Negative BOLD Response Research Articles

Vascular Steal Explains Early Paradoxical Blood Oxygen Level-Dependent Cerebrovascular Response in Brain Regions with Delayed Arterial Transit Times

Introduction: Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) during manipulation of inhaled carbon dioxide (CO₂) can be used to measure cerebrovascular reactivity (CVR) and map regions of exhausted cerebrovascular reserve. These regions exhibit a reduced or negative BOLD response to inhaled CO₂. In this study, we sought to clarify the mechanism behind the negative BOLD response by investigating its time delay (TD). Dynamic susceptibility contrast (DSC) MRI with the injection of a contrast agent was used as the gold standard in order to provide measurement of the blood arrival time to which CVR TD could be compared. We hypothesize that if negative BOLD responses are the result of a steal phenomenon, they should be synchronized with positive BOLD responses from healthy brain tissue, even though the blood arrival time would be delayed. Methods: On a 3-tesla MRI system, BOLD CVR and DSC images were collected in a group of 19 patients with steno-occlusive cerebrovascular disease. For each patient, we generated a CVR magnitude map by regressing the BOLD signal with the end-tidal partial pressure of CO₂ (P_ETCO₂), and a CVR TD map by extracting the time of maximum cross-correlation between the BOLD signal and P_ETCO₂. In addition, a blood arrival time map was generated by fitting the DSC signal with a gamma variate function. ROI masks corresponding to varying degrees of reactivity were constructed. Within these masks, the mean CVR magnitude, CVR TD and DSC blood arrival time were extracted and averaged over the 19 patients. CVR magnitude and CVR TD were then plotted against DSC blood arrival time. Results: The results show that CVR magnitude is highly correlated to DSC blood arrival time. As expected, the most compromised tissues with the longest blood arrival time have the lowest (most negative) CVR magnitude. However, CVR TD shows a noncontinuous relationship with DSC blood arrival time. CVR TD is well correlated to DSC blood arrival time (p < 0.0001) for tissue of positive reactivity, but fails to maintain this trend for tissue of negative reactivity. Regions with negative reactivity have similar CVR TD than healthy regions. Conclusion: These results support the hypothesis that negative reactivity is the result of a steal phenomenon, lowering the BOLD signal as soon as healthier parts of the brain start to react and augment their blood flow. BOLD CVR MRI is capable of identifying this steal distribution, which has particular diagnostic significance as it represents an actual reduction in flow to already compromised tissue.

Spontaneous EEG alpha oscillation interacts with positive and negative BOLD responses in the visual–auditory cortices and default-mode network

The human brain is continually, dynamically active and spontaneous fluctuations in this activity play a functional role in affecting both behavioural and neuronal responses. However, the mechanisms through which this occurs remain poorly understood. Simultaneous EEG-fMRI is a promising technique to study how spontaneous activity modulates the brain's response to stimulation, as temporal indices of ongoing cortical excitability can be integrated with spatially localised evoked responses. Here we demonstrate an interaction between the ongoing power of the electrophysiological alpha oscillation and the magnitude of both positive (PBR) and negative (NBR) fMRI responses to two contrasts of visual checkerboard reversal. Furthermore, the amplitude of pre-stimulus EEG alpha-power significantly modulated the amplitude and shape of subsequent PBR and NBR to the visual stimulus. A nonlinear reduction of visual PBR and an enhancement of auditory NBR and default-mode network NBR were observed in trials preceded by high alpha-power. These modulated areas formed a functionally connected network during a separate resting-state recording. Our findings suggest that the "baseline" state of the brain exhibits considerable trial-to-trial variability which arises from fluctuations in the balance of cortical inhibition/excitation that are represented by respective increases/decreases in the power of the EEG alpha oscillation. The consequence of this spontaneous electrophysiological variability is modulated amplitudes of both PBR and NBR to stimulation. Fluctuations in alpha-power may subserve a functional relationship in the visual-auditory network, acting as mediator for both short and long-range cortical inhibition, the strength of which is represented in part by NBR.

Systemic inflammation alters central 5-HT function as determined by pharmacological MRI

Considerable evidence indicates a link between systemic inflammation and central 5-HT function. This study used pharmacological magnetic resonance imaging (phMRI) to study the effects of systemic inflammatory events on central 5-HT function. Changes in blood oxygenation level dependent (BOLD) contrast were detected in selected brain regions of anaesthetised rats in response to intravenous administration of the 5-HT-releasing agent, fenfluramine (10 mg/kg). Further groups of rats were pre-treated with the bacterial lipopolysaccharide (LPS; 0.5 mg/kg), to induce systemic inflammation, or the selective 5-HT2A receptor antagonist MDL100907 prior to fenfluramine. The resultant phMRI data were investigated further through measurements of cortical 5-HT release (microdialysis), and vascular responsivity, as well as a more thorough investigation of the role of the 5-HT2A receptor in sickness behaviour. Fenfluramine evoked a positive BOLD response in the motor cortex (+ 15.9 ± 2%) and a negative BOLD response in the dorsal raphe nucleus (− 9.9 ± 4.2%) and nucleus accumbens (− 7.7 ± 5.3%). In all regions, BOLD responses to fenfluramine were significantly attenuated by pre-treatment with LPS (p < 0.0001), but neurovascular coupling remained intact, and fenfluramine-evoked 5-HT release was not affected. However, increased expression of the 5-HT2A receptor mRNA and decreased 5-HT2A-dependent behaviour (wet-dog shakes) was a feature of the LPS treatment and may underpin the altered phMRI signal. MDL100907 (0.5 mg/kg), 5-HT2A antagonist, significantly reduced the BOLD responses to fenfluramine in all three regions (p < 0.0001) in a similar manner to LPS. Together these results suggest that systemic inflammation decreases brain 5-HT activity as assessed by phMRI. However, these effects do not appear to be mediated by changes in 5-HT release, but are associated with changes in 5-HT2A-receptor-mediated downstream signalling pathways.

Combined structural and functional imaging reveals cortical deactivations in grapheme-color synaesthesia

Synaesthesia is a heritable condition in which particular stimuli generate specific and consistent sensory percepts or associations in another modality or processing stream. Functional neuroimaging studies have identified potential correlates of these experiences, including, in some but not all cases, the hyperactivation of visuotemporal areas and of parietal areas thought to be involved in perceptual binding. Structural studies have identified a similarly variable spectrum of differences between synaesthetes and controls. However, it remains unclear the extent to which these neural correlates reflect the synaesthetic experience itself or additional phenotypes associated with the condition. Here, we acquired both structural and functional neuroimaging data comparing thirteen grapheme-color synaesthetes with eleven non-synaesthetes. Using voxel-based morphometry and diffusion tensor imaging, we identify a number of clusters of increased volume of gray matter, of white matter or of increased fractional anisotropy in synaesthetes vs. controls. To assess the possible involvement of these areas in the synaesthetic experience, we used nine areas of increased gray matter volume as regions of interest in an fMRI experiment that characterized the contrast in response to stimuli which induced synaesthesia (i.e., letters) vs. those which did not (non-meaningful symbols). Four of these areas showed sensitivity to this contrast in synaesthetes but not controls. Unexpectedly, in two of them, in left lateral occipital cortex and in postcentral gyrus, the letter stimuli produced a strong negative BOLD signal in synaesthetes. An additional whole-brain fMRI analysis identified 14 areas, three of which were driven mainly by a negative BOLD response to letters in synaesthetes. Our findings suggest that cortical deactivations may be involved in the conscious experience of internally generated synaesthetic percepts.

High-Resolution fMRI Reveals Laminar Differences in Neurovascular Coupling between Positive and Negative BOLD Responses

The six cortical layers have distinct anatomical andphysiological properties, like different energy use and different feedforward and feedback connectivity. It is not known if and how layer-specific neural processes are reflected in the fMRI signal. To address this question we used high-resolution fMRI to measure BOLD, CBV, and CBF responses to stimuli that elicit positive and negative BOLD signals in macaque primary visual cortex. We found that regions with positive BOLD responses had parallel increases in CBV and CBF, whereas areas with negative BOLD responses showed a decrease in CBF but an increase in CBV. For positive BOLD responses, CBF and CBV increased in the center of the cortex, but for negative BOLD responses, CBF decreased superficially while CBV increased in the center. Our findings suggest different mechanisms for neurovascular coupling for BOLD increases and decreases, aswell as laminar differences in neurovascular coupling.

Cognitive-Affective Neural Plasticity following Active-Controlled Mindfulness Intervention

Mindfulness meditation is a set of attention-based, regulatory, and self-inquiry training regimes. Although the impact of mindfulness training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures renders difficult distinguishing their respective roles. To resolve this question we conducted a fully randomized 6 week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active-control group. We measured behavioral metacognition and whole-brain blood oxygenation level-dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention in healthy human subjects. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group-by-time interactions on negative affect-related reaction times or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response inhibition and increased recruitment of dorsal anterior cingulate cortex, medial prefrontal cortex, and right anterior insula during negative valence processing. Our findings highlight the importance of active control in MT research, indicate unique neural mechanisms for progressive stages of mindfulness training, and suggest that optimal application of MT may differ depending on context, contrary to a one-size-fits-all approach.

External awareness and GABA-A multimodal imaging study combining fMRI and [18F]flumazenil-PET

Awareness is an essential feature of the human mind that can be directed internally, that is, toward our self, or externally, that is, toward the environment. The combination of internal and external information is crucial to constitute our sense of self. Although the underlying neuronal networks, the so-called intrinsic and extrinsic systems, have been well-defined, the associated biochemical mechanisms still remain unclear. We used a well-established functional magnetic resonance imaging (fMRI) paradigm for internal (heartbeat counting) and external (tone counting) awareness and combined this technique with [(18)F]FMZ-PET imaging in the same healthy subjects. Focusing on cortical midline regions, the results showed that both stimuli types induce negative BOLD responses in the mPFC and the precuneus. Carefully controlling for structured noise in fMRI data, these results were also confirmed in an independent data sample using the same paradigm. Moreover, the degree of the GABAA receptor binding potential within these regions was correlated with the neuronal activity changes associated with external, rather than internal awareness when compared to fixation. These data support evidence that the inhibitory neurotransmitter GABA is an influencing factor in the differential processing of internally and externally guided awareness. This in turn has implications for our understanding of the biochemical mechanisms underlying awareness in general and its potential impact on psychiatric disorders.

Excitatory and inhibitory mechanisms underlying somatosensory habituation

Habituation is a basic process of learning in which repeated exposure to a sensory stimulus leads to a decrease in the strength of neuronal activations and behavioral responses. In addition to increases in neuronal activity, sensory stimuli can also lead to decreases in neuronal activity. Until now, the effects of habituation on stimulus-induced neuronal deactivations have not been investigated. We performed functional magnetic resonance imaging in 30 healthy subjects during repetitive unilateral somatosensory stimulation and combined this analysis with a psychophysiological examination of changes in the perception threshold. Consistent with the literature, we found a time-dependent decrease of the positive blood oxygenation level-dependent (BOLD) response (indicative of habituation) in the primary somatosensory cortex (SI) contralateral to the stimulus. In contrast, the negative BOLD response (NBR) in the ipsilateral SI did not show a decrease in amplitude; instead, an increase in amplitude was found, i.e., a stronger NBR (increased response). The increased NBR was associated with an increased perception threshold of the nonstimulated hand. These findings suggest that habituation is not primarily characterized by a decrease in the neuronal response to repeated stimuli but rather a widespread change in the balance between excitatory and inhibitory effects that favors inhibitory effects.

On the origin of sustained negative BOLD response

Several brain regions exhibit a sustained negative BOLD response (NBR) during specific tasks, as assessed with functional magnetic resonance imaging. The origin of the NBR and the relationships between the vascular/metabolic dynamics and the underlying neural activity are highly debated. Converging evidence indicates that NBR, in human and non-human primates, can be interpreted in terms of decrease in neuronal activity under its basal level, rather than a purely vascular phenomenon. However, the scarcity of direct experimental evidence suggests caution and encourages the ongoing utilization of multimodal approaches in the investigation of this effect.

Is optical imaging spectroscopy a viable measurement technique for the investigation of the negative BOLD phenomenon? A concurrent optical imaging spectroscopy and fMRI study at high field (7T)

Traditionally functional magnetic resonance imaging (fMRI) has been used to map activity in the human brain by measuring increases in the Blood Oxygenation Level Dependent (BOLD) signal. Often accompanying positive BOLD fMRI signal changes are sustained negative signal changes. Previous studies investigating the neurovascular coupling mechanisms of the negative BOLD phenomenon have used concurrent 2D-optical imaging spectroscopy (2D-OIS) and electrophysiology (Boorman et al., 2010). These experiments suggested that the negative BOLD signal in response to whisker stimulation was a result of an increase in deoxy-haemoglobin and reduced multi-unit activity in the deep cortical layers. However, Boorman et al. (2010) did not measure the BOLD and haemodynamic response concurrently and so could not quantitatively compare either the spatial maps or the 2D-OIS and fMRI time series directly. Furthermore their study utilised a homogeneous tissue model in which is predominantly sensitive to haemodynamic changes in more superficial layers.Here we test whether the 2D-OIS technique is appropriate for studies of negative BOLD. We used concurrent fMRI with 2D-OIS techniques for the investigation of the haemodynamics underlying the negative BOLD at 7 Tesla. We investigated whether optical methods could be used to accurately map and measure the negative BOLD phenomenon by using 2D-OIS haemodynamic data to derive predictions from a biophysical model of BOLD signal changes. We showed that despite the deep cortical origin of the negative BOLD response, if an appropriate heterogeneous tissue model is used in the spectroscopic analysis then 2D-OIS can be used to investigate the negative BOLD phenomenon.

Serotonin Transporter Genotype Modulates Subgenual Response to Fearful Faces Using an Incidental Task

This study assessed the impact of serotonin transporter genotype (5-HTTLPR) on regional responses to emotional faces in the amygdala and subgenual cingulate cortex (sgACC), while subjects performed a gender discrimination task. Although we found no evidence for greater amygdala reactivity or reduced amygdala-sgACC coupling in short variant 5-HTTLPR homozygotes (s/s), we observed an interaction between genotype and emotion in sgACC. Only long variant homozygotes (la/la) exhibited subgenual deactivation to fearful versus neutral faces, whereas the effect in s/s subjects was in the other direction. This absence of subgenual deactivation in s/s subjects parallels a recent finding in depressed subjects [Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., et al. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology, 34, 932-943, 2009]. Taken together, the findings suggest that subgenual cingulate activity may play an important role in regulating the impact of aversive stimuli, potentially conferring greater resilience to the effects of aversive stimuli in la/la subjects. Using dynamic causal modeling of functional magnetic resonance imaging data, we explored the effects of genotype on effective connectivity and emotion-specific changes in coupling across a network of regions implicated in social processing. Viewing fearful faces enhanced bidirectional excitatory coupling between the amygdala and the fusiform gyrus, and increased the inhibitory influence of the amygdala over the sgACC, although this modulation of coupling did not differ between the genotype groups. The findings are discussed in relation to the role of sgACC and serotonin in moderating responses to aversive stimuli [Dayan, P., & Huys, Q. J., Serotonin, inhibition, and negative mood. PLoS Comput Biol, 4, e4, 2008; Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., et al. Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness. Am J Psychiatry, 156, 675-682, 1999].

Sustained Negative BOLD Response in Human fMRI Finger Tapping Task

In this work, we investigated the sustained negative blood oxygen level-dependent (BOLD) response (sNBR) using functional magnetic resonance imaging during a finger tapping task. We observed that the sNBR for this task was more extensive than has previously been reported. The cortical regions involved in sNBR are divided into the following three groups: frontal, somatosensory and occipital. By investigating the spatial structure, area, amplitude, and dynamics of the sNBR in comparison with those of its positive BOLD response (PBR) counterpart, we made the following observations. First, among the three groups, the somatosensory group contained the greatest number of activated voxels and the fewest deactivated voxels. In addition, the amplitude of the sNBR in this group was the smallest among the three groups. Second, the onset and peak time of the sNBR are both larger than those of the PBR, whereas the falling edge time of the sNBR is less than that of the PBR. Third, the long distance between most sNBR foci and their corresponding PBR foci makes it unlikely that they share the same blood supply artery. Fourth, the couplings between the sNBR and its PBR counterpart are distinct among different regions and thus should be investigated separately. These findings imply that the origin of most sNBR foci in the finger-tapping task is much more likely to be neuronal activity suppression rather than “blood steal.”

Differential Electrophysiological Coupling for Positive and Negative BOLD Responses during Unilateral Hand Movements

The coupling between neural cellular activity and blood oxygen level-dependent (BOLD) signal is of critical importance to the interpretation of fMRI. Largely unknown, however, is the degree to which different neuronal events (i.e., excitation and inhibition) maintain or disrupt the neural-hemodynamic relationship, especially in humans. In the present study, we compared local electroencephalographic (EEG) oscillations and the positive/negative BOLD responses of simultaneously recorded data from healthy human volunteers performing unilateral finger tapping at graded rates. By quantifying the single-trial modulations of EEG using source imaging, we tested for their correlation with positive BOLD response (PBR) and negative BOLD response (NBR) after coregistering their spatial locations. PBR was found to be overlapped with and correlated to the decrease of alpha (8-13 Hz) and beta (13-30 Hz) band EEG in the contralateral sensorimotor cortex. Regional EEG modulations at the sensorimotor cortex further predicted a spatially distributed and interconnected network of motor-related cortical areas. Alternatively, no significant correlation was found at the ipsilateral sensorimotor cortex between the NBR and EEG despite their spatial overlapping. This differential electrophysiological coupling of the positive and negative BOLD responses suggests that the underlying neuronal events may not only influence the direction of the signal change but also the neural-hemodynamic relationship.

Reproducibility of BOLD localization of interictal activity in patients with focal epilepsy: intrasession and intersession comparisons

Simultaneous EEG-fMRI recordings allow the identification of haemodynamic changes induced by neuronal activity during ictal or interictal epileptiform events (IEDs). We evaluated the reproducibility of continuous EEG-fMRI (cEEG-fMRI) in patients with focal epilepsy. We studied 15 patients with focal epilepsy (8 cryptogenic and 7 symptomatic) and frequent interictal abnormalities. Each patient underwent two cEEG-fMRI acquisitions (runs) in the same day (session) and 8 patients repeated the examination after one month. cEEG-fMRI reproducibility was defined by the existence of partially overlapping clusters between activation maps obtained from different runs. We detected IEDs in 40 out of 46 EEG-fMRI runs and a related significant BOLD-response in all 40 runs. A prevalent positive BOLD response was detected in 12 patients and a prevalent negative response in 3 subjects. Statistical maps included a mean of 10 significant clusters. Nearly 30% of clusters were reproducible in both intrasession and intersession comparisons, with a mean overlap of 30%. Reproducibility did not differ between positive and negative BOLD-responses. Among the reproducible clusters, those with the highest percentage of overlap were concordant with the EEG electric field in all patients and they were localized in the same lobe as the brain lesion in patients with symptomatic epilepsy. We hypothesize that reproducible clusters could be more consistently related to the irritative zone than non-reproducible ones. The evaluation of cluster reproducibility could improve our knowledge of IED-related BOLD response. Moreover, it could enhance the reliability of cEEG-fMRI to identify the irritative zone in focal epileptic patients.

Modeling of the Neurovascular Coupling in Epileptic Discharges

Despite the interest in simultaneous EEG-fMRI studies of epileptic spikes, the link between epileptic discharges and their corresponding hemodynamic responses is poorly understood. In this context, biophysical models are promising tools for investigating the mechanisms underlying observed signals. Here, we apply a metabolic-hemodynamic model to simulated epileptic discharges, in part generated by a neural mass model. We analyze the effect of features specific to epileptic neuronal activity on the blood oxygen level dependent (BOLD) response, focusing on the issues of linearity in neurovascular coupling and on the origin of negative BOLD signals. We found both sub- and supra-linearity in simulated BOLD signals, depending on whether one observes the early or the late part of the BOLD response. The size of these non-linear effects is determined by the spike frequency, as well as by the amplitude of the excitatory activity. Our results additionally indicate a minor deviation from linearity at the neuronal level. According to a phase space analysis, the possibility to obtain a negative BOLD response to an epileptic spike depends on the existence of a long and strong excitatory undershoot. Moreover, we strongly suggest that a combined EEG-fMRI modeling approach should include spatial assumptions. The present study is a step towards an increased understanding of the link between epileptic spikes and their BOLD responses, aiming to improve the interpretation of simultaneous EEG-fMRI recordings in epilepsy.

Cerebral Regulation of Facial Expressions of Pain

Facial expression of affective states plays a key role in social interactions. Interestingly, however, individuals differ substantially in their level of expressiveness, ranging from high expressive to stoic individuals. Here, we investigate which brain mechanisms underlie the regulation of facial expressiveness to acute pain. Facial responses, pain ratings, and brain activity (BOLD-fMRI) evoked by noxious heat and warm (control) stimuli were recorded in 34 human volunteers with different degrees of facial expressiveness. Within-subject and between-subject variations in blood oxygenation level-dependent (BOLD) responses were examined specifically in relation to facial responses. Pain expression was inversely related to frontostriatal activity, consistent with a role in downregulating facial displays. More detailed analyses of the peak activity in medial prefrontal cortex revealed negative BOLD responses to thermal stimuli, an effect generally associated with the default mode network. Given that this negative BOLD response was weaker in low expressive individuals during pain, it could reflect stronger engagement in, or reduced disengagement from, self-reflective processes in stoic individuals. The occurrence of facial expressions during pain was coupled with stronger primary motor activity in the face area and-interestingly-in areas involved in pain processing. In conclusion, these results indicate that spontaneous pain expression reflects activity within nociceptive pathways while stoicism involves the active suppression of expression, a manifestation of learned display rules governing emotional communication and possibly related to an increased self-reflective or introspective focus.

Negative BOLD in the Lateral Geniculate Nucleus: Neuronal Implications and Cortico-Thalamic Feedback

Previous research has demonstrated a sustained negative BOLD response (NBR) that is negatively correlated with the spatio-temporal properties of a visual stimulus. Whilst it has been suggested that the NBR surrounding the positive BOLD response (PBR) may reflect blood-stealing, evidence indicates that the extensive NBR distal to the PBR is a manifestation of neuronal suppression. This study aimed to evaluate NBR in the lateral geniculate nucleus (LGN), and to explore the source of the NBR. fMRI data were obtained from six subjects, while they viewed a grating stimulus. The NBR was identified in the LGN ipsilateral to the stimulus. The results also verified the NBR in V1 ipsilateral to the stimulus and revealed the PBR in bilateral V5. It was concluded that the NBR can be found in the LGN, and is most likely driven by feedback from ipsilateral V1. The finding that the stimulus that stimulates the LGN in one hemisphere can cause extensive suppression in the LGN of the opposite hemisphere rejects the notion that the effect is purely a blood-stealing effect as the two LGN have different blood supplies. The results, together with previous research, indicate that the NBR may reflect neuronal suppression.

Involvement of glutamate in rest‐stimulus interaction between perigenual and supragenual anterior cingulate cortex: A combined fMRI‐MRS study

The brain shows a high degree of activity at rest. The significance of this activity has come increasingly into focus. At present, however, the interaction between this activity and stimulus-induced activity is not well defined. The interaction between a task-negative (perigenual anterior cingulate cortex, pgACC) and task-positive (supragenual anterior cingulate cortex, sgACC) region during a simple task was thus investigated using a combination of fMRI and MRS. Negative BOLD responses in the pgACC were found to show a unidirectional effective connectivity with task-induced positive BOLD responses in the sgACC. This connectivity was shown to be related specifically with glutamate levels in the pgACC. These results demonstrate an interaction between deactivation from resting-state and resting-state glutamate levels in a task-negative region (pgACC), and task-induced activity in a task-positive region (sgACC). This provides insight into the neuronal and biochemical mechanisms by means of which the resting state activity of the brain potentially impacts upon subsequent stimulus-induced activity.

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

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.

Spatial dependence of the negative BOLD response driven by achromatic and S-cone contrast

Spatial dependence of the negative BOLD response driven by achromatic and S-cone contrast