Neuroanatomical dissociation between bottom-up and top-down processes of visuospatial selective attention

Allocation of attentional resources to portions of the available sensory input can be regulated by bottom-up processes, i.e., spontaneous orientation towards an oncoming stimulus (stimulus-driven attention), and by top-down processes, i.e., intentionally and driven by knowledge, expectation and goals. The present study aimed at advancing the understanding of brain networks mediating bottom-up and top-down control of visuospatial attention by employing a paradigm that parametrically varied demands on these two processes. Spatial predictability of peripheral targets was parametrically varied by centrally cueing one, two, three or four of four possible locations. Reaction time decreased linearly with more precise valid cueing of the target location and increased with more precise invalid cueing. Event-related functional magnetic resonance imaging (fMRI) enabled measurement of blood oxygenation level-dependent (BOLD) responses to cues and to targets. A mostly left-hemispheric network consisting of left intraparietal sulcus, inferior and superior parietal lobule, bilateral precuneus, middle frontal gyri including superior frontal sulci, and middle occipital gyri displayed BOLD responses to cues that increased linearly with more precise spatial cueing, indicating engagement by top-down spatial selective attention. In contrast, bilateral temporoparietal junction, cingulate gyrus, right precentral gyrus and anterior and posterior insula, bilateral fusiform gyri, lingual gyri and cuneus displayed BOLD responses to targets that increased with their spatial unpredictability, indicating engagement by stimulus-driven orienting. The results suggest two largely dissociated neural networks mediating top-down and bottom-up control of visuospatial selective attention.     

Atypical neural networks for social orienting in autism spectrum disorders

Autism spectrum disorders (ASD) are characterized by significant social impairments, including deficits in orienting attention following social cues. Behavioral studies investigating social orienting in ASD, however, have yielded mixed results, as the use of naturalistic paradigms typically reveals clear deficits whereas computerized laboratory experiments often report normative behavior. The present study is the first to examine the neural mechanisms underlying social orienting in ASD in order to provide new insight into the social attention impairments that characterize this disorder. Using fMRI, we examined the neural correlates of social orienting in children and adolescents with ASD and in a matched sample of typically developing (TD) controls while they performed a spatial cueing paradigm with social (eye gaze) and nonsocial (arrow) cues. Cues were either directional (indicating left or right) or neutral (indicating no direction), and directional cues were uninformative of the upcoming target location in order to engage automatic processes by minimizing expectations. Behavioral results demonstrated intact orienting effects for social and nonsocial cues, with no differences between groups. The imaging results, however, revealed clear group differences in brain activity. When attention was directed by social cues compared to nonsocial cues, the TD group showed increased activity in frontoparietal attention networks, visual processing regions, and the striatum, whereas the ASD group only showed increased activity in the superior parietal lobule. Significant group × cue type interactions confirmed greater responsivity in task-relevant networks for social cues than nonsocial cues in TD as compared to ASD, despite similar behavioral performance. These results indicate that, in the autistic brain, social cues are not assigned the same privileged status as they are in the typically developing brain. These findings provide the first empirical evidence that the neural circuitry involved in social orienting is disrupted in ASD and highlight that normative behavioral performance in a laboratory setting may reflect compensatory mechanisms rather than intact social attention.     

Continuous ASL perfusion fMRI investigation of higher cognition: quantification of tonic CBF changes during sustained attention and working memory tasks

Arterial spin labeling (ASL) perfusion fMRI is an emerging method in clinical neuroimaging. Its non-invasiveness, absence of low frequency noise, and ability to quantify the absolute level of cerebral blood flow (CBF) make the method ideal for longitudinal designs or low frequency paradigms. Despite the usefulness in the study of cognitive dysfunctions in clinical populations, perfusion activation studies to date have been conducted for simple sensorimotor paradigms or with single-slice acquisition, mainly due to technical challenges. Using our recently developed amplitude-modulated continuous ASL (CASL) perfusion fMRI protocol, we assessed the feasibility of a higher level cognitive activation study in twelve healthy subjects. Taking advantage of the ASL noise properties, we were able to study tonic CBF changes during uninterrupted 6-min continuous performance of working memory and sustained attention tasks. For the visual sustained attention task, regional CBF increases (6-12 ml/100 g/min) were detected in the right middle frontal gyrus, the bilateral occipital gyri, and the anterior cingulate/medial frontal gyri. During the 2-back working memory task, significantly increased activations (7-11 ml/100 g/min) were found in the left inferior frontal/precentral gyri, the left inferior parietal lobule, the anterior cingulate/medial frontal gyri, and the left occipital gyrus. Locations of activated and deactivated areas largely concur with previous PET and BOLD fMRI studies utilizing similar paradigms. These results demonstrate that CASL perfusion fMRI can be successfully utilized for the investigation of the tonic CBF changes associated with high level cognitive operations. Increased applications of the method to the investigation of cognitively impaired populations are expected to follow.     

Asymmetric modulation of human visual cortex activity during 10 degrees lateral gaze (fMRI study)

We used BOLD fMRI to study the differential effects of the direction of gaze on the visual and the ocular motor systems. Fixation of a target straight ahead was compared to fixation of a target 10 degrees to the right and 10 degrees to the left from gaze straight ahead, and to eyes open in complete darkness in thirteen healthy volunteers. While retinotopic coordinates remained the same in all fixation conditions, the fixation target shifted with respect to a head-centered frame of reference. During lateral fixation, deactivations in higher-order visual areas (one ventral cluster in the lingual and fusiform gyri and one dorsal cluster in the postero-superior cuneus) and, as a trend, activations in early visual cortical areas were found predominantly in the hemisphere contralateral to the fixation target. We propose that visual processing is performed predominantly in the hemisphere contralateral to gaze direction, even during small gaze shifts into one visual hemifield. The excitability of visual neurons may be modulated depending on eye position to construct a head-centered frame of reference from a retinotopic input, thus allowing perceptual stability of space during eye movements. A further finding was that BOLD signal increases in fronto-parietal ocular motor and attentional structures were more pronounced during lateral than central fixation.     

Endogenous and exogenous attention shifts are mediated by the same large-scale neural network

Event-related fMRI was used to examine the neural basis of endogenous (top-down) and exogenous (bottom-up) spatial orienting. Shifts of attention were induced by central (endogenous) or peripheral (exogenous) cues. Reaction times on subsequently presented targets showed the expected pattern of facilitation and inhibition in both conditions. No difference in brain activity was observed when the two orienting conditions were contrasted with a liberal threshold, showing that both forms of orienting were mediated by the same neural network. Compared to within-block control trials, both endogenous and exogenous orienting activated a fronto-parietal network consisting of premotor cortex, posterior parietal cortex, medial frontal cortex and right inferior frontal cortex. Within these regions, equally strong activation was observed for both orienting conditions. It is concluded that endogenous and exogenous orienting are mediated by the same large-scale network of frontal and parietal brain areas.     

fMRI-acoustic noise alters brain activation during working memory tasks

Scanner noise during functional magnetic resonance imaging (fMRI) may interfere with brain function and change blood oxygenation level dependent (BOLD) signals, a problem that generally worsens at the higher field strengths. Therefore, we studied the effect of increased acoustic noise on fMRI during verbal working memory (WM) processing. The sound pressure level of scanner noise was increased by 12 dBA from "Quiet" to "Loud" echo planar imaging (EPI) scans by utilizing resonant vibration modes of the gradient coil. A WM paradigm with graded levels of task difficulty was used to further access WM load. Increased scanner noise produced increased BOLD responses (percent signal change) bilaterally in the cerebellum, inferior (IFG), medial (medFG), and superior (SFG) frontal, fusiform (FusG), and the lingual (LG) gyri, and decreased BOLD responses bilaterally in the anterior cingulate gyrus (ACG) and the putamen. This finding suggests greater recruitment of attention resources in these brain regions, probably to compensate for interference due to louder scanner noise. Increased working memory load increased the BOLD signals in IFG and the cerebellum, but decreased the BOLD signals in the putamen and the LG. These findings also support the idea that brain function requires additional attention resources under noisier conditions. Load- and acoustic-noise-related changes in BOLD responses correlated negatively in the WM network. This study demonstrates that MR noise affects brain activation pattern. Future comparisons between studies performed under different acoustic conditions (due to differing magnetic field strengths, pulse sequences, or scanner manufacturers) might require knowledge of the sound pressure level of acoustic noise during fMRI.     

Differential cortical activation during voluntary and reflexive saccades in man

A saccade involves both a step in eye position and an obligatory shift in spatial attention. The traditional division of saccades into two types, the "reflexive" saccade made in response to an exogenous stimulus change in the visual periphery and the "voluntary" saccade based on an endogenous judgement to move gaze, is supported by lines of evidence which include the longer onset latency of the latter and the differential effects of lesions in humans and primates on each. It has been supposed that differences between the two types of saccade derive from differences in how the spatial attention shifts involved in each are processed. However, while functional imaging studies have affirmed the close link between saccades and attentional shifts by showing they activate overlapping cortical networks, attempts to contrast exogenous with endogenous ("covert") attentional shifts directly have not revealed separate patterns of cortical activation. We took the "overt" approach, contrasting whole reflexive and voluntary saccades using event-related fMRI. This demonstrated that, relative to reflexive saccades, voluntary saccades produced greater activation within the frontal eye fields and the saccade-related area of the intraparietal sulci. The reverse contrast showed reflexive saccades to be associated with relative activation of the angular gyrus of the inferior parietal lobule, strongest in the right hemisphere. The frequent involvement of the right inferior parietal lobule in lesions causing hemispatial neglect has long implicated this parietal region in an important, though as yet uncertain, role in the awareness and exploration of space. This is the first study to demonstrate preferential activation of an area in its posterior part, the right angular gyrus, during production of exogenously triggered rather than endogenously generated saccades, a finding which we propose is consistent with an important role for the angular gyrus in exogenous saccadic orienting.     

Occipital gamma-oscillations modulated during eye movement tasks: simultaneous eye tracking and electrocorticography recording in epileptic patients

We determined the spatio-temporal dynamics of cortical gamma-oscillations modulated during eye movement tasks, using simultaneous eye tracking and intracranial electrocorticography (ECoG) recording. Patients with focal epilepsy were instructed to follow a target moving intermittently and unpredictably from one place to another either in an instantaneous or smooth fashion during extraoperative ECoG recording. Target motion elicited augmentation of gamma-oscillations in the lateral, inferior and polar occipital regions in addition to portions of parietal and frontal regions; subsequent voluntary eye movements elicited gamma-augmentation in the medial occipital region. Such occipital gamma-augmentations could not be explained by contaminations of ocular or myogenic artifacts. The degree of gamma-augmentation was generally larger during saccade compared to pursuit trials, while a portion of the polar occipital region showed pursuit-preferential gamma-augmentations. In addition to the aforementioned eye movement task, patients were asked to read a single word popping up on the screen. Gamma-augmentation was elicited in widespread occipital regions following word presentation, while gamma-augmentation in the anterior portion of the medial occipital region was elicited by an involuntary saccade following word presentation rather than word presentation itself. Gamma-augmentation in the lateral, inferior and polar occipital regions can be explained by increased attention to a moving target, whereas gamma-augmentation in the anterior-medial occipital region may be elicited by images in the peripheral field realigned following saccades. In functional studies comparing brain activation between two tasks, eye movement patterns during tasks may need to be considered as confounding factors.     

Control networks and hemispheric asymmetries in parietal cortex during attentional orienting in different spatial reference frames

Neuropsychological research has consistently demonstrated that spatial attention can be anchored in one of several coordinate systems, including those defined with respect to an observer (viewer-centered), to the gravitational vector (environment-centered), or to individual objects (object-centered). In the present study, we used hemodynamic correlates of brain function to investigate the neural systems that mediate attentional control in two competing reference frames. Healthy volunteers were cued to locations defined in either viewer-centered or object-centered space to discriminate the shape of visual targets subsequently presented at the cued locations. Brain responses to attention-directing cues were quantified using event-related functional magnetic resonance imaging. A fronto-parietal control network was activated by attention-directing cues in both reference frames. Voluntary shifts of attention produced increased neural activity bilaterally in several cortical regions including the intraparietal sulcus, anterior cingulate cortex, and the frontal eye fields. Of special interest was the observation of hemispheric asymmetries in parietal cortex; there was significantly greater activity in left parietal cortex than in the right, but this asymmetry was more pronounced for object-centered shifts of attention, relative to viewer-centered shifts of attention. Measures of behavioral performance did not differ significantly between the two reference frames. We conclude that a largely overlapping, bilateral, cortical network mediates our ability to orient spatial attention in multiple coordinate systems, and that the left intraparietal sulcus plays an additional role for orienting in object-centered space. These results provide neuroimaging support for related claims based on findings of deficits in object-based orienting in patients with left parietal lesions.     

BOLD signal in intraparietal sulcus covaries with magnitude of implicitly driven attention shifts

A lot is known about the neural basis of directing attention based on explicit cues. In real life however, attention shifts are rarely directed by explicit cues but rather generated implicitly, for example on the basis of previous experience with a given situation. Here, we aimed at studying attention shifts dependent on recent trial history. While explicitly cued attention shifts involve activity in cortex of the intraparietal sulcus, whether this region is also involved in shifting attention according to recent history is still unknown. We asked observers to detect targets in a stream of visual stimuli with three feature dimensions: color, shape and motion. Critically, target occurrence probability was always higher in one stimulus dimension than in the others, and probabilities switched between dimensions over blocks of trials. After each probability switch, target detection times decreased exponentially for high-probability targets and increased for low-probability targets, compatible with gradual shifts in attention dependent on trial history since the switch. BOLD signal in left prefrontal and intraparietal sulcus regions was higher in the early phase after the switch, while anterior cingulate, cuneus, precuneus, temporal and more anterior frontal regions showed more activation later after the switch. These findings are compatible with the engagement of regions involved in the establishment and maintenance of attentional sets. BOLD signal in left intraparietal sulcus correlated with the size of the performance changes consecutive to the detected targets, suggesting that it reflects the size of attention shifts induced by updating target probabilities over recent trial history.     

Taking an "intentional stance" on eye-gaze shifts: a functional neuroimaging study of social perception in children

During middle childhood, children develop an increasing understanding of intentions and other social information conveyed through dynamic facial cues such as changes in eye-gaze direction. Recent work in our laboratory has focused on using functional magnetic resonance imaging (fMRI) in adults to map the neural circuitry subserving the visual analysis of others' actions and the intentions underlying these actions. In these studies, the superior temporal sulcus (STS) region has been continually implicated in processing shifts in eye gaze. Further, these studies have indicated that STS activity is modulated by the context within which eye-gaze shifts occur, suggesting that this region is involved in social perception via its role in the analysis of the intentions of observed actions. Still, no studies have investigated the neural circuitry supporting eye-gaze processing in children. We used event-related fMRI to examine brain activity in 7- to 10-year-old healthy children observing an animated virtual actor who shifted her eyes towards either a target object or empty space. Consistent with prior studies in adults, the STS, middle temporal gyrus, and inferior parietal lobule were sensitive to the intentions underlying the stimulus character's eye movements. These findings suggest that the neural circuitry underlying the processing of eye gaze and the detection of intentions conveyed through shifts in eye gaze in children are similar to that found previously in adults. We discuss these findings and potential implications for mapping the neurodevelopment of the social cognition and social perception abnormalities characteristic of autism.     

The large-scale neural network for spatial attention displays multifunctional overlap but differential asymmetry

Functional magnetic resonance imaging (fMRI) was used to determine the brain regions activated by two types of covert visuospatial attentional shifts: one based on exogenous spatial priming and the other on foveally presented cues which endogenously regulated the direction of spatial expectancy. Activations were seen in the cortical and subcortical components of a previously characterized attentional network, namely, the frontal eye fields, posterior parietal cortex, the cingulate gyrus, the putamen, and the thalamus. Additional activations occurred in the anterior insula, dorsolateral prefrontal cortex, temporo-occipital cortex in the middle and inferior temporal gyri, the supplementary motor area, and the cerebellum. Direct comparisons showed a nearly complete overlap in the location of activations resulting from the two tasks. However, the spatial priming task displayed a more pronounced rightward asymmetry of parietal activation, and a conjunction analysis showed that the area of posterior parietal cortex jointly activated by both tasks was more extensive in the right hemisphere. Furthermore, the posterior parietal and temporo-occipital activations were more pronounced in the task of endogenous attentional shifts. The results show that both exogenous (based on spatial priming) and endogenous (based on expectancy cueing) shifts of attention are subserved by a common network of cortical and subcortical regions. However, the differences between the two tasks, especially in the degree of rightward asymmetry, suggests that the pattern of activation within this network may show variations that reflect the specific attributes of the attentional task.     

An fMRI Investigation of Cortical Contributions to Spatial and Nonspatial Visual Working Memory

The experiments presented in this report were designed to test the hypothesis that visual working memory for spatial stimuli and for object stimuli recruits separate neuronal networks in prefrontal cortex. We acquired BOLD fMRI data from subjects while they compared each serially presented stimulus to the one that had appeared two or three stimuli previously. Three experiments failed to reject the null hypothesis that prefrontal cortical activity associated with spatial working memory performance cannot be dissociated from prefrontal cortical activity associated with nonspatial working memory performance. Polymodal regions of parietal cortex (inferior and superior parietal lobules), as well as cortex surrounding the superior frontal sulcus (and encompassing the frontal eye fields), also demonstrated equivalent levels of activation in the spatial and object conditions. Posterior cortical regions associated with the ventral visual processing stream (portions of lingual, fusiform, and inferior temporal gyri), however, demonstrated greater object than spatial working memory-related activity, particularly when stimuli varied only along spatial or featural dimensions. These experiments, representing fMRI studies of spatial and object working memory in which the testing procedure and the stimuli were identical in the two conditions, suggest that domain-specific visual working memory processing may be mediated by posterior regions associated with domain-specific sensory processing.     

Using eye movements to investigate selective attention in chronic daily headache

Previous research has demonstrated that chronic pain is associated with biased processing of pain-related information. Most studies have examined this bias by measuring response latencies. The present study extended previous work by recording eye movement behaviour in individuals with chronic headache and in healthy controls while participants viewed a set of images (ie, facial expressions) from 4 emotion categories (pain, angry, happy, neutral). Biases in initial orienting were assessed from the location of the initial shift in gaze, and biases in the maintenance of attention were assessed from the duration of gaze on the picture that was initially fixated, and the mean number of visits, and mean fixation duration per image category. The eye movement behaviour of the participants in the chronic headache group was characterised by a bias in initial shift of orienting to pain. There was no evidence of individuals with chronic headache visiting more often, or spending significantly more time viewing, pain images compared to other images. Both participant groups showed a significantly greater bias to maintain gaze longer on happy images, relative to pain, angry, and neutral images. Results are consistent with a pain-related bias that operates in the orienting of attention on pain-related stimuli, and suggest that chronic pain participants’ attentional biases for pain-related information are evident even when other emotional stimuli are present. Pain-related information-processing biases appear to be a robust feature of chronic pain and may have an important role in the maintenance of the disorder.     

Neural networks underlying endogenous and exogenous visual-spatial orienting

The orienting of visual-spatial attention is fundamental to most organisms and is controlled through external (exogenous) or internal (endogenous) processes. Exogenous orienting is considered to be reflexive and automatic, whereas endogenous orienting refers to the purposeful allocation of attentional resources to a predetermined location in space. Although behavioral, electrophysiological and lesion research in both primates and humans suggests that separate neural systems control these different modes of orienting, previous human neuroimaging studies have largely reported common neuronal substrates. Therefore, event-related FMRI (ER-FMRI) was used to independently examine different components of the orienting response including endogenous facilitation, exogenous facilitation and inhibition of return (IOR). In contrast to previous studies, endogenous versus exogenous facilitation resulted in widespread cortical activation including bilateral temporoparietal junction, bilateral superior temporal gyrus, right middle temporal gyrus, right frontal eye field and left intraparietal sulcus. Conversely, IOR compared to endogenous facilitation resulted in only a single focus of activation in the left superior temporal gyrus. These findings suggest that endogenous orienting activates a large cortical network to achieve internally generated shifts of attentional resources versus the automatic orienting that occurs with exogenous cues. However, similar networks may mediate endogenous orienting and IOR. The activation of the temporoparietal junction suggests that it is involved in more effortful processes, such as endogenous orienting, as well as in attentional reorienting and locating targets. Current results are discussed in terms of the functional development of the visual-spatial attentional system.     

Hemispheric asymmetry in global/local processing: effects of stimulus position and spatial frequency

We examined the neural mechanisms of functional asymmetry between hemispheres in the processing of global and local information of hierarchical stimuli by measuring hemodynamic responses with functional magnetic resonance imaging (fMRI). In a selective attention task, subjects responded to targets at the global or local level of compound letters that were (1) broadband in spatial-frequency spectrum and presented at fixation; (2) broadband and presented randomly to the left or the right of fixation; or (3) contrast balanced (CB) to remove low spatial frequencies (SFs) and presented at fixation. Central broadband stimuli induced stronger activation in the right middle occipital cortex under global relative to local attention conditions but in the left inferior occipital cortex, stronger activation was induced under local relative to global attention conditions. The asymmetry over the occipital cortex was weakened by unilateral presentation and by contrast balancing. The results indicate that the lateralization of global and local processing is modulated by the position and SF spectrum of the compound stimuli. The global attention also produced stronger activation over the medial occipital cortex relative to the local attention under all the stimulus conditions. The nature of these effects is discussed.     

Orienting attention to semantic categories

We investigated the ability to orient attention to a complex, non-perceptual attribute of stimuli-semantic category. Behavioral consequences and neural correlates of semantic orienting were revealed and compared with those of spatial orienting, using event-related functional magnetic-resonance imaging. Semantic orienting significantly shortened response times to identify word stimuli, showing that it is possible to focus attention on non-perceptual attributes of stimuli to enhance behavioral performance. Semantic-orienting cues engaged parietal and frontal areas that were also involved in spatial orienting, but in addition engaged brain areas associated with semantic analysis of words, such as the left anterior inferior frontal cortex. These findings show that attentional orienting selectively engages brain areas with functional specialization for the predicted attributes. They also support the existence of a core frontoparietal network, which controls attentional orienting in speeded response tasks independently of the type of expectations, interacting with task-relevant functionally specialized areas to optimize perception and action.     

Effects of Higher Versus Lower Threat Contexts on Pain-Related Visual Attention Biases: An Eye-Tracking Study of Chronic Pain

In this research, we examined effects of higher versus lower threat contexts on attention biases in more and less pain-fearful chronic pain subgroups via eye-tracking methodology. Within a mixed chronic pain sample (69 women, 29 men), biases in orienting and maintenance of visual attention were assessed during the standardized image pair presentation phase (2,000?ms) of a modified visual dot probe task featuring painful-neutral (P-N) image pairs (lower threat context) and a parallel task in which these P-N pairs cued potential pain (higher threat context). Across both tasks, participants more often oriented toward, gazed longer at, and made more unique fixations upon pain images during P-N pair presentations. Although trait-based fear of pain was not related to any gaze bias index in either task, between task analyses indicated the sample reported more state fear, directed their initial gaze less often, and displayed longer overall gaze durations toward pain images in the higher threat context in which P-N trials signaled potential pain. Results supported the threat interpretation model premise that persons with chronic pain have difficulty disengaging from moderately threatening visual painful cues.

The neural networks underlying endogenous auditory covert orienting and reorienting

Auditory information communicated through vocalizations, music, or sounds in the environment is commonly used to orient and direct attention to different locations in extrapersonal space. The neural networks subserving attention to auditory space remain poorly understood in comparison to our knowledge about attention in the visual system. The present study investigated whether a parietal-prefrontal right-hemisphere network controls endogenous orienting and reorienting of attention to the location of sounds just as it does for visual-spatial information. Seventeen healthy adults underwent event-related functional magnetic resonance imaging (FMRI) while performing an endogenous auditory orienting task, in which peripheral cues correctly (valid) or incorrectly (invalid) specified the location of a forthcoming sound. The results showed that a right precuneus and bilateral temporal-frontal network mediated the reorienting of auditory attention at both short and long stimulus onset asynchronies (SOAs). In contrast, the more automatic stage of auditory reorienting at the shorter SOA was associated with activation in a bilateral inferior parietal-frontal oculomotor network. These findings suggest that the reorienting of auditory attention is generally supported by a similar inferior parietal-frontal network as visual attention, but in both hemispheres. However, peripheral auditory cues also appear to elicit an automatic orienting response to the spatial location of a sound followed by a period of reduced processing of information that occurs in the same location later in time.     

Functional connectivity mapping of the human precuneus by resting state fMRI

Precuneus responds to a wide range of cognitive processes. Here, we examined how the patterns of resting state connectivity may define functional subregions in the precuneus. Using a K-means algorithm to cluster the whole-brain “correlograms” of the precuneus in 225 adult individuals, we corroborated the dorsal-anterior, dorsal-posterior, and ventral subregions, each involved in spatially guided behaviors, mental imagery, and episodic memory as well as self-related processing, with the ventral precuneus being part of the default mode network, as described extensively in earlier work. Furthermore, we showed that the lateral/medial volumes of dorsal anterior and dorsal posterior precuneus are each connected with areas of motor execution/attention and motor/visual imagery, respectively. Compared to the ventral precuneus, the dorsal precuneus showed greater connectivity with occipital and posterior parietal cortices, but less connectivity with the medial superior frontal and orbitofrontal gyri, anterior cingulate cortex as well as the parahippocampus. Compared to dorsal-posterior and ventral precuneus, the dorsal-anterior precuneus showed greater connectivity with the somatomotor cortex, as well as the insula, supramarginal, Heschl's, and superior temporal gyri, but less connectivity with the angular gyrus. Compared to ventral and dorsal-anterior precuneus, dorsal-posterior precuneus showed greater connectivity with the middle frontal gyrus. Notably, the precuneus as a whole has negative connectivity with the amygdala and the lateral and inferior orbital frontal gyri. Finally, men and women differed in the connectivity of precuneus. Men and women each showed greater connectivity with the dorsal precuneus in the cuneus and medial thalamus, respectively. Women also showed greater connectivity with ventral precuneus in the hippocampus/parahippocampus, middle/anterior cingulate gyrus, and middle occipital gyrus, compared to men. Taken together, these new findings may provide a useful platform upon which to further investigate sex-specific functional neuroanatomy of the precuneus and to elucidate the pathology of many neurological illnesses.