The role of neurocritical care: a brief report on the survey results of neurosciences and critical care specialists.

BACKGROUND: Neurocritical care is a new subspecialty field in medicine that intersects with many of the neuroscience and critical care specialties, and continues to evolve in its scope of practice and practitioners. The objective of this study was to assess the perceived need for and roles of neurocritical care intensivists and neurointensive care units among physicians involved with intensive care and the neurosciences. METHODS: An online survey of physicians practicing critical care medicine, and neurology was performed during the 2008 Leapfrog initiative to formally recognize neurocritical care training. RESULTS: The survey closed in July 2009 and achieved a 13% response rate (980/7524 physicians surveyed). Survey respondents (mostly from North America) included 362 (41.4%) neurologists, 164 (18.8%) internists, 104 (11.9%) pediatric intensivists, 82 (9.4%) anesthesiologists, and 162 (18.5%) from other specialties. Over 70% of respondents reported that the availability of neurocritical care units staffed with neurointensivists would improve the quality of care of critically ill neurological/neurosurgical patients. Neurologists were reported as the most appropriate specialty for training in neurointensive care by 53.3%, and 57% of respondents responded positively that neurology residency programs should offer a separate training track for those interested in neurocritical care. CONCLUSION: Broad level of support exists among the survey respondents (mostly neurologists and intensivists) for the establishment of neurological critical care units. Since neurology remains the predominant career path from which to draw neurointensivists, there may be a role for more comprehensive neurointensive care training within neurology residencies or an alternative training track for interested residents.

Use of 64-channel electroencephalography to study neural otolith-evoked responses.

BACKGROUND: The vestibular evoked myogenic potential (VEMP) is a myogenic response that can be used clinically to evaluate the function of the saccule. However, to date, little is known about the thalamo-cortical representation of saccular activation. It is important to understand all aspects of the VEMP, as this test is currently used clinically in the evaluation of saccular function. PURPOSE: To identify the areas of the brain that are activated in response to stimuli used clinically to evoke the VEMP. RESEARCH DESIGN: Electroencephalography (EEG) recordings combined with current density analyses were used to identify the areas of the brain that are activated in response to stimuli presented above VEMP threshold (500 Hz, 120 dB peak SPL [pSPL] tone bursts), as compared to stimuli presented below VEMP threshold (90 dB pSPL, 500 Hz tone bursts). Ten subjects without any history of balance or hearing impairment participated in the study. RESULTS: The neural otolith-evoked responses (NOERs) recorded in response to stimuli presented below VEMP threshold were absent or smaller than NOERs that were recorded in response to stimuli presented above VEMP threshold. Subsequent analyses with source localization techniques, followed by statistical analysis with SPM5 (Statistical Parametric Mapping), revealed several areas that were activated in response to the 120 dB pSPL tone bursts. These areas included the primary visual cortex, the precuneus, the precentral gyrus, the medial temporal gyrus, and the superior temporal gyrus. CONCLUSIONS: The present study found a number of specific brain areas that may be activated by otolith stimulation. Given the findings and source localization techniques (which required limited input from the investigator as to where the sources are believed to be located in the brain) used in the present study as well as the similarity in findings between studies employing galvanic stimuli, fMRI (functional magnetic resonance imaging), and scalp-recorded potentials in response to VEMP-eliciting stimuli, our study provides additional evidence that these brain regions are activated in response to stimuli that can be used clinically to evoke the VEMP.

Multi-site phasic neural activity mediates the execution of an auditory continuous performance task: a PET and electrophysiological study.

BACKGROUND AND PURPOSE: We studied an auditory continuous performance task with positron emission tomography(PET) and EEG-derived current density reconstructions (CDRs) to define the spatial and temporal aspects of auditory attention. METHODS: The CDRs were employed to segregate responses to targets and non-targets at sites identified by PET. We then studied the time course of brain activity using statistical parametric mapping (SPM) of the CDR data. RESULTS: In contrast to target EEG activity, non-targets did not produce significant peaks after 300 ms. Pre-300 ms biphasic activation of auditory, left posterior frontal, left supplemental,and primary motor cortices and the anterior cingulate (AC) and biphasic suppression of posterior cingulate and occipital cortex were identical for targets and non-targets and may mediate the target non-target decision. SPM analysis of post-300 ms CDRs showed cingulate cortices were the first to be reactivated, remained active through 672 ms, and were accompanied by reactivation and deactivation of the same sites observed in the pre-P300 responses. CONCLUSIONS: The cingulate may play an important role in post-decisional activity and control activity at other sites involved in post-decisional cognitive processing.

Multi-site phasic neural activity mediates the execution of an auditory continuous performance task: a PET and electrophysiological study.

BACKGROUND AND PURPOSE: We studied an auditory continuous performance task with positron emission tomography (PET) and EEG-derived current density reconstructions (CDRs) to define the spatial and temporal aspects of auditory attention. METHODS: The CDRs were employed to segregate responses to targets and non-targets at sites identified by PET. We then studied the time course of brain activity using statistical parametric mapping (SPM) of the CDR data. RESULTS: In contrast to target EEG activity, non-targets did not produce significant peaks after 300 ms. Pre-300 ms biphasic activation of auditory, left posterior frontal, left supplemental, and primary motor cortices and the anterior cingulate (AC) and biphasic suppression of posterior cingulate and occipital cortex were identical for targets and non-targets and may mediate the target non-target decision. SPM analysis of post-300 ms CDRs showed cingulate cortices were the first to be reactivated, remained active through 672 ms, and were accompanied by reactivation and deactivation of the same sites observed in the pre-P300 responses. CONCLUSIONS: The cingulate may play an important role in post-decisional activity and control activity at other sites involved in post-decisional cognitive processing.

Cognitive therapy for irritable bowel syndrome is associated with reduced limbic activity, GI symptoms, and anxiety.

This study sought to identify brain regions that underlie symptom changes in severely affected IBS patients undergoing cognitive therapy (CT). Five healthy controls and 6 Rome II diagnosed IBS patients underwent psychological testing followed by rectal balloon distention while brain neural activity was measured with O-15 water positron emission tomography (PET) before and after a brief regimen of CT. Pre-treatment resting state scans, without distention, were compared to post-treatment scans using statistical parametric mapping (SPM). Neural activity in the parahippocampal gyrus and inferior portion of the right cortex cingulate were reduced in the post-treatment scan, compared to pre-treatment (x, y, z coordinates in MNI standard space were -30, -12, -30, P=0.017; 6, 34, -8, P=0.023, respectively). Blood flow values at these two sites in the controls were intermediate between those in the pre- and post-treatment IBS patients. Limbic activity changes were accompanied by significant improvements in GI symptoms (e.g., pain, bowel dysfunction) and psychological functioning (e.g., anxiety, worry). The left pons (-2, -26, -28, P=0.04) showed decreased neural activity which was correlated with post-treatment anxiety scores. Changes in neural activity of cortical-limbic regions that subserve hypervigilance and emotion regulation may represent biologically oriented change mechanisms that mediate symptom improvement of CT for IBS.

Neurodegenerative diseases: an overview of environmental risk factors.

The population of the United States is aging, and an ever-increasing number of Americans are afflicted with neurodegenerative diseases. Because the pathogenesis of many of these diseases remains unknown, we must consider that environmental factors may play a causal role. This review provides an overview of the epidemiologic evidence for environmental etiologies for neurodegenerative diseases such as Alzheimer disease, Parkinson disease, parkinsonian syndromes (multiple system atrophy and progressive supranuclear palsy), and amyotrophic lateral sclerosis. Epidemiologic evidence for an association between environmental agents' exposure and neurodegenerative diseases is not conclusive. However, there are indications that there may be causal links, and the need for more research is obvious.

Mapping the 40-Hz auditory steady-state response using current density reconstructions.

We mapped the 40-Hz aSSR from nine normal subjects using PET-independent low-resolution electroencephalographic tomography (LORETA) as well as PET-weighted LORETA and minimum norm (MinNorm) current density reconstructions. In grand mean data, PET-independent LORETA identified seven sites with peaks in current density in right temporal lobe, right brainstem/cerebellum, right parietal lobe, left cerebellum/temporal lobe, and right frontal lobe. PET-weighted LORETA found six of the same sites as the PET-independent LORETA: the right brainstem source was eliminated and two right-frontal sources were added. Both LORETA analyses revealed considerable phase dispersion across identified sources. In both LORETA analyses, the relative time course of activation measured from an arbitrary starting phase progressed from right temporal lobe to right mid-frontal lobe to right parietal-frontal to right inferior parietal and finally to left cerebellum and left temporal lobe. MinNorm analysis incorporating PET information identified sources in the same locations as specified in the PET data. These sources were synchronized, with their amplitudes peaking almost simultaneously. Both PET-independent and PET-weighted LORETA results suggest that the aSSR is: (1) the result of a reverberating network with two or more groups of sources that recurrently excite each other or (2) the result of sequential auditory processing through various levels of a hierarchical network. In contrast, the PET-weighted MinNorm results suggest that the 40-Hz response represents simultaneous activation over widely spaced areas of the brain, perhaps due to synchronization of gamma-band activity to a common neural clock.

Blood ammonia levels and hepatic encephalopathy.

The importance of measurements of the blood ammonia concentration in the evaluation of patients with known or suspected hepatic encephalopathy (HE) is still disputed in spite of a general acknowledgment that ammonia is important in the pathogenesis of the disorder. Several recent studies have suggested that it is not necessary to utilize arterial blood when measuring ammonia in the blood. Venous blood or a computation of the partial pressure of ammonia gas in blood samples may suffice. The value of blood ammonia measurements is limited by the fact that this is not the variable that is the most important. Ideally, one would like to know how much ammonia enters the brain, not how much is in the blood. The blood-brain barrier (BBB) is the critical and poorly understood element in this relationship. Although both ammonia in the gas and ionic forms cross the BBB, the ease with which this movement occurs is significantly higher in patients with HE. In the absence of simple methods to measure the brain ammonia metabolic rate and to assess the BBB to ammonia in conjunction with measuring the blood ammonia concentration, the variables that would be the most desirable to measure, the use of arterial and/or venous blood measurements needs to be coupled with a complete understanding of the physiology of cerebral ammonia metabolism.

Human testing of pesticides: ethical and scientific considerations.

I reviewed ethical and scientific aspects of 6 human pesticide-dosing studies submitted to the Environmental Protection Agency (EPA) for consideration during the pesticide reregistration process. All had serious ethical or scientific deficiencies-or both-including unacceptable informed consent procedures, unmanaged financial conflicts of interest, inadequate statistical power, inappropriate test methods and endpoints, and distorted results. Given today's knowledge of the effects of pesticides, there is no assurance that any such study can be completely free of short-term risks, long-term risks, or both. Therefore, there is no basis for allowing pesticide studies to continue or for using them during the pesticide reregistration process. An EPA committee that is free from political and financial conflicts of interest should review this practice.

PET imaging of the 40 Hz auditory steady state response.

The auditory steady state response (aSSR) is an oscillatory electrical potential recorded from the scalp induced by amplitude-modulated (AM) or click/tone burst stimuli. Its clinical utility has been limited by uncertainty regarding the specific areas of the brain involved in its generation. To identify the generators of the aSSR, 15O-water PET imaging was used to locate the regions of the brain activated by a steady 1 kHz pure tone, the same tone amplitude modulated (AM) at 40 Hz and the specific regions of the brain responsive to the AM component of the stimulus relative to the continuous tone. The continuous tone produced four clusters of activation. The boundaries of these activated clusters extended to include regions in left primary auditory cortex, right non-primary auditory cortex, left thalamus, and left cingulate. The AM tone produced three clusters of activation. The boundaries of these activated clusters extended to include primary auditory cortex bilaterally, left medial geniculate and right middle frontal gyrus. Two regions were specifically responsive to the AM component of the stimulus. These activated clusters extended to include the right anterior cingulate near frontal cortex and right auditory cortex. We conclude that cortical sites, including areas outside primary auditory cortex, are involved in generating the aSSR. There was an unexpected difference between morning and afternoon session scans that may reflect a pre- versus post-prandial state. These results support the hypothesis that a distributed resonating circuit mediates the generation of the aSSR.

Functional imaging during covert auditory attention in multiple sclerosis.

Recent literature suggests that the brain in multiple sclerosis (MS) undergoes reorganization that subserves the performance of visual and motor tasks. We identified sites of cerebral activity in 16 MS patients while performing a covert attention (CA) task, presented in the auditory modality. Positron emission tomography (PET) revealed activation of rostral/dorsal anterior cingulate cortex (ACC) in normal subjects studied previously. Activity in this region was not significant in MS patients, but there was a large region of activity in superior temporal cortex. Decreased activation of frontal attentional networks and greater activity in sensory/perceptual cortical areas (auditory association cortex) suggests a reduction of transmission along white matter tracts connecting these regions. This study demonstrates cingulate hypoactivity and cerebral reorganization during auditory attention in MS.

Mapping the neural systems that mediate the Paced Auditory Serial Addition Task (PASAT).

The paced auditory serial addition task (PASAT), in which subjects hear a number-string and add the two most-recently heard numbers, is a neuropsychological test sensitive to cerebral dysfunction. We mapped the brain regions activated by the PASAT using positron emission tomography (PET) and 15O-water to measure cerebral blood flow. We parsed the PASAT by mapping sites activated by immediate repetition of numbers and by repetition of the prior number after the presentation of the next number in the series. The PASAT activated dispersed non-contiguous foci in the superior temporal gyri, bifrontal and biparietal sites, the anterior cingulate and bilateral cerebellar sites. These sites are consistent with the elements of the task that include auditory perception and processing, speech production, working memory, and attention. Sites mediating addition were not identified. The extent of the sites activated during the performance of the PASAT accounts for the sensitivity of this test and justifies its use in a variety of seemingly disparate conditions.