Attentional and linguistic interactions in speech perception

The role of attention in speech comprehension is not well understood. We used fMRI to study the neural correlates of auditory word, pseudoword, and nonspeech (spectrally rotated speech) perception during a bimodal (auditory, visual) selective attention task. In three conditions, Attend Auditory (ignore visual), Ignore Auditory (attend visual), and Visual (no auditory stimulation), 28 subjects performed a one-back matching task in the assigned attended modality. The visual task, attending to rapidly presented Japanese characters, was designed to be highly demanding in order to prevent attention to the simultaneously presented auditory stimuli. Regardless of stimulus type, attention to the auditory channel enhanced activation by the auditory stimuli (Attend Auditory>Ignore Auditory) in bilateral posterior superior temporal regions and left inferior frontal cortex. Across attentional conditions, there were main effects of speech processing (word+pseudoword>rotated speech) in left orbitofrontal cortex and several posterior right hemisphere regions, though these areas also showed strong interactions with attention (larger speech effects in the Attend Auditory than in the Ignore Auditory condition) and no significant speech effects in the Ignore Auditory condition. Several other regions, including the postcentral gyri, left supramarginal gyrus, and temporal lobes bilaterally, showed similar interactions due to the presence of speech effects only in the Attend Auditory condition. Main effects of lexicality (word>pseudoword) were isolated to a small region of the left lateral prefrontal cortex. Examination of this region showed significant word>pseudoword activation only in the Attend Auditory condition. Several other brain regions, including left ventromedial frontal lobe, left dorsal prefrontal cortex, and left middle temporal gyrus, showed Attention x Lexicality interactions due to the presence of lexical activation only in the Attend Auditory condition. These results support a model in which neutral speech presented in an unattended sensory channel undergoes relatively little processing beyond the early perceptual level. Specifically, processing of phonetic and lexical-semantic information appears to be very limited in such circumstances, consistent with prior behavioral studies.     

fMRI of the responses to vibratory stimulation of digit tips

Three studies were carried out to assess the applicability of fMRI at 3.0 T to analysis of vibrotaction in humans. A novel piezoelectric device provided clean sinusoidal stimulation at 80 Hz, which was initially applied in separate runs within a scanning session to digits 2 and 5 of the left hand in eight subjects, using a birdcage RF (volume) coil. Significant clusters of activation were found in the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), subcentral gyrus, the precentral gyrus, posterior insula, posterior parietal regions (area 5), and the posterior cingulate. Digit separation in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study carried out in six additional subjects using a surface coil, replicated the main contralateral activation patterns detected in study one and further improved the discrimination of the digits in SI. Significant digit separation was also found in SII and in the posterior insula. A third study to investigate the frequency dependence of the response focused on the effect of an increase in vibrotactile frequency from 30 to 80 Hz, with both frequencies applied to digit 2 during the same scanning session in four new subjects. A significant increase in the number of pixels activated within both SII and the posterior insula was found, while the number of pixels activated in SI declined. No significant change in signal intensity with frequencies was found in any of the activated areas.     

Heterogeneity of Cingulate Contributions to Spatial Attention

Functional magnetic resonance imaging was used to investigate activation patterns within the cingulate region during tasks based on spatial attention. Subjects were asked to detect targets which appeared either at the site indicated by a cue or on the opposite side. A “cue effect” was identified by the presence of shorter reaction times to validly than invalidly cued targets, showing that an anticipatory bias had been generated in the direction of the cue. Target detection accuracy was consistently above 90% although cue effects and reaction times displayed substantial variations, from one task session to another. Activation within the anterior cingulate region was seen in 16 of the 26 sessions but showed no correlation with reaction time. Posterior cingulate activation was seen in only 6 of the 26 sessions. However, a random effects analysis showed that the task-related signal change in this region was strongly correlated with the speed of target detection. A post hoc analysis indicated that this correlation was significant only when cue effects were present. No other part of the cerebral cortex displayed significant correlations with reaction times or cue effects. These results suggest that the cingulate component of the attentional network has at least two functionally segregated sectors, an anterior one in BA 24/32 and a posterior cingulo-retrosplenial one in BA 23/29/30. The posterior sector appears to be associated with the speed of detecting spatial targets, especially when attention is under the influence of a cue-induced anticipatory bias. The anterior cingulate focus did not display such a relationship in our tasks and is likely to mediate other aspects of attentional deployment such as performance monitoring, response selection or target identification.     

Effects of progressive muscle relaxation on cerebral activity: An fMRI investigation

ObjectivesProgressive muscle relaxation (PMR) is one of the self-management relaxation techniques that can be used in the general population and patients with specific issues. However, no study to date has revealed the brain activity associated with PMR. Therefore, we assessed the changes in brain activity induced by PMR using functional magnetic resonance imaging (fMRI).Design and settingWe conducted an intervention study with PMR and control sessions. The subjects were twelve healthy adult men who had no prior experience of PMR.InterventionsSubjects performed a control session in which muscles were repeatedly simply tensed and relaxed. Subsequently, a PMR session took place, during which muscle tension was reduced through a systematic procedure of tensing and relaxing of muscle groups combined with structured breathing.Main outcome measuresWe identified and visualised brain activity based on individual and group-level analysis of fMRI data.ResultsEleven subjects’ data were analysed. In the control session, brain activity broadly changed, while the change was limited to specific parts of the cerebral cortex and limbic system in the PMR session. PMR gradually decreased activity in the superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and posterior cingulate cortex (PCC). In a region of interest (ROI) analysis, interactions between sessions were observed in the putamen, anterior cingulate cortex (ACC), postcentral gyrus (PCG), and insula.ConclusionsThat PMR led to few areas showing changed activity suggests that the technique may suppress brain activity. Even novices may be able to induce such a focused mental state.     

新异刺激模型中的痛觉诱发电位

目的：观察消除了某些心理因素影响后的痛觉诱发电位，以便进一步研究人类疼痛的中枢机制。方法：采用新异刺激(oddball)实验设计来产生痛觉诱发电位。14名被试右手中指给予两种不同强度的电刺激(中等程度的非痛刺激和疼痛刺激)，在两次实验中，分别将两种刺激之一作为新异靶刺激，而将男一种作为标准刺激，记录诱发电位，并比较作为新异靶刺激的疼痛刺激(25Pa)与作为标准刺激的疼痛刺激(75Pa)诱发电位的差异。结果：在数据合格的11名被试中，Cz电极位置25Pa的诱发电位成份与75Pa的诱发电位成份一致，均包括N1、P1、N2三个主要成份，其中25Pa诱发电位N1和P1成份的波幅显著高于75Pa相应成份，而N2成份的波幅在两种疼痛刺激中并无显著差异，两种刺激之间各成份的潜伏期也无统计学差异。偶极子起源分析表明，N1、P1、N2这三个成份可能分别来源于前扣带回、旁中央小叶及扣带回后部。结论：新异刺激设计所得的痛觉诱发电位(75Pa)排除了由疼痛评分及注意等因素所引发的非痛觉特异性认知相关成份，故可更为客观地评价疼痛。     

Neural substrates participating in acquisition of facial familiarity: an fMRI study

The amygdala is related to recognition of faces and emotions, and functional magnetic resonance imaging (fMRI) studies have reported that the amygdala is habituated over time with repetition of facial stimuli. When subjects are presented repeatedly with unfamiliar faces, they come to gradually recognize the unfamiliar faces as familiar. To investigate the brain areas participating in the acquisition of familiarity to repeatedly presented unfamiliar faces, we conducted an fMRI study in 16 healthy subjects. During the task periods, the subjects were instructed to see presented unfamiliar faces repeatedly and to judge whether the face was male or female or whether the face had emotional valences. The experiment consisted of nine sessions. To clarify the brain areas that showed increasing or decreasing activation as the experimental session proceeded, we analyzed the fMRI data using specified linear covariates in the face recognition task from the first session to the ninth session. Imaging data were investigated on a voxel-by-voxel basis for single-group analysis according to the random effect model using Statistical Parametric Mapping. The bilateral posterior cingulate cortices showed significant increases in activity as the experimental sessions proceeded, while the activation in the right amygdala and the left medial fusiform gyrus decreased. Thus, the posterior cingulate cortex may play an important role in the acquisition of facial familiarity.     

Caudal cingulate cortex involvement in pain processing: an inter-individual laser evoked potential source localisation study using realistic head models

Electrophysiological studies have revealed a source of laser pain evoked potentials (LEPs) in cingulate cortex. However, few studies have used realistically shaped head models in the source analysis, which account for individual differences in anatomy and allow detailed anatomical localisation of sources. The aim of the current study was to accurately localise the cingulate source of LEPs in a group of healthy volunteers, using realistic head models, and to assess the inter-individual variability in anatomical location. LEPs, elicited by painful CO(2) laser stimulation of the right forearm, were recorded from 62 electrodes in five healthy subjects. Dipole source localisation (CURRY 4.0) was performed on the most prominent (P2) peak of each LEP data set, using head models derived from each subject's structural magnetic resonance image (MRI).For all subjects, the P2 LEP peak was best explained by a dipole whose origin was in cingulate cortex (mean residual variance was 3.9+/-2.4 %). For four out of five subjects, it was located at the border of the caudal division of left anterior cingulate cortex (area 24/32') with left posterior cingulate cortex (area 23/31). For the fifth subject the dipole was centred in right posterior cingulate cortex (area 31). This study demonstrates that the location of the cingulate source of LEPs is highly consistent across subjects, when analysed in this way, and supports the involvement of caudal cingulate regions in pain processing.     

Stroop performance in normal control subjects: an fMRI study

In an attempt to clarify regional signal intensity changes, which may accompany the performance of the Stroop Color-Word task, healthy subjects were imaged using the fMRI BOLD technique while performing a modified version of the task. Both the AAA and VOA subdivisions of the anterior cingulate cortex were significantly activated during the interference condition; however, only the signal intensity change within the VOA correlated with task performance. Additionally, signal intensity change was significantly increased in the VOA subdivision of the cingulate cortex when controlling for signal intensity change present during the performance of a color naming task. This study extends previous findings by demonstrating that in healthy adults, a subdivision of the cingulate cortex is specifically associated with the cognitive demands present in the interference condition.     

Neural substrates for dividing and focusing attention between simultaneous auditory and visual events

With information constantly bombarding the human sensory systems, how is it that we attend to behaviorally relevant information? The present study examined the behavioral and neural bases of attending to one sense while ignoring another sense (bimodal selective attention) contrasted with attending simultaneously to two senses (bimodal divided attention). In a functional magnetic resonance imaging (fMRI) study, subjects simultaneously heard novel melodies and viewed geometric shapes. They were instructed to actively attend to only one or to both senses (selective or divided attention) or as a baseline condition, passively observe both (bimodal passive). Memory tests for both attended and unattended stimuli validated that subjects were following the attention instructions. Selective attention led to increased activity in relevant sensory cortices while simultaneously leading to decreased activity in irrelevant sensory cortices. The divided attention instruction did not lead to a global increase in sensory cortex activity compared to the bimodal passive baseline condition. However, divided attention did recruit heteromodal areas in the left dorsolateral prefrontal cortex, while selective attention did not recruit any frontal areas. We propose that sustained selective and divided bimodal attention were achieved via distinct neural processes. Selective attention was achieved primarily via modulation of the sensory cortices. Divided attention was achieved for most individuals via recruitment of the middle-dorsolateral prefrontal cortex. However, there was also a trade-off between activity in posterior-dorsolateral prefrontal cortex and sensory regions, such that individuals who demonstrated the best performance during divided attention also showed the greatest recruitment of sensory cortices.     

Alfentanil increases cortical dopamine D2/D3 receptor binding in healthy subjects

Animal studies have shown that opioids modulate the function of dopaminergic neurons. The effect of alfentanil on cortical and thalamic binding of the D2/D3 receptor ligand [(11)C]FLB 457 was evaluated in eight healthy subjects with positron emission tomography. The simplified reference tissue model was used to calculate tracer binding potential (BP) during a baseline condition and target-controlled infusion of alfentanil, and the results were analyzed using a comparison group not receiving opioid. Behavioral and analgesic effects of alfentanil were also evaluated. In the region-of-interest analysis, alfentanil increased the BP of [(11)C]FLB 457 in the medial frontal cortex (P=0.0027), dorsolateral prefrontal cortex (P=0.027) superior temporal cortex (P=0.028), and medial thalamus (P=0.003) These results were confirmed in a voxel-based analysis, which further revealed an opioid-induced increase in [(11)C]FLB 457 BP in the anterior cingulate cortex (P<0.001). Alfentanil induced euphoria (P=0.003) and analgesia (P=0.006) Cheerfulness (r=0.918, P=0.001) and euphoria (r=0.982, P<0.001) were associated with increased BP of [(11)C]FLB 457 in the left posterior cingulate cortex, but the analgesic effect of alfentanil did not correlate with changes in [(11)C]FLB 457 BP. The results of this study demonstrate opioid-dopamine interactions in frontal and temporal cortical regions and the thalamus in healthy subjects. Increased D2/D3 tracer binding during opioid infusion may reflect decreased synaptic dopamine levels. The association of the uplifting effect of alfentanil with increased D2/D3 binding in the posterior cingulate cortex suggests that cortical dopamine may be involved in the behavioral effects of opioids.     

fMRI of thermal pain: effects of stimulus laterality and attention.

Brain activity was studied by fMRI in 18 healthy subjects during stimulation of the thenar eminence of the hand with either warm (non-painful, 40 degrees C) or hot (painful, 46-49 degrees C) stimuli using a contact thermode. Experiments were performed on the right and left hand independently and with two attentional contexts: subjects either attended to pain or attended to a visual global motion discrimination task (to distract them from pain). Group analysis demonstrated that attended warm stimulation of the right hand did not produce any significantly activated clusters. Painful thermal stimulation of either hand elicited significant activity over a large network of brain regions, including insula, inferior frontal gyrus, cingulate gyrus, secondary somatosensory cortex, cerebellum, and medial frontal gyrus (corrected P < 0.05). Insula activity was distributed along its anterior-posterior axis and depended on the hand stimulated and attentional context. In particular, activity within the posterior insula was contralateral to the site of stimulation, tested using regions of interest (ROI) analysis: significant side x site interaction (P = 0.001). With attention diverted from the painful stimulus bilateral anterior insula activity moved posteriorly to midinsula and decreased in extent (ROI analysis: significant main effect of attention (P = 0.03)). The role of the insula in thermosensation and attention is discussed.     

Deriving numerosity and shape from identical visual displays

We presented identical displays of three to five dots in a functional magnetic resonance imaging (fMRI) experiment with normal volunteers. Two distinct directed attention tasks were performed on these displays: In one condition, subjects assessed the numerosity of the display; in the other condition, they assessed the shape of the display. Decisions based on numerosity activated differentially striate and extrastriate visual processing areas as well as left inferior frontal cortex. Decisions based on shape derived from arrangement activated differentially temporoparietal cortex bilaterally, medial posterior cingulate cortex, and left dorsolateral prefrontal cortex. These divergent neural activations in response to identical stimuli suggest that attentional mechanisms are deployed in very different ways in rapid enumeration of visual objects and in linking spatially discrete elements to one form.     

Left temporo-limbic and orbital dysfunction in schizophrenia during odor familiarity and hedonicity judgments

Impairments of olfactory processing in patients with schizophrenia (SZ) have been reported in various olfactory tasks such as detection, discrimination, recognition memory, identification, and naming. The purpose of our study was to determine whether impairments in odor familiarity and hedonicity judgments observed in SZ patients during a previous behavioral study are associated with modifications of the activation patterns in olfactory areas. Twelve SZ patients, and 12 healthy comparison (HC) subjects, were tested using the H2(15)O-PET technique and 48 different odorants delivered during 8 scans. In addition to an odorless baseline condition, they had either to detect odor, or to judge odor familiarity or hedonicity, giving their responses by pressing a button. Regional cerebral blood flows during olfactory conditions were compared with those for baseline condition. Between-group analyses were then performed, and completed by regions of interest analyses. Both groups had equivalent ability for the detection of suprathreshold odorants, but patients found odors less familiar, and pleasant odors less pleasant than HC subjects. These behavioral results were related to functional abnormalities in temporo-limbic and orbital olfactory regions lateralized in the left hemisphere: the posterior part of the piriform cortex and orbital regions for familiarity judgments, the insular gyrus for hedonicity judgments, and the left inferior frontal gyrus and anterior piriform cortex/putamen region for the three olfactory tasks. They mainly resulted from a lack of activation during task conditions in the SZ patients. These data could explain olfactory disturbances and other clinical features of schizophrenia such as anhedonia.     

静息态fMRI观察电刺激诱发肢体持续麻木感

目的 采用静息态fMRI（rs-fMRI）比率低频振幅（fALFF）法检测电刺激诱发肢体持续麻木感时脑功能变化，探讨持续性麻木相关脑机制。方法 对21名健康成人分别在有无电刺激条件下行rs-fMRI，嘱其对同一脉冲电刺激所致麻木感进行强度评分。以fALFF算法分析有无电刺激下rs-fMRI数据，获得存在显著差异脑区；对电刺激下脑fALFF与个体麻木感强度评分进行相关性分析。结果 电刺激下fALFF显著增强脑区包括额叶内侧皮质、前扣带回、两侧颞中回、两侧颞下回和右侧颞极（P均<0.05，FDR校正）；显著减弱脑区包括楔前叶/后扣带回、右侧小脑（P均<0.05，FDR校正）。电刺激下fALFF与个体麻木感评分显著正相关脑区则包括楔前叶/后扣带回和左侧颞中回（P均<0.05，FDR校正）显著负相关脑区为右侧额极和左侧颞下回（P均<0.05，FDR校正）。结论 电刺诱发肢体持续麻木感涉及感觉运动、情绪、认知及默认网络相关脑区；楔前叶/后扣带回、颞叶及额叶部分脑区与个体麻木程度显著相关。     

Cooperation of the anterior cingulate cortex and dorsolateral prefrontal cortex for attention shifting

Attention shifting in the working memory system plays an important role in goal-oriented behavior, such as reading, reasoning, and driving, because it involves several cognitive processes. This study identified brain activity leading to individual differences in attention shifting for dual-task performance by using the group comparison approach. A large-scale pilot study was initially conducted to select suitable good and poor performers. The fMRI experiment consisted of a dual-task condition and two single-task conditions. Under the dual-task condition, participants verified the status of letters while concurrently retaining arrow orientations. The behavioral results indicated that accuracy in arrow recognition was better in the good performers than in the poor performers under the dual-task condition but not under the single-task condition. Dual-task performance showed a positive correlation with mean signal change in the right anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC). Structural equation modeling indicated that effective connectivity between the right ACC and right DLPFC was present in the good performers but not in the poor performers, although activations of the task-dependent posterior regions were modulated by the right ACC and right DLPFC. We conclude that individual differences in attention shifting heavily depend on the functional efficiency of the cingulo-prefrontal network.     

Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems

Myofascial pain of the temporomandibular region (M-TMD) is a common, but poorly understood chronic disorder. It is unknown whether the condition is a peripheral problem, or a disorder of the central nervous system (CNS). To investigate possible CNS substrates of M-TMD, we compared the brain morphology of 15 women with M-TMD to that of 15 age- and gender-matched healthy controls. High-resolution structural brain and brainstem scans were carried out using magnetic resonance imaging (MRI), and data were analyzed using a voxel-based morphometry approach. The M-TMD group evidenced decreased or increased gray matter volume compared to controls in several areas of the trigeminothalamocortical pathway, including brainstem trigeminal sensory nuclei, the thalamus, and the primary somatosensory cortex. In addition, M-TMD individuals showed increased gray matter volume compared to controls in limbic regions such as the posterior putamen, globus pallidus, and anterior insula. Within the M-TMD group, jaw pain, pain tolerance, and pain duration were differentially associated with brain and brainstem gray matter volume. Self-reported pain severity was associated with increased gray matter in the rostral anterior cingulate cortex and posterior cingulate. Sensitivity to pressure algometry was associated with decreased gray matter in the pons, corresponding to the trigeminal sensory nuclei. Longer pain duration was associated with greater gray matter in the posterior cingulate, hippocampus, midbrain, and cerebellum. The pattern of gray matter abnormality found in M-TMD individuals suggests the involvement of trigeminal and limbic system dysregulation, as well as potential somatotopic reorganization in the putamen, thalamus, and somatosensory cortex.     

A PET investigation of the attribution of intentions with a nonverbal task

Several authors have demonstrated that theory of mind is associated with a cerebral pattern of activity involving the medial prefrontal cortex. This study was designed to determine the cerebral regions activated during attribution of intention to others, a task which requires theory-of-mind skills. Eight healthy subjects performed three nonverbal tasks using comic strips while PET scanning was performed. One condition required subjects to attribute intentions to the characters of the comic strips. The other two conditions involved only physical logic and knowledge about objects' properties: one condition involved characters, whereas the other only represented objects. The comparison of the attribution of intention condition with the physical logic with characters condition was associated with rCBF increases in the right middle and medial prefrontal cortex including Brodmann's area (BA) 9, the right inferior prefrontal cortex (BA 47), the right inferior temporal gyrus (BA 20), the left superior temporal gyrus (BA 38), the left cerebellum, the bilateral anterior cingulate, and the middle temporal gyri (BA 21). The comparison of the physical logic with characters condition and the physical logic without characters condition showed the activation of the lingual gyri (BA 17, 18, 19), the fusiform gyri (BA 37), the middle (BA 21) and superior (BA 22, 38) temporal gyri on both sides, and the posterior cingulate. These data suggest that attribution of intentions to others is associated with a complex cerebral activity involving the right medial prefrontal cortex when a nonverbal task is used. The laterality of this function is discussed.     

功能连接密度图观察内侧颞叶癫痫

目的 采用静息态fMRI功能连接密度（FCD）方法观察内侧颞叶癫痫（mTLE）脑功能活动改变的分布模式。方法 分别采集47例mTLE患者与32名正常志愿者（正常对照组）的静息态fMRI数据,通过两样本t检验,观察mTLE患者相对正常对照组的FCD活动改变,并采用基于体素的相关分析观察mTLE患者FCD改变脑区与癫痫病程的关系。结果 与正常对照组相比,mTLE患者发作间期FCD降低区域以双侧内侧颞叶、后扣带回、外侧颞叶和顶叶区为主;FCD增高区域主要分布于双侧感觉运动区（P<0.05,FWR多重校正）。基于体素的相关性分析显示,mTLE病程与双侧内侧颞叶、后扣带回及顶叶区的FCD值呈负相关（P<0.05,FDR多重校正）。结论 mTLE表现为默认网络及感觉运动区的功能连接异常;这些区域功能异常可能与mTLE的病理生理机制有关。     

Olfactory hypersensitivity in migraineurs: a H(2)(15)O-PET study

Olfactory hypersensitivity (OHS) may occur during migraine attacks and seems to be very specific to this form of headache. OHS is also observed during migraine-free periods and is associated with the presence of odour-triggered attacks. Yet the pathophysiology of OHS remains unknown. The aim of our study was to evaluate olfactory processing in migraineurs with OHS and to investigate whether regional cerebral blood flow (rCBF) associated with olfactory stimulation is modified in these patients compared with controls. Eleven migraineurs with OHS and 12 controls participated in a H(2)(15)O-positron emission tomography study, including three scans in which odours were delivered and three scans where only odourless air was delivered. rCBF during olfactory condition was compared with that for the odourless baseline condition. Between-group analyses were performed using voxel-based and region-of-interest analyses. During both olfactory and non-olfactory conditions, we observed higher rCBF in the left piriform cortex and antero-superior temporal gyrus in migraineurs compared with controls. During odour stimulation, migraineurs also showed significantly higher activation than controls in the left temporal pole and significantly lower activation in the frontal (left inferior as well as left and right middle frontal gyri) and temporo-parietal (left and right angular, and right posterior superior temporal gyri) regions, posterior cingulate gyrus and right locus coeruleus. These results could reflect a particular role of both the piriform cortex and antero-superior temporal gyrus in OHS and odour-triggered migraine. Whether these rCBF changes are the cause or a consequence of odour-triggered migraines and interictal OHS remains unknown. Further comparisons between migraineurs with and without OHS are warranted to address this issue. The abnormal cerebral activation patterns during olfactory stimulation might reflect altered cerebrovascular response to olfactory stimulation due to the migraine disease, or an abnormal top-down regulation process related to OHS.     

Cognitive effects of nicotine in humans: an fMRI study

To elucidate the neural correlates of cognitive effects of nicotine, we examined behavioral performance and blood oxygenation level-dependent regional brain activity, using functional magnetic resonance imaging, during a parametric "n-back" task in healthy nonsmoking males after the administration of nicotine (12 microg/kg body weight) or saline. Nicotine, compared to placebo, improved accuracy (P = 0.008) in all active conditions (2%-11%), and had a load-specific effect on latency (P = 0.004; 43.78% decrease at the highest memory load). Within a network of parietal and frontal areas activated by the task (P < 0.05, corrected at the voxel level), nicotine produced an increased response (P < 0.05; uncorrected within the regions of interest) in the anterior cingulate, superior frontal cortex, and superior parietal cortex. It also produced an increased response in the midbrain tectum in all active conditions and in the parahippocampal gyrus, cerebellum, and medial occipital lobe during rest (P = 0.05; uncorrected). The present observations point to altered neuronal activity in a distributed neural network associated with on-line task monitoring and attention and arousal systems as underlying nicotine-related enhancement of attention and working memory in human subjects.