Mario Altamura

Dissociating the Effects of Sternberg Working Memory Demands in Prefrontal Cortex

Earlier neuroimaging studies of working memory (WM) have demonstrated that dorsolateral prefrontal cortex (DLPFC) activity increases as maintenance and load demand increases. However, few studies have carefully disambiguated these two WM processes at the behavioral and physiological levels. The objective of the present functional resonance imaging (fMRI) study was to map within prefrontal cortex locales that are selectively load sensitive, delay sensitive, or both. We studied 18 right-handed normal subjects with fMRI at 3 Tesla during a block design version of the Sternberg task. WM load was manipulated by varying the memory set size (3, 5, or 8 letters). The effect of memory maintenance was examined by employing two time delays (1 s and 6 s) between the letter set and probe stimuli. The DLPFC was strongly activated in load manipulation, whereas activation as a function of delay was restricted to the left premotor regions and Brocas areas. Moreover, regions of prefrontal cortex on the right (BA 46) were found to be exclusively affected by load. These results suggest the possibility that top-down modulation of attention or cognitive control at encoding and/or decisionmaking may be mediated by these areas.

Hippocampal neurochemical pathology in patients at first episode of affective psychosis: a proton magnetic resonance spectroscopic imaging study.

While several studies have suggested a relationship between the hippocampus and psychosis in schizophrenia, fewer studies have specifically investigated the presence of psychosis in mood disorders from a neurobiological perspective. Moreover, a limitation of these earlier studies is that the majority of them were performed in chronic patients. The present proton magnetic resonance spectroscopic imaging (1H-MRSI) study assessed neuronal integrity (as assessed with N-acetylaspartate, NAA) in the hippocampus of patients with a first episode of mood disorders with psychotic symptoms. We studied 17 patients and 17 healthy subjects matched for age and sex. Subjects underwent 1H-MRSI, and measures of NAA, choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in 11 brain regions were obtained, i.e. hippocampus (HIPPO), dorsolateral prefrontal cortex, superior temporal gyrus, inferior frontal gyrus, occipital cortex, anterior and posterior cingulate, centrum semiovale, prefrontal white matter, thalamus and putamen. NAA/CRE ratios in HIPPO of patients were significantly lower than in controls. Sporadic and non-hypothesis-driven results were found in occipital cortex and prefrontal white matter as a main effect of diagnosis, and in superior temporal gyrus as a hemisphere by diagnosis interaction. These results would not survive a Bonferroni correction for the number of ROIs. No correlations were found with the available demographic and clinical data. Therefore, hippocampal neuronal abnormalities are present at the onset of mood disorders with psychotic symptoms. These data suggest that neuronal abnormalities in HIPPO may be associated with psychosis in mood disorders. Since these data were obtained in patients at first episode, they cannot be explained by chronicity of illness or pharmacological treatment.

Selective updating of working memory content modulates meso-cortico-striatal activity.

Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling.

Psychosocial Functioning in Consultation-Liaison Psychiatry Patients: Influence of Psychosomatic Syndromes, Psychopathology and Somatization

Background:This study investigated whether the Diagnostic Criteria for Psychosomatic Research (DCPR) were able to predict psychosocial functioning in addition to psychiatric diagnoses and somatization in consultation-liaison psychiatry (CLP) patients. Method: A consecutive sample of 208 CLP patients were recruited and assessed for sociodemographic and medical data, psychopathology (SCID), psychosomatic syndromes (DCPR structured interview) and somatization (SCL-90-R SOM scale and multisomatoform disorder, MSD). The main endpoints were the mental and physical components of psychosocial functioning (SF-36). Results: A total of 185 (89%) patients had any psychiatric diagnosis, 51 (25%) had MSD positive criteria, 176 (85%) had any DCPR syndrome, and 105 (51%) had multiple DCPR syndromes. Although psychiatric and psychosomatic syndromes were variously associated with psychosocial functioning, hierarchical regression and effect size analyses showed that only DCPR syndromes, particularly demoralization and health anxiety, with somatization but not DSM-IV psychopathology independently predicted poor psychosocial functioning. Conclusions:The presence of psychosomatic syndromes, assessed with DCPR criteria, and high levels of somatization had larger effect size and were independent predictors of the mental and physical components of psychosocial dysfunction, over and above psychopathology. The DCPR classification can provide CLP professionals with a set of sensitive diagnostic criteria for a comprehensive clinical evaluation of psychosomatic syndromes that might play a significant mediating role in the course and the outcome of medical patients referred for psychiatric consultation.

Prefrontal cortex modulation during anticipation of working memory demands as revealed by magnetoencephalography

During the anticipation of task demands frontal control is involved in the assembly of stimulus-response mappings based on current goals. It is not clear whether prefrontal modulations occur in higher-order cortical regions, likely reflecting cognitive anticipation processes. The goal of this paper was to investigate prefrontal modulation during anticipation of upcoming working memory demands as revealed by magnetoencephalography (MEG). Twenty healthy volunteers underwent MEG while they performed a variation of the Sternberg Working Memory (WM) task. Beta band (14–30 Hz) SAM (Synthetic Aperture Magnetometry) analysis was performed. During the preparatory periods there was an increase in beta power (event-related synchronization) in dorsolateral prefrontal cortex (DLPFC) bilaterally, left inferior prefrontal gyrus, left parietal, and temporal areas. Our results provide support for the hypothesis that, during preparatory states, the prefrontal cortex is important for biasing higher order brain regions that are going to be engaged in the upcoming task.

The relationship between personality traits, the 5HTT polymorphisms, and the occurrence of anxiety and depressive symptoms in elite athletes

The purpose of this study was to determine the relationship between personality, the serotonin transporter (5HTT) polymorphisms and the occurrence of anxiety and depressive symptoms in elite athletes. 133 healthy participants completed the NEO Five-Factor Inventory (NEO-FFI). The mood states were assessed using the Profile of Mood States (POMS) questionnaire. The athlete’s mental skills were assessed through the Sport Performance Psychological Inventory (IPPS-48). The occurrence of psychiatric and personality disorders was assessed using the Clinical Interview for DSM-IV Disorders. A polymerase chain reaction was employed to identify genotypes at the 5HTTLPR polymorphism. The 5HTTLPR s/s genotype was associated with both neuroticism (p< 0.001) and tension/anxiety symptoms according to the POMS (p<0.02), cognitive anxiety and emotional arousal control according to the IPPS-48 (p<0.01). Significant correlations were proved between neuroticism and symptoms of anxiety and depression (p<0.05). Neuroticism mediates the association between the 5HTTLPR polymorphism and symptoms of cognitive anxiety and emotional arousal control (p<0.05). These results suggest a significant interaction between the 5HTTLPR polymorphism, neuroticism and sport related stress that predict adverse mental health outcomes in athletes. Identification of homogeneous groups of athletes having predispositions to anxiety and depressive symptoms may help to implement early prevention programs.

Abnormal functional motor lateralization in healthy siblings of patients with schizophrenia

Earlier neuroimaging studies of motor function in schizophrenia have demonstrated reduced functional lateralization in the motor network during motor tasks. Here, we used event-related functional magnetic resonance imaging during a visually guided motor task in 18 clinically unaffected siblings of patients with schizophrenia and 24 matched controls to investigate if abnormal functional lateralization is related to genetic risk for this brain disorder. Whereas activity associated with motor task performance was mainly contralateral with only a marginal ipsilateral component in healthy participants, unaffected siblings had strong bilateral activity with significantly greater response in ipsilateral and contralateral premotor areas as well as in contralateral subcortical motor regions relative to controls. Reduced lateralization in siblings was also identified with a measure of laterality quotient. These findings suggest that abnormal functional lateralization of motor circuitry is related to genetic risk of schizophrenia.

The relationships of personal resources with symptom severity and psychosocial functioning in persons with schizophrenia: results from the Italian Network for Research on Psychoses study

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions.

Toward scale-free like behavior under increasing cognitive load

To understand how cognition and response selection processes might emerge from dynamic brain systems, we analyzed reaction times during the performance of both a working memory task and a choice reaction time task at different levels of “cognitive load.” Our findings suggest a continuous transition—tuned by load—from random behavior toward scale-free like behavior as an expanding connectivity process in a network poised near a critical point.

Psychological Factors Affecting Medical Conditions in Consultation-Liaison Psychiatry

Consultation-liaison (C-L) psychiatry has an important role in the identification and management of psychological problems in patients with medical disorders in general hospitals. The diagnostic tools C-L psychiatrists are usually provided with may reveal to be limited because of particular psychosomatic syndromes and subthreshold psychopathology that are undetected by psychiatric diagnostic criteria. The Diagnostic Criteria for Psychosomatic Research (DCPR) were developed with the aim of providing clinicians with operational criteria for psychosomatic syndromes to overcome the limitations shown by the most often diagnosed disorders in medical settings as adjustment, somatoform, mood, and anxiety disorders. In a group of 66 consecutive C-L psychiatry inpatients, a consistent prevalence of 71% DCPR syndromes was found, particularly secondary functional somatic symptoms, persistent somatization, health anxiety, and demoralization. Their overlap rates with DSM-IV diagnoses showed that the DCPR syndromes were able to identify psychological dimensions (as somatic symptom clustering, anxiety triggered by the current health status, and a feeling state of hopelessness) that do not meet or are not detected by DSM-IV. Furthermore, the DCPR syndromes identified patients with clinically significant functional impairment. These results replicate previous findings in C-L psychiatry using the DCPR categories and pave the way for further research to clarify their mediating role in the course and the outcome variance of medical and psychological problems of hospital inpatients referred for psychiatric consultation.