Nanofabricated high turn-density spiral coils for on-chip electromagneto-optical conversion.

Circuit-integrated electromagnets are fundamental building blocks for on-chip signal transduction, modulation, and tunability, with specific applications in environmental and biomedical micromagnetometry. A primary challenge for improving performance is pushing quality limitations while minimizing size and fabrication complexity and retaining spatial capabilities. Recent efforts have exploited highly involved three-dimensional synthesis, advanced insulation, and exotic material compositions. Here, we present a rapid nanofabrication process that employs electron beam dose control for high-turn-density diamond-embedded flat spiral coils; these coils achieve efficient on-chip electromagnetic-to-optical signal conversion. Our fabrication process relies on fast 12.3 s direct writing on standard poly(methyl methacrylate) as a basis for the metal lift-off process. Prototypes with 70 micrometer overall diameters and 49-470 nm interturn spacings with corresponding inductances of 12.3-12.8 nH are developed. We utilize optical micromagnetometry to demonstrate that magnetic field generation at the center of the structure effectively correlates with finite element modeling predictions. Further designs based on our process can be integrated with photolithography to broadly enable optical magnetic sensing and spin-based computation.

Wireless agents for brain recording and stimulation modalities.

New sensors and modulators that interact wirelessly with medical modalities unlock uncharted avenues for in situ brain recording and stimulation. Ongoing miniaturization, material refinement, and sensitization to specific neurophysiological and neurochemical processes are spurring new capabilities that begin to transcend the constraints of traditional bulky and invasive wired probes. Here we survey current state-of-the-art agents across diverse realms of operation and evaluate possibilities depending on size, delivery, specificity and spatiotemporal resolution. We begin by describing implantable and injectable micro- and nano-scale electronic devices operating at or below the radio frequency (RF) regime with simple near field transmission, and continue with more sophisticated devices, nanoparticles and biochemical molecular conjugates acting as dynamic contrast agents in magnetic resonance imaging (MRI), ultrasound (US) transduction and other functional tomographic modalities. We assess the ability of some of these technologies to deliver stimulation and neuromodulation with emerging probes and materials that provide minimally invasive magnetic, electrical, thermal and optogenetic stimulation. These methodologies are transforming the repertoire of readily available technologies paired with compatible imaging systems and hold promise toward broadening the expanse of neurological and neuroscientific diagnostics and therapeutics.

Wireless in vivo Recording of Cortical Activity by an Ion-Sensitive Field Effect Transistor.

Wireless brain technologies are empowering basic neuroscience and clinical neurology by offering new platforms that minimize invasiveness and refine possibilities during electrophysiological recording and stimulation. Despite their advantages, most systems require on-board power supply and sizeable transmission circuitry, enforcing a lower bound for miniaturization. Designing new minimalistic architectures that can efficiently sense neurophysiological events will open the door to standalone microscale sensors and minimally invasive delivery of multiple sensors. Here we present a circuit for sensing ionic fluctuations in the brain by an ion-sensitive field effect transistor that detunes a single radiofrequency resonator in parallel. We establish sensitivity of the sensor by electromagnetic analysis and quantify response to ionic fluctuations in vitro. We validate this new architecture in vivo during hindpaw stimulation in rodents and verify correlation with local field potential recordings. This new approach can be implemented as an integrated circuit for wireless in situ recording of brain electrophysiology.

Wireless in vivo Recording of Cortical Activity by an Ion-Sensitive Field Effect Transistor.

Wireless brain technologies are empowering basic neuroscience and clinical neurology by offering new platforms that minimize invasiveness and refine possibilities during electrophysiological recording and stimulation. Despite their advantages, most systems require on-board power supply and sizeable transmission circuitry, enforcing a lower bound for miniaturization. Designing new minimalistic architectures that can efficiently sense neurophysiological events will open the door to standalone microscale sensors and minimally invasive delivery of multiple sensors. Here we present a circuit for sensing ionic fluctuations in the brain by an ion-sensitive field effect transistor that detunes a single radiofrequency resonator in parallel. We establish sensitivity of the sensor by electromagnetic analysis and quantify response to ionic fluctuations in vitro . We validate this new architecture in vivo during hindpaw stimulation in rodents and verify correlation with local field potential recordings. This new approach can be implemented as an integrated circuit for wireless in situ recording of brain electrophysiology.

Enhanced magnetic transduction of neuronal activity by nanofabricated inductors quantified via finite element analysis.

Objective.Methods for the detection of neural signals involve a compromise between invasiveness, spatiotemporal resolution, and the number of neurons or brain regions recorded. Electrode-based probes provide excellent response but usually require transcranial wiring and capture activity from limited neuronal populations. Noninvasive methods such as electroencephalography and magnetoencephalography offer fast readouts of field potentials or biomagnetic signals, respectively, but have spatial constraints that prohibit recording from single neurons. A cell-sized device that enhances neurogenic magnetic fields can be used as anin situsensor for magnetic-based modalities and increase the ability to detect diverse signals across multiple brain regions.Approach.We designed and modeled a device capable of forming a tight electromagnetic junction with single neurons, thereby transducing changes in cellular potential to magnetic field perturbations by driving current through a nanofabricated inductor element.Main results.We present detailed quantification of the device performance using realistic finite element simulations with signals and geometries acquired from patch-clamped neuronsin vitroand demonstrate the capability of the device to produce magnetic signals readable via existing modalities. We compare the magnetic output of the device to intrinsic neuronal magnetic fields (NMFs) and show that the transduced magnetic field intensity from a single neuron is more than three-fold higher at its peak (1.62 nT vs 0.51 nT). Importantly, we report on a large spatial enhancement of the transduced magnetic field output within a typical voxel (40 × 40 × 10µm) over 250 times higher than the intrinsic NMF strength (0.64 nT vs 2.5 pT). We use this framework to perform optimizations of device performance based on nanofabrication constraints and material choices.Significance.Our quantifications institute a foundation for synthesizing and applying electromagnetic sensors for detecting brain activity and can serve as a general method for quantifying recording devices at the single cell level.

Applicability of a national strategy for patient-oriented research to people who use(d) substances: a Canadian experience.

BACKGROUND: Europe and North America are in the grips of a devastating overdose crisis. People who use substances often feel unsafe to access healthcare due to fears of stigma, blame, judgement, poor treatment, or other repercussions. As a result, they often avoid, delay, or leave care, resulting in premature death and missed opportunities for care. Internationally, there have been concerted efforts to move towards patient-engaged research to enhance the quality of health care systems and services. In Canada, the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR) initiative promotes engagement of patients as active partners in health care research. As part of a community based patient oriented research project, we critically analyze the SPOR framework to provide insights into what constitutes safer research with people who use(d) substances. METHODS: We undertook a two-stage process that began with a review of community based research principles and the SPOR framework. At the second stage, we undertook a qualitative descriptive study employing focus groups to generate description of the adequacy and appropriateness of the SPOR framework for guiding research with people who use(d) substances on four key dimensions (patient engagement, guiding principles, core areas of engagement and benefits). The data were analyzed using qualitative content analysis to identify key issues and insights. RESULTS: While the SPOR framework includes a range of patient roles, principles and areas for engagement, there are issues and gaps related to essential elements of safe patient-oriented research for people who use substances. These include an individualized focus on patients as partners, lack of recognition of community benefits, power imbalances and distrust due to systemic stigma, engagement as one way capacity building and learning, and lack of accountability for taking action on research findings. CONCLUSIONS: Given the extent of stigma in health care and the ongoing illicit drug policy crisis, strategies for enhancing equitable Patient-Oriented Research (POR) include shifting language from patient partners to community researchers, recognizing power inequities and adding trust and equity as core POR principles including pay equity. Employing community based participatory research as a POR methodology allows the lead researchers to fully engage community throughout the research process, enhances community benefits and accountability for action.

Three-dimensional, multifunctional neural interfaces for cortical spheroids and engineered assembloids.

Three-dimensional (3D), submillimeter-scale constructs of neural cells, known as cortical spheroids, are of rapidly growing importance in biological research because these systems reproduce complex features of the brain in vitro. Despite their great potential for studies of neurodevelopment and neurological disease modeling, 3D living objects cannot be studied easily using conventional approaches to neuromodulation, sensing, and manipulation. Here, we introduce classes of microfabricated 3D frameworks as compliant, multifunctional neural interfaces to spheroids and to assembloids. Electrical, optical, chemical, and thermal interfaces to cortical spheroids demonstrate some of the capabilities. Complex architectures and high-resolution features highlight the design versatility. Detailed studies of the spreading of coordinated bursting events across the surface of an isolated cortical spheroid and of the cascade of processes associated with formation and regrowth of bridging tissues across a pair of such spheroids represent two of the many opportunities in basic neuroscience research enabled by these platforms.

The effect of dietary supplementation with high- or low-dose omega-3 fatty acid on inflammatory pathology after traumatic brain injury in rats.

This study investigated dietary supplementation as a prophylactic for neuroinflammation following traumatic brain injury (TBI) in a preclinical model. Adult male Sprague-Dawley rats received 30 days of supplementation with either water or two dietary supplements. The first consisted of high-dose omega-3 fatty acid (O3FA) (supplement A) along with vitamin D3 and vitamin E. The second had the same ingredients at different doses with an addition of cannabidiol (supplement B). Rats were subjected to an impact TBI and then euthanized 7 days post-injury and neuroinflammation quantified by histological detection of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and CD68, a marker of microglial activity. There was a trend toward increased GFAP staining in injured, unsupplemented animals as compared to sham, unsupplemented animals, consistent with increased activation of astrocytes in response to trauma which was reversed by supplement A but not by supplement B. The pattern of CD68 staining across groups was similar to that of GFAP staining. There was a trend toward an increase in the injured unsupplemented group, relative to sham which was reversed by supplement A but not by supplement B. CD68 staining in injured animals was concentrated in the perivascular domain. The consistency between trends across different measures of neuroinflammation showing benefits of high-dose O3FA supplementation following TBI suggests that the observed effects are real. These findings are preliminary, but they justify further study to determine the functional benefits associated with improvements in histological outcomes and understand associated dose-response curves.

Defining culturally safe primary care for people who use substances: a participatory concept mapping study.

BACKGROUND: People who use substances experience high levels of substance-related stigma, both within and outside of health care settings, which can prevent people from help-seeking and contribute further to health inequities. Recognizing and respecting how political, social, economic, and historical conditions influence health and health care, cultural safety, with origins in addressing Indigenous racism, is a potential strategy for mitigating stigma and marginalization in health care. Using a participatory research approach, we applied the concept of cultural safety to develop a model of safe primary care from the perspective of people who use substances. METHODS: People who use or used substances were involved in all phases of the research and led data collection. Study participants (n = 75) were 42.5 years old on average; half identified as female and one quarter as Indigenous. All were currently using or had previous experience with substances (alcohol and/or other drugs) and were recruited through two local peer-run support agencies. Concept mapping with hierarchical cluster analysis was used to develop the model of safe primary care, with data collected over three rounds of focus groups. RESULTS: Participants identified 73 unique statements to complete the focus prompt: "I would feel safe going to the doctor if …" The final model consisted of 8 clusters that cover a wide range of topics, from being treated with respect and not being red-flagged for substance use, to preserving confidentiality, advocacy for good care and systems change, and appropriate accommodations for anxiety and the effects of poverty and criminalization. CONCLUSIONS: Developing a definition of safe care (from the patient perspective) is the necessary first step in creating space for positive interactions and, in turn, improve care processes. This model provides numerous concrete suggestions for providers, as well as serving as starting point for the development of interventions designed to foster system change.

Impact of overdose prevention sites during a public health emergency in Victoria, Canada.

The primary objective of this study was to examine the impacts associated with implementation of overdose preventions sites (OPSs) in Victoria, Canada during a declared provincial public health overdose emergency. A rapid case study design was employed with three OPSs constituting the cases. Data were collected through semi-structured interviews with 15 staff, including experiential staff, and 12 service users. Theoretically, we were informed by the Consolidated Framework for Implementation Research. This framework, combined with a case study design, is well suited for generating insight into the impacts of an intervention. Zero deaths were identified as a key impact and indicator of success. The implementation of OPSs increased opportunities for early intervention in the event of an overdose, reducing trauma for staff and service users, and facilitated organizational transitions from provision of safer supplies to safer spaces. Providing a safer space meant drug use no longer needed to be concealed, with the effect of mitigating drug related stigma and facilitating a shift from shame and blame to increasing trust and development of relationships with increased opportunities to provide connections to other services. These impacts were achieved with few new resources highlighting the commitment of agencies and harm reduction workers, particularly those with lived experience, in achieving beneficial impacts. Although mitigating harms of overdose, OPSs do not address the root problem of an unsafe drug supply. OPSs are important life-saving interventions, but more is needed to address the current contamination of the illicit drug supply including provision of a safer supply.

Characterization of neurite dystrophy after trauma by high speed structured illumination microscopy and lattice light sheet microscopy.

BACKGROUND: Unbiased screening studies have repeatedly identified actin-related proteins as one of the families of proteins most influenced by neurotrauma. Nevertheless, the status quo model of cytoskeletal reorganization after neurotrauma excludes actin and incorporates only changes in microtubules and intermediate filaments. Actin is excluded in part because it is difficult to image with conventional techniques. However, recent innovations in fluorescent microscopy provide an opportunity to image the actin cytoskeleton at super-resolution resolution in living cells. This study applied these innovations to an in vitro model of neurotrauma. NEW METHOD: New methods are introduced for traumatizing neurons before imaging them with high speed structured illumination microscopy or lattice light sheet microscopy. Also, methods for analyzing structured illumination microscopy images to quantify post-traumatic neurite dystrophy are presented. RESULTS: Human induced pluripotent stem cell-derived neurons exhibited actin organization typical of immature neurons. Neurite dystrophy increased after trauma but was not influenced by jasplakinolide treatment. The F-actin content of dystrophies varied greatly from one dystrophy to another. COMPARISON WITH EXISTING METHODS: In contrast to fixation dependent methods, these methods capture the evolution of the actin cytoskeleton over time in a living cell. In contrast to prior methods based on counting dystrophies, this quantification scheme parameterizes the severity of a given dystrophy as it evolves from a local swelling to an almost-perfect spheroid that threatens to transect the neurite. CONCLUSIONS: These methods can be used to investigate genetic factors and therapeutic interventions that modulate the course of neurite dystrophy after trauma.

High-density functional-RNA arrays as a versatile platform for studying RNA-based interactions.

We are just beginning to unravel the myriad of interactions in which non-coding RNAs participate. The intricate RNA interactome is the foundation of many biological processes, including bacterial virulence and human disease, and represents unexploited resources for the development of potential therapeutic interventions. However, identifying specific associations of a given RNA from the multitude of possible binding partners within the cell requires robust high-throughput systems for their rapid screening. Here, we present the first demonstration of functional-RNA arrays as a novel platform technology designed for the study of such interactions using immobilized, active RNAs. We have generated high-density RNA arrays by an innovative method involving surface-capture of in vitro transcribed RNAs. This approach has significant advantages over existing technologies, particularly in its versatility in regards to binding partner character. Indeed, proof-of-principle application of RNA arrays to both RNA-small molecule and RNA-RNA pairings is demonstrated, highlighting their potential as a platform technology for mapping RNA-based networks and for pharmaceutical screening. Furthermore, the simplicity of the method supports greater user-accessibility over currently available technologies. We anticipate that functional-RNA arrays will find broad utility in the expanding field of RNA characterization.

Method for High Speed Stretch Injury of Human Induced Pluripotent Stem Cell-derived Neurons in a 96-well Format.

Traumatic brain injury (TBI) is a major clinical challenge with high morbidity and mortality. Despite decades of pre-clinical research, no proven therapies for TBI have been developed. This paper presents a novel method for pre-clinical neurotrauma research intended to complement existing pre-clinical models. It introduces human pathophysiology through the use of human induced pluripotent stem cell-derived neurons (hiPSCNs). It achieves loading pulse duration similar to the loading durations of clinical closed head impact injury. It employs a 96-well format that facilitates high throughput experiments and makes efficient use of expensive cells and culture reagents. Silicone membranes are first treated to remove neurotoxic uncured polymer and then bonded to commercial 96-well plate bodies to create stretchable 96-well plates. A custom-built device is used to indent some or all of the well bottoms from beneath, inducing equibiaxial mechanical strain that mechanically injures cells in culture in the wells. The relationship between indentation depth and mechanical strain is determined empirically using high speed videography of well bottoms during indentation. Cells, including hiPSCNs, can be cultured on these silicone membranes using modified versions of conventional cell culture protocols. Fluorescent microscopic images of cell cultures are acquired and analyzed after injury in a semi-automated fashion to quantify the level of injury in each well. The model presented is optimized for hiPSCNs but could in theory be applied to other cell types.

Stretch Injury of Human Induced Pluripotent Stem Cell Derived Neurons in a 96 Well Format.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity with limited therapeutic options. Traumatic axonal injury (TAI) is an important component of TBI pathology. It is difficult to reproduce TAI in animal models of closed head injury, but in vitro stretch injury models reproduce clinical TAI pathology. Existing in vitro models employ primary rodent neurons or human cancer cell line cells in low throughput formats. This in vitro neuronal stretch injury model employs human induced pluripotent stem cell-derived neurons (hiPSCNs) in a 96 well format. Silicone membranes were attached to 96 well plate tops to create stretchable, culture substrates. A custom-built device was designed and validated to apply repeatable, biofidelic strains and strain rates to these plates. A high content approach was used to measure injury in a hypothesis-free manner. These measurements are shown to provide a sensitive, dose-dependent, multi-modal description of the response to mechanical insult. hiPSCNs transition from healthy to injured phenotype at approximately 35% Lagrangian strain. Continued development of this model may create novel opportunities for drug discovery and exploration of the role of human genotype in TAI pathology.

An improved method for surface immobilisation of RNA: application to small non-coding RNA-mRNA pairing.

Characterisation of RNA and its intermolecular interactions is increasing in importance as the inventory of known RNA functions continues to expand. RNA-RNA interactions are central to post-transcriptional gene regulation mechanisms in bacteria, and the interactions of bacterial small non-coding RNAs (sRNAs) with their mRNA targets are the subject of much current research. The technology of surface plasmon resonance (SPR) is an attractive approach to studying these interactions since it is highly sensitive, and allows interaction measurements to be recorded in real-time. Whilst a number of approaches exist to label RNAs for surface-immobilisation, the method documented here is simple, quick, efficient, and utilises the high-affinity streptavidin-biotin interaction. Specifically, we ligate a biotinylated nucleotide to the 3' end of RNA using T4 RNA ligase. Although this is a previously recognised approach, we have optimised the method by our discovery that the incorporation of four or more adenine nucleotides at the 3' end of the RNA (a poly-A-tail) is required in order to achieve high ligation efficiencies. We use this method within the context of investigating small non-coding RNA (sRNA)-mRNA interactions through the application of surface technologies, including quantitative SPR assays. We first focus on validating the method using the recently characterised Escherichia coli sRNA-mRNA pair, MicA-ompA, specifically demonstrating that the addition of the poly-A-tail to either RNA does not affect its subsequent binding interactions with partner molecules. We then apply this method to investigate the novel interactions of a Vibrio cholerae Qrr sRNA with partner mRNAs, hapR and vca0939; RNA-RNA pairings that are important in mediating pathogenic virulence. The calculated binding parameters allow insights to be drawn regarding sRNA-mRNA interaction mechanisms.

Hfq binding changes the structure of Escherichia coli small noncoding RNAs OxyS and RprA, which are involved in the riboregulation of rpoS.

OxyS and RprA are two small noncoding RNAs (sRNAs) that modulate the expression of rpoS, encoding an alternative sigma factor that activates transcription of multiple Escherichia coli stress-response genes. While RprA activates rpoS for translation, OxyS down-regulates the transcript. Crucially, the RNA binding protein Hfq is required for both sRNAs to function, although the specific role played by Hfq remains unclear. We have investigated RprA and OxyS interactions with Hfq using biochemical and biophysical approaches. In particular, we have obtained the molecular envelopes of the Hfq-sRNA complexes using small-angle scattering methods, which reveal key molecular details. These data indicate that Hfq does not substantially change shape upon complex formation, whereas the sRNAs do. We link the impact of Hfq binding, and the sRNA structural changes induced, to transcript stability with respect to RNase E degradation. In light of these findings, we discuss the role of Hfq in the opposing regulatory functions played by RprA and OxyS in rpoS regulation.

The impact of GPX1 on the association of groundwater selenium and depression: a Project FRONTIER study.

BACKGROUND: Prior animal model and human-based studies have linked selenium concentrations to decreased risk for depression; however, this work has not focused on household groundwater levels or specific depressive symptoms. The current study evaluated the link between groundwater selenium levels and depression. We also sought to determine if a functional polymorphism in the glutathione peroxidase 1 (GPX1) gene impacted this link. METHODS: We used a cross-sectional design to analyze data from 585 participants (183 men and 402 women) from Project FRONTIER, a study of rural health in West Texas. Residential selenium concentrations were estimated using Geospatial Information System (GIS) analyses. Linear regression models were created using Geriatric Depression Scale (GDS-30) total and subfactor scores as outcome variables and selenium concentrations as predictor variables. Analyses were re-run after stratification of the sample on GPX1 Pro198Leu genotype (rs1050454). RESULTS: Selenium levels were significantly and negatively related to all GDS and subfactor scores accounting for up to 17% of the variance beyond covariates. Selenium was most strongly protective against depression among homozygous carriers of the C allele at the Pro198Leu polymorphism of the GPX1 gene. Analyses also point towards a gene-environmental interaction between selenium exposure and GPX1 polymorphism. CONCLUSION: Our results support the link between groundwater selenium levels and decreased depression symptoms. These findings also highlight the need to consider the genetics of the glutathione peroxidase system when examining this relationship, as variation in the GPX1 gene is related to depression risk and significantly influences the protective impact of selenium, which is indicative of a gene-environment interaction.

Characterization of MicA interactions suggests a potential novel means of gene regulation by small non-coding RNAs.

MicA is a small non-coding RNA that regulates ompA mRNA translation in Escherichia coli. MicA has an inhibitory function, base pairing to the translation initiation region of target mRNAs through short sequences of complementarity, blocking their ribosome-binding sites. The MicA structure contains two stem loops, which impede its interaction with target mRNAs, and it is thought that the RNA chaperone protein Hfq, known to be involved in MicA regulation of ompA, may structurally remodel MicA to reveal the ompA-binding site for cognate pairing. To further characterize these interactions, we undertook biochemical and biophysical studies using native MicA and a 'stabilized' version, modified to mimic the conformational state of MicA where the ompA-binding site is exposed. Our data corroborate two proposed roles for Hfq: first, to bring both MicA and ompA into close proximity, and second, to restructure MicA to allow exposure of the ompA-binding site for pairing, thereby demonstrating the RNA chaperone function of Hfq. Additionally, at accumulated MicA levels, we identified a Mg(2+)-dependent self-association that occludes the ompA-recognition region. We discuss the potential contribution of an Mg(2+)-mediated conformational switch of MicA for the regulation of MicA function.

Are boys and girls that different? An analysis of traumatic brain injury in children.

INTRODUCTION: The Phillips Report on traumatic brain injury (TBI) in Ireland found that injury was more frequent in men and that gender differences were present in childhood. This study determined when gender differences emerge and examined the effect of gender on the mechanism of injury, injury type and severity and outcome. METHODS: A national prospective, observational study was conducted over a 2-year period. All patients under 17 years of age referred to a neurosurgical service following TBI were included. Data on patient demographics, events surrounding injury, injury type and severity, patient management and outcome were collected from 'on-call' logbooks and neurosurgical admissions records. RESULTS: 342 patients were included. Falls were the leading cause of injury for both sexes. Boys' injuries tended to involve greater energy transfer and involved more risk-prone behaviour resulting in a higher rate of other (non-brain) injury and a higher mortality rate. Intentional injury occurred only in boys. While injury severity was similar for boys and girls, significant gender differences in injury type were present; extradural haematomas were significantly higher in boys (p=0.014) and subdural haematomas were significantly higher in girls (p=0.011). Mortality was 1.8% for girls and 4.3% for boys. CONCLUSIONS: Falls were responsible for most TBI, the home is the most common place of injury and non-operable TBI was common. These findings relate to all children. Significant gender differences exist from infancy. Boys sustained injuries associated with a greater energy transfer, were less likely to use protective devices and more likely to be injured deliberately. This results in a different pattern of injury, higher levels of associated injury and a higher mortality rate.

The contribution of retrospective memory, attention and executive functions to the prospective and retrospective components of prospective memory following TBI.

PRIMARY OBJECTIVE: Despite the prevalence of prospective memory (PM) problems, relatively little is known about the processes underlying impairment following TBI. This study sought to examine PM performance, using a multiple-task, multiple-response video-based paradigm in which initial encoding of the cue-action associations was ensured (Video-Assessment of Prospective Memory; VAPM). RESEARCH DESIGN: VAPM was designed to allow easy identification of reasons for failure (i.e. cue detection and/or specific action retrieval). Patients with moderate/severe TBI (n = 32) and matched controls (n = 16) also completed standardized neuropsychological assessment including evaluation of episodic retrospective memory (RM), attention, information processing, executive functions and mood. MAIN OUTCOMES AND RESULTS: As a group, those with TBI were impaired on PM tasks with 50% failing to complete at least 2/6 required tasks despite near perfect performance by controls. Individual profile analyses revealed different reasons for impairment, with RM contributing significantly to both the prospective and retrospective components. This was supported by correlational analyses illustrating a significant relationship between cue detection and RM measures, in addition to measures of executive functions and attention. CONCLUSIONS: The contribution of RM to both components of PM, along with the finding of heterogeneity in performance among participants have important implications for theoretical understanding and clinical practice.