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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Glutamate and GABA concentration changes in the globus pallidus internus of Parkinson's patients during performance of implicit and declarative memory tasks: a report of two subjects.

The basal ganglia, typically associated with motor function, are involved in human cognitive processes, as demonstrated in behavioral, lesion, and noninvasive functional neuroimaging studies. Here we report task-contingent changes in concentrations of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) in the globus pallidus internus (GPi) of two patients with Parkinson's disease undergoing deep brain stimulation surgery by utilizing in-vivo microdialysis measurements during performance of implicit and declarative memory tasks. Performance of an implicit memory task (weather prediction task-WPT) was associated with increased levels of glutamate and GABA in the GPi compared to their concentrations at baseline. On the other hand, performance of a declarative memory task (verbal learning task-VLT) was associated with decreased levels of glutamate and GABA in GPi compared to baseline during the encoding and immediate recall phase with less conclusive results during the delayed recall phase. These results are in line with hypothesized changes in these neurotransmitter levels: an increase of excitatory (Glu) input from subthalamic nucleus (STN) to GPi during implicit memory task performance and a decrease of inhibitory inputs (GABA) from globus pallidus externus (GPe) and striatum to GPi during declarative memory performance. Consistent with our previous report on in-vivo neurotransmitter changes during tasks in STN, these data provide corroborative evidence for the direct involvement of basal ganglia in cognitive functions and complements our model of the functional circuitry of basal ganglia in the healthy and Parkinson's disease affected brain.

Reference frames in virtual spatial navigation are viewpoint dependent.

Spatial navigation in the mammalian brain relies on a cognitive map of the environment. Such cognitive maps enable us, for example, to take the optimal route from a given location to a known target. The formation of these maps is naturally influenced by our perception of the environment, meaning it is dependent on factors such as our viewpoint and choice of reference frame. Yet, it is unknown how these factors influence the construction of cognitive maps. Here, we evaluated how various combinations of viewpoints and reference frames affect subjects' performance when they navigated in a bounded virtual environment without landmarks. We measured both their path length and time efficiency and found that (1) ground perspective was associated with egocentric frame of reference, (2) aerial perspective was associated with allocentric frame of reference, (3) there was no appreciable performance difference between first and third person egocentric viewing positions and (4) while none of these effects were dependent on gender, males tended to perform better in general. Our study provides evidence that there are inherent associations between visual perspectives and cognitive reference frames. This result has implications about the mechanisms of path integration in the human brain and may also inspire designs of virtual reality applications. Lastly, we demonstrated the effective use of a tablet PC and spatial navigation tasks for studying spatial and cognitive aspects of human memory.

Motor cortex stimulation for neuropathic pain syndromes: a case series experience.

Neuropathic pain is a chronic condition lacking effective management and responding poorly to standard treatment protocols. Motor cortex stimulation has emerged as a new and promising therapeutic tool with outcomes potentially affected by the specific causes and location. In this study we report a series of eight cases in the neurosurgery practice of one of the authors (R.J.B.), including neuropathic pain syndromes of trigeminal or thalamic origin with or without anesthesia dolorosa. Pain relief was evaluated on the basis of comparison of Visual Analog scores at baseline and at 3 months after surgery. In addition, we assessed differences in pain relief outcomes between cases with trigeminal neuralgia and thalamic stroke, as well as cases with or without anesthesia dolorosa (i.e. pain with numbness of the affected area). Visual Analog Scale scores showed a statistically significant decrease of 4.19 (P=0.002) at 3 months follow-up compared with baseline. Pain relief levels in four of five patients in the subgroup with facial pain were higher than 50%, and none of the patients in the subgroup with thalamic and phantom limb pain showed such a good outcome. Furthermore, we found larger pain relief levels in facial pain conditions with versus without anesthesia dolorosa. These results point to utility of motor cortex stimulation in relieving neuropathic pain, as well as better outcomes for patients with facial pain and anesthesia dolorosa. Future studies should incorporate methods to noninvasively trial those patients who may benefit from surgical implantation to predict the outcomes and maximize their negative predictive value.

Changes in GABA and glutamate concentrations during memory tasks in patients with Parkinson's disease undergoing DBS surgery.

Until now direct neurochemical measurements during memory tasks have not been accomplished in the human basal ganglia. It has been proposed, based on both functional imaging studies and psychometric testing in normal subjects and in patients with Parkinson's disease (PD), that the basal ganglia is responsible for the performance of feedback-contingent implicit memory tasks. To measure neurotransmitters, we used in vivo microdialysis during deep brain stimulation (DBS) surgery. We show in the right subthalamic nucleus (STN) of patients with PD a task-dependent change in the concentrations of glutamate and GABA during an implicit memory task relative to baseline, while no difference was found between declarative memory tasks. The five patients studied had a significant decrease in the percent concentration of GABA and glutamate during the performance of the weather prediction task (WPT). We hypothesize, based on current models of basal ganglia function, that this decrease in the concentration is consistent with expected dysfunction in basal ganglia networks in patients with PD.

Assessments of nursing home guidelines for quality of care provided to residents with multiple sclerosis.

This study assessed the opinions of nursing directors about quality guidelines developed by the National Multiple Sclerosis Society (NMSS) to assist with the care of nursing home residents with multiple sclerosis (MS). Data were collected in a survey of nursing directors at 800 nursing facilities, with 64 nursing directors participating (8.2% response rate). Participating nursing facilities are similar to other nursing homes for facility characteristics and the number of MS residents receiving care. Large majorities of participants thought these NMSS guidelines were important to the development of care plans and staff training. However, most nursing directors were unaware of these guidelines.

The need for mental health care among informal caregivers assisting people with multiple sclerosis.

The objective of this study was to identify characteristics of informal caregivers and people with multiple sclerosis (MS) receiving assistance that are associated with the caregiver's perceived need for mental health care. Survey data were collected in interviews with 530 caregivers and analyzed using a logistic regression model. We found that older caregiver age significantly decreased the odds of caregivers' perceived need for mental health treatment. Better mental health domains of health-related quality of life among caregivers, as measured by the 8-item Short Form Health Status Survey (SF-8), also were associated with decreased odds of the need for mental health care. In contrast, the caregiver's feeling that providing assistance was emotionally draining or the belief that this assistance threatened the caregiver/care recipient relationship significantly increased the odds of caregivers' needing mental health treatment. Health professionals treating informal caregivers should be sensitive to the impact that providing assistance has on the emotions, relationships, and mental health needs of caregivers.

Factors affecting employment among informal caregivers assisting people with multiple sclerosis.

The objective of this study was to identify characteristics of informal caregivers, caregiving, and the people with multiple sclerosis (MS) receiving assistance that are associated with reduced caregiver employment. Data were collected during telephone interviews with 530 MS caregivers, including 215 employed caregivers, with these survey data analyzed using logistic regression. Poorer cognitive ability by the care recipient to make decisions about daily tasks and more caregiving hours per week predicted reduced caregiver employment. Better physical health domains of caregiver quality of life were associated with significantly lower odds of reduced employment. Health professionals treating informal caregivers, as well as those treating people with MS, need to be aware of respite, support, and intervention programs available to MS caregivers and refer them to these programs, which could reduce the negative impact of caregiving on employment.

Health-related quality of life among Latinos with multiple sclerosis.

This study identifies characteristics associated with health-related quality of life (HRQOL) among Latinos with multiple sclerosis (MS). Data were collected from 99 Latinos with MS, with multiple linear regression models utilized to analyze these data. Marital status, MS symptoms, depressive symptoms, treatment at MS clinics, and satisfaction with insurance coverage of MS-related care were significantly linked with physical HRQOL. Marital status, employment, access to MS-focused care, and need for mental health care were significantly associated with mental health dimensions of HRQOL. Identifying characteristics associated with better HRQOL among Latinos with MS should facilitate approaches that address the health needs of this community.

Caregiver perceptions of accomplishment from assisting people with multiple sclerosis.

OBJECTIVES: Identify factors of informal caregivers, caregiving, and people with multiple sclerosis (MS) receiving assistance that are associated with perceptions of caregiver accomplishment. METHODS: National data were collected in a telephone interview survey of 530 informal caregivers and analyzed using an ordered logistic regression model to identify factors associated with perceptions of caregiver accomplishment among 442 of these informal caregivers (caregivers providing all data in their survey responses needed for the regression model). RESULTS: We found that age of the person with MS and duration of caregiving measured by the number of hours per week the caregiver assisted the person with MS were significantly linked to positive perceptions of accomplishment. Conversely, the caregiver's perception that assisting the person with MS was emotionally draining, a spousal relationship, and caregiver education levels were significantly associated with negative perceptions of accomplishment. CONCLUSIONS: Health professionals treating people with MS and their caregivers should be sensitive to the impact caregiving has on the emotional needs of caregivers and to the unique support needs of spousal caregivers. Health practitioners also should be sensitive to the variety of benefit-finding themes expressed by caregivers to facilitate the caregivers' efforts to discover gains in their experiences assisting people with MS, such as perceptions that caregiving provides a sense of accomplishment.