Pattern recognition analyses of brain activation elicited by happy and neutral faces in unipolar and bipolar depression

Objectives: Recently, pattern recognition approaches have been used to classify patterns of brain activity elicited by sensory or cognitive processes. In the clinical context, these approaches have been mainly applied to classify groups of individuals based on structural magnetic resonance imaging (MRI) data. Only a few studies have applied similar methods to functional MRI (fMRI) data. Methods: We used a novel analytic framework to examine the extent to which unipolar and bipolar depressed individuals differed on discrimination between patterns of neural activity for happy and neutral faces. We used data from 18 currently depressed individuals with bipolar I disorder (BD) and 18 currently depressed individuals with recurrent unipolar depression (UD), matched on depression severity, age, and illness duration, and 18 age- and gender ratio-matched healthy comparison subjects (HC). fMRI data were analyzed using a general linear model and Gaussian process classifiers. Results: The accuracy for discriminating between patterns of neural activity for happy versus neutral faces overall was lower in both patient groups relative to HC. The predictive probabilities for intense and mild happy faces were higher in HC than in BD, and for mild happy faces were higher in HC than UD (all p < 0.001). Interestingly, the predictive probability for intense happy faces was significantly higher in UD than BD (p = 0.03). Conclusions: These results indicate that patterns of whole-brain neural activity to intense happy faces were significantly less distinct from those for neutral faces in BD than in either HC or UD. These findings indicate that pattern recognition approaches can be used to identify abnormal brain activity patterns in patient populations and have promising clinical utility as techniques that can help to discriminate between patients with different psychiatric illnesses.

High-field FMRI reveals brain activation patterns underlying saccade execution in the human superior colliculus.

BACKGROUND: The superior colliculus (SC) has been shown to play a crucial role in the initiation and coordination of eye- and head-movements. The knowledge about the function of this structure is mainly based on single-unit recordings in animals with relatively few neuroimaging studies investigating eye-movement related brain activity in humans. METHODOLOGY/PRINCIPAL FINDINGS: The present study employed high-field (7 Tesla) functional magnetic resonance imaging (fMRI) to investigate SC responses during endogenously cued saccades in humans. In response to centrally presented instructional cues, subjects either performed saccades away from (centrifugal) or towards (centripetal) the center of straight gaze or maintained fixation at the center position. Compared to central fixation, the execution of saccades elicited hemodynamic activity within a network of cortical and subcortical areas that included the SC, lateral geniculate nucleus (LGN), occipital cortex, striatum, and the pulvinar. CONCLUSIONS/SIGNIFICANCE: Activity in the SC was enhanced contralateral to the direction of the saccade (i.e., greater activity in the right as compared to left SC during leftward saccades and vice versa) during both centrifugal and centripetal saccades, thereby demonstrating that the contralateral predominance for saccade execution that has been shown to exist in animals is also present in the human SC. In addition, centrifugal saccades elicited greater activity in the SC than did centripetal saccades, while also being accompanied by an enhanced deactivation within the prefrontal default-mode network. This pattern of brain activity might reflect the reduced processing effort required to move the eyes toward as compared to away from the center of straight gaze, a position that might serve as a spatial baseline in which the retinotopic and craniotopic reference frames are aligned.

Effect of nicotine on brain activation during performance of a working memory task

Nicotine influences cognition and behavior, but the mechanisms by which these effects occur are unclear. By using positron emission tomography, we measured cognitive activation (increases in relative regional cerebral blood flow) during a working memory task [2-back task (2BT)] in 11 abstinent smokers and 11 ex-smokers. Assays were performed both after administration of placebo gum and 4-mg nicotine gum. Performance on the 2BT did not differ between groups in either condition, and the pattern of brain activation by the 2BT was consistent with reports in the literature. However, in the placebo condition, activation in ex-smokers predominated in the left hemisphere, whereas in smokers, it occurred in the right hemisphere. When nicotine was administered, activation was reduced in smokers but enhanced in ex-smokers. The lateralization of activation as a function of nicotine dependence suggests that chronic exposure to nicotine or withdrawal from nicotine affects cognitive strategies used to perform the memory task. Furthermore, the lack of enhancement of activation after nicotine administration in smokers likely reflects tolerance.

Absence of LPA1 receptor results in altered pattern of limbic activation after tail suspension test

Stress serves as an adaptive mechanism and helps organisms to cope with life-threatening situations. However, individual vulnerability to stress and dysregulation of this system may precipitate stress-related disorders such as depression. The neurobiological circuitry in charge of dealing with stressors has been widely studied in animal models. Recently our group has demonstrated a role for lysophosphatidic acid (LPA) through the LPA1 receptor in vulnerability to stress, in particular the lack of this receptor relates to robust decrease of adult hippocampal neurogenesis and induction of anxious and depressive states. Nevertheless, the specific abnormalities in the limbic circuit in reaction to stress remains unclear. The aim of this study is to examine the differences in the brain activation pattern in the presence or absence of LPA1 receptor after acute stress. For this purpose, we have studied the response of maLPA1-null male mice and normal wild type mice to an intense stressor: Tail Suspension Test. Activation induced by behaviour of brain regions involved in mood regulation was analysed by stereological quantification of c-Fos immunoreactive positive cells. We also conducted multidimensional scaling analysis in order to unravel coativation between structures. Our results revealed hyperactivity of stress-related structures such as amygdala and paraventricular nucleus of the hypothalamus in the knockout model and different patterns of coactivation in both genotypes using a multidimensional map. This data provides further evidence to the engagement of the LPA1 receptors in stress regulation and sheds light on different neural pathways under normal and vulnerability conditions that can lead to mood disorders.

Quantifying the heritability of task-related brain activation and performance during the N-back working memory task: A twin fMRI study

Working memory-related brain activation has been widely studied, and impaired activation patterns have been reported for several psychiatric disorders. We investigated whether variation in N-back working memory brain activation is genetically influenced in 60 pairs of twins, (29 monozygotic (MZ), 31 dizygotic (DZ); mean age 24.4 ± 1.7S.D.). Task-related brain response (BOLD percent signal difference of 2 minus 0-back) was measured in three regions of interest. Although statistical power was low due to the small sample size, for middle frontal gyrus, angular gyrus, and supramarginal gyrus, the MZ correlations were, in general, approximately twice those of the DZ pairs, with non-significant heritability estimates (14-30%) in the low-moderate range. Task performance was strongly influenced by genes (57-73%) and highly correlated with cognitive ability (0.44-0.55). This study, which will be expanded over the next 3 years, provides the first support that individual variation in working memory-related brain activation is to some extent influenced by genes.

Heritability of working memory brain activation

Although key to understanding individual variation in task-related brain activation, the genetic contribution to these individual differences remains largely unknown. Here we report voxel-by-voxel genetic model fitting in a large sample of 319 healthy, young adult, human identical and fraternal twins (mean ± SD age, 23.6 ±1.8 years) who performed an n-back working memory task during functional magnetic resonance imaging (fMRI) at a high magnetic field (4 tesla). Patterns of task-related brain response (BOLD signal difference of 2-back minus 0-back) were significantly heritable, with the highest estimates (40 - 65%) in the inferior, middle, and superior frontal gyri, left supplementary motor area, precentral and postcentral gyri, middle cingulate cortex, superior medial gyrus, angular gyrus, superior parietal lobule, including precuneus, and superior occipital gyri. Furthermore, high test-retest reliability for a subsample of 40 twins indicates that nongenetic variance in the fMRI brain response is largely due to unique environmental influences rather than measurement error. Individual variations in activation of the working memory network are therefore significantly influenced by genetic factors. By establishing the heritability of cognitive brain function in a large sample that affords good statistical power, and using voxel-by-voxel analyses, this study provides the necessary evidence for task-related brain activation to be considered as an endophenotype for psychiatric or neurological disorders, and represents a substantial new contribution to the field of neuroimaging genetics. These genetic brain maps should facilitate discovery of gene variants influencing cognitive brain function through genome-wide association studies, potentially opening up new avenues in the treatment of brain disorders.

Where there's smoke, there's fire : the brain reactivity of chronic smokers to anti-smoking stimuli

Contexte: Plusieurs études ont démontré que les indices environnementaux associés à la cigarette peuvent provoquer des envies de consommer (« cravings ») chez les fumeurs, ce qui nuit aux efforts d’abandon de la substance et favorise le maintien du tabagisme. Un bon nombre d’études en imagerie cérébrale ont examiné les bases neurophysiologiques de cette caractéristique clinique. Le tabagisme se caractérise aussi par l’incapacité des représentations négatives de la consommation (méfaits médicaux et sociaux) d’influencer la consommation des fumeurs. Étonnamment toutefois, très peu de travaux de recherche se sont intéressés à examiner les bases neurophysiologiques de cette insouciance envers les méfaits de la cigarette chez les fumeurs. En utilisant l'imagerie cérébrale fonctionnelle, l'objectif de cette étude était: d’examiner la réponse neurophysiologique des fumeurs chroniques à des images qui illustrent les effets négatifs de la cigarette (campagne anti-tabac); d’examiner le caractère affectif de cette réactivité utilisant des conditions contrôles (c.-à-d., images aversives non-liées au tabac et appétitives liées au tabac); d'examiner la connectivité fonctionnelle durant cette tâche entre les systèmes affectifs et exécutifs (une interaction qui peut favoriser ou entraver l'impact des évènements aversifs). Méthodes: 30 fumeurs chroniques ont passé une session de neuroimagerie durant laquelle ils devaient regarder des images appétitives et aversives de cigarettes, des images aversives non-reliées au tabac et des images neutres. Résultats: Les images aversives liés au tabagisme suscitent une plus grande activation dans le cortex médial préfrontal, l'amygdale, le gyrus frontal inférieur et le cortex orbitofrontal latéral en comparaison avec les images neutres, mais une moins grande activation dans des structures médiaux / sous-corticales comparé aux images aversives non-reliés et images appétitives reliées aux tabac. L’activité du système exécutif présente une connectivité fonctionnelle négative avec le système affectif lorsque les images aversives sont liées au tabac, mais pas quand elles ne le sont pas. Conclusions: Le modèle d'activation du cerveau observé suggère qu’il y a un biais dans la réactivité des fumeurs chroniques lorsqu’ils observent des représentations négatives de la consommation du tabac. L’activité du système exécutif cérébral semble promouvoir chez les fumeurs une baisse d’activité dans des régions impliquées dans la genèse d’une réponse physiologique affective; il s’agit d’un mécanisme qui permettrait de réduire l’impact persuasif de ces représentations des méfaits de la cigarette sur la consommation des fumeurs.

Gaze fixations predict brain activation during the voluntary regulation of picture-induced negative affect

Recent studies have identified a distributed network of brain regions thought to support cognitive reappraisal processes underlying emotion regulation in response to affective images, including parieto-temporal regions and lateral/medial regions of prefrontal cortex (PFC). A number of these commonly activated regions are also known to underlie visuospatial attention and oculomotor control, which raises the possibility that people use attentional redeployment rather than, or in addition to, reappraisal as a strategy to regulate emotion. We predicted that a significant portion of the observed variance in brain activation during emotion regulation tasks would be associated with differences in how participants visually scan the images while regulating their emotions. We recorded brain activation using fMRI and quantified patterns of gaze fixation while participants increased or decreased their affective response to a set of affective images. fMRI results replicated previous findings on emotion regulation with regulation differences reflected in regions of PFC and the amygdala. In addition, our gaze fixation data revealed that when regulating, individuals changed their gaze patterns relative to a control condition. Furthermore, this variation in gaze fixation accounted for substantial amounts of variance in brain activation. These data point to the importance of controlling for gaze fixation in studies of emotion regulation that use visual stimuli.

Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation

Anhedonia, the loss of pleasure or interest in previously rewarding stimuli, is a core feature of major depression. While theorists have argued that anhedonia reflects a reduced capacity to experience pleasure, evidence is mixed as to whether anhedonia is caused by a reduction in hedonic capacity. An alternative explanation is that anhedonia is due to the inability to sustain positive affect across time. Using positive images, we used an emotion regulation task to test whether individuals with depression are unable to sustain activation in neural circuits underlying positive affect and reward. While up-regulating positive affect, depressed individuals failed to sustain nucleus accumbens activity over time compared with controls. This decreased capacity was related to individual differences in self-reported positive affect. Connectivity analyses further implicated the fronto-striatal network in anhedonia. These findings support the hypothesis that anhedonia in depressed patients reflects the inability to sustain engagement of structures involved in positive affect and reward.

Where, when and why brain activation differs for bilinguals and monolinguals during picture naming and reading aloud

Using functional magnetic resonance imaging, we found that when bilinguals named pictures or read words aloud, in their native or nonnative language, activation was higher relative to monolinguals in 5 left hemisphere regions: dorsal precentral gyrus, pars triangularis, pars opercularis, superior temporal gyrus, and planum temporale. We further demonstrate that these areas are sensitive to increasing demands on speech production in monolinguals. This suggests that the advantage of being bilingual comes at the expense of increased work in brain areas that support monolingual word processing. By comparing the effect of bilingualism across a range of tasks, we argue that activation is higher in bilinguals compared with monolinguals because word retrieval is more demanding; articulation of each word is less rehearsed; and speech output needs careful monitoring to avoid errors when competition for word selection occurs between, as well as within,language.

A model of the dynamic relationship between blood flow and volume changes during brain activation

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen level-dependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBV proportional to CBFPhi has been used extensively in the literature. Two similar models, the Balloon (Buxton et al., 1998) and the Windkessel (Mandeville et al., 1999), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

Activation pattern of neutrophils from blood of elderly individuals with -related denture stomatitis

We have identified impaired neutrophils in elderly individuals which could be involved with -related denture stomatitis (DS), an oral infection predominantly caused by , affecting especially elderly individuals using dental prosthesis. However, specific mechanisms performed by neutrophil contributing to the susceptibility of the elderly to DS are not fully understood. This study evaluated activation features of blood neutrophils from elderly and young individuals with DS. Blood neutrophils cultured with . from elderly subjects secreted decreased levels of CXCL8. However, . challenged-neutrophils from DS patients produced high IL-4 and IL-10, and low GM-CSF levels, regardless of age. Additional elastase activity of neutrophils from both elderly groups was detected after incubation with . , but only neutrophils from elderly DS demonstrated high myeloperoxidase activity. Therefore, DS patients have affected neutrophils, and the advance of age intensifies these damages. In sumamry, individuals with -related denture stomatitis presented variation in the neutrophil phenotype and activation. Such alterations were more intense in neutrophils from infected elderly individuals.

Brain activation during anticipation of sound sequences

Music consists of sound sequences that require integration over time. As we become familiar with music, associations between notes, melodies, and entire symphonic movements become stronger and more complex. These associations can become so tight that, for example, hearing the end of one album track can elicit a robust image of the upcoming track while anticipating it in total silence. Here, we study this predictive “anticipatory imagery” at various stages throughout learning and investigate activity changes in corresponding neural structures using functional magnetic resonance imaging. Anticipatory imagery (in silence) for highly familiar naturalistic music was accompanied by pronounced activity in rostral prefrontal cortex (PFC) and premotor areas. Examining changes in the neural bases of anticipatory imagery during two stages of learning conditional associations between simple melodies, however, demonstrates the importance of fronto-striatal connections, consistent with a role of the basal ganglia in “training” frontal cortex (Pasupathy and Miller, 2005). Another striking change in neural resources during learning was a shift between caudal PFC earlier to rostral PFC later in learning. Our findings regarding musical anticipation and sound sequence learning are highly compatible with studies of motor sequence learning, suggesting common predictive mechanisms in both domains.

Brain activation during craving for alcohol measured by positron emission tomography

OBJECTIVE: Craving for alcohol is probably involved in acquisition and maintenance of alcohol dependence to a substantial degree. However, the brain substrates and mechanisms that underlie alcohol craving await more detailed elucidation. METHOD: Positron emission tomography was used to map regional cerebral blood flow (CBF) in 21 detoxified patients with alcohol dependence during exposure to alcoholic and non-alcoholic beverages. RESULTS: During the alcohol condition compared with the control condition, significantly increased CBF was found in the ventral putamen. Additionally, activated areas included insula, dorsolateral prefrontal cortex and cerebellum. Cerebral blood flow increase in these regions was related to self-reports of craving assessed in the alcoholic patients. CONCLUSIONS: In this investigation, cue-induced alcohol craving was associated with activation of brain regions particularly involved in brain reward mechanisms, memory and attentional processes. These results are consistent with studies on craving for other addictive substances and may offer strategies for more elaborate studies on the neurobiology of addiction.