A fronto-parietal neural model for visuospatial processing during actionobservation and imitation: A simulated fMRI assessment

Presenter: Hyuk Oh                          Status: Graduate Student

Authors: Hyuk Oh, Allen R. Braun, James A. Reggia, Rodolphe J. Gentili


Abstract: Action observation and imitation are critical human sensorimotor capabilities that heavily rely on the mirror neuron system (MNS). Although much previous experimental and computational work has focused on the MNS, the processing of the viewpoint between a demonstrator and an imitator has received relatively little attention. Therefore, this work proposes a neurally plausible MNS model which examines the relationships between fronto-parietal components of the MNS and parietal visuospatial processing during action observation and imitation. The fronto-parietal network modeled here includes: i) the inferior frontal gyrus (IFG) that produces neural commands; ii) the inferior parietal lobule (IPL) that computes the sensorimotor predictions; iii) the parietal regions identified as the superior parietal lobule (SPL) and the intraparietal sulcus (IPS) that encode view-independent representations of the observed action and iv) the middle temporal region that provides the view-dependent representations of the observed action. Here the SPL/IPS, IFG, and IPL are modeled with artificial neural networks to mimic the neural mechanisms of action observation and imitation. In agreement with previous experimental work, the findings revealed that the IFG component of this neural model reproduced synthetic functional magnetic resonance imaging blood oxygenation level-dependent responses that: i) were similar for both action observation and execution and ii) represented neural activities of both view-independent and view-dependent neural populations. These results suggest that the visuospatial transformation processes in the SPL/IPS remaps the observed action into the egocentric frame of reference of the imitator, allowing him/her to imitate the action independently of the perspective from which it was previously observed.


An Objective Assessment of Cognitive Workload during Ambulation in Individuals with and without Unilateral Lower Limb Amputation

Presenter: Emma Shaw                                Status: Graduate Student

Authors: Emma Shaw, Jeremy Rietschel, Craig McDonald, Matthew Miller, Kyle Jaquess, Li-Chuan Lo, Bradford Hendershot, Alison Pruziner, Rodolphe Gentili, Bradley Hatfield


Abstract: Safe ambulation within a real-world environment often requires the concurrent performance of secondary tasks (e.g. attending to oncoming traffic while crossing a street). Due to limited attentional resources available for cognitive processes, the manner in which such resources are allocated during ambulation is of much interest. In particular, individuals with lower limb amputation may require additional attentional resources to ambulate with their prosthetic limb. Here, we present a novel and objective approach for the assessment of cognitive workload during ambulation. In the ongoing study, EEG was recorded from 10 individuals with and 12 individuals without unilateral lower limb amputation as they performed cognitive tasks of varying difficulty (easy and hard). All tasks were performed while seated and while walking on a treadmill in a Computer Assisted Rehabilitation Environment at Walter Reed National Military Medical Center. Attentional reserve was assessed by evaluating the P3a component of the event-related potential, an index of the involuntary orienting of attention, elicited by intermittently presented task-irrelevant novel complex auditory stimuli. To quantify the P3a component, a temporal-spatial principal components analysis was performed. Results from the study suggest ambulation imposes additional cognitive workload in all individuals. However, further analysis of the EEG data will be performed to directly compare healthy individuals to individuals with lower limb amputation during ambulation. We predict ambulation will impose additional cognitive workload in individuals with lower limb amputation compared to healthy individuals. The present study provides support for the utility of EEG as an objective real-time assessment of cognitive workload during ambulation within an ecologically valid environment. This work was supported by the DoD Defense Health Program (NF90UG) and the DoD-VA Extremity Trauma & Amputation Center of Excellence. Views expressed are those of the authors and do not reflect the official policy or position of the Departments of the Army, Navy, or Defense, or the U.S. Government.


Changes in Blood Oxygen Level-Dependent (BOLD) Response to Affective Picture Viewing After Acute Exercise

Presenter: Lauren Weiss                              Status: Graduate Student

Authors: Weiss, L.R., Spechler, P., Alfini, A.J., Smith, T.J., Verber, M. & Smith, J.C.


Abstract: A single session of exercise is known to decrease negative affect and increase positive affect, but little is known regarding the brain systems underlying exercise–induced changes in affective responsiveness. We aimed to determine differences in brain activation during emotional picture viewing after an acute bout of moderate intensity exercise compared to seated rest.  Nine healthy young adults (ages 20-30) completed two conditions on different days; a 30-minute session of a) seated rest or b) moderate intensity exercise on a cycle ergometer. Following rest and exercise, functional magnetic resonance imaging (fMRI) data were acquired while participants viewed a randomly ordered presentation of 30 arousing pleasant, 30 arousing unpleasant, and 30 neutral pictures from the International Affective Picture System.  Each picture was shown for 4 sec, with a 10-14 sec inter-picture interval. The order of exercise and rest was counterbalanced.  The fMRI data were analyzed using standard preprocessing methods in the Analysis of Functional NeuroImages (ANFI) software. Paired t-tests were performed on the BOLD signal to compare exercise and rest conditions for each picture category.  During pleasant picture viewing, exercise resulted in greater activation in two frontal and four parietal regions, and reduced activation in bilateral temporal lobe regions and posterior cingulate, compared to rest (p<.01). During unpleasant images, brain activation was lower after exercise versus rest in the left cingulate gyrus, right parahippocampal gyrus, and right superior occipital gyrus (p<.01). There were no regions that showed increased activation in response to unpleasant pictures after exercise compared to rest. During neutral pictures, less activation occurred after exercise in two right parietal regions, with greater activity in left middle temporal gyrus (p<.01).  A 30-minute session of moderate-intensity cycling resulted in changes in neural responses to affective stimuli. The reduced temporal lobe and increased frontal and parietal lobe activation during pleasant pictures, paired with the consistently decreased brain activation in response to unpleasant images following exercise, suggests a neural basis for changes in affective responsiveness and improved mood after exercise.



Presenter: Farzad Ehtemam                                    Status: Graduate Student

Authors: Farzad Ehtemam, Ryan M. Sapp, James M. Hagberg, and Ross H. Miller


Abstract: Humans can walk at a given speed using a range of mechanically feasible step rates.  When the choice of step rate is unconstrained, we tend to choose a moderate rate near the center of this range. The mechanisms behind this subconscious choice are unknown, but a popular hypothesis supported by data is that the preferentially chosen step rate minimizes the rate of metabolic energy expenditure.  An implicit assumption of this “minimum energy” hypothesis is that the nervous system monitors and regulates muscle energy metabolism. Repeated activation of muscles during movement requires energy consumption (e.g. the ATP used in powering the crossbridge cycle), which must be matched by energy production through substrate metabolism. Energy consumption as an optimality criterion in human gait has been widely studied, but the energy production side of this relationship has received minimal attention.  In this study, we examined energy production (substrate oxidation of fat and carbohydrates) when walking at a range of step rates. Due to the traditionally observed U-shaped relationship between step rate and energy rate in walking, we hypothesized the oxidation rate of the substrate producing the majority of energy to be U-shaped.   In summary, we saw that the U-shaped relationship between metabolic rate and step rate was explained by fat oxidation, which was also U-shaped, unlike carbohydrate oxidation. Protein oxidation was also U-shaped with respect to step rate, but this relationship was assumed, not measured. Thus, when subjects walked at non-preferred step rates, energy expenditure increased, and fat was used as the fuel to provide this additional energy.  This result provides an energy-production perspective on decision-making in the gait mechanics of humans. Evolutionary studies of movement in biological systems might also find this substrate minimization important in the context of ecological constraints that shaped the basic patterns of bipedal motion.


Individual cognitive-motor responses during practice of a reaching task executed under different levels of task difficulty

Presenter: Isabelle Shuggi                           Status: Graduate Student

Authors: Isabelle M. Shuggi, Hyuk Oh, Patricia A. Shewokis, Rodolphe J. Gentili


Abstract: Although a large body of work has focused on motor learning, a limited number of studies on the interaction between cognitive workload and motor learning have been conducted. In addition, while many studies examined the cognitive workload under various levels of task difficulty, how individuals respond differently to a given challenge was generally not considered. However, for a given task difficulty, individuals can have different cognitive-motor responses and thus perform differently throughout practice. The optimal challenge point framework can capture such relative task difficulty, where the nominal task difficulty is independent and the functional task difficulty is dependent of the performer’s capabilities. Here the cognitive-motor performance was examined in a task where participants had to acquire a new sensorimotor mapping to perform, through a head-controlled device, reaching movements at two levels of nominal difficulty. A low and a high level of nominal difficulty were implemented by having a slow and fast velocity at which the robotic arm moved in a 2D workspace, respectively. The cognitive workload was assessed with the NASA TLX survey and the human performance was examined by analyzing the kinematics of the robotic arm. The results revealed that participants in the fast velocity group had a higher cognitive workload than those in the slow velocity group. More importantly, a clustering analysis based on the cognitive workload scores for all the participants revealed the emergence of three groups having a low, medium and high mental workload. Overall, it was observed that: i) as the level of cognitive workload increased the kinematic performance declined; ii) the slow group tended to be more homogenous, having individuals with more similar levels of mental workload than the fast group and iii) independently of the level of mental workload, a similar rate of improvement across the three groups was observed during the practice duration considered here. Individual differences between participants in combination with the nominal and functional task difficulty may explain these results, which generally suggest that for the same challenge various cognitive-motor responses can be produced as well as the same response occurring for two different levels of task difficulty. This work contributes to understanding the dynamics between mental workload and motor learning processes as well as to inform assistive technologies for individuals with motor impairments.



Neural rhythm synchronizes with imagined acoustic rhythm

Presenter: Francisco Cervantes Constantino                                 Status: Graduate Student

Authors: Francisco Cervantes Constantino, Jonathan Z. Simon


Abstract: Perceptual flling-in is one mechanism to handle missing sensory information, possibly operating by interpolation from context cues.  While driven by sensory data, filled-in epochs are a direct outcome of endogenous neural processes.   We created conditions to observe steady neural oscillations driven by contextual but not real sensory input, thus entirely reflecting endogenous neural processes.    Brief noise masker probes were pseudo-randomly added to a long, rhythmic, acoustic pulse train. In half of the masker probes, the ongoing rhythmic pulse train was also omitted for the duration of the masker probe. Listeners were asked to report whether probes had been perceived-rhythmic or not.    Analysis of neural responses at the main rhythm rate shows that false positive trials showed higher evoked rhythmic power and higher trial-to-trial rhythmic phase coherence, than did correct rejection trials.     In modulation rates relevant to human speech communication, as in the rate tested here, we propose that the presence of neural dynamics synchronized to an actual rhythm (or sound modulation) directs the subjective experience of a sound as rhythmic (or modulated), even when such synchronized dynamics is not supported by sensory data - in analogy to some illusions or hallucinations.  This strategy underlies an internal model generated to extract meaning from complex sound mixtures, as in the problem of active listening to multiple speakers.  It also raises the question of contextual interpolation as a common-principled strategy found in other sensory modes.


Concurrent changes in motor performance, mental workload and self-efficacy throughout multi-sessions learning of arm reaching movements

Presenter: Helena Wu                                  Status: Undergraduate Student

Authors: Helena Wu, Isabelle M. Shuggi, Arianna Moreno, Hyuk Oh, Patricia A. Shewokis, Rodolphe J. Gentili


Abstract: Despite numerous studies that have examined motor learning, there are a relatively limited number that have particularly examined the simultaneous changes between motor performance, cognitive workload, and self-efficacy when considering multiple practice sessions. Therefore, changes in kinematic performance, mental workload, and self-efficacy were examined throughout several practice sessions. During these sessions, a new sensorimotor mapping had to be acquired in order to execute a reaching task with a virtual robotic arm via a head-controlled device. The human motor performance was evaluated by analyzing the kinematics of the wrist of the robotic effector, while cognitive workload and self-efficacy were assessed with the NASA TLX and self-efficacy surveys, respectively. The results from the multiple practice sessions revealed that as participants improved their kinematic performance, their cognitive workload progressively reduced while self-efficacy increased. These findings suggest that as human performance improved and became more automatic, the attentional resources needed were reduced and participants had an increase in confidence to perform the reaching task well. This work is the first step towards understanding motor learning processes in relationship to cognitive workload and self-efficacy as well as inform assistive systems for individuals with severe sensorimotor impairments.


Cross-Sectional Analyses Elucidate the Role of Cardiovascular Risk Factors in Multiple Sclerosis

Presenter: Tim Barry                                    Status: Undergraduate Student

Authors: Tim Barry, Peter Kosa, Tianxia Wu, Bibi Bielekova


Abstract: Multiple sclerosis (MS) is the most common immune-mediated disease of the central nervous system. Given the central nervous system's reliance on the cardiovascular system, we predicted that progression of clinical disability in MS patients would correlate with cardiovascular disease. To test our hypothesis, we collected data on four cardiovascular risk factors -- total serum cholesterol, mean arterial pressure, pulse pressure, and BMI -- from a cohort of 417 people, some of whom had relapsing-remitting MS (RR-MS), some of whom had progressive MS, and the rest of whom were healthy volunteers. We assessed the clinical disability of the subjects using the Expanded Disability Status Scale and the Scripps Neurological Rating Scale. We discovered that progressive MS females had significantly elevated cholesterol levels with respect to RR-MS and healthy females. No such cholesterol difference emerged among the male subjects. Among other cardiovascular risk factors, we observed small effects of BMI and pulse pressure on disability in MS patients. Our study highlights the fact that, at least in some patients, the accumulation of disability is not driven solely by inflammation, but also likely by cardiovascular pathology.


Longer habituation periods enhance olfactory discrimination

Presenter: Taj Keshav                                  Status: Undergraduate Student

Authors: Taj Keshav, Ricardo C. Araneda


Abstract:         Habituation is an important phenomenon across all sensory modalities that allows animals to tune out a stimulus that is not longer relevant;  in the habituated state, the animal is more attentive to novel stimuli.  The detection of a novel sensory stimulus, such as a new odor or sound from a habituated state is known as dishabituation.  Therefore, habituation and dishabituation are crucial for the appropriate interpretation and response to external cues. In olfaction, behavioral habituation-dishabituation (H-D) is the most common approach to determine discrimination to odor pairs by animals. In this behavioral paradigm, a mouse is exposed in sequential trials to the same odor (or odor mixture), which produces habituation to that odor. Upon presentation of a novel odor, dishabituation is observed as an increased interest by the mouse for the stimulus, indicating that it is recognized as different.   . Despite the simplicity of this paradigm, the mechanisms underlying H-D and the role that habituation may have in altering an animal’s perception of novelty are not well-understood. Using a the classical H-D paradigm we found that C57 BL/6 mice are unable to discriminate between two structurally similar odors, the L- and D- carvone isomers and +/- limonene isomers, after a short period of habituation. However, after an extended period of exposure to the first odor, or extended habituation, the mice significantly discriminate one enantiomer from the other, as shown by an increased investigation of the second odor during dishabituation. This data suggests that the olfactory habituation consist of multiple processes, with different time courses, which alter innate odor precepts.  Thus, depending of the state of habituation of an animal, a novel odor may appear as similar leading to conclude that the odor pair is not discriminated. 


Microglial colonization and interactions with synapses in the developing reward circuitry

Presenter: Isobel Hawes                              Status: Undergraduate Student

Authors: Isobel Hawes, Lindsay DeBiase, Zachary Fusfeld, Antonello Bonci


Abstract: Microglia are abundant within brain regions that process information about reward and subtle perturbations in maturation of the reward circuitry may be linked to susceptibility to developing substance dependence. However, the properties of microglia within the developing reward circuitry are poorly defined and it is not known whether these cells participate in synaptic pruning and circuit maturation. We used transgenic mice that express EGFP within microglia to quantify the density, morphology, and phagocytic capacity, of these cells in three key regions of the reward circuitry: the ventral tegmental area (VTA), the nucleus accumbens (NAc), and the medial prefrontal cortex (mPFC). Microglial density peaked during early postnatal periods in all three regions and then declined sharply to adult levels. However, in the NAc, microglial density peaked at postnatal day (P) 10-12, while in the VTA and mPFC microglial density peaked at P14-16, suggesting that achievement of adult microglial distribution in different brain regions follows a distinct time course. In the visual system, phagocytosis of synapses is most pronounced in microglial cells with a sparsely-branched, amoeboid morphology. Morphology of microglial cells within the reward circuitry became significantly more complex as development progressed, with prominent branching evident in all investigated brain regions by P12. This rapid anatomical maturation suggests that microglial participation in synaptic pruning within the reward circuitry may parallel that observed in the visual system and peak within the first postnatal week of life. However, preliminary analysis of microglial phagocytotic capacity through immunostaining for CD68, a lysosomal marker, indicates that microglial CD68 content is equal across time points in all assessed brain regions. Together these observations raise the possibility that maturation of microglial morphology and tissue distribution may be regulated independently from phagocytotic activity. Future studies will define the full time course of microglial-mediated synaptic pruning within distinct regions of the reward circuitry and determine whether disruption of these processes affects responses to exposure to drugs of abuse.


Molecular Characterization of Nociceptive Neurons in the Amygdala and their Anatomical Projections

Presenter: Garshasb Soroosh                                  Status: Undergraduate Student

Authors: Garshasb Soroosh, Torri Wilson, Simon Arango, Yarimar Carrasquillo


Abstract: The central nucleus of the amygdala (CeA) is a limbic brain region that responds to peripheral nociceptive stimuli, suggesting that the amygdala is an important site for the modulation of pain. Consistent with this, studies have shown that extracellular signal-regulated kinase (ERK) is activated and modulates peripheral hypersensitivity in neurons in the CeA in mouse models of inflammatory pain. Previous studies have shown, however, that neurons in the CeA are functionally and molecularly heterogeneous, though the functional roles of these molecularly distinct neurons that are important to pain modulation are unknown. The current study uses a mouse model of peripheral inflammatory pain to molecularly characterize nociceptive neurons (neurons that respond to noxious stimuli) in the CeA. Fluorescent immunostaining was performed on brains from mice exposed to short-term (3h) or long-term (10-11w) peripheral inflammation, and control. Neurons in the CeA were targeted for characterization and quantified based on their expression of PKC-δ, somatostatin, CRF, and pERK, a molecular marker of synaptic plasticity. ERK was found to be activated in CeA neurons expressing PKC-δ 3h after peripheral inflammation, while less than 1% of PKC-δ positive CeA cells express FosB, another marker or synaptic plasticity, 3h after peripheral inflammation. ERK was also found to be activated in the CeA following prolonged peripheral inflammation and is expressed in PKC-δ positive cells, along with somatostatin and CRF being expressed in a subset of CeA neurons at this time point. Further research will use florescent tracers to identify where molecularly-identified nociceptive neurons in the CeA project, specifically looking at two major projection sites for neurons in the CeA: the dorsal substantia innominata (SId) and the bed nucleus of the stria terminalis (BNST).