Failure of deactivation in bipolar disorder during performance of an fMRI adapted version of the Stroop task.

INTRODUCTION: Few studies have examined the functional brain correlates of the performance of the Stroop task in bipolar disorder (BD). It is also not known whether it is associated with failure of de-activation in the default mode network, as has been found in studies using other tasks. METHODS: Twenty-four BD patients and 48 age, sex and educationally estimated intellectual quotient (IQ) matched healthy subjects (HS) underwent a functional MRI during performance of the counting Stroop task. Task-related activations (incongruent versus congruent condition) and de-activations (incongruent versus fixation) were examined using whole-brain, voxel-based methodology. RESULTS: Both the BD patients and the HS showed activation in a cluster encompassing the left dorsolateral and ventrolateral prefrontal cortex and the rostral anterior cingulate cortex and supplementary motor area, with no differences between them. The BD patients, however, showed significant failure of de-activation in the medial frontal cortex and the posterior cingulate cortex/precuneus. CONCLUSIONS: The failure to find activation differences between BD patients and controls suggests that the 'regulative' component of cognitive control remains intact in the disorder, at least outside episodes of illness. The failure of de-activation found adds to evidence documenting trait-like default mode network dysfunction in the disorder.

Activation and deactivation patterns in schizophrenia during performance of an fMRI adapted version of the stroop task.

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.

Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites.

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. P values were derived through parametric bootstrapping of the linear mixed-effects models (denoted Pboot). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of N-acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol (Pboot > .90), N-acetylaspartate and N-acetylaspartylglutamate (Pboot = .13), or glutamate and glutamine (Pboot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (Pboot = .08), aspartate (Pboot > .90), glutathione (Pboot > .90), or lactate (Pboot = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020 Online supplemental material is available for this article.

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites.

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.

Big GABA: Edited MR spectroscopy at 24 research sites.

Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.

Elevated midline-parietal gamma band noise power in schizophrenia but not in bipolar patients.

Gamma oscillations are key in coordinating brain activity and seem to be altered in schizophrenia. In previous work, we studied the spatial distribution of a noise power measure (scalp-recorded electroencephalographic activity unlocked to stimuli) and found higher magnitudes in the gamma band related to symptoms and cognition in schizophrenia. In the current study, we sought to replicate those findings and to study its specificity for schizophrenia in a completely independent sample. A principal component analysis (PCA) was used to determine the factorial structure of gamma noise power acquired with an electroencephalographic recording during an odd-ball P300 paradigm in the 250- to 550-ms window in 70 patients with schizophrenia (16 patients with first episode), 45 bipolar patients and 65 healthy controls. Clinical and cognitive correlates of the resulting factors were also assessed. Three factors arose from the PCA. The first displayed a midline-parietal distribution (roughly corresponding to the default mode network), the second was centro-temporal and the third anterior-frontal. Schizophrenia but not bipolar patients showed higher gamma noise power loadings in the first factor in comparison with controls. Scores for this factor were significantly and directly associated with positive and total symptoms in patients and inversely associated with global cognition in all participants. The results of this study replicate those of our previous publication and suggest an elevated midline-parietal gamma noise power specific to schizophrenia. The gamma noise power measure seems to be a useful tool for studying background oscillatory activity during performance of cognitive tasks.

Neural Substrates of Auditory Emotion Recognition Deficits in Schizophrenia.

Deficits in auditory emotion recognition (AER) are a core feature of schizophrenia and a key component of social cognitive impairment. AER deficits are tied behaviorally to impaired ability to interpret tonal ("prosodic") features of speech that normally convey emotion, such as modulations in base pitch (F0M) and pitch variability (F0SD). These modulations can be recreated using synthetic frequency modulated (FM) tones that mimic the prosodic contours of specific emotional stimuli. The present study investigates neural mechanisms underlying impaired AER using a combined event-related potential/resting-state functional connectivity (rsfMRI) approach in 84 schizophrenia/schizoaffective disorder patients and 66 healthy comparison subjects. Mismatch negativity (MMN) to FM tones was assessed in 43 patients/36 controls. rsfMRI between auditory cortex and medial temporal (insula) regions was assessed in 55 patients/51 controls. The relationship between AER, MMN to FM tones, and rsfMRI was assessed in the subset who performed all assessments (14 patients, 21 controls). As predicted, patients showed robust reductions in MMN across FM stimulus type (p = 0.005), particularly to modulations in F0M, along with impairments in AER and FM tone discrimination. MMN source analysis indicated dipoles in both auditory cortex and anterior insula, whereas rsfMRI analyses showed reduced auditory-insula connectivity. MMN to FM tones and functional connectivity together accounted for ∼50% of the variance in AER performance across individuals. These findings demonstrate that impaired preattentive processing of tonal information and reduced auditory-insula connectivity are critical determinants of social cognitive dysfunction in schizophrenia, and thus represent key targets for future research and clinical intervention. SIGNIFICANCE STATEMENT: Schizophrenia patients show deficits in the ability to infer emotion based upon tone of voice [auditory emotion recognition (AER)] that drive impairments in social cognition and global functional outcome. This study evaluated neural substrates of impaired AER in schizophrenia using a combined event-related potential/resting-state fMRI approach. Patients showed impaired mismatch negativity response to emotionally relevant frequency modulated tones along with impaired functional connectivity between auditory and medial temporal (anterior insula) cortex. These deficits contributed in parallel to impaired AER and accounted for ∼50% of variance in AER performance. Overall, these findings demonstrate the importance of both auditory-level dysfunction and impaired auditory/insula connectivity in the pathophysiology of social cognitive dysfunction in schizophrenia.

Are negative symptoms really related to cognition in schizophrenia?

Previous studies have generally found a relationship between negative and cognitive symptoms in schizophrenia. The present study investigated the relationship between the 5 PANSS factors of a recent consensus model developed by NIMH researchers, and cognitive performance as assessed with the MATRICS Consensus Cognitive Battery (MCCB) in 80 patients with schizophrenia using correlation and regression analyses. The PANSS Cognitive factor showed a small to moderate significant association with MCCB Speed of processing, Working memory, Verbal learning, the Neurocognitive composite score, and the Overall composite score. Notably, however, no relationship was found between the PANSS Negative factor and any of the MCCB scores. The Positive, Excited and Depressed factors also did not show associations with the MCCB. These results highlight the need for refined assessment instruments and support the relative independence of cognition from other domains of psychopathology, including negative symptoms, in patients with schizophrenia.

Is it possible to combine different psychotic symptom scales in bipolar disorder?

It has been suggested that data on positive and negative psychotic symptoms in patients with schizophrenia as assessed using different scales may be combined. For the first time, we assessed correlations between the positive syndrome subscale of the Positive and Negative Syndrome Scale (PANSS-P) and the Scale for the Assessment of Positive Symptoms (SAPS), and between the negative syndrome subscale of the Positive and Negative Syndrome Scale (PANSS-N) and the Scale for the Assessment of Negative Symptoms (SANS) in patients with bipolar disorder. We also aimed to confirm these correlations in patients with schizophrenia. This cross-sectional study was conducted with a group of 94 patients (40 diagnosed with bipolar disorder, 54 with schizophrenia). Assessments were carried out using the PANSS, SAPS and SANS. Large significant correlations were found between the PANSS-P and SAPS, and between the PANSS-N and SANS, in both the bipolar disorder group and the schizophrenia group. These results confirm previous findings regarding correlations between these scales in schizophrenia, and support the hypothesis that similar correlations exist in bipolar disorder. Therefore, our data support the potential usefulness in collaborative research of combining results from different scales for the assessment of psychotic symptoms in patients with bipolar disorder.

Cognición y calidad de vida en pacientes con esquizofrenia: utilidad de la MATRICS Consensus Cognitive Battery / Cognition and quality of life in patients with schizophrenia: usefullness of the MATRICS Consensus Cognitive Battery

El déficit cognitivo es un síntoma nuclear de la esquizofrenia. La iniciativa Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) del National Institute of Mental Health (NIMH) de Estados Unidos se planteó como objetivo desarrollar una batería cognitiva de consenso para evaluar en un contexto clínico los diferentes dominios cognitivos afectados en estos pacientes. El resultado de ese trabajo fue el desarrollo de la MATRICS Consensus Cognitive Battery (MCCB). La estandarización y obtención de datos normativos en nuestro medio ha sido realizada recientemente. Los objetivos del presente trabajo fueron: a) estudiar el funcionamiento cognitivo medido con la MCCB en una muestra de pacientes con esquizofrenia y comparar los resultados con un grupo control, y b) estudiar la relación entre los diferentes dominios cognitivos y la calidad de vida en el grupo de pacientes con esquizofrenia. Se realizó el estudio con un grupo de 40 pacientes con diagnóstico de esquizofrenia según los criterios de la cuarta edición del Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), y un grupo control de 40 sujetos pareados por sexo y edad. Los resultados mostraron un déficit cognitivo de los pacientes con esquizofrenia en todos los dominios cognitivos evaluados por la MCCB, así como la utilidad de la MCCB en el estudio de la función cognitiva en nuestro medio. Además, se encontraron correlaciones significativas entre la calidad de vida y algunos dominios cognitivos: velocidad de proceso (0,398; p = 0,011), aprendizaje y memoria verbal (0,456; p = 0,003), y razonamiento y solución de problemas (0,496; p = 0,001) (AU)

Cognitive dysfunction is a nuclear symptom of schizophrenia. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative of the U.S. National Institute of Mental Health (NIMH) set as one of its objectives the development of a consensus cognitive battery for the clinical assessment of the different cognitive domains that are impaired in these patients. The result of this was the MATRICS Consensus Cognitive Battery (MCCB). The standardization and obtention of normative data of the battery in our milieu was recently carried out. The objectives of the present investigation were a) to study the cognitive performance of a sample of schizophrenic patients as assessed by the MCCB and to compare the results with a control group; b) to study the relationship between the different cognitive domains and quality of life in the sample of schizophrenic patients. The study was carried out with a group of 40 patients diagnosed with schizophrenia according to DSM-IV criteria, and a control group of 40 subjects who were matched by age and gender. Results show cognitive deficits in the patient group across all the cognitive domains assessed by the MCCB, as well as the usefulness of the MCCB in the study of cognitive function in our milieu. In addition, significant correlations were found between quality of life and some of the cognitive domains: speed of processing (0.398; p = 0.011), verbal learning and memory (0.456; p = 0.003), and reasoning and problem solving (0.496; p = 0.001) (AU)

[Cognitive deficit in schizophrenia: MATRICS Consensus Cognitive Battery]. / Déficit cognitivo en la esquizofrenia: MATRICS Consensus Cognitive Battery.

Cognitive deficits constitute a core symptom in schizophrenia, are difficult to treat, and have special relevance regarding prognosis and functional outcome. The search for pharmacological strategies for improving cognition in schizophrenic patients has been hindered by the lack of a consensus regarding instruments for cognitive assessment. The 'Measurement and Treatment Research to Improve Cognition in Schizophrenia' (MATRICS) initiative of the U.S. National Institute of Mental Health (NIMH) set the development of a consensus cognitive battery as one of its objectives. In a first phase, the seven cognitive domains which have been shown to be impaired in schizophrenia and that were to be assessed were identified: Speed of processing, Attention/Vigilance, Working memory, Verbal learning, Visual learning, Reasoning and problem solving, and Social cognition. In a second phase, the MATRICS Consensus Cognitive Battery (MCCB) was developed. This is a cognitive assessment battery composed of ten instruments, which assess the seven domains in a little over one hour. The MCCB has been standardized in U.S. population, and the Spanish standardization has been recently published.

Déficit cognitivo en la esquizofrenia: MATRICS Consensus Cognitive Battery / Cognitive deficit in schizophrenia: MATRICS Consensus Cognitive Battery

El déficit cognitivo en la esquizofrenia es un síntoma nuclear, de difícil tratamiento en la actualidad, y que tiene especial relevancia en el pronóstico y capacidad funcional de los pacientes. La búsqueda de estrategias farmacológicas que demuestren eficacia en la mejoría cognitiva de pacientes con esquizofrenia ha presentado como una importante barrera la ausencia de instrumentos de evaluación cognitiva consensuados y utilizados de manera generalizada. La iniciativa Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) del National Institute of Mental Health (NIMH) de Estados Unidos ha tenido como uno de sus objetivos el desarrollo de una batería cognitiva de consenso. En una primera fase estableció los siete dominios cognitivos afectados en la esquizofrenia que habían de evaluarse: velocidad de proceso, atención/vigilancia, memoria de trabajo, aprendizaje y memoria verbal, aprendizaje y memoria visual, razonamiento y solución de problemas y, por último, cognición social. Posteriormente se desarrolló la MATRICS Consensus Cognitive Battery, una batería de evaluación cognitiva formada por 10 instrumentos con los que en algo más de una hora se evalúan los siete dominios cognitivos. Este instrumento se ha estandarizado en población estadounidense y recientemente se ha publicado la estandarización en España (AU)

Cognitive deficits constitute a core symptom in schizophrenia, are difficult to treat, and have special relevanceregarding prognosis and functional outcome. The search for pharmacological strategies for improving cognition in schizophrenic patients has been hindered by the lack of a consensus regarding instruments for cognitive assessment. The ‘Measurement and Treatment Research to Improve Cognition in Schizophrenia’ (MATRICS) initiative of the U.S. National Institute of Mental Health (NIMH) set the development of a consensus cognitive battery as one of its objectives. In a first phase, the seven cognitive domains which have been shown to be impaired in schizophrenia and that were to be assessed were identified: Speed of processing, Attention/Vigilance, Working memory, Verbal learning, Visual learning, Reasoning and problem solving, and Social cognition. In a second phase, the MATRICS Consensus Cognitive Battery (MCCB) was developed. This is a cognitive assessment battery composed of ten instruments, which assess the seven domains in a little over one hour. The MCCB has been standardized in U.S. population, and the Spanish standardization has been recently published (AU)

Constructive thinking, rational intelligence and irritable bowel syndrome.

AIM: To evaluate rational and experiential intelligence in irritable bowel syndrome (IBS) sufferers. METHODS: We recruited 100 subjects with IBS as per Rome II criteria (50 consulters and 50 non-consulters) and 100 healthy controls, matched by age, sex and educational level. Cases and controls completed a clinical questionnaire (including symptom characteristics and medical consultation) and the following tests: rational-intelligence (Wechsler Adult Intelligence Scale, 3rd edition); experiential-intelligence (Constructive Thinking Inventory); personality (NEO personality inventory); psychopathology (MMPI-2), anxiety (state-trait anxiety inventory) and life events (social readjustment rating scale). Analysis of variance was used to compare the test results of IBS-sufferers and controls, and a logistic regression model was then constructed and adjusted for age, sex and educational level to evaluate any possible association with IBS. RESULTS: No differences were found between IBS cases and controls in terms of IQ (102.0 +/- 10.8 vs 102.8 +/- 12.6), but IBS sufferers scored significantly lower in global constructive thinking (43.7 +/- 9.4 vs 49.6 +/- 9.7). In the logistic regression model, global constructive thinking score was independently linked to suffering from IBS [OR 0.92 (0.87-0.97)], without significant OR for total IQ. CONCLUSION: IBS subjects do not show lower rational intelligence than controls, but lower experiential intelligence is nevertheless associated with IBS.

Influence of psychological distress on characteristics of symptoms in patients with GERD: the role of IBS comorbidity.

UNLABELLED: A link between gastroesophageal reflux disease (GERD) and psychological distress has been suggested; psychological factors may modulate the characteristics of symptoms. Besides, irritable bowel syndrome (IBS) frequently coexists with GERD so it may be hypothesized that psychological distress in GERD might be an epiphenomenon of IBS comorbidity. AIMS: Evaluate the association of psychological distress with GERD, the influence of psychological factors on symptoms, whether psychological distress is explained by a subset of GER patients, and if coexistence with IBS would be a surrogate marker. METHODS: We performed a prospective case-control study. Cases were patients diagnosed with GERD reporting heartburn at least 2 days per week as the main complaint. Controls were matched healthy subjects without or occasional symptoms. All individuals completed a set of validated questionnaires to evaluate GERD and IBS symptoms and psychological distress (SCL-90R). RESULTS: Ninety-two patients and 92 controls were included. Fifty-seven patients and six controls fulfilled Rome II criteria for IBS. Body mass index (BMI), somatization, and IBS were independently related to GERD. Patients with and without IBS were not different in any measure of psychological distress. Characteristics of symptoms did not correlate to psychological measures. Cluster analysis isolated a cluster of nondistressed from distressed subjects. A higher proportion of GERD patients than controls were classified as distressed (29.7% versus 7.7%). No variable (including IBS) distinguished nondistressed from distressed GERD patients, except for sex. CONCLUSIONS: Nearly one-third of GERD patients attending a gastroenterologist office are psychological distressed; they cannot be identified by features of symptoms or IBS comorbidity so a specific anamnesis under the scope of a biopsychosocial model is warranted.

Determinants of quality of life in irritable bowel syndrome.

OBJECTIVES: Health-related quality of life (HRQOL) is a main outcome in irritable bowel syndrome (IBS), but most studies have been conducted on moderate-severe patients. We sought to ascertain the relative contribution of severity, anxiety, and personality to impairment of HRQOL in a sample representative of the entire IBS spectrum. MATERIALS AND METHODS: IBS consulters, IBS nonconsulters, and controls were invited to complete questionnaires designed to measure severity of IBS (Functional Bowel Disease Severity Index), anxiety (State-trait Anxiety Inventory), personality (Minnesota Multiphasic Personality Inventory-2), and HRQOL [Short Form 36 (SF-36)]. The SF-36 scores of the study groups were compared, and a multiple regression model was constructed. RESULTS: Sixty-six IBS consulters, 70 nonconsulters, and 117 controls were studied. All 3 groups differed in terms of SF-36 physical (46.5+/-9.4 vs. 50.5+/-8.0 vs. 54.5+/-6.0) and mental composite scores (38.2+/-12.5 vs. 43.2+/-12.0 vs. 46.7+/-10.6). Although physical scores were linked to hypochondriasis (beta=-0.39; P<0.001), severity of pain (beta=-0.28; P<0.001), and age, mental scores were associated with state anxiety (beta=-0.36; P<0.001) and trait anxiety (beta=-0.40; P<0.001). CONCLUSIONS: HRQOL is impaired in all subgroups of IBS sufferers, with the degree of impairment depending mostly on symptom severity and psychologic factors (hypochondriasis and anxiety).