Functional reorganization of the auditory pathways (or lack thereof) in callosal agenesis is predicted by monaural sound localization performance.

Neuroimaging studies show that permanent peripheral lesions such as unilateral deafness cause functional reorganization in the auditory pathways. However, functional reorganization of the auditory pathways as a result of higher-level damage or abnormalities remains poorly investigated. A relatively recent behavioural study points to functional changes in the auditory pathways in some, but interestingly not in all, of the acallosal individuals that were tested. The present study uses fMRI to investigate auditory activities in both cerebral hemispheres in those same acallosal subjects in order to directly investigate the contributions of ipsilateral and contralateral functional pathways reorganization. Predictions were made that functional reorganization could be predicted from behavioural performance. As reported previously in a number of neuroimaging studies, results showed that in neurologically intact subjects, binaural stimulation induced balanced activities between both hemispheres, while monaural stimulation induced strong contralateral activities and weak ipsilateral activities. In accordance with behavioural predictions, some acallosal subjects showed patterns of auditory cortical activities that were similar to those observed in neurologically intact subjects while others showed functional reorganization of the auditory pathways. Essentially they showed a significant increase and a significant decrease of neural activities in the contralateral and/or ipsilateral pathways, respectively. These findings indicate that at least in some acallosal subjects, functional reorganization inside the auditory pathways does contribute to compensate for the absence of the corpus callosum.

Global motion stimuli and form-from-motion stimuli: common characteristics and differential activation patterns.

We used functional Magnetic Resonance Imaging (fMRI) to explore the areas underlying the processing of two similar motion stimuli that evoke different types of processing. The results indicated that while form-from-motion (FFM) stimuli activated both lateral occipital complex (LOC) and MT complex (MT+), only the LOC remained significantly activated when contrasted with a global motion stimulus (GMS) with different coherence levels. Because of the large number of common characteristics shared between the stimuli, this contrast enabled us to isolate the regions implicated in form processing. The GMS on the other hand only activated MT+, reaching maximal intensity for low coherence. Overall, these data illustrate how two similar motion stimuli can elicit the participation of different cortical visual regions.

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.

Individual variation in neural correlates of sadness in children: a twin fMRI study.

Functional neuroimaging studies show substantial individual variation in brain activation accompanying the experience of emotion, including sadness. Here we used functional magnetic resonance imaging (fMRI) in 104 pairs of 8-year-old twins (47 MZ, 57 DZ) to assess genetic-environmental contributions to individual differences in neural activation in two prefrontal cortex (PFC) areas previously shown to be involved in sadness. No genetic effects were found for any area, individual environmental factors entirely accounting for individual variation in brain activation related to sadness. Sadness being the prevailing mood in depression, these findings may be of relevance to the etiology of childhood depressive disorders.

Increased striatal gray matter densities in patients with schizophrenia and substance use disorder: a voxel-based morphometry study.

We sought to investigate the link between substance abuse and increased striatal gray matter densities (GMD) in schizophrenia, using voxel-based morphometry (VBM). Increased striatal GMD were found in patients with schizophrenia and substance use disorder (n=12), but not schizophrenia only patients (n=11), compared to healthy volunteers (n=15).

Processing of social emotion in patients with schizophrenia and substance use disorder: an fMRI study.

The lifetime prevalence of substance use disorders among schizophrenia patients is close to 50%. The negative consequences of substance abuse in schizophrenia are well documented, but the aetiology of this comorbid condition remains unknown. Mounting evidence suggests that dual-diagnosis patients have fewer negative symptoms and better social skills, compared to non-abusing patients. We hypothesized that schizophrenia patients with substance use disorder (SCZ-SUD) would display increased cerebral activations in response to socioemotional stimuli, relative to patients with no SUD (SCZ). Schizophrenia patients (DSM-IV criteria) were divided into two groups: patients with (n=12) and without (n=11) substance use (alcohol and/or cannabis). Using functional magnetic resonance imaging (fMRI), patients were scanned during passive viewing of an emotional film excerpt with social content. Loci of activation were identified in the right mPFC (BA 10) and the right supramarginal gyrus (BA 40) in SCZ-SUD patients, and in the left pons in SCZ patients. Relative to SCZ patients, increased loci of activation were found in the right superior parietal cortex (BA 7) and the left medial prefrontal cortex (BA 10) in SCZ-SUD patients, who reported higher subjective emotional experience on a self-report scale. To our knowledge, this is the first fMRI study to assess social emotions in dual-diagnosis schizophrenia. Our results suggest that socioemotional processing may be less impaired in dual diagnosis, which recruited brain regions seemingly involved in "social cognition." Further studies on the topic are warranted.

Neural correlates of the affect regulation model in schizophrenia patients with substance use history: a functional magnetic resonance imaging study.

BACKGROUND: The lifetime prevalence of substance use disorders among schizophrenia patients is close to 50%. The negative consequences of substance abuse in schizophrenia are well documented, but the etiology of this comorbid condition remains unknown. According to the affect regulation model, schizophrenia patients abuse drugs in order to cope with their negative affects. Supporting the model, clinical studies have shown that dual-diagnosis patients have less blunting of affect and that they experience more negative affect. We hypothesized that patients with a history of substance use would have increased cerebral activations in response to aversive stimuli when compared to abstinent patients. METHOD: Schizophrenia patients were divided into 2 groups: patients with (SCZ-SU group; N = 12) and without (SCZ group; N = 11) a current or past substance use disorder (alcohol, cannabis, and/or LSD). Diagnoses were made according to DSM-IV criteria. Using functional magnetic resonance imaging (fMRI), patients were scanned during passive viewing of emotionally negative pictures (International Affective Picture System). Data were gathered from September 2001 to December 2003. RESULTS: Subjectively, the emotional experience induced by viewing the negative pictures was rated significantly higher in the SCZ-SU group than in the SCZ group (p = .008). Neurally, in the SCZ-SU group, significant loci of activation were identified in the right medial prefrontal cortex (Brodmann's area [BA] 10), left medial prefrontal cortex (BA 10), right orbitofrontal cortex (BA 47), and left amygdala. No significant loci of activation were observed in the SCZ group. CONCLUSIONS: These results suggest that the functioning of the medial prefrontal cortex, thought to be impaired in patients with prominent negative symptoms, is more preserved in dual-diagnosis schizophrenia. This relative preservation could be primary or secondary to substance use.

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.

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.

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

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.

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.

Restoration of frontal activation during a treatment with quetiapine: an fMRI study of blunted affect in schizophrenia.

This study investigated changes in cerebral activation related to emotion processing in schizophrenia patients with blunted or flat affect (FA+) during treatment with quetiapine. Using functional magnetic resonance imaging (fMRI), brain activation in 12 FA+ schizophrenia patients during passive viewing of sad film excerpts was studied before and after a median of 5.5-months treatment with quetiapine. Random-effects 'paired sample t-test' analyses of brain activation before quetiapine (contrast=sad-neutral, before-after) revealed significant activation in the brainstem (pons, medulla). After quetiapine, the same contrast showed significant prefrontal activation (BA 9, 10 and 11). Activation of key prefrontal areas involved in emotion processing and significant symptoms improvement as measured by the subjective rating scale and PANSS suggests the potential effect of quetiapine in improving blunted affect related symptoms (i.e., passive withdrawal, emotional withdrawal, social avoidance) in schizophrenia.

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.

Separate neural circuits for primary emotions? Brain activity during self-induced sadness and happiness in professional actors.

The question of whether distinct or similar neural substrates underlie primary emotions has not been resolved yet. To address this issue, we used fMRI to scan professional actors during self-induced states of sadness and happiness. Results demonstrated that, relative to an emotionally Neutral state, both the Sad and the Happy states were associated with significant loci of activation, bilaterally, in the orbitofrontal cortex, and in the left medial prefrontal cortex, left ventrolateral prefrontal cortex, left anterior temporal pole, and right pons. These loci of activation were localized distinctly within these regions, that is, in different sub-regions. These results suggest that sadness and happiness may be associated with similar brain regions but distinct sub-regions and neural circuits.

Excitable gap composition in the presence of antiarrhythmic drugs in common human atrial flutter.

BACKGROUND AND OBJECTIVE: Recurrence of atrial flutter (AFl) on antiarrhythmic drugs is frequently observed. To determine the reasons for drug inefficacy, the electrophysiological parameters of AFl were studied in eight patients without drug, six patients on sotalol (Sot), eight patients on amiodarone (Amio) and four patients on propafenone (PPF) who presented to the electrophysiology laboratory for conversion of AFl by rapid atrial pacing. METHODS: A quadripolar electrode catheter was positioned in the right atrium in the pathway of the AFl circuit. The duration and composition of the excitable gap (EG) were determined by premature stimuli during AFl. RESULTS: The EG in AFl recurring on Sot (80 +/- 25 ms), Amio (78 +/- 13 ms) and PPF (83 +/- 26 ms) was not significantly different from that without drug (88 +/- 14 ms). Furthermore, a fully excitable portion of the EG was present whether with or without drug. CONCLUSIONS: AFl recurrence on Amio, PPF or Sot is associated with the continued presence of an EG and fully excitable portion. These findings explain the persistent viability of the AFl circuit despite drug therapy in these patients.

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.

"Change the mind and you change the brain": effects of cognitive-behavioral therapy on the neural correlates of spider phobia.

Questions pertaining to the neurobiological effects of psychotherapy are now considered among the most topical in psychiatry. With respect to this issue, positron emission tomography (PET) findings indicate that cognitive and behavioral modifications, occurring in a psychotherapeutic context, can lead to regional brain metabolic changes in patients with major depression or obsessive-compulsive disorder. The goal of the present functional magnetic resonance imaging (fMRI) study, which constitutes the first neuroimaging investigation of the effects of cognitive-behavioral therapy (CBT) using an emotional activation paradigm, was to probe the effects of CBT on the neural correlates of spider phobia. In order to do so, fMRI was used in subjects suffering from spider phobia (n = 12) to measure, before and after effective CBT, regional brain activity during the viewing of film excerpts depicting spiders. Normal control subjects were also scanned (once) while they were exposed to the same film excerpts. Results showed that, in phobic subjects before CBT, the transient state of fear triggered, during the viewing of the phobogenic stimuli, was correlated with significant activation of the right dorsolateral prefrontal cortex (Brodmann area-BA 10), the parahippocampal gyrus, and the visual associative cortical areas, bilaterally. For normal control subjects (n = 13), only the left middle occipital gyrus and the right inferior temporal gyrus were significantly activated. In phobic subjects before CBT, the activation of the dorsolateral prefrontal cortex (BA 10) may reflect the use of metacognitive strategies aimed at self-regulating the fear triggered by the spider film excerpts, whereas the parahippocampal activation might be related to an automatic reactivation of the contextual fear memory that led to the development of avoidance behavior and the maintenance of spider phobia. After successful completion of CBT, no significant activation was found in the dorsolateral prefrontal cortex (BA 10) or the parahippocampal gyrus. These findings suggest that a psychotherapeutic approach, such as CBT, has the potential to modify the dysfunctional neural circuitry associated with anxiety disorders. They further indicate that the changes made at the mind level, within a psychotherapeutic context, are able to functionally "rewire" the brain.