Chronic Pelvic Pain Syndrome in Men is Associated with Reduction of Relative Gray Matter Volume in the Anterior Cingulate Cortex Compared to Healthy Controls

Although chronic pelvic pain syndrome impairs the life of millions of people worldwide, the exact pathomechanisms involved remain to be elucidated. As with other chronic pain syndromes, the central nervous system may have an important role in chronic pelvic pain syndrome. Thus, we assessed brain alterations associated with abnormal pain processing in patients with chronic pelvic pain syndrome.

Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex

The right posterior parietal cortex (PPC) is critically involved in visual exploration behaviour, and damage to this area may lead to neglect of the left hemispace. We investigated whether neglect-like visual exploration behaviour could be induced in healthy subjects using theta burst repetitive transcranial magnetic stimulation (rTMS). To this end, one continuous train of theta burst rTMS was applied over the right PPC in 12 healthy subjects prior to a visual exploration task where colour photographs of real-life scenes were presented on a computer screen. In a control experiment, stimulation was also applied over the vertex. Eye movements were measured, and the distribution of visual fixations in the left and right halves of the screen was analysed. In comparison to the performance of 28 control subjects without stimulation, theta burst rTMS over the right PPC, but not the vertex, significantly decreased cumulative fixation duration in the left screen-half and significantly increased cumulative fixation duration in the right screen-half for a time period of 30 min. These results suggest that theta burst rTMS is a reliable method of inducing transient neglect-like visual exploration behaviour.

The role of the human posterior parietal cortex in memory-guided saccade execution: a double-pulse transcranial magnetic stimulation study

The present study investigated the role of the right posterior parietal cortex (PPC) in the triggering of memory-guided saccades by means of double-pulse transcranial magnetic stimulation (dTMS). Shortly before saccade onset, dTMS with different interstimulus intervals (ISI; 35, 50, 65 or 80 ms) was applied. For contralateral saccades, dTMS significantly decreased saccadic latency with an ISI of 80 ms and increased saccadic gain with an ISI of 65 and 80 ms. Together with the findings of a previous study during frontal eye field (FEF) stimulation the present results demonstrate similarities and differences between both regions in the execution of memory-guided saccades. Firstly, dTMS facilitates saccade triggering in both regions, but the timing is different. Secondly, dTMS over the PPC provokes a hypermetria of contralateral memory-guided saccades that was not observed during FEF stimulation. The results are discussed within the context of recent neurophysiological findings in monkeys.

Nerve Injury-Induced Neuropathic Pain Causes Disinhibition of the Anterior Cingulate Cortex

Neuropathic pain caused by peripheral nerve injury is a debilitating neurological condition of high clinical relevance. On the cellular level, the elevated pain sensitivity is induced by plasticity of neuronal function along the pain pathway. Changes in cortical areas involved in pain processing contribute to the development of neuropathic pain. Yet, it remains elusive which plasticity mechanisms occur in cortical circuits. We investigated the properties of neural networks in the anterior cingulate cortex (ACC), a brain region mediating affective responses to noxious stimuli. We performed multiple whole-cell recordings from neurons in layer 5 (L5) of the ACC of adult mice after chronic constriction injury of the sciatic nerve of the left hindpaw and observed a striking loss of connections between excitatory and inhibitory neurons in both directions. In contrast, no significant changes in synaptic efficacy in the remaining connected pairs were found. These changes were reflected on the network level by a decrease in the mEPSC and mIPSC frequency. Additionally, nerve injury resulted in a potentiation of the intrinsic excitability of pyramidal neurons, whereas the cellular properties of interneurons were unchanged. Our set of experimental parameters allowed constructing a neuronal network model of L5 in the ACC, revealing that the modification of inhibitory connectivity had the most profound effect on increased network activity. Thus, our combined experimental and modeling approach suggests that cortical disinhibition is a fundamental pathological modification associated with peripheral nerve damage. These changes at the cortical network level might therefore contribute to the neuropathic pain condition.

The Role of the Right Posterior Parietal Cortex in Letter Migration between Words

When briefly presented with pairs of words, skilled readers can sometimes report words with migrated letters (e.g., they report hunt when presented with the words hint and hurt). These letter migration phenomena have been often used to investigate factors that influence reading such as letter position coding. However, the neural basis of letter migration is poorly understood. Previous evidence has implicated the right posterior parietal cortex (PPC) in processing visuospatial attributes and lexical properties during word reading. The aim of this study was to assess this putative role by combining an inhibitory TMS protocol with a letter migration paradigm, which was designed to examine the contributions of visuospatial attributes and lexical factors. Temporary interference with the right PPC led to three specific effects on letter migration. First, the number of letter migrations was significantly increased only in the group with active stimulation (vs. a sham stimulation group or a control group without stimulation), and there was no significant effect on other error types. Second, this effect occurred only when letter migration could result in a meaningful word (migration vs. control context). Third, the effect of active stimulation on the number of letter migrations was lateralized to target words presented on the left. Our study thus demonstrates that the right PPC plays a specific and causal role in the phenomenon of letter migration. The nature of this role cannot be explained solely in terms of visuospatial attention, rather it involves an interplay between visuospatial attentional and word reading-specific factors.

Prefrontal Thinning Affects Functional Connectivity and Regional Homogeneity of the Anterior Cingulate Cortex in Depression

Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment.

Resting state cerebral blood flow and objective motor activity reveal basal ganglia dysfunction in schizophrenia

Reduced motor activity has been reported in schizophrenia and was associated with subtype, psychopathology and medication. Still, little is known about the neurobiology of motor retardation. To identify neural correlates of motor activity, resting state cerebral blood flow (CBF) was correlated with objective motor activity of the same day. Participants comprised 11 schizophrenia patients and 14 controls who underwent magnetic resonance imaging with arterial spin labeling and wrist actigraphy. Patients had reduced activity levels and reduced perfusion of the left parahippocampal gyrus, left middle temporal gyrus, right thalamus, and right prefrontal cortex. In controls, but not in schizophrenia, CBF was correlated with activity in the right thalamic ventral anterior (VA) nucleus, a key module within basal ganglia-cortical motor circuits. In contrast, only in schizophrenia patients positive correlations of CBF and motor activity were found in bilateral prefrontal areas and in the right rostral cingulate motor area (rCMA). Grey matter volume correlated with motor activity only in the left posterior cingulate cortex of the patients. The findings suggest that basal ganglia motor control is impaired in schizophrenia. In addition, CBF of cortical areas critical for motor control was associated with volitional motor behavior, which may be a compensatory mechanism for basal ganglia dysfunction.

Electroencephalographic topography measures of experienced utility

Economic theory distinguishes two concepts of utility: decision utility, objectively quantifiable by choices, and experienced utility, referring to the satisfaction by an obtainment. To date, experienced utility is typically measured with subjective ratings. This study intended to quantify experienced utility by global levels of neuronal activity. Neuronal activity was measured by means of electroencephalographic (EEG) responses to gain and omission of graded monetary rewards at the level of the EEG topography in human subjects. A novel analysis approach allowed approximating psychophysiological value functions for the experienced utility of monetary rewards. In addition, we identified the time windows of the event-related potentials (ERP) and the respective intracortical sources, in which variations in neuronal activity were significantly related to the value or valence of outcomes. Results indicate that value functions of experienced utility and regret disproportionally increase with monetary value, and thus contradict the compressing value functions of decision utility. The temporal pattern of outcome evaluation suggests an initial (∼250 ms) coarse evaluation regarding the valence, concurrent with a finer-grained evaluation of the value of gained rewards, whereas the evaluation of the value of omitted rewards emerges later. We hypothesize that this temporal double dissociation is explained by reward prediction errors. Finally, a late, yet unreported, reward-sensitive ERP topography (∼500 ms) was identified. The sources of these topographical covariations are estimated in the ventromedial prefrontal cortex, the medial frontal gyrus, the anterior and posterior cingulate cortex and the hippocampus/amygdala. The results provide important new evidence regarding “how,” “when,” and “where” the brain evaluates outcomes with different hedonic impact.

Reduced Cerebral Blood Flow Within the Default-Mode Network and Within Total Gray Matter in Major Depression

The default-mode network (DMN) was shown to have aberrant blood oxygenation-level-dependent (BOLD) activity in major depressive disorder (MDD). While BOLD is a relative measure of neural activity, cerebral blood flow (CBF) is an absolute measure. Resting-state CBF alterations have been reported in MDD. However, the association of baseline CBF and CBF fluctuations is unclear in MDD. Therefore, the aim was to investigate the CBF within the DMN in MDD, applying a strictly data-driven approach. In 22 MDD patients and 22 matched healthy controls, CBF was acquired using arterial spin labeling (ASL) at rest. A concatenated independent component analysis was performed to identify the DMN within the ASL data. The perfusion of the DMN and its nodes was quantified and compared between groups. The DMN was identified in both groups with high spatial similarity. Absolute CBF values within the DMN were reduced in MDD patients (p<0.001). However, after controlling for whole-brain gray matter CBF and age, the group difference vanished. In patients, depression severity was correlated with reduced perfusion in the DMN in the posterior cingulate cortex and the right inferior parietal lobe. Hypoperfusion within the DMN in MDD is not specific to the DMN. Still, depression severity was linked to DMN node perfusion, supporting a role of the DMN in depression pathobiology. The finding has implications for the interpretation of BOLD functional magnetic resonance imaging data in MDD.

The effects of catecholamine depletion on the neural response to fearful faces in remitted depression

Recent evidence suggests that increased psychophysiological response to negatively valenced emotional stimuli found in major depressive disorder (MDD) may be associated with reduced catecholaminergic neurotransmission. Fourteen unmedicated, remitted subjects with MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover trial. Subjects were exposed to fearful (FF) and neutral faces (NF) during a scan with [15O]H2O positron emission tomography to assess the brain-catecholamine interaction in brain regions previously associated with emotional face processing. Treatment with AMPT resulted in significantly increased, normalized cerebral blood flow (CBF) in the left inferior temporal gyrus (ITG) and significantly decreased CBF in the right cerebellum across conditions and groups. In RMDD, flow in the left posterior cingulate cortex (PCC) increased significantly in the FF compared to the NF condition after AMPT, but remained unchanged after placebo, whereas healthy controls showed a significant increase under placebo and a significant decrease under AMPT in this brain region. In the left dorsolateral prefrontal cortex (DLPFC), flow decreased significantly in the FF compared to the NF condition under AMPT, and increased significantly under placebo in RMDD, whereas healthy controls showed no significant differences. Differences between AMPT and placebo of within-session changes in worry-symptoms were positively correlated with the corresponding changes in CBF in the right subgenual prefrontal cortex in RMDD. In conclusion, this study provided evidence for a catecholamine-related modulation of the neural responses to FF expressions in the left PCC and the left DLPFC in subjects with RMDD that might constitute a persistent, trait-like abnormality in MDD.

Comparative Behavioral and Neural Effects of Tryptophan and Catecholamine Depletion in Remitted Depression

Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and catecholamines play common and differential roles in the pathophysiology of depression.

Zazen meditation and no-task resting EEG compared with LORETA intracortical source localization

Meditation is a self-induced and willfully initiated practice that alters the state of consciousness. The meditation practice of Zazen, like many other meditation practices, aims at disregarding intrusive thoughts while controlling body posture. It is an open monitoring meditation characterized by detached moment-to-moment awareness and reduced conceptual thinking and self-reference. Which brain areas differ in electric activity during Zazen compared to task-free resting? Since scalp electroencephalography (EEG) waveforms are reference-dependent, conclusions about the localization of active brain areas are ambiguous. Computing intracerebral source models from the scalp EEG data solves this problem. In the present study, we applied source modeling using low resolution brain electromagnetic tomography (LORETA) to 58-channel scalp EEG data recorded from 15 experienced Zen meditators during Zazen and no-task resting. Zazen compared to no-task resting showed increased alpha-1 and alpha-2 frequency activity in an exclusively right-lateralized cluster extending from prefrontal areas including the insula to parts of the somatosensory and motor cortices and temporal areas. Zazen also showed decreased alpha and beta-2 activity in the left angular gyrus and decreased beta-1 and beta-2 activity in a large bilateral posterior cluster comprising the visual cortex, the posterior cingulate cortex and the parietal cortex. The results include parts of the default mode network and suggest enhanced automatic memory and emotion processing, reduced conceptual thinking and self-reference on a less judgmental, i.e., more detached moment-to-moment basis during Zazen compared to no-task resting.

Rivastigmine effects on EEG spectra and three-dimensional LORETA functional imaging in Alzheimer's disease

OBJECTIVE The objective of the study is to investigate the electrocortical and the global cognitive effects of 3 months rivastigmine medication in a group of mild to moderate Alzheimer's disease patients. MATERIALS AND METHODS Multichannel EEG and cognitive performances measured with the Mini Mental State Examination in a group of 16 patients with mild to moderate Alzheimer's Disease were collected before and 3 months after the onset of rivastigmine medication. RESULTS Spectral analysis of the EEG data showed a significant power decrease in the delta and theta frequency bands during rivastigmine medication, i.e., a shift of the power spectrum towards 'normalization'. Three-dimensional low resolution electromagnetic tomography (LORETA) functional imaging localized rivastigmine effects in a network that includes left fronto-parietal regions, posterior cingulate cortex, bilateral parahippocampal regions, and the hippocampus. Moreover, a correlation analysis between differences in the cognitive performances during the two recordings and LORETA-computed intracortical activity showed, in the alpha1 frequency band, better cognitive performance with increased cortical activity in the left insula. CONCLUSION The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.

I feel good whether my friends win or my foes lose: brain mechanisms underlying feeling similarity.

People say they enjoy both seeing a preferred social group succeed and seeing an adversary social group fail. At the same time, they state they dislike seeing a preferred social group fail and seeing an adversary social group succeed. The current magnetic resonance imaging study investigated whether-and if so, how-such similarities in reported feeling states are reflected in neural activities. American football fans anticipated success and failure situations for their favorite or their adversary teams. The data support the idea that feeling similarities and divergences expressed in verbal reports carry with them significant neural similarities and differences, respectively. Desired (favorite team likely to win and adversary team likely to lose) rather than undesired (favorite team likely to lose and adversary team likely to win) outcomes were associated with heightened activity in the supramarginal gyrus, posterior cingulate cortex, insula, and cerebellum. Precuneus activity additionally distinguished anticipated desirable outcomes for favorite versus adversary teams.