Boualem Mensour

Neural circuitry underlying voluntary suppression of sadness

BACKGROUND The ability to voluntarily self-regulate negative emotion is essential to a healthy psyche. Indeed, a chronic incapacity to suppress negative emotion might be a key factor in the genesis of depression and anxiety. Regarding the neural underpinnings of emotional self-regulation, a recent functional neuroimaging study carried out by our group has revealed that the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex are involved in voluntary suppression of sexual arousal. As few things are known, still, with respect to the neural substrate underlying volitional self-regulation of basic emotions, here we used functional magnetic resonance imaging to identify the neural circuitry associated with the voluntary suppression of sadness. METHODS Twenty healthy female subjects were scanned during a Sad condition and a Suppression condition. In the Sad condition, subjects were instructed to react normally to sad film excerpts whereas, in the Suppression condition, they were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. RESULTS Transient sadness was associated with significant loci of activation in the anterior temporal pole and the midbrain, bilaterally, as well as in the left amygdala, left insula, and right ventrolateral prefrontal cortex (VLPFC) (Brodmann area [BA] 47). Correlational analyses carried out between self-report ratings of sadness and regional blood oxygen level dependent (BOLD) signal changes revealed the existence of positive correlations in the right VLPFC (BA 47), bilaterally, as well as in the left insula and the affective division of the left anterior cingulate gyrus (BA 24/32). In the Suppression condition, significant loci of activation were noted in the right DLPFC (BA 9) and the right orbitofrontal cortex (OFC) (BA 11), and positive correlations were found between the self-report ratings of sadness and BOLD signal changes in the right OFC (BA 11) and right DLPFC (BA 9). CONCLUSIONS These results confirm the key role played by the DLPFC in emotional self-regulation. They also indicate that the right DLPFC and right OFC are components of a neural circuit implicated in voluntary suppression of sadness.

Effect of neurofeedback training on the neural substrates of selective attention in children with attention-deficit/hyperactivity disorder: A functional magnetic resonance imaging study

Attention Deficit Hyperactivity Disorder (AD/HD) is a neurodevelopmental disorder mainly characterized by impairments in cognitive functions. Functional neuroimaging studies carried out in individuals with AD/HD have shown abnormal functioning of the anterior cingulate cortex (ACC) during tasks involving selective attention. In other respects, there is mounting evidence that neurofeedback training (NFT) can significantly improve cognitive functioning in AD/HD children. In this context, the present functional magnetic resonance imaging (fMRI) study was conducted to measure the effect of NFT on the neural substrates of selective attention in children with AD/HD. Twenty AD/HD children--not taking any psychostimulant and without co-morbidity-participated to the study. Fifteen children were randomly assigned to the Experimental (EXP) group (NFT), whereas the other five children were assigned to the Control (CON) group (no NFT). Subjects from both groups were scanned 1 week before the beginning of the NFT (Time 1) and 1 week after the end of this training (Time 2), while they performed a Counting Stroop task. At Time 1, for both groups, the Counting Stroop task was associated with significant loci of activation in the left superior parietal lobule. No activation was noted in the ACC. At Time 2, for both groups, the Counting Stroop task was still associated with significant activation of the left superior parietal lobule. This time, however, for the EXP group only there was a significant activation of the right ACC. These results suggest that in AD/HD children, NFT has the capacity to normalize the functioning of the ACC, the key neural substrate of selective attention.

Neural basis of emotional self-regulation in childhood

Emotional self-regulation plays a pivotal role in socialization and moral development. This capacity critically depends on the development of the prefrontal cortex (PFC). The present functional magnetic resonance imaging study was conducted to identify the neural circuitry underlying voluntary self-regulation of sadness in healthy girls (aged 8-10). A 2 x 2 factorial design was implemented with Emotion (No Sadness vs. Sadness) and Regulation (No Reappraisal vs. Reappraisal) as factors. In the No Reappraisal conditions, subjects were instructed to react normally to neutral and sad film excerpts whereas in the Reappraisal conditions, subjects were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. A significant interaction of the Emotion and Regulation factors revealed that reappraisal of sad film excerpts was associated with bilateral activations of the lateral PFC (LPFC; Brodmann areas [BA] 9 and 10), orbitofrontal cortex (OFC; BA 11), and medial PFC (BA 9 and 10). Significant loci of activations were also detected in the right anterior cingulate cortex (BA 24/32) and right ventrolateral PFC (BA 47). In an identical study previously conducted by our group in adult women [Biol Psychiatry 53 (2003) 502], reappraisal of sad film excerpts was associated with activation of the right OFC (BA 11) and right LPFC (BA 9). The greater number of prefrontal loci of activation found in children relative to adults during voluntary self-regulation of sadness may be related to the immaturity of the prefronto-limbic connections in childhood.

The impact of individual differences on the neural circuitry underlying sadness

Several functional neuroimaging studies have been carried out in healthy subjects to investigate the neural correlates of sadness. Importantly, there is little consistency among the results of these studies. Hypothesizing that individual differences may account for the discrepancies among these investigations, we conducted two functional magnetic resonance imaging (fMRI) studies to identify the neural circuitry underlying this basic emotion. In these two methodologically identical studies, two different groups (n = 10 for each study) of healthy female subjects were scanned while they were experiencing a transient state of sadness induced by viewing sad film excerpts. In the first of these studies, sadness was correlated with significant loci of activation in the anterior temporal pole and insula (P < 0.05, corrected). In the second study, however, sadness was correlated with significant activation in the orbitofrontal and medial prefrontal cortices (P < 0.05, corrected). In addition, individual statistical parametric maps revealed a marked degree of interindividual variability in both Study 1 and Study 2. These results strongly support the view that individual differences may be responsible for the inconsistencies found in the literature regarding the neural substrates of sadness and of other basic emotions. These findings also suggest that individual data should be reported in addition to group data, because they provide useful information about the variability present in the subjects investigated and, thus, about the typicality and generalizability of the results.

Brain activity during emotionally negative pictures in schizophrenia with and without flat affect : An fMRI study

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.

Neural correlates of sad feelings in healthy girls

Emotional development is indisputably one of the cornerstones of personality development during infancy. According to the differential emotions theory (DET), primary emotions are constituted of three distinct components: the neural-evaluative, the expressive, and the experiential. The DET further assumes that these three components are biologically based and functional nearly from birth. Such a view entails that the neural substrate of primary emotions must be similar in children and adults. Guided by this assumption of the DET, the present functional magnetic resonance imaging study was conducted to identify the neural correlates of sad feelings in healthy children. Fourteen healthy girls (aged 8-10) were scanned while they watched sad film excerpts aimed at externally inducing a transient state of sadness (activation task). Emotionally neutral film excerpts were also presented to the subjects (reference task). The subtraction of the brain activity measured during the viewing of the emotionally neutral film excerpts from that noted during the viewing of the sad film excerpts revealed that sad feelings were associated with significant bilateral activations of the midbrain, the medial prefrontal cortex (Brodmann area [BA] 10), and the anterior temporal pole (BA 21). A significant locus of activation was also noted in the right ventrolateral prefrontal cortex (BA 47). These results are compatible with those of previous functional neuroimaging studies of sadness in adults. They suggest that the neural substrate underlying the subjective experience of sadness is comparable in children and adults. Such a similitude provides empirical support to the DET assumption that the neural substrate of primary emotions is biologically based.

Reorganization of the auditory, visual and multimodal areas in early deaf individuals.

Plasticity resulting from early sensory deprivation has been investigated in both animals and humans. After sensory deprivation, brain areas that are normally associated with the lost sense are recruited to carry out functions in the remaining intact modalities. Previous studies have reported that it is almost exclusively the visual dorsal pathway which is affected by auditory deprivation. The purpose of the current study was to further investigate the possible reorganization of visual ventral stream functions in deaf individuals in both the auditory and the visual cortices. Fifteen pre-lingual profoundly deaf subjects were compared with a group of 16 hearing subjects. We used fMRI (functional magnetic resonance imaging) to explore the areas underlying the processing of two similar visual motion stimuli that however were designed to evoke different types of processing: (1) a global motion stimulus (GMS) which preferentially activates regions of the dorsal visual stream, and (2) a form-from-motion (FFM) stimulus which is known to recruit regions from both visual streams. No significant differences between deaf and hearing individuals were found in target visual and auditory areas when the motion and form components of the stimuli were isolated (contrasted with a static visual image). However, increases in activation were found in the deaf group in the superior temporal gyrus (BA 22 and 42) and in an area located at the junction of the parieto-occipital sulcus and the calcarine fissure (encompassing parts of the cuneus, precuneus and the lingual gyrus) for the GMS and FFM conditions as well as for the static image, relative to a baseline condition absent of any visual stimulation. These results suggest that the observed cross-modal recruitment of auditory areas in deaf individuals does not appear to be specialized for motion processing, but rather is present for both motion and static visual stimuli.

Differential hemodynamic brain activity in schizophrenia patients with blunted affect during quetiapine treatment

Abstract: Blood-oxygenation-level-dependent (BOLD) brain changes underlying response to quetiapine were examined using passive viewing of emotionally negative stimuli. Twelve DSM-IV schizophrenia patients with blunted affect (BA+) were scanned before and after 22 weeks of quetiapine treatment. Whole-brain, voxel-based methods were used to assess the differential hemodynamic response to quetiapine. In addition, a post hoc comparison to an independent group of 11 schizophrenia patients without blunted affect (BA−) was performed to compare them with BA+ (postquetiapine) in response to emotion processing. A 22-week treatment with quetiapine resulted in significant clinical improvement in the 12 study completers (mean ± SD posttreatment PANSS blunted affect score of 5.50 ± 0.76 at baseline to 2.08 ± 1.00 at end point; t = 7.78, df = 11, P < 0.0001). Treatment response was associated with significant BOLD changes: increases in prefrontal cortex activation particularly in the right dorsolateral prefrontal cortex (DLPFC, BA 46) and the right anterior cingulate cortex (ACC, BA 32); and in the left putamen, right anterior temporal pole (ATP), and right amygdala. Conversely, before treatment with quetiapine, the same subjects activated the midbrain bilaterally and the right pons. The post hoc conjunctional analyses demonstrated that BA− subjects activated the left ACC, left insula, left ATP (BA 21), left ATP (BA 38), left amygdala, and right medial prefrontal cortex. Quetiapine seems to affect clinical recovery by modulating the functioning of specific brain regions. Unique BOLD changes in the putamen and DLPFC with quetiapine, in the BA+ postquetiapine, may reflect modality-specific effects. Controlled studies are needed to further assess these preliminary findings.

Increased grey matter densities in schizophrenia patients with negative symptoms after treatment with quetiapine : a voxel-based morphometry study

Among new-generation antipsychotics, quetiapine was found to be associated with a partial ‘normalization’ of reduced functional activation in prefrontal and temporal areas and studies conducted by our group found a clinical improvement in negative symptoms in addition to restoration of frontal activation in schizophrenia patients with blunted affect after treatment with quetiapine. Here we investigated the parallelism between improved clinical symptoms and grey mater density (GMD) changes in the frontal region after quetiapine treatment in 15 schizophrenia patients. We hypothesize that improvement in clinical symptoms will be associated with change in GMD in prefrontal regions of interest. By using voxel-based morphometry, paired t-test random-effect analysis showed a significant increase in GMD bilaterally in the inferior frontal cortex/orbitofrontal gyrus and anterior cingulate cortex after 5.5 months of treatment with quetiapine. This GMD increase was associated with a significant improvement in negative symptoms. When GMD was correlated with psychiatric assessment scores, there was a negative correlation between GMD in the anterior cingulate cortex and the Rating Scale for Emotional Blunting score (r=−665, P=0.008) and between the orbitofrontal gyrus and the total Positive and Negative Syndrome Scale negative score (r=−764, P=0.001). Results suggest that increased GMD in some frontal regions are associated with an improvement of negative symptoms. Although not unique to quetiapine, it would be reasonable to attribute the GMD changes in the study to treatment.

Neural correlates of sad feelings in schizophrenia with and without blunted affect.

Objective: There have been reports that patients with schizophrenia have decreased activity in the prefrontal cortex during emotion processing. However, findings have been confounded by sample nonspecificity and explicit cognitive task interference with emotion processing. We aimed to further investigate this by examining the ventrolateral prefrontal cortex (VLPFC) activation in response to the passive viewing of sad film excerpts. Methods: We presented film excerpts depicting sad and neutral social situations to 25 schizophrenia patients (14 with blunted affect [BA+] and 11 without blunted affect [BA-]) in an implicit perception task to evoke prefronto-limbic activity illustrated by blood oxygenation level–dependent functional magnetic resonance imaging. Results: A random-effects analysis (2-sample t test) using statistical parametric mapping indicated that BA+ patients differed from BA–patients at a 0.05 level (P corrected for multiple comparisons). Consistent with our a priori hypothesis, BA–patients (relative to BA+ patients) showed significant activation in the right VLPFC. An exploratory analysis revealed the following loci of activation: caudate nucleus, VLPFC, middle prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, and anterior temporal pole in the BA–group; and hippocampus, cerebellum, anterior temporal pole, and midbrain in the BA+ group. Conclusions: We observed not only hypofrontality in the BA+ group but also dysfunctional circuitry distributed throughout the brain. The temporal and midbrain activation seen in the BA+ group may indicate that these brain regions were working harder to compensate for inactivation in other regions. These distributed dysfunctional circuits may form the neural basis of blunted affect through impairment of emotion processing in the brain that prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as blunted affect.