Altered processing of contextual information during fear extinction in PTSD: an fMRI study.

Medial prefrontal cortical areas have been hypothesized to underlie altered contextual processing in posttraumatic stress disorder (PTSD). We investigated brain signaling of contextual information in this disorder. Eighteen PTSD subjects and 16 healthy trauma-exposed subjects underwent a two-day fear conditioning and extinction paradigm. On day 1, within visual context A, a conditioned stimulus (CS) was followed 60% of the time by an electric shock (conditioning). The conditioned response was then extinguished (extinction learning) in context B. On day 2, recall of the extinction memory was tested in context B. Skin conductance response (SCR) and functional magnetic resonance imaging (fMRI) data were collected during context presentations. There were no SCR group differences in any context presentation. Concerning fMRI data, during late conditioning, when context A signaled danger, PTSD subjects showed dorsal anterior cingulate cortical (dACC) hyperactivation. During early extinction, when context B had not yet fully acquired signal value for safety, PTSD subjects still showed dACC hyperactivation. During late extinction, when context B had come to signal safety, they showed ventromedial prefrontal cortex (vmPFC) hypoactivation. During early extinction recall, when context B signaled safety, they showed both vmPFC hypoactivation and dACC hyperactivation. These findings suggest that PTSD subjects show alterations in the processing of contextual information related to danger and safety. This impairment is manifest even prior to a physiologically-measured, cue-elicited fear response, and characterized by hypoactivation in vmPFC and hyperactivation in dACC.

Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling.

How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model's prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information.

Physiological noise in human cerebellar fMRI.

OBJECTIVES: To compare physiological noise contributions in cerebellar and cerebral regions of interest in high-resolution functional magnetic resonance imaging (fMRI) data acquired at 7T, to estimate the need for physiological noise removal in cerebellar fMRI. MATERIALS AND METHODS: Signal fluctuations in high resolution (1 mm isotropic) 7T fMRI data were attributed to one of the following categories: task-induced BOLD changes, slow drift, signal changes correlated with the cardiac and respiratory cycles, signal changes related to the cardiac rate and respiratory volume per unit of time or other. [Formula: see text] values for all categories were compared across regions of interest. RESULTS: In this high-resolution data, signal fluctuations related to the phase of the cardiac cycle and cardiac rate were shown to be significant, but comparable between cerebellar and cerebral regions of interest. However, respiratory related signal fluctuations were increased in the cerebellar regions, with explained variances that were up to 80 % higher than for the primary motor cortex region. CONCLUSION: Even at a millimetre spatial resolution, significant correlations with both cardiac and respiratory RETROICOR components were found in all healthy volunteer data. Therefore, physiological noise correction is highly likely to improve the temporal signal-to-noise ratio (SNR) for cerebellar fMRI at 7T, even at high spatial resolution.

Distinct contributions of Brodmann areas 1 and 2 to body ownership.

Although body ownership-i.e. the feeling that our bodies belong to us-modulates activity within the primary somatosensory cortex (S1), it is still unknown whether this modulation occurs within a somatotopically defined portion of S1. We induced an illusory feeling of ownership for another person's finger by asking participants to hold their palm against another person's palm and to stroke the two joined index fingers with the index and thumb of their other hand. This illusion (numbness illusion) does not occur if the stroking is performed asynchronously or by the other person. We combined this somatosensory paradigm with ultra-high field functional magnetic resonance imaging finger mapping to study whether illusory body ownership modulates activity within different finger-specific areas of S1. The results revealed that the numbness illusion is associated with activity in Brodmann area (BA) 1 within the representation of the finger stroking the other person's finger and in BA 2 contralateral to the stroked finger. These results show that changes in bodily experience modulate the activity within certain subregions of S1, with a different finger-topographical selectivity between the representations of the stroking and of the stroked hand, and reveal that the high degree of somatosensory specialization in S1 extends to bodily self-consciousness.

Diagnostic methods and treatment options for focal cortical dysplasia.

Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high-frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high-field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Proof for a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Although review of current strategies underscores the serious shortcomings of treatment-resistant cases, initial evidence from novel approaches suggests that future success is possible.