Cortical Thickness Alterations in Chronic Pain Disorder: An Exploratory MRI Study.

OBJECTIVE: Chronic pain disorder (CPD) has been associated with brain changes, especially in limbic circuits. However, in most patients with chronic pain, depression or anxiety is a common comorbidity. In this exploratory and naturalistic study, we investigated brain cortical thickness (CTh) differences between patients with CPD and healthy controls, with consideration of concurrent psychiatric symptoms. METHODS: Twenty-three patients with CPD and 23 age- and sex-matched healthy volunteers were included in this study. CTh was estimated using Freesurfer on high-resolution three-dimensional T1-weighted images acquired with a 3T scanner. Group differences were investigated using an analysis of covariance model that included age, sex, and Beck Depression Inventory I and Trait Anxiety Inventory scores as covariates. The relationship between CTh and Toronto Alexithymia Scale (TAS-20) scores was also investigated in patients. Data were corrected for multiplicity using the False Discovery Rate approach (q < .05). RESULTS: The comparison between groups using demographics and Beck Depression Inventory I scores as covariates showed thinner cortex in patients compared with controls, after correction for multiplicity in the left precentral (F(1,42) = 21.9, p < .05) and postcentral gyri (F(1,42) = 26.9, p < .05) and in the left inferior temporal sulcus (F(1,42) = 19.6, p < .05). Moreover, using the Trait Anxiety Inventory as covariate, a trend toward significance (p < .001 uncorrected) was seen for the left precentral gyrus (F(1,42) = 13.8), right middle frontal (F(1,42) = 14.3) and inferior parietal gyri (F(1,42) = 13.4), and right anterior temporal pole (F(1,42) = 15.9). CONCLUSIONS: The results indicate that brain morphological differences between patients with chronic pain disorder and healthy controls are localized to regions that correspond to sensory as well as affective dimensions of pain processing.

A Comparison of Dual Attention, Eye Movements, and Exposure Only during Eye Movement Desensitization and Reprocessing for Posttraumatic Stress Disorder: Results from a Randomized Clinical Trial.

BACKGROUND: Currently, there is controversy on the possible benefits of dual-attention tasks during eye movement desensitization and reprocessing (EMDR) for patients with posttraumatic stress disorder (PTSD). METHODS: A total of 139 consecutive patients (including 85 females) suffering from PTSD were allocated randomly among 3 different treatment conditions: exposure with eyes moving while fixating on the therapist's moving hand (EM), exposure with eyes fixating on the therapist's nonmoving hand (EF), and exposure without explicit visual focus of attention as control condition (EC). Except for the variation in stimulation, treatment strictly followed the standard EMDR manual. Symptom changes from pre- to posttreatment were measured with the Clinician-Administered PTSD Scale (CAPS) by an investigator blinded to treatment allocation. RESULTS: In total, 116 patients completed the treatment, with an average of 4.6 sessions applied. Intention-to-treat analysis revealed a significant improvement in PTSD symptoms with a high overall effect size (Cohen's d = 1.96, 95% CI: 1.67-2.24) and a high remission rate of PTSD diagnosis (79.8%). In comparison to the control condition, EM and EF were associated with significantly larger pre-post symptom decrease (ΔCAPS: EM = 35.8, EF = 40.5, EC = 31.0) and significantly larger effect sizes (EM: d = 2.06, 95% CI: 1.55-2.57, EF: d = 2.58, 95% CI: 2.01-3.11, EC: d = 1.44, 95% CI: 0.97-1.91). No significant differences in symptom decrease and effect size were found between EM and EF. CONCLUSIONS: Exposure in combination with an explicit external focus of attention leads to larger PTSD symptom reduction than exposure alone. Eye movements have no advantage compared to visually fixating on a nonmoving hand.

[Functional and Somatoform Disorders in the Mirror of ICD-10 Routine Data]. / Funktionelle und somatoforme Störungen im Spiegel von ICD-10-Routinedaten.

The ICD-10 offers the possibility of double coding of diagnoses in functional disorders on the one hand, somatoform disorders on the other side. The current S3 guideline for "dealing with patients with non-specific, functional and somatoform physical complaints" states that "[...] in most cases, the specialty of the (initial) examiner and not the clinical constellation seems to define how a diagnosis is made". Based on selective routine data of the Daimler BKK for the years 2008-2010 frequencies of specific functional diagnoses were compared with those of somatoform disorders, additional diagnoses analyzed and compared with epidemiological data from the Federal Health Monitoring System. The incidence found in epidemiological studies of somatoform disorders cannot be found in present routine data. Functional disorders were more frequently diagnosed than somatoform disorders. Certain additional diagnoses that may provide clues to etiological relations are rarely used. As the validity, reliability and purpose of ICD-10 invoicing diagnoses is debatable, there seems to be an imbalance relevant for the health care system. Non-adherence to the guidelines may prevent adequate quality and quantity of patient care.

Is the Medial Prefrontal Cortex Necessary for Theory of Mind?

BACKGROUND: Successful social interaction relies on the ability to attribute mental states to other people. Previous functional neuroimaging studies have shown that this process, described as Theory of Mind (ToM) or mentalization, is reliably associated with activation of the medial prefrontal cortex (mPFC). However, this study presents a novel and surprising finding that provides new insight into the role of the mPFC in mentalization tasks. METHODOLOGY/PRINCIPAL FINDINGS: Twenty healthy individuals were recruited from a wide range of ages and social backgrounds. Participants underwent functional magnetic resonance imaging (fMRI) while viewing a well-established ToM visual paradigm involving moving triangles. Functional MRI data were analyzed using a classical general linear model. No activation was detected in the medial prefrontal cortex (mPFC) during movement patterns that typically elicit ToM. However, increased activity was observed in the right middle occipital gyrus, right temporoparietal junction (TPJ), left middle occipital gyrus and right inferior frontal gyrus. No correlation was found between participants' age and BOLD response. CONCLUSIONS/SIGNIFICANCE: In contrast with previous neuroimaging research, our findings support the notion that mPFC function is not critical for reasoning about the mental states of others; furthermore, our data indicate that the right TPJ and right inferior frontal gyrus are able to perform mentalization without any contributions from the mPFC.

Frequency shifts in the anterior default mode network and the salience network in chronic pain disorder.

BACKGROUND: Recent functional imaging studies on chronic pain of various organic etiologies have shown significant alterations in both the spatial and the temporal dimensions of the functional connectivity of the human brain in its resting state. However, it remains unclear whether similar changes in intrinsic connectivity networks (ICNs) also occur in patients with chronic pain disorder, defined as persistent, medically unexplained pain. METHODS: We compared 21 patients who suffered from chronic pain disorder with 19 age- and gender-matched controls using 3T-fMRI. All neuroimaging data were analyzed using both independent component analysis (ICA) and power spectra analysis. RESULTS: In patients suffering from chronic pain disorder, the fronto-insular 'salience' network (FIN) and the anterior default mode network (aDMN) predominantly oscillated at higher frequencies (0.20 - 0.24 Hz), whereas no significant differences were observed in the posterior DMN (pDMN) and the sensorimotor network (SMN). CONCLUSIONS: Our results indicate that chronic pain disorder may be a self-sustaining and endogenous mental process that affects temporal organization in terms of a frequency shift in the rhythmical dynamics of cortical networks associated with emotional homeostasis and introspection.

Neural correlates of deficits in pain-related affective meaning construction in patients with chronic pain disorder.

OBJECTIVE: Psychological and neural mechanisms of the affective dimension of pain are known to be disturbed in patients with chronic pain disorder. The aim of this functional magnetic resonance imaging study was to assess the neurofunctional and behavioral measures underlying the ability to construct pain-related affective meaning in a painful situation by comparing 21 clinically and psychometrically well-characterized patients with persistent non-nociceptive somatoform pain with 19 healthy controls. METHODS: The functional magnetic resonance imaging task involved viewing pictures depicting human hands and feet in different painful and nonpainful situations. Participants were asked to estimate the perceived pain intensity. These data were correlated with behavioral measures of depression, alexithymia, and general cognitive and emotional empathy. RESULTS: In a hypothesis-driven region-of-interest analysis, the healthy control group exhibited greater activation of the left perigenual anterior cingulate cortex than patients with pain (Montreal Neurological Institute coordinates (x y z)=-8 38 0; cluster extent=54 voxels; T=4.28; p=.006 corrected for multiple comparisons at cluster level). No group differences in the activation of the anterior insular cortex were found. Scores on self-assessment instruments (Beck Depression Inventory I, Interpersonal Reactivity Index, and 20-item Toronto Alexithymia Scale) did not influence neuroimaging results. CONCLUSIONS: Our results suggest that patients with chronic medically unexplained pain have an altered neural pain perception process owing to decreased activation of empathetic-affective networks, which we interpret as a deficit in pain-related affective meaning construction. These findings may lead to a more specific and detailed neurobiological understanding of the clinical impression of disturbed affect in patients with chronic pain disorder.

Functional network connectivity of pain-related resting state networks in somatoform pain disorder: an exploratory fMRI study.

BACKGROUND: Without stimulation, the human brain spontaneously produces highly organized, low-frequency fluctuations of neural activity in intrinsic connectivity networks (ICNs). Furthermore, without adequate explanatory nociceptive input, patients with somatoform pain disorder experience pain symptoms, thus implicating a central dysregulation of pain homeostasis. The present study aimed to test whether interactions among pain-related ICNs, such as the default mode network (DMN), cingular-insular network (CIN) and sensorimotor network (SMN), are altered in somatoform pain during resting conditions. METHODS: Patients with somatoform pain disorder and healthy controls underwent resting functional magnetic resonance imaging that lasted 370 seconds. Using a data-driven approach, the ICNs were isolated, and the functional network connectivity (FNC) was computed. RESULTS: Twenty-one patients and 19 controls enrolled in the study. Significant FNC (p < 0.05, corrected for false discovery rate) was detected between the CIN and SMN/anterior DMN, the anterior DMN and posterior DMN/SMN, and the posterior DMN and SMN. Interestingly, no group differences in FNC were detected. LIMITATIONS: The most important limitation of this study was the relatively short resting state paradigm. CONCLUSION: To our knowledge, our results demonstrated for the first time the resting FNC among pain-related ICNs. However, our results suggest that FNC signatures alone are not able to characterize the putative central dysfunction underpinning somatoform pain disorder.

Acupuncture-induced pain relief and the human brain's default mode network - an extended view of central effects of acupuncture analgesia.

As a complementary medical procedure, acupuncture has a significant impact on the treatment of acute and chronic pain. Though the physiological mechanisms behind this method are still unclear, acupuncture has been claimed to rely also on changes in the central nervous system. Recent functional imaging studies indicate that the so-called default mode network (DMN) which consists of cortical midline structures and lateral parietal regions plays an important role in these processes. This brief overview describes the effects of analgesic acupuncture on the DMN architecture. The stronger interplay between systems dedicated to endogenous analgesia (periaqueductal gray), affective processing (anterior cingulate cortex, amygdala), memory (hippocampus), and self-projective thinking (DMN) following this therapy supports the notion that acupuncture is a mind-body therapy which helps to reintegrate important neural dimensions of inner life and to establish psychophysical pain homeostasis.

Aftermath of sexual abuse history on adult patients suffering from chronic functional pain syndromes: an fMRI pilot study.

OBJECTIVE: This preliminary study investigates the neural substrates of empathy-induced pain in multisomatoform pain patients "with vs. without" a history of sexual abuse during childhood. METHODS: Using functional magnetic resonance imaging (fMRI) and behavioral measurements, we compared eight abused with eight nonabused patients using an established empathy-for-pain paradigm. RESULTS: Higher activations in left lateral and medial superior frontal gyrus as well as a nonsignificant activation of the right supplementary motor area in abused patients were detected. The nonabused participants showed higher activation of left hippocampus. There was no significant difference in subjective pain ratings between the groups. CONCLUSION: Although the number of participants still needs to be increased, our main findings mirror the clinical impression and support the notion of perturbed neuroprocessing of grievous stimuli in chronic pain patients with a history of sexual abuse.