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Functional anatomy of intrinsic alertness: Evidence for a fronto-parietal-thalamic-brainstem network in the right hemisphere
Abstract
Alertness, the most basic intensity aspect of attention, probably is a prerequisite for the more complex and capacity demanding domains of attention selectivity. Behaviorally, intrinsic alertness represents the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time measurements without preceding warning stimuli. Up until now only parts of the cerebral network subserving alertness have been revealed in animal, lesion, and functional imaging studies. Here, in a 15O-butanol PET activation study in 15 right-handed young healthy male volunteers for this basic attention function we found an extended right hemisphere network including frontal (anterior cingulate-dorsolateral cortical)-inferior parietal-thalamic (pulvinar and possibly the reticular nucleus) and brainstem (ponto-mesencephalic tegmentum, possibly involving the locus coeruleus) structures, when subjects waited for and rapidly responded to a centrally presented white dot by pressing a response key with the right-hand thumb.
... We also expected a left lateralization of the alerting network (Fan et al. 2005;Yanaka et al. 2010) and a right lateralization of the orienting network (Thiebaut de Schotten et al. 2011). Additionally, we expected that the alerting network would recruit projection tracts, given that the anterior alerting system depends on cortico-subcortical interactions (Clemens et al. 2011;Sturm et al. 1999;Sturm and Willmes 2001). Finally, we predicted that the executive attention network would chiefly rely on white matter tracts connecting the frontal lobe with the rest of the brain. ...
... Finally, activations involving association fronto-parietal tracts such as the left SLF III were found. This set of results is not only congruent with previous findings (Clemens et al. 2011;Coull et al. 2001;Fan et al. 2005;Sturm et al. 1999;Sturm and Willmes 2001;Yanaka et al. 2010), but also offers a broad picture of the phasic alerting system. The temporal areas seem to be a crucial hub for the auditory warning system, and this area FAT. ...
... Indeed, connections to the left occipital and frontal areas were positively correlated with better use of the warning signals. In our main results (when we compared tone present versus tone absent trials), we did not find an involvement of midbrain or thalamic areas (Chica et al. 2016;Clemens et al. 2011;Haupt et al. 2019;Sturm et al. 1999;Sturm and Willmes 2001) or projection thalamic white matter tracts (Ge et al. 2013;Luna et al. 2021;Niogi et al. 2010), as have been found in other studies. However, when we explored the correlation between brain activation and behavior, we observed an involvement of the left anterior thalamic radiation. ...
Attention is a heterogeneous function theoretically divided into different systems. While functional magnetic resonance imaging (fMRI) has extensively characterized their functioning, the role of white matter in cognitive function has gained recent interest due to diffusion-weighted imaging advancements. However, most evidence relies on correlations between white matter properties and behavioral or cognitive measures. This study used a new method that combines the signal from distant voxels of fMRI images using the probability of structural connection given by high-resolution normative tractography. We analyzed three fMRI datasets with a visual perceptual task and three attentional manipulations: phasic alerting, spatial orienting, and executive attention. The phasic alerting network engaged temporal areas and their communication with frontal and parietal regions, with left hemisphere dominance. The orienting network involved bilateral fronto-parietal and midline regions communicating by association tracts and interhemispheric fibers. The executive attention network engaged a broad set of brain regions and white matter tracts connecting them, with a particular involvement of frontal areas and their connections with the rest of the brain. These results partially confirm and extend previous knowledge on the neural substrates of the attentional system, offering a more comprehensive understanding through the integration of structure and function.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00429-024-02824-1.
... The construct is generally defined as the attentional capacity to maintain performance over time. Given the diversity of terms and measures linked to vigilance, some authors deem it as a nonunitary concept (Langner & Eickhoff, 2013;Luna et al., 2018;Sturm et al., 1999). In this vein, Luna et al. distinguish two components of vigilance: executive vigilance (EV) and arousal vigilance (AV). ...
Halperin and Schulz’s neurodevelopmental model postulates that the onset of attention-deficit/hyperactivity disorder (ADHD) in childhood is due to subcortical alterations, whereas the disorder’s trajectory into adulthood depends on the development of executive functions. Based on a dimensional framework of ADHD, Coll-Martín et al. (2021) found support for the model in an adult community sample assessed on arousal and executive vigilance. The present study is a preregistered (https://osf.io/tkdq7) close replication of Coll-Martín et al. expressly aimed to test the two predictions of the model. A sample of college students (N = 292 valid; 49% women; 18–30 years, M = 21.7) from a Spanish university completed self-reports of ADHD symptoms in childhood (retrospectively) and adulthood and performed the online version of an attentional task (the ANTI-Vea). Our preregistered hypotheses achieved an acceptable statistical power for the effects of interest, even after accounting for random measurement error. Despite this, none of them replicated the findings of the original study: Only the unexpected negative correlation between executive vigilance and symptoms in childhood was significant, thereby not supporting the theoretical predictions. The lack of support for the dissociation pattern hypothesized by the neurodevelopmental model was robust to multiverse and exploratory analyses. At least in terms of vigilance, ADHD symptoms seem to share altered neurocognitive pathways across the lifespan, regardless of their time of onset. This challenges the notion of late-onset ADHD as a condition neuropsychologically distinct from child-onset ADHD. Future studies need to include complementary assessment methods and clinical groups.
... The changes in PCr/Pi in the right hemisphere showed a performance-related dependency between higher levels of PCr/Pi in the temporal region, and scores in PVT (0.1 percentile) and SPAN task (Fig. S6). SD and alertness-related studies showed a right hemisphere dependency in neuronal activation in the right hemisphere [36][37][38][39][40] . ...
The inverse effects of creatine supplementation and sleep deprivation on high energy phosphates, neural creatine, and cognitive performances suggest that creatine is a suitable candidate for reducing the negative effects of sleep deprivation. With this, the main obstacle is the limited exogenous uptake by the central nervous system (CNS), making creatine only effective over a long-term diet of weeks. Thus far, only repeated dosing of creatine over weeks has been studied, yielding detectable changes in CNS levels. Based on the hypothesis that a high extracellular creatine availability and increased intracellular energy consumption will temporarily increase the central creatine uptake, subjects were orally administered a high single dose of creatinemonohydrate (0.35 g/kg) while performing cognitive tests during sleep deprivation. Two consecutive ³¹P-MRS scans, ¹H-MRS, and cognitive tests were performed each at evening baseline, 3, 5.5, and 7.5 h after single dose creatine (0.35 g/kg) or placebo during sub-total 21 h sleep deprivation (SD). Our results show that creatine induces changes in PCr/Pi, ATP, tCr/tNAA, prevents a drop in pH level, and improves cognitive performance and processing speed. These outcomes suggest that a high single dose of creatine can partially reverse metabolic alterations and fatigue-related cognitive deterioration.
... 61,63 These sleepdeprivation studies also demonstrated significant decreases of brain activity in prefrontal and posterior parietal cortexes, which is in line with reported significant correlations between (right lateralized) fronto-parietal-thalamic-brainstem areas on the one hand and alertness and sustained attention or vigilance on the other. [64][65][66] These findings corroborate the above-mentioned effects of sleep loss on cognition. What's more, patients with COPD-suffering from chronic hypoxemia-seem to show diverging neuropsychological test results. ...
Study objectives
As the effects of general slowness and decreased attentional capacity on higher executive attention have not been fully taken into account in the sleep apnea literature, we statistically controlled for basic attentional performance in evaluating executive attention per se in sleep apnea patients.
Design
A case-controlled design was used with comparison of basic and executive attentional tasks.
Participants
Thirty-six polysomnographically diagnosed patients (mean apnea-hypopnea index = 60.5 ± SD 31.6) participated, together with 32 healthy controls.
Measurements and Results
Neuropsychological tests included Trail Making part A and B, Symbol Digit Modalities (SDMT), Digit Span forward and backward, Stroop Color-Word, Five-Point design fluency, and an Attentional Flexibility task. Patients’ vigilance data indicated time-on-task decrements after 10 minutes. Moreover, their performance was significantly reduced on the SDMT (effect size d = 0.93), the Digit Span forward task (d = 0.44), the number of errors on the basic 2-choice reaction time subtest of the Attentional Flexibility task (d = 0.74) and the mean RT on the actual Attentional Flexibility subtest (d = 0.54). It has been argued that the latter poor performance was probably primarily related to the task’s phonologic loop component of working memory rather than to an attentional switching deficit per se. No other performance differences were found between patients and healthy controls.
Conclusions
In addition to vigilance decrements, attentional capacity deficits clearly emerge, ie, slowed information processing and decreased short-term memory span. However, no specific clinical indications for executive attentional deficits—such as disinhibition, distractibility, perseveration, attentional switching dysfunction, decreased design fluency, or an impaired central executive of working memory—are found in patients with severe sleep apnea. Their cognitive performance seems very similar to the cognitive decline found after sleep loss and qualitatively different from patients with chronic obstructive pulmonary disease, suggesting sleepiness as the primary factor in a parsimonious explanation for the attention deficits in sleep apnea, without the need to assume prefrontal brain damage.
Lower executive attention is expected to be associated with higher social anxiety. However, previous studies have reported inconsistent results. This study examines how the interaction of intrinsic alertness, orienting, and executive attention are associated with social anxiety. A total of 100 participants completed the Attention Network Test and Japanese version of the Liebowitz Social Anxiety Scale. The results of hierarchical multiple regression analyses showed the three-way interaction effect of intrinsic alertness, orienting, and executive attention on social anxiety. Lower executive attention was associated with higher social anxiety when intrinsic alertness was at a high level and orienting was at a low level. These results indicate that when examining the relationship between executive attention and social anxiety, we need to consider intrinsic alertness and orienting.
Conventional Buddhist texts illustrate meditation as a condition of relaxed alertness that must fend against extreme hypoarousal (sleep, drowsiness) and extreme hyperarousal (restlessness). Theoretical, neurophysiological, and neuroimaging investigations of meditation have highlighted the relaxing effects and hypoarousing without emphasizing the alertness-promoting effects. Here we performed a systematic review supported by an activation-likelihood estimate (ALE) meta-analysis in an effort to counterbalance the surfeit of scholarship emphasizing the hypoarousing and relaxing effects of different forms of Buddhist meditation. Specifically, the current systematic review-cum-meta-analytical review seeks to highlight more support for meditation’s wake-promoting effects by drawing from neuroimaging research during wakefulness and meditation. In this systematic review and meta-analysis of 22 fMRI studies, we aim to highlight support for Buddhist meditation’s wake-promoting or arousing effects by identifying brain regions associated with alertness during meditation. The most significant peaks were localized medial frontal gyrus (MFG) and precuneus. We failed to determine areas ostensibly common to alertness-related meditation such as the medial prefrontal cortex (mPFC), superior parietal lobule, basal ganglia, thalamus, most likely due to the relatively fewer fMRI investigations that used wakefulness-promoting meditation techniques. Also, we argue that forthcoming research on meditation, related to alertness or wakefulness, continues to adopt a multi-modal method to investigate the correlation between actual behaviors and neural networks connected to Buddhist meditation. Moreover, we recommend the implementation of fMRI paradigms on Buddhist meditation with clinically diagnosed participants to complement recent trends in psychotherapy such as mindfulness-based cognitive therapy (MBCT).
Nine positron emission tomography (PET) studies of human visual information processing were reanalyzed to determine the consistency across experiments of blood flow increases during active tasks relative to passive viewing of the same stimulus array. No consistent blood flow increases were found in cerebral cortex outside of the visual system, but increases were seen in the thalamus and cerebellum. Although most tasks involve increases in arousal, establishing an intention or behavioral goal, setting up control structures for sequencing task operations, detecting targets, etc., these operations do not produce blood flow increases, detectable with the present methods, in localized cortical regions that are common across tasks. Common subcortical regions, however, may be involved.
A left cerebellar and a medial cerebellar focus reflected motor-related processes. Blood flow increases in these regions only occurred in experiments in which the subject made an overt response and were largest when the response was made in the active but not passive condition. These motor-related processes were more complex than simple motor execution, however, since increases were still present when the response was made in both the active and passive conditions. These cerebellar increases may reflect processes related to response selection.Blood flow increases in a right cerebellar region were not motor-related. Increases were not modulated by the presence or absence of motor responses during either the active or passive conditions, and increases were sensitive to within-experiment variables that held the motor response constant. Increases occurred in both language and nonlanguage tasks and appeared to involve a general nonmotor process, but the nature of that process was difficult to specify.
A right thalamic focus was sensitive to variables related to focal attention, suggesting that this region was involved in attentional engagement. Right thalamic increases were also correlated over conditions with increases in the left and medial cerebellum, perhaps reflecting additional contributions from motor-related nuclei receiving cerebellar projections.
Blood flow increases in a left thalamic focus were completely uncorrelated over conditions with increases in the right thalamus, indicating that it was involved in different functions. Both the left thalamus and right cerebellum yielded larger blood flow increases when subjects performed a complex rather than simple language task, possibly reflecting a language-related pathway. Blood flow increases in the left thalamus were also observed, however, during nonlanguage tasks.
The efficacy of game-like computerised adaptive training programmes for intensity aspects of attention (alertness and vigilance) and selectivity aspects of attention (selective and divided attention) was studied in patients with left or right focal brain damage of vascular aetiology. Each patient received consecutive training in the two most impaired of the four attention domains. Control tests were performed by means of a standardised computerised attention test battery comprising tests for the four attention functions. Assessment was carried out at the beginning and after each of two training periods of 14 one-hour sessions each. There were significant specific training effects for both intensity aspects (alertness and vigilance), and also for response time in the selective attention and error rate in the divided attention task. For selectivity aspects of attention, reaction time also improved after training of basic attention domains. The application of inferential single case procedures revealed not only a high degree of specific training effects in individual cases but also a substantial number of deteriorations in performance after non-specific training of basic attention problems by tasks requiring selectivity of attention. The results are discussed in the light of a hierarchical organisation of attention functions.
Vigilance behavior, or watch keeping, involves the focusing of attention on the detection of subtle changes in the environment that occur over a long period of time. We investigated the time course of changes in brain activity during the continuous performance of a 60-min auditory vigilance task. The task required the detection of an intensity drop that occurred in 5% of the auditory stimuli. Six 1-min samples of cerebral blood flow (CBF) and electroencephalographic (EEG) activity were obtained at l0-min intervals during the vigilance performance. Changes in CBF were measured by means of positron emission tomography (PET). Performance data (hits, false alarms, reaction time) were analyzed across six 10-min blocks. Eight healthy male volunteers participated in the study. During the 60-min test, the number of correct detections (hits) did not change, but both the reaction time and EEG activity in the theta (4 to 7 Hz) range progressively increased across testing. CBF in several subcortical structures (thalamus, substantia innominata, and putamen) and cortical areas (ventrolateral, dorsolateral, and orbital frontal cortex; parietal cortex; and temporal cortex) decreased as a function of time-on-task; changes in the cortical regions were limited to the right hemisphere. Blood flow also decreased in the temporalis muscles. At the same time, CBF increased in several visual cortical areas including the left and right fusiform gyri. Furthermore, the thalamic blood-flow response co-varied with that in the substantia innominata, the ponto-mesencephalic tegmentum, and the anterior cingulate cortex. The right ventrolateral-frontal blood-flow response covaried with that in the right parietal, orbitofrontal, and dorsolateral frontal cortex. 'Iko main conclusions are drawn from the obtained data. First, we suggest that the observed time-related changes in reaction time, EEG activity, and blood flow in the temporalis muscles are related to changes in the level of arousal (alertness) and that CBF changes in the thalamus-related neural circuitry represent a brain correlate of such changes. Second, we speculate that time-related CBF decreases in cortical regions of the right hemisphere underlie a shift from controlled to automatic attentional processing of the auditory stimuli.
This paper concerns the spatial and intensity transformations that map one image onto another. We present a general technique that facilitates nonlinear spatial (stereotactic) normalization and image realignment. This technique minimizes the sum of squares between two images following nonlinear spatial deformations and transformations of the voxel (intensity) values. The spatial and intensity transformations are obtained simultaneously, and explicitly, using a least squares solution and a series of linearising devices. The approach is completely noninteractive (automatic), nonlinear, and noniterative. It can be applied in any number of dimensions.
Various applications are considered, including the realignment of functional magnetic resonance imaging (MRI) time-series, the linear (affine) and nonlinear spatial normalization of positron emission tomography (PET) and structural MRI images, the coregistration of PET to structural MRI, and, implicitly, the conjoining of PET and MRI to obtain high resolution functional images.
"Laboratory researches on prolonged visual search led to the development of an experimental situation in which the trend of ability at synthetic look-out duties was studied throughout long watchkeeping spells by the automatic production of occasional brief and barely visible signals. These stimuli were given at irregular intervals… ." Interpretation of results is made in terms of a conditioned stimulus formulation. 25 references. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The anatomical correlates of extrapersonal visual neglect were investigated in 110 right-handed stroke patients with lesions confined to the right hemisphere. Neglect is much more frequently associated with retrorolandic damage, as compared with frontal lesions. The inferior parietal lobule appears to be the area most frequently involved in patients with cortical lesions showing signs of neglect. When the cerebral lesion is confined to deep structures, neglect occurs much more frequently when grey nuclei such as the thalamus and the basal ganglia are damaged; a remarkable number of negative cases were, however, found. Conversely, lesions limited to the subcortical white matter are rarely associated with neglect. The relevance of these results to anatomophysiological models of directed attention and neglect is discussed.
Recruiting responses and related synchronous activities appear to be mediated by thalamic inhibition originating in nucleus reticularis thalami, a structure jointly regulated by an ascending projection from mesencephalic reticular formation and a descending influence from the frontal cortex. Extracellular unit activity was recorded in the anterior nucleus reticularis thalami (RVA) during recruiting responses, augmenting responses, stimulation of the mesencephalic reticular formation (MRF), and cryogenic blockade of the inferior thalamic peduncle (ITP). During recruiting responses, RVA units responded to medial thalamic (MT) stimulation with prolonged high frequency bursts. Analysis of the post-stimulus time histograms of these responses showed them to have the same latency, duration, incrementing character, and envelope shape as the phasic thalamic inhibitory postsynaptic potentials (IPSPs) which appear to mediate recruiting responses. Brief stimulation of the MRF, which abolishes recruiting responses and thalamic IPSPs, prevented the response of RVA units to MT stimuli, and inhibited the spontaneous discharge of these units for 20 sec or more. We propose that the desynchronizing effect of MRF activation results from the abolition of thalamic inhibition originating in RVA. Cryogenic blockade of the ITP, which abolishes recruiting responses in the thalamus and cortex, also prevented R units from responding to MT stimuli. This result suggests that the MT activates R units via a thalamo-frontocortico-R pathway and explains the long latency of R bursts and thalamic IPSPs following MT stimulation. R cells that fired prolonged bursts during recruiting responses did not respond during augmenting responses. This result suggests that separate thalamic inhibitory mechanisms are involved in these two types of synchronization.
Following ligation of the right middle cerebral artery, rats were hyperactive for 2 to 3 weeks whether activity was measured by running wheel revolutions or open field observations. Assays of brain catecholamines revealed 30 percent reductions of norepinephrine in the injured and uninjured cortex and locus coeruleus and a 20 percent reduction of dopamine in the substantia nigra. In contrast, rats with left middle cerebral artery ligations did not become hyperactive and did not show any significant change in catecholamines in any of the brain areas studied. Right and left hemispheric infarctions were comparable in their locations and extent of tissue damage. This lateralization of behavioral and biochemical response to cerebral infarction may be the consequence of anatomical or physiological asymmetries in the brain.