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Prism Adaptation (PA) is used to alleviate spatial neglect. We combined immersive virtual reality with a depth-sensing camera to develop virtual prism adaptation therapy (VPAT), which block external visual cues and easily quantify and monitor errors than conventional PA. We conducted a feasibility study to investigate whether VPAT can induce behavioral adaptations by measuring after-effect and identifying which cortical areas were most significantly activated during VPAT using functional near-infrared spectroscopy (fNIRS). Fourteen healthy subjects participated in this study. The experiment consisted of four sequential phases (pre-VPAT, VPAT-10°, VPAT-20°, and post-VPAT). To compare the most significantly activated cortical areas during pointing in different phases against pointing during the pre-VPAT phase, we analyzed changes in oxyhemoglobin concentration using fNIRS during pointing. The pointing errors of the virtual hand deviated to the right-side during early pointing blocks in the VPAT-10° and VPAT-20° phases. There was a left-side deviation of the real hand to the target in the post-VPAT phase, demonstrating after-effect. The most significantly activated channels during pointing tasks were located in the right hemisphere, and possible corresponding cortical areas included the dorsolateral prefrontal cortex and frontal eye field. In conclusion, VPAT may induce behavioral adaptation with modulation of the dorsal attentional network., (© 2022. The Author(s).)

Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We resampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers compared to right-handers showed average differences of surface area asymmetry within the fusiform cortex, the anterior insula, the anterior middle cingulate cortex, and the precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB , TUBA1B , TUBB3 , TUBB4A , MAP2 , and NME7 -mutations in the latter can cause left to right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and the inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas nonheritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

For animals to survive, they must interact with their environment, taking in sensory information and making appropriate motor responses. Early on during vertebrate evolution, this was accomplished with neural circuits located mostly within the spinal cord and brainstem. As the cerebral cortex evolved, it provided additional and powerful advantages for assessing environmental cues and guiding appropriate responses. Importantly, the cerebral cortex was added onto an already functional nervous system. Moreover, every cortical area, including areas traditionally considered sensory, provides input to the subcortical motor structures that are bottlenecks for driving action. These facts have important ramifications for cognitive aspects of motor control. Here we consider the evolution of cortical mechanisms for attention from the perspective of having to work through these subcortical bottlenecks. From this perspective, many features of attention can be explained, including the preferential engagement of some cortical areas at the cost of disengagement from others to improve appropriate behavioral responses., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Growing experimental evidence points at relationships between the phase of a cortical or bodily oscillation and behavior, using various circular statistical tests. Here, we systematically compare the performance (sensitivity, False Positive rate) of four circular statistical tests (some commonly used, i.e. Phase Opposition Sum, Circular Logistic Regression, others less common, i.e., Watson test, Modulation Index). We created semi-artificial datasets mimicking real two-alternative forced choice experiments with 30 participants, where we imposed a link between a simulated binary behavioral outcome with the phase of a physiological oscillation. We systematically varied the strength of phase-outcome coupling, the coupling mode (1:1 to 4:1), the overall number of trials and the relative number of trials in the two outcome conditions. We evaluated different strategies to estimate phase-outcome coupling chance level, as well as significance at the individual or group level. The results show that the Watson test, although seldom used in the experimental literature, is an excellent first intention test, with a good sensitivity and low False Positive rate, some sensitivity to 2:1 coupling mode and low computational load. Modulation Index, initially designed for continuous variables but that we find useful to estimate coupling between phase and a binary outcome, should be preferred if coupling mode is higher than 2:1. Phase Opposition Sum, coupled with a resampling procedure, is the only test retaining a good sensitivity in the case of a large unbalance in the number of occurrences of the two behavioral outcomes., Competing Interests: Declaration of Competing Interest The authors declare that no competing interests exist., (Copyright © 2021. Published by Elsevier Inc.)

Network neuroscience has relied on a node-centric network model in which cells, populations and regions are linked to one another via anatomical or functional connections. This model cannot account for interactions of edges with one another. In this study, we developed an edge-centric network model that generates constructs 'edge time series' and 'edge functional connectivity' (eFC). Using network analysis, we show that, at rest, eFC is consistent across datasets and reproducible within the same individual over multiple scan sessions. We demonstrate that clustering eFC yields communities of edges that naturally divide the brain into overlapping clusters, with regions in sensorimotor and attentional networks exhibiting the greatest levels of overlap. We show that eFC is systematically modulated by variation in sensory input. In future work, the edge-centric approach could be useful for identifying novel biomarkers of disease, characterizing individual variation and mapping the architecture of highly resolved neural circuits.

We investigated the global structure of intrinsic cross-frequency dynamics by systematically examining power-based temporal associations among a broad range of oscillation frequencies both within and across EEG-based current sources (sites). We focused on power-based associations that could reveal unique timescale dependence independently of interacting frequencies. Large spectral-power fluctuations across all sites occurred at two characteristic timescales, sub-second and seconds, yielding distinct patterns of cross-frequency associations. On the fast sub-second timescale, within-site (local) associations were consistently between pairs of β-γ frequencies differing by a constant Δf (particularly Δf ~ 10 Hz at posterior sites and Δf ~ 16 Hz at lateral sites) suggesting that higher-frequency oscillations are organized into Δf amplitude-modulated packets, whereas cross-site (long-distance) associations were all within-frequency (particularly in the >30 Hz and 6-12 Hz ranges, suggestive of feedforward and feedback interactions). On the slower seconds timescale, within-site (local) associations were characterized by a broad range of frequencies selectively associated with ~10 Hz at posterior sites and associations among higher (>20 Hz) frequencies at lateral sites, whereas cross-site (long-distance) associations were characterized by a broad range of frequencies at posterior sites selectively associated with ~10 Hz at other sites, associations among higher (>20 Hz) frequencies among lateral and anterior sites, and prevalent associations at ~10 Hz. Regardless of timescale, within-site (local) cross-frequency associations were weak at anterior sites indicative of frequency-specific operations. Overall, these results suggest that the fast sub-second-timescale coordination of spectral power is limited to local amplitude modulation and insulated within-frequency long-distance interactions (likely feedforward and feedback interactions), while characteristic patterns of cross-frequency interactions emerge on the slower seconds timescale. The results also suggest that the occipital α oscillations play a role in organizing higher-frequency oscillations into ~10 Hz amplitude-modulated packets to communicate with other regions. Functional implications of these timescale-dependent cross-frequency associations await future investigations., Competing Interests: The authors have declared that no competing interests exist.

Objective: Current brain-computer interface (BCI) studies demonstrate the potential to decode neural signals obtained from structured and trial-based tasks to drive actuators with high performance within the context of these tasks. Ideally, to maximize utility, such systems will be applied to a wide range of behavioral settings or contexts. Thus, we explore the potential to augment such systems with the ability to decode abstract behavioral contextual states from neural activity., Approach: To demonstrate the feasibility of such context decoding, we used electrocorticography (ECoG) and stereo-electroencephalography (sEEG) data recorded from the cortical surface and deeper brain structures, respectively, continuously across multiple days from three subjects. During this time, the subjects were engaged in a range of naturalistic behaviors in a hospital environment. Behavioral contexts were labeled manually from video and audio recordings; four states were considered: engaging in dialogue, rest, using electronics, and watching television. We decode these behaviors using a factor analysis and support vector machine (SVM) approach., Main Results: We demonstrate that these general behaviors can be decoded with high accuracies of 73% for a four-class classifier for one subject and 71% and 62% for a three-class classifier for two subjects., Significance: To our knowledge, this is the first demonstration of the potential to disambiguate abstract naturalistic behavioral contexts from neural activity recorded throughout the day from implanted electrodes. This work motivates further study of context decoding for BCI applications using continuously recorded naturalistic activity in the clinical setting.

The retrosplenial cortex (RSC) has recently begun to gain widespread interest because of its anatomical connectivity with other well-known memory structures, such as the hippocampus and anterior thalamus, and its role in spatial, contextual, and episodic memory. Although much of the current work on the RSC is focused on spatial cognition, there is also an extensive literature that shows that the RSC plays a critical role in a variety of conditioning tasks that have no obvious spatial component. Many of these studies suggest that the RSC is involved in identifying and encoding behaviorally significant cues, particularly those cues that predict reinforcement or the need for a behavioral response. Consistent with this idea, recent studies have shown that RSC neurons also encode cues in spatial navigation tasks. In this article, we review these findings and suggest that the encoding of cues is an important component of the RSC contribution to many forms of learning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

People differ greatly in their financial risk taking behaviour. This heterogeneity has been associated with differences in brain activity, but only in laboratory settings using constrained behaviours. However, it is important to understand how these measures transfer to real life conditions, because the willingness to invest in riskier assets has a direct and considerable effect on long-term wealth accumulation. In a large fMRI study of 157 working age men (39.0 ± 6.4 SD years), we first show that activity in the anterior insula during the assessment of risky vs. safe choices in an investing task is associated with self-reported real-life active stock trading. We then show that this association remains intact when we control for financial constraints, education, the understanding of financial matters, and cognitive abilities. Finally, we use comprehensive measures of preferences and beliefs about risk taking to show that these two channels mediate the association between brain activation in the anterior insula and real-life active stock trading.

In 2000, a landmark case report described the concurrent restoration of consciousness and thalamo-frontal connectivity after severe brain injury (Laureys et al., ). Being a single case however, this study could not disambiguate whether the result was specific to the restoration of consciousness per se as opposed to the return of complex cognitive function in general or simply the temporal evolution of post-injury pathophysiological events. To test whether the restoration of thalamo-cortical connectivity is specific to consciousness, 20 moderate-to-severe brain injury patients (from a recruited sample of 42) underwent resting-state functional magnetic resonance imaging within a week after injury and again six months later. As described in the single case report, we find thalamo-frontal connectivity to be increased at the chronic, compared with the acute, time-point. The increased connectivity was independent of whether patients had already recovered consciousness prior to the first assessment or whether they recovered consciousness in-between the two. Conversely, we did find an association between restoration of thalamo-frontal connectivity and the return of complex cognitive function. While we did replicate the findings of Laureys et al. (), our data suggests that the restoration of thalamo-frontal connectivity is not as tightly linked to the reemergence of consciousness per se. However, the degree to which the return of connectivity is linked to the return of complex cognitive function, or to the evolution of other time-dependent post-injury mechanisms, remains to be understood., (© 2017 Wiley Periodicals, Inc.)

It is well known that the insular cortex (Brodmann areas 13, 14, 15, and 16) located deep inside the Sylvian fissure is associated with mental functions such as perception, language, cognition, affect, and movement. In particular, the insular cortex has been linked to interoception, which is the representation of bodily physiological states that is used to regulate bodily states and mental functions. Recently, a common principle to explain such functions of the insular cortex has been proposed. The principle posits that the anterior insula generates predictions of future bodily states, computes the error by comparing the prediction with the actual sensory signals, and integrates the body with the mind by minimizing the prediction error. This article describes the functions of the insular cortex, and discusses the possibility that an error-minimizing function can affect decision-making to regulate behaviors.

Cognitive neuroscientists in the late 20th century began the task of identifying the part(s) of the brain concerned with normal behavior as manifest in the psychological capacities as affective powers, reasoning, behaving purposively and the pursuit of goals, following introduction of the 'functional magnetic resonance imaging' (fMRI) method for identifying brain activity. For this research program to be successful two questions require satisfactory answers. First, as the fMRI method can currently only be used on stationary subjects, to what extent can neuropsychological tests applicable to such stationary subjects be correlated with normal behavior. Second, to what extent can correlations between the various neuropsychological tests on the one hand, and sites of brain activity determined with fMRI on the other, be regarded as established. The extent to which these questions have yet received satisfactory answers is reviewed, and suggestions made both for improving correlations of neuropsychological tests with behavior as well as with the results of fMRI-based observations., (Copyright © 2016. Published by Elsevier Ltd.)

The brainstem nucleus locus coeruleus (LC) innervates the entire central nervous system and is the primary source of norepinephrine (NE) to the neocortex. While classically considered a homogenous modulator of forebrain activity by virtue of highly widespread and divergent axons, recent behavioral and pharmacological evidence suggest this nucleus may execute distinct operations within functionally distinct terminal fields. Summarized in this review are the anatomical and physiological properties of the nucleus within a historical context that led to the interpretation of the nucleus as a homogeneous entity with uniform and simultaneous actions throughout its terminal fields. Also included are findings from several laboratories which point to a more nuanced model of LC/NE function that parallels that seen in other forebrain-projecting monoaminergic nuclei. Such compartmentalized models of the nucleus promote the idea that specific LC circuits are involved in discrete behavioral operations, and therefore, by identifying the networks that are engaged by LC, the substrates for these behaviors can be identified and manipulated. Perturbations in the functional anatomy and physiology of this system may be related to neuropsychiatric conditions associated with dysregulation of the LC-noradrenergic system such as attention deficit hyperactivity disorder. Recent findings regarding the organization and operation of the LC/NE system collectively challenge the classical view of the nucleus as a relatively homogenous modulator of forebrain activity and provide the basis for a renewed scientific interest in this region of the brain. This article is part of a Special Issue entitled SI: Noradrenergic System., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Recent work has suggested that reward prediction errors elicit a positive voltage deflection in the scalp-recorded electroencephalogram (EEG); an event sometimes termed a reward positivity. However, a strong test of this proposed relationship remains to be defined. Other important questions remain unaddressed: such as the role of the reward positivity in predicting future behavioral adjustments that maximize reward. To answer these questions, a three-armed bandit task was used to investigate the role of positive prediction errors during trial-by-trial exploration and task-set based exploitation. The feedback-locked reward positivity was characterized by delta band activities, and these related EEG features scaled with the degree of a computationally derived positive prediction error. However, these phenomena were also dissociated: the computational model predicted exploitative action selection and related response time speeding whereas the feedback-locked EEG features did not. Compellingly, delta band dynamics time-locked to the subsequent bandit (the P3) successfully predicted these behaviors. These bandit-locked findings included an enhanced parietal to motor cortex delta phase lag that correlated with the degree of response time speeding, suggesting a mechanistic role for delta band activities in motivating action selection. This dissociation in feedback vs. bandit locked EEG signals is interpreted as a differentiation in hierarchically distinct types of prediction error, yielding novel predictions about these dissociable delta band phenomena during reinforcement learning and decision making., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Increase in the area and neuron number of the cerebral cortex over evolutionary time systematically changes its computational properties. One of the fundamental developmental mechanisms generating the cortex is a conserved rostrocaudal gradient in duration of neuron production, coupled with distinct asymmetries in the patterns of axon extension and synaptogenesis on the same axis. A small set of conserved sensorimotor areas with well-defined thalamic input anchors the rostrocaudal axis. These core mechanisms organize the cortex into two contrasting topographic zones, while systematically amplifying hierarchical organization on the rostrocaudal axis in larger brains. Recent work has shown that variation in 'cognitive control' in multiple species correlates best with absolute brain size, and this may be the behavioral outcome of this progressive organizational change., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The exquisite architecture of cortex incorporates a myriad of inhibitory interneuron types. Until recently, the dearth of techniques for cell type identification in awake animals has made it difficult to link interneuron activity with circuit function, computation and behavior. This situation has changed dramatically in recent years with the advent of novel tools for targeting genetically distinct interneuron types so their activity can be observed and manipulated. The association of different interneuron subtypes with specific circuit functions, such as gain modulation or disinhibition, is starting to reveal canonical circuit motifs conserved across neocortical regions. Moreover, it appears that some interneuron types are recruited at specific behavioral events and likely control the flow of information among and within brain areas at behavioral time scales. Based on these results we propose that interneuron function goes beyond network coordination and interneurons should be viewed as integral elements of cortical computations serving behavior., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cognitive and motor processes are essential for optimal athletic performance. Individuals trained in different skills and sports may have specialized cognitive abilities and motor strategies related to the characteristics of the activity and the effects of training and expertise. Most studies have investigated differences in motor-related cortical potential (MRCP) during self-paced tasks in athletes but not in stimulus-related tasks. The aim of the present study was to identify the differences in performance and MRCP between skilled and novice martial arts athletes during two different types of tasks: a sustained attention task and a transient attention task. Behavioral and electrophysiological data from twenty-two martial arts athletes were obtained while they performed a continuous performance task (CPT) to measure sustained attention and a cued continuous performance task (c-CPT) to measure transient attention. MRCP components were analyzed and compared between groups. Electrophysiological data in the CPT task indicated larger prefrontal positive activity and greater posterior negativity distribution prior to a motor response in the skilled athletes, while novices showed a significantly larger response-related P3 after a motor response in centro-parietal areas. A different effect occurred in the c-CPT task in which the novice athletes showed strong prefrontal positive activity before a motor response and a large response-related P3, while in skilled athletes, the prefrontal activity was absent. We propose that during the CPT, skilled athletes were able to allocate two different but related processes simultaneously according to CPT demand, which requires controlled attention and controlled motor responses. On the other hand, in the c-CPT, skilled athletes showed better cue facilitation, which permitted a major economy of resources and "automatic" or less controlled responses to relevant stimuli. In conclusion, the present data suggest that motor expertise enhances neural flexibility and allows better adaptation of cognitive control to the requested task.

Behavioral studies suggest that humans evolve the capacity to cope with anxiety induced by the awareness of death's inevitability. However, the neurocognitive processes that underlie online death-related thoughts remain unclear. Our recent functional MRI study found that the processing of linguistic cues related to death was characterized by decreased neural activity in human insular cortex. The current study further investigated the time course of neural processing of death-related linguistic cues. We recorded event-related potentials (ERP) to death-related, life-related, negative-valence, and neutral-valence words in a modified Stroop task that required color naming of words. We found that the amplitude of an early frontal/central negativity at 84-120 ms (N1) decreased to death-related words but increased to life-related words relative to neutral-valence words. The N1 effect associated with death-related and life-related words was correlated respectively with individuals' pessimistic and optimistic attitudes toward life. Death-related words also increased the amplitude of a frontal/central positivity at 124-300 ms (P2) and of a frontal/central positivity at 300-500 ms (P3). However, the P2 and P3 modulations were observed for both death-related and negative-valence words but not for life-related words. The ERP results suggest an early inverse coding of linguistic cues related to life and death, which is followed by negative emotional responses to death-related information.

Motor impairment is the most relevant clinical feature in Parkinson's disease (PD). Functional imaging studies on motor impairment in PD have revealed changes in the cortical motor circuits, with particular involvement of the fronto-striatal network. The aim of this study was to assess brain activations during the performance of three different motor exercises, characterized by progressive complexity, using a functional fMRI multiple block paradigm, in PD patients and matched control subjects. Unlike from single-task comparisons, multi-task comparisons between similar exercises allowed to analyse brain areas involved in motor complexity planning and execution. Our results showed that in the single-task comparisons the involvement of primary and secondary motor areas was observed, consistent with previous findings based on similar paradigms. Most notably, in the multi-task comparisons a greater activation of supplementary motor area and posterior parietal cortex in PD patients, compared with controls, was observed. Furthermore, PD patients, compared with controls, had a lower activation of the basal ganglia and limbic structures, presumably leading to the impairment in the higher levels of motor control, including complexity planning and execution. The findings suggest that in PD patients occur both compensatory mechanisms and loss of efficiency and provide further insight into the pathophysiological role of distinct cortical and subcortical areas in motor dysfunction.

During rest, the cerebral cortex displays rich, coordinated patterns of spontaneous activity. The mechanism that shapes these patterns is largely unknown. Here we demonstrate that a Hebbian-like, sustained process plays a role in focusing these coherent patterns. Human subjects used an fMRI-based neurofeedback (NF) paradigm to intensely activate the dorsal anterior cingulate cortex for a single epoch (30 min). Resting-state correlations between all of the cortical voxels' BOLD time courses (functional connectivity) were mapped before, immediately after, and one day after the NF session. We found that the single epoch of cortical activation induced a lasting restructuring of the functional connections according to a Hebbian-like rule. Therefore, the change (increase and decrease) in functional connectivity strength of cortical voxels during rest reflected the level of their prior coactivation during the NF epoch. Interestingly, the effect was significantly enhanced 1 d after the NF activation epoch. The effect was evident in each subject individually, indicating its potential as a diagnostic window into the personal history of prior brain activations of both healthy and abnormal individuals.

Background: Cerebral dysfunction is a common feature of both chronic alcohol abusers and binge drinkers. Here, we aimed to study whether, at equated behavioral performance levels, binge drinkers exhibited increased neural activity while performing simple cognitive tasks., Methods: Thirty-two participants (16 binge drinkers and 16 matched controls) were scanned using functional magnetic resonance imaging (fMRI) while performing an n-back working memory task. In the control zero-back (N0) condition, subjects were required to press a button with the right hand when the number "2" was displayed. In the two-back (N2) condition, subjects had to press a button when the displayed number was identical to the number shown two trials before., Results: fMRI analyses revealed higher bilateral activity in the pre-supplementary motor area in binge drinkers than matched controls, even though behavioral performances were similar. Moreover, binge drinkers showed specific positive correlations between the number of alcohol doses consumed per occasion and higher activity in the dorsomedial prefrontal cortex, as well as between the number of drinking occasions per week and higher activity in cerebellum, thalamus and insula while performing the N2 memory task., Conclusions: Binge alcohol consumption leads to possible compensatory cerebral changes in binge drinkers that facilitate normal behavioral performance. These changes in cerebral responses may be considered as vulnerability factors for developing adult substance use disorders.

How does the brain decide between actions? Is it through comparisons of abstract representations of outcomes or through a competition in a sensorimotor map defining the actions themselves? Here, I review strengths and limitations of both of these proposals, and suggest that decisions emerge through a distributed consensus across many levels of representation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cognitive task demands in one sensory modality (T1) can have beneficial effects on a secondary task (T2) in a different modality, due to reduced top-down control needed to inhibit the secondary task, as well as crossmodal spread of attention. This contrasts findings of cognitive load compromising a secondary modality's processing. We manipulated cognitive load within one modality (visual) and studied the consequences of cognitive demands on secondary (auditory) processing. 15 healthy participants underwent a simultaneous EEG-fMRI experiment. Data from 8 participants were obtained outside the scanner for validation purposes. The primary task (T1) was to respond to a visual working memory (WM) task with four conditions, while the secondary task (T2) consisted of an auditory oddball stream, which participants were asked to ignore. The fMRI results revealed fronto-parietal WM network activations in response to T1 task manipulation. This was accompanied by significantly higher reaction times and lower hit rates with increasing task difficulty which confirmed successful manipulation of WM load. Amplitudes of auditory evoked potentials, representing fundamental auditory processing showed a continuous augmentation which demonstrated a systematic relation to cross-modal cognitive load. With increasing WM load, primary auditory cortices were increasingly deactivated while psychophysiological interaction results suggested the emergence of auditory cortices connectivity with visual WM regions. These results suggest differential effects of crossmodal attention on fundamental auditory processing. We suggest a continuous allocation of resources to brain regions processing primary tasks when challenging the central executive under high cognitive load.

Background: Auditory verbal hallucinations (AVH), a prominent symptom of schizophrenia, are often highly distressing for patients. Better understanding of the pathogenesis of hallucinations could increase therapeutic options. Magnetoencephalography (MEG) provides direct measures of neuronal activity and has an excellent temporal resolution, offering a unique opportunity to study AVH pathophysiology., Methods: Twelve patients (10 paranoid schizophrenia, 2 psychosis not otherwise specified) indicated the presence of AVH by button-press while lying in a MEG scanner. As a control condition, patients performed a self-paced button-press task. AVH-state and non-AVH state were contrasted in a region-of-interest (ROI) approach. In addition, the two seconds before AVH onset were contrasted with the two seconds after AVH onset to elucidate a possible triggering mechanism., Results: AVH correlated with a decrease in beta-band power in the left temporal cortex. A decrease in alpha-band power was observed in the right inferior frontal gyrus. AVH onset was related to a decrease in theta-band power in the right hippocampus., Conclusions: These results suggest that AVH are triggered by a short aberration in the theta band in a memory-related structure, followed by activity in language areas accompanying the experience of AVH itself.

Both behavioral and neurophysiological evidence shows the advantage of object visualizers in object-related tasks relative to spatial visualizers. It is still unclear, in which stage the advantage appears. In this study, a behavioral experiment revealed that spatial visualizers' performance decreased evidently from short delay to long delay in a high-load condition, but object visualizers performed stably. In addition, an event-related potential experiment found the slow cortical potentials for the spatial visualizer to be more negative in relation to object visualizers in the 1800-3800 ms stage, although spatial visualizers performed worse than the object visualizers. Therefore, the processing advantage of object visualizers, which is caused by the higher neural efficiency of object visualizers than spatial visualizers in object tasks, seems to be at the retention stage rather than the encoding stage.

Pathology underlying behavioral variant frontotemporal dementia (bvFTD) is heterogeneous, with the most common pathologies being Pick's disease (PiD), corticobasal degeneration (CBD), and FTLD-TDP type 1. Clinical features are unhelpful in differentiating these pathologies. We aimed to determine whether imaging atrophy patterns differ across these pathologies in bvFTD subjects. We identified 15 bvFTD subjects that had volumetric MRI during life and autopsy: five with PiD, five CBD, and five FTLD-TDP type 1. Voxel-based morphometry was used to assess atrophy patterns in each bvFTD group compared to 20 age- and gender-matched controls. All three pathological groups showed gray matter loss in frontal lobes, although specific patterns of atrophy differed across groups: PiD showed widespread loss in frontal lobes with additional involvement of anterior temporal lobes; CBD showed subtle patterns of loss involving posterior lateral and medial superior frontal lobe; and FTLD-TDP type 1 showed widespread loss in frontal, temporal, and parietal lobes. Greater parietal loss was observed in FTLD-TDP type 1 compared to both other groups, and greater anterior temporal and medial frontal loss was observed in PiD compared to CBD. Imaging patterns of atrophy in bvFTD vary according to pathological diagnosis and may therefore be helpful in predicting these pathologies in bvFTD.

Higher brain function depends on task-dependent information flow between cortical regions. Converging lines of evidence suggest that interactions between cortical regions and the central thalamus play a key role in establishing the dynamic patterns of functional connectivity that normally support these processes. In patients with chronic disturbances of cognitive function due to severe brain injury, dysfunction of this circuitry likely plays a crucial role in pathogenesis. However, assaying thalamocortical interactions is challenging even in healthy subjects and more so in severely impaired patients. To approach this problem, we apply a dynamical-systems approach to motivate an analysis of the electroencephalogram (EEG). We begin with a model for a single thalamocortical module [Robinson PA, Rennie CJ, Rowe DL (2002) Phys Rev E Stat Nonlin Soft Matter Phys 65:041924; Robinson PA, Rennie CJ, Wright JJ, Bourke PD (1998) Phys Rev E Stat Nonlin Soft Matter Phys 58:3557-3571]. When two such modules interact via shared thalamic inhibition, multistable behavior emerges; each mode is characterized by a different pattern of coherence between cortical regions. This observation suggests that changing patterns of cortical coherence are a hallmark of normal thalamocortical dynamics. In a preliminary study, we test this idea by analyzing the EEG of a patient with chronic brain injury, who has a marked improvement in behavior and frontal brain metabolism in response to zolpidem. The analysis shows that following zolpidem administration, changing patterns of coherence are identified between the frontal lobes and between frontal and distant brain regions. These observations support the role of the central thalamus in the organization of patterns of cortical interactions and suggest how indexes of thalamocortical dynamics can be extracted from the EEG.

Objective: To assess the recovery process in patients after an acute optic neuritis (ON) attack, comparing static and dynamic visual functions., Methods: In this prospective controlled study, 21 patients with unilateral, first-ever ON were followed over the course of 1 year. Standard visual tests, visual evoked potentials, and optical coherence tomography were assessed repeatedly. In addition, we developed a novel set of motion perceptual tasks to test dynamic visual deficits. fMRI examinations were performed to study the neuronal correlates for the behavioral findings., Results: Four months after the acute phase, the affected eyes had returned to normal performance levels in the routine visual testing. However, motion perception remained impaired throughout the 12-month period. In agreement with the clinical findings, fMRI studies showed recovery in cortical activation during static object recognition, as opposed to sustained deficit in tasks that require motion perception., Conclusions: Sustained motion perception deficit following ON may explain the continued visual complaints of patients long after recovery of visual acuity. Cortical activation patterns suggest that if plastic processes in higher visual regions contribute to the recovery of vision, this may be limited to static visual functions. Alternatively, cortical activation may reflect the visual percept (intact for visual acuity and impaired for motion perception), rather than demonstrating plastic processes. We suggest that motion perception should be included in the routine ophthalmologic tests following ON.

In the present study, the possibility of component-specific self-regulation of the contingent negative variation (CNV) and the functional significance of the iCNV (initial or early CNV component) and tCNV (terminal or late CNV component) were investigated in twenty-four healthy volunteers. The subjects were able to achieve control over a particular CNV component within four sessions. Regulation of the tCNV was more successful than for the iCNV. Specific control over iCNV was associated with strategies mainly related to the pre-stimulus interval or the warning stimulus (S1), while regulation of the tCNV was assigned to activities during the whole interstimulus interval or around the imperative stimulus (S2). It can be concluded that component-specific regulation of the CNV can be used in studies of the psychophysiological meaning of this potential, representing different stages of information processing. The role of cortical pre-activation in the generation of the iCNV and the phasic performance-directed activation of the tCNV can be hypothesized.

Functional neuroimaging studies in humans have shown that nociceptive stimuli elicit activity in a wide network of cortical areas commonly labeled as the "pain matrix" and thought to be preferentially involved in the perception of pain. Despite the fact that this "pain matrix" has been used extensively to build models of where and how nociception is processed in the human brain, convincing experimental evidence demonstrating that this network is specifically related to nociception is lacking. The aim of the present study was to determine whether there is at least a subset of the "pain matrix" that responds uniquely to nociceptive somatosensory stimulation. In a first experiment, we compared the fMRI brain responses elicited by a random sequence of brief nociceptive somatosensory, non-nociceptive somatosensory, auditory and visual stimuli, all presented within a similar attentional context. We found that the fMRI responses triggered by nociceptive stimuli can be largely explained by a combination of (1) multimodal neural activities (i.e., activities elicited by all stimuli regardless of sensory modality) and (2) somatosensory-specific but not nociceptive-specific neural activities (i.e., activities elicited by both nociceptive and non-nociceptive somatosensory stimuli). The magnitude of multimodal activities correlated significantly with the perceived saliency of the stimulus. In a second experiment, we compared these multimodal activities to the fMRI responses elicited by auditory stimuli presented using an oddball paradigm. We found that the spatial distribution of the responses elicited by novel non-target and novel target auditory stimuli resembled closely that of the multimodal responses identified in the first experiment. Taken together, these findings suggest that the largest part of the fMRI responses elicited by phasic nociceptive stimuli reflects non nociceptive-specific cognitive processes., (Copyright © 2010 Elsevier Inc. All rights reserved.)

In speech perception, a functional hierarchy has been proposed by recent functional neuroimaging studies: core auditory areas on the dorsal plane of superior temporal gyrus (STG) are sensitive to basic acoustic characteristics, whereas downstream regions, specifically the left superior temporal sulcus (STS) and middle temporal gyrus (MTG) ventral to Heschl's gyrus (HG) are responsive to abstract phonological features. What is unclear so far is the relationship between the dorsal and ventral processes, especially with regard to whether low-level acoustic processing is modulated by high-level phonological processing. To address the issue, we assessed sensitivity of core auditory and downstream regions to acoustic and phonological variations by using within- and across-category lexical tonal continua with equal physical intervals. We found that relative to within-category variation, across-category variation elicited stronger activation in the left middle MTG (mMTG), apparently reflecting the abstract phonological representations. At the same time, activation in the core auditory region decreased, resulting from the top-down influences of phonological processing. These results support a hierarchical organization of the ventral acoustic-phonological processing stream, which originates in the right HG/STG and projects to the left mMTG. Furthermore, our study provides direct evidence that low-level acoustic analysis is modulated by high-level phonological representations, revealing the cortical dynamics of acoustic and phonological processing in speech perception. Our findings confirm the existence of reciprocal progression projections in the auditory pathways and the roles of both feed-forward and feedback mechanisms in speech perception.

Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.

The co-expression of behavioral and neural events represents a situation conducive to Hebbian-type neuroplasticity and may provide a reasonable explanation for how the amount of movement during the perinatal period contributes to neuromotor development. Direct current-coupled electrographic recordings in premature infants indicate that the majority of the electrographic activity is exhibited in a slow frequency range that is either distorted or not visible using traditional recording methods. Therefore, we provide a description of the behavioral correlates of direct current-coupled electrographic recordings in six premature human infants (3 males and 3 females; 30-34 weeks). We report, in concert with prior data, that electrographic activity and movements occur in tightly coupled discrete bouts. Surprisingly, spontaneous activity transients, which are slow, high amplitude, multiband electrographic events, typically precede startles; thereby revealing a previously unknown coupling of early neural and behavioral events in humans. Taken together, the present findings open novel venues for studying and dissecting mammalian neuromotor development., (Copyright 2010 Elsevier B.V. All rights reserved.)

This paper explores the implications of a recently published theory that relates the experience of qualia to the attractor activity in networks of pyramidal cells in the cerebral cortex. The paper builds on this theory, and aims to link activity in different networks to the nature of the qualia experienced. Some basic links between network activity and qualia experiences are initially presented, showing the importance of learning, and the paper then proceeds to relate these mechanisms to the qualia experienced during sensory perception. The paper argues that attractor behavior in networks of layer 2/3 pyramidal neurons could underpin the vivid sensory qualia of perception, and attractor behavior in networks of layer 5A pyramidal neurons could have a role in the more understanding kind of perceptual qualia. Communication between these networks is explored to suggest their involvement in putting incoming sensory information into the context of all prior experience, and the understanding that could result.

The predisposition of human beings toward spiritual feeling, thinking, and behaviors is measured by a supposedly stable personality trait called self-transcendence. Although a few neuroimaging studies suggest that neural activation of a large fronto-parieto-temporal network may underpin a variety of spiritual experiences, information on the causative link between such a network and spirituality is lacking. Combining pre- and post-neurosurgery personality assessment with advanced brain-lesion mapping techniques, we found that selective damage to left and right inferior posterior parietal regions induced a specific increase of self-transcendence. Therefore, modifications of neural activity in temporoparietal areas may induce unusually fast modulations of a stable personality trait related to transcendental self-referential awareness. These results hint at the active, crucial role of left and right parietal systems in determining self-transcendence and cast new light on the neurobiological bases of altered spiritual and religious attitudes and behaviors in neurological and mental disorders., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Processing stimuli in one sensory modality is known to result in suppression of other sensory-specific cortices. Additionally, behavioral experiments suggest that the primary consequence of paying attention to a specific sensory modality is poorer task performance in the unattended sensory modality. This study was designed to determine how focusing attention on the auditory or visual modality impacts neural activity in cortical regions responsible for processing stimuli in the unattended modality., Methods: Functional MRI data were collected in 15 participants who completed a cued detection paradigm. This task allowed us to assess the effects of modality-specific attention both during the presence and the absence of targets in the attended modality., Results: The results of this experiment demonstrate that attention to a single sensory modality can result in decreased activity in cortical regions that process information from an unattended sensory modality (cross-modal deactivations). The effects of attention are likely additive with stimulus-driven effects with the largest deactivations being observed during modality-specific selective attention, in the presence of a stimulus in that modality., Conclusion: Modality-specific selective attention results in behavioral decrements in unattended sensory modalities. The imaging results presented here provide a neural signature (cross-modal deactivation) for modality-specific selective attention.

In this study, electroencephalography (EEG) was used to examine the relationship between two leading hypotheses of cognitive aging, the inhibitory deficit and the processing speed hypothesis. We show that older adults exhibit a selective deficit in suppressing task-irrelevant information during visual working memory encoding, but only in the early stages of visual processing. Thus, the employment of suppressive mechanisms are not abolished with aging but rather delayed in time, revealing a decline in processing speed that is selective for the inhibition of irrelevant information. EEG spectral analysis of signals from frontal regions suggests that this results from excessive attention to distracting information early in the time course of viewing irrelevant stimuli. Subdividing the older population based on working memory performance revealed that impaired suppression of distracting information early in the visual processing stream is associated with poorer memory of task-relevant information. Thus, these data reconcile two cognitive aging hypotheses by revealing that an interaction of deficits in inhibition and processing speed contributes to age-related cognitive impairment.

Letters and speech sounds are the basic units of correspondence between spoken and written language. Associating auditory information of speech sounds with visual information of letters is critical for learning to read; however, the neural mechanisms underlying this association remain poorly understood. The present functional magnetic resonance imaging study investigates the automaticity and behavioral relevance of integrating letters and speech sounds. Within a unimodal auditory identification task, speech sounds were presented in isolation (unimodally) or bimodally in congruent and incongruent combinations with visual letters. Furthermore, the quality of the visual letters was manipulated parametrically. Our analyses revealed that the presentation of congruent visual letters led to a behavioral improvement in identifying speech sounds, which was paralleled by a similar modulation of cortical responses in the left superior temporal sulcus. Under low visual noise, cortical responses in superior temporal and occipito-temporal cortex were further modulated by the congruency between auditory and visual stimuli. These cross-modal modulations of performance and cortical responses during an unimodal auditory task (speech identification) indicate the existence of a strong and automatic functional coupling between processing of letters (orthography) and speech (phonology) in the literate adult brain.

The present study aimed at investigating changes in behavior (shooting precision) and electrophysiological variables (absolute alpha power) during the motor learning of practical pistol shooting. The sample was composed of 23 healthy subjects, right-handed, male, between 18 and 20 years of age. The task consisted of four learning blocks. A One-way ANOVA with repeated measures and a post hoc analysis were employed to observe modifications on behavioral and electrophysiological measures (p<0.05). The results showed significative differences between blocks according to motor learning, and a significant improvement in shooting's accuracy from both blocks. It was observed a decrease in alpha power in all electrodes examined during task execution when compared with baseline and learning control blocks. The findings suggest that alpha power decreases as the function of the motor learning task when subjects are engaged in the motor execution.

Transcranial magnetic stimulation (TMS) is increasingly used to modify brain activity noninvasively and to study brain-behavior relations. However, results can be variable and the conditions that affect the functional efficacy of TMS remain unclear. Here we show that on-line TMS can either facilitate or suppress perceptual functions depending on the baseline level of activity of the targeted brain region. When TMS was applied over the motion selective region V5/MT during a simple motion-detection task, subjects' motion-detection ability was impaired. Similarly, suppression of V5/MT activity using off-line 1 Hz repetitive TMS (rTMS) disrupted performance in a subsequent motion-detection task. However, paradoxically, on-line V5/MT TMS had a facilitatory effect on motion detection if V5/MT had been suppressed by off-line 1-Hz rTMS prior to the motion-detection task. These results demonstrate that TMS can have an unexpected facilitatory effect on behavior when the targeted neural population is in a suppressed state. Our findings provide further evidence for the view that the effects of TMS are modulated by the initial activation state of the targeted neural population.

Expectations about the magnitude of impending pain exert a substantial effect on subsequent perception. However, the neural mechanisms that underlie the predictive processes that modulate pain are poorly understood. In a combined behavioral and high-density electrophysiological study we measured anticipatory neural responses to heat stimuli to determine how predictions of pain intensity, and certainty about those predictions, modulate brain activity and subjective pain ratings. Prior to receiving randomized laser heat stimuli at different intensities (low, medium or high) subjects (n=15) viewed cues that either accurately informed them of forthcoming intensity (certain expectation) or not (uncertain expectation). Pain ratings were biased towards prior expectations of either high or low intensity. Anticipatory neural responses increased with expectations of painful vs. non-painful heat intensity, suggesting the presence of neural responses that represent predicted heat stimulus intensity. These anticipatory responses also correlated with the amplitude of the Laser-Evoked Potential (LEP) response to painful stimuli when the intensity was predictable. Source analysis (LORETA) revealed that uncertainty about expected heat intensity involves an anticipatory cortical network commonly associated with attention (left dorsolateral prefrontal, posterior cingulate and bilateral inferior parietal cortices). Relative certainty, however, involves cortical areas previously associated with semantic and prospective memory (left inferior frontal and inferior temporal cortex, and right anterior prefrontal cortex). This suggests that biasing of pain reports and LEPs by expectation involves temporally precise activity in specific cortical networks.

Asymmetries in upper limb performance are a fundamental aspect of human behavior. This phenomenon, commonly known as handedness, has inspired a great deal of research over the course of the past century garnering interest across a multitude of scientific domains. In the present paper, a thorough review of this literature is provided focusing on the current state of knowledge regarding neuro-anatomical and behavior-based arm asymmetries. It is hoped that this information will provide a basis for new insights regarding the design and implementation of future studies regarding arm laterality.

Multiple neuronal systems contribute to the promotion and maintenance of the wake state, which is characterized by cortical activation and behavioral arousal. Using predominantly glutamate as a neurotransmitter, neurons within the reticular formation of the brainstem give rise to either ascending projections into the forebrain or descending projections into the spinal cord to promote through relays fast cortical activity or motor activity with postural muscle tone. Using acetylcholine, cholinergic neurons in the brainstem project to forebrain relays and others in the basal forebrain to the cortex, by which they stimulate fast gamma activity during waking and during rapid eye movement or paradoxical sleep (PS). Other neuromodulatory systems, such as noradrenergic locus coeruleus neurons, give rise to highly diffuse projections through brain and spinal cord and simultaneously stimulate cortical activation and behavioral arousal. Although such neuromodulatory systems were thought to be redundant, a recently discovered peptide called orexin (Orx) or hypocretin, contained in diffusely projecting neurons of the hypothalamus, was found to be essential for the maintenance of waking with muscle tone, since in its absence narcolepsy with cataplexy occurred. Orx neurons discharge during active waking and cease firing during sleep. Since cholinergic neurons discharge during waking and PS, they would stimulate cortical activation in association with muscle tone when orexinergic neurons are also active but would stimulate cortical activation with muscle atonia when orexinergic neurons are silent, as in natural PS, or absent, as in pathological narcolepsy with cataplexy.

Emotional facial expressions can engender similar expressions in others. However, adaptive social and motivational behavior can require individuals to suppress, conceal, or override prepotent imitative responses. We predicted, in line with a theory of "emotion contagion," that when viewing a facial expression, expressing a different emotion would manifest as behavioral conflict and interference. We employed facial electromyography (EMG) and functional magnetic resonance imaging (fMRI) to investigate brain activity related to this emotion expression interference (EEI) effect, where the expressed response was either concordant or discordant with the observed emotion. The Simon task was included as a nonemotional comparison for the fMRI study. Facilitation and interference effects were observed in the latency of facial EMG responses. Neuroimaging revealed activation of distributed brain regions including anterior right inferior frontal gyrus (brain area [BA] 47), supplementary motor area (facial area), posterior superior temporal sulcus (STS), and right anterior insula during emotion expression-associated interference. In contrast, nonemotional response conflict (Simon task) engaged a distinct frontostriatal network. Individual differences in empathy and emotion regulatory tendency predicted the magnitude of EEI-evoked regional activity with BA 47 and STS. Our findings point to these regions as providing a putative neural substrate underpinning a crucial adaptive aspect of social/emotional behavior.

Background: In non-human primates grasp-related sensorimotor transformations are accomplished in a circuit involving the anterior intraparietal sulcus (area AIP) and both the ventral and the dorsal sectors of the premotor cortex (vPMC and dPMC, respectively). Although a human homologue of such a circuit has been identified whether activity within this circuit varies depending on handedness has yet to be investigated., Methodology/principal Findings: We used functional magnetic resonance imaging (fMRI) to explicitly test how handedness modulates activity within human grasping-related brain areas. Right- and left-handers subjects were requested to reach towards and grasp an object with either the right or the left hand using a precision grip while scanned. A kinematic study was conducted with similar procedures as a behavioral counterpart for the fMRI experiment. Results from a factorial design revealed significant activity within the right dPMC, the right cerebellum and AIP bilaterally. The pattern of activity within these areas mirrored the results found for the behavioral study., Conclusion/significance: Data are discussed in terms of an handedness-independent role for the right dPMC in monitoring hand shaping, the need for bilateral AIP activity for the performance of precision grip movements which varies depending on handedness and the involvement of the cerebellum in terms of its connections with AIP. These results provide the first compelling evidence of specific grasping related neural activity depending on handedness.

Scientists in many different fields have been attracted to the study of habits because of the power habits have over behavior and because they invoke a dichotomy between the conscious, voluntary control over behavior, considered the essence of higher-order deliberative behavioral control, and lower-order behavioral control that is scarcely available to consciousness. A broad spectrum of behavioral routines and rituals can become habitual and stereotyped through learning. Others have a strong innate basis. Repetitive behaviors can also appear as cardinal symptoms in a broad range of neurological and neuropsychiatric illness and in addictive states. This review suggests that many of these behaviors could emerge as a result of experience-dependent plasticity in basal ganglia-based circuits that can influence not only overt behaviors but also cognitive activity. Culturally based rituals may reflect privileged interactions between the basal ganglia and cortically based circuits that influence social, emotional, and action functions of the brain.

The Urge-to-Cough is a component of the brain motivation system that mediates cognitive responses to cough stimuli. There are six stages to the cough motivation-to-action system: (1) stimulus, the trigger for the neural event; (2) urge, the physical need to respond to the stimulus; (3) desire, translation of urge into a central neural targeted goal; (4) action, physical response that satisfies the urge-desire; (5) evidence, feedback to the neural system on the action; (6) reward, sensory system that determines if the urge was satisfied. Urge-to-Cough is related to three fundamental types of cough: (1) reflex cough, (2) voluntary cough, and (3) behavioral cough. Urge-to-Cough with reflex cough can be studied by measuring the sensations elicited by a cough stimulus. Neural processes with voluntary cough can be studied using magnitude production cognitive psychometric methods. Results of these studies have shown if the subjects can reliably estimate their Urge-to-Cough, the urge increases with increasing cough stimulus, there is a correlation between the Urge-to-Cough and cough intensity, there is a threshold for eliciting the sensation of the urge that precedes the motor cough behavior, subjects can voluntarily produce coughs of varying magnitudes, the motor cough pattern is directly related to the perceived magnitude of a cough, volitional triggers of a cough are directly related to the reflex cough pattern, and neural triggers of cough initiate a stereotypic motor output. Understanding the Urge-to-Cough motivation-to-action system opens new strategies for research on central neural cough mechanisms.