Álvaro Díez

Spatial distribution and cognitive correlates of gamma noise power in schizophrenia.

BACKGROUND Brain activity is less organized in patients with schizophrenia than in healthy controls (HC). Noise power (scalp-recorded electroencephalographic activity unlocked to stimuli) may be of use for studying this disorganization. Method Fifty-four patients with schizophrenia (29 minimally treated and 25 stable treated), 23 first-degree relatives and 27 HC underwent clinical and cognitive assessments and an electroencephalographic recording during an oddball P300 paradigm to calculate noise power magnitude in the gamma band. We used a principal component analysis (PCA) to determine the factor structure of gamma noise power values across electrodes and the clinical and cognitive correlates of the resulting factors. RESULTS The PCA revealed three noise power factors, roughly corresponding to the default mode network (DMN), frontal and occipital regions respectively. Patients showed higher gamma noise power loadings in the first factor when compared to HC and first-degree relatives. In the patients, frontal gamma noise factor scores related significantly and inversely to working memory and problem-solving performance. There were no associations with symptoms. CONCLUSIONS There is an elevated gamma activity unrelated to task processing over regions coherent with the DMN topography in patients with schizophrenia. The same type of gamma activity over frontal regions is inversely related to performance in tasks with high involvement in these frontal areas. The idea of gamma noise as a possible biological marker for schizophrenia seems promising. Gamma noise might be of use in the study of underlying neurophysiological mechanisms involved in this disease.

Impaired prefrontal synaptic gain in people with psychosis and their relatives during the mismatch negativity

The mismatch negativity (MMN) evoked potential, a preattentive brain response to a discriminable change in auditory stimulation, is significantly reduced in psychosis. Glutamatergic theories of psychosis propose that hypofunction of NMDA receptors (on pyramidal cells and inhibitory interneurons) causes a loss of synaptic gain control. We measured changes in neuronal effective connectivity underlying the MMN using dynamic causal modeling (DCM), where the gain (excitability) of superficial pyramidal cells is explicitly parameterised. EEG data were obtained during a MMN task—for 24 patients with psychosis, 25 of their first‐degree unaffected relatives, and 35 controls—and DCM was used to estimate the excitability (modeled as self‐inhibition) of (source‐specific) superficial pyramidal populations. The MMN sources, based on previous research, included primary and secondary auditory cortices, and the right inferior frontal gyrus. Both patients with psychosis and unaffected relatives (to a lesser degree) showed increased excitability in right inferior frontal gyrus across task conditions, compared to controls. Furthermore, in the same region, both patients and their relatives showed a reversal of the normal response to deviant stimuli; that is, a decrease in excitability in comparison to standard conditions. Our results suggest that psychosis and genetic risk for the illness are associated with both context‐dependent (condition‐specific) and context‐independent abnormalities of the excitability of superficial pyramidal cell populations in the MMN paradigm. These abnormalities could relate to NMDA receptor hypofunction on both pyramidal cells and inhibitory interneurons, and appear to be linked to the genetic aetiology of the illness, thereby constituting potential endophenotypes for psychosis. Hum Brain Mapp 37:351–365, 2016.

Elevated noise power in gamma band related to negative symptoms and memory deficit in schizophrenia

BACKGROUND There is an increasing consideration for a disorganized cerebral activity in schizophrenia, perhaps relating to a synaptic inhibitory deficit in the illness. Noise power (scalp-recorded electroencephalographic activity unlocked to stimuli) may offer a non-invasive window to assess this possibility. METHODS 29 minimally-treated patients with schizophrenia (of which 17 were first episodes) and 27 healthy controls underwent clinical and cognitive assessments and an electroencephalographic recording during a P300 paradigm to calculate signal-to-noise ratio and noise power magnitudes in the theta and gamma bands. RESULTS In comparison to controls, a significantly higher gamma noise power was common to minimally-treated and first episode patients over P3, P4, T5 and Fz electrode sites. Those high values were directly correlated to negative symptom severity and inversely correlated to verbal memory scores in the patients. There were no differences in signal-to-noise ratio magnitudes among the groups. Gamma noise power at Fz discriminated significantly between patients and controls. No significant differences were found in theta noise power or in gamma noise power over the other electrode sites between the groups of patients and controls. LIMITATIONS We have not assessed phase-locked and non-phase locked power changes, a complementary approach that may yield useful information. CONCLUSIONS Gamma noise power may represent a useful and non-invasive tool for studying brain dysfunction in psychotic illness. These results suggest an inefficient activation pattern in schizophrenia.

Frontal gamma noise power and cognitive domains in schizophrenia

The cognitive deficit profile is different among individuals with schizophrenia. We quantified the amount of electroencephalographic activity unlocked to stimuli onset (noise power) over frontal regions regarding deficit in cognitive domains. Forty-six patients with schizophrenia and 27 healthy controls underwent clinical, cognitive and electrophysiological assessments. Noise power studies may be considered complementary but not equivalent to induced power studies. We compared gamma and theta noise power magnitude during a P300 paradigm between subsets of patients divided according to cognitive deficit in key domains and controls. Patients displayed higher gamma noise power activity at Fz site and significantly lower performance in all cognitive domains when compared to controls. The subset of patients with cognitive deficit for working memory and problem solving/executive functions domains displayed significantly higher frontal-lateral noise power values in comparison to the subset of patients without cognitive deficit and controls. Patients with significant cognitive deficits in domains with greater frontal contribution are also characterized by an abnormally higher gamma band noise power over the frontal region. Our data may endorse various biological subsets within schizophrenia, characterized by the presence or absence of a significant cognitive deficit in frontal domains.

Decreased entropy modulation of EEG response to novelty and relevance in schizophrenia during a P300 task

Abstract The analysis of the interaction between novelty and relevance may be of interest to test the aberrant salience hypothesis of schizophrenia (SCH). In comparison with other neuroimaging techniques, such as functional magnetic resonance imaging, electroencephalography (EEG) provides high temporal resolution. Therefore, EEG is useful to analyze transient dynamics in neural activity, even in the range of milliseconds. In this study, EEG activity from 31 patients with SCH and 38 controls was analyzed using Shannon spectral entropy (SE) and median frequency (MF). The aim of the study was to quantify differences between distractor (i.e., novelty) and target (i.e., novelty and relevance) tones in an auditory oddball paradigm. Healthy controls displayed a larger SE decrease in response to target stimulus than in response to distractor tones. SE decrease was accompanied by a significant and widespread reduction of MF (i.e., a significant slowing of EEG activity). In comparison with controls, patients showed a significant reduction of changes in SE in response to both target and distractor tones. These differences were also observed in patients that only received a minimal treatment prior to EEG recording. Furthermore, significant changes in SE were inversely correlated to positive and total symptoms severity for SCH patients. Our findings support the notion that SCH is associated with a reduced response to both novelty and relevance during an auditory P300 task.

Gamma Power and Cognition in Patients with Schizophrenia and Their First-Degree Relatives

Background: Gamma oscillations are essential for functional neural assembly formation underlying higher cerebral functions. Previous studies concerning gamma band power in schizophrenia have yielded diverse results. Methods: In this study, we assessed gamma band power in minimally treated patients with schizophrenia, their first-degree relatives and healthy controls during an oddball paradigm performance, as well as the relation between gamma power and cognitive performance. Results: We found a higher gamma power in the patient group than in the healthy controls at the P3, P4, Fz, Pz and T5 sites. Compared with their relatives, gamma power in the patients was only marginally higher over P3 and P4. We found a nearly significant inverse association between gamma power at F4 and Tower of London performance in the patients, as well as a significant inverse association between gamma power at T5 and verbal memory and working memory scores in the relatives. Conclusion: These results support higher total gamma power in association with schizophrenia and its inverse association with cognitive performance in patients and their first-degree relatives.

Limbic hyperactivity associated to verbal memory deficit in schizophrenia

In schizophrenia there seems to be an inefficient activation of prefrontal and hippocampal regions. Patients tend to show worse cognitive performance in functions subserved by those regions as compared to healthy controls in spite of higher regional activation. However, the association between activation abnormalities and cognitive deficits remains without being understood. In the present study, we compared cerebral perfusion using single-photon emission tomography (SPECT) in patients and controls to study the association between activation patterns and cognitive performance in this disease. The SPECT studies were simultaneously obtained with an electrophysiological recording during a P300 paradigm to elicit P3a and P3b components. We included 23 stable patients with paranoid schizophrenia and 29 healthy controls that underwent clinical and cognitive assessments. Patients with schizophrenia showed an increased perfusion in the right hippocampus with respect to healthy controls, they also displayed a statistically significant inverse association between perfusion in the left hippocampus and verbal memory performance. Healthy controls showed an inverse association between perfusion in the left dorsolateral prefrontal (DLPFC) region and working memory performance. P3b but not P3a amplitude was significantly lower in patients. The limbic overactivation in the patients may contribute to their cognitive deficits in verbal memory.

A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains

This large multi‐center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi‐modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first‐degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event‐related potential (N = 515), lateral ventricular volume (N = 798), and the cognitive measures block design (N = 3,089), digit span (N = 1,437), and the Ray Auditory Verbal Learning Task (N = 2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p = 0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p = 0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p = 0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.

Structural correlates of cognitive deficit and elevated gamma noise power in schizophrenia.

The aim of this study was to assess the relation between cognition, gray matter (GM) volumes and gamma noise power (amount of background oscillatory activity in the gamma band) in schizophrenia.

Cognitive outcome and gamma noise power unrelated to neuregulin 1 and 3 variation in schizophrenia

BackgroundNeuregulins are a family of signalling proteins that orchestrate a broad range of cellular responses. Four genes encoding Neuregulins 1–4 have been identified so far in vertebrates. Among them, Neuregulin 1 and Neuregulin 3 have been reported to contribute to an increased risk for developing schizophrenia. We hypothesized that three specific variants of these genes (rs6994992 and rs3924999 for Neuregulin 1 and rs10748842 for Neuregulin 3) that have been related to this illness may modify information processing capacity in the cortex, which would be reflected in electrophysiological parameters (P3b amplitude or gamma noise power) and/or cognitive performance.MethodsWe obtained DNA from 31 patients with schizophrenia and 23 healthy controls and analyzed NRG1 rs6994992, NRG1 rs3924999 and NRG3 rs10748842 promoter polymorphisms by allelic discrimination with real-time polymerase chain reaction (PCR). We compared cognitive outcome, P300 amplitude parameters and an electroencephalographic measure of noise power in the gamma band between the groups dichotomized according to genotype.ResultsContrary to our hypothesis, we could not detect any significant influence of variation in Neuregulin 1/Neuregulin 3 polymorphisms on cognitive performance or electrophysiological parameters of patients with schizophrenia.ConclusionsDespite our findings, we cannot discard that other genetic variants and, more likely, interactions between those variants and with genetic variation related to different pathways may still influence cerebral processing in schizophrenia.