Faculty Affiliation and Disclosures
Dr. Cavanna is honorary research fellow at the Institute of Neurology, Queen Square in London, the United Kingdom, and consultant neurologist in the Department of Neurology at Amedeo Avogadro University in Novara, Italy.
Disclosures: Dr. Cavanna receives grant/research support from Amedeo Avogadro University.
Submitted for publication: April 23, 2007; Accepted for publication: June 18, 2007.
Please direct all correspondence to: Andrea E. Cavanna, MD, Institute of Neurology, Queen Square, London WC1N3BG, UK; E-mail: A.Cavanna@ion.ucl.ac.uk.
This article reviews the rapidly growing literature on the functional anatomy and behavioral correlates of the precuneus, with special reference to imaging neuroscience studies using hamodynamic techniques. The precuneus, along with adjacent areas within the posteromedial parietal cortex, is among the most active cortical regions according to the “default mode” of brain function during the conscious resting state, whereas it selectively deactivates in a number of pathophysiological conditions (ie, sleep, vegetative state, drug-induced anesthesia), and neuropsychiatric disorders (ie, epilepsy, Alzheimer’s disease, and schizophrenia) characterized by impaired consciousness. These findings, along with the widespread connectivity pattern, suggest that the precuneus may play a central role in the neural network correlates of consciousness. Specifically, its activity seems to correlate with self-reflection processes, possibly involving mental imagery and episodic/autobiographical-memory retrieval.
Functional Anatomy of the Posteromedial Parietal Lobe
The medial aspect of the posterior parietal lobe has historically been referred to as the precuneus, or quadrate lobule of Foville.1 This cortical region was named after its geometrical appearance and topographical location, since it is situated immediately in front of the triangular-shaped convolution of the cuneus. It lies buried in the depths of the longitudinal fissure and encased by the sagittal sinus and bridging veins: the hidden location, coupled with the rarity of isolated lesions, made it traditionally resistant to scientific exploration.2 As a consequence, the precuneus has long remained one of the less accurately mapped areas of the whole cortical surface. However, its strategic location and widespread connectivity patterns suggest that it is a major association area that may subserve a variety of behavioral functions, which the modern era of neuroimaging has begun to unravel. After briefly reviewing the current knowledge about the anatomical and cytoarchitectonic structure of the precuneus, along with its widespread connectivity patterns, this article provides an overview on the behavioral correlates of this cortical region, as disclosed by functional imaging studies involving both normal and altered-conscious states and higher-order cognitive tasks.
The cytoarchitecture of the posteromedial parietal cortex and posterior cingulate gyrus has recently been reviewed by Vogt and Laureys3 and Cavanna and Trimble.4 The cytoarchitectonic map of Brodmann5 still dominates the present concepts of the structural organization of the human cerebral cortex, since it serves, via a popular brain atlas,6 as an anatomical reference for functional imaging studies. The territory of the precuneus mainly corresponds to the mesial extent of Brodmann area (BA) 7, which also occupies most of the lateral parietal cortex above the intraparietal sulcus.7,8 An adjacent cytoarchitectonic region has been proposed to be part of the precuneus, according to some authors,9,10 BA 31, which is positioned between the cingulate and splenial sulci, belongs to both posterior cingulate and precuneate cortices (Figure 1). However, the medial surface of BA 7 is easily distinguished from posterior cingulate and retrosplenial cortices by its representative parietal cytoarchitecture, characterized by fully differentiated isocortex with vertically oriented clumps of dendrites in layers III and IV, a thicker layer IV, a relatively larger layer IIIc neurons than those in layer Va (the opposite of cingulate architecture), and a noticeable thinning of cortex as a whole.3,11 On the other hand, BA 31 appears to be a cortical transition zone from the medial parietal areas to the posterior cingulate, presenting an apparent shift in cytoarchitecture from parietal isocortex to limbic cortex.
The knowledge about the connectivity patterns of the precuneus is based mainly on axonal tracing studies7 in the macaque brain, which is the closest approximation to the human brain in conventional anatomical tracing experiments. A recent study by Parvizi and colleagues,12 using modern anterograde and retrograde axonal tracers, provided a comprehensive map of both afferent and efferent, subcortical and cortical connections of all cytoarchitectonic areas within the posteromedial parietal cortex. Overall, the extent of the connectivity of the precuneus is widespread and involves higher association cortical and subcortical structures. Cortical connections include the adjacent posterior cingulate and retrosplenial cortices, the arietal operculum, inferior and superior parietal lobules, intraparietal sulcus, mid-dorsolateral prefrontal cortex, temporo-parieto-occipital cortex, and medial prestriate cortex. The main subcortical connections are with the dorsalmost sector of the thalamus, the claustrum, the dorsolateral caudate nucleus, putamen, the zona incerta, and several brainstem structures, including the pretectal area, the superior colliculus, the nucleus reticularis tegmenti pontis, and the basis pontis. Notably, no direct connections between the precuneus and primary sensory regions have been described. The primary motor cortex, the monoaminergic nuclei of the brainstem, and the sensory thalamic nuclei are also void of any connections with the posteromedial cortical regions. Therefore, it seems reasonable to assume that precuneus activity influences an extensive network of cortical and subcortical structures involved in elaborating highly integrated and associative information, rather than directly processing external stimuli.
Behavioral Correlates of the Precuneus
The “Default Mode” of Brain Activity During Conscious Rest
Brain functional imaging studies from the mid 1990s13,14 first suggested that cerebral blood flow (CBF) and metabolism may vary across different cortical regions during the silent resting state, being somewhat greater in the medial parietal, medial occipital, and mid-dorsolateral prefrontal areas. A landmark study by Raichle and colleagues15 used the oxygen-extraction fraction, a measure that represents the change in the proportion of oxygen delivered to oxygen utilized, to effectively demonstrate that despite changes in CBF and oxygen consumption, a metabolic equilibrium is reached in terms of neuronal activity when normal subjects are in a resting state (ie, lying in the scanner, awake, eyes closed, with cognition unconstrained by experimental stimulation or specific behavioral instructions from the investigators except to rest quietly). The researchers found that during the baseline resting state, a neural network comprising the precuneus and posteromedial parietal region, along with lateral parietal, ventromedial prefrontal, mid-dorsolateral prefrontal, and anterior temporal cortices, exhibits a remarkably high metabolic activity (so-called hot spots). Moreover, the tonic level of activity of the precuneate cortex and of the other hot spots of the brain characteristically decreases when subjects are engaged in goal-directed cognitive processing or perceptual tasks (task-induced deactivations [TIDs]). In other words, when obliged to perform an active task, the brain seems to suspend baseline processes, producing deactivations in the regions subserving those processes.14,16,17 The magnitude of some of these decreases in activity has been noted to vary with such factors as task difficulty and the emotional state of the subject.18 Taken together, this high baseline metabolic rate and the predilection for TIDs suggest the existence of an organized baseline state of neural activity, which is referred to as “the default mode of brain function”.15,16,19
Within this conceptual framework, the precuneus is of particular interest, because it shows the highest metabolic activity in the baseline resting state among these zones, consuming about 35% more glucose than any other area of the cerebral cortex (Figure 2).16 Over the last few years, the notion17-20 that the brain has a default or intrinsic mode of functioning has received increasing attention. Objections have been raised about the biological and scientific significance of the default mode of brain function: the main arguments have been summarized in a timely commentary by Morcom and Fletcher.20 It has been claimed that the case for a default mode does not survive a critical evaluation. Specifically, while it is generally accepted that a high level of energy expenditure of the brain at rest indicates that the resting state is active, a few authors20 do not agree that this activity has a special status compared with that in any other task or that the brain’s energy budget is informative about the nature of a default mode. Moreover, it has been pointed out that there are insufficient grounds for affording the resting state a privileged status in accounts of human behavior.
Although the behavioral correlates of this default-mode network activity have proven traditionally difficult to identify and relatively little is known about the purpose and significance of the spontaneous mental processing taking place during rest, several lines of evidence4 point toward a pivotal role in the neural network correlates of conscious experience. Recent functional imaging studies4 have demonstrated that the precuneus and adjacent posteromedial cortical regions show a profound deactivation in pathophysiological altered states of consciousness, such as slow-wave sleep and rapid eye movement sleep, the hypnotic state, pharmacologically induced general anaesthesia, and vegetative state. A few neuropsychiatric conditions characterized by reduced (eg, Alzheimer’s disease, schizophrenia) or temporarily abolished (eg, epilepsy) self-awareness have also been shown to correlate with significant deactivations in precuneus and default mode areas. The following sections are intended to provide an overview on these intriguing brain-behavior correlations.
Sleep and Hypnosis
Over the last few years, positron emission tomography (PET) studies21-24 have yielded original data on the functional neuroanatomy of human sleep. The precuneus, along with lateral parietal and prefrontal cortices, were found to be significantly less active than the rest of the brain during slow-wave sleep/deep sleep21 and rapid eye movement sleep.22,23 In a PET experiment exploring the neural correlates of hypnosis, regional (rCBF) decreases were found in the precuneus, posterior cingulate and right inferior parietal lobule.24 The interpretation of this selective deactivation is uncertain. However, since the impaired consciousness of the self and its environment represents a key feature shared by the different sleep stages and the hypnotic state, these observations seem to provide further evidence for an active participation of the precuneus in the conscious processes of high-order self-representation.25
Anesthetic drugs are known to possess general mechanisms of action such as at the γ-aminobutyric acid A receptor and are likely to reduce neuron activity throughout the brain; however recent research has identified particularly susceptible regions whose modulation seems to be most closely associated with conscious functions. Fiset and colleagues26 used PET to investigate changes in rCBF during a general anaesthetic infusion, set to produce a gradual transition from the awake state to unconsciousness. In addition to a generalized decrease in global CBF, propofol-induced anaesthesia was characterized by marked regional flow decrements in the precuneus, the posterior cingulate, the cuneus, the medial thalamus and frontal cortical regions. Moreover, the progressive decrease in precuneus/posterior cingulate activity correlated directly with the deepening of sedation, and inversely with the restoring of consciousness. It has been demonstrated that halothane also decreases rCBF in the precuneus and adjacent posterior cingulate cortex, suggesting that many anesthetics target the posteromedial parietal lobe as an endpoint to induce loss of consciousness.27 These results support the hypothesis that anaesthetics induce behavioral changes via an effect on specific neuronal networks, including the precuneus, that are implicated in the regulation of arousal and performance of associative conscious functions.
Over the last decade, subjects in vegetative state—the ultimate state of conscious incapacity—have been intensely investigated by means of PET and statistical parametric mapping.28 Functional neuroimaging findings from these patients identified markedly impaired function of the precuneus and posterior cingulate cortex, together with prefrontal and parieto-temporal association areas. Interestingly enough, the precuneus is among the first regions of the brain to resume its activity if patients regain consciousness. Laureys and colleagues29 reported that the functional relationship between the posteromedial cortex and the thalamus is altered during the vegetative state but regains near-normal values once the patients recover consciousness. Moreover, preliminary data29 show that overall cerebral metabolism in the minimally conscious state is decreased to values slightly higher but comparable to those observed in the vegetative state. In fact, the precuneus and adjacent posterior cingulate cortex seem to be brain regions that differentiate patients in minimally conscious states from those in vegetative state.
Generalized epilepsies (absences, tonic-clonic seizures) entail, by definition, complete loss of consciousness. Absence seizures are characterized by rather stereotyped phenomenological features, consisting of a brisk interruption of the patient’s behavior, with staring, unresponsiveness, and possible eyelid fluttering or mild myoclonic spasms. No subjective experience accompanies these relatively common types of seizures, as they entail a sudden “black-out” of both the general level of awareness and the phenomenal contents of consciousness.30,31 Recent studies of patients with generalized spike-wave activity32-34 have achieved excellent standards of spatial and temporal resolution by coupling functional magnetic resonance imaging (fMRI) with simultaneous electroencephalogram (EEG) recordings. Quite interestingly, preliminary EEG-fMRI findings confirmed that generalized seizures may selectively involve certain networks, while sparing others. In particular, they demonstrated bilateral thalamic activation and cortical signal decrease in a characteristic distribution of association areas that are most active during conscious rest, including midline precuneus/posterior cingulate, lateral parietal, and prefrontal cortices.
The neurobiological changes associated with complex partial seizures (ie, focal seizures accompanied by varying degrees of consciousness impairment) have also been recently addressed by functional imaging studies.35,36 Interictal and ictal single photon emission computed tomography with early injection during complex partial seizures in patients with hippocampal sclerosis showed ictal hyperperfusion in the temporal lobe ipsilateral to the seizure focus along with ipsilateral middle frontal and precentral gyrus and both occipital lobes. Conversely, the ipsilateral precuneus, along with the frontal lobes and contralateral posterior cerebellum showed marked hypoperfusion.35 A recent EEG-fMRI study by Laufs and colleagues36 demonstrated that interictal epileptic discharges affect activity in the brain network comprising precuneus, medial frontal, and temporo-parietal cortices only in patients with temporal lobe epilepsy who have complex partial seizures, possibly as a result of the repeated episodes of transient impairment of consciousness.
Although it has been known for some time that regional decreases in CBF exist in both normal aging and dementia, only in the last few years imaging studies37-40 have shown that hypometabolism in early-stage Alzheimer’s disease is localized to specific cortical regions, including the precuneus and posterior cingulate. The results of fMRI studies37,38 have found compelling evidence that patterns of resting-state connectivity are decreased in normal aging but more so in patients with dementia. Thus, departures from a normal degree of default-mode activity may be important in the clinical etiology of age-related brain diseases.39 Furthermore, the observed deactivations of the precuneus and posteromedial cortex, when involved in goal-oriented behaviors (TIDs), show peculiar changes in populations with Alzheimer’s disease and mild cognitive impairment.37,38 In fact, Alzheimer’s disease patients fail to deactivate from the hypermetabolic activity of the resting state, and instead display a pattern of moderate precuneus activation with the onset of a cognitive task.
A large study by Buckner and colleagues40 analyzed data obtained from 764 participants to in vivo imaging studies and consistently found amyloid deposition in posteromedial and lateral parietal cortex, correlating with prominent atrophy and metabolic abnormalities. Moreover, given the commonality of projections from the intralaminar nuclei of the thalamus to all regions of the medial parietal cortex, Parvizi and colleagues12 suggested that these connections are central to the function of the precuneus and interrelated medial parietal areas at rest and during goal-directed tasks. Therefore, the progressive disruption of the thalamocortical pathways resulting from Alzheimer’s disease is likely to contribute to the observed reversal of deactivation patterns in elderly demented populations. Some behavioral features of Alzheimer’s disease, including loss of arousal and self-awareness, could be partially accounted for by the abnormal neuropathological changes affecting the functional connectivity between the anterior intralaminar nuclei and the precuneus.
TIDs in the midline regions showing high metabolism at rest have been investigated in other clinical populations. Schizophrenia is a neuropsychiatric disorder characterized by marked disturbances of insight, a multifactorial behavioral construct involving introspection, emotion, and aspects of self-awareness.41 Recently, a fMRI controlled study by Harrison and colleagues42 examined whether the midline TIDs phenomenon is altered in schizophrenia and related to patients’ symptoms, level of emotional awareness, and cognitive task performance. The mechanism proposed to explain midline TIDs refers to the change of brain activity that occurs when attention is shifted from the normally self-focused resting state to externally focused attention when performing cognitively demanding tasks.15 In general, the greater the cognitive load of the task, the greater interruption of self-directed attention and larger TID effect observed.43 Quite interestingly, in the schizophrenia group the magnitude of TIDs of the precuneus/posterior cingulate area was significantly greater than in control subjects but failed to show any correlation with cognitive task performance. Although there is no clear-cut explanation for this preliminary finding, it is likely that the alterations in self-directed thoughts and the emotional disturbances occurring in schizophrenia selectively influence the midline cortical deactivation pattern in the posteromedial parietal cortex.
Precuneus and Self-Consciousness
A major challenge for theorists of the default mode of brain functioning is to determine how TIDs and selective hypometabolism in pathophysiological conditions affecting consciousness relate to resting-state mentation. One possibility is that when an individual is awake and alert and yet not actively engaged in particular cognitive task, the precuneus and interconnected posterior cingulate and medial prefrontal cortices subserve continuous information-gathering and representation of the self and external world.16 This hypothesis fits nicely with the observed functional TIDs: When non-self-referential goal-directed processes are to be performed, the resting-state processes are interrupted, reflecting a necessary reduction in resources devoted to general information gathering and evaluation. As a consequence, it would seem to be a default activity of the brain with rather obvious evolutionary significance: When the successful performance of a task demands focused attention, such broad information-gathering activity needs to be curtailed.15,16,43 Likewise, Binder and colleagues14 suggested that precuneus activity during conscious resting states supports conceptual processing operating on internal stores of information (endogenous signals) rather than “perceptual” functions (concerned with sources of information external to the brain). In other words, this area seems to contribute to the self-referential “thought” processing that humans experience during resting consciousness.
In a summary of work considering a variety of functional imaging data, Vogeley and Fink44 found that spatial tasks involving explicit first-person perspective-taking and spatial attention engage both medial and lateral parietal regions, particularly on the right side (see also Trimble45). Moreover, the precuneus and the other “hot spots” that characterize the default mode of the resting state have been consistently shown to be activated in such processes as retrieval or consolidation of episodic memory (especially with vivid imagery and autobiographical contents [see Trimble and Cavanna46]), and conscious representation of information in the form of mental images and spontaneous thoughts.47
Importantly, recent imaging studies48-50 involving episodic memory retrieval tasks have highlighted clear dissociations between the precuneus and the neighboring posterior cingulate cortex, which have traditionally been grouped together as a functional unit within the medial parietal region. In a fMRI study designed to separate the neural substrates of the different components of recognition memory retrieval, Yonelinas and colleagues48 found that the precuneus was related to familiarity whereas the posterior cingulate was related to recollection (see also Desalaar and colleagues49). Another study using a novel fMRI approach based on timing differences sought to map the time course of autobiographical memory retrieval and segregated brain areas contributing to initial access (precuneus) and later elaboration and maintenance (posterior cingulate) of episodic memories.50 These functional distinctions fit well with the different anatomical connectivity of these structures with the medial temporal lobe.3
Furthermore, this model is neuroanatomically acceptable in that the identified regions comprise a network of areas that are relatively distant (as measured by cortico-cortical connections) from primary sensory areas and could thus be expected to participate primarily in conceptual rather than perceptual functions. Overall, during the baseline resting state this neural system is likely to be engaged in higher mental functions involving something similar to contemplative thought against a background of general body awareness, upon which any extended consciousness is constructed.
Finally, another line of evidence51-54 points toward a central role for the precuneus in the internal mentation processes of self-consciousness. An interaction between precuneus and prefrontal cortex has been postulated in states of consciousness characterized by a high level of reflective self-awareness.51,52 Lou and colleagues53 found a medial parietal-prefrontal core in the enhanced consciousness state of yoga meditation, by measuring cerebral blood distribution with PET in experienced yoga teachers. In a functional imaging study aimed at identifying the neural correlates of visual awareness, Kjaer and colleagues54 used brief subliminal and supraliminal verbal stimuli while measuring CBF distribution with PET. The major finding of this study was the differential recruiting of precuneus and dorsolateral prefrontal cortex in the right hemisphere when visual-verbal stimulation lasted long enough to elicit awareness, suggesting critical involvement of these higher-order associative cortices in visual-verbal awareness.
The role of global changes and interactions between the precuneus and the frontopolar regions is not yet clear. However, the functional linkage between these systems and the thalamic- and reticular-activating system points toward a pivotal role for the precuneus in self-consciousness, especially when viewed in relation to the high level of resting metabolism displayed by this area. Taken together, these findings provide strong, albeit preliminary, evidence that this richly connected multimodal associative area belongs to the neural network subserving awareness and producing a conscious self-percept, a process that possibly runs in the background (by default) during silent rest.
Over the last few years, functional neuroimaging studies have started unravelling unexpected functional attributes for the precuneus, a cortical region located in the posteromedial portion of the parietal lobe which has widespread connections with both associative areas and subcortical structures. The posteromedial parietal areas are amongst the brain structures displaying the highest resting metabolic rates (“hot spots”) and are characterized by transient decreases in the tonic activity during engagement in non self-referential goal-directed tasks (“default mode of brain function”). On the other hand, precuneus activation has been documented in healthy subjects engaged in self-related mental representation and episodic/autobiographical memory retrieval. Moreover, selective precuneal hypometabolism has been reported in a wide range of altered conscious states, such as sleep, hypnosis, drug-induced anesthesia, vegetative state, and in neuropsychiatric conditions characterized by impaired consciousness (eg, Alzheimer’s disease, epilepsy, schizophrenia). Taken together, these findings provide strong, albeit preliminary, evidence that this richly connected multimodal associative area belongs to the neural network subserving awareness and producing a conscious self-percept, a process that possibly runs in the background (by default) during silent rest.
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