right anterior cingulate area in a covariate analysis. Our observations suggest that a large right anterior cingulate is related to a temperamental disposition to fear and anticipatory worry in both genders and that a higher prevalence of these traits in women may be coupled with a greater expansion of this brain region.

Myelination of language-related areas in the developing brain

Background: The rapid development of language abilities in early childhood coincides with a similarly accelerated progression in brain maturation. Objective: To quantitate myelination in the lateral part of the verbal left hemisphere from birth to 3 years in the living human brain. Methods: One hundred children (mean age 16.6 months) were examined using three-dimensional MRI, and a subgroup of 40 children were also evaluated behaviorally. The volume of myelinated white matter was measured in language-related temporal and frontal regions and in the central sensorimotor region. A method was developed to compose a movie sequence for all the myelination process using volumetric data. Results: A plot of age against relative volume of myelinated white matter graphically detailed the myelination progress in the lateral brain. The changes started in sensorimotor white matter and the Heschl gyrus and ultimately extended to the language-related areas. Both comprehension and production regions showed a very similar myelination course, suggesting simultaneous maturation of the temporofrontal language network. The movie sequence of white matter images dynamically displayed the anatomic details of myelin deposition in this part of the brain. The analysis of language performance showed acceleration in childrens vocabulary after 18 months, once a rapid myelination phase was attained in the language brain. Conclusions: This volumetric study may contribute to further characterize the early stages of brain maturation by showing the fine progression of myelin deposition in the language domains and illustrating its relationship to childrens vocabulary acquisition.

Mapping brain response to pain in fibromyalgia patients using temporal analysis of FMRI.

Background Nociceptive stimuli may evoke brain responses longer than the stimulus duration often partially detected by conventional neuroimaging. Fibromyalgia patients typically complain of severe pain from gentle stimuli. We aimed to characterize brain response to painful pressure in fibromyalgia patients by generating activation maps adjusted for the duration of brain responses. Methodology/Principal Findings Twenty-seven women (mean age: 47.8 years) were assessed with fMRI. The sample included nine fibromyalgia patients and nine healthy subjects who received 4 kg/cm2 of pressure on the thumb. Nine additional control subjects received 6.8 kg/cm2 to match the patients for the severity of perceived pain. Independent Component Analysis characterized the temporal dynamics of the actual brain response to pressure. Statistical parametric maps were estimated using the obtained time courses. Brain response to pressure (18 seconds) consistently exceeded the stimulus application (9 seconds) in somatosensory regions in all groups. fMRI maps following such temporal dynamics showed a complete pain network response (sensory-motor cortices, operculo-insula, cingulate cortex, and basal ganglia) to 4 kg/cm2 of pressure in fibromyalgia patients. In healthy subjects, response to this low intensity pressure involved mainly somatosensory cortices. When matched for perceived pain (6.8 kg/cm2), control subjects showed also comprehensive activation of pain-related regions, but fibromyalgia patients showed significantly larger activation in the anterior insula-basal ganglia complex and the cingulate cortex. Conclusions/Significance The results suggest that data-driven fMRI assessments may complement conventional neuroimaging for characterizing pain responses and that enhancement of brain activation in fibromyalgia patients may be particularly relevant in emotion-related regions.

The lateral asymmetry of the human brain studied by volumetric magnetic resonance imaging.

Improvements in in vivo imaging methods have boosted research on brain asymmetry aimed at further establishing putative anatomical substrates for brain functional lateralization and particularly to explain left-hemisphere specialization for language. We analyzed volume asymmetries for major anatomical divisions of the lateral (perisylvian) brain region and their relative white matter content. A total of 100 healthy right-handed subjects were examined with 3D magnetic resonance imaging (MRI). The insular plane was used to limit the lateral brain, and the sylvian fissure and central sulcus to define frontal, parietal, temporal, and temporo-parieto-occipital regions. Results revealed a frontal region showing similar volumes in both hemispheres, a parietal region and a temporal region both larger in the left hemisphere, and a temporo-parieto-occipital region with predominantly right-sided asymmetry. Volume measurements of the parietal, temporal, and temporo-parieto-occipital regions complemented each other and accounted for 58% of planum temporale area variations. All study regions showed significant asymmetry for relative white matter content (percentage of white matter relative to region volume). White matter asymmetry, however, was particularly relevant for the frontal and temporal regions showing a highly frequent left-sided pattern (frontal region, 90%; temporal region, 91% of subjects). Leftward asymmetry in these two regions occurred in both genders, although hemisphere differences were significantly larger in men. Results from this MRI volume analysis of structural asymmetries in the lateral brain region complement data obtained by other methods and suggest a high occurrence of leftward asymmetry for relative white matter content in language-related regions.

Cross-Sectional and Longitudinal Assessment of Structural Brain Alterations in Melancholic Depression

BACKGROUND Whole-brain imaging approaches may contribute to the characterization of neuroanatomic alterations in major depression, especially in clinically homogenous patient groups such as those with melancholic features. We assessed brain anatomic alterations, both cross-sectionally and longitudinally, in patients with melancholic depression using a whole-brain voxel-wise approach. METHODS Whole-brain magnetic resonance images were collected from a relatively aged sample of 70 consecutively recruited major depressive disorder inpatients with melancholic features and from a group of 40 healthy control subjects. All patients were clinically followed for at least 2 years, and a subset of 30 depressive patients and 20 control subjects were rescanned after a 7-year period. Imaging data were analyzed with voxel- and tensor-based morphometry techniques. RESULTS Melancholic patients showed gray matter reductions in the left insula and white matter increases in the upper brainstem tegmentum. Male patients showed gray matter decreases in the right thalamus, and periventricular white matter reductions were specifically observed in older patients. Volume decreases in the left insula, hippocampus, and lateral parietal cortex predicted a slower recovery after treatment initiation. In longitudinal assessment, white matter of the upper brainstem tegmentum showed a different temporal evolution between groups. Additionally, bilateral gray matter reductions in the insulae were associated with the number of relapses during follow-up. CONCLUSIONS Structural alterations were identified in regions potentially related to relevant aspects of melancholia pathophysiology. Longitudinal analyses indicated region-specific interactions of baseline alterations with age as well as a significant association of clinical severity with focal changes occurring over time.

The Effect of Medial Frontal and Posterior Parietal Demyelinating Lesions on Stroop Interference

Functional imaging has consistently shown that attention-related areas of medial frontal and posterior parietal cortices are active during the attentional conflict induced by color naming in the presence of distracting words (Stroop task). Such studies, however, have provided few details of the correlational nature between observed regional brain activations and reaction time delay occurring in this situation. We analyzed the effect of medial frontal and posterior parietal lesions on the Stroop response in a group of patients with multiple sclerosis, a neurological disorder in which Stroop response speed is affected to varying degrees. Forty-five patients were assessed using a computer-presented verbal version of the Stroop task and specific MRI protocol. Demyelination areas were measured on five anatomical divisions of the medial frontal white matter and on white matter of the posterior parietal lobe. We found that a combination of frontal and parietal lesion measurements accounted for 45% of the Stroop interference time variance. Patients with more right frontal than left parietal demyelination showed slowed Stroop responses, whereas the predominance of lesions in the left posterior parietal region was associated with a reduced Stroop interference. These results may contribute to defining the specific participation of these attention-related brain areas in the conflict of attention represented by the Stroop paradigm. They also help to explain the variability of the Stroop effect in multiple sclerosis patients and suggest that the Stroop test does not assess just a single cognitive operation, but rather the combined effect of anatomically segregated neural processes.

Functional magnetic resonance imaging study of frontal lobe activation during word generation in obsessive-compulsive disorder.

BACKGROUND Functional imaging studies have demonstrated abnormal patterns of brain activity in obsessive-compulsive disorder, which consistently suggest the alteration of frontal lobe functioning. We performed a brain activation study in obsessive-compulsive disorder using a cognitive task involving the frontal lobes. METHODS Twenty patients and 20 healthy control subjects were assessed with functional magnetic resonance imaging during a phonologically guided word generation task. The study analysis was based on the comparison of group average time-course functional changes occurring at the site of largest frontal cortex activation during alternating rest and task periods. RESULTS In terms of relative signal changes, patients showed a significantly greater activation during word generation and a defective suppression of this activation during the following rest period. Both abnormal imaging findings significantly correlated with the severity of the clinical process assessed by the Yale-Brown Obsessive-Compulsive Scale. CONCLUSIONS The results indicate that functional magnetic resonance imaging during cognitive challenge may be useful to reveal distinctive features of latent brain dysfunction in obsessive-compulsive disorder.

Task-Induced Deactivation from Rest Extends beyond the Default Mode Brain Network

Activity decreases, or deactivations, of midline and parietal cortical brain regions are routinely observed in human functional neuroimaging studies that compare periods of task-based cognitive performance with passive states, such as rest. It is now widely held that such task-induced deactivations index a highly organized ‘default-mode network’ (DMN): a large-scale brain system whose discovery has had broad implications in the study of human brain function and behavior. In this work, we show that common task-induced deactivations from rest also occur outside of the DMN as a function of increased task demand. Fifty healthy adult subjects performed two distinct functional magnetic resonance imaging tasks that were designed to reliably map deactivations from a resting baseline. As primary findings, increases in task demand consistently modulated the regional anatomy of DMN deactivation. At high levels of task demand, robust deactivation was observed in non-DMN regions, most notably, the posterior insular cortex. Deactivation of this region was directly implicated in a performance-based analysis of experienced task difficulty. Together, these findings suggest that task-induced deactivations from rest are not limited to the DMN and extend to brain regions typically associated with integrative sensory and interoceptive processes.