Functional Neuroimaging Technologies Research Articles

Current progress on characteristics of intracranial electrophysiology related to prolonged disorders of consciousness

Prolonged disorders of consciousness (pDOC) are pathological conditions of alterations in consciousness caused by various severe brain injuries, profoundly affecting patients' life ability and leading to a huge burden for both the family and society. Exploring the mechanisms underlying pDOC and accurately assessing the level of consciousness in the patients with pDOC provide the basis of developing therapeutic strategies. Research of non-invasive functional neuroimaging technologies, such as functional magnetic resonance (fMRI) and scalp electroencephalography (EEG), have demonstrated that the generation, maintenance and disorders of consciousness involve functions of multiple cortical and subcortical brain regions, and their networks. Invasive intracranial neuroelectrophysiological technique can directly record the electrical activity of subcortical or cortical neurons with high signal-to-noise ratio and spatial resolution, which has unique advantages and important significance for further revealing the brain function and disease mechanism of pDOC. Here we reviewed the current progress of pDOC research based on two intracranial electrophysiological signals, spikes reflecting single-unit activity and field potential reflecting multi-unit activities, and then discussed the current challenges and gave an outlook on future development, hoping to promote the study of pathophysiological mechanisms related to pDOC and provide guides for the future clinical diagnosis and therapy of pDOC.

Sex-Related Variations in the Brain Motor-Network Connectivity at Rest during Puberty

The development of functional neuroimaging technologies has resulted in a flood of mathematical models that investigate functional brain connections in health and disease. Motor network activity in the resting state and its response to puberty remains to be investigated. Variations between sexes in puberty may appear not just in brain regions involved in sexual and emotional activities, but also in cognitive and motor abilities that are active even when the individual is resting. The aim of this study was to investigate the interactions of the motor subnetwork in the resting state of healthy males and females aged 12 and 16. This study used the OpenNeuro Dataset ds004169:1.0.7, Queensland Twin IMaging. The MRI signals were preprocessed to get adjacency matrices from the sensory/somatomotor and cerebellar networks in the Power atlas. Network topology was analyzed using the centrality measures of strength, hubness, and leverage. The strength of the nodes increases with age in both sex groups. Both sexes had right hemisphere dominance in the cerebellar-mouth subnetwork and left dominance in the cerebellar-hand subnetwork. Eleven leverage centrality regions were common to all groups, the most relevant were the Precuneus, the cingulum postcentral and the supplementary motor area. In both sexes, hubs at age 12 were detected only in the right hemisphere. This dominance was reduced at age 16. Understanding connectivity changes in the brain during rest may enable the identification of neurophysiological mechanisms of cognitive and behavioral development that may contribute to long-term psychological well-being in adolescents.

Intraoperative Stimulation Mapping in Neurosurgery for Anesthesiologists—Part 1: The Technical Nuances

AbstractBrain mapping has evolved tremendously in the past decade, fueled by advances in functional neuroimaging technology in neuro-oncology and epilepsy surgery. Despite this, wide anatomic-functional interindividual variability and intraoperative brain shift continue to challenge neurosurgeons performing surgery within or near eloquent brain regions. As such, intraoperative direct cortical and subcortical stimulation mapping remains the gold standard for localizing eloquent brain regions with precision for a safe and tailored resection. Intraoperative stimulation mapping (ISM) allows for maximizing the extent of resection while minimizing postoperative neurological deficits, resulting in better patient outcomes. Understanding the technical nuances of ISM is imperative for the anesthesiologist to provide better anesthetic management tailored to the surgery and stimulation mapping planned. A comprehensive search was performed on electronic databases to identify articles describing intraoperative cortical and subcortical mapping, language, and motor mapping. In the first part of this narrative review, we summarize the salient technical aspects of ISM and the common neurophysiological tasks assessed intraoperatively relevant to the anesthesiologist.

Functional Neuroimaging in Patients With Disorders of Consciousness: Caution Advised.

Functional Neuroimaging in Patients With Disorders of Consciousness: Caution Advised.

Reliability and similarity of resting state functional connectivity networks imaged using wearable, high-density diffuse optical tomography in the home setting

BackgroundWhen characterizing the brain's resting state functional connectivity (RSFC) networks, demonstrating networks' similarity across sessions and reliability across different scan durations is essential for validating results and possibly minimizing the scanning time needed to obtain stable measures of RSFC. Recent advances in optical functional neuroimaging technologies have resulted in fully wearable devices that may serve as a complimentary tool to functional magnetic resonance imaging (fMRI) and allow for investigations of RSFC networks repeatedly and easily in non-traditional scanning environments. MethodsResting-state cortical hemodynamic activity was repeatedly measured in a single individual in the home environment during COVID-19 lockdown conditions using the first ever application of a 24-module (72 sources, 96 detectors) wearable high-density diffuse optical tomography (HD-DOT) system. Twelve-minute recordings of resting-state data were acquired over the pre-frontal and occipital regions in fourteen experimental sessions over three weeks. As an initial validation of the data, spatial independent component analysis was used to identify RSFC networks. Reliability and similarity scores were computed using metrics adapted from the fMRI literature. ResultsWe observed RSFC networks over visual regions (visual peripheral, visual central networks) and higher-order association regions (control, salience and default mode network), consistent with previous fMRI literature. High similarity was observed across testing sessions and across chromophores (oxygenated and deoxygenated haemoglobin, HbO and HbR) for all functional networks, and for each network considered separately. Stable reliability values (described here as a <10% change between time windows) were obtained for HbO and HbR with differences in required scanning time observed on a network-by-network basis. DiscussionUsing RSFC data from a highly sampled individual, the present work demonstrates that wearable HD-DOT can be used to obtain RSFC measurements with high similarity across imaging sessions and reliability across recording durations in the home environment. Wearable HD-DOT may serve as a complimentary tool to fMRI for studying RSFC networks outside of the traditional scanning environment and in vulnerable populations for whom fMRI is not feasible.

New Perspectives on the Neurobiology of Sign Languages.

The first 40 years of research on the neurobiology of sign languages (1960-2000) established that the same key left hemisphere brain regions support both signed and spoken languages, based primarily on evidence from signers with brain injury and at the end of the 20th century, based on evidence from emerging functional neuroimaging technologies (positron emission tomography and fMRI). Building on this earlier work, this review focuses on what we have learned about the neurobiology of sign languages in the last 15-20 years, what controversies remain unresolved, and directions for future research. Production and comprehension processes are addressed separately in order to capture whether and how output and input differences between sign and speech impact the neural substrates supporting language. In addition, the review includes aspects of language that are unique to sign languages, such as pervasive lexical iconicity, fingerspelling, linguistic facial expressions, and depictive classifier constructions. Summary sketches of the neural networks supporting sign language production and comprehension are provided with the hope that these will inspire future research as we begin to develop a more complete neurobiological model of sign language processing.

Brain-Wide Diffuse Optical Tomography Based on Cap-Based, Whole-Head fNIRS Recording.

Diffuse optical tomography (DOT), based on functional near-infrared spectroscopy, is a portable, low-cost, noninvasive functional neuroimaging technology for studying the human brain in normal and diseased conditions. The goal of the present study was to evaluate the performance of a cap-based brain-wide DOT (BW-DOT) framework in mapping brain-wide networked activities. We first analyzed point-spread-function (PSF)-based metrics on a realistic head geometry. Our simulation results indicated that these metrics of the optode cap varied across the brain and were of lower quality in brain areas deep or away from the optodes. We further reconstructed brain-wide resting-state networks using experimental data from healthy participants, which resembled the template networks established in the fMRI literature. The preliminary results of the present study highlight the importance of evaluating PSF-based metrics on realistic head geometries for DOT and suggest that BW-DOT technology is a promising functional neuroimaging tool for studying brain-wide neural activities and large-scale neural networks, which was not available by patch-based DOT. A full-scope evaluation and validation in more realistic head models and more participants are needed in the future to establish the findings of the present study further.Clinical relevance- Via simulations and experimental evaluation, this work establishes a novel framework to image large-scale brain networks, which benefits the patient population, such as bedridden patients, infants, etc., who otherwise cannot undergo conventional brain monitoring modalities like fMRI and PET.

Multi-source brain computing with systematic fusion for smart health

With the progress of artificial intelligence, big data and functional neuroimaging technologies, brain computing has rapidly advanced our understanding of brain intelligence and brain disorders. We argue that existing data analytical methods have become insufficient for brain computing when dealing with multiple brain big data sources, because such methods mainly focus on flattening strategies and fail to work well for systematic understanding of the constituent elements of cognition, emotion and disease, as well as the intra- and inter-relations within and among themselves. To address this problem, we present in this paper a novel multi-source brain computing platform by Data-Brain driven systematic fusion. First, we formalize a series of behaviors surrounding the Brain Informatics-based investigation process, and present a conceptual model to systematically represent content and context of functional neuroimaging data. Then, we propose the systematic brain computing framework with multi-aspect fusion and inference to understand brain specificity and give uncertainty quantification, as well as its inspiration and applications for translational studies on brain health. In particular, a graph matching-based task search algorithm is introduced to help systematic experimental design and data sampling with multiple cognitive tasks. The study increases the interpretability and transparency of brain computing findings by inferring and testing multiple hypotheses taking into consideration the effect of evidence combination. Finally, multiple sources of knowledge (K), information (I) and data (D) are driven by a KID loop as the thinking space to inspire never-ending learning and multi-dimensional interactions in the connected social–cyber–physical spaces. Experimental results have demonstrated the efficacy of the proposed brain computing method with systematic fusion.

Pathogenesis and brain functional imaging in nocturnal enuresis: A review.

Nocturnal enuresis is a common and distressing developmental disease, which may cause various degrees of psychosocial stress and impairment to self-esteem in affected children as well as agitation to their parents or caregivers. Nevertheless, the etiology and pathogenesis of nocturnal enuresis are not understood. Currently, nocturnal enuresis is generally considered a multifactorial disease associated with a complex interaction of somatic, psychosocial, and environmental factors. A variety of postulations have been proposed to explain the occurrence and progression of nocturnal enuresis, including hereditary aberration, abnormal circadian rhythm of antidiuretic hormone secretion during sleep, bladder dysfunction, abnormal sleep, difficulties in arousal, neuropsychological disorders, and maturational delays of the brain. In recent decades, the introduction of functional neuroimaging technologies has provided new approaches for uncovering the mechanisms underlying nocturnal enuresis. The main neuroimaging modalities have included brain morphometry based on structural magnetic resonance imaging (MRI), task-based and event-related functional MRI (fMRI), and resting-state fMRI. The relevant studies have indicated that nocturnal enuresis is associated with functional and structural alterations of the brain. In this review, we briefly summarized the popular hypotheses regarding the pathogenesis of nocturnal enuresis and the current progress of functional neuroimaging studies in examining the underlying mechanisms thereof.

Evolution in the Treatment of Psychiatric Disorders: From Psychosurgery to Psychopharmacology to Neuromodulation.

The treatment of psychiatric patients presents significant challenges to the clinical community, and a multidisciplinary approach to diagnosis and management is essential to facilitate optimal care. In particular, the neurosurgical treatment of psychiatric disorders, or “psychosurgery,” has held fascination throughout human history as a potential method of influencing behavior and consciousness. Early evidence of such procedures can be traced to prehistory, and interest flourished in the nineteenth and early twentieth century with greater insight into cerebral functional and anatomic localization. However, any discussion of psychosurgery invariably invokes controversy, as the widespread and indiscriminate use of the transorbital lobotomy in the mid-twentieth century resulted in profound ethical ramifications that persist to this day. The concurrent development of effective psychopharmacological treatments virtually eliminated the need and desire for psychosurgical procedures, and accordingly the research and practice of psychosurgery was dormant, but not forgotten. There has been a recent resurgence of interest for non-ablative therapies, due in part to modern advances in functional and structural neuroimaging and neuromodulation technology. In particular, deep brain stimulation is a promising treatment paradigm with the potential to modulate abnormal pathways and networks implicated in psychiatric disease states. Although there is enthusiasm regarding these recent advancements, it is important to reflect on the scientific, social, and ethical considerations of this controversial field.

Neurology of ecstatic religious and similar experiences: ecstatic, orgasmic, and musicogenic seizures. Stendhal syndrome and autoscopic phenomena

All human experiences, including mystical and religious ones, are the result of brain functional activity. Thanks to the study of cases of ecstatic epilepsy with structural (MRI) and functional neuroimaging (fMRI, PET, SPECT) and neurophysiological technologies (recording and stimulation with intracranial electrodes), we now have a better knowledge of certain mental states which involve pleasant and affective symptoms and clarity of mind. These ecstatic experiences are thought to be caused by the activation of the anterior insular cortex and some neuronal networks (basically related to mirror neurons and salience) participating in introspection, social cognition, memory, and emotional processes. Thus, neuroscience could explain in a retrospective way some facts surrounding the situations of such relevant figures as Paul the Apostle, Teresa de Cepeda y Ahumada, and Dostoevsky, whose origin was previously considered paranormal or supernatural. Ecstatic epilepsy shares symptoms and mechanisms with orgasmic epilepsy (spontaneous orgasms in the course of epileptic seizures), musicogenic epilepsy (epileptic seizures triggered by listening to a certain musical piece), and also with Stendhal syndrome (neuropsychiatric disturbances caused when an individual is exposed to large amounts of art) and some autoscopic phenomena (out-of-body experiences that occasionally take place in imminent death situations). In all these events, there are pleasant and affective symptoms which have a great impact on patients.

Electrophysiological Source Imaging: A Noninvasive Window to Brain Dynamics.

Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.

Relationship between amplitude of resting-state fNIRS global signal and EEG vigilance measures.

Most of the prior studies of functional connectivity in both healthy and diseased brain utilized resting-state functional magnetic resonance imaging (fMRI) as a measure to represent the temporal synchrony in blood oxygenation level dependent (BOLD) signals across brain regions. To eliminate the impact of widely distributed global signal component across the brain, many studies have adopted global signal regression (GSR) as a pre-processing approach to regress the global signal component out of BOLD signals followed by computing hemodynamic connectivity. However, the procedure of global signal regression has been debated as physiologically relevant component may be present in global signal. In this study, we aimed to address the controversy of global signal using functional non-invasive neuroimaging technology, i.e. functional near-infrared spectroscopy (fNIRS), which measures hemodynamic signals by probing local changes in oxygen consumption, a common imaging contrast measured by BOLD fMRI. In the current study, we acquired simultaneous EEG and fNIRS signals, both in high-density configuration and whole-brain coverage, in healthy individuals at eyes-open and eyes-closed resting state and at three different body positions. We explored the underlying relationship between fNIRS global signal and EEG vigilance, and have identified negative correlation between fNIRS global signal and EEG vigilance across the physiological variations of measurements.

What we know now: education, neuroscience and transdisciplinary autism research

Background: Knowledge about the brain has been growing rapidly since the 1990s as a result of developments in neuroscientific research linked to improvements in functional neuroimaging and other brain imaging technologies. As the brain is the ‘principal organ involved in learning’ (1), it would seem reasonable to assume that education should be one of the chief beneficiaries of this research, leading to advances in our understanding of how people learn, the development of new curricula and innovative teaching and learning approaches. However, the linkage between neuroscience and education has, historically, always been weak, and, we suggest, continues to be so, notwithstanding important research initiatives since the year 2000.Purpose: The purpose of this paper is to critically explore current theoretical understanding of joint neuroscientific and educational research, herein referred to as ‘neuroeducational’ research. There is a particular focus on a critique of the transdisciplinary model as applied in a study of imitation in learners with autism.Main argument and sources of evidence: The review of the literature in the first half of the paper identifies the key barriers to neuroeducational research, including neuromyths, lack of shared understanding, the problem of the translation of neuroscientific findings to schools and clashing research assumptions, methodologies and traditions. However, a model of transdisciplinarity is presented as a possible way forward. This model is tested in the second half of the paper against the experiences of the authors in conducting transdisciplinary research in autism and imitation in the secondary classroom. Here, we develop the concepts of ‘transfer affordances’, ‘transfer challenges’ and ‘transfer opportunities’ to structure our analysis of the various dimensions of the transdisciplinary research process. These new concepts are defined, and their relevance and utility explained.Conclusions: The main conclusion of the paper is that the transdisciplinary research process within neuroeducation is complex, far from fully understood and requires further mapping. It is proposed that the concepts of ‘transfer affordances’, ‘transfer challenges’ and ‘transfer opportunities’ are useful theoretical ideas in pursuit of this aim.

Neurología del éxtasis y fenómenos aledaños: epilepsia extática, orgásmica y musicogénica. Síndrome de Stendhal. Fenómenos autoscópicos

All human experiences, including mystical and religious ones, are the result of brain functional activity. Thanks to the study of cases of ecstatic epilepsy with structural (MRI) and functional neuroimaging (fMRI, PET, SPECT) and neurophysiological technologies (recording and stimulation with intracranial electrodes), we now have a better knowledge of certain mental states which involve pleasant and affective symptoms and clarity of mind. These ecstatic experiences are thought to be caused by the activation of the anterior insular cortex and some neuronal networks (basically related to mirror neurons and salience) participating in introspection, social cognition, memory, and emotional processes. Thus, neuroscience could explain in a retrospective way some facts surrounding the situations of such relevant figures as Paul the Apostle, Teresa de Cepeda y Ahumada, and Dostoevsky, whose origin was previously considered paranormal or supernatural. Ecstatic epilepsy shares symptoms and mechanisms with orgasmic epilepsy (spontaneous orgasms in the course of epileptic seizures), musicogenic epilepsy (epileptic seizures triggered by listening to a certain musical piece), and also with Stendhal syndrome (neuropsychiatric disturbances caused when an individual is exposed to large amounts of art) and some autoscopic phenomena (out-of-body experiences that occasionally take place in imminent death situations). In all these events, there are pleasant and affective symptoms which have a great impact on patients.

Prefrontal Cortex Activation Upon a Demanding Virtual Hand-Controlled Task: A New Frontier for Neuroergonomics.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive vascular-based functional neuroimaging technology that can assess, simultaneously from multiple cortical areas, concentration changes in oxygenated-deoxygenated hemoglobin at the level of the cortical microcirculation blood vessels. fNIRS, with its high degree of ecological validity and its very limited requirement of physical constraints to subjects, could represent a valid tool for monitoring cortical responses in the research field of neuroergonomics. In virtual reality (VR) real situations can be replicated with greater control than those obtainable in the real world. Therefore, VR is the ideal setting where studies about neuroergonomics applications can be performed. The aim of the present study was to investigate, by a 20-channel fNIRS system, the dorsolateral/ventrolateral prefrontal cortex (DLPFC/VLPFC) in subjects while performing a demanding VR hand-controlled task (HCT). Considering the complexity of the HCT, its execution should require the attentional resources allocation and the integration of different executive functions. The HCT simulates the interaction with a real, remotely-driven, system operating in a critical environment. The hand movements were captured by a high spatial and temporal resolution 3-dimensional (3D) hand-sensing device, the LEAP motion controller, a gesture-based control interface that could be used in VR for tele-operated applications. Fifteen University students were asked to guide, with their right hand/forearm, a virtual ball (VB) over a virtual route (VROU) reproducing a 42 m narrow road including some critical points. The subjects tried to travel as long as possible without making VB fall. The distance traveled by the guided VB was 70.2 ± 37.2 m. The less skilled subjects failed several times in guiding the VB over the VROU. Nevertheless, a bilateral VLPFC activation, in response to the HCT execution, was observed in all the subjects. No correlation was found between the distance traveled by the guided VB and the corresponding cortical activation. These results confirm the suitability of fNIRS technology to objectively evaluate cortical hemodynamic changes occurring in VR environments. Future studies could give a contribution to a better understanding of the cognitive mechanisms underlying human performance either in expert or non-expert operators during the simulation of different demanding/fatiguing activities.

Prefrontal Cortical Activity During Discourse Processing

Discourse is a commonly occurring and cognitively demanding form of naturalistic communication (e.g., conversation, event narration, personal and fictional narratives, text reading/generation). Because of the prevalence of these communication acts in daily routines (e.g., educational, vocational, and social), disrupted discourse is an important target for treatment of persons with cognitive-communication (CC) disorders (American Speech-Language Hearing Association, 2005). However, there is a paucity of information with regard to the underlying cognitive architecture and processing demands associated with the various forms of discourse in non-brain-injured adults. This is, in part, due to a number of methodological constraints of functional neuroimaging technologies such as functional magnetic resonance imaging that severely limit ecologically typical communication acts such as listening and speaking during scanning. To circumvent these issues, this pilot investigation used functional near infrared spectroscopy (fNIRS) to monitor hemodynamic activity in the prefrontal cortex (PFC) during natural discourse-processing tasks in 13 neurologically healthy adult participants. Task demands were manipulated across a variety of discourse types to elucidate the associated neural and cognitive resources. Results indicate that the comprehension of well-organized discourse text is minimally demanding on the PFC. However, discourse production places a significant burden on the PFC and these processing demands generally reflect the relative complexity of the discourse task. These findings are discussed in terms of potential clinically relevant implications with regard to the elicitation, assessment, and remediation of CC impairments in clinical populations.

Historical Perspectives on the Behavioral Function of the Insula.

The advent of functional neuroimaging technology has seen increased interest in the behavioral function of the region of cerebral cortex known as the insula. Localization of function for this brain region has been slow to develop as it is rarely affected in isolation by naturally occurring structural brain injury and many of the behaviors with which it has been associated are not measured by traditional neuropsychological tests. While it is widely acknowledged that the name originated with Johann-Christian Reil (1809), who is more famous for coining the term Bpsychiatry^ (Binder et al. 2007) little has been written in the English language literature of historical conceptions of the function of insular cortex. One exception was the pioneering electrical stimulation study of patients treated surgically for focal seizures originating within or near insular cortex at the Montreal Neurological Institute (Penfield and Faulk 1955) that noted: BEarly anatomists and physiologists regarded it diversely as a center for speech (Rose 1928), or for taste (von Bechterew 1899)^ (p. 445). Both references are to papers published in German. Rose (1928) was a comparative cytoarchitectonic study of insular cortex in several species including the bat, hedgehog, lemur, baboon, and human. It is known for the identification of so-called von Economo neurons in the insula (Ŝimic and Hof 2015). In contrast, the reference to von Bechterew (1899) is incorrect. As clarified by Soros (This issue), the early conception of the insula as primary taste cortex should be credited to Gorschkow (1901) who conducted ablation studies on dogs in Bechterew’s laboratory. Primary taste cortex remains the behavioral functionmost commonly attributed to the insula inmodern neuroscience textbooks (e.g., Kolb and Whishaw 2014), even though this brain region is now considered to play a muchmore diverse role in human behavior (Gasquoine 2014).

Brain responses to food and weight loss

In this symposium report, we examine how functional neuroimaging has revolutionized the study of human eating behaviour. In the last 20 years, functional magnetic resonance and positron emission tomography techniques have enabled researchers to understand how the human brain regions that control homeostatic and hedonic eating respond to food in physiological and pathological states. Hypothalamic, brainstem, limbic and cortical brain areas form part of a well-co-ordinated brain system that responds to central and peripheral neuronal, hormonal and nutrient signals. Even in physiological conditions, it promotes the consumption of energy-dense food, because this is advantageous in evolutionary terms. Its function is dysregulated in the context of obesity so as to promote weight gain and resist weight loss. Pharmacological and bariatric surgical interventions might be more successful than lifestyle interventions in inducing weight loss and maintenance because, unlike dieting, they reduce not only hunger but also the reward value of food through their actions in homeostatic and hedonic brain regions. Functional neuroimaging is a research tool that cannot be used in isolation; its findings become meaningful and useful only when combined with data from direct measures of eating behaviour. The neuroimaging technology is continuously improving and is expected to contribute further to the in-depth understanding of the obesity phenotype and accelerate the development of more effective and safer treatments for the condition.

Retraction Note: Neuroradiological advances detect abnormal neuroanatomy underlying neuropsychological impairments: the power of PET imaging

Medical imaging has made a major contribution to cerebral dysfunction due to inherited diseases, as well as injuries sustained with modern living, such as car accidents, falling down, and work-related injuries. These injuries, up until the introduction of sensitive techniques such as positron emission tomography (PET), were overlooked because of heavy reliance on structural imaging techniques such as MRI and CT. These techniques are extremely insensitive for dysfunction caused by such underlying disorders. We believe that the use of these highly powerful functional neuroimaging technologies, such as PET, has substantially improved our ability to assess these patients properly in the clinical setting, to determine their natural course, and to assess the efficacy of various interventional detections. As such the contribution from the evolution of PET technology has substantially improved our knowledge and ability over the past 3 decades to help patients who are the victims of serious deficiencies due to these injuries. In particular, in recent years the use of PET/CT and soon PET/MRI will provide the best option for a structure-function relationship in these patients. We are of the belief that the clinical effectiveness of PET in managing these patients can be translated to the use of this important approach in bringing justice to the victims of many patients who are otherwise uncompensated for disorders that they have suffered without any justification. Therefore, legally opposing views about the relevance of PET in the court system by some research groups may not be justifiable. This has proven to be the case in many court cases, where such imaging techniques have been employed either for criminal or financial compensation purposes in the past 2 decades.