Corticolimbic Circuitry in Chronic Pain Tracks Pain Intensity Relief Following Exposure In Vivo.

Background: A subset of patients with chronic pain who receive exposure in vivo (EXP) treatment experience clinically relevant relief of pain intensity. Although pain relief is not an explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some patients but not others. This longitudinal study therefore aimed to characterize brain plasticity as well as to explore pretreatment factors related to pain relief. Methods: Resting-state functional magnetic resonance imaging data were acquired in 30 patients with chronic pain. Twenty-three patients completed EXP, and 6-month follow-up data were available in 20 patients (magnetic resonance imaging data in 17 patients). Pain-free control data were acquired at two time points (n = 29, n = 21). Seed-based resting-state functional connectivity (rsFC) analyses were performed, with seeds in the amygdala, hippocampus, and nucleus accumbens. Results: Pain relief after EXP was highly variable, with 60% of patients reporting a clinically relevant improvement. Amygdala rsFC with the middle frontal gyrus decreased significantly over time in patients but was not associated with pain relief. In contrast, greater pain relief was associated with greater decreases over time in hippocampus rsFC with the precuneus, which was related to reductions in catastrophizing (EXP therapeutic target) as well. Greater pain relief was also associated with lower pretreatment rsFC between nucleus accumbens and postcentral gyrus. Conclusions: While changes in hippocampus rsFC were associated with pain relief after EXP, pretreatment nucleus accumbens rsFC showed potential prognostic value. Our findings further support the importance of corticolimbic circuitry in chronic pain, emphasizing its relation to pain relief and identifying potential underlying mechanisms and prognostic factors, warranting further testing in independent samples.

Contributions of Cerebro-Cerebellar Default Mode Connectivity Patterns to Memory Performance in Mild Cognitive Impairment.

BACKGROUND: The cerebral default mode network (DMN) can be mapped onto specific regions in the cerebellum, which are specifically vulnerable to atrophy in Alzheimer's disease (AD) patients. OBJECTIVE: We set out to determine whether there are specific differences in the interaction between the cerebral and cerebellar DMN in amnestic mild cognitive impairment (aMCI) patients compared to healthy controls using resting-state functional MRI and whether these differences are relevant for memory performance. METHODS: Eighteen patients with aMCI were age and education-matched to eighteen older adults and underwent 3T MR-imaging. We performed seed-based functional connectivity analysis between the cerebellar DMN seeds and the cerebral DMN. RESULTS: Our results showed that compared to healthy older adults, aMCI patients showed lower anti-correlation between the cerebellar DMN and several cerebral DMN regions. Additionally, we showed that degradation of the anti-correlation between the cerebellar DMN and the medial frontal cortex is correlated with worse memory performance in aMCI patients. CONCLUSION: These findings provide evidence that the cerebellar DMN and cerebral DMN are negatively correlated during rest in older individuals, and suggest that the reduced anti-correlated impacts the modulatory role of the cerebellum on cognitive functioning, in particular on the executive component of memory functions in neurodegenerative diseases.

The impact of early visual cortex transcranial magnetic stimulation on visual working memory precision and guess rate.

Neuroimaging studies have demonstrated that activity patterns in early visual areas predict stimulus properties actively maintained in visual working memory. Yet, the mechanisms by which such information is represented remain largely unknown. In this study, observers remembered the orientations of 4 briefly presented gratings, one in each quadrant of the visual field. A 10Hz Transcranial Magnetic Stimulation (TMS) triplet was applied directly at stimulus offset, or midway through a 2-second delay, targeting early visual cortex corresponding retinotopically to a sample item in the lower hemifield. Memory for one of the four gratings was probed at random, and participants reported this orientation via method of adjustment. Recall errors were smaller when the visual field location targeted by TMS overlapped with that of the cued memory item, compared to errors for stimuli probed diagonally to TMS. This implied topographic storage of orientation information, and a memory-enhancing effect at the targeted location. Furthermore, early pulses impaired performance at all four locations, compared to late pulses. Next, response errors were fit empirically using a mixture model to characterize memory precision and guess rates. Memory was more precise for items proximal to the pulse location, irrespective of pulse timing. Guesses were more probable with early TMS pulses, regardless of stimulus location. Thus, while TMS administered at the offset of the stimulus array might disrupt early-phase consolidation in a non-topographic manner, TMS also boosts the precise representation of an item at its targeted retinotopic location, possibly by increasing attentional resources or by injecting a beneficial amount of noise.

Visual hallucinations in schizophrenia investigated with functional magnetic resonance imaging.

We investigated a 27-year old patient with paranoid schizophrenia. Brain activity related to visual hallucinations was found in higher visual areas corresponding to the content of the hallucinations (faces, bodies, scenes) and the hippocampus. We assume that the hippocampal activity is related to the retrieval of visual images from memory and that sensory cortex activity is related to the vividness of the perceptual experience.

Pain response in depersonalization: a functional imaging study using hypnosis in healthy subjects.

BACKGROUND: Depersonalization (DP) is characterized by persistent or recurrent episodes of detachment from one's self with reduced pain perception being a common feature. Alterations in the body schema similar to the cortico-limbic disconnection syndrome of pain asymbolia are suggested to be responsible for DP. In this study we used hypnosis to induce DP in healthy subjects and to examine neural patterns of pain perception in the state of DP by means of functional magnetic resonance imaging (fMRI). METHODS: Pain perception was investigated in 7 healthy subjects with high susceptibility to hypnosis in three different mental states: waking state (N-W), hypnotic relaxation (H-R) and hypnotic DP (H-DP). Pain was induced with electrical stimulation to the median nerve at the right wrist. fMRI measurements were performed during all states. RESULTS: Nociceptive stimuli led to an activation of the well described pain network including somatosensory and insular regions and the cerebellum. Activation was markedly reduced in the contralateral somatosensory cortex, parietal cortex (Brodmann area 40, BA40), prefrontal cortex (BA9), putamen and the ipsilateral amygdala during H-DP. Subjects also reported a significant decrease in pain intensity from N-W to H-DP. CONCLUSION: Pain response during H-DP was reduced in sensory and affective pain-related areas, reflecting the diminished intensity of the perceived pain. Moreover, a network of cortical and subcortical areas that have been implicated in the perception of the own body was less responsive during DP, which might point to a specific neural mechanism underlying the 'out-of-body' experience. Although the small number of subjects does not allow a generalization of our findings, H-DP seems to be a promising tool for the investigation of psychological and biological mechanisms of self-inflicted injuries as well as the mind-body interplay within the realm of psychosomatic disorders.

The spatiotemporal pattern of auditory cortical responses during verbal hallucinations.

Functional magnetic resonance imaging (fMRI) studies can provide insight into the neural correlates of hallucinations. Commonly, such studies require self-reports about the timing of the hallucination events. While many studies have found activity in higher-order sensory cortical areas, only a few have demonstrated activity of the primary auditory cortex during auditory verbal hallucinations. In this case, using self-reports as a model of brain activity may not be sensitive enough to capture all neurophysiological signals related to hallucinations. We used spatial independent component analysis (sICA) to extract the activity patterns associated with auditory verbal hallucinations in six schizophrenia patients. SICA decomposes the functional data set into a set of spatial maps without the use of any input function. The resulting activity patterns from auditory and sensorimotor components were further analyzed in a single-subject fashion using a visualization tool that allows for easy inspection of the variability of regional brain responses. We found bilateral auditory cortex activity, including Heschl's gyrus, during hallucinations of one patient, and unilateral auditory cortex activity in two more patients. The associated time courses showed a large variability in the shape, amplitude, and time of onset relative to the self-reports. However, the average of the time courses during hallucinations showed a clear association with this clinical phenomenon. We suggest that detection of this activity may be facilitated by examining hallucination epochs of sufficient length, in combination with a data-driven approach.

Enhanced vividness of mental imagery as a trait marker of schizophrenia?

We assessed the vividness of mental imagery in schizophrenia patients in the context of psychopathology and cognitive abilities. A questionnaire on the vividness of mental imagery (Questionnaire Upon Mental Imagery [QMI]) and a hallucination scale were administered to 50 patients with paranoid schizophrenia. The related perceptual and cognitive skills, general intelligence level, and psychomotor speed were measured as covariates with a battery of performance tests. All measures were statistically compared to a group of 50 age- and sex-matched healthy controls. The schizophrenia group obtained higher values both for vividness of imagery and occurrence of hallucinations. These differences were independent of general intelligence and psychomotor speed and did not correlate with individual psychopathology. The correlation between the hallucination and imagery scales themselves was very low. These results suggest that patients with schizophrenia experience a significantly greater vividness of mental imagery than healthy controls, which does not seem to be an effect of other group differences or individual psychopathology (e.g., frequency of hallucinations). Vividness of mental imagery might thus prove to be an independent trait marker of schizophrenia.

Functional connectivity as revealed by spatial independent component analysis of fMRI measurements during rest.

Cortical functional connectivity, as indicated by the concurrent spontaneous activity of spatially segregated regions, is being studied increasingly because it may determine the reaction of the brain to external stimuli and task requirements and it is reportedly altered in many neurological and psychiatric disorders. In functional magnetic resonance imaging (fMRI), such functional connectivity is investigated commonly by correlating the time course of a chosen "seed voxel" with the remaining voxel time courses in a voxel-by-voxel manner. This approach is biased by the actual choice of the seed voxel, however, because it only shows functional connectivity for the chosen brain region while ignoring other potentially interesting patterns of coactivation. We used spatial independent component analysis (sICA) to assess cortical functional connectivity maps from resting state data. SICA does not depend on any chosen temporal profile of local brain activity. We hypothesized that sICA would be able to find functionally connected brain regions within sensory and motor regions in the absence of task-related brain activity. We also investigated functional connectivity patterns of several parietal regions including the superior parietal cortex and the posterior cingulate gyrus. The components of interest were selected in an automated fashion using predefined anatomical volumes of interest. SICA yielded connectivity maps of bilateral auditory, motor and visual cortices. Moreover, it showed that prefrontal and parietal areas are also functionally connected within and between hemispheres during the resting state. These connectivity maps showed an extremely high degree of consistency in spatial, temporal, and frequency parameters within and between subjects. These results are discussed in the context of the recent debate on the functional relevance of fluctuations of neural activity in the resting state.