John D. Medaglia

Controllability of structural brain networks

Cognitive function is driven by dynamic interactions between large-scale neural circuits or networks, enabling behaviour. However, fundamental principles constraining these dynamic network processes have remained elusive. Here we use tools from control and network theories to offer a mechanistic explanation for how the brain moves between cognitive states drawn from the network organization of white matter microstructure. Our results suggest that densely connected areas, particularly in the default mode system, facilitate the movement of the brain to many easily reachable states. Weakly connected areas, particularly in cognitive control systems, facilitate the movement of the brain to difficult-to-reach states. Areas located on the boundary between network communities, particularly in attentional control systems, facilitate the integration or segregation of diverse cognitive systems. Our results suggest that structural network differences between cognitive circuits dictate their distinct roles in controlling trajectories of brain network function.

Review: cognitive network neuroscience

Network science provides theoretical, computational, and empirical tools that can be used to understand the structure and function of the human brain in novel ways using simple concepts and mathematical representations. Network neuroscience is a rapidly growing field that is providing considerable insight into human structural connectivity, functional connectivity while at rest, changes in functional networks over time (dynamics), and how these properties differ in clinical populations. In addition, a number of studies have begun to quantify network characteristics in a variety of cognitive processes and provide a context for understanding cognition from a network perspective. In this review, we outline the contributions of network science to cognitive neuroscience. We describe the methodology of network science as applied to the particular case of neuroimaging data and review its uses in investigating a range of cognitive functions including sensory processing, language, emotion, attention, cognitive control, learning, and memory. In conclusion, we discuss current frontiers and the specific challenges that must be overcome to integrate these complementary disciplines of network science and cognitive neuroscience. Increased communication between cognitive neuroscientists and network scientists could lead to significant discoveries under an emerging scientific intersection known as cognitive network neuroscience.

Emergence of system roles in normative neurodevelopment

Significance The human brain is a complex system displaying intricate, dynamic functions. In a multidisciplinary effort, the recent application of tools from network science to characterize the interconnected nature of the brain has enabled a tremendous advance in our understanding of cognition. Here, we develop and apply an extension of these tools to define and characterize the role of cognitive systems in the larger scale brain network, and to map how these roles change during adolescent development, providing an important context for understanding psychopathology. Our results are also consistent with the hypothesis that individual variation in network configuration implies differential vulnerability to cognitive abilities or deficits. Adult human cognition is supported by systems of brain regions, or modules, that are functionally coherent at rest and collectively activated by distinct task requirements. However, an understanding of how the formation of these modules supports evolving cognitive capabilities has not been delineated. Here, we quantify the formation of network modules in a sample of 780 youth (aged 8–22 y) who were studied as part of the Philadelphia Neurodevelopmental Cohort. We demonstrate that the brain’s functional network organization changes in youth through a process of modular evolution that is governed by the specific cognitive roles of each system, as defined by the balance of within- vs. between-module connectivity. Moreover, individual variability in these roles is correlated with cognitive performance. Collectively, these results suggest that dynamic maturation of network modules in youth may be a critical driver for the development of cognition.

Optimally controlling the human connectome: the role of network topology

To meet ongoing cognitive demands, the human brain must seamlessly transition from one brain state to another, in the process drawing on different cognitive systems. How does the brain’s network of anatomical connections help facilitate such transitions? Which features of this network contribute to making one transition easy and another transition difficult? Here, we address these questions using network control theory. We calculate the optimal input signals to drive the brain to and from states dominated by different cognitive systems. The input signals allow us to assess the contributions made by different brain regions. We show that such contributions, which we measure as energy, are correlated with regions’ weighted degrees. We also show that the network communicability, a measure of direct and indirect connectedness between brain regions, predicts the extent to which brain regions compensate when input to another region is suppressed. Finally, we identify optimal states in which the brain should start (and finish) in order to minimize transition energy. We show that the optimal target states display high activity in hub regions, implicating the brain’s rich club. Furthermore, when rich club organization is destroyed, the energy cost associated with state transitions increases significantly, demonstrating that it is the richness of brain regions that makes them ideal targets.

Medial prefrontal cortex hyperactivation during social exclusion in borderline personality disorder

Frontal systems dysfunction and abandonment fears represent central features of borderline personality disorder (BPD). BPD subjects (n=10) and matched non-psychiatric comparison subjects (n=10) completed a social-cognitive task with two confederates instructed to either include or exclude subjects from a circumscribed interaction. Evoked cerebral blood oxygenation in frontal cortex was measured using 16-channel functional near infrared spectroscopy. BPD subjects showed left medial prefrontal cortex hyperactivation during social exclusion suggesting potential dysfunction of frontolimbic circuitry.

The Nature of Processing Speed Deficits in Traumatic Brain Injury: is Less Brain More?

The cognitive constructs working memory (WM) and processing speed are fundamental components to general intellectual functioning in humans and highly susceptible to disruption following neurological insult. Much of the work to date examining speeded working memory deficits in clinical samples using functional imaging has demonstrated recruitment of network areas including prefrontal cortex (PFC) and anterior cingulate cortex (ACC). What remains unclear is the nature of this neural recruitment. The goal of this study was to isolate the neural networks distinct from those evident in healthy adults and to determine if reaction time (RT) reliably predicts observable between-group differences. The current data indicate that much of the neural recruitment in TBI during a speeded visual scanning task is positively correlated with RT. These data indicate that recruitment in PFC during tasks of rapid information processing are at least partially attributable to normal recruitment of PFC support resources during slowed task processing.

The Rich Get Richer: Brain Injury Elicits Hyperconnectivity in Core Subnetworks

There remains much unknown about how large-scale neural networks accommodate neurological disruption, such as moderate and severe traumatic brain injury (TBI). A primary goal in this study was to examine the alterations in network topology occurring during the first year of recovery following TBI. To do so we examined 21 individuals with moderate and severe TBI at 3 and 6 months after resolution of posttraumatic amnesia and 15 age- and education-matched healthy adults using functional MRI and graph theoretical analyses. There were two central hypotheses in this study: 1) physical disruption results in increased functional connectivity, or hyperconnectivity, and 2) hyperconnectivity occurs in regions typically observed to be the most highly connected cortical hubs, or the “rich club”. The current findings generally support the hyperconnectivity hypothesis showing that during the first year of recovery after TBI, neural networks show increased connectivity, and this change is disproportionately represented in brain regions belonging to the brains core subnetworks. The selective increases in connectivity observed here are consistent with the preferential attachment model underlying scale-free network development. This study is the largest of its kind and provides the unique opportunity to examine how neural systems adapt to significant neurological disruption during the first year after injury.

Abnormal prefrontal cortical response during affective processing in borderline personality disorder.

Emotion dysregulation is a hallmark feature of borderline personality disorder (BPD) and is associated with a dysfunction of prefrontal (PFC)-limbic systems. The purpose of the present study was to examine PFC function in BPD during the experience and suppression of sadness. Subjects were females with BPD (N=9) and age-, gender-, and IQ-matched non-psychiatric comparison subjects (N=8). Evoked hemodynamic oxygenated hemoglobin (oxy-Hb) was examined in PFC using functional near-infrared spectroscopy while subjects viewed neutral or sad images and were instructed to either maintain or suppress their emotional reactions. No group differences in behavioral ratings of sadness suppression or mean levels of evoked oxy-Hb were observed. BPD and control subjects, however, recruited homologous regions of lateral PFC during emotional suppression, with right lateral PFC activation for BPD subjects associated with difficulty suppressing sadness, whereas an inverse relationship was observed in left lateral PFC for healthy controls. Exploratory analyses revealed that the slope of the rise in oxy-Hb in medial PFC during transient sadness was positive and steep for healthy controls. Conversely, BPD subjects showed a negative and shallow slope, which was associated with severity of clinical symptoms. These results suggest that BPD subjects may show abnormal evoked oxy-Hb in medial PFC during transient sadness, with recruitment of right lateral PFC in BPD associated with reported difficulty in suppressing emotion. This abnormal cortical response, possibly in tandem with subcortical-limbic regions, may underlie symptoms of emotion dysregulation in BPD.

Neural Recruitment after Mild Traumatic Brain Injury Is Task Dependent: A Meta-analysis

Individuals with mild traumatic brain injury (TBI) often have deficits in processing speed and working memory (WM) and there is a growing literature using functional imaging studies to document these deficits. However, divergent results from these studies revealed both hypoactivation and hyperactivation of neural resources after injury. We hypothesized that at least part of this variance can be explained by distinct demands between WM tasks. Notably, in this literature some WM tasks use discrete periods of encoding, maintenance, and retrieval, whereas others place continuous demands on WM. The purpose of this meta-analysis is to examine the differences in neural recruitment after mTBI to determine if divergent findings can be explained as a function of task demand and cognitive load. A comprehensive literature review revealed 14 studies using functional magnetic resonance imaging to examine brain activity of individuals with mTBI during working memory tasks. Three of the fourteen studies included reported hypoactivity, five reported hyperactivity, and the remaining six reported both hypoactivity and hyperactivity. Studies were grouped according to task type and submitted to GingerALE maximum likelihood meta-analyses to determine the most consistent brain activation patterns. The primary findings from this meta-analysis suggest that the discrepancy in activation patterns is at least partially attributable to the classification of WM task, with hyperactivation being observed in continuous tasks and hypoactivation being observed during discrete tasks. We anticipate that differential task load expressed in continuous and discrete WM tasks contributes to these differences. Implications for the interpretation of fMRI signals in clinical samples are discussed.

The Less BOLD, the Wiser: Support for the latent resource hypothesis after traumatic brain injury

Previous studies of the BOLD response in the injured brain have revealed neural recruitment relative to controls during working memory tasks in several brain regions, most consistently the right prefrontal cortex and anterior cingulate cortices. We previously proposed that the recruitment observed in this literature represents auxiliary support resources, and that recruitment of PFC is not abnormal or injury specific and should reduce as novelty and challenge decrease. The current study directly tests this hypothesis in the context of practice of a working memory task. It was hypothesized that individuals with brain injury would demonstrate recruitment of previously indicated regions, behavioral improvement following task practice, and a reduction in the BOLD signal in recruited regions after practice. Individuals with traumatic brain injury and healthy controls performed the n‐back during fMRI acquisition, practiced each task out of the scanner, and returned to the scanner for additional fMRI n‐back acquisition. Statistical parametric maps demonstrated a number of regions of recruitment in the 1‐back in individuals with brain injury and a number of corresponding regions of reduced activation in individuals with brain injury following practice in both the 1‐back and 2‐back. Regions of interest demonstrated reduced activation following practice, including the anterior cingulate and right prefrontal cortices. Individuals with brain injury demonstrated modest behavioral improvements following practice. These findings suggest that neural recruitment in brain injury does not represent reorganization but a natural extension of latent mechanisms that engage transiently and are contingent upon cerebral challenge. Hum Brain Mapp, 2012.