Locus Coeruleus Is Associated with Higher Openness to Experience and IQ: Implications for the Noradrenergic System for Novelty Seeking in Daily Life.

Novelty exposure and the upregulation of the noradrenergic (NA) system have been suggested as crucial for developing cognitive reserve and resilience against neurodegeneration. Openness to experience (OE), a personality trait associated with interest in novel experiences, may play a key role in facilitating this process. High-OE individuals tend to be more curious and encounter a wider range of novel stimuli throughout their lifespan. To investigate the relationship between OE and the main core of the NA system, the locus coeruleus (LC), as well as its potential mediation of IQ-a measure of cognitive reserve-MRI structural analyses were conducted on 135 healthy young adults. Compared with other neuromodulators' seeds, such as dorsal and median raphe-5-HT, ventral tegmental area-DA-, and nucleus basalis of Meynert-Ach-, the results indicated that higher LC signal intensity correlated with greater OE and IQ. Furthermore, mediation analyses revealed that only the LC played a mediating role between OE and IQ. These findings shed light on the neurobiology of personality and emphasize the importance of LC-NA system integrity in a novelty-seeking behavior. They provide a psychobiological explanation for how OE expression can contribute to the maintenance of the NA system, enhancing cognitive reserve and resilience against neurodegeneration.

Greater physical fitness ( VO 2 max ) in healthy older adults associated with increased integrity of the locus coeruleus-noradrenergic system.

AIM: Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater Vo 2 max - a measure of oxygen uptake and physical fitness (PF). METHODS: We hypothesized that greater Vo 2 max would be related to greater Locus Coeruleus (LC) MRI signal intensity. In a sample of 41 healthy subjects, we performed Voxel-Based Morphometry analyses, then repeated for the other neuromodulators as a control procedure (Serotonin, Dopamine and Acetylcholine). RESULTS: As hypothesized, greater Vo 2 max related to greater LC signal intensity, and weaker associations emerged for the other neuromodulators. CONCLUSION: This newly established link between Vo 2 max and LC-NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the NA system as a possible key factor building Reserve, it also provides ground for increasing LC-NA system resilience to neurodegeneration via Vo 2 max enhancement.

Meditation Experience is Associated with Increased Structural Integrity of the Pineal Gland and greater total Grey Matter maintenance.

Growing evidence demonstrates that meditation practice supports cognitive functions including attention and interoceptive processing, and is associated with structural changes across cortical networks including prefrontal regions, and the insula. However, the extent of subcortical morphometric changes linked to meditation practice is less appreciated. A noteworthy candidate is the Pineal Gland, a key producer of melatonin, which regulates circadian rhythms that augment sleep-wake patterns, and may also provide neuroprotective benefits to offset cognitive decline. Increased melatonin levels as well as increased fMRI BOLD signal in the Pineal Gland has been observed in mediators vs. controls. However, it is not known if long-term meditators exhibit structural change in the Pineal Gland linked to lifetime duration of practice. In the current study we performed Voxel-based morphometry (VBM) analysis to investigate: 1) whether long-term meditators (LTMs) (n=14) exhibited greater Pineal Gland integrity compared to a control group (n=969), 2) a potential association between the estimated lifetime hours of meditation (ELHOM) and Pineal Gland integrity, and 3) whether LTMs show greater Grey Matter (GM) maintenance (BrainPAD) that is associated with Pineal Gland integrity. The results revealed greater Pineal Gland integrity and lower BrainPAD scores (younger brain age) in LTMs compared to controls. Exploratory analysis revealed a positive association between ELHOM and greater signal intensity in the Pineal Gland but not with GM maintenance as measured by BrainPAD score. However, greater Pineal integrity and lower BrainPAD scores were correlated in LTMs. The potential mechanisms by which meditation influences Pineal Gland function, hormonal metabolism, and GM maintenance are discussed - in particular melatonin's roles in sleep, immune response, inflammation modulation, and stem cell and neural regeneration.

Dissociating the impact of alexithymia and impaired self-awareness on emotional distress and aggression after traumatic brain injury.

OBJECTIVE: Alexithymia, a deficit in identifying and describing feelings, is prevalent in traumatic brain injury (TBI). Sometimes referred to as "emotional unawareness," we sought to investigate whether alexithymia after TBI was related to, or distinct from, impaired self-awareness (ISA) and whether the two predicted differentiable emotional and aggression profiles. Further, the mediating role of frontal system behaviors (disinhibition, dysexecutive function, apathy) was explored. METHOD: Participants with TBI (N = 40) from diverse backgrounds completed self-report measures of alexithymia, emotional distress, aggression, and frontal system behaviors. For the assessment of ISA, significant other ratings were obtained to identify discrepancies from self-ratings. Data were analyzed quantitatively using independent samples t tests, correlations, partial correlations, and simple mediation. RESULTS: There was a negative correlation between alexithymia and ISA. Alexithymia, but not ISA, was associated with higher expressions of emotional distress and aggression even after controlling for the effects of ISA via partial correlations. Exploratory analyses found that frontal system behaviors mediated the relationships between alexithymia and aggression and alexithymia and emotional distress. CONCLUSIONS: Alexithymia is more accurately conceptualized as an emotional processing deficit than an awareness deficit. Indeed, self-awareness may be a prerequisite for the ability to identify alexithymic tendencies. Negative psychological effects of alexithymia are compounded by poorer executive function and disinhibition and call for the development of TBI-specific alexithymia screening tools and interventions. Alexithymia interventions are best delivered in conjunction with rehabilitation of emotion regulation and executive function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Greater physical fitness (Vo2Max) in healthy older adults associated with increased integrity of the Locus Coeruleus-Noradrenergic system.

Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater Vo2max - a measure of oxygen uptake and physical fitness (PF). In the current study, we hypothesised that greater Vo2 max would be related to greater Locus Coeruleus (LC) MRI signal intensity. As hypothesised, greater Vo2max related to greater LC signal intensity across 41 healthy adults (age range 60-72). As a control procedure, in which these analyses were repeated for the other neuromodulators' seeds (for Serotonin, Dopamine and Acetylcholine), weaker associations emerged. This newly established link between Vo2max and LC-NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the noradrenergic system as a possible key factor building Reserve, it also provide grounds for increasing LC-NA system resilience to neurodegeneration via Vo2max enhancement.

Pharmacological Manipulations of Physiological Arousal and Sleep-Like Slow Waves Modulate Sustained Attention.

Sustained attention describes our ability to keep a constant focus on a given task. This ability is modulated by our physiological state of arousal. Although lapses of sustained attention have been linked with dysregulations of arousal, the underlying physiological mechanisms remain unclear. An emerging body of work proposes that the intrusion during wakefulness of sleep-like slow waves, a marker of the transition toward sleep, could mechanistically account for attentional lapses. This study aimed to expose, via pharmacological manipulations of the monoamine system, the relationship between the occurrence of sleep-like slow waves and the behavioral consequences of sustained attention failures. In a double-blind, randomized-control trial, 32 healthy human male participants received methylphenidate, atomoxetine, citalopram or placebo during four separate experimental sessions. During each session, electroencephalography (EEG) was used to measure neural activity while participants completed a visual task requiring sustained attention. Methylphenidate, which increases wake-promoting dopamine and noradrenaline across cortical and subcortical areas, improved behavioral performance whereas atomoxetine, which increases dopamine and noradrenaline predominantly over frontal cortices, led to more impulsive responses. Additionally, citalopram, which increases sleep-promoting serotonin, led to more missed trials. Based on EEG recording, citalopram was also associated with an increase in sleep-like slow waves. Importantly, compared with a classical marker of arousal such as α power, only slow waves differentially predicted both misses and faster responses in a region-specific fashion. These results suggest that a decrease in arousal can lead to local sleep intrusions during wakefulness which could be mechanistically linked to impulsivity and sluggishness.SIGNIFICANCE STATEMENT We investigated whether the modulation of attention and arousal could not only share the same neuromodulatory pathways but also rely on similar neuronal mechanisms; for example, the intrusion of sleep-like activity within wakefulness. To do so, we pharmacologically manipulated noradrenaline, dopamine, and serotonin in a four-arm, randomized, placebo-controlled trial and examined the consequences on behavioral and electroencephalography (EEG) indices of attention and arousal. We showed that sleep-like slow waves can predict opposite behavioral signatures: impulsivity and sluggishness. Slow waves may be a candidate mechanism for the occurrence of attentional lapses since the relationship between slow-wave occurrence and performance is region-specific and the consequences of these local sleep intrusions are in line with the cognitive functions carried by the underlying brain regions.

Impaired metacognition and reduced neural signals of decision confidence in adults with traumatic brain injury.

OBJECTIVE: Metacognition reflects our capacity to monitor or evaluate other cognitive states as they unfold during task performance, for example, our level of confidence in the veracity of a memory. Impaired metacognition is seen in patients with traumatic brain injury (TBI) and substantially impacts their ability to manage functional difficulties during recovery. Recent evidence suggests that metacognitive representations reflect domain-specific processes (e.g., memory vs. perception) acting jointly with generic confidence signals mediated by widespread frontoparietal networks. The impact of neurological insult on metacognitive processes across different cognitive domains following TBI remains unknown. METHOD: To assess metacognitive accuracy, we measured decision confidence across both a perceptual and memory task in patients with TBI (n = 27) and controls (n = 28). During the metacognitive tasks, continuous electroencephalography was recorded, and event-related potentials (ERP) were analyzed. RESULTS: First, we observed a deficit in metacognitive efficiency across both tasks suggesting that patients show a loss of perceptual and memorial evidence available for confidence judgments despite equivalent accuracy levels to controls. Second, a late positive-going ERP waveform (500-700 ms) was greater in amplitude for high versus low-confidence judgements for controls across both task domains. By contrast, in patients with TBI, the same ERP waveform did not vary by confidence level suggesting a deficient or attenuated neural marker of decision confidence postinjury. CONCLUSIONS: These findings suggest that diffuse damage to putative frontoparietal regions in patients disrupts domain-general metacognitive accuracy and electrophysiological signals that accumulate evidence of decision confidence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Bridge between the Breath and the Brain: Synchronization of Respiration, a Pupillometric Marker of the Locus Coeruleus, and an EEG Marker of Attentional Control State.

Yogic and meditative traditions have long held that the fluctuations of the breath and the mind are intimately related. While respiratory modulation of cortical activity and attentional switching are established, the extent to which electrophysiological markers of attention exhibit synchronization with respiration is unknown. To this end, we examined (1) frontal midline theta-beta ratio (TBR), an indicator of attentional control state known to correlate with mind wandering episodes and functional connectivity of the executive control network; (2) pupil diameter (PD), a known proxy measure of locus coeruleus (LC) noradrenergic activity; and (3) respiration for evidence of phase synchronization and information transfer (multivariate Granger causality) during quiet restful breathing. Our results indicate that both TBR and PD are simultaneously synchronized with the breath, suggesting an underlying oscillation of an attentionally relevant electrophysiological index that is phase-locked to the respiratory cycle which could have the potential to bias the attentional system into switching states. We highlight the LC's pivotal role as a coupling mechanism between respiration and TBR, and elaborate on its dual functions as both a chemosensitive respiratory nucleus and a pacemaker of the attentional system. We further suggest that an appreciation of the dynamics of this weakly coupled oscillatory system could help deepen our understanding of the traditional claim of a relationship between breathing and attention.

Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age and Disease: An MRI Structural Study for the Alzheimer's Disease Neuroimaging Initiative.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the locus coeruleus-noradrenergic system (LC-NA) originating in the brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 mild cognitive impairment, 135 Alzheimer's disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD-an objective measure, which compares an individual's structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual's age). Further analyses were carried out on reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the serotoninergic (5-HT), dopaminergic (DA) and cholinergic (Ach) systems were contrasted with the noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems. Results supported by Bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g., cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

Young and restless, old and focused: Age-differences in mind-wandering frequency and phenomenology.

The consistently observed age-accompanied diminution in mind-wandering stands seemingly opposed to accounts that present mind-wandering as a failure of executive control. This study examined the impact of aging on the frequency and phenomenology of mind-wandering and investigated distinct variables mediating age-related differences in unintentional and intentional mind-wandering. Thirty-four younger and 34 healthy older adults completed a neuropsychological test battery and contrast change detection task embedded with experience sampling probes asking participants to discriminate the nature of their thoughts. Results revealed age-related decreases in unintentional and intentional mind-wandering, but equivalent task accuracy. Parallel mediations demonstrated that older adults reduced their unintentional mind-wandering through having less anxiety and greater task engagement than younger adults. Despite the evidence of age-related decline on cognitive function tests, neither executive function nor task demand variables further contributed to the model. Our results adjudicate between competing theories, highlighting the roles of affective and motivational factors in unintentional mind-wandering. Intentional mind-wandering showed no significant associations with the neuropsychological measures; however, intentional mind-wandering was associated with more false alarms, which was mediated by greater reaction time variability (RTV). In the context of the exploitation/exploration framework, we suggest that younger adults were more inclined to intentionally mind-wander, indexed by increased RTV, while preserving comparable performance accuracy to older adults. Conversely, older adults exploited greater task focus, marked by reduced RTV, with less bias toward, or resources for, exploration of the mind-wandering space. Therefore, dispositional and strategic factors should be considered in future investigations of mind-wandering across the lifespan. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Prefrontal Modulation of Visual Processing and Sustained Attention in Aging, a tDCS-EEG Coregistration Approach.

The ability to sustain attention is integral to healthy cognition in aging. The right PFC (rPFC) is critical for maintaining high levels of attentional focus. Whether plasticity of this region can be harnessed to support sustained attention in older adults is unknown. We used transcranial direct current stimulation to increase cortical excitability of the rPFC, while monitoring behavioral and electrophysiological markers of sustained attention in older adults with suboptimal sustained attention capacity. During rPFC transcranial direct current stimulation, fewer lapses of attention occurred and electroencephalography signals of frontal engagement and early visual attention were enhanced. To further verify these results, we repeated the experiment in an independent cohort of cognitively typical older adults using a different sustained attention paradigm. Again, prefrontal stimulation was associated with fewer attentional lapses. These experiments suggest the rPFC can be manipulated in later years to increase top-down modulation over early sensory processing and improve sustained attention performance. This holds valuable information for the development of neurorehabilitation protocols to ameliorate age-related deficits in this capacity.

Coupling of respiration and attention via the locus coeruleus: Effects of meditation and pranayama.

The locus coeruleus (LC) has established functions in both attention and respiration. Good attentional performance requires optimal levels of tonic LC activity, and must be matched to task consistently. LC neurons are chemosensitive, causing respiratory phrenic nerve firing to increase frequency with higher CO2 levels, and as CO2 level varies with the phase of respiration, tonic LC activity should exhibit fluctuations at respiratory frequency. Top-down modulation of tonic LC activity from brain areas involved in attentional regulation, intended to optimize LC firing to suit task requirements, may have respiratory consequences as well, as increases in LC activity influence phrenic nerve firing. We hypothesize that, due to the physiological and functional overlaps of attentional and respiratory functions of the LC, this small neuromodulatory nucleus is ideally situated to act as a mechanism of synchronization between respiratory and attentional systems, giving rise to a low-amplitude oscillation that enables attentional flexibility, but may also contribute to unintended destabilization of attention. Meditative and pranayama practices result in attentional, emotional, and physiological enhancements that may be partially due to the LC's pivotal role as the nexus in this coupled system. We present original findings of synchronization between respiration and LC activity (via fMRI and pupil dilation) and provide evidence of a relationship between respiratory phase modulation and attentional performance. We also present a mathematical dynamical systems model of respiratory-LC-attentional coupling, review candidate neurophysiological mechanisms of changes in coupling dynamics, and discuss implications for attentional theory, meditation, and pranayama, and possible therapeutic applications.

Plasticity of the Right-Lateralized Cognitive Reserve Network in Ageing.

Cognitive reserve (CR) is the phenomenon where older adults with more cognitively stimulating environments show less age-related cognitive decline. The right-lateralized fronto-parietal network has been proposed to significantly contribute to CR and visual attention in ageing. In this study we tested whether plasticity of this network may be harnessed in ageing.We assessed CR and parameters of visual attention capacity in older adults. Transcranial direct current stimulation (tDCS) was employed to increase right fronto-parietal activity during a lateralized whole-report task. At baseline, older adults with greater CR showed a stronger hemifield asymmetry in processing speed towards the left visual-field, indicative of stronger involvement of the right hemisphere in these individuals. Correspondingly, processing speed improved during right prefrontal tDCS. Older adults with lower levels of CR showed tDCS-related improvements in processing speed in the left but not right hemifield: thus tDCS temporarily altered their processing speed asymmetry to resemble that of their high reserve peers.The finding that stronger right hemisphere involvement is related to CR supports Robertson's theory. Furthermore, preserved plasticity within the right prefrontal cortex in older adults suggests this is a viable target area to improve visual processing speed, a hallmark of age-related decline.

The Effects of Methylphenidate on the Neural Signatures of Sustained Attention.

BACKGROUND: Although it is well established that methylphenidate (MPH) enhances sustained attention, the neural mechanisms underpinning this improvement remain unclear. We examined how MPH influenced known electrophysiological precursors of lapsing attention over different time scales. METHODS: We measured the impact of MPH, compared with placebo, on behavioral and electrocortical markers while healthy adults (n = 40) performed a continuous monitoring paradigm designed to elicit attentional lapses. RESULTS: MPH led to increased rates of target detection, and electrophysiological analyses were conducted to identify the mechanisms underlying these improvements. Lapses of attention were reliably preceded by progressive increases in alpha activity that emerged over periods of several seconds. MPH led to an overall suppression of alpha activity across the entire task but also diminished the frequency of these maladaptive pretarget increases through a reduction of alpha variability. A drug-related linear increase in the amplitude of the frontal P3 event-related component was also observed in the pretarget timeframe (3 or 4 seconds). Furthermore, during immediate target processing, there was a significant increase in the parietal P3 amplitude with MPH, indicative of enhanced perceptual evidence accumulation underpinning target detection. MPH-related enhancements occurred without significant changes to early visual processing (visual P1 and 25-Hz steady-state visual evoked potential). CONCLUSIONS: MPH serves to reduce maladaptive electrophysiological precursors of lapsing attention by acting selectively on top-down endogenous mechanisms that support sustained attention and target detection with no significant effect on bottom-up sensory excitability. These findings offer candidate markers to monitor the therapeutic efficacy of psychostimulants or to predict therapeutic responses.

Domain-specific and domain-general processes underlying metacognitive judgments.

Metacognition and self-awareness are commonly assumed to operate as global capacities. However, there have been few attempts to test this assumption across multiple cognitive domains and metacognitive evaluations. Here, we assessed the covariance between "online" metacognitive processes, as measured by decision confidence judgments in the domains of perception and memory, and error awareness in the domain of attention to action. Previous research investigating metacognition across task domains have not matched stimulus characteristics across tasks raising the possibility that any differences in metacognitive accuracy may be influenced by local task properties. The current experiment measured metacognition in perceptual, memorial and attention tasks that were closely matched for stimulus characteristics. We found that metacognitive accuracy across the three tasks was dissociated suggesting that domain specific networks support an individual's capacity for accurate metacognition. This finding was independent of objective performance, which was controlled using a staircase procedure. However, response times for metacognitive judgments and error awareness were associated suggesting that shared mechanisms determining how these meta-level evaluations unfold in time may underlie these different types of decision. In addition, the relationship between these laboratory measures of metacognition and reports of everyday functioning from participants and their significant others (informants) was investigated. We found that informant reports, but not self reports, predicted metacognitive accuracy on the perceptual task and participants who underreported cognitive difficulties relative to their informants also showed poorer metacognitive accuracy on the perceptual task. These results are discussed in the context of models of metacognitive regulation and neuropsychological evidence for dissociable metacognitive systems. The potential for the refinement of metacognitive assessment in clinical populations is also discussed.

Connecting Self-Awareness and Error-Awareness in Patients with Traumatic Brain Injury.

Impaired self-awareness after traumatic brain injury (TBI) is often seen in stark contrast to the observations of significant-others, who are acutely aware of the difficulties experienced by patients. Our objective was to investigate the relationship between metacognitive knowledge in daily life and emergent awareness of errors during laboratory tasks, since the breakdown of error detection mechanisms may impose limitations on the recovery of metacognitive knowledge after TBI. We also examined the extent to which these measures of awareness can predict dysexecutive behaviors. A sample of TBI patients (n=62) and their significant-others, provided reports of daily functioning post injury. In addition, patients underwent a neuropsychological assessment and were instructed to signal their errors during go/no-go tests. Interrelationships between metacognitive and emergent levels of awareness were examined, after controlling for the influence of secondary cognitive variables. Significant-other ratings correlated with errors made by the patients on neuropsychological tests but not with their premorbid function. Patients who under-reported daily life difficulties or over-reported their competency, compared to significant-other reports, were less likely to show awareness of laboratory errors. Emergent awareness was also identified as the sole predictor of performance on the modified six-element test, an ecologically valid test of multitasking. The online breakdown of error awareness after brain injury is related to difficulties with metacognitive awareness as reported in daily life, and is also predictive of dysexecutive behaviors. These findings are discussed in the context of multidimensional and neural models of awareness and error monitoring.

Characterising neural signatures of successful aging: Electrophysiological correlates of preserved episodic memory in older age.

While aging is associated with a gradual decline in memory, substantial preservation of function is observed in certain individuals and dissecting this heterogeneity is paramount to understanding successful aging. A cohort of elderly individuals were classified according to their level of memory preservation and administered a test of episodic memory in which participants were cued to learn or simply read each word and then to identify previously presented items in a delayed recognition phase. Mathematical modelling revealed that relatively preserved memory function was specifically linked to a faster rate of memorial evidence accumulation (drift rate). Analysis of event-related potentials at encoding revealed that high-performing elderly exhibited signals over parietal regions that discriminated between words to be learned vs. read for an additional 300-ms compared to young subjects suggesting a compensatory encoding mechanism that was absent in the low-performing group. At recognition, parietal signals associated with recollection processes discriminated previously learned words from read words in the young and high-performing old but not in low-performing old. These results reveal that successful aging is associated with specific adaptive neural markers during both encoding and retrieval.

Impaired auditory selective attention ameliorated by cognitive training with graded exposure to noise in patients with traumatic brain injury.

Patients who suffer traumatic brain injury frequently report difficulty concentrating on tasks and completing routine activities in noisy and distracting environments. Such impairments can have long-term negative psychosocial consequences. A cognitive control function that may underlie this impairment is the capacity to select a goal-relevant signal for further processing while safeguarding it from irrelevant noise. A paradigmatic investigation of this problem was undertaken using a dichotic listening task (study 1) in which comprehension of a stream of speech to one ear was measured in the context of increasing interference from a second stream of irrelevant speech to the other ear. Controls showed an initial decline in performance in the presence of competing speech but thereafter showed adaptation to increasing audibility of irrelevant speech, even at the highest levels of noise. By contrast, patients showed linear decline in performance with increasing noise. Subsequently attempts were made to ameliorate this deficit (study 2) using a cognitive training procedure based on attention process training (APT) that included graded exposure to irrelevant noise over the course of training. Patients were assigned to adaptive and non-adaptive training schedules or to a no-training control group. Results showed that both types of training drove improvements in the dichotic listening and in naturalistic tasks of performance in noise. Improvements were also seen on measures of selective attention in the visual domain suggesting transfer of training. We also observed augmentation of event-related potentials (ERPs) linked to target processing (P3b) but no change in ERPs evoked by distractor stimuli (P3a) suggesting that training heightened tuning of target signals, as opposed to gating irrelevant noise. No changes in any of the above measures were observed in a no-training control group. Together these findings present an ecologically valid approach to measure selective attention difficulties after brain injury, and provide a means to ameliorate these deficits.

Connecting clinical and experimental investigations of awareness in traumatic brain injury.

Questionnaire-based demonstrations of impaired self-awareness (SA) after traumatic brain injury (TBI) are not always supported by experimental studies of in-the-moment or online awareness. This chapter begins by describing the clinical phenomenon of impaired SA, how it is measured, and why its interdependency with mechanisms of online awareness may provide the scaffolding from which appraisals of cognitive functioning can be accurately revised following a brain injury. We review research that has measured unawareness of errors in routine action in TBI patients and propose more rigorous methodological approaches to studying the emergent properties of awareness with greater clarity in the laboratory. We discuss how neuropsychological and electrophysiologic studies are beginning to inform our understanding of impaired error processing in TBI patients and we highlight recent theory proposing that online metacognitive processes accumulate evidence of erroneous responses in a graded fashion. Neural signals with amplitudes that scale with the strength of accruing evidence and peak latencies that mark the threshold at which awareness emerges represent important neural mechanisms to examine the breakdown of error awareness after brain injury. We also discuss how errors can be investigated in relation to different sources of evidence that contribute to aware experiences after brain injury. Finally, we explore conditions beyond error signaling, and how different "objects of insight" that require retrospective and prospective judgments of confidence need to be examined in relation to the clinical phenomenon of impaired SA.

The effects of immunologic brainstem encephalopathy on cognitive function following awakening from a progressive autoimmune coma.

We describe a unique patient who experienced a progressive autoimmune coma from age 14 to 17. The patient awoke after treatment with immunosuppressant medication. Although alertness, verbalization, and mobilization markedly improved, the patient reported persistent cognitive difficulties. Neuropsychological assessment from age 21 showed impairments in selective attention, distractibility, and memory. Conversely, higher-order executive functions were preserved. Electrophysiological analysis also identified abnormal neural signatures of selective attention. Eighteen months after the neuropsychological assessment, voxel-based morphometry revealed reduced white matter in the medulla compared to controls. The findings are discussed in terms of the impact of brainstem encephalopathy on cognitive mechanisms.