Donna L. Murdaugh

fMRI reactivity on a delay discounting task predicts weight gain in obese women

Obesity can be accompanied by abnormalities in executive function and related neural circuitry. A useful task for studying executive function is delay discounting (DD), in which an individual chooses between sooner and delayed, but greater, amounts of money or other commodities. We previously found that obese compared to normal-weight women made more immediate choices on a monetary DD task, or had greater delay discounting. In the present study, we performed functional magnetic resonance imaging (fMRI) of obese women during performance of a DD of money task. Confirming the results of previous studies, we found that more difficult compared to easy DD trials resulted in activation in putative executive function areas of the brain, the middle and inferior frontal gyri, and medial prefrontal cortex. Most interestingly, we also found that less activation in executive function areas such as the inferior, middle, and superior frontal gyri on difficult vs. easy DD trials predicted a greater rate of weight gain over the subsequent 1.3-2.9 years. These results suggest that suboptimal functioning of executive function areas such as prefrontal cortex contributes to the progression of obesity.

Differential Deactivation during Mentalizing and Classification of Autism Based on Default Mode Network Connectivity

The default mode network (DMN) is a collection of brain areas found to be consistently deactivated during task performance. Previous neuroimaging studies of resting state have revealed reduced task-related deactivation of this network in autism. We investigated the DMN in 13 high-functioning adults with autism spectrum disorders (ASD) and 14 typically developing control participants during three fMRI studies (two language tasks and a Theory-of-Mind (ToM) task). Each study had separate blocks of fixation/resting baseline. The data from the task blocks and fixation blocks were collated to examine deactivation and functional connectivity. Deficits in the deactivation of the DMN in individuals with ASD were specific only to the ToM task, with no group differences in deactivation during the language tasks or a combined language and self-other discrimination task. During rest blocks following the ToM task, the ASD group showed less deactivation than the control group in a number of DMN regions, including medial prefrontal cortex (MPFC), anterior cingulate cortex, and posterior cingulate gyrus/precuneus. In addition, we found weaker functional connectivity of the MPFC in individuals with ASD compared to controls. Furthermore, we were able to reliably classify participants into ASD or typically developing control groups based on both the whole-brain and seed-based connectivity patterns with accuracy up to 96.3%. These findings indicate that deactivation and connectivity of the DMN were altered in individuals with ASD. In addition, these findings suggest that the deficits in DMN connectivity could be a neural signature that can be used for classifying an individual as belonging to the ASD group.

Greater Impulsivity is Associated with Decreased Brain Activation in Obese Women during a Delay Discounting Task

Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD), or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual’s ‘indifference point’, or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain.

Changes in intrinsic connectivity of the brain's reading network following intervention in children with autism.

While task‐based neuroimaging studies have identified alterations in neural circuitry underlying language processing in children with autism spectrum disorders [ASD], resting state functional magnetic resonance imaging [rsfMRI] is a promising alternative to the constraints posed by task‐based fMRI. This study used rsfMRI, in a longitudinal design, to study the impact of a reading intervention on connectivity of the brain regions involved in reading comprehension in children with ASD. Functional connectivity was examined using group independent component analysis (GICA) and seed‐based correlation analysis of Brocas and Wernickes areas, in three groups of participants: an experimental group of ASD children (ASD‐EXP), a wait list control group of ASD children (ASD‐WLC), and a group of typically developing (TD) control children. Both GICA and seed‐based analyses revealed stronger functional connectivity of Brocas and Wernickes areas in the ASD‐EXP group postintervention. Additionally, improvement in reading comprehension in the ASD‐EXP group was correlated with greater connectivity in both Brocas and Wernickes area in the GICA identified reading network component. In addition, increased connectivity between the Brocas area and right postcentral and right STG, and the Wernickes area and LIFG, were also correlated with greater improvement in reading comprehension. Overall, this study revealed widespread changes in functional connectivity of the brains reading network as a result of intervention in children with ASD. These novel findings provide valuable insights into the neuroplasticity of brain areas underlying reading and the impact of intensive intervention in modifying them in children with ASD. Hum Brain Mapp 36:2965–2979, 2015.

The Impact of Reading Intervention on Brain Responses Underlying Language in Children With Autism.

Deficits in language comprehension have been widely reported in children with autism spectrum disorders (ASD), with behavioral and neuroimaging studies finding increased reliance on visuospatial processing to aid in language comprehension. However, no study to date, has taken advantage of this strength in visuospatial processing to improve language comprehension difficulties in ASD. This study used a translational neuroimaging approach to test the role of a visual imagery‐based reading intervention in improving the brain circuitry underlying language processing in children with ASD. Functional magnetic resonance imaging (MRI), in a longitudinal study design, was used to investigate intervention‐related change in sentence comprehension, brain activation, and functional connectivity in three groups of participants (age 8–13 years): an experimental group of ASD children (ASD‐EXP), a wait‐list control group of ASD children (ASD‐WLC), and a group of typically developing control children. After intervention, the ASD‐EXP group showed significant increase in activity in visual and language areas and right‐hemisphere language area homologues, putamen, and thalamus, suggestive of compensatory routes to increase proficiency in reading comprehension. Additionally, ASD children who had the most improvement in reading comprehension after intervention showed greater functional connectivity between left‐hemisphere language areas, the middle temporal gyrus and inferior frontal gyrus while reading high imagery sentences. Thus, the findings of this study, which support the principles of dual coding theory [Paivio 2007], suggest the potential of a strength‐based reading intervention in changing brain responses and facilitating better reading comprehension in ASD children. Autism Res 2015.

Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging

Newly emerging theories suggest that the brain does not function as a cohesive unit in autism, and this discordance is reflected in the behavioral symptoms displayed by individuals with autism. While structural neuroimaging findings have provided some insights into brain abnormalities in autism, the consistency of such findings is questionable. Functional neuroimaging, on the other hand, has been more fruitful in this regard because autism is a disorder of dynamic processing and allows examination of communication between cortical networks, which appears to be where the underlying problem occurs in autism. Functional connectivity is defined as the temporal correlation of spatially separate neurological events. Findings from a number of recent fMRI studies have supported the idea that there is weaker coordination between different parts of the brain that should be working together to accomplish complex social or language problems. One of the mysteries of autism is the coexistence of deficits in several domains along with relatively intact, sometimes enhanced, abilities. Such complex manifestation of autism calls for a global and comprehensive examination of the disorder at the neural level. A compelling recent account of the brain functioning in autism, the cortical underconnectivity theory, provides an integrating framework for the neurobiological bases of autism. The cortical underconnectivity theory of autism suggests that any language, social, or psychological function that is dependent on the integration of multiple brain regions is susceptible to disruption as the processing demand increases. In autism, the underfunctioning of integrative circuitry in the brain may cause widespread underconnectivity. In other words, people with autism may interpret information in a piecemeal fashion at the expense of the whole. Since cortical underconnectivity among brain regions, especially the frontal cortex and more posterior areas, has now been relatively well established, we can begin to further understand brain connectivity as a critical component of autism symptomatology. A logical next step in this direction is to examine the anatomical connections that may mediate the functional connections mentioned above. Diffusion Tensor Imaging (DTI) is a relatively novel neuroimaging technique that helps probe the diffusion of water in the brain to infer the integrity of white matter fibers. In this technique, water diffusion in the brain is examined in several directions using diffusion gradients. While functional connectivity provides information about the synchronization of brain activation across different brain areas during a task or during rest, DTI helps in understanding the underlying axonal organization which may facilitate the cross-talk among brain areas. This paper will describe these techniques as valuable tools in understanding the brain in autism and the challenges involved in this line of research.

Brain responses mediating idiom comprehension: Gender and hemispheric differences

Processing figurative language, such as idioms, is unique in that it requires one to make associations between words and non-literal meanings that are contextually appropriate. At the neural level, processing idiomatic phrases has been linked to recruitment of bilateral dorsolateral prefrontal cortices (DLPFC), the left temporal cortex, superior medial prefrontal gyrus (MPFC), and the left inferior frontal gyrus (LIFG). This functional MRI study examined the brain responses associated with processing idiomatic compared to literal sentences. In addition, gender differences in neural responses associated with language comprehension were also explored. In an fMRI scanner, thirty-six healthy adult volunteers viewed sentences that were either literal or idiomatic in nature, and answered subsequent comprehension questions. This sentence comprehension tasks activated mainly prefrontal language areas (LIFG, LSFG, and RMFG). Consistent with previous findings, idiomatic sentences showed increased response in LIFG. These results are discussed in the backdrop of the graded salience hypothesis. Furthermore, we found gender differences in brain activation and functional connectivity during this task. Women showed greater overall activation than men when comprehending literal and idiomatic sentences; whereas men had significantly greater functional connectivity between LIFG and LMTG than women across tasks. Overall, the findings of this study highlight the gender differences in neural responses associated with figurative language comprehension.

Brain Mechanisms Underlying Reading the Mind from Eyes, Voice, and Actions

Evidence from cognitive and social neuroscience research suggests that Theory of Mind (ToM), the ability to attribute mental states to others, is mediated by a group of brain regions collectively known as the ToM network. Nevertheless, there is significant variability in the functional activation of regions within this network across tasks. The goal of the present functional magnetic resonance imaging (fMRI) study was to examine the common and differential neural mechanisms of two aspects of ToM processing (emotion/mental-state recognition and intentional attribution) using three distinct, but complementary ToM tasks (Reading the Mind in the Eyes (RMIE), Reading the Mind in the Voice (RMIV), and Intentional Causal Attribution) in healthy adults. Participant accuracy was significantly worse in the ToM compared to the control condition across all tasks. Brain activation analyses replicated previously reported activation in inferior frontal gyrus (IFG) and middle temporal gyrus extending to posterior superior temporal sulcus (pSTS) in RMIE. Activation in the fusiform gyrus and bilateral middle temporal gyrus extending to temporo-parietal junction (TPJ) was unique to causality task. A region-of-interest analysis revealed shared activation in left IFG for RMIE and RMIV as well as TPJ recruitment specific to the causality task. The role of right TPJ in the causality task was further supported by a percent signal change analysis. A conjunction analysis revealed overlap in left IFG, left precentral gyrus, and left superior frontal gyrus activity across all tasks. These findings highlight common and differential recruitment of ToM regions according to task demand.

“Decoding versus comprehension”: Brain responses underlying reading comprehension in children with autism

HighlightsWe used fMRI to examine reading comprehension deficits in children with autism.Children completed a word similarities task in the MRI scanner.Hypoactivation and underconnectivity found in ASD in semantic processing regions.Altered reading network response may underlie comprehension deficits in ASD. Abstract Despite intact decoding ability, deficits in reading comprehension are relatively common in children with autism spectrum disorders (ASD). However, few neuroimaging studies have tested the neural bases of this specific profile of reading deficit in ASD. This fMRI study examined activation and synchronization of the brain’s reading network in children with ASD with specific reading comprehension deficits during a word similarities task. Thirteen typically developing children and 18 children with ASD performed the task in the MRI scanner. No statistically significant group differences in functional activation were observed; however, children with ASD showed decreased functional connectivity between the left inferior frontal gyrus (LIFG) and the left inferior occipital gyrus (LIOG). In addition, reading comprehension ability significantly positively predicted functional connectivity between the LIFG and left thalamus (LTHAL) among all subjects. The results of this study provide evidence for altered recruitment of reading‐related neural resources in ASD children and suggest specific weaknesses in top‐down modulation of semantic processing.

The efficacy of a pilot pediatric cognitive remediation summer program to prepare for transition of care

ABSTRACT This study assessed the efficacy of a time-sensitive cognitive remediation summer program (CRSP) that provided patients and their families with tools to help mitigate neurocognitive deficits and promote independence to foster precursor transition of medical care skills. A total of 38 participants (aged 9–15) were included in one of the CRSPs offered yearly from 2013 to 2016. A longitudinal design was employed and at each evaluation time point, one week before start of the CRSP (pre-testing) and within three weeks after the end of the program (post-testing)), participants were administered measures of executive functioning in addition to parent ratings of behavior, executive functioning, and adaptive skills (Year 1–Year 4). In Year 4, additional measures were collected, including parenting style and parent engagement and involvement in the program. Results from Year 1 to Year 4 (n = 35) demonstrated that participants in the CRSP showed significant improvement on neuropsychological testing in sustained and selective attention, planning, and cognitive flexibility. Robust changes in parent ratings of adaptive functioning from pre- to post-treatment were also found. Specific to Year 4 (n = 13), results revealed that participants showed improvement in levels of independence with at least one of the individualized goals focused on during the program. This study provided a systematic method to gauge the levels of instruction necessary to reach goals, a crucial tool in skill-teaching. Overall, our study provides evidence for the efficacy of the CRSP and validates a feasible intervention that can be integrated into standard of care for pediatric medical populations.