Molecular concentration of deoxyHb in human prefrontal cortex predicts the emergence and suppression of consciousness.

This is the first study to use fNIRS to explore anaesthetic depth and awakening during surgery with general anaesthesia. A 16 channel continuous wave (CW) functional near-infrared system (fNIRS) was used to monitor PFC activity. These outcomes were compared to BIS measures. The results indicate that deoxyHb concentration in the PFC varies during the suppression and emergence of consciousness. During suppression, deoxyHb levels increase, signalling the deactivation of the PFC, while during emergence, deoxyHb concentration drops, initiating PFC activation and the recovery of consciousness. Furthermore, BIS and deoxyHb concentrations in the PFC display a high negative correlation throughout the different anaesthetic phases. These findings suggest that deoxyHb could be a reliable marker for monitoring anaesthetic depth, and that the PFC intervenes in the suppression and emergence of consciousness.

The sooner patients begin neurorehabilitation, the better their functional outcome.

PRIMARY OBJECTIVE: To determine whether early neurorehabilitation improves a patient's functional recovery. RESEARCH DESIGN: A retrospective study was carried out on patients with severe traumatic brain injury (TBI) who underwent a minimum of 4 months of integral and multidisciplinary neurorehabilitation. METHODS AND PROCEDURES: Fifty-eight patients with severe TBI were assessed at admission and at discharge using the FIM + FAM scale. Two groups were formed based on time elapsed from brain injury to onset of rehabilitation. The early treatment group (ET) included patients who began rehabilitation within the first 9 months post-trauma; the late treatment group (LT) began after the 9-month cut-off date. Intra- and between-group analysis of FIM + FAM scores were carried out at admission and discharge. Multiple linear regression was used to determine the best predictors for functional rehabilitation. MAIN OUTCOMES AND RESULTS: After neurorehabilitation, all subjects showed significant improvement in cognitive, motor, communication and psychosocial functioning. Moreover, the ET group showed better global functional outcome at discharge than patients who began later treatment. The best predictors for functional neurorehabilitation were months since injury, age, GCS score and months of treatment. CONCLUSIONS: It is concluded that the sooner patients begin neurorehabilitation, the better their functional outcome.

Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome.

BACKGROUND: Some patients awaken from coma (that is, open the eyes) but remain unresponsive (that is, only showing reflex movements without response to command). This syndrome has been coined vegetative state. We here present a new name for this challenging neurological condition: unresponsive wakefulness syndrome (abbreviated UWS). DISCUSSION: Many clinicians feel uncomfortable when referring to patients as vegetative. Indeed, to most of the lay public and media vegetative state has a pejorative connotation and seems inappropriately to refer to these patients as being vegetable-like. Some political and religious groups have hence felt the need to emphasize these vulnerable patients' rights as human beings. Moreover, since its first description over 35 years ago, an increasing number of functional neuroimaging and cognitive evoked potential studies have shown that physicians should be cautious to make strong claims about awareness in some patients without behavioral responses to command. Given these concerns regarding the negative associations intrinsic to the term vegetative state as well as the diagnostic errors and their potential effect on the treatment and care for these patients (who sometimes never recover behavioral signs of consciousness but often recover to what was recently coined a minimally conscious state) we here propose to replace the name. CONCLUSION: Since after 35 years the medical community has been unsuccessful in changing the pejorative image associated with the words vegetative state, we think it would be better to change the term itself. We here offer physicians the possibility to refer to this condition as unresponsive wakefulness syndrome or UWS. As this neutral descriptive term indicates, it refers to patients showing a number of clinical signs (hence syndrome) of unresponsiveness (that is, without response to commands) in the presence of wakefulness (that is, eye opening).

Information communication networks in severe traumatic brain injury.

In this study we explored the use of coherence and Granger causality (GC) to separate patients in minimally conscious state (MCS) from patients with severe neurocognitive disorders (SND) that show signs of awareness. We studied 16 patients, 7 MCS and 9 SND with age between 18 and 49 years. Three minutes of ongoing electroencephalographic (EEG) activity was obtained at rest from 19 standard scalp locations, while subjects were alert but kept their eyes closed. GC was formulated in terms of linear autoregressive models that predict the evolution of several EEG time series, each representing the activity of one channel. The entire network of causally connected brain areas can be summarized as a graph of incompletely connected nodes. The 19 channels were grouped into five gross anatomical regions, frontal, left and right temporal, central, and parieto-occipital, while data analysis was performed separately in each of the five classical EEG frequency bands, namely delta, theta, alpha, beta, and gamma. Our results showed that the SND group consistently formed a larger number of connections compared to the MCS group in all frequency bands. Additionally, the number of connections in the delta band (0.1-4 Hz) between the left temporal and parieto-occipital areas was significantly different (P < 0.1%) in the two groups. Furthermore, in the beta band (12-18 Hz), the input to the frontal areas from all other cortical areas was also significantly different (P < 0.1%) in the two groups. Finally, classification of the subjects into distinct groups using as features the number of connections within and between regions in all frequency bands resulted in 100% classification accuracy of all subjects. The results of this study suggest that analysis of brain connectivity networks based on GC can be a highly accurate approach for classifying subjects affected by severe traumatic brain injury.

The Infrascanner, a handheld device for screening in situ for the presence of brain haematomas.

PURPOSE: Early identification and treatment of intracranial haematomas in patients sustaining traumatic brain injury is fundamental to successful treatment. This pilot study evaluates the Infrascanner as a handheld medical screening tool for detection, in situ, of brain haematomas in patients with head injury. METHODS: This study included 35 TBI patients aged 17-76 (M = 47.6), admitted to the neurosurgical intensive care unit and observation unit of a University Hospital in a Level 1 trauma centre. The Infrascanner NIRS device uses near infrared light measurements to calculate optical density in brain regions. RESULTS: Results show Infrascanner sensitivity at 89.5% and specificity at 81.2%. PPV was 85% and NPV 86.7%. The device detected 90% of extra-axial, 88.9% of intra-axial and 93.3% of non-surgical haematomas (less than 25 mL). PPV for this classification was 82.3%; 87.5% sensitivity was found when the Infrascanner exam was performed within 12 hours post-trauma, whereas after 12 hours post-trauma, exams had 90.1% sensitivity. CONCLUSIONS: This study demonstrates that the Infrascanner is useful in initial examinations and screenings of patients with head injury as an adjunct to a CT scan or when it is not available and may allow earlier treatment and reduce secondary injury caused by present and delayed haematomas.

The prognostic value of the temporal course of S100beta protein in post-acute severe brain injury: A prospective and observational study.

PRIMARY OBJECTIVE: To study the predictive capacity of early S100beta samples for long-term outcome prediction after severe TBI. METHODS AND PROCEDURES: Eighty-seven patients with severe TBI were studied. Clinical and CT scan were taken at admission. S100beta concentration was quantified at admission and 24, 48 and 72 hours post-TBI (days 0, 1, 2 and 3). Outcome was assessed 12 months after discharge using Glasgow Outcome Score (GOS). RESULTS: Significant negative correlations were found between 1-year GOS and S100beta concentrations on days 1-3, but not on day 0. Deceased patients showed higher S100beta concentration than survivors on days 1-3. Good (GOS = 4-5) vs poor outcome (GOS = 1-3) differed significantly on day 3. Death outcome was independently predicted by day 2 (>2.37 microg l(-1)), day 3 (>1.41 microg l(-1)) samples and absence of pupillary reaction. Poor outcome was predicted independently only by pupillary reaction and the 72-hour sample (>1.1 microg l(-1)), but this predictive model was less satisfactory than the predictive model for death. CONCLUSIONS: A temporal profile of S100beta release from admission to 72 hours post-TBI is strongly recommended for use in identifying patients at risk of developing a worse outcome. The S100beta protein might be an early biomarker for predicting long-term outcome in patients with acute severe TBI.

A Frontal Neuropsychological Profile in Fitness to Drive.

Traffic accidents are a global concern due to the elevated mortality rates of both drivers and pedestrians. The World Health Organization declared 2011-2020 as the Decade of Action for Road Safety, endorsing initiatives to reduce traffic-related deaths. Yet, despite these incentives, fatal accidents still occur. Different studies have linked deficits in executive functions to risky driving attitudes and crashes. The present study focuses on demographic, cognitive and personality factors, related to the prefrontal cortex, that are characteristic of drivers prone to risky behavior behind the wheel. The penalty Points System was used to classify drivers as "safe", with no point loss over a two-year period, or "risky", with full point loss during the same interval. A neuropsychological assessment of prefrontal cognitive functions was carried out on each group to identify variables associated with safe and risky behavior. Neuropsychological indexes were obtained from a continuous performance task without cue (Simple Attention), a continuous performance task with cue (Conditioned Attention), the Tower of Hanoi test and the Neurologically-related Changes in Personality Inventory (NECHAPI). A Discriminant Analysis (DA) found that education level, reaction times in Simple and Conditioned Attention, learning errors in the Tower of Hanoi and vulnerability in the personality test, best predicted whether drivers were likely to be in the safe or risky group. Finally, a cross-validation analysis performed on the same sample correctly classified 87.5% of the drivers. These data suggest that prefrontal dysfunction contributes to risky behavior behind the wheel. The inclusion of cognitive programs to identify and train drivers with this propensity could reduce risky driving, and consequently, save lives on the road.

A clinical profile of memory impairment in humans due to endogenous glucocorticoid excess.

OBJECTIVE: Glucocorticoid excess is commonly related to neuropsychiatric and neurological disorders, with memory impairment typically found among these disorders. The objective of this study is to offer a clinical profile of memory deficits resulting from exposure to chronic stress-level elevations of endogenous glucocorticoids in patients with Cushing's Syndrome (CS). STUDY SUBJECTS: Thirty female participants of matching age and education level were studied: 15 had untreated CS (mean age 38 +/- 14) and 15 were healthy. In all patients, CS was confirmed by histology of the lesion after surgery. DESIGN: Different learning and memory processes were assessed using an adapted version of Luria's Memory Words-Revised task (LMW-R). Participants' performances were measured in an immediate condition and, 30 min later, in a delayed condition. Attentional and executive functions were also evaluated. RESULTS: Our data show that chronic exposure to elevated levels of cortisol is clinically associated with significant working memory deficits, which included less shot-term memory volume, slow learning rate, memory contamination and no accurate perception of own performance. Patients also show impairment in the delayed recall task. No relation was detected between learning and delayed conditions. CS group did not differ significantly from control group in basic attentional and executive functioning. CONCLUSIONS: Our clinical profile of memory deficits related to CS relates chronic exposure to hypercortisolemia to impaired attentional-dependent working memory and delayed recall process, suggesting that cortisol levels play a critical role in the modulation of learning and memory. Possible damage to hippocampus and extrahippocampal areas is discussed.

Prefrontal neural dynamics in consciousness.

The Prefrontal Cortex (PFC) is one of the principal brain regions studied in consciousness. Previous investigations suggest that the PFC is an important neural hub in both awareness and the manipulation of the content of consciousness. Despite a consensus in the scientific community regarding PFC function in cortico-cortical networks, there is still intense debate as to its role in the thalamocortical network and the formation of content of consciousness. The objective of this research is to provide a comprehensive review of the possible implications of PFC activity in awareness, with a focus on thalamic neural pathways that could explain perceptual alterations in the content of consciousness. We posit that the PFC and its connection with nonspecific thalamic nuclei could be responsible for the functional integration of sensory perception into a unique conscious content. This cortico-thalamocortical neural loop would denote a small closed-loop subnetwork within the thalamocortical system that organizes the flow of temporal and spatial information to maintain a subjective stream of consciousness. In particular, attentional top-down mechanisms between the PFC and the reticular thalamic nucleus could influence the formation of the content of consciousness through their capacity to regulate thalamic activity. Summarizing, the PFC acts as a dynamic and multifunctional neural hub that recalibrates global neural dynamics and regulates interactive brain processes associated with consciousness.

The hemodynamics of cognitive control: the level of concentration of oxygenated hemoglobin in the superior prefrontal cortex varies as a function of performance in a modified Stroop task.

The purpose of this study was to establish the relationship between the hemodynamic response of prefrontal cortex (PFC) and individual differences in cognitive control, as measured by a color-word interference task. Twenty-five healthy volunteers were observed through functional near infrared spectroscopy (fNIRS) while performing a modified Stroop paradigm. Mean concentration levels of oxygenated hemoglobin (oxy-Hb) were correlated with behavioral performance in the conflict task. Those with shorter reaction times had higher levels of oxy-Hb concentration in superior dorsolateral PFC. Our results are the first to show a positive correlation between behavioral performance and oxy-Hb levels in superior dorsolateral PFC in a cognitive conflict task. These results suggest that the availability of oxygen in the superior PFC, possibly linked to an increase in metabolism, may be related to attention level and effectiveness of cognitive control.

Does dorsolateral prefrontal cortex (DLPFC) activation return to baseline when sexual stimuli cease? The role of DLPFC in visual sexual stimulation.

A fundamental question in human sexuality regards the neural substrate underlying sexually-arousing representations. Lesion and neuroimaging studies suggest that dorsolateral pre-frontal cortex (DLPFC) plays an important role in regulating the processing of visual sexual stimulation. The aim of this Functional Near-Infrared Spectroscopy (fNIRS) study was to explore DLPFC structures involved in the processing of erotic and non-sexual films. fNIRS was used to image the evoked-cerebral blood oxygenation (CBO) response in 15 male and 15 female subjects. Our hypothesis is that a sexual stimulus would produce DLPFC activation during the period of direct stimulus perception ("on" period), and that this activation would continue after stimulus cessation ("off" period). A new paradigm was used to measure the relative oxygenated hemoglobin (oxyHb) concentrations in DLPFC while subjects viewed the two selected stimuli (Roman orgy and a non-sexual film clip), and also immediately following stimulus cessation. Viewing of the non-sexual stimulus produced no overshoot in DLPFC, whereas exposure to the erotic stimulus produced rapidly ascendant overshoot, which became even more pronounced following stimulus cessation. We also report on gender differences in the timing and intensity of DLPFC activation in response to a sexually explicit visual stimulus. We found evidence indicating that men experience greater and more rapid sexual arousal when exposed to erotic stimuli than do women. Our results point out that self-regulation of DLPFC activation is modulated by subjective arousal and that cognitive appraisal of the sexual stimulus (valence) plays a secondary role in this regulation.

A lasting post-stimulus activation on dorsolateral prefrontal cortex is produced when processing valence and arousal in visual affective stimuli.

This paper introduces a new paradigm in the study of emotional processes through functional neuroimaging. We study whether the valence and arousal of visual stimuli influence neuroimaging of the evoked hemodynamic changes. Using functional near-infrared spectroscopy (fNIRS), we investigate evoked-cerebral blood oxygenation (CBO) changes in dorsolateral prefrontal cortex (DLPFC) during direct exposure to different emotion-eliciting stimuli ('on' period), and during the period directly following stimulus cessation ('off' period). We hypothesize that the evoked-CBO, rather than return to baseline after stimulus cessation, would show either overshoot or undershoot. The study includes 30 healthy subjects and a total of 9 stimuli, which consist of video-clips with different emotional content. The total sample of trials studied (270) is classified according to the valence and arousal ratings given by the subjects. Results show a more robust activation in DLPFC during the 'off' period than during the 'on' period, depending on the subjective degree of arousal given to the stimulus. Our findings provide the first fNIRS evidence showing that an increment in subjective arousal leads to activation in DLPFC which persists after stimulus cessation and this does not occur with non-arousing stimuli. Neuroimaging studies must consider the duration and affective dimensions of the stimulus as well as the duration of the scanning to specify how much of the recorded response is analyzed. Not accounting for this difference may contribute to confusion in the data interpretation.

Safe driving and executive functions in healthy middle-aged drivers.

The introduction of the point system driver's license in several European countries could offer a valid framework for evaluating driving skills. This is the first study to use this framework to assess the functional integrity of executive functions in middle-aged drivers with full points, partial points or no points on their driver's license (N = 270). The purpose of this study is to find differences in executive functions that could be determinants in safe driving. Cognitive tests were used to assess attention processes, processing speed, planning, cognitive flexibility, and inhibitory control. Analyses for covariance (ANCOVAS) were used for group comparisons while adjusting for education level. The Bonferroni method was used for correcting for multiple comparisons. Overall, drivers with the full points on their license showed better scores than the other two groups. In particular, significant differences were found in reaction times on Simple and Conditioned Attention tasks (both p-values < 0.001) and in number of type-III errors on the Tower of Hanoi task (p = 0.026). Differences in reaction time on attention tasks could serve as neuropsychological markers for safe driving. Further analysis should be conducted in order to determine the behavioral impact of impaired executive functioning on driving ability.

Differential time course and intensity of PFC activation for men and women in response to emotional stimuli: a functional near-infrared spectroscopy (fNIRS) study.

Using functional near-infrared spectroscopy (fNIRS) we recorded prefrontal cortex (PFC) activation during positive, negative and neutral film clips, based on affective ratings according to their valence and arousal, to assess gender differences in cerebral activation in 15 male and 15 female volunteers. To record PFC activation, five movie clips were presented on a 17-in. TFT screen. The recordings included a pre-stimulus 5-s local baseline and "on" and "off" segments of data, referring to fNIRS Oxy-Hb levels while stimulation (movie clip) was present and during an inter-stimulus blank screen. Our data showed gender differences in the delay period to initial PFC activation and in the course and intensity of activation produced by affective visual stimuli. During the exposure or "on" period of the stimuli we observed more pronounced overshoot and undershoot in men versus women across the range of emotions elicited. This effect was even more pronounced following stimulus cessation ("off" period). The results indicate that gender and the duration of recordings may affect the results of emotional neuroimaging studies.

Executive n-back tasks for the neuropsychological assessment of working memory.

Working memory (WM) has been defined as a cerebral function which allows us to maintain and manipulate information "online". One of the most widely used paradigms to assess WM is the n-back test. Despite its extensive application, some authors have questioned its capacity to assess the manipulation of WM load. The present study introduces a new version of the n-back test to carry out this assessment. We use functional near-infrared spectroscopy (fNIRS) to evaluate prefrontal cortex (PFC) activation. The modified n-back requires monitoring of sequentially presented stimuli (in this case the days of the week). The target response relates to a stimulus which appears previously, from 0 to 2 items back, on the computer screen. Our data reveals that while modified and unmodified n-back activate the same regions of the left PFC, our modified 2-back version shows significantly higher activation in the left dorsolateral PFC (DLPFC) and the left frontal opercula. These results suggest that increased complexity in verbal WM tasks entail greater executive control, which would lead to an increase in cerebral blood flow to the areas associated with verbal WM. Therefore, an increase in the manipulation of WM load in verbal tasks reflects greater physiological activity in the left DLPFC and the left frontal opercula. The modified n-back test may also be incorporated into the armamentarium of valid instruments for the neuropsychological assessment of the maintenance and manipulation of verbal information in tasks requiring working memory.

Reaction Time and Attention: Toward a New Standard in the Assessment of ADHD? A Pilot Study.

UNLABELLED: This pilot study shows results of an experiment comparing reaction times (RTs) and attentional performance between an ADHD group of 30 children and 30 controls, both Spanish speaking. The experiment was carried out using the Seville computerized neuropsychological battery (SNB). OBJECTIVE: This study had two goals: One was to test sensitivity of SNB for attention deficits in ADHD and the second was to detect differences in RTs between ADHD and controls. Possible explanations and implications of such differences are also discussed. METHOD: SNB computerized system was used to assess RTs and accuracy, and alternate forms of continuous performance task were used. RESULTS: Results showed high sensitivity of some of the SNB tests, especially cancellation tests. RTs were significantly different between groups. CONCLUSION: SNB represents a helpful tool for detection of attention deficits, and RT indices represent the most significant variable in differentiation of both groups studied.

Dementia Due to Head Trauma: An obscure name for a clear neurocognitive syndrome.

This paper questions the DSM IV TR criteria for Dementia Due to Head Trauma (DDHT). We studied 20 consecutive traumatic brain injury (TBI) patients and checked them for this criteria. We found the diagnosis criteria to be oversensitive and lacking in specificity, consequently raising the possibility for all subjects who have sustained severe TBI to be diagnosed with dementia. A careful analysis of data and literature showed that nearly half of these patients were able to return to work after undergoing an intensive and holistic rehabilitation program, indicating a reversal of the "dementia". Severe head injury produces a set of multiple cognitive deficits that shouldn't be considered dementia. The term "Severe Neurocognitive Disorder" is suggested for use instead of DDHT for the cognitive deterioration of severe TBI patients.

Restoring cortical connectivity directionality and synchronization is essential to treating disorder of consciousness.

The design of neurorehabilitation therapy to treat subjects with altered consciousness provides opportunities and challenges to professionals involved with the care for these severely ill patients. While there is an increased interest in determining methods to restore consciousness in these patients, the process is complex and challenging, due in part to the diverse aetiology of these states of consciousness, and also to the intricate cerebral connectivity involved in their treatment. The present case study examines a patient who showed signs of emergence from the vegetative state after neurorehabilitation using The Combined Method Therapy (CMT). In this case, neurorehabilitation therapy was applied simultaneously with pharmacological treatment, stimulation, and neuroimaging techniques to help adjust drug dosage. The results of this study suggest that this combined approach to treatment promoted connectivity among posterior and anterior cortical regions aiding emergence from the vegetative state.

A chronometric functional sub-network in the thalamo-cortical system regulates the flow of neural information necessary for conscious cognitive processes.

The thalamo-cortical system has been defined as a neural network associated with consciousness. While there seems to be wide agreement that the thalamo-cortical system directly intervenes in vigilance and arousal, a divergence of opinion persists regarding its intervention in the control of other cognitive processes necessary for consciousness. In the present manuscript, we provide a review of recent scientific findings on the thalamo-cortical system and its role in the control and regulation of the flow of neural information necessary for conscious cognitive processes. We suggest that the axis formed by the medial prefrontal cortex and different thalamic nuclei (reticular nucleus, intralaminar nucleus, and midline nucleus), represents a core component for consciousness. This axis regulates different cerebral structures which allow basic cognitive processes like attention, arousal and memory to emerge. In order to produce a synchronized coherent response, neural communication between cerebral structures must have exact timing (chronometry). Thus, a chronometric functional sub-network within the thalamo-cortical system keeps us in an optimal and continuous functional state, allowing high-order cognitive processes, essential to awareness and qualia, to take place.

Synchronization between the anterior and posterior cortex determines consciousness level in patients with traumatic brain injury (TBI).

Survivors of traumatic brain injury (TBI) often suffer disorders of consciousness as a result of a breakdown in cortical connectivity. However, little is known about the neural discharges and cortical areas working in synchrony to generate consciousness in these patients. In this study, we analyzed cortical connectivity in patients with severe neurocognitive disorder (SND) and in the minimally conscious state (MCS). We found two synchronized networks subserving consciousness; one retrolandic (cognitive network) and the other frontal (executive control network). The synchrony between these networks is severely disrupted in patients in the MCS as compared to those with better levels of consciousness and a preserved state of alertness (SND). The executive control network could facilitate the synchronization and coherence of large populations of distant cortical neurons using high frequency oscillations on a precise temporal scale. Consciousness is altered or disappears after losing synchrony and coherence. We suggest that the synchrony between anterior and retrolandic regions is essential to awareness, and that a functioning frontal lobe is a surrogate marker for preserved consciousness. This article is part of a Special Issue entitled: Brain Integration.