Frank G. Hillary

Resting network plasticity following brain injury.

The purpose of this study was to examine neural network properties at separate time-points during recovery from traumatic brain injury (TBI) using graph theory. Whole-brain analyses of the topological properties of the fMRI signal were conducted in 6 participants at 3 months and 6 months following severe TBI. Results revealed alterations of network properties including a change in the degree distribution, reduced overall strength in connectivity, and increased “small-worldness” from 3 months to 6 months post injury. The findings here indicate that, during recovery from injury, the strength but not the number of network connections diminishes, so that over the course of recovery, the network begins to approximate what is observed in healthy adults. These are the first data examining functional connectivity in a disrupted neural system during recovery.

Cerebral activation patterns during working memory performance in multiple sclerosis using FMRI.

Working memory deficits are common in Multiple Sclerosis (MS) and have been identified behaviorally in numerous studies. Despite recent advance in functional magnetic resonance imaging (fMRI), few published studies have examined cerebral activations associated with working memory dysfunction in MS. The present study examines brain activation patterns during performance of a working memory task in individuals with clinically definite MS, compared to healthy controls (HC). fMRI was performed using a 1.5 Tesla GE scanner during a modified Paced Auditory Serial Addition Test (mPASAT). Participants were 6 individuals with MS with working memory impairment as evidenced on neuropsychological testing, 5 individuals with MS without working memory impairment, and 5 HC. Groups were demographically equivalent. Data were analyzed using Statistical Parametric Mapping (SPM99) software, with a stringent significance level (alpha < .005, voxel extent ≥ 8). Both MS groups and the HC group were able to perform the task, with comparable performance in terms of numbers of correct responses. Activation patterns within the HC and MS not-impaired groups were noted in similar brain regions, consistent with published observations in healthy samples. That is, activations were lateralized to the left hemisphere, involving predominantly frontal regions. In contrast, the MS impaired group showed greater right frontal and right parietal lobe activation, when compared with the HC group. Thus, it appears that working memory dysfunction in MS is associated with altered patterns of cerebral activation that are related to the presence of cognitive impairment, and not solely a function of MS. This research was supported by the Henry H. Kessler Foundation, the Hyde and Watson Foundation and the Kirby Foundation. The authors wish to thank Rinki Jajoo for her help with data management, as well as Dr. Scott Millis and Dr. Dane Cook for their statistical advice. Dr. Christopher Christodoulou is now in the Department of Neurology, State University of New York at Stony Brook. Dr. Joseph Ricker is now in the Department of Physical Medicine and Rehabilitation, University of Pittsburgh.

Prefrontal modulation of working memory performance in brain injury and disease.

The inter‐related cognitive constructs of working memory (WM) and processing speed are fundamental components to general intellectual functioning in humans. Importantly, both WM and processing speed are highly susceptible to disruption in cases of brain injury, neurologic illness, and even in normal aging. A goal of this article is to summarize and critique the functional imaging studies of speeded working memory in neurologically impaired populations. This review focuses specifically on the role of the lateral prefrontal cortex in mediating WM performance and integrates the relevant WM literature in healthy adults with the current findings in the clinical literature. One important finding emerging from a summary of this literature is the dissociable contributions made by ventrolateral and dorsolateral prefrontal cortex (VLPFC and DLPFC) in guiding performance on tasks of WM. Throughout this review, it is shown that when cerebral resources are challenged, it is DLPFC, and often right DLPFC specifically, that plays a critical role in modulating WM functioning. In addition, this article will examine the relationship between task performance and brain activation across studies to clarify the role of increased DLPFC activity in clinical samples. Finally, explanations are offered for the observed increased DLPFC activation and the potentially unique role of right DLPFC in mediating WM performance during periods of cerebral challenge. Hum. Brain Mapp, 2006.

The neural correlates of cognitive fatigue in traumatic brain injury using functional MRI

Primary objective: The present study used fMRI (functional magnetic resonance imaging) to objectively assess cognitive fatigue in persons with traumatic brain injury (TBI). It was hypothesized that while performing a cognitive task, TBI participants would show increased brain activity over time, indicative of increased cerebral ‘effort’ which might manifest as the subjective feeling of cognitive fatigue. Methods and procedures: Functional MRI was used to track brain activity across time while 11 TBI patients with moderate–severe injury and 11 age-matched healthy controls (HCs) performed a modified Symbol Digit Modalities Task (mSDMT). Cognitive fatigue was operationally defined as a relative increase in cerebral activation across time compared to that seen in HCs. ROIs were derived from the Chauduri and Behan model of cognitive fatigue. Main outcomes and results: While performing the mSDMT, participants with a TBI showed increased activity, while HCs subsequently showed decreased activity in several regions including the middle frontal gyrus, superior parietal cortex, basal ganglia and anterior cingulate. Conclusions: Increased brain activity exhibited by participants with a TBI might represent increased cerebral effort which may be manifested as cognitive fatigue. Functional MRI appears to be a potentially useful tool for understanding the neural mechanisms associated with cognitive fatigue in TBI.

Automatic search for fMRI connectivity mapping: An alternative to Granger causality testing using formal equivalences among SEM path modeling, VAR, and unified SEM

Modeling the relationships among brain regions of interest (ROIs) carries unique potential to explicate how the brain orchestrates information processing. However, hurdles arise when using functional MRI data. Variation in ROI activity contains sequential dependencies and shared influences on synchronized activation. Consequently, both lagged and contemporaneous relationships must be considered for unbiased statistical parameter estimation. Identifying these relationships using a data-driven approach could guide theory-building regarding integrated processing. The present paper demonstrates how the unified SEM attends to both lagged and contemporaneous influences on ROI activity. Additionally, this paper offers an approach akin to Granger causality testing, Lagrange multiplier testing, for statistically identifying directional influence among ROIs and employs this approach using an automatic search procedure to arrive at the optimal model. Rationale for this equivalence is offered by explicating the formal relationships among path modeling, vector autoregression, and unified SEM. When applied to simulated data, biases in estimates which do not consider both lagged and contemporaneous paths become apparent. Finally, the use of unified SEM with the automatic search procedure is applied to an empirical data example.

An Investigation of Working Memory Rehearsal in Multiple Sclerosis Using fMRI

The present study examined patterns of cerebral activation during a working memory (WM) rehearsal task in individuals diagnosed with multiple sclerosis (MS) and in healthy adults. BOLD functional magnetic resonance imaging (fMRI)was performed using a 1.5TGE scanner to assess activation during aWMtask adapted fromthe Sternberg paradigm (Sternberg, 1969). Participants included 8 individuals diagnosed with MS, and 5 healthy controls (HCs) matched for age and education. Task difficulty was manipulated by increasing the length of time that strings of letters were to be rehearsed. Findings revealed increased right prefrontal cortex activation and increased right temporal lobe activation in individuals diagnosed with MS compared to HCs. The potential explanations for increased right hemisphere activation in persons with MS are discussed.

Examination of processing speed deficits in multiple sclerosis using functional magnetic resonance imaging.

Although it is known that processing speed deficits are one of the primary cognitive impairments in multiple sclerosis (MS), the underlying neural mechanisms responsible for impaired processing speed remain undetermined. Using BOLD functional magnetic resonance imaging, the current study compared the brain activity of 16 individuals with MS to 17 healthy controls (HCs) during performance of a processing speed task, a modified version of the Symbol Digit Modalities Task. Although there were no differences in performance accuracy, the MS group was significantly slower than HCs. Although both groups showed similar activation involving the precentral gyrus and occipital cortex, the MS showed significantly less cerebral activity than HCs in bilateral frontal and parietal regions, similar to what has been reported in aging samples during speeded tasks. In the HC group, processing speed was mediated by frontal and parietal regions, as well as the cerebellum and thalamus. In the MS group, processing speed was mediated by insula, thalamus and anterior cingulate. It therefore appears that neural networks involved in processing speed differ between MS and HCs, and our findings are similar to what has been reported in aging, where damage to both white and gray matter is linked to processing speed impairments.

Functionally activated brain imaging (O-15 PET and fMRI) in the study of learning and memory after traumatic brain injury.

Advances in functional imaging technology and cognitive neuropsychology have resulted in paradigms in which participants can perform cognitive tasks during functional image acquisition. We will discuss the application of two approaches (oxygen-15 positron emission tomography and functional magnetic resonance imaging) that have recently been used to examine components of learning and memory following traumatic brain injury (TBI). Activated functional brain imaging findings that we will discuss may suggest possible functional reallocation and reorganization of brain substrates involved in verbal learning and memory following brain injury. The findings also are clearly in line with other research that indicates a prominent role for the frontal lobes in learning and memory functioning, and support the concept of distributed neural networks for memory-related functions, cognitive load, and the potential for examining brain re-organization after injury.

Extended unified SEM approach for modeling event-related fMRI data

There has been increasing emphasis in fMRI research on the examination of how regions covary in a distributed neural network. Event-related data designs present a unique challenge to modeling how couplings among regions change in the presence of experimental manipulations. The present paper presents the extended unified SEM (euSEM), a novel approach for acquiring effective connectivity maps with event-related data. The euSEM adds to the unified SEM, which models both lagged and contemporaneous effects, by estimating the direct effects that experimental manipulations have on blood-oxygen-level dependent activity as well as the modulating effects the manipulations have on couplings among regions. Monte Carlos simulations included in this paper offer support for the models ability to recover covariance patterns used to estimate data. Next, we apply the model to empirical data to demonstrate feasibility. Finally, the results of the empirical data are compared to those found using dynamic causal modeling. The euSEM provides a flexible approach for modeling event-related data as it may be employed in an exploratory, partially exploratory, or entirely confirmatory manner.

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.