Christiane M. Thiel

Cerebral correlates of alerting, orienting and reorienting of visuospatial attention: an event-related fMRI study.

The identification of brain systems contributing to different aspects of visuospatial attention is of both clinical and theoretical interest. Cued target detection tasks provide a simple means to dissociate attentional subcomponents, such as alerting, orienting or reorienting of attention. Event-related functional magnetic resonance imaging (fMRI) was used to study neural correlates of these distinct attentional processes. Volunteers were scanned while performing a centrally cued target detection task. Four different types of trials (no cue, neutral cue, valid cue and invalid cue trials) with targets appearing either in the right or left hemifield were randomly intermixed. Behaviourally, the data provided evidence for alerting, spatial orienting and reorienting of attention. Neurally, the alerting effect was seen in bilaterally increased extrastriatal blood oxygenation level-dependent (BOLD) activity in neutral as compared to no cue trials. Neural correlates of spatial orienting were seen in anterior cingulate cortex, which was more active during valid as compared to neutral cue trials. Neural correlates of reorienting of attention, that is, higher BOLD activity to invalid as compared to validly cued trials were evident in several brain regions including left and right intraparietal sulcus, right temporo-parietal junction and middle frontal gyrus bilaterally. The data suggest that frontal and parietal regions are specifically involved in reorienting rather than orienting attention to a spatial position. Alerting effects were seen in extrastriate regions which suggest that increased phasic alertness results in a top-down modulation of neural activity in visual processing areas.

Development of attentional networks: an fMRI study with children and adults.

Data on the development of the attentional systems remain scarce. We used structural and event-related functional magnetic resonance imaging to investigate differences in the neural mechanisms associated with alerting, reorienting, and executive control of attention between children (ages 8 to 12 years) and adults, while controlling for effects of performance and brain morphology. Behaviorally, children exhibited a numerically smaller alerting effect and significantly larger invalidity (reorienting) and interference (executive control of attention) effects. Neurally, children showed significantly reduced brain activation in a priori defined regions-of-interest in right-sided frontal-midbrain regions during alerting, in the right-sided temporo-parietal junction during reorienting of attention, and in the dorsolateral prefrontal cortex during executive control of attention. In addition, children activated significantly more brain regions outside the a priori defined regions-of-interest, such as the superior frontal gyrus during reorienting and the superior temporal gyrus during executive control of attention. Functional group differences overlapped with structural group differences in gray matter volume in particular within the frontopolar areas. The data suggest that there is a transition from functional yet immature systems supporting attentional functions in children to the more definitive adult networks and that the differences observed may reflect both developmental changes in cognitive strategies and morphology.

Nicotine Modulates Reorienting of Visuospatial Attention and Neural Activity in Human Parietal Cortex

Prior studies in animals and humans indicate that reorienting of visuospatial attention is modulated by the cholinergic agonist nicotine. We have previously identified neural correlates of alerting and reorienting attention in humans and found that the parietal cortex is specifically involved in reorienting. This study investigates whether the alerting and reorienting systems, especially in the parietal cortex, are modulated by nicotine. We used event-related functional magnetic resonance imaging (fMRI) and studied 15 nonsmoking volunteers under placebo and nicotine (NICORETTE® polacrilex gum 1 and 2 mg). Subjects performed a cued target detection task with four different types of randomly intermixed trials (no, neutral, valid, and invalid cue trials). Alerting was captured by comparing BOLD activity and reaction times (RTs) in neutrally cued trials with no cue trials. Reorienting was isolated by comparing invalidly with validly cued trials. On the behavioral level, nicotine affected reorienting of attention by speeding RTs in invalidly cued trials; alerting was not affected by nicotine. Neurally, however, nicotine modulated both attentional systems. Pharmacologic effects on alerting-related brain activity were mainly evident as modulation of BOLD responses in the right angular gyrus and right middle frontal gyrus due to a reduction of neural activity in no cue trials. In the reorienting system, effects of nicotine were mainly evident in the left intraparietal sulcus and precuneus and due to a reduction of neural activity in invalidly cued trials. We conclude that nicotine enhances reorienting of attention in visuospatial tasks and that one behavioral correlate of speeded RTs is reduced parietal activity.

Cholinergic Modulation of Experience-Dependent Plasticity in Human Auditory Cortex

The factors that influence experience-dependent plasticity in the human brain are unknown. We used event-related functional magnetic resonance imaging (fMRI) and a pharmacological manipulation to measure cholinergic modulation of experience-dependent plasticity in human auditory cortex. In a differential aversive conditioning paradigm, subjects were presented with high (1600 Hz) and low tones (400 Hz), one of which was conditioned by pairing with an electrical shock. Prior to presentation, subjects were given either a placebo or an anticholinergic drug (0.4 mg iv scopolamine). Experience-dependent plasticity, expressed as a conditioning-specific enhanced BOLD response, was evident in auditory cortex in the placebo group, but not with scopolamine. This study provides in vivo evidence that experience-dependent plasticity, evident in hemodynamic changes in human auditory cortex, is modulated by acetylcholine.

The modulatory effects of nicotine on parietal cortex activity in a cued target detection task depend on cue reliability

This functional magnetic resonance imaging study investigates the effects of nicotine in a cued target detection task when changing cue reliability. Fifteen non-smoking volunteers were studied under placebo and nicotine (Nicorette polacrilex gum 1 and 2 mg). Validly and invalidly cued trials were arranged in blocks with high, middle and low cue reliability. Two effects of nicotine were investigated: its influence on i) parietal cortex activity underlying the processing of invalid vs. valid trials (i.e. validity effect) and ii) neural activity in the context of low, middle and high informative value of the cue (i.e. cue reliability effect). Nicotine did not affect behavioral performance. However, nicotine reduced the difference in the blood oxygenation level dependent (BOLD) signal between invalid and valid trials in the right intraparietal sulcus. The reduction of parietal activity in invalid trials was smaller in the low cue reliability condition. The same posterior parietal region exhibited a nicotinic modulation of BOLD activity in valid trials which was dependent on cue reliability: Nicotine specifically enhanced the neural activity during valid trials in the context of low cue reliability, i.e. when subjects are already in a state of low certainty. We speculate that the right intraparietal sulcus might be part of two networks working in parallel: one responsible for reorienting attention and the other for the cholinergic modulation of cue reliability. By reducing the use of the cue, nicotine modulates parietal activity related to reorienting attention in conditions with higher cue certainty. On the other hand, nicotine increases parietal activity in states of low certainty. This enhanced activation might influence brain regions, such as the posterior cingulate, directly involved in the processing of cue reliability.

Behavioral and neural effects of nicotine on visuospatial attentional reorienting in non-smoking subjects.

The cholinergic neurotransmitter system has been proposed to be involved in the processing of probabilistic top-down information provided by endogenous cues in location-cueing paradigms. It has been shown that the behavioral and neural effects of a nicotinic cholinergic stimulation resemble the effects obtained by manipulating the validity of the spatial cues: enhancing cortical nicotine levels and decreasing cue validity both reduce the reaction time difference between invalidly and validly cued targets (ie, the ‘validity effect’) as well as neural activity related to attentional reorienting in parietal brain regions. In the present study, we investigated whether the behavioral and neural effects of nicotine in location-cueing paradigms are dependent upon different a priori cue validities. Twenty-four subjects were investigated in a double-blind placebo-controlled between-subject design with functional magnetic resonance imaging. Nicotine was administered to non-smoking volunteers via polacrilex gums (Nicorette®, 2 mg) before performing a location-cueing paradigm with valid and invalid cues in the context of 90 and 60% cue validity in the MR scanner. Nicotine significantly reduced the validity effect in the 90% but not in the 60% cue validity condition. Fronto-parietal and cingulate regions showed stronger nicotinic reductions of reorienting-related neural activity in the high than in the low cue validity condition. Our data reveal an interaction effect between the pharmacological and cognitive modulation of attentional reorienting, which is evident at both a behavioral as well as the neuronal level.

Relationship between anxiety and serotonin in the ventral striatum.

Rats were tested in an elevated plus-maze on two consecutive days. Based on the percentage of time spent in the open arms on the 1st day, they were divided into two subgroups with either low or high anxiety levels. A post-mortem neurochemical analysis showed that animals with high anxiety had lower ventral striatal tissue levels of 5-HT. No such differences were found for 5-HT in other brain areas or in dopamine and norepinephrine levels. The ventral striatal 5-HT levels correlated with plus-maze behavior on the 2nd but not 1st day. These data suggest that individual differences in ventral striatal 5-HT interact with plus-maze behavior, which may help to explain why serotonergic drugs can have inconsistent effects in this paradigm.

Effects of Acute Psychosocial Stress on Working Memory Related Brain Activity in Men

Acute psychosocial stress in humans triggers the release of glucocorticoids (GCs) and influences performance in declarative and working memory (WM) tasks. These memory systems rely on the hippocampus and prefrontal cortex (PFC), where GC‐binding receptors are present. Previous studies revealed contradictory results regarding effects of acute stress on WM‐related brain activity. We combined functional magnetic resonance imaging with a standardized psychosocial stress protocol to investigate the effects of acute mental stress on brain activity during encoding, maintenance, and retrieval of WM. Participants (41 healthy young men) underwent either a stress or a control procedure before performing a WM task. Stress increased salivary cortisol levels and tended to increase WM accuracy. Neurally, stress‐induced increases in cortical activity were evident in PFC and posterior parietal cortex (PPC) during WM maintenance. Furthermore, hippocampal activity was modulated by stress during encoding and retrieval with increases in the right anterior hippocampus during WM encoding and decreases in the left posterior hippocampus during retrieval. Our study demonstrates that stress increases activity in PFC and PPC specifically during maintenance of items in WM, whereas effects on hippocampal activity are restricted to encoding and retrieval. The finding that psychosocial stress can increase and decrease activity in two different hippocampal areas may be relevant for understanding the often‐reported phase‐dependent opposing behavioral effects of stress on long‐term memory. Hum Brain Mapp, 2010.

Dichotic Pitch activates Pitch Processing Centre in Heschl's Gyrus

Although several neuroimaging studies have reported pitch-evoked activations at the lateral end of Heschls gyrus, it is still under debate whether these findings truly represent activity in relation to the perception of pitch or merely stimulus-related features of pitch-evoking sounds. We investigated this issue in a functional magnetic resonance imaging (fMRI) experiment using pure tones in noise and dichotic pitch sequences, which either contained a melody or a fixed pitch. Dichotic pitch evokes a sensation of pitch only in binaural listening conditions, while the monaural signal cannot be distinguished from random noise. Our data show similar neural activations for both tones in noise and dichotic pitch, which are perceptually similar, but physically different. Pitch-related activation was found at the lateral end of Heschls gyrus in both hemispheres, providing new evidence for a general involvement of this region in pitch processing. In line with prior studies, we found melody-related activation in Planum temporale and Planum polare, but not in primary auditory areas. These results support the view of a general representation of pitch in auditory cortex, irrespective of the physical attributes of the pitch-evoking sound.

Scopolamine but Not Lorazepam Modulates Face Repetition Priming: A Psychopharmacological fMRI Study

Repetition priming is a basic form of learning associated with decreased neuronal responses following stimulus repetition. In this experiment, we address cholinergic and GABAergic modulation of repetition priming in a face recognition paradigm. In experiment 1, we used event-related functional magnetic resonance imaging (fMRI) in combination with pharmacological challenge where participants were given placebo, lorazepam (2mg po), or scopolamine (0.4mg IV) prior to study. Behavioral data showed intact priming for famous faces in the placebo and lorazepam group but impaired priming following scopolamine. In within-group analyses, a right fusiform region showed a fame by repetition interaction characterized by a response decrease to repetition of famous faces and a response enhancement to repetition of unfamous faces in the placebo group. In subjects treated with lorazepam, a main effect of repetition, driven by response decreases to repetition of famous faces, was seen in this right fusiform region. No significant repetition effects were found after scopolamine. In experiment 2, we further investigated behaviorally the cholinergic impairment of repetition priming. Participants were given either placebo or scopolamine (0.4mg IV) after study. Behavioral data showed intact priming for famous faces in the placebo and scopolamine group. The results suggest that scopolamine but not lorazepam impair repetition priming for famous faces in a face recognition paradigm. These cholinergic impairments are likely to reflect interference with acquisition processes during study that may co-occur with a modulation of right fusiform decreases to repetition of famous faces.