Thomas A. Daniel

Compromised hippocampus-striatum pathway as a potential imaging biomarker of mild-traumatic brain injury and posttraumatic stress disorder

Military service members risk acquiring posttraumatic stress disorder (PTSD) and mild‐traumatic brain injury (mTBI), with high comorbidity. Owing to overlapping symptomatology in chronic mTBI or postconcussion syndrome (PCS) and PTSD, it is difficult to assess the etiology of a patients condition without objective measures. Using resting‐state functional MRI in a novel framework, we tested the hypothesis that their neural signatures are characterized by functionally hyperconnected brain regions which are less variable over time. Additionally, we predicted that such connectivities possessed the highest ability in predicting the diagnostic membership of a novel subject (top‐predictors) in addition to being statistically significant.

Delayed match-to-sample in working memory: A BrainMap meta-analysis

Working memory (WM), or the ability to temporarily store and manipulate information, is one of the most widely studied constructs in cognitive psychology. Since its inception, it has become one of the leading explanations for how humans are able to operate on a cognitive level. The current study probed the neural networks underlying one of the most commonly used tasks, delayed match-to-sample (DMTS), to study WM. An activation likelihood estimation (ALE) analysis of 42 functional neuroimaging studies (626 participants) was conducted to demonstrate neural network engagement during DMTS. Results demonstrated strong convergence in brain regions commonly associated with the working memory construct (i.e., dorsolateral prefrontal cortex, fusiform gyrus, and posterior parietal cortex). However, neural activation in two regions frequently attributed to WM were absent from this meta-analysis: the anterior cingulate and the rostral prefrontal cortex, suggesting that these regions may be more sensitive to task or stimuli characteristics. In a post-hoc analysis, we deconstructed the DMTS meta-analysis to examine nonverbal versus verbal stimuli, and found notable neurofunctional differences such that DMTS using nonverbal stimuli consistently engaged the right middle frontal gyrus (BA 6/46) and precuneus (BA 7) more so than verbal stimuli based DMTS. These results provide a foundation for future models of functional connectivity that may elucidate subtle differences in working memory attributable to pathological processes.

Exploring the Neurocircuitry Underpinning Predictability of Threat in Soldiers with PTSD Compared to Deployment Exposed Controls.

Background: Prior work examining emotional dysregulation observed in posttraumatic stress disorder (PTSD) has primarily been limited to fear-learning processes specific to anticipation, habituation, and extinction of threat. In contrast, the response to threat itself has not been systematically evaluated. Objective: To explore potential disruption in fear conditioning neurocircuitry in service members with PTSD, specifically in response to predictable versus unpredictable threats. Method: In the current study, active-duty U.S. Army soldiers with (PTSD group; n = 38) and without PTSD (deployment-exposed controls; DEC; n = 40), participated in a fear-conditioning study in which threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or UCS alone (i.e., unpredictable). Threat expectation, skin conductance response (SCR), and functional magnetic resonance imaging (fMRI) signal to predictable and unpredictable threats (i.e., UCS) were assessed. Results: Both groups showed greater threat expectancy and diminished threat-elicited SCRs to predictable compared to unpredictable threat. Significant group differences were observed within the amygdala, hippocampus, insula, and superior and middle temporal gyri. Contrary to our predictions, the PTSD group showed a diminished threat-related response within each of these brain regions during predictable compared to unpredictable threat, whereas the DEC group showed increased activation. Conclusion: Although, the PTSD group showed greater threat-related diminution, hypersensitivity to unpredictable threat cannot be ruled out. Furthermore, pre-trauma, trait-like factors may have contributed to group differences in activation of the neurocircuitry underpinning fear conditioning.

Examining Microstructural White Matter in Active Duty Soldiers with a History of Mild Traumatic Brain Injury and Traumatic Stress

Background: There is a high comorbidity of posttraumatic stress (PTS) and mild traumatic brain injury (mTBI), with largely overlapping symptomatology, in military service members. Objective: To examine white matter integrity associated with PTS and mTBI as assessed using diffusion tensor imaging (DTI). Method: Seventy-four active-duty U.S. soldiers with PTS (n = 16) and PTS with co-morbid history of mTBI (PTS/mTBI; n = 28) were compared to a military control group (n = 30). Participants received a battery of neurocognitive and clinical symptom measures. The number of abnormal DTI values was determined (>2 SDs from the mean of the control group) for fractional anisotropy (FA) and mean diffusivity (MD), and then compared between groups. In addition, mean DTI values from white matter tracts falling into three categories were compared between groups: (i) projection tracts: superior, middle, and inferior cerebellar peduncles, pontine crossing tract, and corticospinal tract; (ii) association tracts: superior longitudinal fasciculus; and (iii) commissure tracts: cingulum bundle (cingulum-cingulate gyrus and cingulum-hippocampus), and corpus callosum. Results: The comorbid PTS/mTBI group had significantly greater traumatic stress, depression, anxiety, and post-concussive symptoms, and they performed worse on neurocognitive testing than those with PTS alone and controls. The groups differed greatly on several clinical variables, but contrary to what we hypothesized, they did not differ greatly on primary and exploratory analytic approaches of hetero-spatial whole brain DTI analyses. Conclusion: The findings suggest that psychological health conditions rather than pathoanatomical changes may be contributing to symptom presentation in this population.

A negative stimulus movement effect in pigeons

Rhesus monkeys and humans perform more accurately in matching-to-sample tasks when the sample stimulus moves through space (Washburn et al., 1989; Washburn, 1993). This Stimulus Movement Effect (SME) is believed to be due to movement increasing attention toward the sample stimulus, creating an easier discrimination between the sample and choice stimuli. To date, there is no evidence for this phenomenon in a non-mammalian species. In the current study, we investigate the possibility of an SME in an avian species. Across three experiments, pigeons were tested with moving and stationary sample stimuli in a non-matching- to-sample task. The area and velocity by which the sample stimulus traveled was manipulated but no advantage for moving over stationary sample trials was found within or across sessions. Even when a delay condition was implemented, there was no advantage for moving sample trials. Contrary to the results found in humans and monkeys, pigeons performed better when the sample was stationary, a negative SME, and no evidence was found that stimulus movement increases discrimination performance.

Temporal dynamics of task switching and abstract-concept learning in pigeons

The current study examined whether pigeons could learn to use abstract concepts as the basis for conditionally switching behavior as a function of time. Using a mid-session reversal task, experienced pigeons were trained to switch from matching-to-sample (MTS) to non-matching-to-sample (NMTS) conditional discriminations within a session. One group had prior training with MTS, while the other had prior training with NMTS. Over training, stimulus set size was progressively doubled from 3 to 6 to 12 stimuli to promote abstract concept development. Prior experience had an effect on the initial learning at each of the set sizes but by the end of training there were no group differences, as both groups showed similar within-session linear matching functions. After acquiring the 12-item set, abstract-concept learning was tested by placing novel stimuli at the beginning and end of a test session. Prior matching and non-matching experience affected transfer behavior. The matching experienced group transferred to novel stimuli in both the matching and non-matching portion of the sessions using a matching rule. The non-matching experienced group transferred to novel stimuli in both portions of the session using a non-matching rule. The representations used as the basis for mid-session reversal of the conditional discrimination behaviors and subsequent transfer behavior appears to have different temporal sources. The implications for the flexibility and organization of complex behaviors are considered.

Visual object complexity limits pigeon short-term memory.

The study of visual memory has repeatedly shown qualitatively similar visual short-term memory (VSTM) systems between human and many nonhuman species. In studies of human VSTM using change detection, increasing visual object complexity has an inverse effect on accuracy. In the current study, we assessed the functional relationship between visual object complexity and memory performance in visual change detection in pigeons and humans. Visual object complexity was quantified for each object type within each species using visual target search. Change detection performance was inversely related to object complexity in both species, suggesting that pigeon VSTM, like human VSTM, is limited by visual object complexity. Human participants were able to use a verbal-labeling strategy to mitigate some of the effect of visual object complexity, suggesting a qualitative difference in how the two species may solve certain visual discriminations. Considering the visual complexity of novel objects may also help explain previous failures to transfer relational rules to novel visual objects.

Primacy and Recency Effects for Taste.

Historically, much of what we know about human memory has been discovered in experiments using visual and verbal stimuli. In two experiments, participants demonstrated reliably high recognition for nonverbal liquids. In Experiment 1, participants showed high accuracy for recognizing tastes (bitter, salty, sour, sweet) over a 30-s delay in a recognition task, even when the probe stimulus was only a different concentration within the same taste. In Experiment 2, participants tasted three liquids and showed both primacy and recency effects in a serial-position recognition task with varying delay lengths (15, 30, 45, 60 s). Recognition for liquids at the end of a list was most evident with shorter delay lengths (i.e., recency). Recognition for liquids at the start of the list was most evident with longer delay lengths (i.e., primacy). These data show that not only is gustatory information stored and maintained in working memory, but that memory for these liquids follow a recency-to-primacy shift in recognition memory.

Demonstration and validation of a new pressure-based MRI-safe pain tolerance device

BACKGROUND One of the barriers to studying the behavioral and emotional effects of pain using functional Magnetic Resonance Imaging (fMRI) is the absence of a commercially available, MRI-compatible, pressure-based algometer to elicit pain. The present study sought to address this barrier through creation and validation of a novel MRI-safe apparatus capable of delivering incremental, measurable amounts of pressure inside a scanning bore. NEW METHOD We introduced an MR-safe device used to administer pressure-based pain. To test against a commercially available, MRI-incompatible algometer (AlgoMed), 199 participants reported their pain tolerance for both devices. A second experiment tested the validity of pressure-based pain in an MRI environment by comparing brain activation with established neural networks for pain. 10 participants performed an identical procedure to test for pain tolerance while being scanned in a 7T MRI scanner. RESULTS Results support the validity and reliability of our novel device. In Study 1, pain tolerance with this device was strongly correlated with pain tolerance as measured by a commercially available algometer (r=0.78). In Study 2, this device yielded BOLD activation within the insula (BA 13) and anterior cingulate gyrus (BA 24); as pressure increased, activation in these areas parametrically increased. COMPARISON WITH EXISTING METHOD These findings correspond to other studies using thermal, electrical, or mechanical pain applications. Behavioral and functional data demonstrate that this new device is a valid method of administering pressure-related pain in MRI environments. CONCLUSIONS Our novel MRI-safe device is a valid instrument to measure and administer pressure-based pain.

North American Football Fans show Neurofunctional Differences in Response to Violence: Implications for Public Health and Policy

While social and behavioral effects of violence in the media have been studied extensively, much less is known about how sports affect perceptions of violence. The current study examined neurofunctional differences between fans and non-fans of North American football (a contact sport) while viewing violent imagery. Participants viewed images of violence in both football and non-football settings while high-resolution functional magnetic resonance imaging (fMRI) data were acquired from their brains. Neurological activation was compared between these violence types and between groups. Fans of football show diminished activation in brain regions involved in pain perception and empathy such as the anterior cingulate cortex, fusiform gyrus, insula, and temporal pole when viewing violence in the context of football compared to more broadly violent images. Non-fans of football showed no such effect for the types of violent imagery and had higher activation levels than fans of football for the specified brain regions. These differences show that fans of football may perceive violence differently when it is in the context of football. These fan attitudes have potential policy implications for addressing the issue of concussions in North American football.