Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the -521Cmayor queT DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic-hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region

Media Reporting of Neuroscience Depends on Timing, Topic and Newspaper Type

The rapid developments in neuroscientific techniques raise high expectations among the general public and therefore warrant close monitoring of the translation to the media and daily-life applications. The need of empirical research into neuroscience communication is emphasized by its susceptibility to evoke misconceptions and polarized beliefs. As the mass media are the main sources of information about (neuro-)science for a majority of the general public, the objective of the current research is to quantify how critically and accurately newspapers report on neuroscience as a function of the timing of publication (within or outside of periods of heightened media attention to neuroscience, termed “news waves”), the topic of the research (e.g. development, health, law) and the newspaper type (quality, popular, free newspapers). The results show that articles published during neuroscience news waves were less neutral and more optimistic, but not different in accuracy. Furthermore, the overall tone and accuracy of articles depended on the topic; for example, articles on development often had an optimistic tone whereas articles on law were often skeptical or balanced, and articles on health care had highest accuracy. Average accuracy was rather low, but articles in quality newspapers were relatively more accurate than in popular and free newspapers. Our results provide specific recommendations for researchers and science communicators, to improve the translation of neuroscience findings through the media: 1) Caution is warranted during periods of heightened attention (news waves), as reporting tends to be more optimistic; 2) Caution is also warranted not to follow topic-related biases in optimism (e.g., development) or skepticism (e.g., law); 3) Researchers should keep in mind that overall accuracy of reporting is low, and especially articles in popular and free newspapers provide a minimal amount of details. This indicates that researchers themselves may need to be more active in preventing misconceptions to aris

Antisocial Behavior and Callous Unemotional Traits in Youth: A Biosocial Approach

Early life presence of antisocial behavior (e.g., aggression/delinquency) and psychopathic/callous-unemotional (CU) traits (lacking empathy/remorse, shallow affect) are precursors to juvenile crime and criminal offending in adulthood. Etiological research on antisocial/CU tendencies has implicated both neurobiological (e.g., alterations in brain function and structure) and environmental (social adversity, prenatal stress) underpinnings. It has been proposed that reward and punishment processing deficits may induce problematic traits and behavior, such that antisocial/CU tendencies may be linked to hypersensitivity to rewards and hyposensitivity to punishment. Studies in this area have generated inconsistent findings and focused primarily on adult and clinical samples, leaving youth and community samples underexplored. Burgeoning evidence has supported a biosocial basis of antisocial/CU tendencies – neurobiological deficits combine with psychosocial environmental risks to influence its development. Even fewer studies have investigated the joint effects of brain correlates and psychosocial environmental influence. This dissertation evaluated the neural and environmental bases of externalizing and CU tendencies. Adolescents from the community (n = 52, age range = 12-16) and their caregivers came for a 2 part in-person study. At Brooklyn College, caregivers completed assessments on their child’s externalizing behavior (Child Behavior Checklist; Achenbach & Edelbrock, 1991) and CU traits (Inventory of Callous Unemotional Traits; Frick, 2004). Information on social adversity and prenatal maternal stress were collected 4 years prior at enrollment. Adolescents were then invited to the City University of New York Advanced Science Research Center for functional and structural magnetic resonance imaging (MRI). During the fMRI scan, participants completed the modified version of the Monetary Incentive Delay Task to assess neural activity to rewards and punishments. The overall aims of this study are trifold: (1) to evaluate whether neural correlates in youth are implicated in the development of antisocial behavior and CU traits (Aims 1 and 2); (2) to determine if environmental factors are linked to externalizing/CU outcomes and aberrant neural correlates (Aim 3); and (3) to explore if environmental risks will moderate the relationship between neural correlates and antisocial/CU tendencies (Aim 4). In Aim1, we found that CU traits and externalizing behavior were negatively associated with neural activation in the ventral striatum (VST) in response to reward anticipation. A similar association was found between CU traits and amygdala responses during reward anticipation. In Aim 2, we found positive associations between externalizing behaviors and gray matter volume (GMV) in the caudate/putamen, and a negative association between callousness and GMV in the amygdala. In Aim 3, we found a marginally significant effect of prenatal maternal stress on unemotional traits (but not other subscales or externalizing outcomes). There were no significant associations between environmental and brain variables. In Aim 4, we found high social adversity and heightened neural response to reward anticipation in the amygdala predicted higher levels of uncaring and CU total scores. High social adversity also combined with lower response in the amygdala to punishment anticipation to predict higher levels of delinquency. Higher prenatal maternal stress in combination with lower response in the VST during both reward and punishment anticipation was associated with higher levels of CU traits. The overarching objective of this study is to achieve a more comprehensive understanding on the etiological basis of antisocial/CU tendencies by incorporating neurobiological and environmental processes, fostering early identification and prevention/intervention of disruptive behavioral disorders among those with CU traits

La estimación de redes de conectividad cerebral mediante señal fMRI para la caracterización del envejecimiento sano y patológico (deterioro cognitivo leve)

[spa] Los datos obtenidos a partir de señal fMRI son cada vez más utilizados en diferentes disciplinas, entre las cuales se encuentra la psicología. El hecho de tratarse de una herramienta no invasiva que proporciona información de las características del cerebro y su actividad hacen de estas imágenes un complemento muy valioso tanto en la práctica profesional como en la investigación de diferentes ámbitos. Sin embargo, su análisis resulta ciertamente más complejo de lo que podría parecer: utilizar esta herramienta requiere de equipos multidisciplinares que puedan hacer frente a todo lo que supone el análisis de este tipo de información. Los estudios con señal fMRI pueden realizarse en un amplio abanico de poblaciones diferentes, desde participantes sanos hasta participantes con diferentes patologías, tanto físicas como psicológicas. Una de estas poblaciones es la que engloba la tercera edad: participantes mayores que pueden sufrir algún tipo de deterioro de diferente gravedad, mientras que otros se encuentran cognitivamente preservados. Entre los participantes con deterioro cognitivo encontramos una categoría diagnóstica de interés creciente: el deterioro cognitivo leve. Las personas con este diagnóstico realizan sus actividades de la vida diaria casi con total independencia, aunque empiezan a presentar un deterioro relativamente reconocible. La mayoría sufren de deterioro en la memoria, aunque en algunos casos también se ven afectadas otras capacidades como el lenguaje. Se suele definir como un paso entre el envejecimiento normal y la demencia, aunque algunas de estas personas mantienen el diagnóstico durante años y no llegan a aumentar su deterioro. Así pues, la investigación en esta temática es cada vez más necesaria para entender tanto las características de esta patología como su diferenciación de la población sana del mismo rango de edad. La presente tesis doctoral tiene como objetivo estudiar la conectividad cerebral a través de fMRI en personas con deterioro cognitivo leve, así como personas con las capacidades cognitivas preservadas. Para ello será necesario identificar las técnicas de análisis más utilizadas para estos datos en la actualidad, estudiar la conectividad funcional en envejecimiento sano y también en envejecimiento con deterioro, procurando proporcionar herramientas que solventen las problemáticas estadísticas más habituales en este ámbito. Se han desarrollado tres estudios para alcanzar los objetivos propuestos. El Estudio 1 consta de una revisión bibliográfica de la literatura científica acerca del estudio del deterioro cognitivo leve a través de fMRI. El Estudio 2 se centra en la descripción de la conectividad funcional en envejecimiento sano para discernir sus principales características de patrones de conectividad, así como sus diferencias entre grupos de edades. Finalmente, el Estudio 3 compara los patrones de conectividad de 10 personas diagnosticadas de MCI con 10 participantes sanos apareados en sexo, edad y grado de escolaridad. En relación directa con los objetivos de la presente tesis, así como con los resultados obtenidos en los tres estudios llevados a cabo, se han podido extraer tres conclusiones principales. En primer lugar, quedó verificada la amplia variedad de aproximaciones estadísticas que se emplean actualmente para el estudio de la patología MCI a través de datos fMRI. Los objetivos de las investigaciones consultadas seguían líneas comunes o similares, aunque los resultados clínicos a los que se llegaba necesitan, en general, de más estudios para profundizar en la temática y poder generalizar los resultados obtenidos. Se ha constatado la necesidad de incluir los detalles relacionados con los análisis de conectividad funcional, puesto que en numerosos casos se ha echado de menos valiosa información para que puedan ser reproducidos o replicados. En segundo lugar, se ha verificado la existencia de cambios en los patrones de conectividad funcional en envejecimiento sano. El número e intensidad de conexiones entre regiones disminuía de forma progresiva a medida que aumentaba la edad de los participantes, teniendo en cuenta que se trabajaba con los participantes clasificados en grupos de edad, mostrando el declive más agudo en los participantes entre 75 y 79 años. Sin embargo, los participantes a partir de 80 años mostraron un pico más elevado en este sentido, probablemente relacionado con mecanismos de compensación o por teoría de supervivencia. Por último, el estudio de las diferencias en patrones de conectividad cerebral de los pacientes con MCI respecto a controles sanos permitió subrayar la existencia de dichas diversidades, aunque en muchos casos fueran relativamente sutiles. El aumento de la conectividad funcional que experimentan algunas regiones de los pacientes MCI quedó constatado, a la vez que la disminución de la conectividad en otras. La clasificación de las regiones cerebrales en clústeres permite ver diferencias en función del grupo, especialmente en relación a las regiones de la DMN anterior. Por todo lo expuesto, será importante profundizar en el estudio de los patrones de conectividad tanto en envejecimiento sano como patológico. Por un lado, es importante estudiar los grupos de edad entre 75 y 79 años de participantes sanos, así como a partir de 80 años, para entender los mecanismos que producen las diferencias tan abruptas entre ellos. Por otro lado, se deberán investigar la distribución de las regiones de la DMN anterior en pacientes MCI a partir del análisis de clústeres para confirmar su posible uso como biomarcador y facilitar así el diagnóstico de dicha patología.[eng] Nowadays, fMRI data is often used in many disciplines, among which we can find Psychology. Nevertheless, its statistical analysis could be more complex of what it could seem. The election of the statistical approach could be very different comparing different studies and are often related with the group resources. fMRI studies could be applied in a wide variety of populations, from healthy participants to people diagnosed by different pathologies, both physical and psychological. One of those populations is the elderly: old age participants that have more probabilities to develop any impairment of different gravity, while others are full cognitive preserved. Among the participants with cognitive impairment, we find a diagnostic category of increasing interest: mild cognitive impairment (MCI). People with this diagnostic can deal with daily activities with almost total independence, although they start to present some impairment that could be recognizable. Most of them suffer of memory impairment, even though they could have affectation in other abilities as language. It is usually defined as an intermediate step between normal aging and dementia, in spite of some of the people maintain this diagnostic during many years and never progress in more impairment. Therefore, research in this topic is everyday more necessary, keeping in mind the increasing of life expectancy, to understand the characteristics of this pathology as well as its differences with healthy population in the same age. The present doctoral thesis aims to study brain connectivity patterns with fMRI in people diagnosed of mild cognitive impairment just as well as healthy elderly individuals. To get this objective it will be necessary to identify the currently most popular analysis techniques for this type of data, as well as to study functional connectivity in healthy aging and impaired aging, trying to provide tools to resolve the most common statistical issues in this area. According to the objectives of our research, and directly to the results obtained, three main conclusions could be extracted. In the first place, it is confirmed that many statistical approaches are used to study MCI pathology with fMRI data. The objectives of the consulted publications were similar, although the clinical results needed, in general, more studies to obtain deep information in the topic and to generalize the results. The need to include all details related to functional connectivity analysis was verified, because in numerous articles there was a lack of information that permit reproduce or replicate the study. In the second place, the existence of changes in functional connectivity patterns in healthy aging was validated. The number and intensity of connections between regions shows a progressive diminution with age, showing the most noticeable decline in participants between 75 and 79 years old. However, participants with 80 or more show more connectivity, probably related with compensatory mechanisms. Lastly, the study of the differences in connectivity patterns between MCI patients and healthy controls permitted to emphasize the existence of differences, even though in some cases were subtle. Some brain regions showed an increase of connectivity, while others showed a decrease, in MCI patients in comparison to healthy controls. The classification provided by the cluster analysis allows to confirm the differences between groups, especially in the anterior DMN regions. With all of this, it is important to delve into the study of functional connectivity patterns as much in healthy and pathological aging. On one hand, it is important to study age groups from 75 to 79 years old and after 80, to understand the mechanisms that produce so many differences between them. On the other hand, the distribution of the anterior DMN regions in cluster analysis should be more investigated to confirm its possible use as a biomarker to facilitate the MCI diagnostic

The invisible body:the neural mechanisms of non-conscious and conscious processing of emotional bodies

How do we process emotions expressed by bodies when we don’t realize we are looking at them? This research made body postures invisible for participants by using the “continuous flash suppression” method. It turned out that processing bodily emotions is very different from processing faces, and is different across emotions (e.g. neutral, fearful, angry), both when participants consciously see them and when they see them outside their awareness. The research also looked in detail at the brain activity with the 7T MRI scanner, and found that understanding bodily actions involves a large network across the brain. This research provides insights in the way we understand actions and emotions