Functional Connectivity Analysis of Visually Evoked ERPs for Mild Cognitive Impairment: Pilot Study.

Mild cognitive impairment (MCI) is considered the early stage of Alzheimer's disease, characterized as mild memory loss. A novel method of functional connectivity (FC) analysis can be used to detect MCI before memory is significantly impaired allowing for preventative measures to be taken. FC examines interactions between EEG channels to grant insight on underlying neural networks and analyze the effects of MCI. Applying FC method of weighted phase lag index (wPLI) to P300 ERPs provided insight on the link between the pathology of Alzheimer's disease and cognitive loss. wPLI was analyzed per frequency band (θ, α, µ, ß) and by channel combination groups (intra-hemispheric short, intra-hemispheric long, inter-hemispheric short, inter-hemispheric long, transverse). MCI was found to have a statistically significant lower ΔwPLIP300 compared to normal controls in the µ intra-hemispheric short (p = 0.0286), µ intra-hemispheric long (p = 0.0477), µ inter-hemispheric short (p = 0.0018) and the α intra-hemispheric short (p = 0.0423). Results indicate a possible deficiency in the dorsal visual processing pathway among MCI subjects as well as an unbalanced coordination between the two hemispheres.

Exploring the Effects of Offline Paradigms and Feature Extraction Techniques on Performance of Motor Imagery Brain-Computer Interface: Longitudinal Pilot Study.

Motor Imagery (MI) Brain-Computer Interface (BCI) is a popular way of allowing disabled and healthy individuals to use brain signals to communicate with their environment, despite the technical and human factor challenges that affect MI BCI classification performance. This study explored the influence of paradigm choice and phase synchronization-based features on classification performance by comparing primary datasets to older supplemental datasets. Area Under the Curve (AUC) Receiver Operating Characteristics (ROC) curve was the metric for classification performance. Results showed that using both advanced paradigms and features significantly improved both classification and usability; TD-CSP-wPLI (16-30Hz) and S-CSP-wPLI (12-15Hz) frequency bands produced the most noticeable change in performance.

Anterior-Posterior Balance Perturbation Protocol Using Lifelike Virtual Reality Environment.

Virtual reality (VR) paradigms have proved to be a valid method to challenge and perturb balance. There is little consensus in the literature on the best protocol design to perturb balance and induce postural sway. Current VR interventions still lack a well-defined standardized metric to generate a virtual environment that can perturb balance in an efficacious, lifelike, and repeatable manner. The objective of this study was to investigate different configurations of amplitude and frequency in an anterior-posterior translation VR environment, that is, lifelike and scaled. Thirteen young adults with no conditions affecting balance were recruited. Balance was challenged by anterior-posterior sinusoidal movement of the lab image within the VR headset. Four different amplitudes of the sinusoidal movement were tested: 1, 5, 10, and 20 cm, with each amplitude being presented at 2 test frequencies : 0.5 and 0.25 Hz. Mean center of pressure velocity was significantly greater than baseline at 0.5 Hz and amplitudes of 10 and 20 cm. Mean center of pressure at approximate entropy was greater than baseline at 0.5 Hz and amplitude of 20 cm. The results suggest that sinusoidal movement of a realistic VR environment produces altered balance compared with baseline quiet standing, but only under specific movement parameters.

The Cognitive Demands of Gait Retraining in Runners: An EEG Study.

High impact forces during running have been associated with tibial stress injuries. Previous research has demonstrated increasing step rate will decrease impact forces during running. However, no research has determined the cognitive demand of gait retraining. The primary purpose was to determine the cognitive demand and effectiveness of field-based gait retraining. We hypothesized that in-field gait retraining would alter running mechanics without increasing cognitive workload as measured by EEG following learning. Runners with a history of tibial injury completed a gait retraining protocol which included a baseline run, retraining phase, practice phase, and re-assessment following retraining protocol. Results demonstrated an increase in the theta, beta, and gamma power within prefrontal cortex during new learning and corresponding return to baseline following skill acquisition and changes across alpha, beta, gamma, mu, and theta in the motor cortex (p < .05). In the midline superior parietal cortex, spectral power was greater for theta activity during new learning with a corresponding alpha suppression. Overall, the results demonstrated the use of EEG as an effective tool to measure cognitive demand for implicit motor learning and the effectiveness of in-field gait retraining.

Facial Recognition Task for the Classification of Mild Cognitive Impairment with Ensemble Sparse Classifier.

Conventional methods for detecting mild cognitive impairment (MCI) require cognitive exams and follow-up neuroimaging, which can be time-consuming and expensive. A great need exists for objective and cost-effective biomarkers for the early detection of MCI. This study uses a sequential imaging oddball paradigm to determine if familiar, unfamiliar, or inverted faces are effective visual stimuli for the early detection of MCI. Unlike the traditional approach where the amplitude and latency of certain deflection points of event-related potentials (ERPs) are selected as electrophysiological biomarkers (or features) of MCI, we used the entire ERPs as potential biomarkers and relied on an advanced machine-learning technique, i.e. an ensemble of sparse classifier (ESC), to choose the set of features to best discriminate MCI from healthy controls. Five MCI subjects and eight age-matched controls were given the MoCA exam before EEG recordings in a sensory-deprived room. Traditional time-domain comparisons of averaged ERPs between the two groups did not yield any statistical significance. However, ESC was able to discriminate MCI from controls with 95% classification accuracy based on the averaged ERPs elicited by familiar faces. By adopting advanced machine-learning techniques such as ESC, it may be possible to accurately diagnose MCI based on the ERPs that are specifically elicited by familiar faces.

Exercise-heat stress with and without water replacement alters brain structures and impairs visuomotor performance.

Effects of exercise-heat stress with and without water replacement on brain structure and visuomotor performance were examined. Thirteen healthy adults (23.6 ± 4.2 years) completed counterbalanced 150 min trials of exercise-heat stress (45°C, 15% RH) with water replacement (EHS) or without (~3% body mass loss; EHS-DEH) compared to seated rest (CON). Anatomical scans and fMRI Blood-Oxygen-Level-Dependent responses during a visuomotor pacing task were evaluated. Accuracy decreased (P < 0.05) despite water replacement during EHS (-8.2 ± 6.8% vs. CON) but further degraded with EHS-DEH (-8.3 ± 6.4% vs. EHS and -16.5 ± 10.2% vs. CON). Relative to CON, EHS elicited opposing volumetric changes (P < 0.05) in brain ventricles (-5.3 ± 1.7%) and periventricular structures (cerebellum: 1.5 ± 0.8%) compared to EHS-DEH (ventricles: 6.8 ± 3.4, cerebellum: -0.7 ± 0.7; thalamus: -2.7 ± 1.3%). Changes in plasma osmolality (EHS: -3.0 ± 2.1; EHS-DEH: 9.3 ± 2.1 mOsm/kg) were related (P < 0.05) to thalamus (r = -0.45) and cerebellum volume (r = -0.61) which, in turn, were related (P < 0.05) to lateral (r = -0.41) and fourth ventricle volume (r = -0.67) changes, respectively; but, there were no associations (P > 0.50) between structural changes and visuomotor accuracy. EHS-DEH increased neural activation (P < 0.05) within motor and visual areas versus EHS and CON. Brain structural changes are related to bidirectional plasma osmolality perturbations resulting from exercise-heat stress (with and without water replacement), but do not explain visuomotor impairments. Negative impacts of exercise-heat stress on visuomotor tasks are further exacerbated by dehydration.

The relationships between physical capacity and biomechanical plasticity in old adults during level and incline walking.

Old compared to young adults exhibit increased hip and decreased ankle mechanical output during walking - a phenomenon known as biomechanical plasticity. Previous comparison studies suggest that low compared to high capacity old adults exhibit larger magnitudes of this plasticity, however the precise relationship between capacity and plasticity magnitude remains unclear. The purpose of this study was to quantify the relationships between physical capacity and biomechanical plasticity magnitude during level and incline walking. Data were collected for 32 old adults walking over level and inclined (+10°) surfaces at self-selected, comfortable speeds. Physical capacity was measured using the Short-Form Health Survey Physical Component (SF-36 PC) and biomechanical plasticity was quantified by ratios of hip extensor to ankle plantarfexor peak torques, angular impulses, peak positive powers, and positive work (larger ratios indicate larger magnitudes of plasticity). SF-36 PC scores correlated positively with all four biomechanical plasticity ratios during level walking and three of the four ratios during incline walking. Some of the biomechanical plasticity ratios correlated positively with comfortable walking speeds and stride frequencies, indicating better walking performance with larger magnitudes of plasticity. Additionally, all four biomechanical plasticity ratios were larger during incline compared to level walking, suggesting the need for larger magnitudes of plasticity during the more difficult task. These results indicate that larger magnitudes of biomechanical plasticity afford functional benefits such as increased level and incline walking performance for old adults. Increased walking performance has the potential to increase quality of life in the growing population of old adults.

Spectral and temporal electroencephalography measures reveal distinct neural networks for the acquisition, consolidation, and interlimb transfer of motor skills in healthy young adults.

OBJECTIVE: Plasticity of the central nervous system likely underlies motor learning. It is however unclear, whether plasticity in cortical motor networks is motor learning stage-, activity-, or connectivity-dependent. METHODS: From electroencephalography (EEG) data, we quantified effective connectivity by the phase slope index (PSI), neuronal activity by event-related desynchronization, and sensorimotor integration by N30 during the stages of visuomotor skill acquisition, consolidation, and interlimb transfer. RESULTS: Although N30 amplitudes and event-related desynchronization in parietal electrodes increased with skill acquisition, changes in PSI correlated most with motor performance in all stages of motor learning. Specifically, changes in PSI between the premotor, supplementary motor, and primary motor cortex (M1) electrodes correlated with skill acquisition, whereas changes in PSI between electrodes representing M1 and the parietal and primary sensory cortex (S1) correlated with skill consolidation. The magnitude of consolidated interlimb transfer correlated with PSI between bilateral M1s and between S1 and M1 in the non-practiced hemisphere. CONCLUSIONS: Spectral and temporal EEG measures but especially PSI correlated with improvements in complex motor behavior and revealed distinct neural networks in the acquisition, consolidation, and interlimb transfer of motor skills. SIGNIFICANCE: A complete understanding of the neuronal mechanisms underlying motor learning can contribute to optimizing rehabilitation protocols.

Remodeling of cortical activity for motor control following upper limb loss.

OBJECTIVE: Upper extremity loss presents immediate and lasting challenges for motor control. While sensory and motor representations of the amputated limb undergo plasticity to adjacent areas of the sensorimotor homunculus, it remains unclear whether laterality of motor-related activity is affected by neural reorganization following amputation. METHODS: Using electroencephalography, we evaluated neural activation patterns of formerly right hand dominant persons with upper limb loss (amputees) performing a motor task with their residual right limb, then their sound left limb. We compared activation patterns with left- and right-handed persons performing the same task. RESULTS: Amputees have involvement of contralateral motor areas when using their sound limb and atypically increased activation of posterior parietal regions when using the affected limb. When using the non-amputated left arm, patterns of activation remains similar to right handed persons using their left arm. CONCLUSIONS: A remodeling of activations from traditional contralateral motor areas into posterior parietal areas occurs for motor planning and execution when using the amputated limb. This may reflect an amputation-specific adaptation of heightened visuospatial feedback for motor control involving the amputated limb. SIGNIFICANCE: These results identify a neuroplastic mechanism for motor control in amputees, which may have great relevance to development of motor rehabilitation paradigms and prosthesis adaptation.

Reliability of Visual and Somatosensory Feedback in Skilled Movement: The Role of the Cerebellum.

The integration of vision and somatosensation is required to allow for accurate motor behavior. While both sensory systems contribute to an understanding of the state of the body through continuous updating and estimation, how the brain processes unreliable sensory information remains to be fully understood in the context of complex action. Using functional brain imaging, we sought to understand the role of the cerebellum in weighting visual and somatosensory feedback by selectively reducing the reliability of each sense individually during a tool use task. We broadly hypothesized upregulated activation of the sensorimotor and cerebellar areas during movement with reduced visual reliability, and upregulated activation of occipital brain areas during movement with reduced somatosensory reliability. As specifically compared to reduced somatosensory reliability, we expected greater activations of ipsilateral sensorimotor cerebellum for intact visual and somatosensory reliability. Further, we expected that ipsilateral posterior cognitive cerebellum would be affected with reduced visual reliability. We observed that reduced visual reliability results in a trend towards the relative consolidation of sensorimotor activation and an expansion of cerebellar activation. In contrast, reduced somatosensory reliability was characterized by the absence of cerebellar activations and a trend towards the increase of right frontal, left parietofrontal activation, and temporo-occipital areas. Our findings highlight the role of the cerebellum for specific aspects of skillful motor performance. This has relevance to understanding basic aspects of brain functions underlying sensorimotor integration, and provides a greater understanding of cerebellar function in tool use motor control.

Distinctive laterality of neural networks supporting action understanding in left- and right-handed individuals: An EEG coherence study.

Prior work has demonstrated that perspective and handedness of observed actions can affect action understanding differently in right and left-handed persons, suggesting potential differences in the neural networks underlying action understanding between right and left-handed individuals. We sought to evaluate potential differences in these neural networks using electroencephalography (EEG). Right- and left-handed participants observed images of tool-use actions from egocentric and allocentric perspectives, with right- and left-handed actors performing the actions. Participants judged the outcome of the observed actions, and response accuracy and latency were recorded. Behaviorally, the highest accuracy and shortest latency was found in the egocentric perspective for right- and left-handed observers. Handedness of subject showed an effect on accuracy and latency also, where right-handed observers were faster to respond than left-handed observers, but on average were less accurate. Mu band (8-10 Hz) cortico-cortical coherence analysis indicated that right-handed observers have coherence in the motor dominant left parietal-premotor networks when looking at an egocentric right or allocentric left hands. When looking in an egocentric perspective at a left hand or allocentric right hand, coherence was lateralized to right parietal-premotor areas. In left-handed observers, bilateral parietal-premotor coherence patterns were observed regardless of actor handedness. These findings suggest that the cortical networks involved in understanding action outcomes are dependent on hand dominance, and notably right handed participants seem to utilize motor systems based on the limb seen performing the action. The decreased accuracy for right-handed participants on allocentric images could be due to asymmetrical lateralization of encoding action and motoric dominance, which may interfere with translating allocentric limb action outcomes. Further neurophysiological studies will determine the specific processes of how left- and right-handed participants understand actions.

Ventral encoding of functional affordances: a neural pathway for identifying errors in action.

Functional tool usage is a critical aspect of our daily lives. Not only must we know which tools to use for a specific action goal, we must also know how to manipulate those tools in meaningful way to achieve the goal of the action. The purpose of this study was to identify the regions of the brain critical to supporting the process of understanding errors in tool manipulation. Using fMRI, neural activations were recorded while subjects were presented with images demonstrating typical action scenes (screwdriver used on a screw), but with the tool being manipulated either correctly (screwdriver held by handle) or incorrectly (screwdriver held by bit rather than handle). Activations in fMRI for identifying correct over incorrect tool manipulation were seen along the canonical parietofrontal action network, while activations for identifying incorrect over correct tool manipulation were primarily seen at superior temporal areas and insula. We expand our hypotheses about ventral brain networks identifying contextual error to further suggest mechanisms for understanding functional tool actions, which collectively we regard as functional affordances. This proposes a fundamental role for ventral brain areas in functional action understanding.

Context and hand posture modulate the neural dynamics of tool-object perception.

Prior research has linked visual perception of tools with plausible motor strategies. Thus, observing a tool activates the putative action-stream, including the left posterior parietal cortex. Observing a hand functionally grasping a tool involves the inferior frontal cortex. However, tool-use movements are performed in a contextual and grasp specific manner, rather than relative isolation. Our prior behavioral data has demonstrated that the context of tool-use (by pairing the tool with different objects) and varying hand grasp postures of the tool can interact to modulate subjects' reaction times while evaluating tool-object content. Specifically, perceptual judgment was delayed in the evaluation of functional tool-object pairings (Correct context) when the tool was non-functionally (Manipulative) grasped. Here, we hypothesized that this behavioral interference seen with the Manipulative posture would be due to increased and extended left parietofrontal activity possibly underlying motor simulations when resolving action conflict due to this particular grasp at time scales relevant to the behavioral data. Further, we hypothesized that this neural effect will be restricted to the Correct tool-object context wherein action affordances are at a maximum. 64-channel electroencephalography (EEG) was recorded from 16 right-handed subjects while viewing images depicting three classes of tool-object contexts: functionally Correct (e.g. coffee pot-coffee mug), functionally Incorrect (e.g. coffee pot-marker) and Spatial (coffee pot-milk). The Spatial context pairs a tool and object that would not functionally match, but may commonly appear in the same scene. These three contexts were modified by hand interaction: No Hand, Static Hand near the tool, Functional Hand posture and Manipulative Hand posture. The Manipulative posture is convenient for relocating a tool but does not afford a functional engagement of the tool on the target object. Subjects were instructed to visually assess whether the pictures displayed correct tool-object associations. EEG data was analyzed in time-voltage and time-frequency domains. Overall, Static Hand, Functional and Manipulative postures cause early activation (100-400ms post image onset) of parietofrontal areas, to varying intensity in each context, when compared to the No Hand control condition. However, when context is Correct, only the Manipulative Posture significantly induces extended neural responses, predominantly over right parietal and right frontal areas [400-600ms post image onset]. Significant power increase was observed in the theta band [4-8Hz] over the right frontal area, [0-500ms]. In addition, when context is Spatial, Manipulative posture alone significantly induces extended neural responses, over bilateral parietofrontal and left motor areas [400-600ms]. Significant power decrease occurred primarily in beta bands [12-16, 20-25Hz] over the aforementioned brain areas [400-600ms]. Here, we demonstrate that the neural processing of tool-object perception is sensitive to several factors. While both Functional and Manipulative postures in Correct context engage predominantly an early left parietofrontal circuit, the Manipulative posture alone extends the neural response and transitions to a late right parietofrontal network. This suggests engagement of a right neural system to evaluate action affordances when hand posture does not support action (Manipulative). Additionally, when tool-use context is ambiguous (Spatial context), there is increased bilateral parietofrontal activation and, extended neural response for the Manipulative posture. These results point to the existence of other networks evaluating tool-object associations when motoric affordances are not readily apparent and underlie corresponding delayed perceptual judgment in our prior behavioral data wherein Manipulative postures had exclusively interfered in judging tool-object content.

Testing perceptual limits of functional units: Are there "automatic" tendencies to associate tools and objects?

Prior work has demonstrated a unique network involving the insula, temporal cortex, and precuneus in evaluating appropriate relationships between tool-object pairings under instruction [20]. However, are there automatic tendencies to evaluate appropriate tool-object pairings? Using electroencephalography (EEG), we emulated our prior work to identify neural mechanisms that, in the absence of task-related consciousness, differentiate functionally matching from mismatching tool-object pairs. This was compared to any activation consistent with this using environmental image pairs. In addition, based on the paradigm we were able to discern any naïve processes that distinguish tools from non-tool environmental images. Results show that without task-related consciousness, the left occipitotemporal gyrus is preferentially active for tools compared to environmental images. Tool-object match and mismatch each versus control images show differences relative to a control image over the left temporal cortex, extending into the insula, yet there was no difference between tool-object match and mismatch. This suggests that there is no clear neural mechanism for continual evaluation of tool matching from mismatching, though there is for broad picture classifications. Taken together with our previous results, this creates a discussion for the role of intention when determining such relationships.

Neural activation for conceptual identification of correct versus incorrect tool-object pairs.

Appropriate tool-object pairing is a natural part of our lives. When preparing to clean our teeth, we know that a toothbrush is useful, but not a screwdriver. The neural correlates of this pairing process remain unclear. We recorded 64-channel electroencephalography to determine neural correlates of identification of tool-object matches and mismatches. Subjects were shown a target tool (e.g. spoon) later paired with an object that was either a conceptual match (e.g. bowl) or mismatch (e.g. wood). To verify that activity was not related to general concept of match-mismatch, in a second condition subjects saw non-tool environmental items (e.g. bird) later paired with a conceptual match (e.g. nest) or mismatch (e.g. spider web). Analysis was focused on time bins after each picture, using standardized low-resolution brain electromagnetic tomography (sLORETA). Tool-object match versus mismatch revealed significant differences in the posterior cingulate, precuneus, left insula and superior temporal gyrus. These patterns were not present for environmental match versus mismatch. This work suggests a specific network in comprehending tool-based pairings, but not extensive to other pairings. The posterior cingulate, precuneus, insula and superior temporal gyrus preferentially differentiates tool-object matching and mismatching, identifying a potential locus related to impairments in comprehending appropriate and inappropriate tool-object relationships that arise after neural injury.

Theta frequency band activity and attentional mechanisms in visual and proprioceptive demand.

In a companion manuscript we reported reduced electroencephalographic (EEG) activation at traditional sensorimotor areas in knee movements with high levels of task difficulty modulated by varying visual and proprioceptive sensory demands. Given that reduced cortical activity with more complex tasks is counter-intuitive, we suggested that high order cognitive-motor areas may show increased EEG activation to compensate for the observed decrease in sensorimotor regions. To test this hypothesis, we evaluated theta band activation at anterior frontal regions in a secondary analysis of our previous data. Unlike activation at sensorimotor areas, anterior frontal responses increased with each level of task difficulty as modulated by precision of visual targeting and/or proprioceptive demands from adding masses to the leg. Activity was increased as both unimodal visual and proprioceptive requirements became more demanding, but showed greater sensitivity to visual over proprioceptive processing requirements. Each level of bimodal task demands showed increasing activation, which was consistently greater when modulated through visual demands. These results are consistent with our hypothesis of increased contribution of anterior frontal regions for motor control in lower extremity movements with increasing sensory demands and further support different mechanisms for internally and externally guided movement.

Electroencephalographic reactivity to unimodal and bimodal visual and proprioceptive demands in sensorimotor integration.

We used electroencephalography to see how the brain deals with altered sensory processing demands in lower extremity movements. In unimodal conditions, sensory processing demands were altered with subjects performing movement to a small or large visual target, or with a small or large weight to modify proprioception. In bimodal conditions, both weight and targets needed to be met. We assessed activity over primary sensorimotor, premotor and parietal areas before and during knee movements. In unimodal conditions, the primary sensorimotor area showed the least sensitivity to the maximally increased sensory demand in both vision and proprioception, while the premotor region was most sensitive to proprioceptive demands, and the parietal region showed greatest sensitivity to visual demands. In bimodal conditions, intermediate levels of sensory processing demand maximally increased activation at premotor and parietal regions. However, when visual and proprioceptive demands were both maximal, activation decreased and was similar to that seen with the lowest level of sensory processing demand. As behavior was consistent across conditions while activation at these regions decreased, we suggest that additional brain areas, possibly high order cognitive and attentional regions, may be required to augment the function of the traditional sensorimotor network in lower extremity movements with increasingly difficult sensory processing demands.

The Neuroscience of Storing and Molding Tool Action Concepts: How "Plastic" is Grounded Cognition?

Choosing how to use tools to accomplish a task is a natural and seemingly trivial aspect of our lives, yet engages complex neural mechanisms. Recently, work in healthy populations has led to the idea that tool knowledge is grounded to allow for appropriate recall based on some level of personal history. This grounding has presumed neural loci for tool use, centered on parieto-temporo-frontal areas to fuse perception and action representations into one dynamic system. A challenge for this idea is related to one of its great benefits. For such a system to exist, it must be very plastic, to allow for the introduction of novel tools or concepts of tool use and modification of existing ones. Thus, learning new tool usage (familiar tools in new situations and new tools in familiar situations) must involve mapping into this grounded network while maintaining existing rules for tool usage. This plasticity may present a challenging breadth of encoding that needs to be optimally stored and accessed. The aim of this work is to explore the challenges of plasticity related to changing or incorporating representations of tool action within the theory of grounded cognition and propose a modular model of tool-object goal related accomplishment. While considering the neuroscience evidence for this approach, we will focus on the requisite plasticity for this system. Further, we will highlight challenges for flexibility and organization of already grounded tool actions and provide thoughts on future research to better evaluate mechanisms of encoding in the theory of grounded cognition.

Why is that Hammer in My Coffee? A Multimodal Imaging Investigation of Contextually Based Tool Understanding.

Appropriate tool-object pairing is a natural part of our lives. When preparing to stir coffee, we know that a hammer is useful for some tasks but that it is not appropriate in this behavioral context. The neural correlates of this context-tool pairing process remain unclear. In the current work, we used event-related electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to determine neural correlates for differentiating contextually correct and incorrect tool use. Subjects were shown images depicting correct (e.g., spoon used to stir coffee) or incorrect (e.g., hammer used to stir coffee) tool use. We identified distinct regional and temporal activations for identifying incorrect versus correct tool use. The posterior cingulate, insula, and superior temporal gyrus preferentially differentiated incorrect tool-object usage, while occipital, parietal, and frontal areas were active in identifying correct tool use. Source localized EEG analysis confirmed the fMRI data and showed phases of activation, where incorrect tool-use activation (0-200 ms) preceded occipitotemporal activation for correct tool use (300-400 ms). This work extends our previous findings to better identify the neural substrate for contextual evaluation of tool use, and may contribute to our understanding of neurological disorders resulting in tool-use deficits.