Peter Boesiger

Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder

BACKGROUNDnAlthough recent neuroimaging and therapeutic transcranial magnetic cortex stimulation (TMS) studies suggest imbalance between left and right dorsolateral prefrontal cortex (DLPFC) in major depressive disorder (MDD) the fundamental neuropsychological characterization of left DLPFC hypoactivity and right DLPFC hyperactivity in MDD remains poorly understood.nnnMETHODSnWe used event-related functional magnetic resonance imaging (fMRI) to investigate neural activity in left and right DLPFC related to unattended (unexpected) and attended (expected) judgment of emotions. Participating in the study were 20 medication-free patients with MDD and 30 healthy subjects.nnnRESULTSnThe MDD patients showed hypoactivity in the left DLPFC during both unattended and attended emotional judgment and hyperactivity in the right DLPFC during attended emotional judgment. In contrast to healthy subjects, left DLPFC activity during emotional judgment was not parametrically modulated by negative emotional valence and was inversely modulated by positive emotional valence in MDD patients. Hyperactivity in the right DLPFC correlated with depression severity.nnnCONCLUSIONSnResults demonstrate that left DLPFC hypoactivity is associated with negative emotional judgment rather than with emotional perception or attention while right DLPFC hyperactivity is linked to attentional modulation. Left-right DLPFC imbalance is characterized in neuropsychological regard, which bridges the gap from resting metabolism and therapeutic repetitive transcranial magnetic stimulation effects to functional neuroanatomy of altered emotional-cognitive interaction in MDD.

Altered Negative BOLD Responses in the Default-Mode Network during Emotion Processing in Depressed Subjects

Studies using functional magnetic resonance imaging (fMRI) show predominant negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network such as the pregenual anterior cingulate cortex, the ventromedial prefrontal cortex, and the posterior cingulate cortex. Patients with major depressive disorder (MDD) show emotional–cognitive disturbances, which have been associated with alterations within the default-mode network. However, it remains unclear whether these default-mode network alterations are related to abnormalities in NBRs. We therefore investigated neural activity in the default-mode network during different emotional tasks in patients with MDD in an event-related fMRI design. MDD patients showed significantly reduced NBRs in several regions of the default-mode network. Decreased NBRs in MDD patients correlated with depression severity and feelings of hopelessness. In sum, our findings demonstrate that default-mode network NBRs are reduced in MDD and modulate these patients abnormally negative emotions.

The Relationship Between Aberrant Neuronal Activation in the Pregenual Anterior Cingulate, Altered Glutamatergic Metabolism, and Anhedonia in Major Depression

CONTEXTnMajor depressive disorder (MDD) is characterized by diverse metabolic and functional abnormalities that occur in, among other regions, the pregenual anterior cingulate cortex (pgACC), a cortical region linked to anhedonia.nnnOBJECTIVESnTo contextualize metabolic, functional, and clinical parameters and thus to reveal cellular mechanisms related to anhedonia.nnnDESIGNnThe pgACC was investigated using a combined functional magnetic resonance imaging and magnetic resonance spectroscopic approach. Negative blood oxygenation level-dependent (BOLD) activations in the pgACC were assessed during emotional stimulation. Quantitative J-resolved magnetic resonance spectroscopy in the pgACC enabled simultaneous determination of glutamine, glutamate, N-acetylaspartate, glucose, and gamma-aminobutyric acid concentrations. Subjective emotional intensity ratings as well as various clinical parameters were determined.nnnSETTINGnThe patients were recruited and evaluated in the Department of Psychiatry, University of Zurich, while the measurements were performed in the Institute of Biomedical Engineering, University of Zurich and the Technical University Zurich.nnnPARTICIPANTSnNineteen unmedicated patients with MDD and 24 healthy subjects.nnnMAIN OUTCOME MEASURESnReduced glutamine levels and lower functional responses in pgACC in anhedonic depressed patients were expected to be the predominant effect of abnormal glutamatergic transmission. It was further tested if, among patients, the ratings of emotional intensity on visual stimulation predicted the amount of metabolic and functional alterations in terms of reduced relative metabolite concentrations and BOLD changes.nnnRESULTSnPatients with highly anhedonic MDD show decreased glutamine but normal glutamate and gamma-aminobutyric acid concentrations, with glutamine concentrations being dissociated from glucose concentrations. Glutamate and N-acetylaspartate concentrations in pgACC correlate with negative BOLD responses induced by emotional stimulation in MDD; whereas in healthy subjects, negative BOLD responses correlate with gamma-aminobutyric acid instead. Negative BOLD responses as well as glutamate and N-acetylaspartate concentrations correlate with emotional intensity ratings, an anhedonia surrogate, in those with MDD but not in healthy subjects.nnnCONCLUSIONnAberrant neuronal activation patterns of the pgACC in anhedonic depression are related to deficits of glutamatergic metabolism.

Evaluation of left ventricular segmental wall motion in hypertrophic cardiomyopathy with myocardial tagging.

BackgroundSegmental wall motion was assessed noninvasively in eight patients with hypertrophic cardiomyopathy and six healthy volunteers by magnetic resonance myocardial tagging. Methods and ResultsLocalization scans were performed for determination of the true short-axis views of the left ventricle (double-angulated view). Spatial modulation of magnetization was used to produce a rectangular grid of landmarks. Distortion of the grid was assessed at end diastole, mid systole, and end systole with multiphase gradient echos. Image sets were acquired at three different planes, namely, the base, the equator, and the apex. Quantitative evaluation was carried out by computer-assisted image analysis. Each individual grid crossing point was identified automatically and the displacement calculated. A polar coordinate system with the center of gravity as motion reference point was chosen to assess fractional rotation and radial displacement at the endocardial, midwall, and epicardial layers of the septal, anterior, posterior, and inferior regions. A wringing motion of the left ventricle with a clockwise rotation of 5.0 ± 2.4° at the base and a counterclockwise rotation of −9.6 ± 2.9° at the apex was observed in control subjects. An equal rotation of 5.0 ± 2.5° at the base and a slightly reduced rotation of −7.3 ± 5.2° at the apex was found in patients with hypertrophic cardiomyopathy. A transmural gradient in fractional rotation and radial displacement was observed, with the highest values in the endocardial layer. Rotation in patients with hypertrophic cardiomyopathy was significantly less than in normal volunteers in the posterior region of the equatorial and apical planes. Furthermore, radial displacement was significantly reduced in the septum and inferior wall. In the anterior and posterior wall segments, a reduction of the radial displacement was observed only in the epicardium and midwall layers. ConclusionsMagnetic resonance myocardial tagging allows the noninvasive assessment of regional wall motion. Both in normal volunteers and in patients with hypertrophic cardiomyopathies, cardiac motion occurs in a complex mode, with the base and the apex rotating in opposite directions and the equatorial plane as a transitional zone (wringing motion). A reduced cardiac rotation can be observed in patients with hypertrophic cardiomyopathy mainly in the posterior region, whereas a reduced radial displacement is found in the inferior septal zone.

Increased self‐focus in major depressive disorder is related to neural abnormalities in subcortical‐cortical midline structures

Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and reflect upon their self, which has been described as increased self‐focus. Although subcortical‐cortical midline structures have been associated with reflection and introspection of oneself in healthy subjects, the neural correlates of the abnormally increased attribution of negative emotions to oneself, i.e. negative self‐attribution, as hallmark of the increased self‐focus in MDD remain unclear. The aim of the study was, therefore, to investigate the neural correlates during judgment of self‐relatedness of positive and negative emotional stimuli thereby testing for emotional self‐attribution. Using fMRI, we investigated 27 acute MDD patients and compared them with 25 healthy subjects employing a paradigm that focused on judgment of self‐relatedness when compared with mere perception of the very same emotional stimuli. Behaviourally, patients with MDD showed significantly higher degrees of self‐relatedness of specifically negative emotional stimuli when compared with healthy subjects. Neurally, patients with MDD showed significantly lower signal intensities in various subcortical and cortical midline regions like the dorsomedial prefrontal cortex (DMPFC), supragenual anterior cingulate cortex, precuneus, ventral striatum (VS), and the dorsomedial thalamus (DMT). Signal changes in the DMPFC correlated with depression severity and hopelessness whereas those in the VS and the DMT were related to judgment of self‐relatedness of negative emotional stimuli. In conclusion, we present first evidence that the abnormally increased negative self‐attribution as hallmark of the increased self‐focus in MDD might be mediated by altered neural activity in subcortical‐cortical midline structures. Hum Brain Mapp, 2009.

Segregated neural representation of distinct emotion dimensions in the prefrontal cortex-an fMRI study.

Emotions are frequently characterized by distinct dimensions such as valence, intensity, and recognition. However, the exact neural representation of these dimensions in different prefrontal cortical regions remains unclear. One of the problems in revealing prefrontal cortical representation is that the very same regions are also involved in cognitive functions associated with emotion processing. We therefore conducted an fMRI study involving the viewing of emotional pictures (using the International Affective Picture System; IAPS) and controlled for associated cognitive processing like judgment and preceding attention. Functional activation was correlated with subjective post-scanning ratings of valence, intensity, and recognition. Valence significantly correlated with the functional response in ventromedial prefrontal cortex (VMPFC) and dorsolateral prefrontal cortex (DLPFC), intensity with activation in ventrolateral prefrontal cortex (VLPFC) and dorsomedial prefrontal cortex (DMPFC), and recognition with the functional response in perigenual anterior cingulate cortex (PACC). In conclusion, our results indicate segregated neural representation of the different emotion dimensions in different prefrontal cortical regions.

Transfer insensitive labeling technique (TILT): application to multislice functional perfusion imaging.

Cerebral blood flow can be studied in a multislice mode with a recently proposed perfusion sequence using inversion of water spins as an endogenous tracer without magnetization transfer artifacts. The magnetization transfer insensitive labeling technique (TILT) has been used for mapping blood flow changes at a microvascular level under motor activation in a multislice mode. In TILT, perfusion mapping is achieved by subtraction of a perfusion‐sensitized image from a control image. Perfusion weighting is accomplished by proximal blood labeling using two 90° radiofrequency excitation pulses. For control preparation the labeling pulses are modified such that they have no net effect on blood water magnetization. The percentage of blood flow change, as well as its spatial extent, has been studied in single and multislice modes with varying delays between labeling and imaging. The average perfusion signal change due to activation was 36.9 ± 9.1% in the single‐slice experiments and 38.1 ± 7.9% in the multislice experiments. The volume of activated brain areas amounted to 1.51 ± 0.95 cm3 in the contralateral primary motor (M1) area, 0.90 ± 0.72 cc in the ipsilateral M1 area, 1.27 ± 0.39 cm3 in the contralateral and 1.42 ± 0.75 cm3 in the ipsilateral premotor areas, and 0.71 ± 0.19 cm3 in the supplementary motor area.J. Magn. Reson. Imaging 1999;9:454–461.

Affective judgment and beneficial decision making: ventromedial prefrontal activity correlates with performance in the Iowa Gambling Task.

Damasio proposes in his somatic marker theory that not only cognitive but also affective components are critical for decision making. Since affective judgment requires an interplay between affective and cognitive components, it might be considered a key process in decision making that has been linked to neural activity in ventromedial prefrontal cortex (VMPFC). Using functional magnetic resonance imaging (fMRI), we examined the relationship between VMPFC, emotionally (unexpected)‐ and cognitively (expected)‐accentuated affective judgment, and beneficial decision making (Iowa Gambling Task; IGT) in healthy subjects. Neuronal activity in the VMPFC during unexpected affective judgment significantly correlated with both global and final performance in the IGT task. These findings suggest that the degree to which subjects recruit the VMPFC during affective judgment is related to beneficial performance in decision making in gambling. Hum Brain Mapp 2006.

Resolving fiber crossing using advanced fast marching tractography based on diffusion tensor imaging.

Magnetic resonance diffusion tensor tractography is a powerful tool for the non-invasive depiction of the white matter architecture in the human brain. However, due to limitations in the underlying tensor model, the technique is often unable to reconstruct correct trajectories in heterogeneous fiber arrangements, such as axonal crossings. A novel tractography method based on fast marching (FM) is proposed which is capable of resolving fiber crossings and also permits trajectories to branch. It detects heterogeneous fiber arrangements by incorporating information from the entire diffusion tensor. The FM speed function is adapted to the local tensor characteristics, allowing in particular to maintain the front evolution direction in crossing situations. In addition, the FMs discretization error is reduced by increasing the number of considered possible front evolution directions. The performance of the technique is demonstrated in artificial data and in the healthy human brain. Comparisons with standard FM tractography and conventional line propagation algorithms show that, in the presence of interfering structures, the proposed method is more accurate in reconstructing trajectories. The in vivo results illustrate that the elucidated major white matter pathways are consistent with known anatomy and that multiple crossings and tract branching are handled correctly.

Reduced negative BOLD responses in the default-mode network and increased self-focus in depression

Abstract Objectives. Functional imaging studies in major depressive disorder (MDD) indicate abnormal resting state neural activity and negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network (DMN). Methods. Since activity in DMN regions has been associated with self-relatedness, we investigated neural activity in these regions during self-related emotional judgement and passive picture viewing in 25 patients with MDD and 25 healthy controls in an event-related fMRI design. Results. Behaviourally, MDD subjects showed significantly higher ratings of self-relatedness that also correlated with depression symptoms such as hopelessness. Neuroimaging results in MDD patients showed significantly lower negative BOLD responses (NBRs) in anterior medial cortical regions during judgement of self-relatedness while posterior medial regions showed increased NBRs. Unlike in healthy subjects, the anterior medial cortical NBRs were no longer parametrically modulated by the degree of self-relatedness in MDD patients. Conclusions. Our findings suggest that reduced NBRs in the anterior regions of the default-mode network may signify decoupling from self-relatedness in MDD patients with the consecutive abnormal increase of self-focus.