Human anterior insula signals salience and deviations from expectations via bursts of beta oscillations.

Functional imaging studies indicate that the insula encodes the salience of stimuli and deviations from expectations, signals that can mobilize cognitive resources and facilitate learning. However, there is no information about the physiological underpinnings of these phenomena beyond changing BOLD signals. To shed light on this question, we analyzed intracerebral local field potentials (LFPs) in five patients with epilepsy of both genders performing a virtual reality task that featured varying odds of monetary rewards and losses. Upon outcome disclosure, the anterior (but not the posterior) insula generated bursts of beta oscillations whose amplitudes were lower for neutral than positive and negative outcomes, consistent with a salience signal. Moreover, beta burst power was higher when outcomes deviated from expectations, whether the outcome was better or worse than expected, indicating that the insula provides an unsigned prediction error signal. Last, in relation to insular beta bursts, many higher-order cortical areas exhibited robust changes in LFP activity that ranged from spectrally nonspecific or differentiated increases in gamma power to bursts of beta activity that closely resembled the insular beta bursts themselves. Critically, the activity of these other cortical regions was more closely tied in time to insular bursts than task events, suggesting that they are associated with particularly significant cognitive phenomena. Overall, our findings suggest that the insula signals salience and prediction errors via amplitude modulations of beta bursts, which coincide with the near simultaneous recruitment of vast cortical territories.NEW & NOTEWORTHY Functional imaging studies indicate that the anterior insula encodes salience and deviations from expectations. Beyond changing BOLD signals, however, the physiological underpinnings of these signals are unknown. By recording local field potentials in patients with epilepsy, we found that the anterior insula generates large bursts of beta oscillations whose amplitude is modulated by the salience of outcomes and deviations from expectations. Moreover, insular beta bursts coincide with the activation of many high-order cortical areas.

The Oscillatory ReConstruction Algorithm adaptively identifies frequency bands to improve spectral decomposition in human and rodent neural recordings.

Neural oscillations are routinely analyzed using methods that measure activity in fixed frequency bands (e.g., alpha, 8-12 Hz), although the frequency of neural signals varies within and across individuals based on numerous factors including neuroanatomy, behavioral demands, and species. Furthermore, band-limited activity is an often assumed, typically unmeasured model of neural activity, and band definitions vary considerably across studies. Together, these factors mask individual differences and can lead to noisy spectral estimates and interpretational problems when linking electrophysiology to behavior. We developed the Oscillatory ReConstruction Algorithm ("ORCA"), an unsupervised method to measure the spectral characteristics of neural signals in adaptively identified bands, which incorporates two new methods for frequency band identification. ORCA uses the instantaneous amplitude, phase, and frequency of activity in each band to reconstruct the signal and directly quantify spectral decomposition performance using each of four different models. To reduce researcher bias, ORCA provides spectral estimates derived from the best model and requires minimal hyperparameterization. Analyzing human scalp EEG data during eyes-open and eyes-closed "resting" conditions, we first identify variability in the frequency content of neural signals across subjects and electrodes. We demonstrate that ORCA significantly improves spectral decomposition compared with conventional methods and captures the well-known increase in low-frequency activity during eye closure in electrode- and subject-specific frequency bands. We further illustrate the utility of our method in rodent CA1 recordings. ORCA is a novel analytic tool that allows researchers to investigate how nonstationary neural oscillations vary across behaviors, brain regions, individuals, and species.NEW & NOTEWORTHY Neural oscillations show substantial variability within and across individuals and brain regions, yet most existing studies analyze oscillations using canonical, fixed-frequency bands. Thus, there is an ongoing need for tools that capture oscillatory variability in neural signals. Toward this end, Oscillatory ReConstruction Algorithm is a novel and adaptive analytic tool that allows researchers to measure neural oscillations with more precision and less researcher bias.

Context-dependent spatially periodic activity in the human entorhinal cortex.

The spatially periodic activity of grid cells in the entorhinal cortex (EC) of the rodent, primate, and human provides a coordinate system that, together with the hippocampus, informs an individual of its location relative to the environment and encodes the memory of that location. Among the most defining features of grid-cell activity are the 60° rotational symmetry of grids and preservation of grid scale across environments. Grid cells, however, do display a limited degree of adaptation to environments. It remains unclear if this level of environment invariance generalizes to human grid-cell analogs, where the relative contribution of visual input to the multimodal sensory input of the EC is significantly larger than in rodents. Patients diagnosed with nontractable epilepsy who were implanted with entorhinal cortical electrodes performing virtual navigation tasks to memorized locations enabled us to investigate associations between grid-like patterns and environment. Here, we report that the activity of human entorhinal cortical neurons exhibits adaptive scaling in grid period, grid orientation, and rotational symmetry in close association with changes in environment size, shape, and visual cues, suggesting scale invariance of the frequency, rather than the wavelength, of spatially periodic activity. Our results demonstrate that neurons in the human EC represent space with an enhanced flexibility relative to neurons in rodents because they are endowed with adaptive scalability and context dependency.

Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders.

OBJECTIVE: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016. DESIGN: Here we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses. CONCLUSION: Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

In vivo measurements of limbic glutamate and GABA concentrations in epileptic patients during affective and cognitive tasks: A microdialysis study.

Limbic system structures such as the amygdala (AMG) and the hippocampus (HIPP) are involved in affective and cognitive processing. However, because of the limitations in noninvasive technology, absolute concentrations of the neurotransmitters underlying limbic system engagement are not known. Here, we report changes in the concentrations of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) in the HIPP and the AMG of patients with nonlesional temporal lobe epilepsy undergoing surgery for intracranial subdural and depth electrode implantation. We utilized an in-vivo microdialysis technique while subjects were engaged in cognitive tasks with or without emotional content. The performance of an emotion learning task (EmoLearn) was associated with a significant increase in the concentration of glutamate in the HIPP when images with high valence content were processed, as compared to its concentration while processing images with low valence. In addition, significantly decreased levels of glutamate were found in the AMG when images with predominantly low valence content were processed, as compared to its concentration at baseline. The processing of face stimuli with anger/fear content (FaceMatch task) was accompanied with significantly decreased concentrations of GABA in the AMG and HIPP compared to its levels at the baseline. The processing of shapes on the other hand was accompanied with a significantly decreased concentration of the glutamate in the AMG as well as in the HIPP compared to the baseline. Finally, the performance of a nondeclarative memory task (weather prediction task-WPT) was associated with relatively large and opposite changes in the GABA levels compared to the baseline in the AMG (decrease) and the HIPP (increase). These data are relevant for showing an involvement of the amygdala and the hippocampus in emotional processing and provide additional neurochemical clues towards a more refined model of the functional circuitry of the human limbic system.

Processing of auditory feedback in perisylvian and insular cortex.

When we speak, we not only make movements with our mouth, lips, and tongue, but we also hear the sound of our own voice. Thus, speech production in the brain involves not only controlling the movements we make, but also auditory and sensory feedback. Auditory responses are typically suppressed during speech production compared to perception, but how this manifests across space and time is unclear. Here we recorded intracranial EEG in seventeen pediatric, adolescent, and adult patients with medication-resistant epilepsy who performed a reading/listening task to investigate how other auditory responses are modulated during speech production. We identified onset and sustained responses to speech in bilateral auditory cortex, with a selective suppression of onset responses during speech production. Onset responses provide a temporal landmark during speech perception that is redundant with forward prediction during speech production. Phonological feature tuning in these "onset suppression" electrodes remained stable between perception and production. Notably, the posterior insula responded at sentence onset for both perception and production, suggesting a role in multisensory integration during feedback control.

Phase coding of spatial representations in the human entorhinal cortex.

The grid-like activity pattern of cells in the mammalian entorhinal cortex provides an internal reference frame for allocentric self-localization. The same neurons maintain robust phase couplings with local field oscillations. We found that neurons of the human entorhinal cortex display consistent spatial and temporal phase locking between spikes and slow gamma band local field potentials (LFPs) during virtual navigation. The phase locking maintained an environment-specific map over time. The phase tuning of spikes to the slow gamma band LFP revealed spatially periodic phase grids with environment-dependent scaling and consistent alignment with the environment. Using a Bayesian decoding model, we could predict the avatar's position with near perfect accuracy and, to a lesser extent, that of heading direction as well. These results imply that the phase of spikes relative to spatially modulated gamma oscillations encode allocentric spatial positions. We posit that a joint spatiotemporal phase code can implement the combined neural representation of space and time in the human entorhinal cortex.

Health-related quality of life among African Americans with multiple sclerosis.

OBJECTIVE: Identify factors associated with health-related quality of life (HRQOL) among African Americans with multiple sclerosis (MS). DESIGN: A survey cohort was recruited from the Registry of the North American Research Committee On Multiple Sclerosis (NARCOMS) Project. Data were collected from 131 African Americans with MS, with 111 participants providing all data needed for analyses of physical domains and 103 participants providing all data needed for analyses of mental health domains of HRQOL using multiple linear regression models. RESULTS: Worsening MS symptoms and greater interference of MS symptoms with daily life were associated with significantly lower physical domains of HRQOL. Respondents reporting that their principal care physician who had a greater understanding of how MS symptoms affected their daily lives tended to have significantly higher physical dimensions of HRQOL. A previous diagnosis of depression and agreement that participants were sometimes embarrassed in public due to their MS were associated with significantly lower mental health aspects of HRQOL. CONCLUSION: Findings highlight the importance of the positive association between the level of understanding by the principal care physician of how MS symptoms affect the lives of African Americans and their physical dimensions of HRQOL. Physicians treating African Americans with MS need to understand how MS symptoms impact the life of these patients as a key component to providing culturally competent care.

A Platform for Cognitive Monitoring of Neurosurgical Patients During Hospitalization.

Intracranial recordings in epilepsy patients are increasingly utilized to gain insight into the electrophysiological mechanisms of human cognition. There are currently several practical limitations to conducting research with these patients, including patient and researcher availability and the cognitive abilities of patients, which limit the amount of task-related data that can be collected. Prior studies have synchronized clinical audio, video, and neural recordings to understand naturalistic behaviors, but these recordings are centered on the patient to understand their seizure semiology and thus do not capture and synchronize audiovisual stimuli experienced by patients. Here, we describe a platform for cognitive monitoring of neurosurgical patients during their hospitalization that benefits both patients and researchers. We provide the full specifications for this system and describe some example use cases in perception, memory, and sleep research. We provide results obtained from a patient passively watching TV as proof-of-principle for the naturalistic study of cognition. Our system opens up new avenues to collect more data per patient using real-world behaviors, affording new possibilities to conduct longitudinal studies of the electrophysiological basis of human cognition under naturalistic conditions.

Comparisons of Latinos, African Americans, and Caucasians with multiple sclerosis.

OBJECTIVE: Identify racial/ethnic differences among people with multiple sclerosis (MS) in demographics, MS disease characteristics, and health services received. PARTICIPANTS: We analyzed enrollment data from the Registry of the North American Research Committee on Multiple Sclerosis (NARCOMS) Project to compare 26,967 Caucasians, 715 Latinos, and 1,313 African Americans with MS. DESIGN: Racial/ethnic analyses of NARCOMS data focused on descriptive characteristics, using ANOVA and chi-square tests to identify significant differences in means and frequencies among Caucasians, Latinos, and African Americans. RESULTS: We identified significant racial/ethnic differences in demographics, MS disease characteristics, and treatments. Caucasians were older when first MS symptoms were experienced (30.1 years) and at MS diagnosis (37.4 years) than Latinos (28.6 years and 34.5 years) or African Americans (29.8 years and 35.8 years). Larger proportions of Latinos reported normal function for mobility and bladder/bowel function compared to Caucasians. Larger proportions of Latinos (44.2 percent) and African Americans (45.8 percent) reported at least mild depression compared to only 38.7 percent of Caucasians. Larger proportions of Latinos never received mental health care or care from rehabilitation specialists than Caucasians or African Americans. A larger proportion of African Americans had never been treated by a neurologist specializing in MS and a smaller proportion of African Americans received care at a MS clinic than Caucasians or Latinos. CONCLUSIONS: Our findings highlight the need for future analyses to determine if age, disease duration, MS symptoms, and disability levels provide additional insights into racial/ethic differences in the use of MS-related providers.

Informal care giving to more disabled people with multiple sclerosis.

PURPOSE: About 30% of the people with multiple sclerosis (MS) require some form of home care assistance and 80% of that assistance is provided by informal or unpaid care givers. This study focusses on the care givers for 530 more disabled people with MS, with the objective of learning more about informal care giving to people with greater dependency and need for assistance. METHOD: The data presented in this study were collected in a national survey of 530 people who provided informal care to more disabled people with MS. RESULTS: Almost half of these care givers reported that they provided more than 20 h of care per week to the person with MS, with more than 9 in 10 shopping for groceries, doing indoor housework, preparing meals or providing transportation for the person with MS. More than 4 in 10 employed care givers reduced the amount of time worked in the previous 12 months because of their care giving responsibilities. Although more than half of the MS care givers in our study reported that care giving was demanding, time consuming or challenging, about 90% of these MS care givers were happy that they could help. About two in three of these MS care givers found that care giving was rewarding, with more than 8 in 10 proud of the care they provided. CONCLUSIONS: More than a quarter of the informal care givers to people with MS thought they would benefit from treatment or counselling provided by mental health professionals. Not only it is necessary to provide access to mental health services for people with MS, but it is also important to assure that their informal care givers also have access to appropriate mental health care, given the scope of their care giving responsibilities.

Volume-Staged CyberKnife Stereotactic Radiosurgery for Treatment of Drug-Resistant Epilepsy for a Spetzler-Martin Grade V Arteriovenous Malformation: A Case Report and Review of the Literature.

BACKGROUND: Evidence to support the use of stereotactic radiosurgery (SRS) in the treatment of epilepsy secondary to cerebral arteriovenous malformations (AVMs) is emerging. However, these studies have not clearly demonstrated the use of SRS in the treatment of drug-resistant epilepsy (DRE) in high Spetzler-Martin grade (IV-V) AVMs. CASE DESCRIPTION: We present a 48-year-old woman with DRE secondary to a Spetzler-Martin grade V cerebral AVM. She was treated with volume-staged SRS (VS-SRS) and achieved near-complete resolution of her seizures with incomplete obliteration of the AVM. Six years after treatment, she has experienced no serious complications. CONCLUSIONS: VS-SRS successfully controlled seizures (Engel Outcome Measure of 1A) in a patient with intractable, DRE secondary to a high-grade cerebral AVM.

Unifying Pathophysiological Explanations for Sports-Related Concussion and Concussion Protocol Management: Literature Review.

OBJECTIVE: There is a plethora of theories about the pathophysiology behind a sport-related concussion. In this review of the literature, the authors evaluated studies on the pathophysiology of sport-related concussion and professional athlete return-to-play guidelines. The goal of this article is to summarize the most common hypotheses for sport-related concussion, evaluate if there are common underlying mechanisms, and determine if correlations are seen between published mechanisms and the most current return-to-play recommendations. METHODS: Two authors selected papers from the past 5 years for literature review involving discussion of sport-related concussion and pathophysiology, pathology, or physiology of concussion using mutually agreed-upon search criteria. After the articles were filtered based on search criteria, pathophysiological explanations for concussion were organized into tables. Following analysis of pathophysiology, concussion protocols and return-to-play guidelines were obtained via a Google search for the major professional sports leagues and synthesized into a summary table. RESULTS: Out of 1112 initially identified publications, 53 met our criteria for qualitative analysis. The 53 studies revealed 5 primary neuropathological explanations for sport-related concussion, regardless of the many theories talked about in the different papers. These 5 explanations, in order of predominance in the articles analyzed, were (1) tauopathy, (2) white matter changes, (3) neural connectivity alterations, (4) reduction in cerebral perfusion, and (5) gray matter atrophy. Pathology may be sport specific: white matter changes are seen in 47% of football reports, tauopathy is seen in 50% of hockey reports, and soccer reports 50% tauopathy as well as 50% neural connectivity alterations. Analysis of the return-to-play guidelines across professional sports indicated commonalities in concussion management despite individual policies. CONCLUSIONS: Current evidence on pathophysiology for sport-related concussion does not yet support one unifying mechanism, but published hypotheses may potentially be simplified into 5 primary groups. The unification of the complex, likely multifactorial mechanisms for sport-related concussion to a few common explanations, combined with unique findings within individual sports presented in this report, may help filter and link concussion pathophysiology in sport. By doing so, the authors hope that this review will help guide future concussion research, treatment, and management.

Patient perceptions of multiple sclerosis-related care: comparisons by practice specialty of principal care physician.

Do people with multiple sclerosis who receive the majority of their care from neurologists perceive access to and quality of their care differently than people receiving their care from medical internists, family/general practitioners, and other types of physicians? The objective of this study is to identify any patient-identified differences in MS-related care by the practice specialty of the principal care physician, as well as differences by practice specialty in satisfaction with access to physician services and differences in patient perceptions of quality. Data were collected by surveying 1,518 people with MS throughout the United States and grouped by practice specialty of principal care physician (neurologist, internal medicine, family/general practice, and other physicians). Significant differences were observed by practice specialty of the principal care physician in physician understanding of various aspects of MS, satisfaction with access to MS-focused care, and quality of MS-focused care, with neurologists associated with better patient perceptions. Patients consider MS-related care superior when it is delivered by neurologists compared to MS patients receiving care from medical internists, family/general practitioners, and other physicians.

Thoracic, Lumbar, and Sacral Pedicle Screw Placement Using Stryker-Ziehm Virtual Screw Technology and Navigated Stryker Cordless Driver 3: Technical Note.

OBJECT: Utilization of pedicle screws (PS) for spine stabilization is common in spinal surgery. With reliance on visual inspection of anatomical landmarks prior to screw placement, the free-hand technique requires a high level of surgeon skill and precision. Three-dimensional (3D), computer-assisted virtual neuronavigation improves the precision of PS placement and minimization steps. METHODS: Twenty-three patients with degenerative, traumatic, or neoplastic pathologies received treatment via a novel three-step PS technique that utilizes a navigated power driver in combination with virtual screw technology. (1) Following visualization of neuroanatomy using intraoperative CT, a navigated 3-mm match stick drill bit was inserted at an anatomical entry point with a screen projection showing a virtual screw. (2) A Navigated Stryker Cordless Driver with an appropriate tap was used to access the vertebral body through a pedicle with a screen projection again showing a virtual screw. (3) A Navigated Stryker Cordless Driver with an actual screw was used with a screen projection showing the same virtual screw. One hundred and forty-four consecutive screws were inserted using this three-step, navigated driver, virtual screw technique. RESULTS: Only 1 screw needed intraoperative revision after insertion using the three-step, navigated driver, virtual PS technique. This amounts to a 0.69% revision rate. One hundred percent of patients had intraoperative CT reconstructed images taken to confirm hardware placement. CONCLUSIONS: Pedicle screw placement utilizing the Stryker-Ziehm neuronavigation virtual screw technology with a three step, navigated power drill technique is safe and effective.

Compassionate conservatism: federal funding for the Ryan White CARE Act during the Bush administration.

President George W. Bush has proposed modest increases, when he has proposed any at all, in funding for the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act during his administration, and Congress has appropriated little funding increase since fiscal year 2004. Growing numbers of Americans living with HIV or AIDS, 40 000 people newly infected with HIV each year, and Centers for Disease Control and Prevention-recommended efforts to identify people with undiagnosed HIV infection indicate an increasing need for services funded by CARE Act programs. Inadequate CARE Act funding harms the most vulnerable people with HIV.

Urban/rural differences in health insurance coverage among people with multiple sclerosis.

PURPOSE: To present urban/rural analyses of health insurance coverage among people with multiple sclerosis (MS). This research also combined all survey respondents from each urban/rural area into one group of people with MS in health maintenance organizations (HMOs)/managed care and another group of people with MS who have other health insurance plans to compare any differences in coverage. METHODS: We interviewed 1,518 people with MS living in all 50 states. Survey results were analyzed using SPSS. RESULTS: Most people with MS in each urban/rural area had health insurance coverage (92-95%), with significant urban/rural differences observed in HMO/managed care enrollments. We found no urban/rural differences among people with MS in HMOs/managed care, or among people with MS with other health insurance plans, in satisfaction with coverage of routine care and MS-focused care, or with perceptions of how coverage enables utilization of health services. However, we found that people with MS in HMOs/managed care were more satisfied than people with MS with other health insurance with their coverage of routine care and perceived that their coverage enabled greater utilization of routine care and needed medications. CONCLUSIONS: We found no significant differences in satisfaction with MS-focused care or with perceptions of how well coverage enables utilization of MS-focused care or needed assistive devices between people with MS in HMOs/managed care and people with MS who have other health insurance.

Recent trends in advance directives at nursing home admission and one year after admission.

PURPOSE: Advance directives are important planning and decision-making tools for individuals in nursing homes. DESIGN AND METHODS: By using the nursing facility Minimum Data Set, we examined the prevalence of advance directives at admission and 12 months post-admission. RESULTS: The prevalence of having any advance directive at admission declined slightly from 2000 to 2004, whereas the prevalence of having any advanced directive at 12 months after admission increased slightly during the same period. Compared with admissions, residents at 12 months post-admission were more likely to have their decisions made by family members and to have advance directives of any type. IMPLICATIONS: The results suggest that greater use of advance directives in nursing homes may depend on additional information and support from nursing facility personnel and the health and social services professionals who are in contact with individuals moving toward nursing home admission, as well as those who remain in facilities over time.

Satisfaction with mental health care among people with multiple sclerosis in urban and rural areas.

OBJECTIVES: This study explored urban and rural differences in mental health needs and treatments among people with multiple sclerosis, as well as their satisfaction with access to and quality of mental health care. METHODS: Data were collected in a nationwide survey of 1,518 people with multiple sclerosis. RESULTS: More than 40 percent of people with multiple sclerosis in each urban or rural area had received a diagnosis of depression, and more than 90 percent of them received mental health services, regardless of location of residence. However, rural residents were significantly less likely than their urban counterparts to receive the recommended combined medication and psychotherapy for treatment of depression. CONCLUSIONS: Current mental health care systems, even in rural areas, are capable of reaching out to patients with neuromedical illnesses, such as multiple sclerosis. Patients perceive some limitations in quality and accessibility, and recommended treatment differs between urban and rural areas.

Utilization of rehabilitation therapies by nursing home residents with MS at admission.

OBJECTIVE: To identify factors associated with the utilization of physical and occupational therapies by nursing home residents with multiple sclerosis (MS) at admission to the facility. DESIGN: The study analyzed 27,264 admission assessments for residents with MS recorded in the national Minimum Data Set (MDS) between June, 1998 and June, 2003. A multiple linear regression model was employed to analyze the MDS data. The total number of minutes of physical and occupational therapies provided are the dependent variables. Independent variables are demographic characteristics, payment source, behavioral symptoms, and a range of health-related characteristics. RESULTS: The use of physical and occupational therapies by residents with MS at admission to the nursing facility was significantly associated with payment source, controlling for other independent variables. CONCLUSIONS: When reimbursement is available these therapies are more likely to be prescribed or requested. Since provision of these rehabilitative services diminishes disability and handicap, expanded Medicaid coverage may reduce long term health care costs and also improve the quality of life.