Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load

BACKGROUND: Recent functional MRI (fMRI) studies have demonstrated that there is an intrinsically organized default mode network (DMN) in the resting brain, primarily made up of the posterior cingulate cortex (PCC) and the medial prefrontal cortex (MPFC). Several previous studies have found that the DMN is minimally disturbed during different resting-state conditions with limited cognitive demand. However, this conclusion was drawn from the visual inspection of the functional connectivity patterns within the DMN and no statistical comparison was performed. METHODOLOGY/PRINCIPAL FINDINGS: Four resting-state fMRI sessions were acquired: 1) eyes-closed (EC) (used to generate the DMN mask); 2) EC; 3) eyes-open with no fixation (EO); and 4) eyes-open with a fixation (EO-F). The 2-4 sessions were counterbalanced across participants (n = 20, 10 males). We examined the statistical differences in both functional connectivity and regional amplitude of low frequency fluctuation (ALFF) within the DMN among the 2-4 resting-state conditions (i.e., EC, EO, and EO-F). Although the connectivity patterns of the DMN were visually similar across these three different conditions, we observed significantly higher functional connectivity and ALFF in both the EO and the EO-F conditions as compared to the EC condition. In addition, the first and second resting EC conditions showed significant differences within the DMN, suggesting an order effect on the DMN activity. CONCLUSIONS/SIGNIFICANCE: Our findings of the higher DMN connectivity and regional spontaneous activities in the resting state with the eyes open suggest that the participants might have more non-specific or non-goal-directed visual information gathering and evaluation, and mind wandering or daydreaming during the resting state with the eyes open as compared to that with the eyes closed, thus providing insights into the understanding of unconstrained mental activity within the DMN. Our results also suggest that it should be cautious when choosing the type of a resting condition and designating the order of the resting condition in multiple scanning sessions in experimental design

Offline Memory Reprocessing: Involvement of the Brain's Default Network in Spontaneous Thought Processes

BACKGROUND: Spontaneous thought processes (STPs), also called daydreaming or mind-wandering, occur ubiquitously in daily life. However, the functional significance of STPs remains largely unknown. METHODOLOGY/PRINCIPAL FINDING: Using functional magnetic resonance imaging (fMRI), we first identified an STPs-network whose activity was positively correlated with the subjects' tendency of having STPs during a task-free state. The STPs-network was then found to be strongly associated with the default network, which has previously been established as being active during the task-free state. Interestingly, we found that offline reprocessing of previously memorized information further increased the activity of the STPs-network regions, although during a state with less STPs. In addition, we found that the STPs-network kept a dynamic balance between functional integration and functional separation among its component regions to execute offline memory reprocessing in STPs. CONCLUSION/SIGNIFICANCE: These findings strengthen a view that offline memory reprocessing and STPs share the brain's default network, and thus implicate that offline memory reprocessing may be a predetermined function of STPs. This supports the perspective that memory can be consolidated and modified during STPs, and thus gives rise to a dynamic behavior dependent on both previous external and internal experiences

Orienting asymmetries and lateralized processing of sounds in humans

<p>Abstract</p> <p>Background</p> <p>Lateralized processing of speech is a well studied phenomenon in humans. Both anatomical and neurophysiological studies support the view that nonhuman primates and other animal species also reveal hemispheric differences in areas involved in sound processing. In recent years, an increasing number of studies on a range of taxa have employed an orienting paradigm to investigate lateralized acoustic processing. In this paradigm, sounds are played directly from behind and the direction of turn is recorded. This assay rests on the assumption that a hemispheric asymmetry in processing is coupled to an orienting bias towards the contralateral side. To examine this largely untested assumption, speech stimuli as well as artificial sounds were presented to 224 right-handed human subjects shopping in supermarkets in Germany and in the UK. To verify the lateralized processing of the speech stimuli, we additionally assessed the brain activation in response to presentation of the different stimuli using functional magnetic resonance imaging (fMRI).</p> <p>Results</p> <p>In the naturalistic behavioural experiments, there was no difference in orienting behaviour in relation to the stimulus material (speech, artificial sounds). Contrary to our predictions, subjects revealed a significant left bias, irrespective of the sound category. This left bias was slightly but not significantly stronger in German subjects. The fMRI experiments confirmed that the speech stimuli evoked a significant left lateralized activation in BA44 compared to the artificial sounds.</p> <p>Conclusion</p> <p>These findings suggest that in adult humans, orienting biases are not necessarily coupled with lateralized processing of acoustic stimuli. Our results – as well as the inconsistent orienting biases found in different animal species – suggest that the orienting assay should be used with caution. Apparently, attention biases, experience, and experimental conditions may all affect head turning responses. Because of the complexity of the interaction of factors, the use of the orienting assay to determine lateralized processing of sound stimuli is discouraged.</p

Never Resting Brain: Simultaneous Representation of Two Alpha Related Processes in Humans

Brain activity is continuously modulated, even at “rest”. The alpha rhythm (8–12 Hz) has been known as the hallmark of the brain's idle-state. However, it is still debated if the alpha rhythm reflects synchronization in a distributed network or focal generator and whether it occurs spontaneously or is driven by a stimulus. This EEG/fMRI study aimed to explore the source of alpha modulations and their distribution in the resting brain. By serendipity, while computing the individually defined power modulations of the alpha-band, two simultaneously occurring components of these modulations were found. An ‘induced alpha’ that was correlated with the paradigm (eyes open/ eyes closed), and a ‘spontaneous alpha’ that was on-going and unrelated to the paradigm. These alpha components when used as regressors for BOLD activation revealed two segregated activation maps: the ‘induced map’ included left lateral temporal cortical regions and the hippocampus; the ‘spontaneous map’ included prefrontal cortical regions and the thalamus. Our combined fMRI/EEG approach allowed to computationally untangle two parallel patterns of alpha modulations and underpin their anatomical basis in the human brain. These findings suggest that the human alpha rhythm represents at least two simultaneously occurring processes which characterize the ‘resting brain’; one is related to expected change in sensory information, while the other is endogenous and independent of stimulus change

“Thinking about Not-Thinking”: Neural Correlates of Conceptual Processing during Zen Meditation

Recent neuroimaging studies have identified a set of brain regions that are metabolically active during wakeful rest and consistently deactivate in a variety the performance of demanding tasks. This “default network” has been functionally linked to the stream of thoughts occurring automatically in the absence of goal-directed activity and which constitutes an aspect of mental behavior specifically addressed by many meditative practices. Zen meditation, in particular, is traditionally associated with a mental state of full awareness but reduced conceptual content, to be attained via a disciplined regulation of attention and bodily posture. Using fMRI and a simplified meditative condition interspersed with a lexical decision task, we investigated the neural correlates of conceptual processing during meditation in regular Zen practitioners and matched control subjects. While behavioral performance did not differ between groups, Zen practitioners displayed a reduced duration of the neural response linked to conceptual processing in regions of the default network, suggesting that meditative training may foster the ability to control the automatic cascade of semantic associations triggered by a stimulus and, by extension, to voluntarily regulate the flow of spontaneous mentation

Neural Correlates of Visual Aesthetics – Beauty as the Coalescence of Stimulus and Internal State

How do external stimuli and our internal state coalesce to create the distinctive aesthetic pleasures that give vibrance to human experience? Neuroaesthetics has so far focused on the neural correlates of observing beautiful stimuli compared to neutral or ugly stimuli, or on neural correlates of judging for beauty as opposed to other judgments. Our group questioned whether this approach is sufficient. In our view, a brain region that assesses beauty should show beauty-level-dependent activation during the beauty judgment task, but not during other, unrelated tasks. We therefore performed an fMRI experiment in which subjects judged visual textures for beauty, naturalness and roughness. Our focus was on finding brain activation related to the rated beauty level of the stimuli, which would take place exclusively during the beauty judgment. An initial whole-brain analysis did not reveal such interactions, yet a number of the regions showing main effects of the judgment task or the beauty level of stimuli were selectively sensitive to beauty level during the beauty task. Of the regions that were more active during beauty judgments than roughness judgments, the frontomedian cortex and the amygdala demonstrated the hypothesized interaction effect, while the posterior cingulate cortex did not. The latter region, which only showed a task effect, may play a supporting role in beauty assessments, such as attending to one's internal state rather than the external world. Most of the regions showing interaction effects of judgment and beauty level correspond to regions that have previously been implicated in aesthetics using different stimulus classes, but based on either task or beauty effects alone. The fact that we have now shown that task-stimulus interactions are also present during the aesthetic judgment of visual textures implies that these areas form a network that is specifically devoted to aesthetic assessment, irrespective of the stimulus type

Large-Scale Brain Networks in Board Game Experts: Insights from a Domain-Related Task and Task-Free Resting State

Cognitive performance relies on the coordination of large-scale networks of brain regions that are not only temporally correlated during different tasks, but also networks that show highly correlated spontaneous activity during a task-free state. Both task-related and task-free network activity has been associated with individual differences in cognitive performance. Therefore, we aimed to examine the influence of cognitive expertise on four networks associated with cognitive task performance: the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network). During fMRI scanning, fifteen grandmaster and master level Chinese chess players (GM/M) and fifteen novice players carried out a Chinese chess task and a task-free resting state. Modulations of network activity during task were assessed, as well as resting-state functional connectivity of those networks. Relative to novices, GM/Ms showed a broader task-induced deactivation of DMN in the chess problem-solving task, and intrinsic functional connectivity of DMN was increased with a connectivity pattern associated with the caudate nucleus in GM/Ms. The three other cognitive networks did not exhibit any difference in task-evoked activation or intrinsic functional connectivity between the two groups. These findings demonstrate the effect of long-term learning and practice in cognitive expertise on large-scale brain networks, suggesting the important role of DMN deactivation in expert performance and enhanced functional integration of spontaneous activity within widely distributed DMN-caudate circuitry, which might better support high-level cognitive control of behavior

rTMS of the Left Dorsolateral Prefrontal Cortex Modulates Dopamine Release in the Ipsilateral Anterior Cingulate Cortex and Orbitofrontal Cortex

Background: Brain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson’s disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of noninvasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine (DA). Methodology/Principal Findings: Healthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [ 11 C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [ 11 C]FLB 457 binding potential (BP) in the ipsilateral subgenual anterior cingulate cortex (ACC) (BA 25/12), pregenual ACC (BA 32) and medial orbitofrontal cortex (BA 11). There were no significant changes in [ 11 C]FLB 457 BP following right DLPFC rTMS. Conclusions/Significance: To our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [ 11 C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help t

Brain correlates of pro-social personality traits: a voxel-based morphometry study

Of the five personality dimensions described by the Big Five Personality Model (Costa and McCrae 1992), Extraversion and Agreeableness are the traits most commonly associated with a pro-social orientation. In this study we tested whether a pro-social orientation, as expressed in terms of Extraversion and Agreeableness, is associated with a specific grey matter phenotype. Fifty-two healthy participants underwent magnetic resonance imaging (MRI) and completed the NEO-Five Factor Inventory (NEO-FFI), a self-report measure of the Big Five personality traits. Voxel-based morphometry (VBM) was used to investigate the correlation between brain structure and the personality traits of Agreeableness and Extraversion. We found that Extraversion was negatively correlated with grey matter density in the middle frontal and orbitofrontal gyri while Agreeableness was negatively correlated with grey matter density in the inferior parietal, middle occipital and posterior cingulate gyri. No positive correlations were found. These results suggest that pro-social personality traits seem to be associated with decreases in grey matter density in more frontal regions for Extraversion, and more posterior regions for Agreeableness.This research was funded by the Portuguese Foundation for Science and Technology (FCT): PIC/IC/83290/2007, which is supported by FEDER (POFC - COMPETE), and postdoctoral grant number: SFRH/BPD/75014/2010