A Whole-Brain and Cross-Diagnostic Perspective on Functional Brain Network Dysfunction.

A wide variety of mental disorders have been associated with resting-state functional network alterations, which are thought to contribute to the cognitive changes underlying mental illness. These observations appear to support theories postulating large-scale disruptions of brain systems in mental illness. However, existing approaches isolate differences in network organization without putting those differences in a broad, whole-brain perspective. Using a graph distance approach-connectome-wide similarity-we found that whole-brain resting-state functional network organization is highly similar across groups of individuals with and without a variety of mental diseases. This similarity was observed across autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Nonetheless, subtle differences in network graph distance were predictive of diagnosis, suggesting that while functional connectomes differ little across health and disease, those differences are informative. These results suggest a need to reevaluate neurocognitive theories of mental illness, with a role for subtle functional brain network changes in the production of an array of mental diseases. Such small network alterations suggest the possibility that small, well-targeted alterations to brain network organization may provide meaningful improvements for a variety of mental disorders.

Mapping the human brain's cortical-subcortical functional network organization.

Understanding complex systems such as the human brain requires characterization of the system's architecture across multiple levels of organization - from neurons, to local circuits, to brain regions, and ultimately large-scale brain networks. Here we focus on characterizing the human brain's large-scale network organization, as it provides an overall framework for the organization of all other levels. We developed a highly principled approach to identify cortical network communities at the level of functional systems, calibrating our community detection algorithm using extremely well-established sensory and motor systems as guides. Building on previous network partitions, we replicated and expanded upon well-known and recently-identified networks, including several higher-order cognitive networks such as a left-lateralized language network. We expanded these cortical networks to subcortex, revealing 358 highly-organized subcortical parcels that take part in forming whole-brain functional networks. Notably, the identified subcortical parcels are similar in number to a recent estimate of the number of cortical parcels (360). This whole-brain network atlas - released as an open resource for the neuroscience community - places all brain structures across both cortex and subcortex into a single large-scale functional framework, with the potential to facilitate a variety of studies investigating large-scale functional networks in health and disease.

No behavioral or ERP evidence for a developmental lag in visual working memory capacity or filtering in adolescents and adults with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) patients have both working memory (WM) and attention problems. Good attention skills are important for WM performance; individuals have higher WM capacity when being able to prevent storage of irrelevant information through efficient filtering. Since it is unknown how filtering ability is associated with WM performance in ADHD, this was investigated in the present study. A visuospatial working memory (VSWM) change detection task with distracting stimuli was administered to adolescents (12-16 years old) and adults (20-46 years old) with and without ADHD matched on education/IQ. Besides performance, contralateral delay activity (CDA) was measured; a neural correlate of the number of targets and distracters encoded and maintained in WM during the retention interval. Performance data showed similar WM-load, WM-distracter interference and developmental effects in ADHD and control groups. Adolescents' performance on the WM task deteriorated more than that of adults in the presence of distracters and with higher WM-load, irrespective of Diagnosis. The CDA data suggested that initially all groups encoded/maintained distracting information, but only adults were able to bounce this information from memory later in the retention interval, leading to better WM performance. The only effect of Diagnosis was a smaller CDA in adolescents and adults with ADHD than in age/IQ-matched controls when maintaining a low 1-item load, which was possibly related to an inability to keep attention focused at cued stimuli with low task demands. Overall, the development of filtering efficiency and VSWM storage capacity in adolescents with ADHD was not different from that in typically developing peers.

Electrophysiological evidence for immature processing capacity and filtering in visuospatial working memory in adolescents.

The present study investigated the development of visuospatial working memory (VSWM) capacity and the efficiency of filtering in VSWM in adolescence. To this end, a group of IQ-matched adults and adolescents performed a VSWM change detection task with manipulations of WM-load and distraction, while performance and electrophysiological contralateral delay activity (CDA) were measured. The CDA is a lateralized ERP marker of the number of targets and distracters that are selectively encoded/maintained in WM from one hemifield of the memory display. Significantly lower VSWM-capacity (Cowan's K) was found in adolescents than adults, and adolescents' WM performance (in terms of accuracy and speed) also suffered more from the presence of distracters. Distracter-related CDA responses were partly indicative of higher distracter encoding/maintenance in WM in adolescents and were positively correlated with performance measures of distracter interference. This correlation suggests that the higher interference of distracters on WM performance in adolescents was caused by an inability to block distracters from processing and maintenance in WM. The lower visuospatial WM-capacity (K) in adolescents in the high load (3 items) condition was accompanied by a trend (p<.10) towards higher CDA amplitudes in adolescents than adults, whereas CDA amplitudes in the low load (1 item) condition were comparable between adolescents and adults. These findings point to immaturity of frontal-parietal WM-attention networks that support visuospatial WM processing in adolescence.

Electrophysiological evidence for different effects of working memory load on interference control in adolescents than adults.

The present study investigated how the development of interference control is influenced by the development of working memory (WM) capacity during adolescence. In a dual-task, 17 adolescents (12-16 years) and 19 adults (18-48 years) performed a gender word-face Stroop task, while WM-capacity was manipulated by a concurrently performed N-back task. Behavior (reaction times, % errors and % misses) and event-related potentials associated with the detection (N450) of the Stroop conflict and response selection (sustained positivity; SP) were measured without or with a concurrent WM load. Adolescents had lower accuracy on N-back and Stroop trials than adults. N450 results showed Stroop conflict above temporal-occipital cortex which was suggested to be caused by processing of distracter faces. This N450 conflict response was smaller in adults and only present when holding a simultaneous WM-load, whereas adolescents' N450 conflict responses were already present without a concurrent WM-load and did not further increase with load. These N450 results indicate poorer distracter suppression in adolescence which is suggested to be due to insufficient attentional resources for top-down control. Irrespective of WM-load, adolescents also had larger parietal SP conflict responses than adults, suggesting inefficient response selection in case of activation of two conflicting responses. The main conclusion is that adolescents have worse distracter suppression than adults, caused by lower availability of resources for top-down control.

Complementary systems for understanding action intentions.

How humans understand the intention of others' actions remains controversial. Some authors have suggested that intentions are recognized by means of a motor simulation of the observed action with the mirror-neuron system [1-3]. Others emphasize that intention recognition is an inferential process, often called "mentalizing" or employing a "theory of mind," which activates areas well outside the motor system [4-6]. Here, we assessed the contribution of brain regions involved in motor simulation and mentalizing for understanding action intentions via functional brain imaging. Results show that the inferior frontal gyrus (part of the mirror-neuron system) processes the intentionality of an observed action on the basis of the visual properties of the action, irrespective of whether the subject paid attention to the intention or not. Conversely, brain areas that are part of a "mentalizing" network become active when subjects reflect about the intentionality of an observed action, but they are largely insensitive to the visual properties of the observed action. This supports the hypothesis that motor simulation and mentalizing have distinct but complementary functions for the recognition of others' intentions.

Relationship of delay aversion and response inhibition to extinction learning, aggression, and sexual behaviour.

Impulsivity is an important symptom of many psychiatric disorders, and can be divided into two subtypes: response inhibition deficits and delay aversion. In the present study, we investigated the relationship between delay aversion and response inhibition, both to each other and to locomotion, extinction of conditioned responses, sexual behaviour, and aggressive behaviour. To that end, we quantified the behaviour of 24 rats in several tests. To measure response inhibition, rats were trained in a stop-signal task. In this operant task, rats were rewarded food if they inhibited execution of a response after presentation of an audible stop-signal. Delay aversion was measured in an operant task in which rats made a choice between a small, immediately available reward and a large reward available after a delay. The results showed that delay aversion and response inhibition were independent. Responses during extinction and various measures of aggressive behaviour were positively correlated to delay aversion. The speed of go-trials in the stop-task was correlated to non-aggressive behaviour. We conclude that the role of response inhibition in various behaviours is small, but delay aversion in particular contributes to several other behaviours, such as aggressive behaviour and extinction.