Anti-neuronal anti-bodies in patients with early psychosis.

It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n=70) or a clinical high-risk for psychosis (n=6) and controls (n=34). We investigated the serum prevalence of 24 anti-neuronal autoantibodies: IgG antibodies for anti-N-methyl-d-aspartate-type glutamate receptor (anti-NMDAR), glutamate and γ-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2). Anti-NMDA IgG antibodies were positive with serum titer 1:320 in one patient with a clinical high risk for psychosis. He did not receive a diagnosis of encephalitis after comprehensive neurological evaluation. All other antineuronal autoantibodies were negative and there were no additional findings with immunohistochemistry of brain issues.

Dorsomedial prefontal cortex supports spontaneous thinking per se.

Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc.

Precuneus functioning differentiates first-episode psychosis patients during the fantasy movie Alice in Wonderland.

BACKGROUND: While group-level functional alterations have been identified in many brain regions of psychotic patients, multivariate machine-learning methods provide a tool to test whether some of such alterations could be used to differentiate an individual patient. Earlier machine-learning studies have focused on data collected from chronic patients during rest or simple tasks. We set out to unravel brain activation patterns during naturalistic stimulation in first-episode psychosis (FEP). METHOD: We recorded brain activity from 46 FEP patients and 32 control subjects viewing scenes from the fantasy film Alice in Wonderland. Scenes with varying degrees of fantasy were selected based on the distortion of the 'sense of reality' in psychosis. After cleaning the data with a novel maxCorr method, we used machine learning to classify patients and healthy control subjects on the basis of voxel- and time-point patterns. RESULTS: Most (136/194) of the voxels that best classified the groups were clustered in a bilateral region of the precuneus. Classification accuracies were up to 79.5% (p = 5.69 × 10-8), and correct classification was more likely the higher the patient's positive-symptom score. Precuneus functioning was related to the fantasy content of the movie, and the relationship was stronger in control subjects than patients. CONCLUSIONS: These findings are the first to show abnormalities in precuneus functioning during naturalistic information processing in FEP patients. Correlational findings suggest that these alterations are associated with positive psychotic symptoms and processing of fantasy. The results may provide new insights into the neuronal basis of reality distortion in psychosis.

Cortical salience network activation precedes the development of delusion severity.

BACKGROUND: Delusion is the most characteristic symptom of psychosis. While researchers suggested an association between changes of the cortical salience network (CSN) and delusion, whether these CSN findings are a cause or a consequence of delusion remains unknown. METHOD: To assess the effect of CSN functioning to forthcoming changes in delusion scores, we measured brain activation with 3-T functional magnetic resonance imaging in two independent samples of first-episode psychosis patients (total of 27 patients and 23 healthy controls). During scanning, the patients evaluated statements about whether an individual's psychosis-related experiences should be described as a mental illness, and control statements that were also evaluated by healthy controls. Symptoms were assessed at the baseline and at 2 months follow-up with Brief Psychiatric Rating Scale. RESULTS: Both tasks activated the CSN in comparison with rest. Activation of CSN ('illness evaluation v. control task' contrast) in patients positively correlated with worsening of or less improvement in delusions at the 2-month follow-up assessment. This finding was independent of delusion and clinical insight scores at the baseline evaluation. CONCLUSIONS: Our findings link symptom-evaluation-related CSN functioning to severity of delusion and, importantly, add a new layer of evidence for the contribution of CSN functioning to the longitudinal course of delusions.

Improving diffusion MRI using simultaneous multi-slice echo planar imaging.

In diffusion MRI, simultaneous multi-slice single-shot EPI acquisitions have the potential to increase the number of diffusion directions obtained per unit time, allowing more diffusion encoding in high angular resolution diffusion imaging (HARDI) acquisitions. Nonetheless, unaliasing simultaneously acquired, closely spaced slices with parallel imaging methods can be difficult, leading to high g-factor penalties (i.e., lower SNR). The CAIPIRINHA technique was developed to reduce the g-factor in simultaneous multi-slice acquisitions by introducing inter-slice image shifts and thus increase the distance between aliased voxels. Because the CAIPIRINHA technique achieved this by controlling the phase of the RF excitations for each line of k-space, it is not directly applicable to single-shot EPI employed in conventional diffusion imaging. We adopt a recent gradient encoding method, which we termed "blipped-CAIPI", to create the image shifts needed to apply CAIPIRINHA to EPI. Here, we use pseudo-multiple replica SNR and bootstrapping metrics to assess the performance of the blipped-CAIPI method in 3× simultaneous multi-slice diffusion studies. Further, we introduce a novel image reconstruction method to reduce detrimental ghosting artifacts in these acquisitions. We show that data acquisition times for Q-ball and diffusion spectrum imaging (DSI) can be reduced 3-fold with a minor loss in SNR and with similar diffusion results compared to conventional acquisitions.

Timing of human cortical functions during cognition: role of MEG.

Understanding of sensory and cognitive brain processes requires information about activation timing within and between different brain sites. Such data can be obtained by magnetoencephalography (MEG) that tracks cortical activation sequences with a millisecond temporal accuracy. MEG is gaining a well-established role in human neuroscience, complementing with its excellent temporal resolution the spatially more focused brain imaging methods. As examples of MEG's role in cognitive neuroscience, we discuss time windows related to cortical processing of sensory and multisensory stimuli, effects of the subject's own voice on the activity of their auditory cortex, timing of brain activation in reading, and cortical dynamics of the human mirror-neuron system activated when the subject views another person's movements.

Cognitive response profile of the human fusiform face area as determined by MEG.

Activation in or near the fusiform gyrus was estimated to faces and control stimuli. Activation peaked at 165 ms and was strongest to digitized photographs of human faces, regardless of whether they were presented in color or grayscale, suggesting that face- and color-specific areas are functionally separate. Schematic sketche evoked approximately 30% less activation than did face photographs. Scrambling the locations of facial features reduced the response by approximately 25% in either hemisphere, suggesting that configurational versus analytic processing is not lateralized at this latency. Animal faces evoked approximately 50% less activity, and common objects, animal bodies or sensory controls evoked approximately 80% less activity than human faces. The (small) responses evoked by meaningless control images were stronger when they included surfaces and shading, suggesting that the fusiform gyrus may use these features in constructing its face-specific response. Putative fusiform activation was not significantly related to stimulus repetition, gender or emotional expression. A midline occipital source significantly distinguished between faces and control images as early as 110 ms, but was more sensitive to sensory qualities. This source significantly distinguished happy and sad faces from those with neutral expressions. We conclude that the fusiform gyrus may selectively encode faces at 165 ms, transforming sensory input for further processing.

Audiovisual integration of letters in the human brain.

Letters of the alphabet have auditory (phonemic) and visual (graphemic) qualities. To investigate the neural representations of such audiovisual objects, we recorded neuromagnetic cortical responses to auditorily, visually, and audiovisually presented single letters. The auditory and visual brain activations first converged around 225 ms after stimulus onset and then interacted predominantly in the right temporo-occipito-parietal junction (280345 ms) and the left (380-540 ms) and right (450-535 ms) superior temporal sulci. These multisensory brain areas, playing a role in audiovisual integration of phonemes and graphemes, participate in the neural network supporting the supramodal concept of a "letter." The dynamics of these functions bring new insight into the interplay between sensory and association cortices during object recognition.

Left-hemisphere dominance for processing of vowels: a whole-scalp neuromagnetic study.

Brain activation of 11 healthy right-handed subjects was studied with magnetoencephalography to estimate individual hemispheric dominance for speech sounds. The auditory stimuli comprised binaurally presented Finnish vowels, tones, and piano notes in groups of two or four stimuli. The subjects were required to detect whether the first and the last item in a group were the same. In the left hemisphere, vowels evoked significantly stronger (37-79%) responses than notes and tones, whereas in the right hemisphere the responses to different stimuli did not differ significantly. Specifically, in the two-stimulus task, all 11 subjects showed left-hemisphere dominance in the vowel vs tone comparison. This simple paradigm may be helpful in non-invasive evaluation of language lateralization.

Patterns of brain activity during visual imagery of letters.

Cortical signals associated with visual imagery of letters were recorded from 10 healthy adults with a whole-scalp 122-channel neuromagnetometer. The auditory stimulus sequence consisted of 20 different phonemes corresponding to single letters of the Roman alphabet and of tone pips (17%), delivered once every 1.5 sec in a random order. The subjects were instructed to visually imagine the letter corresponding to the auditory stimulus and to examine its visuospatial properties: The associated brain activity was compared with activity evoked by the same stimuli when the subjects just detected the intervening tones. All subjects produced broad imagery-related responses over multiple cortical regions. After initial activation of the auditory cortices, the earliest imagery-related responses originated in the left prerolandic area 320 msec after the voice onset. They were followed within 70 msec by signals originating in the posterior parietal lobe close to midline (precuneus) and, 100 msec later, in the posterior superior temporal areas, predominantly in the left hemisphere. The activations were sustained and partially overlapping in time. Imagery-related activity in the left lateral occipital cortex was observed in two subjects, and weak late activity in the calcarine cortex in one subject. Real audiovisually presented letters activated multiple brain regions, and task-induced visuospatial processing of these stimuli further increased activity in some of these regions and activated additional areas: Some of these areas were activated during imagery as well. The results suggest that certain brain areas involved in high-level visual perception are activated during visual imagery and that the extent of imagery-related activity is dictated by the requirements of the stimuli and the task.

Human auditory cortex is activated by omissions of auditory stimuli.

Cortical signals associated with infrequent tone omissions were recorded from 9 healthy adults with a whole-head 122 channel neuromagnetometer. The stimulus sequence consisted of monaural (left or right) 50-ms 1-kHz tones repeated every 0.2 or 0.5 s, with 7% of the tones randomly omitted. Tones elicited typical responses in the supratemporal auditory cortices. Omissions evoked strong responses over temporal and frontal areas, independently of the side of stimulation, with peak amplitudes at 145-195 ms. Response amplitudes were 60% weaker when the subject was not attending to the stimuli. Omission responses originated in supratemporal auditory cortices bilaterally, indicating that auditory cortex plays an important role in the brain's modelling of temporal characteristics of the auditory environment. Additional activity was observed in the posterolateral frontal cortex and in the superior temporal sulcus, more often in the right than in the left hemisphere.