Papers by Pilar Salgado-Pineda
Journal of Psychiatric Research
Frontiers in Human Neuroscience
Regularization may be used as an alternative to dimensionality reduction when the number of varia... more Regularization may be used as an alternative to dimensionality reduction when the number of variables in a model is much larger than the number of available observations. In a recent study from our group regularized regression was employed to quantify brain functional connectivity in a sample of healthy controls using a brain parcellation and resting state fMRI images. Here regularization is applied to evaluate resting state connectivity abnormalities at the voxel level in a sample of patients with schizophrenia. Specifically, ridge regression is implemented with different degrees of regularization. Results are compared to those delivered by the weighted global brain connectivity method (GBC), which is based on averaged bivariate correlations and from the non-redundant connectivity method (NRC), a dimensionality reduction approach that applies supervised principal component regressions. Ridge regression is able to detect a larger set of abnormally connected regions than both GBC and...
NeuroImage: Clinical
Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia (SZ) defined by anomalous... more Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia (SZ) defined by anomalous perception of speech. Anomalies of processing external speech stimuli have also been reported in people with AVH, but it is unexplored which specific dimensions of language are processed differently. Using a speech perception task (passive listening), we here targeted the processing of deixis, a key dimension of language governing the contextual anchoring of speech in interpersonal context. We designed naturalistic speech stimuli that were either non-personal and fact-reporting ('low-deixis' condition), or else involved rich deictic devices such as the grammatical first and second persons, direct questions, and vocatives ('high-deixis'). We asked whether neural correlates of deixis obtained with fMRI would distinguish patients with and without frequent hallucinations (AVHÂ +Â vs AVH-) from controls and each other. Results showed that high-deixis relative to low-deixis was associated with clusters of increased activation in the bilateral middle temporal gyri extending into the temporal poles and the inferior parietal cortex, in all groups. The AVHÂ +Â and AVH- groups did not differ. When unifying them, the SZ group as a whole showed altered activity in the precuneus, midline regions and inferior parietal cortex. These results fail to confirm deictic processing anomalies specific to patients with AVH, but reveal such anomalies across SZ. Hypoactivation of this network may relate to a cognitive mechanism for attributing and anchoring thought and referential speech content in context.
MetodologÃa de las ciencias del comportamiento, 2002
Acta Psychiatrica Scandinavica, 2022
Funding information The funding sources had no role in the design and conduct of the study; colle... more Funding information The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication. Methods: Patients with a FEM or FEP underwent a clinical assessment. Prodromes were evaluated with the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R). Chi-squared tests were conducted to assess specific prodromal symptoms, risk factors or markers of vulnerability between groups. Significant prodromal symptoms were entered in a stepwise forward logistic regression model. The probabilities of a gradual versus rapid onset pattern of the prodromes were computed with logistic regression models. Results: The total sample included 108 patients (FEM = 72, FEP = 36). Social isolation was associated with the prodromal stage of a FEP whilst Increased energy or goal-directed activity with the prodrome to a FEM. Physically slowed down presented the most gradual onset whilst Increased energy presented the most rapid. The presence of obstetric complications and difficulties in writing and reading during childhood were risk factors for FEP. As for markers of vulnerability, impairment in premorbid adjustment was characteristic of FEP patients. No specific risk factor or marker of vulnerability was identified for FEM. Conclusion: Early characteristics differentiating FEP from FEM were identified. These findings might help shape early identification and preventive intervention programmes.
Schizophrenia Research, 2021
An altered sense of self-awareness and agency has been proposed to underlie symptoms of schizophr... more An altered sense of self-awareness and agency has been proposed to underlie symptoms of schizophrenia. In this study, we used the enfacement illusion paradigm - in which perception of another person's face leads to changes in perception of one's own peri-personal space - to examine the brain correlates of the sense of agency and its potential disruption in schizophrenia. Thirty-three schizophrenic patients and 27 healthy controls underwent fMRI scanning during performance of a task designed to elicit the enfacement illusion. Activations were examined using whole-brain analysis and also in an a priori identified region of interest (ROI) in the temporoparietal junction (TPJ), a region that has been described as involved in self/other differentiation and sense of agency. Both groups showed a pattern of cortical activation involving the pre and postcentral cortex, Rolandic operculum, insula, parietal, temporal and occipital cortex bilaterally as well as TPJ (but only right-side in patients). Examination of the TPJ ROI revealed significantly reduced activation on the left in the patients that was associated with poorer insight. The findings suggest brain functional abnormality in schizophrenia related to the formation or maintenance of processes related to self and/or agency. Decreased function in the TPJ may have a role in the impaired insight seen in patients with the disorder.
NeuroImage: Clinical, 2021
Highlights • Scenic stimuli might offer a better understanding of emotional processing than faces... more Highlights • Scenic stimuli might offer a better understanding of emotional processing than faces.• Emotional scenes were presented to schizophrenia patients and healthy controls.• Schizophrenia patients tend to misclassify emotional images as fear.• Schizophrenia patients hyperactivated regions involved in fear and disgust processing.• Patients’ brain response did not differ from controls in response to happy and sad scenes.
Journal of Psychiatric Research, 2021
The Stroop task, which examines an aspect of executive function/cognitive control, the ability to... more The Stroop task, which examines an aspect of executive function/cognitive control, the ability to inhibit prepotent responses, has been relatively little examined in schizophrenia, and the findings have been inconsistent. Whether performance of this task is associated with failure of de-activation in the disorder is also uncertain. We examined 42 schizophrenic patients and 61 healthy controls during performance of an fMRI-adapted version of the Stroop task, the counting Stroop task. Task-related activations (incongruent > congruent condition) and de-activations (baseline > incongruent) were examined using whole-brain, voxel-based methods. In the healthy controls, task performance was found to be associated with activations in the left dorsolateral prefrontal cortex and the dorsal anterior cingulate cortex, among other regions. De-activations were seen in the medial frontal cortex, the middle and posterior cingulate gyrus and cuneus, the parahippocampal gyrus and the hippocampus. The schizophrenic patients did not show reduced activation compared to the healthy controls. They did, however, show failure of de-activation in the medial frontal cortex. Our negative finding with respect to hypoactivation during performance of a task requiring inhibition of prepotent responses suggests that brain functional abnormality in schizophrenia may not affect all aspects of executive function/cognitive control. The finding of medial frontal cortex failure of de-activation adds to existing findings of default mode network dysfunction in the disorder.
European Neuropsychopharmacology, 2019
Background: Copy number variants (CNVs) at the 16p11.2 and at the 22q11.2 locus are among the mos... more Background: Copy number variants (CNVs) at the 16p11.2 and at the 22q11.2 locus are among the most common psychiatric genetic risk factors with large effect size. The 16p11.2 deletion (16pDel) has been associated with Autism spectrum disorder (ASD) and the reciprocal duplication (16pDup) with Schizophrenia (SZ) and ASD. The 22q11.2 deletion (22qDel) has been associated with SZ and the reciprocal duplication (22qDup) with ASD. Several studies have demonstrated a large effect size of these variants on brain structure. Almost nothing is known, however, on the alterations of functional connectivity (FC) associated with genomic variants. Our goals are: 1) to characterize and compare patterns of FC associated with these 4 CNVs 2) investigate if these patterns may provide insight in the FC observed in idiopathic autism. Methods: We used fMRI data from 20 16p11.2 and 52 22q11.2 deletion carriers, 21 16p11.2 and 12 22q11.2 duplication carriers and 128 controls. Data was acquired from the Simons VIP and a 22q project at UCLA. The idiopathic autism group was comprised of 672 (363 controls, 309 ASD) individuals from ABIDE cohort. fMRI data were corrected for slice timing and subject motion and registered to MNI space using the NIAK pipeline. Timepoints with excessive headmotion (> 0.5mm) were removed. Subjects with low time points, poor T1/EPI coregistration were excluded. FC was estimated as the pairwise correlation between the average time series of 64 brain regions. A linear model was fitted to each connection with genetic status, subject motion, sex and site as explanatory factors. The effect of the 4 genetic groups were then tested by posthoc contrasts. Each contrast was controlled for false discovery rate (FDR) across all connections at q < 5%. The 16p11.2 and 22q11.2 connectivity patterns were compared to the autism cohort using spatial correlation of the individual connectome with the CNV derived pattern of connectivity alterations. Results: The 16pDel is associated with an overall increase in connectivity: 258 connections were significantly altered (FDR corrected) and only 3 connections show underconnectivity. 4 seed regions were involved in nearly half (44 %) of these altered connections (caudate nucleus, putamen, dorsolateral somatomotor network, orbitofrontal cortex). The 16pDup is associated with an overall underconnectivity but none of the individual connections survived FDR. The 22qDel is associated with an overall decrease in connectivity. 98 connections were significantly altered and of those, only 3 were overconnected. The underconnectivity pattern originates mainly from regions in the Limbic network, and the Frontal network. The 22qDup is associated with an overall increase in connectivity but due to small sample size, only 9 individual connections survive FDR correction. Preliminary results show that these connectivity patterns are significantly enriched in individuals with idiopathic autism compared to control subjects.
European Neuropsychopharmacology, 2019
Schizophrenia research, Jan 25, 2018
Brain functional changes reported in schizophrenia include reduced prefrontal cortex activation (... more Brain functional changes reported in schizophrenia include reduced prefrontal cortex activation (hypofrontality), increased frontal activation (hyperfrontality) and failure of de-activation in the medial frontal cortex. The relative importance of these changes is unestablished. A 'discovery' sample of 32 schizophrenic patients and 32 controls was used to establish regions of altered activation and de-activation in the patients. The discriminatory power of these regions was examined using receiver-operator characteristics (ROC) analysis in two 'test' samples, one of 83 patients with chronic schizophrenia and 83 healthy controls, and the other of 31 first-episode patients and 31 healthy controls. The discovery sample revealed reduced activation in the prefrontal cortex and other regions, and failure of de-activation in the medial frontal cortex. Failure of de-activation had significantly greater power to distinguish the chronic patients from the healthy controls than h...
Journal of Nuclear Medicine
Our goal was to study cerebral blood flow (CBF) changes after surgery in a group of 15 patients w... more Our goal was to study cerebral blood flow (CBF) changes after surgery in a group of 15 patients with idiopathic normal pressure hydrocephalus (NPH). We used hexamethylpropyleneamine oxime SPECT and statistical parametric mapping (SPM), an image analysis method that does not require prior selection of regions of interest. Our study showed areas of significant increase in perfusion in specific regions of both frontal lobes and the right parietal lobe. Regions of increased perfusion were found in the left prefrontal dorsolateral areas (Brodmann's areas 9 and 45 or 47), right frontal premotor area (Brodmann's area 44), right medial prefrontal region (Brodmann's area 10 or 32), right frontal white matter area (superior longitudinalis fasciculus), and right basal ganglia (lenticular nucleus, putamen, and globus pallidus). In the right hemisphere, another region of increased perfusion was found in the inferior parietal lobule (Brodmann's area 40). The 2 areas most related t...
Background: Functional imaging abnormality has been proposed as a trait marker or endophenotype f... more Background: Functional imaging abnormality has been proposed as a trait marker or endophenotype for schizophrenia. Although studies examining dorsolateral prefrontal cortex activation in relatives of schizophrenic patients have not had consistent findings, failure of de-activation in the medial frontal cortex may be a promising alternative candidate.
Revista de neurologia
Functional magnetic resonance imaging (fMRI) offers an important advantage over other functional ... more Functional magnetic resonance imaging (fMRI) offers an important advantage over other functional neuroimaging techniques used with children because of its harmlessness. Previous studies conducted with adults with alexia suggested two ways the brain can reorganise reading after a brain injury affecting the left hemisphere, one contralateral and the other ipsilateral. We describe a study carried out using fMRI of a 10 year old girl with an injury to the left hemisphere caused by a fishing harpoon when she was 6 years old. As a result of the accident the girl presented a right hemiparesia. The girl s parents and teachers also reported difficulties in the acquisition of reading writing and arithmetic, as well as a certain degree of attentional deficit. An fMRI exploration was performed while the girl was doing the Stroop test. The structural MR images showed left hemisphere cortical lesions in the orbital and angular gyrus regions, in addition to the caudate and putamen nuclei, and in t...
The World Journal of Biological Psychiatry, 2009
Patients with schizophrenia consistently fail to perform facial affect recognition tasks as accur... more Patients with schizophrenia consistently fail to perform facial affect recognition tasks as accurately as healthy controls. So far, the effects of different antipsychotic drugs on this deficit, as well as the mechanisms through which these drugs may exert their influence on face processing models, remain poorly understood. Twenty-five hospitalised acute schizophrenic patients were randomised to either haloperidol or risperidone following their admission. Patients performed a facial affect discrimination task. In order to differentiate drug effects on perceptive versus semantic processing of faces, the evaluation also included two facial identity discrimination tasks (inverted and upright faces). All evaluations were performed before treatment initiation, after 2 weeks and after 4 weeks of treatment. Compared with patients receiving haloperidol, patients receiving risperidone showed better discrimination of facial affect and inverted faces, but not of upright faces. Differential drug effects were most prominent 2 weeks after treatment initiation. Performance on inverted faces accounted for only 1% of the variance in affect discrimination. Additionally, there was an inverse relationship between negative symptoms and performance on upright-face identification and affect discrimination, with the strongest and most significant correlation being for affect discrimination. Our findings suggest that the preferential effect of risperidone on affect discrimination is unlikely to be due to global effects on general face processing. Moreover, although risperidone appears to enhance the processing of individual salient facial features, this effect cannot explain the improvement in affect recognition. We conclude that risperidone may specifically act on the processing of emotion-laden information.
Schizophrenia Research, 2007
Schizophrenia is characterized by cognitive, social, and emotional impairments and by psychotic s... more Schizophrenia is characterized by cognitive, social, and emotional impairments and by psychotic symptoms. Neuroimaging studies have reported abnormalities within the prefrontal cortex and it has been hypothesized that schizophrenia results from poor or miswired anatomical/functional connections. We have compared the functional connectivity within the frontal cortex in control and schizophrenic subjects during the realization of a Continuous Performance Task. The connectivity pattern within the frontal cortex was uncovered by the analysis of the correlation matrix computed from the fMRI time series in frontal areas for 14 schizophrenic patients and 14 control subjects. In control subjects, the right dorsolateral prefrontal cortex (DLFCr) activity correlated i) positively with the left dorsolateral prefrontal cortex and the posterior part of the supplementary motor area, ii) negatively with the medial and anterior/inferior part of the frontal cortex. In the schizophrenic group, these relations were abolished or strongly lowered. The negative relation between the DLFCr and the medial frontal cortex has been proposed to play a key role in setting a harmonious balance between the direction of attention to the external world and the expression of the individual believes and self-referential activities, and therefore, the impaired relation of right DLFCr with other frontal areas could explain a distorted perception of external world in relation with internal motivations.
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Papers by Pilar Salgado-Pineda