Hue selectivity from recurrent circuitry in Drosophila.

In the perception of color, wavelengths of light reflected off objects are transformed into the derived quantities of brightness, saturation and hue. Neurons responding selectively to hue have been reported in primate cortex, but it is unknown how their narrow tuning in color space is produced by upstream circuit mechanisms. We report the discovery of neurons in the Drosophila optic lobe with hue-selective properties, which enables circuit-level analysis of color processing. From our analysis of an electron microscopy volume of a whole Drosophila brain, we construct a connectomics-constrained circuit model that accounts for this hue selectivity. Our model predicts that recurrent connections in the circuit are critical for generating hue selectivity. Experiments using genetic manipulations to perturb recurrence in adult flies confirm this prediction. Our findings reveal a circuit basis for hue selectivity in color vision.

Functional network properties in schizophrenia and bipolar disorder assessed with high-density electroencephalography.

BACKGROUND: The study of the cortical functional network properties in schizophrenia (SZ) may benefit from the use of graph theory parameters applied to high-density electroencephalography (EEG). Connectivity Strength (CS) assesses global synchrony of the network, and Shannon Graph Complexity (SGC) summarizes the network distribution of link weights and allows distinguishing between primary and secondary pathways. Their joint use may help in understanding the underpinnings of the functional network hyperactivation and task-related hypomodulation previously described in psychoses. METHODS: We used 64-sensor EEG recordings during a P300 oddball task in 128 SZ patients (96 chronic, CR, and 32 first episodes, FE), as well as 46 bipolar disorder (BD) patients, and 92 healthy controls (HC). Pre-stimulus and modulation (task-response minus pre-stimulus windows values) of CS and SGC were assessed in the theta band (4-8 Hz) and the broadband (4-70 Hz). RESULTS: Compared to HC, SZ patients (CR and FE) showed significantly higher pre-stimulus CS values in the broadband, and both SZ and BD patients showed lower theta-band CS modulation. SGC modulation values, both theta-band and broadband, were also abnormally reduced in CR patients. Statistically significant relationships were found in the theta band between SGC modulation and both CS pre-stimulus and modulation values in patients. CS altered measures in patients were additionally related to their cognitive outcome and negative symptoms. A primary role of antipsychotics in these results was ruled out. CONCLUSIONS: Our results linking SGC and CS alterations in psychotic patients supported a hyperactive and hypomodulatory network mainly involving connections in secondary pathways.

Corollary Discharge Dysfunction as a Possible Substrate of Anomalous Self-experiences in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Corollary discharge mechanism suppresses the conscious auditory sensory perception of self-generated speech and attenuates electrophysiological markers such as the auditory N1 Event-Related Potential (ERP) during Electroencephalographic (EEG) recordings. This phenomenon contributes to self-identification and seems to be altered in people with schizophrenia. Therefore, its alteration could be related to the anomalous self-experiences (ASEs) frequently found in these patients. STUDY DESIGN: To analyze corollary discharge dysfunction as a possible substrate of ASEs, we recorded EEG ERP from 43 participants with schizophrenia and 43 healthy controls and scored ASEs with the 'Inventory of Psychotic-Like Anomalous Self-Experiences' (IPASE). Positive and negative symptoms were also scored with the 'Positive and Negative Syndrome Scale for Schizophrenia' (PANSS) and with the 'Brief Negative Symptom Scale' (BNSS) respectively. The N1 components were elicited by two task conditions: (1) concurrent listening to self-pronounced vowels (talk condition) and (2) subsequent non-concurrent listening to the same previously self-uttered vowels (listen condition). STUDY RESULTS: The amplitude of the N1 component elicited by the talk condition was lower compared to the listen condition in people with schizophrenia and healthy controls. However, the difference in N1 amplitude between both conditions was significantly higher in controls than in schizophrenia patients. The values of these differences in patients correlated significantly and negatively with the IPASE, PANSS, and BNSS scores. CONCLUSIONS: These results corroborate previous data relating auditory N1 ERP amplitude with altered corollary discharge mechanisms in schizophrenia and support corollary discharge dysfunction as a possible underpinning of ASEs in this illness.

Corollary discharge function in healthy controls: Evidence about self-speech and external speech processing.

As we speak, corollary discharge mechanisms suppress the auditory conscious perception of the self-generated voice in healthy subjects. This suppression has been associated with the attenuation of the auditory N1 component. To analyse this corollary discharge phenomenon (agency and ownership), we registered the event-related potentials of 42 healthy subjects. The N1 and P2 components were elicited by spoken vowels (talk condition; agency), by played-back vowels recorded with their own voice (listen-self condition; ownership) and by played-back vowels recorded with an external voice (listen-other condition). The N1 amplitude elicited by the talk condition was smaller compared with the listen-self and listen-other conditions. There were no amplitude differences in N1 between listen-self and listen-other conditions. The P2 component did not show differences between conditions. Additionally, a peak latency analysis of N1 and P2 components between the three conditions showed no differences. These findings corroborate previous results showing that the corollary discharge mechanisms dampen sensory responses to self-generated speech (agency experience) and provide new neurophysiological evidence about the similarities in the processing of played-back vowels with our own voice (ownership experience) and with an external voice.

Hue selectivity from recurrent circuitry in Drosophila.

A universal principle of sensory perception is the progressive transformation of sensory information from broad non-specific signals to stimulus-selective signals that form the basis of perception. To perceive color, our brains must transform the wavelengths of light reflected off objects into the derived quantities of brightness, saturation and hue. Neurons responding selectively to hue have been reported in primate cortex, but it is unknown how their narrow tuning in color space is produced by upstream circuit mechanisms. To enable circuit level analysis of color perception, we here report the discovery of neurons in the Drosophila optic lobe with hue selective properties. Using the connectivity graph of the fly brain, we construct a connectomics-constrained circuit model that accounts for this hue selectivity. Unexpectedly, our model predicts that recurrent connections in the circuit are critical for hue selectivity. Experiments using genetic manipulations to perturb recurrence in adult flies confirms this prediction. Our findings reveal the circuit basis for hue selectivity in color vision.

Real-life outcomes in biotypes of psychotic disorders based on neurocognitive performance.

Aiming at discerning potential biotypes within the psychotic syndrome, we have recently reported the possible existence of two clusters or biotypes across schizophrenia and bipolar disorder characterized by their cognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) instrument and validated with independent biological and clinical indexes (Fernández-Linsenbarth et al. in Schizophr Res 229:102-111, 2021). In this previous work, the group with larger cognitive deficits (N = 93, including 69 chronic schizophrenia, 17 first episodes (FE) of schizophrenia and 7 bipolar disorder patients) showed smaller thalamus and hippocampus volume and hyper-synchronic electroencephalogram than the group with milder deficits (N = 105, including 58 chronic schizophrenia, 25 FE and 22 bipolar disorder patients). We predicted that if these biotypes indeed corresponded to different cognitive and biological substrates, their adaptation to real life would be different. To this end, in the present work we have followed up the patients' population included in that work at 1st and 3rd years after the date of inclusion in the 2021 study and we report on the statistical comparisons of each clinical and real-life outcomes between them. The first cluster, with larger cognitive deficits and more severe biological alterations, showed during that period a decreased capacity for job tenure (1st and 3rd years), more admissions to a psychiatric ward (1st year) and a higher likelihood for quitting psychiatric follow-up (3rd year). Patients in the second cluster, with moderate cognitive deficits, were less compliant with prescribed treatment at the 3rd year. The differences in real-life outcomes may give additional external validity to that yielded by biological measurements to the described biotypes based on neurocognition.

Prevalence of Anal High-Risk Human Papilloma Virus Infection and Abnormal Anal Cytology among Women Living with HIV.

Background: Women living with human immunodeficiency virus (HIV), WLWHs, are at high risk of developing anal cancer associated with high-risk human papilloma virus infection (HR-HPV). We analyzed the prevalence of anal HR-HPV infection and abnormal anal cytology in a cohort of WLWHs and assessed the risk factors for anal HR-HPV infection. Methods: We present a single-center, observational cross-sectional study. WLWHs who underwent anal cytology and anal human papilloma virus (HPV) testing were selected. High-resolution anoscopy was performed in cases of abnormal anal cytology. All suspicious lesions were biopsied. A univariate and multivariate logistic regression model was used to analyze risk factors for abnormal anal screening. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, 400 WLWHs were studied. Of them, 334 met the eligibility criteria and were enrolled in the study. Abnormal anal cytology was detected in 39.5% of patients, and anal HR-HPV in 40.1%, with HPV 16 in 33 (26.6%) of them. Concomitant HR-HPV cervical infection was the only independent risk factor for HR-HPV anal infection (OR 1.67 95% CI, p < 0.001). Conclusions: WLWHs have a high prevalence of HR-HPV anal infection and anal cytologic abnormalities. HR-HPV cervical infection is the main predictor of HR-HPV anal infection.

Relation between EEG resting-state power and modulation of P300 task-related activity in theta band in schizophrenia.

There is some consistency in previous EEG findings that patients with schizophrenia have increased resting-state cortical activity. Furthermore, in previous work, we have provided evidence that there is a deficit in the modulation of bioelectrical activity during the performance of a P300 task in schizophrenia. Our hypothesis here is that a basal hyperactivation would be related with altered ability to change or modulate cortical activity during a cognitive task. However, no study so far, to the best of our knowledge, has studied the association between resting-state activity and task-related modulation. With this aim, we used a dual EEG paradigm (resting state and oddball task for elicitation of the P300 evoked potential) in a sample of patients with schizophrenia (n = 100), which included a subgroup of patients with first episode psychosis (n = 30), as well as a group of healthy controls (n = 93). The study measures were absolute power for resting-state; and spectral entropy (SE) and connectivity strength (CS) for P300-task data, whose modulation had been previously found to be altered in schizophrenia. Following the literature on P300, we focused our study on the theta frequency band. As expected, our results showed an increase in resting state activity and altered task-related modulation. Moreover, we found an inverse relationship between the amount of resting-state activity and modulation of task-related activity. Our results confirm our hypothesis and support the idea that a greater amount of resting theta-band synchrony could hamper the modulation of signal regularity (quantified by SE) and activity density (measured by CS) during the P300 task performance. This association was found in both patients and controls, suggesting the existence of a common mechanism and a possible ceiling effect in schizophrenia patients in relation to a decreased inhibitory function that limits their cortical reactivity to the task.

Analysis of the functional EEG network in an Ecuadorian schizophrenia sample

Background and objectives: Higher mental functions depend on global functional coordination of the brain. Our aim was to study the baseline condition and modulation of functional networks in a previously unevaluated clinical population, compare the results with a population from another country, and analyze their relationship with cognitive functioning.MethodsWe evaluated the functioning of brain networks by EEG in 24 patients with schizophrenia and 32 healthy Ecuadorian controls. EEG recordings were made at rest and while performing a P300 task. Small world (SW), Path Length (PL), clustering coefficient (CLC) and connective strength (CS) values were calculated in both conditions. The values obtained were compared between groups, with the results of Spanish patients, and the relationship between the connective parameters and the cognitive performance of the participants was analyzed.ResultsHigher PL, CLC and CS values were identified in patients diagnosed with schizophrenia compared to controls (in basal condition) and lower SW values in this same condition. Ecuadorian patients obtained higher values than Spanish patients in the PL and CLC parameters and lower values for the SW parameter, despite these differences, the pattern of alteration in both samples followed the same trend. Finally, the alteration of CS, SW, CLC and PL parameters at baseline was related to cognitive performance.ConclusionThe connective alterations identified in Ecuadorian schizophrenic patients are consistent with those found in another sample with different genetic, environmental and cultural conditions. In addition, these alterations were associated with worse performance in different cognitive domains. (AU)

Search for schizophrenia and bipolar biotypes using functional network properties.

INTRODUCTION: Recent studies support the identification of valid subtypes within schizophrenia and bipolar disorder using cluster analysis. Our aim was to identify meaningful biotypes of psychosis based on network properties of the electroencephalogram. We hypothesized that these parameters would be more altered in a subgroup of patients also characterized by more severe deficits in other clinical, cognitive, and biological measurements. METHODS: A clustering analysis was performed using the electroencephalogram-based network parameters derived from graph-theory obtained during a P300 task of 137 schizophrenia (of them, 35 first episodes) and 46 bipolar patients. Both prestimulus and modulation of the electroencephalogram were included in the analysis. Demographic, clinical, cognitive, structural cerebral data, and the modulation of the spectral entropy of the electroencephalogram were compared between clusters. Data from 158 healthy controls were included for further comparisons. RESULTS: We identified two clusters of patients. One cluster presented higher prestimulus connectivity strength, clustering coefficient, path-length, and lower small-world index compared to controls. The modulation of clustering coefficient and path-length parameters was smaller in the former cluster, which also showed an altered structural connectivity network and a widespread cortical thinning. The other cluster of patients did not show significant differences with controls in the functional network properties. No significant differences were found between patients´ clusters in first episodes and bipolar proportions, symptoms scores, cognitive performance, or spectral entropy modulation. CONCLUSION: These data support the existence of a subgroup within psychosis with altered global properties of functional and structural connectivity.

Altered gamma band noise power in schizophrenia and bipolar patients during a cognitive task

Background and Objectives: “Noise power” (NP) is a measure that allows the assessment of the fast-firing synchronization of neural oscillations. We aimed to replicate higher gamma NP values in frontal and midline regions in patients with schizophrenia and re-evaluate its specificity to this disorder. We also aimed to assess the relationship of higher gamma NP values with drug treatment, chronicity, cognition and symptoms.MethodsGamma NP values were obtained from electroencephalograms recorded during an oddball paradigm from 29 patients with schizophrenia, 27 with bipolar disorder and 36 healthy controls. We compared these values between the groups to evaluate the specificity to diagnosis. Altered gamma NP values were compared between the patients who had and had not received different treatments to assess the relationship with drug treatment. We also analyse the correlation between gamma NP values and chronicity, symptoms, and cognition.ResultsCompared to controls, patients with schizophrenia presented increased gamma NP values in frontal and parietal midline regions, while bipolar patients showed increased gamma NP in the left frontal region. There was no significant relationship between drug treatment or chronicity with altered values. Increased gamma NP correlated with higher negative symptom scores in the schizophrenia group, but not with cognitive impairment in any of the groups of patients.ConclusionsWe replicated an increase in gamma NP in patients with schizophrenia and found that this alteration was also present in a milder form in bipolar patients. These alterations seem to be independent of pharmacological treatment and illness duration. (AU)

Event-related potentials associated to N-back test performance in schizophrenia.

Mapping of Event-Related Potentials (ERP) associated with auditory and visual odd-ball paradigms has shown consistent differences between healthy controls and schizophrenia patients. It may be hypothesized that higher task attentional/cognitive demand will result in larger differences in these paradigms, which may help understanding the substrates of cognitive deficits in this syndrome. To this aim, we performed an EEG study comparing the effects of increasing the attentional/cognitive load of an auditory N-back task on the Event-Related Potential in 50 subjects with schizophrenia (11 first episodes) and 35 healthy controls. We considered a post-target window of 1000 ms to explore possible between groups differences in N100, P300, and Late Slow Wave (LSW), and compared these components between 0-back ('lower attentional/cognitive load) and 1-back ('higher attentional/cognitive load') conditions. Our results showed that N100 and LSW amplitude increase from 0- to 1-back condition was significantly larger in healthy controls compared to schizophrenia patients. Furthermore, LSW amplitude difference between 0- and 1-back conditions positively correlated with performance in the behavioral cognitive assessment. Taken together, these results support that higher task attentional/cognitive load (0-back vs. 1-back condition) increase N100 amplitude differences and reveal new findings related to the LSW component in schizophrenia.

Neurobiological underpinnings of cognitive subtypes in psychoses: A cross-diagnostic cluster analysis.

Schizophrenia and bipolar disorder include patients with different characteristics, which may hamper the definition of biomarkers. One of the dimensions with greater heterogeneity among these patients is cognition. Recent studies support the identification of different patients' subgroups along the cognitive domain using cluster analysis. Our aim was to validate clusters defined on the basis of patients' cognitive status and to assess its relation with demographic, clinical and biological measurements. We hypothesized that subgroups characterized by different cognitive profiles would show differences in an array of biological data. Cognitive data from 198 patients (127 with chronic schizophrenia, 42 first episodes of schizophrenia and 29 bipolar patients) were analyzed by a K-means cluster approach and were compared on several clinical and biological variables. We also included 155 healthy controls for further comparisons. A two-cluster solution was selected, including a severely impaired group and a moderately impaired group. The severely impaired group was associated with higher illness duration and symptoms scores, lower thalamus and hippocampus volume, lower frontal connectivity and basal hypersynchrony in comparison to controls and the moderately impaired group. Moreover, both patients' groups showed lower cortical thickness and smaller functional connectivity modulation than healthy controls. This study supports the existence of different cognitive subgroups within the psychoses with different neurobiological underpinnings.

Connectivity strength of the EEG functional network in schizophrenia and bipolar disorder.

The application of graph theory measures in the study of functional brain networks allows for the description of their general properties and their alterations in mental illness. Among these measures, connectivity strength (CS) estimates the degree of functional connectivity of the whole network. Previous studies in schizophrenia patients have reported higher baseline CS values and modulation deficits in EEG spectral properties during cognitive activity. The specificity of these alterations and their relationships with pharmacological treatments remain unknown. Therefore, in the present study, we assessed functional CS on EEG-based brain networks in 79 schizophrenia and 29 bipolar patients in addition to 63 healthy controls. The subjects performed a P300 task during the EEG recordings from which the pre-stimulus and the task-related modulation CS values were computed in the global and theta bands. These values were compared between the groups and between the patients who had and had not received different treatments. The global band pre-stimulus CS was significantly higher in the schizophrenia group compared with the bipolar and control groups. Theta band CS modulation was decreased in schizophrenia and bipolar patients. Treatment with antipsychotics, lithium, benzodiazepines, and anticonvulsants did not significantly alter these CS values. The first-episode and chronic schizophrenia patients did not show significant differences in CS values. Higher global band pre-stimulus CS values were associated with worse general cognition in schizophrenia patients. These data support increased connectivity in the whole-brain network that is specific to schizophrenia and suggest a general hyper-synchronized basal state that might hamper cognition in this syndrome.

Basal forebrain GABAergic innervation of olfactory bulb periglomerular interneurons.

KEY POINTS: Basal forebrain long-range projections to the olfactory bulb are important for olfactory sensitivity and odour discrimination. Using optogenetics, it was confirmed that basal forebrain afferents mediate IPSCs on granule and deep short axon cells. It was also shown that they selectively innervate specific subtypes of periglomerular (PG) cells. Three different subtypes of type 2 PG cells receive GABAergic IPSCs from the basal forebrain but not from other PG cells. Type 1 PG cells, in contrast, do not receive inputs from the basal forebrain but do receive inhibition from other PG cells. These results shed new light on the complexity and specificity of glomerular inhibitory circuits, as well as on their modulation by the basal forebrain. ABSTRACT: Olfactory bulb circuits are dominated by multiple inhibitory pathways that finely tune the activity of mitral and tufted cells, the principal neurons, and regulate odour discrimination. Granule cells mediate interglomerular lateral inhibition between mitral and tufted cells' lateral dendrites whereas diverse subtypes of periglomerular (PG) cells mediate intraglomerular lateral inhibition between their apical dendrites. Deep short axon cells form broad intrabulbar inhibitory circuits that regulate both populations of interneurons. Little is known about the extrabulbar GABAergic circuits that control the activity of these various interneurons. We examined this question using patch-clamp recordings and optogenetics in olfactory bulb slices from transgenic mice. We showed that axonal projections emanating from diverse basal forebrain GABAergic neurons densely project in all layers of the olfactory bulb. These long-range GABAergic projections provide a prominent synaptic input on granule and short axon cells in deep layers as well as on selective subtypes of PG cells. Specifically, three different subclasses of type 2 PG cells receive robust and target-specific basal forebrain inputs but have little local interactions with other PG cells. In contrast, type 1 PG cells are not innervated by basal forebrain fibres but do interact with other PG cells. Thus, attention-regulated basal forebrain inputs regulate inhibition in all layers of the olfactory bulb with a previously overlooked synaptic complexity that further defines interneuron subclasses.

A Pool of Postnatally Generated Interneurons Persists in an Immature Stage in the Olfactory Bulb.

Calretinin (CR)-expressing periglomerular (PG) cells are the most abundant interneurons in the glomerular layer of the olfactory bulb. They are predominately generated postnatally from the septal and dorsal subventricular zones that continue producing them well into adulthood. Yet, little is known about their properties and functions. Using transgenic approaches and patch-clamp recording in mice of both sexes we show that CR(+) PG cells of both septal and dorsal origin have homogeneous morphological and electrophysiological properties. However, unlike other PG cells, these axonless neurons express a surprisingly small repertoire of voltage-activated channels and do not fire or fire at most a single and often small action potential. Moreover, they are not innervated by olfactory sensory neurons and receive little synaptic inputs from mitral or tufted cells at excitatory synapses where NMDA receptors predominate. These membrane and synaptic properties, that resemble those of newborn immature neurons not yet integrated in the network, persist over time and limit the recruitment of CR(+) PG cells by afferent inputs that strongly drive local network activity. Together, our results show that postnatally generated CR(+) PG cells continuously supply a large pool of neurons with unconventional properties. These data also question the contribution of CR(+) PG cells in olfactory bulb computation.SIGNIFICANCE STATEMENT Calretinin-expressing PG cells are by far the most abundant interneurons in the glomerular layer of the olfactory bulb. They are continuously produced during postnatal life, including adulthood, from neural stem cells located in the subventricular zones. Surprisingly, unlike other postnatally generated newborn neurons that quickly integrate into preexisting olfactory bulb networks, calretinin-expressing PG cells retain immature properties that limit their recruitment in local network activity for weeks, if not months, as if they would never fully mature. The function of this so far unsuspected pool of latent neurons is still unknown.

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.

Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives.

The "dysconnection hypothesis" of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition-that is, increased cortical excitability-in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis. Hum Brain Mapp 38:3262-3276, 2017. © 2017 Wiley Periodicals, Inc.

Relaciones entre síntomas psicóticos subclínicos y rendimiento cognitivo en la población general / Relationship between subclinical psychotic symptoms and cognitive performance in the general population

Introducción. En la población general, los síntomas psicóticos subclínicos se han asociado con mayores dificultades funcionales en la vida real, pero desconocemos si estos síntomas están asociados a un peor rendimiento cognitivo. El estudio de la relación entre las alteraciones cognitivas y estos síntomas puede, además, ayudarnos a comprender mejor las dificultades que presentan los pacientes con psicosis, en los que estas alteraciones cognitivas están presentes. Métodos. Realizamos evaluaciones clínicas y cognitivas en 203 sujetos de la población general mediante los instrumentos Community Assessment of Psychic Experiences, Brief Assessment of Cognition in Schizophrenia, Wechsler Adult Intelligence Scale y Wisconsin Card Sorting Test. Se evaluó la relación de los síntomas psicóticos subclínicos positivos y negativos con la edad y el rendimiento cognitivo. Además, se evaluó la influencia de los síntomas depresivos subclínicos sobre la posible relación entre síntomas positivos y negativos subclínicos y las alteraciones cognitivas. Resultados. Encontramos una relación inversa del rendimiento en la prueba de velocidad motora tanto con la frecuencia de síntomas positivos como con el distrés y la frecuencia de los síntomas negativos. También encontramos una relación directa entre el distrés de los síntomas positivos y el rendimiento en función ejecutiva. La puntuación en síntomas depresivos subclínicos se asoció con ambas escalas subclínicas, positiva y negativa. Conclusiones. Los síntomas psicóticos subclínicos están relacionados con déficits cognitivos en la población general, similares a los observados en poblaciones clínicas (AU)

Introduction. Subclinical psychotic symptoms are associated to negative life outcomes in the general population, but their relationship with cognitive performance is still not well understood. Assessing the relationship between performance in cognitive domains and subclinical psychotic symptoms in the general population may also help understand the handicap attributed to clinical psychosis, in which these alterations are present. Methods. Subclinical and cognitive assessments were obtained in 203 participants from the general population by means of the Community Assessment of Psychic Experiences, the Brief Assessment of Cognition in Schizophrenia, the Wechsler Adults Intelligence Scale and the Wisconsin Card Sorting Test. The positive and negative subclinical symptoms and their relationship with age and cognition were examined, followed by assessing the influence of subclinical depression scores on the possible relationships between those subclinical psychotic symptoms and cognitive deficits. Results. Inverse relationships were found between frequency in the Community Assessment of Psychic Experiences positive dimension and motor speed, and frequency and distress in the Community Assessment of Psychic Experiences negative dimension and motor speed. A direct relationship was also found between distress scores of the positive dimension and executive functions. Both positive and negative subclinical symptoms were related to depression scores. Conclusions. Psychotic symptoms, similar to those in the clinical population, may be associated with cognitive deficits in the general population (AU)