Cortical metabolic arrangement during olfactory processing:proposal for a 18F-FDG PET/CT methodological approach

The aim of this article is to investigate the cortical metabolic arrangements in olfactory processing by using 18F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. Twenty-six normosmic individuals (14 women and 12 men; mean age 46.710 years) were exposed to a neutral olfactory condition (NC) and, after 1 month, to a pure olfactory condition (OC) in a relatively ecological environment, that is, outside the scanner. All the subjects were injected with 185-210 megabecquerel of 18F FDG during both stimulations. Statistical parametric mapping version 2 was used in order to assess differences between NC and OC. As a result, we found a significant higher glucose consumption during OC in the cuneus, lingual, and parahippocampal gyri, mainly in the left hemisphere. During NC, our results show a relative higher glucose metabolism in the left superior, inferior, middle, medial frontal, and orbital gyri as well as in the anterior cingulate cortex. The present investigation, performed with a widely available functional imaging clinical tool, may help to better understand the neural responses associated to olfactory processing in healthy individuals and in patients with olfactory disorders by acquiring data in an ecologic, noise-free, and resting condition in which possible cerebral activations related to unwanted attentional processes might be avoided

The motivation and pleasure dimension of negative symptoms: neural substrates and behavioral outputs.

A range of emotional and motivation impairments have long been clinically documented in people with schizophrenia, and there has been a resurgence of interest in understanding the psychological and neural mechanisms of the so-called "negative symptoms" in schizophrenia, given their lack of treatment responsiveness and their role in constraining function and life satisfaction in this illness. Negative symptoms comprise two domains, with the first covering diminished motivation and pleasure across a range of life domains and the second covering diminished verbal and non-verbal expression and communicative output. In this review, we focus on four aspects of the motivation/pleasure domain, providing a brief review of the behavioral and neural underpinnings of this domain. First, we cover liking or in-the-moment pleasure: immediate responses to pleasurable stimuli. Second, we cover anticipatory pleasure or wanting, which involves prediction of a forthcoming enjoyable outcome (reward) and feeling pleasure in anticipation of that outcome. Third, we address motivation, which comprises effort computation, which involves figuring out how much effort is needed to achieve a desired outcome, planning, and behavioral response. Finally, we cover the maintenance emotional states and behavioral responses. Throughout, we consider the behavioral manifestations and brain representations of these four aspects of motivation/pleasure deficits in schizophrenia. We conclude with directions for future research as well as implications for treatment

Breaking Apart the Reinforcement Learning Deficit in Schizophrenia

Reinforcement learning deficits have long been associated with schizophrenia. However, tasks traditionally used to assess these deficits often rely on multiple processing streams leaving the etiology of these task deficits unclear. In the current study, we borrowed a recent framework from computational neuroscience, which separates reinforcement-learning into two distinct systems, model-based and model-free. Under this framework, the model-free system learns about the value of actions in the immediate context, while the model-based system learns about the value of actions in both immediate and subsequent states that may be encountered as a result of their actions. Using a decision task that has been previously validated to assess relative reliance on each system we showed that individuals with schizophrenia demonstrated decreased model-based but intact model-free learning estimates. Furthermore, parameter estimates of model-based behavior correlated positively with IQ, suggesting that model-based deficits in schizophrenia may relate to reduced intellectual function. These findings specify reinforcement-learning deficits in schizophrenia by showing both intact and disturbed components. Such findings and computational frameworks provide meaningful insights as researchers continue to characterize decision-making circuitry in schizophrenia as a means to discover new pathways for interventions

Voxelbasierte Morphometrie: Untersuchung zur Hirnvolumetrie bei Parosmikern

Die Parosmie ist eine qualitative Riechstörung, für die in der Normalbevölkerung eine Prävalenz von 4% angegeben wird. Kennzeichnend für eine Parosmie ist die subjektiv veränderte Wahrnehmung von Riechstoffen, wobei die gestörte Riechwahrnehmung meist als unangenehm geschildert wird. Die Ätiopathogenese der Parosmie ist bisher nicht bekannt, jedoch belegen Studien, dass Parosmiker geringere Volumina des Bulbus olfactorius (OB) aufweisen als Nicht-Parosmiker. Ziel der vorliegenden Untersuchung war es, mithilfe der auf MRT-Datensätzen basierenden Voxelbasierten Morphometrie (VBM) Riechareale volumetrisch zu untersuchen, die dem OB funktionell nachgeschaltet sind. Untersucht wurden 22 Patienten mit einer Parosmie und 22 qualitativ riechgesunde, alters- und geschlechtskontrollierte Vergleichspersonen, deren quantitative Riechleistung der der Parosmiker entsprach. Im Ergebnis zeigte sich bei der Analyse des gesamten Großhirns bei den Parosmikern eine signifikante Reduktion der grauen Substanz im linken anterioren Inselkortex im Vergleich zur Kontrollgruppe. In einer Subanalyse, die nur primäre und sekundäre Riechareale verglich, zeigte sich außerdem eine signifikante Reduktion der grauen Substanz auch im rechten anterioren Inselkortex. Darüber hinaus waren im linken anterioren Cortex cinguli, im linken medialen orbitofrontalen und piriformen Kortex sowie in der Hippocampusformation beidseits signifikante kortikale Volumenverluste zu verzeichnen. Zusammenfassend sind bei Parosmikern solche Areale von einer Volumenreduktion betroffen, die eine Rolle bei der Riechwahrnehmung, Riechunterscheidung, dem Riechgedächtnis und der emotionalen Bewertung von Riechstoffen spielen. Die vorliegende Untersuchung liefert Hinweise auf eine mögliche Korrelation zwischen einer Volumenreduktion in den o. g. Arealen und ihren Funktionen

Conative Dysfunction in Schizophrenia: A New Empirically-Derived Framework

Conative dysfunction, defined as deficits in performing motivated or volitional action leading to the functional outcome of reduced goal-directed activity (RGDA), is explored as a fundamental and highly impairing aspect of schizophrenia. It is proposed that conative dysfunction is multifaceted and may take different forms within different individuals. Although many such factors have already been studied in schizophrenia, this has been done in a piecemeal fashion, not permitting comparisons among multiple forms of conative dysfunction to determine which ones are most impacted by the disorder or which may cluster within individuals. Thus, the heterogeneity and interrelationships between these factors has not been adequately assessed. A broad range of motivational and volitional tests, representing aspects of conative functioning drawn from a variety of fields including personality, neuropsychology, motivational psychology and psychopathology are administered to a sample of schizophrenia outpatients. Several of these have not previously been examined in the context of schizophrenia. Three research questions are addressed, including; 1) whether distinct conative “types,” characterized by separable dysfunctions, exist; 2) whether some conative functions are more impacted than others in schizophrenia, and whether this depends upon the between-individual variability addressed in question one; and 3) which conative factors are most predictive of poor functional outcomes (i.e., RGDA) in schizophrenia. These questions are addressed via 1) cluster analysis, 2) a series of profile analyses, and 3) a series of regression analyses. Findings support the existence of two distinct patterns of conative dysfunction within schizophrenia, each associated with a set of specific characteristics. One cluster is characterized by difficulty energizing (an executive function subserved by the superior medial prefrontal cortex) and reduced reward sensitivity, while the other is characterized by increased punishment sensitivity, boredom proneness, and various self-reported cognitive, volitional and emotional pathologies, in the context of intact motivation. Distinct aspects of conative dysfunction in each cluster contribute significantly to RGDA, especially boredom propensity, reward sensitivity, intrinsic motivation, and various executive functions. Comparisons are drawn between each cluster and existing clinical typologies. Implications of each of these findings for future research, clinical assessment and intervention are discussed

Hedonics, Reward Prediction, and Reinforcement Learning in Schizophrenia: Relationships to Anhedonia and Avolition

Anhedonia (a reduced experience of pleasure) and avolition (a reduction in goal-directed activity) are common features of schizophrenia that have substantial effects on functional outcome, but are poorly understood and treated. Here, we examine the potential contributions of three processes involved in the translation of reward information in the environment into goal-directed action among medicated individuals with schizophrenia. The first process, hedonics, or the enjoyment of pleasant experiences, was examined using an fMRI study of emotional experience in response to affective stimuli. Results were similar between patients and controls at a group level, but patients with greater anhedonia/avolition demonstrated reduced self-reports and brain activity in response to positive stimuli in ventral striatum and amygdala, regions associated with salience and reward. The second process we examined was reward prediction, which describes anticipatory responses to cues that predict reward. This process is thought to be mediated by the mesolimbic dopamine system, which shows evidence of dysregulation in schizophrenia. We examined reward prediction using a Pavlovian paradigm with monetary reward, using fMRI to examine brain responses during reward anticipation and receipt. Responses to reward receipt were largely intact in schizophrenia, while anticipation responses in ventral striatum, a major target of dopaminergic afferents, were reduced in those patients who were higher in anhedonia/avolition. The final process we examined was reinforcement learning, or the process by which positive and negative feedback influences trial-and-error choice behavior. Participants underwent fMRI during a reinforcement learning task with probabilistic feedback. Evidence from behavior and computational modeling suggested impairment in learning from positive feedback. However, neuroimaging data revealed largely intact striatal activation during both choice and feedback, a surprising result given the role of dopaminergic influence on corticostriatal circuits in mediating reinforcement learning. Instead, there was some evidence for reduced cortical responses to choice execution among patients, and to positive feedback among those patients higher in anhedonia/avolition. Together, these studies suggest that impairments in hedonics, reward prediction, and reinforcement learning may play a role in anhedonia/avolition in schizophrenia, but that these impairments are not sufficient causes of these symptoms; impairments in other higher-level cognitive processes are also likely to contribute

Sustained and Transient Reward Effect on Cognitive Control in Schizophrenia: The Relevance of Negative Symptoms

Schizophrenia (SCZ) is characterized by severe cognitive impairments and amotivation, generally referred to as negative symptoms, including anhedonia and/or avolition. Amotivation tends to exist in prodromal patients and persist over the illness course regardless of successful antipsychotic medications, which are known to reduce positive symptoms, including hallucination and delusions (e.g., (Horan, Blanchard, Clark, & Green, 2008; Tarbox et al., 2013). Importantly, amotivation is a promising predictor for later social functioning in SCZ, even after accounting for patients\u27 cognitive impairments (e.g., (Evensen et al., 2012; Faerden et al., 2010). Despite this crucial impact on functioning outcome in SCZ, to date, no study has systematically investigated neural mechanism underlying amotivation in SCZ. To date, it has been well documented that many of cognitive impairments in SCZ may reflect a core deficit of non-emotional context processing, supported by the dorsolateral prefrontal cortex (DLPFC), and defined by the ability to maintain non-emotional context information necessary to regulate upcoming behavioral response towards goal-directed behavior (e.g., (Cohen, Barch, Carter, & Servan-Schreiber, 1999). Recent evidence from both animal and healthy human neuroimaging work suggests that the DLPFC plays a crucial role in representing and integrating reward-related context information. However, it has been unexplored whether individuals with SCZ can represent and integrate reward-related contextual information to modulate cognitive control function implicated in the DLPFC. Thirty-six individuals with SCZ and twenty-seven healthy controls (HC) underwent behavioral and fMRI data collection at 3Tsela while performing a modified response conflict processing task under two contexts, that is, no-reward baseline and reward contexts. Participants first performed baseline conditions without any knowledge regarding the future potential for incentives (Baseline-Context; BCXT). Each trial started with a baseline cue, XX that was pre-instructed to participants as being irrelevant to the task. After each cue, XX, either a house or building picture (with overlaid words that are either congruent or incongruent) was presented to each participant one at a time. The job of the task was to categorize each picture as either a house or a building by pressing a certain button while ignoring the overlaid word. Following the baseline condition, participants performed additional reward blocks on which they were told that they could win money on some trials by performing fast (faster than their median correct reaction times (RT) in the baseline and accurately). Each trial was then preceded either by a $20 cue (Reward-Cue; RC), indicating that a fast and correct response would be rewarded or by a XX cue (Reward-Context; RCXT), indicating zero money would be possible on the trial. After the target stimulus, participants received immediate feedback regarding the reward points they earned on the trials, as well as their cumulative earning in points. As such, this response conflict task paradigm enabled examination of: (1) reward context effects by comparing performance and brain activity when the cue, XX was presented in the baseline context versus in the reward context (BCXT vs. RCXT trials cued by the same cue, XX ) and (2) reward cue effects by comparing performance during RC (cued by$20 ) versus RCXT (cued by XX ) within reward blocks. Importantly, by employing a mixed state-item fMRI design, I investigated both sustained (block-based) context-dependent and transient (trial-by-trial) reward-related cue activity at both behavioral and neural levels

Procesamiento emocional en psicosis: un estudio de neuroimagen funcional

Las alteraciones en el procesamiento emocional han sido ampliamente descritas en la esquizofrenia (Cohen & Minor, 2008; Kring & Moran, 2008). Estas alteraciones emocionales se han relacionado tanto con los síntomas negativos como los síntomas positivos de la enfermedad. En relación con las alucinaciones auditivas algunos modelos explicativos destacan el papel crítico de los factores emocionales en la fisiopatología de las mismas. El desarrollo de las técnicas de neuroimagen ha permitido el estudio de las bases neurobiológicas de las funciones cerebrales mediante técnicas no invasivas. Pocos de estos estudios han investigado la asociación entre las alucinaciones y las alteraciones emocionales mediante el uso de un paradigma auditivo emocional. Para el análisis de los datos obtenidos de la resonancia magnética (RM) se ha utilizado dos enfoques, los modelos guiados por el paradigma y los modelos guiados por los datos. Para este estudio se ha utilizado el Análisis de Componentes Independientes (ICA) que es un método de análisis especialmente útil para la descomposición de la activación cerebral durante el procesamiento de las tareas cognitivas complejas sin necesidad de introducir un modelo previo obteniendo las redes funcionales implicadas en el proceso estudiado. Objetivos: 1. Identificar las redes funcionales implicadas en el procesamiento de un estímulo auditivo emocional y neutro en un grupo de pacientes psicóticos con y sin alucinaciones auditivas y en un grupo de sujetos sanos. 2. Estudiar las diferencias cualitativas en las redes funcionales identificadas entre los tres grupos de estudio. Hipótesis: Los pacientes con y sin alucinaciones auditivas mostrarán diferencias en las redes funcionales responsables del procesamiento de las palabras emocionales y neutras escuchadas. Material y método: Se reclutaron tres grupos de sujetos: 41 pacientes con diagnóstico del espectro psicótico (27 con alucinaciones auditivas y 14 sin alucinaciones auditivas) y 31 sujetos sanos. A los participantes se les realizó una RM funcional en la que se aplicó un paradigma auditivo con dos sesiones una con palabras emocionales y otra con palabras neutras. El análisis de los datos se realizó con un enfoque multivariante, con ICA. Resultados: 1. En la sesión emocional se identificaron las siguientes redes funcionales: • En controles se identificaron 4 redes: temporal, fronto-parieto-temporal, subcortical-fronto-temoporal y occipito-cerebelar; • En pacientes con alucinaciones auditivas se identificaron 5 redes: temporal, fronto-parieto-temporal, subcortical-fronto-temporal, límbica y occipito-cerebelar; • En los pacientes sin alucinaciones auditivas se identificaron 4 redes: temporal, fronto-parieto, fronto-temporal, fronto-parietal. • 2. En la sesión neutra se identificaron: • En controles, 3 redes funcionales: temporal y fronto-parietal derecha/izquierda; • En pacientes con alucinaciones auditivas, 2 redes: temporal y fronto-parietal derecha; • En pacientes sin alucinaciones auditivas, 2 redes: temporal y fronto-parietal derecha.Background: Alterations in emotional processing have been widely described in schizophrenia (Cohen & Minor, 2008, Kring & Moran, 2008). These emotional disorders have symptoms related to both negative and positive symptoms. In relation to auditory hallucinations some explanatory models highlight the critical role of emotional factors in its pathophysiology. The development of neuroimaging techniques has allowed the study of the neurobiological basis of brain function. Few studies have investigated association between hallucinations and emotional disorders. For the analysis of data from magnetic resonance imaging (MRI) has used two approaches, guided by the paradigm models and models guided by the data. For this study we used the Independent Component Analysis (ICA). This approach is a model-independent multivariate statistical computational technique designed to extract spatially independent and temporally synchronous activity patterns in brain regions, giving functional covariance in brain regions. The present study has two principal aims. First, we aim to analyze differences in functionally connected networks between control subjects and non-affective psychotic patients during passive listening to an emotional auditory paradigm using an ICA approach. Secondly, we aim to compare patients with non-affective psychosis and auditory hallucinations with non-hallucinatory patients. Methods: A total of 41 male patients with non-affective psychosis diagnosis, 27 with chronic auditory hallucinations and 14 without hallucinations, were recruited. Thirty-one healthy controls were also examined. Participants underwent functional MRI was applied in the auditory paradigm with two sessions with each other with emotional words and neutral words. The data analysis was performed using a multivariate approach with ICA. Results: Limbic networks responded differently in patients with auditory hallucinations compared to healthy controls and patients without auditory hallucinations. Unlike control subjects and non-hallucinators, the group of hallucinatory patients showed an increase of activity in the parahippocampal gyrus and the amygdala during the emotional session. Conclusions: These findings may reflect an increase in parahippocampal gyrus and amygdala activity during passive listening of emotional words in patients with schizophrenia and auditory hallucinations