Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis

RATIONALE: Many studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-D-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2A agonist model). OBJECTIVES: The aim of the present study was to directly compare the two models of psychosis using an intraindividual crossover design. MATERIALS AND METHODS: Fifteen healthy subjects participated in a randomized, double-blind, crossover study with a low and a high dose of the 5HT2A agonist dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine. During electroencephalographic recording, the subjects were performing the AX-version of a continuous performance test (AX-CPT). A source analysis of MMN was performed on the basis of a four-source model of MMN generation. RESULTS: Nine subjects completed both experimental days with the two doses of both drugs. Overall, we found blunted MMN and performance deficits in the AX-CPT after both drugs. However, the reduction in MMN activity was overall more pronounced after S-ketamine intake, and only S-ketamine had a significant impact on the frontal source of MMN. CONCLUSIONS: The NDMA antagonist model and the 5HT2A agonist model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis

Evidence for Training-Induced Plasticity in Multisensory Brain Structures: An MEG Study

Multisensory learning and resulting neural brain plasticity have recently become a topic of renewed interest in human cognitive neuroscience. Music notation reading is an ideal stimulus to study multisensory learning, as it allows studying the integration of visual, auditory and sensorimotor information processing. The present study aimed at answering whether multisensory learning alters uni-sensory structures, interconnections of uni-sensory structures or specific multisensory areas. In a short-term piano training procedure musically naive subjects were trained to play tone sequences from visually presented patterns in a music notation-like system [Auditory-Visual-Somatosensory group (AVS)], while another group received audio-visual training only that involved viewing the patterns and attentively listening to the recordings of the AVS training sessions [Auditory-Visual group (AV)]. Training-related changes in cortical networks were assessed by pre- and post-training magnetoencephalographic (MEG) recordings of an auditory, a visual and an integrated audio-visual mismatch negativity (MMN). The two groups (AVS and AV) were differently affected by the training. The results suggest that multisensory training alters the function of multisensory structures, and not the uni-sensory ones along with their interconnections, and thus provide an answer to an important question presented by cognitive models of multisensory training

Cerebral cortical thickness in chronic pain due to knee osteoarthritis: the effect of pain duration and pain densitization

Objective This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. Methods Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females). Results Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age-controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. Conclusion With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role

A transition from unimodal to multimodal activations in four sensory modalities in humans: an electrophysiological study

<p>Abstract</p> <p>Background</p> <p>To investigate the long-latency activities common to all sensory modalities, electroencephalographic responses to auditory (1000 Hz pure tone), tactile (electrical stimulation to the index finger), visual (simple figure of a star), and noxious (intra-epidermal electrical stimulation to the dorsum of the hand) stimuli were recorded from 27 scalp electrodes in 14 healthy volunteers.</p> <p>Results</p> <p>Results of source modeling showed multimodal activations in the anterior part of the cingulate cortex (ACC) and hippocampal region (Hip). The activity in the ACC was biphasic. In all sensory modalities, the first component of ACC activity peaked 30–56 ms later than the peak of the major modality-specific activity, the second component of ACC activity peaked 117–145 ms later than the peak of the first component, and the activity in Hip peaked 43–77 ms later than the second component of ACC activity.</p> <p>Conclusion</p> <p>The temporal sequence of activations through modality-specific and multimodal pathways was similar among all sensory modalities.</p

Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task

Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia

Vestibular inputs modulate somatosensory cortical processing

The vestibular system is unique among the senses because of the entirely multisensory nature of its cortical projections. Neuroanatomical and neuroimaging studies show that vestibular stimulation activates somatosensory areas, and particularly the so-called parieto-insular vestibular cortex (PIVC) in the monkey, while deactivating visual areas. Further, recent psychophysical studies showed that vestibular stimulation facilitates detection of electrocutaneous stimuli, suggesting a vestibular-somatosensory perceptual interaction. However, the functional mechanism underlying this perceptual facilitation remains unclear. We therefore recorded somatosensory potentials evoked by left median nerve stimulation, before and immediately after left cold caloric vestibular stimulation (CVS), in a small-scale study of eight healthy volunteers. CVS selectively enhanced the N80 component recorded over both ipsilateral and contralateral somatosensory areas, without significantly affecting earlier or later components. Interestingly, the N80 component has been localised to the parietal operculum, which includes the human homologue of the monkey PIVC, and is thus a prime neuroanatomical candidate for vestibular-somatosensory convergence. As a control, we measured visual evoked potentials to reversing checkerboard patterns and found no effects of vestibular stimulation. This rules out explanations based on indirect effects of vestibular modulations, such as general arousal or supramodal spatial attention. We believe our results provide the first clue linking brain structure to function for the interaction between vestibular and somatosensory systems

Pseudoneglect for mental alphabet lines is affected by prismatic adaptation

While patients with right parietal damage and spatial neglect bisect lines to the right, the general population bisects lines to the left; a phenomenon known as pseudoneglect. The leftward bias also occurs for mental representations, such as number and alphabet lines. Prismatic adaptation can have a dramatic eVect on attentional bias and corrects neglect and pseudoneglect for physical and mental number lines. This study examined whether prismatic adaptation can correct leftward bisection biasesfor alphabet lines, which may have a diVerent spatial arrangement compared to number lines. In pre-adaptation testing, students (n = 42) were shown letter trigrams (e.g. C H P) and judged whether the alphabetical distance before or after the inner-letter was larger. Participants were then split into three groups and were adapted to left-shifting, control or right-shifting prims. After adaptation, the mental alphabet bisection task was re-administered. The length of left side of the alphabet lines was overestimated by all three groups in the pre-adaptation phase. Right-shifting prisms and control spectacles had no eVect on the leftward bias whereas exposure to left-shifting prisms corrected the bias. The results replicate an eVect observed for mental number lines and demonstrate that low-level sensory-motor shifts can correct attentional biases associated with high-level representations, such as letters