Walter Sturm

On the Functional Neuroanatomy of Intrinsic and Phasic Alertness

Intrinsic and phasic alertness are the most basic aspects of attention intensity probably constituting the basis for the more complex and capacity-demanding aspects of attention selectivity. Intrinsic alertness represents the cognitive control of wakefulness and arousal and is typically assessed by simple reaction time tasks without a preceding warning stimulus. Phasic alertness, in contrast, is called for in reaction time tasks in which a warning stimulus precedes the target, and it represents the ability to increase response readiness subsequent to external cueing. We report PET and fMRI data from both the literature and our own experiments to delineate the cortical and subcortical networks subserving alertness, sustained attention (as another aspect of attention intensity), and spatial orienting of attention. Irrespective of stimulus modality, there seems to exist a mostly right-hemispheric frontal, parietal, thalamic, and brain-stem network which is coactivated by alerting and orienting attentional demands. These findings corroborate both the hypothesis of a frontal modulation of brain-stem activation probably via the reticular nucleus of the thalamus and of a coactivation of the posterior attention system involved in spatial orienting by the anterior alerting network. Under conditions of phasic alertness there are additional activations of left-hemisphere frontal and parietal structures which are interpreted as basal aspects of attention selectivity rather than additional features of alerting.

Functional anatomy of intrinsic alertness: evidencefor a fronto-parietal-thalamic-brainstem network in theright hemisphere

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.

Do Specific Attention Deficits Need Specific Training

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 o...

Effects of Blood Estrogen Level on Cortical Activation Patterns during Cognitive Activation as Measured by Functional MRI

Modulation of the blood estrogen level as it occurs during the menstrual cycle has a strong influence on both neuropsychological and neurophysiological parameters. One of currently preferred hypotheses is that the menstrual cycle hormones modulate functional hemispheric lateralization. We examined six male and six female subjects by functional magnetic resonance imaging (fMRI) to image cortical activation patterns associated with cognitive and motor activation to determine whether these changes during the menstrual cycle can be visualized. Female subjects, who did not use oral contraceptives, were scanned twice, once during the menses and once on the 11/12 day of the menstrual cycle. A word-stem-completion task, a mental rotation task and a simple motor task were performed by all subjects. Our data provide evidence that the menstrual cycle hormones influence the overall level of cerebral hemodynamics to a much stronger degree than they influence the activation pattern itself. No differences were seen between male subjects and female subjects during the low estrogen phase. During both neuropsychological tasks blood estrogen level had a profound effect on the size but not on the lateralization or the localization of cortical activation patterns. The female brain under estrogen showed a marked increase in perfusion in cortical areas involved in both cognitive tasks, whereas the hemodynamic effects during the motor tasks were less pronounced. This might be due to differences in neuronal or endothelian receptor concentration, differences in synaptic function, or, most likely, changes in the cerebrovascular anatomy in different cortical regions.

Network for auditory intrinsic alertness: a PET study.

Intrinsic alertness designates the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time (RT) measurements without preceding warning stimuli. Until now, cerebral networks subserving alertness after visual and somatosensory stimulation have been reported. Studies concerning other intensity aspects of alertness like sustained attention and vigilance, on the other hand, have been performed in the auditory modality, too. In a 15O-butanol PET-activation study in 10 right-handed young healthy male volunteers an intrinsic alertness network was studied for the auditory modality. In contrast with a sensorimotor control condition we found an extended predominantly right-hemisphere network similar to those reported for other sensory modalities including frontal, cingular, inferior parietal, temporal and thalamic structures, when subjects waited for and rapidly responded to a 1000 Hz tone signal by pressing a response key with the right-hand thumb. There were, however, some differences in the topography of the frontal, temporal and thalamic activations between auditory and visual stimulation which are discussed with respect to similar results for auditory vigilance and auditory selective attention tasks reported in the literature.

Estradiol Modulates Functional Brain Organization during the Menstrual Cycle: An Analysis of Interhemispheric Inhibition

According to the hypothesis of progesterone-mediated interhemispheric decoupling (Hausmann and Güntürkün, 2000), functional cerebral asymmetries (FCAs), which are stable in men and change during the menstrual cycle in women, are generated by interhemispheric inhibition of the dominant on the nondominant hemisphere. The change of lateralization during the menstrual cycle in women might indicate that sex hormones play an important role in modulating FCAs. We used functional magnetic resonance imaging to examine the role of estradiol in determining cyclic changes of interhemispheric inhibition. Women performed a word-matching task, while they were scanned twice during the cycle, once during the menstrual and once during the follicular phase. By use of a connectivity analysis we found that the inhibitory influence of left-hemispheric language areas on homotopic areas of the right hemisphere is strongest during the menses, resulting in a pronounced lateralization. During the follicular phase, due to rising estradiol levels, inhibition and thus functional cerebral asymmetries are reduced. These results reveal a powerful neuromodulatory action of estradiol on the dynamics of functional brain organization in the female brain. They may further contribute to the ongoing discussion of sex differences in brain function in that they help explain the dynamic part of functional brain organization in which the female differs from the male brain.

Mental fatigue and temporal preparation in simple reaction-time performance

Performance decrements attributed to mental fatigue have been found to be especially pronounced in tasks that involve the voluntary control of attention. Here we explored whether mental fatigue from prolonged time on task (TOT) also impairs temporal preparation for speeded action in a simple reaction-time task. Temporal preparation is enabled by a warning signal presented before the imperative stimulus and usually results in shorter reaction time (RT). When the delay between warning and imperative stimuli - the foreperiod (FP) - varies between trials, responses are faster with longer FPs. This pattern has been proposed to arise from either voluntary attentional processes (temporal orienting) or automatic trial-to-trial learning (trace conditioning). The former account suggests a selective RT increase on long-FP trials with fatigue; the latter account suggests no such change. Over a work period of 51 min, we found the typical increase in overall RT but no selective RT increase after long FPs. This additivity indicates that TOT-induced mental fatigue generally reduces cognitive efficiency but leaves temporal preparation under time uncertainty unaffected. We consider this result more consistent with the trace-conditioning account of temporal preparation.

Systems level modeling of a neuronal network subserving intrinsic alertness.

Cognitive control of alertness in unwarned situations (intrinsic alertness) relies on a predominantly right hemisphere cortical and subcortical network. In a previous functional activation study, we have demonstrated that this network comprises the anterior cingulate gyrus, the dorsolateral and polar frontal as well as the inferior parietal cortex, the thalamus and ponto-mesencephalic parts of the brain stem. The aim of this study was to study effective connectivity of this network by employing structural equation modeling. Fifteen right-handed male subjects participated in the PET study. The functional network showed stronger connectivity in the right hemisphere. Furthermore, there were strong effective connections between thalamus and brainstem on the one hand and between thalamus and anterior cingulate on the other. Our results suggest that the anterior cingulate functions as the central coordinating structure for the right hemispheric neural network of intrinsic alertness and that the anterior cingulate gyrus is modulated mainly by prefrontal and parietal cortex.

Comparison of cerebral blood flow acquired by simultaneous [15O]water positron emission tomography and arterial spin labeling magnetic resonance imaging.

Until recently, no direct comparison between [15O]water positron emission tomography (PET) and arterial spin labeling (ASL) for measuring cerebral blood flow (CBF) was possible. With the introduction of integrated, hybrid magnetic resonance (MR)-PET scanners, such a comparison becomes feasible. This study presents results of CBF measurements recorded simultaneously with [15O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [15O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant (P<0.05) correlation was observed between the two modalities; the whole-brain CBF values determined with PET and pCASL were 43.3 ±6.1 mL and 51.9 ± 7.1 mL per 100 g per minute, respectively. The gray/white matter (GM/WM) ratio of CBF was 3.0 for PET and 3.4 for pCASL. A paired t-test revealed differences in regional CBF between ASL and PET with higher ASL-CBF than PET-CBF values in cortical areas. Using an integrated, hybrid MR-PET a direct simultaneous comparison between ASL and [15O]water PET became possible for the first time so that temporal, physiologic, and functional variations were avoided. Regional and individual differences were found despite the overall similarity between ASL and PET, requiring further detailed investigations.

Recovery from hemineglect: differential neurobiological effects of optokinetic stimulation and alertness training.

We prospectively investigated by means of neuropsychological tests and functional magnetic resonance imaging (fMRI) the behavioural and neural effects of a 3-week optokinetic stimulation (OKS) training in 7 patients with chronic visuospatial neglect resulting from right-hemisphere lesions. Behaviourally, OKS caused both a short- and a long-term (4 weeks) improvement of performance in a neglect test battery (compared to a 3-week baseline period). This amelioration of neglect symptoms was associated with increases of neural activity during an fMRI spatial attention task bilaterally in the middle frontal gyrus and the precuneus. Additional left hemisphere increases in neural activity were observed in the cingulate gyrus, angular gyrus, middle temporal gyrus and occipital cortex. This pattern of activation represents a combination of areas normally involved in spatial attention plus a compensatory recruitment of left hemisphere areas. These results were then compared with data from our previous study (Thimm et al., 2006) which employed an alertness training (AIXTENT) with an otherwise identical treatment study design. After the OKS training there was more activation bilaterally in the precuneus than after the AIXTENT training. In contrast, after AIXTENT training there was more activation bilaterally in frontal cortex. Taken together, the results show that amelioration of neglect can be induced by both OKS and alertness training. The data furthermore suggest that the differential activations of frontal or parietal areas may reflect the specific impact of the two types of training either on an anterior system for the control of attention intensity (AIXTENT) or on the posterior system of spatial attention (OKS).