Mu Opioid Receptor Binding Correlates with Nicotine Dependence and Reward in Smokers

The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine''s rewarding effects. We employed PET imaging with [¹¹C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BP_ND) of [¹¹C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [¹¹C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward.     

Decoding the different states of visual attention using functional and effective connectivity features in fMRI data

The present paper concentrates on the impact of visual attention task on structure of the brain functional and effective connectivity networks using coherence and Granger causality methods. Since most studies used correlation method and resting-state functional connectivity, the task-based approach was selected for this experiment to boost our knowledge of spatial and feature-based attention. In the present study, the whole brain was divided into 82 sub-regions based on Brodmann areas. The coherence and Granger causality were applied to construct functional and effective connectivity matrices. These matrices were converted into graphs using a threshold, and the graph theory measures were calculated from it including degree and characteristic path length. Visual attention was found to reveal more information during the spatial-based task. The degree was higher while performing a spatial-based task, whereas characteristic path length was lower in the spatial-based task in both functional and effective connectivity. Primary and secondary visual cortex (17 and 18 Brodmann areas) were highly connected to parietal and prefrontal cortex while doing visual attention task. Whole brain connectivity was also calculated in both functional and effective connectivity. Our results reveal that Brodmann areas of 17, 18, 19, 46, 3 and 4 had a significant role proving that somatosensory, parietal and prefrontal regions along with visual cortex were highly connected to other parts of the cortex during the visual attention task. Characteristic path length results indicated an increase in functional connectivity and more functional integration in spatial-based attention compared with feature-based attention. The results of this work can provide useful information about the mechanism of visual attention at the network level.     

参与不同难度数字计算的脑区——脑功能磁共振成像研究

本研究用功能磁共振成像技术观察了人脑进行不同难度数字加减计算时的脑区激活情况,并探讨大脑皮层和皮层下结构在数字计算中的作用.用Siemens 1.5 Tesla磁共振机对16名右利手健康志愿者进行简单及复杂数字加减任务的fMRI扫描.实验采用组块设计.刺激任务分为简单加减计算任务、复杂加减计算任务和基线任务.用SPM99软件进行数据分析和脑功能区定位.分别比较同一任务各个脑区平均激活强度和同一脑区在两种任务中的激活强度.结果显示,简单及复杂加减计算激活的被试者的脑区基本相同,激活的皮层区主要见于额叶、顶叶、枕叶、扣带回、丘脑及小脑;简单及复杂加减计算激活的皮层下结构包括两侧尾状核、左纹状体边缘区等基底核结构和丘脑.在简单及复杂计算中,纹状体与皮质结构(额叶、顶叶)间激活强度均无显著性差异.简单计算与复杂计算比较,右顶叶,在复杂任务时出现激活,在简单任务时未出现激活.上述结果提示,完成数字计算任务的脑区除了额叶、顶叶、扣带回等皮层结构外,大脑皮层下的一些结构如纹状体、纹状体边缘区,也是参与数字计算的重要部位.皮层下结构纹状体和优势半球的纹状体边缘区参与了数字工作记忆,可能是进行数字计算神经环路的重要组成部位.右项叶(缘上回)只在复杂任务出现激活,该区可能是视空间记忆和加工的重要部位.     

Functional Magnetic Resonance Imaging Investigation of the Effects of Neurofeedback Training on the Neural Bases of Selective Attention and Response Inhibition in Children with Attention-Deficit/Hyperactivity Disorder

Two functional magnetic resonance imaging (fMRI) experiments were undertaken to measure the effect of neurofeedback training (NFT), in AD/HD children, on the neural substrates of selective attention and response inhibition. Twenty unmedicated AD/HD children participated to these experiments. Fifteen children were randomly assigned to the Experimental (EXP) group whereas the other five children were randomly assigned to the Control (CON) group. Only subjects in the EXP group underwent NFT. EXP subjects were trained to enhance the amplitude of the SMR (12–15 Hz) and beta 1 activity (15–18 Hz), and decrease the amplitude of theta activity (4–7 Hz). Subjects from both groups were scanned one week before the beginning of NFT (Time 1) and 1 week after the end of NFT (Time 2), while they performed a “Counting Stroop” task (Experiment 1) and a Go/No-Go task (Experiment 2). At Time 1, in both groups, the Counting Stroop task was associated with significant activation in the left superior parietal lobule. For the Go/No-Go task, no significant activity was detected in the EXP and CON groups. At Time 2, in both groups, the Counting Stroop task was associated with significant activation of the left superior parietal lobule. This time, however, there were significant loci of activation, in the EXP group, in the right ACC, left caudate nucleus, and left substantia nigra. No such activation loci were seen in CON subjects. For the Go/No-Go task, significant loci of activation were noted, in the EXP group, in the right ventrolateral prefrontal cortex, right ACcd, left thalamus, left caudate nucleus, and left substantia nigra. No significant activation of these brain regions was measured in CON subjects. These results suggest that NFT has the capacity to functionally normalize the brain systems mediating selective attention and response inhibition in AD/HD children.     

A Functional Magnetic Resonance Imaging (fMRI) Study of Cue-Induced Smoking Craving in Virtual Environments

Smokers who are exposed to smoking-related cues show cardiovascular reactivity and smoking craving compared with their responses to neutral cues, and increased cue reactivity predicts decreased likelihood of successful cessation. Several brain imaging studies suggested four candidate brain regions that might differ in gray matter volumes and densities between smokers and nonsmokers. However, in these studies, smokers were only exposed to smoking-related objects. In our pilot study utilizing a virtual reality (VR) technique, virtual environments (VEs) were more immersive and evoked smoking craving more effectively than traditionally used methods. In this study, we sought to test whether smokers could experience cue-induced smoking craving inside the MRI scanner by using the VR system. The smoking cue reactivity scenario was based in part on our preliminary task and consisted of 2D and 3D (or VE) conditions. The group mean of participants had increased activity in the prefrontal cortex (PFC), left anterior cingulate gyrus (ACC), left supplementary motor area, left uncus, right inferior temporal gyrus, right lingual gyrus, and right precuneus in the 2D condition. Areas of differential activation in the 3D condition were as follows: left superior temporal gyrus, right superior frontal gyrus, and left inferior occipital gyrus in the 3D condition. This finding is consistent with those of previous studies of nicotine craving showing PFC and ACC activation. However, in the 3D condition, the PFC including the superior frontal gyrus as well as the superior temporal gyrus, inferior occipital gyrus, and cerebellum were activated. Therefore, in the 3D condition, participants seemed to have more attention, visual balance, and coordinating movement than in the 2D condition.     

Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention

Background

Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task.

Methodology/Principal Findings

For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [¹¹C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus.

Conclusions/Significance

These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.     

Complex Visual Search in Children and Adolescents: Effects of Age and Performance on fMRI Activation

Complex visuospatial processing relies on distributed neural networks involving occipital, parietal and frontal brain regions. Effects of physiological maturation (during normal brain development) and proficiency on tasks requiring complex visuospatial processing have not yet been studied extensively, as they are almost invariably interrelated. We therefore aimed at dissociating the effects of age and performance on functional MRI (fMRI) activation in a complex visual search task. In our cross-sectional study, healthy children and adolescents (n = 43, 19 females, 7-17 years) performed a complex visual search task during fMRI. Resulting activation was analysed with regard to the differential effects of age and performance. Our results are compatible with an increase in the neural network''s efficacy with age: within occipital and parietal cortex, the core regions of the visual exploration network, activation increased with age, and more so in the right than in the left hemisphere. Further, activation outside the visual search network decreased with age, mainly in left inferior frontal, middle temporal, and inferior parietal cortex. High-performers had stronger activation in right superior parietal cortex, suggesting a more mature visual search network. We could not see effects of age or performance in frontal cortex. Our results show that effects of physiological maturation and effects of performance, while usually intertwined, can be successfully disentangled and investigated using fMRI in children and adolescents.     

Brain Activity Changes in Cognitive Networks in Relapsing-Remitting Multiple Sclerosis – Insights from a Longitudinal fMRI Study

Background

Extrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS), but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology.

Methods

13 MS patients and 15 healthy controls (HC) underwent MRI including fMRI (go/no-go task), neurological and neuropsychological exams at baseline (BL) and follow-up (FU; minimum 12, median 20 months). We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA) plots served to assess fMRI signal variability.

Results

Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC) demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT) performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance.

Conclusions

Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and the strategic importance of specific brain areas for cognitive processes in MS.     

Electrical Neuroimaging Reveals Timing of Attentional Control Activity in Human Brain

Voluntarily shifting attention to a location of the visual field improves the perception of events that occur there. Regions of frontal cortex are thought to provide the top-down control signal that initiates a shift of attention, but because of the temporal limitations of functional brain imaging, the timing and sequence of attentional-control operations remain unknown. We used a new analytical technique (beamformer spatial filtering) to reconstruct the anatomical sources of low-frequency brain waves in humans associated with attentional control across time. Following a signal to shift attention, control activity was seen in parietal cortex 100–200 ms before activity was seen in frontal cortex. Parietal cortex was then reactivated prior to anticipatory biasing of activity in occipital cortex. The magnitudes of early parietal activations were strongly predictive of the degree of attentional improvement in perceptual performance. These results show that parietal cortex, not frontal cortex, provides the initial signals to shift attention and indicate that top-down attentional control is not purely top down.     

A preliminary study suggests that nicotine and prefrontal dopamine affect cortico‐striatal areas in smokers with performance feedback

Nicotine and tonic dopamine (DA) levels [as inferred by catechol‐O‐methyl tranferase (COMT) Val158Met genotype] interact to affect prefrontal processing. Prefrontal cortical areas are involved in response to performance feedback, which is impaired in smokers. We investigated whether there is a nicotine × COMT genotype interaction in brain circuitry during performance feedback of a reward task. We scanned 23 healthy smokers (10 Val/Val homozygotes, 13 Met allele carriers) during two fMRI sessions while subjects were wearing a nicotine or placebo patch. A significant nicotine × COMT genotype interaction for BOLD signal during performance feedback in cortico‐striatal areas was seen. Activation in these areas during the nicotine patch condition was greater in Val/Val homozygotes and reduced in Met allele carriers. During negative performance feedback, the change in activation in error detection areas such as anterior cingulate cortex (ACC)/superior frontal gyrus on nicotine compared to placebo was greater in Val/Val homozygotes compared to Met allele carriers. With transdermal nicotine administration, Val/Val homozygotes showed greater activation with performance feedback in the dorsal striatum, area associated with habitual responding. In response to negative feedback, Val/Val homozygotes had greater activation in error detection areas, including the ACC, suggesting increased sensitivity to loss with nicotine exposure. Although these results are preliminary due to small sample size, they suggest a possible neurobiological mechanism underlying the clinical observation that Val/Val homozygotes, presumably with elevated COMT activity compared to Met allele carriers and therefore reduced prefrontal DA levels, have poorer outcomes with nicotine replacement therapy .     

Neurocognitive variation in smoking behavior and withdrawal: genetic and affective moderators

A burgeoning literature suggests that attentional factors are associated with smoking behavior (e.g. direct nicotine effects and smoking withdrawal). This study examined differences in attentional processing between nonsmokers, satiated smokers and overnight nicotine-deprived smokers by comparing the amplitude of the P300 (P3) component of the event-related brain potential (ERP) elicited during a go–nogo task. We also examined the moderating effects of a common dopamine receptor genotype and state negative affect (SNA) on this ERP index of attention. Nonsmokers relative to smokers had greater nogo P3 amplitude. Carrying the A1 allele at the dopamine receptor D2 ( DRD2 ) Taq1A polymorphism site moderated the effects of withdrawal on nogo P3 amplitude, suggesting the A1 allele is a vulnerability marker for withdrawal-related attentional deficits. Increased SNA also predicted attenuated P3 amplitude among deprived smokers. These findings suggest that DRD2 status and SNA moderate the effects of smoking status and withdrawal on neurocognitive variation during attentional processing. This research contributes to a better understanding of the role of individual differences and attentional processing in smoking behavior.     

Conscious awareness of flicker in humans involves frontal and parietal cortex

Even when confined to the same spatial location, flickering and steady light evoke very different conscious experiences because of their distinct temporal patterns. The neural basis of such differences in subjective experience remains uncertain . Here, we used functional MRI in humans to examine the neural structures involved in awareness of flicker. Participants viewed a single point source of light that flickered at the critical flicker fusion (CFF) threshold, where the same stimulus is sometimes perceived as flickering and sometimes as steady (fused) . We were thus able to compare brain activity for conscious percepts that differed qualitatively (flickering or fused) but were evoked by identical physical stimuli. Greater brain activation was observed on flicker (versus fused) trials in regions of frontal and parietal cortex previously associated with visual awareness in tasks that did not require detection of temporal patterns . In contrast, greater activation was observed on fused (versus flicker) trials in occipital extrastriate cortex. Our findings indicate that activity of higher-level cortical areas is important for awareness of temporally distinct visual events in the context of a nonspatial task, and they thus suggest that frontal and parietal regions may play a general role in visual awareness.     

Levodopa Effects on Hand and Speech Movements in Patients with Parkinson’s Disease: A fMRI Study

Levodopa (L-dopa) effects on the cardinal and axial symptoms of Parkinson’s disease (PD) differ greatly, leading to therapeutic challenges for managing the disabilities in this patient’s population. In this context, we studied the cerebral networks associated with the production of a unilateral hand movement, speech production, and a task combining both tasks in 12 individuals with PD, both off and on levodopa (L-dopa). Unilateral hand movements in the off medication state elicited brain activations in motor regions (primary motor cortex, supplementary motor area, premotor cortex, cerebellum), as well as additional areas (anterior cingulate, putamen, associative parietal areas); following L-dopa administration, the brain activation profile was globally reduced, highlighting activations in the parietal and posterior cingulate cortices. For the speech production task, brain activation patterns were similar with and without medication, including the orofacial primary motor cortex (M1), the primary somatosensory cortex and the cerebellar hemispheres bilaterally, as well as the left- premotor, anterior cingulate and supramarginal cortices. For the combined task off L-dopa, the cerebral activation profile was restricted to the right cerebellum (hand movement), reflecting the difficulty in performing two movements simultaneously in PD. Under L-dopa, the brain activation profile of the combined task involved a larger pattern, including additional fronto-parietal activations, without reaching the sum of the areas activated during the simple hand and speech tasks separately. Our results question both the role of the basal ganglia system in speech production and the modulation of task-dependent cerebral networks by dopaminergic treatment.     

Trait anxiety and neural efficiency of abstract reasoning: An fMRI investigation

Worries preoccupy the working memory capacity in anxious individuals, thereby affecting their performance during tasks that require efficient attention regulation. According to the attentional control theory (ACT), trait anxiety affects the processing efficiency, i.e. the effort required for task performance, more than the accuracy of task performance. We investigated the relation between trait anxiety and neural response for a reasoning task in healthy subjects. Functional magnetic resonance imaging (fMRI) was carried out on 22 healthy participants and blood oxygenation level dependent (BOLD) contrast estimates were extracted from a priori regions of interest (ROIs) that were earlier implicated in reasoning (i.e., bilaterally caudate head, globus pallidus, thalamus, prefrontal cortex [rostral, dorsal and ventral regions], inferior parietal lobule and middle occipital gyrus). Controlling for the effects of age, gender, state anxiety and depressive symptoms, for equivalent levels of task performance, trait anxiety of the participants was found to be associated with an increase in task related BOLD activation in right globus pallidus, left thalamus and left middle occipital gyrus. Our results suggest a reduced processing efficiency for reasoning in high trait anxiety subjects and provides important brain–behaviour relationships with respect to sub-clinical anxiety.     

Differential activation of MAP kinase signaling pathways and nuclear factor-kappaB in bronchoalveolar cells of smokers and nonsmokers

BACKGROUND: Prolonged exposure of alveolar macrophages (AM) to components of tobacco smoke, including nicotine and aromatic hydrocarbons, may lead to alterations in activation of cellular signaling pathways. In this study, we compared the spontaneous and LPS-stimulated activation of MAP kinases and NF-kappaB in bronchoalveolar cells (BAC) from smokers and nonsmokers. MATERIAL AND METHODS: BAC, which were predominantly comprised of AM, were obtained by bronchoalveolar lavage of healthy volunteering adult smokers and nonsmokers. Nuclear and cytoplasmic extracts were prepared from cell lysates. Activation of NF-kappaB was assessed by electrophoretic mobility shift assay. Degradation of the inhibitor of NF-kappaB (IkappaB) and total MAP kinases were assessed by Western blot analysis. Activation of MAP kinases, ERK, SAPK/JNK, and p38 were assessed by immunoprecipitation of cell lysates and kinase assays. RESULTS: LPS induced the activation of NF-kappaB in a dose-dependent manner, but BAC from smokers were approximately 10 times more sensitive, and showed faster kinetics of activation of NF-kappaB than BAC from nonsmokers. All three classes of MAP kinase-ERK, SAPK, and p38-were simultaneously activated by LPS in BAC from smokers and nonsmokers. However, the individual MAP kinases exhibited differential kinetics of activation. Activation of p38 was more rapid in BAC from smokers, whereas the activation of ERK and SAPK was similar in both groups. CONCLUSION: The differences in activation of NF-kappaB and MAP kinases in BAC from smokers and nonsmokers may relate to the differences in their microenvironment in situ as affected by chronic exposure to cigarette smoke. These differences may contribute to the increased susceptibility of smokers to infections, including infection with HIV-1, and lung disease.     

Distributed network actions by nicotine increase the threshold for spike-timing-dependent plasticity in prefrontal cortex

Nicotine enhances attention and working memory by activating nicotinic acetylcholine receptors (nAChRs). The prefrontal cortex (PFC) is critical for these cognitive functions and is also rich in nAChR expression. Specific cellular and synaptic mechanisms underlying nicotine's effects on cognition remain elusive. Here we show that nicotine exposure increases the threshold for synaptic spike-timing-dependent potentiation (STDP) in layer V pyramidal neurons of the mouse PFC. During coincident presynaptic and postsynaptic activity, nicotine reduces dendritic calcium signals associated with action potential propagation by enhancing GABAergic transmission. This results from a series of presynaptic actions involving different PFC interneurons and multiple nAChR subtypes. Pharmacological block of nAChRs or GABA(A) receptors prevented nicotine's actions and restored STDP, as did increasing dendritic calcium signals with stronger postsynaptic activity. Thus, by activating nAChRs distributed throughout the PFC neuronal network, nicotine affects PFC information processing and storage by increasing the amount of postsynaptic activity necessary to induce STDP.     

An fMRI Study of Nicotine-Deprived Smokers' Reactivity to Smoking Cues during Novel/Exciting Activity

Engaging in novel/exciting (“self-expanding”) activities activates the mesolimbic dopamine pathway, a brain reward pathway also associated with the rewarding effects of nicotine. This suggests that self-expanding activities can potentially substitute for the reward from nicotine. We tested this model among nicotine-deprived smokers who, during fMRI scanning, played a series of two-player cooperative games with a relationship partner. Games were randomized in a 2 (self-expanding vs. not) x 2 (cigarette cue present vs. absent) design. Self-expansion conditions yielded significantly greater activation in a reward region (caudate) than did non-self-expansion conditions. Moreover, when exposed to smoking cues during the self-expanding versus the non-self-expanding cooperative games, smokers showed less activation in a cigarette cue-reactivity region, a priori defined [temporo-parietal junction (TPJ)] from a recent meta-analysis of cue-reactivity. In smoking cue conditions, increases in excitement associated with the self-expanding condition (versus the non-self-expanding condition) were also negatively correlated with TPJ activation. These results support the idea that a self-expanding activity promoting reward activation attenuates cigarette cue-reactivity among nicotine-deprived smokers. Future research could focus on the parameters of self-expanding activities that produce this effect, as well as test the utility of self-expansion in clinical interventions for smoking cessation.     

Effects of inhaled nicotine on instrumental learning of blood pressure responses.

The present study investigated the effects of biofeedback of arterial blood pressure on cortical, peripheral, and psychological measures and the dependence of these effects on nicotine. Four groups of subjects, nonsmokers, and habitual smokers who smoked cigarettes during the experimental sessions containing 0.3, 0.8, or 1.5 mg nicotine, respectively, participated in a feedback paradigm in which continuous feedback of mean blood pressure was provided for intervals of 8 s each. While tonic blood pressure did not differ between the groups, the ability to modulate blood pressure (under feedback conditions) was restricted in smokers as compared to nonsmoking subjects; increasing nicotine dosage was accompanied by poorer performance. Independently of habitual smoking and nicotine doses, heart rate increased during feedback and under conditions of blood pressure increase. In smokers, activity in the alpha band was reduced in a dose-dependent manner. Slow cortical potentials (SCPs) during the feedback interval varied with self-induced blood pressure changes in nonsmokers (blood pressure increase was accompanied by reduced surface-negative potential shifts and vice versa), while SCP variations during feedback conditions were small in smokers, more so under the influence of 0.3 and 0.8-mg nicotine, less so under 1.5 mg. Verbal reports suggest that awareness of performance strategies may not be a necessary variable for performance on the blood pressure regulation task.     

Effects of cholinergic enhancement on visual stimulation, spatial attention, and spatial working memory

We compared behavioral and neural effects of cholinergic enhancement between spatial attention, spatial working memory (WM), and visual control tasks, using fMRI and the anticholinesterase physostigmine. Physostigmine speeded responses nonselectively but increased accuracy selectively for attention. Physostigmine also decreased activations to visual stimulation across all tasks within primary visual cortex, increased extrastriate occipital cortex activation selectively during maintained attention and WM encoding, and decreased parietal activation selectively during maintained attention. Finally, lateralization of occipital activation as a function of the visual hemifield toward which attention or memory was directed was decreased under physostigmine. In the case of attention, this effect correlated strongly with a decrease in a behavioral measure of selective spatial processing. Our results suggest that, while cholinergic enhancement facilitates visual attention by increasing activity in extrastriate cortex generally, it accomplishes this in a manner that reduces expectation-driven selective biasing of extrastriate cortex.     

Task-guided selection of the dual neural pathways for reading

The visual perception of words is known to activate the auditory representation of their spoken forms automatically. We examined the neural mechanism for this phonological activation using transcranial magnetic stimulation (TMS) with a masked priming paradigm. The stimulation sites (left superior temporal gyrus [L-STG] and inferior parietal lobe [L-IPL]), modality of targets (visual and auditory), and task (pronunciation and lexical decision) were manipulated independently. For both within- and cross-modal conditions, the repetition priming during pronunciation was eliminated when TMS was applied to the L-IPL, but not when applied to the L-STG, whereas the priming during lexical decision was eliminated when the L-STG, but not the L-IPL, was stimulated. The observed double dissociation suggests that the conscious task instruction modulates the stimulus-driven activation of the lateral temporal cortex for lexico-phonological activation and the inferior parietal cortex for spoken word production, and thereby engages a different neural network for generating the appropriate behavioral response.