Task-related Deactivation Research Articles

Mindfulness-based Neurofeedback: A Systematic Review of EEG and fMRI studies.

Neurofeedback concurrent with mindfulness meditation may reveal meditation effects on the brain and facilitate improved mental health outcomes. Here, we systematically reviewed EEG and fMRI studies of mindfulness meditation with neurofeedback (mbNF) and followed PRISMA guidelines. We identified 10 fMRI reports, consisting of 177 unique participants, and 9 EEG reports, consisting of 242 participants. Studies of fMRI focused primarily on downregulating the default-mode network (DMN). Although studies found decreases in DMN activations during neurofeedback, there is a lack of evidence for transfer effects, and the majority of studies did not employ adequate controls, e.g. sham neurofeedback. Accordingly, DMN decreases may have been confounded by general task-related deactivation. EEG studies typically examined alpha, gamma, and theta frequency bands, with the most robust evidence supporting the modulation of theta band activity. Both EEG and fMRI mbNF have been implemented with high fidelity in clinical populations. However, the mental health benefits of mbNF have not been established. In general, mbNF studies would benefit from sham-controlled RCTs, as well as clear reporting (e.g. CRED-NF).

The relationship between resting-state amplitude fluctuations and memory-related deactivations of the default mode network in young and older adults.

The default mode network (DMN) typically exhibits deactivations during demanding tasks compared to periods of relative rest. In functional magnetic resonance imaging (fMRI) studies of episodic memory encoding, increased activity in DMN regions even predicts later forgetting in young healthy adults. This association is attenuated in older adults and, in some instances, increased DMN activity even predicts remembering rather than forgetting. It is yet unclear whether this phenomenon is due to a compensatory mechanism, such as self-referential or schema-dependent encoding, or whether it reflects overall reduced DMN activity modulation in older age. We approached this question by systematically comparing DMN activity during successful encoding and tonic, task-independent, DMN activity at rest in a sample of 106 young (18-35 years) and 111 older (60-80 years) healthy participants. Using voxel-wise multimodal analyses, we assessed the age-dependent relationship between DMN resting-state amplitude (mean percent amplitude of fluctuation, mPerAF) and DMN fMRI signals related to successful memory encoding, as well as their modulation by age-related hippocampal volume loss, while controlling for regional grey matter volume. Older adults showed lower resting-state DMN amplitudes and lower task-related deactivations. However, a negative relationship between resting-state mPerAF and subsequent memory effect within the precuneus was observed only in young, but not older adults. Hippocampal volumes showed no relationship with the DMN subsequent memory effect or mPerAF. Lastly, older adults with higher mPerAF in the DMN at rest tend to show higher memory performance, pointing towards the importance of a maintained ability to modulate DMN activity in old age.

Unbalance between working memory task-activation and task-deactivation networks in epilepsy: Simultaneous EEG-fMRI study.

Working memory (WM) is a cognitive function involving emergent properties of theta oscillations and large-scale network interactions. The synchronization of WM task-related networks in the brain enhanced WM performance. However, how these networks regulate WM processing is not well known, and the alteration of the interaction among these networks may play an important role in patients with cognitive dysfunction. In this study, we used simultaneous EEG-fMRI to examine the features of theta oscillations and the functional interactions among activation/deactivation networks during the n-back WM task in patients with idiopathic generalized epilepsy (IGE). The results showed that there was more enhancement of frontal theta power along with WM load increase in IGE, and the theta power was positively correlated with the accuracy of the WM tasks. Moreover, fMRI activations/deactivations correlated with n-back tasks were estimated, and we found that the IGE group had increased and widespread activations in high-load WM tasks, including the frontoparietal activation network and task-related deactivation areas, such as the default mode network and primary visual and auditory networks. In addition, the network connectivity results demonstrated decreased counteraction between the activation network and deactivation network, and the counteraction was correlated with the higher theta power in IGE. These results indicated the important role of the interactions between activation and deactivation networks during the WM process, and the unbalance among them may indicate the pathophysiological mechanism of cognitive dysfunction in generalized epilepsy.

Failure of deactivation in bipolar disorder during performance of an fMRI adapted version of the Stroop task

IntroductionFew studies have examined the functional brain correlates of the performance of the Stroop task in bipolar disorder (BD). It is also not known whether it is associated with failure of de-activation in the default mode network, as has been found in studies using other tasks. MethodsTwenty-four BD patients and 48 age, sex and educationally estimated intellectual quotient (IQ) matched healthy subjects (HS) underwent a functional MRI during performance of the counting Stroop task. Task-related activations (incongruent versus congruent condition) and de-activations (incongruent versus fixation) were examined using whole-brain, voxel-based methodology. ResultsBoth the BD patients and the HS showed activation in a cluster encompassing the left dorsolateral and ventrolateral prefrontal cortex and the rostral anterior cingulate cortex and supplementary motor area, with no differences between them. The BD patients, however, showed significant failure of de-activation in the medial frontal cortex and the posterior cingulate cortex/precuneus. ConclusionsThe failure to find activation differences between BD patients and controls suggests that the ‘regulative’ component of cognitive control remains intact in the disorder, at least outside episodes of illness. The failure of de-activation found adds to evidence documenting trait-like default mode network dysfunction in the disorder.

Conflict- and error-related theta activities are coupled to BOLD signals in different brain regions

Both conflict and error processing have been linked to the midfrontal theta power (4–8 Hz) increase as indicated by EEG studies and greater hemodynamic activity in the anterior midcingulate cortex (aMCC) as indicated by fMRI studies. Conveniently, the source of the midfrontal theta power was estimated in or nearby aMCC. However, previous studies using concurrent EEG and fMRI recordings in resting-state or other cognitive tasks observed only a negative relationship between theta power and BOLD signal in the brain regions typically showing task-related deactivations. In this study, we used a simultaneous EEG-fMRI technique to investigate a trial-by-trial coupling between theta power and hemodynamic activity during the performance of two conflict tasks. Independent component analysis (ICA) was applied to denoise the EEG signal and select individual midfrontal EEG components, whereas group ICA was applied to fMRI data to obtain a functional parcellation of the frontal cortex. Using a linear mixed-effect model, theta power was coupled with the peak of hemodynamic responses from various frontal, cingulate, and insular cortical sites to unravel the potential brain sources that contribute to conflict- and error-related theta variability. Although several brain regions exhibited conflict-related increases in hemodynamic activity, the conflict pre-response theta showed only a negative correlation to BOLD signal in the midline area 9 (MA9), a region exhibiting conflict-sensitive deactivation. Conversely, and more expectedly, error-related theta showed a positive relationship to activity in the aMCC. Our results provide novel evidence suggesting that the amplitude of pre-response theta reflects the process of active inhibition that suppresses the MA9 activity. This process is affected independently by the stimulus congruency, reaction times variance, and is susceptible to the time-on-task effect. Finally, it predicts the commitment of an omission error. Together, our findings highlight that conflict- and error-related theta oscillations represent fundamentally different processes.

Memory enhancement with stimulants: Differential neural effects of methylphenidate, modafinil, and caffeine. A pilot study

Human memory is susceptible to manipulation in many respects. While consolidation is well known to be prone to disruption, there is also growing evidence for the enhancement of memory function. Beside cognitive strategies and mnemonic training, the use of stimulants may improve memory processing in healthy adults. In this single-dose, double-blind, within-subject, randomized, placebo-controlled pilot study, 20 mg methylphenidate (N = 13) or 200 mg modafinil (N = 12) or 200 mg caffeine (N = 14) were administrated to in total 39 healthy participants while performing a declarative memory task. Each participant received only one substance and functional magnetic resonance imaging (fMRI) was used to assess drug-dependent memory effects of the substance for encoding and recognition compared to task-related activation under placebo. While methylphenidate showed some behavioral effect regarding memory recall performance, on the neural level, methylphenidate-dependent deactivations were found in fronto-parietal and temporal regions during recognition of previously learned words. No BOLD alterations were seen during encoding. Caffeine led to deactivations in the precentral gyrus during encoding whereas modafinil did not show any BOLD signal alterations at all. These results should be interpreted with caution since this a pilot study with several limitations, most importantly the small number of participants per group. However, our main finding of task-related deactivations may point to a drug-dependent increase of efficiency in physiological response to memory processing.

Activation and deactivation patterns in schizophrenia during performance of an fMRI adapted version of the stroop task

The Stroop task, which examines an aspect of executive function/cognitive control, the ability to inhibit prepotent responses, has been relatively little examined in schizophrenia, and the findings have been inconsistent. Whether performance of this task is associated with failure of de-activation in the disorder is also uncertain. We examined 42 schizophrenic patients and 61 healthy controls during performance of an fMRI-adapted version of the Stroop task, the counting Stroop task. Task-related activations (incongruent > congruent condition) and de-activations (baseline > incongruent) were examined using whole-brain, voxel-based methods. In the healthy controls, task performance was found to be associated with activations in the left dorsolateral prefrontal cortex and the dorsal anterior cingulate cortex, among other regions. De-activations were seen in the medial frontal cortex, the middle and posterior cingulate gyrus and cuneus, the parahippocampal gyrus and the hippocampus. The schizophrenic patients did not show reduced activation compared to the healthy controls. They did, however, show failure of de-activation in the medial frontal cortex. Our negative finding with respect to hypoactivation during performance of a task requiring inhibition of prepotent responses suggests that brain functional abnormality in schizophrenia may not affect all aspects of executive function/cognitive control. The finding of medial frontal cortex failure of de-activation adds to existing findings of default mode network dysfunction in the disorder.

Object-Location Memory Training in Older Adults Leads to Greater Deactivation of the Dorsal Default Mode Network

Substantial evidence indicates that cognitive training can be efficacious for older adults, but findings regarding training-related brain plasticity have been mixed and vary depending on the imaging modality. Recent years have seen a growth in recognition of the importance of large-scale brain networks on cognition. In particular, task-induced deactivation within the default mode network (DMN) is thought to facilitate externally directed cognition, while aging-related decrements in this neural process are related to reduced cognitive performance. It is not yet clear whether task-induced deactivation within the DMN can be enhanced by cognitive training in the elderly. We previously reported durable cognitive improvements in a sample of healthy older adults (age range = 60–75) who completed 6 weeks of process-based object-location memory training (N = 36) compared to an active control training group (N = 31). The primary aim of the current study is to evaluate whether these cognitive gains are accompanied by training-related changes in task-related DMN deactivation. Given the evidence for heterogeneity of the DMN, we examine task-related activation/deactivation within two separate DMN branches, a ventral branch related to episodic memory and a dorsal branch more closely resembling the canonical DMN. Participants underwent functional magnetic resonance imaging (fMRI) while performing an untrained object-location memory task at four time points before, during, and after the training period. Task-induced (de)activation values were extracted for the ventral and dorsal DMN branches at each time point. Relative to visual fixation baseline: (i) the dorsal DMN was deactivated during the scanner task, while the ventral DMN was activated; (ii) the object-location memory training group exhibited an increase in dorsal DMN deactivation relative to the active control group over the course of training and follow-up; (iii) changes in dorsal DMN deactivation did not correlate with task improvement. These results indicate a training-related enhancement of task-induced deactivation of the dorsal DMN, although the specificity of this improvement to the cognitive task performed in the scanner is not clear.

Neural Mechanisms of Parental Communicative Adjustments in Spoken Language

During cultural transmission, caregivers typically adjust their form of speech according to the presumed characteristics of an infant/child, a phenomenon known as infant/child directed speech (IDS/CDS) or “parentese.” Although ventromedial prefrontal cortex (vmPFC) damage was previously found to be associated with failure in adjusting non-verbal communicative behaviors, little is known about the neural mechanisms of verbal communicative adjustments, such as IDS/CDS. In the current study, 30 healthy mothers with preschool-age children underwent functional magnetic resonance imaging (fMRI) while performing a picture naming task which required them to name an object for either a child or an adult. In the picture naming task, mothers exhibited a longer naming duration in the toward-child condition than the toward-adult control condition. Naming an object for a child, compared with naming it for an adult, resulted in greater involvement in the vmPFC and other regions (e.g., cerebellum) in the global caregiving network. In particular, the vmPFC exhibited task-related deactivation and decreased functional connectivity with the supplementary motor, precentral, postcentral, and supramarginal regions. These findings suggest that the vmPFC, which is included in the default mode network, is involved in optimizing communicative behaviors for the inter-generational transmission of knowledge. This function of the vmPFC may be considered as a prosocial drive to lead to prosocial communicative behaviors depending on the context. This study provides a better understanding of the neural mechanisms involved in communicative adjustments for children and insight into related applied research fields such as parenting, pedagogy, and education.

Importance of the Primary Motor Cortex in Development of Human Hand/Finger Dexterity.

Hand/finger dexterity is well-developed in humans, and the primary motor cortex (M1) is believed to play a particularly important role in it. Here, we show that efficient recruitment of the contralateral M1 and neuronal inhibition of the ipsilateral M1 identified by simple hand motor and proprioceptive tasks are related to hand/finger dexterity and its ontogenetic development. We recruited healthy, right-handed children (n = 21, aged 8–11 years) and adults (n = 23, aged 20–26 years) and measured their brain activity using functional magnetic resonance imaging during active and passive right-hand extension–flexion tasks. We calculated individual active control-related activity (active–passive) to evaluate efficient brain activity recruitment and individual task-related deactivation (neuronal inhibition) during both tasks. Outside the scanner, participants performed 2 right-hand dexterous motor tasks, and we calculated the hand/finger dexterity index (HDI) based on their individual performance. Participants with a higher HDI exhibited less active control-related activity in the contralateral M1 defined by the active and passive tasks, independent of age. Only children with a higher HDI exhibited greater ipsilateral M1 deactivation identified by these tasks. The results imply that hand/finger dexterity can be predicted by recruitment and inhibition styles of the M1 during simple hand sensory–motor tasks.

Evidence for default mode network dysfunction in borderline personality disorder.

Although executive and other cognitive deficits have been found in patients with borderline personality disorder (BPD), whether these have brain functional correlates has been little studied. This study aimed to examine patterns of task-related activation and de-activation during the performance of a working memory task in patients with the disorder. Sixty-seven DSM-IV BPD patients and 67 healthy controls underwent fMRI during the performance of the n-back task. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups. On corrected whole-brain analysis, there were no activation differences between the BPD patients and the healthy controls during the main 2-back v. baseline contrast, but reduced activation was seen in the precentral cortex bilaterally and the left inferior parietal cortex in the 2-back v. 1-back contrast. The patients showed failure of de-activation affecting the medial frontal cortex and the precuneus, plus in other areas. The changes did not appear to be attributable to previous history of depression, which was present in nearly half the sample. In this study, there was some, though limited, evidence for lateral frontal hypoactivation in BPD during the performance of an executive task. BPD also appears to be associated with failure of de-activation in key regions of the default mode network.

Longitudinal brain functional changes between mania and euthymia in bipolar disorder.

While widespread cortical and subcortical brain functional abnormalities have been found in bipolar disorder, the changes that take place between illness phases and recovery are less clearly documented. Only a small number of longitudinal studies of manic patients, in particular, have been carried out. Twenty-six bipolar patients underwent fMRI during performance of the n-back working memory task when manic and again after recovery. Twenty-six matched healthy controls were also scanned on two occasions. Task-related activations and de-activations were examined. When manic, the patients showed clusters of significantly reduced activation in the left dorsolateral prefrontal cortex (DLPFC)/precentral cortex and the parietal cortex/superior precuneus bilaterally. They also showed failure of de-activation in the ventromedial frontal cortex (vmPFC). After recovery, activation in the left DLPFC/precentral cortex and in the bilateral parietal cortex/superior precuneus clusters increased significantly. However, failure of de-activation remained present in the vmPFC. Recovery from mania is associated with normalization of DLPFC and parietal hypoactivation, but not with vmPFC failure of de-activation, which accordingly appears to represent a trait abnormality in the disorder.

Exercise challenge alters Default Mode Network dynamics in Gulf War Illness

BackgroundGulf War Illness (GWI) affects 30% of veterans from the 1991 Gulf War and has no known cause. Everyday symptoms include pain, fatigue, migraines, and dyscognition. A striking syndromic feature is post-exertional malaise (PEM). This is recognized as an exacerbation of everyday symptoms following a physically stressful or cognitively demanding activity. The underlying mechanism of PEM is unknown. We previously reported a novel paradigm that possibly captured evidence of PEM by utilizing fMRI scans taken before and after sub-maximal exercises. We hypothesized that A) exercise would be a sufficient physically stressful activity to induce PEM and B) Comparison of brain activity before and after exercise would provide evidence of PEM’s effect on cognition. We reported two-exercise induced GWI phenotypes with distinct changes in brain activation patterns during the completion of a 2-back working memory task (also known as two-back > zero-back).ResultsHere we report unanticipated findings from the reverse contrast (zero-back > two-back), which allowed for the identification of task-related deactivation patterns. Following exercise, patients developed a significant increase in deactivation patterns within the Default Mode Network (DMN) that was not seen in controls. The DMN is comprised of regions that are consistently down regulated during external goal-directed activities and is often altered within many neurological disease states.ConclusionsExercise-induced alterations within the DMN provides novel evidence of GWI pathophysiology. More broadly, results suggest that task-related deactivation patterns may have biomarker potential in Gulf War Illness.

How does methylphenidate affect default mode network? A systematic review.

Methylphenidate is a widely-used drug for the treatment of attention deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Sustained-attention deficits and poorer task performance in these disorders have been associated with default mode network (DMN) dysfunction in fMRI studies. DMN is a set of brain areas more activated during the resting-state. Under the execution of external tasks, there is an attenuation of DMN activity. In healthy individuals, DMN and task-positive network are anticorrelated. It has been suggested that methylphenidate could normalize the attenuated task-related DMN deactivation in attention- and inhibitory control-related disorders and that such normalization could improve task performance. To explore the hypothesis of DMN deactivation after methylphenidate administration, we conducted a systematic review of the literature. After a systematic search, 12 studies were included in this review. For eligibility, studies were required to measure the effects of methylphenidate administration on the DMN activity. Eleven studies showed evidence of MPH-induced improvements in brain areas related to DMN. The results suggest a normalization of brain circuits in individuals with DMN dysfunction. Our preliminary findings strongly suggest methylphenidate improves DMN dysfunction presented in ADHD and other neuropsychiatric disorders. Further studies are needed to better understand this effect and expand comprehension of methylphenidate action mechanisms.

The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy.

Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n=276), postoperative cognitive change (n=126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n=37 and 34). mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE.

Voluntary modulation of mental effort investment: an fMRI study

Mental effort is a common phenomenological construct deeply linked to volition and self-control. While it is often assumed that the amount of exertion invested in a task can be voluntarily regulated, the neural bases of such faculty and its behavioural effects are yet insufficiently understood. In this study, we investigated how the instructions to execute a demanding cognitive task either “with maximum exertion” or “as relaxed as possible” affected performance and brain activity. The maximum exertion condition, compared to relaxed execution, was associated with speeded motor responses without an accuracy trade-off, and an amplification of both task-related activations in dorsal frontoparietal and cerebellar regions, and task-related deactivations in default mode network (DMN) areas. Furthermore, the visual cue to engage maximum effort triggered an anticipatory widespread increase of activity in attentional, sensory and executive regions, with its peak in the brain stem reticular activating system. Across individuals, this surge of activity in the brain stem, but also in medial wall cortical regions projecting to the adrenal medulla, positively correlated with increases in heart rate, suggesting that the intention to willfully modulate invested effort involves mechanisms related to catecholaminergic transmission and a suppression of DMN activity in favor of externally-directed attentional processes.

AGE-RELATED NETWORK DYSFUNCTION: CONTRIBUTIONS OF NEURAL ACTIVITY TO RISK FOR LATE-ONSET AD

This presentation will focus on an age-related shift in neural activity in key circuits that could contribute to boosting progression of Alzheimer's pathology and illuminate the risk conferred by aging in late onset sporadic AD. Neural hyperactivity in aging is associated with memory impairment in outbred rats and non-human primates. Hyperactive hippocampal neurons in those species are similarly localized to increased activation detected by high resolution functional magnetic resonance imaging (fMRI) in elderly humans, a condition that is further augmented in patients with mild cognitive impairment. In addition to the effects of aging on hippocampal circuits, reciprocally connected cortical networks demonstrate alterations in both aging and in prodromal AD. In particular, posterior regions of the default mode network (DMN) that are sites of early amyloid deposition show impaired task-related deactivation in older adults. Studies of the homologous connectional anatomy across species could provide information about the condition of such networks in aging, independent AD pathology. Activation of neural activity was monitored by expression of the immediate early gene cFos to map heightened excitability in behaviorally characterized aged rats. Induction of neural activity was assessed by cFos mRNA expression using quantitative in situ hybridization. Consistent with neurophysiological recording data, greater cFos induction was localized in the hippocampus of aged memory impaired rats compared to unimpaired aged cohorts and young adults. Similar increased cFos was observed in a network of cortical sites, including retrosplenial and parietal regions of the posterior DMN. Pharmacological treatment that reduced excess cFos induction in the hippocampus also normalized cFos induction in posterior DMN. Reduction of neural activity reduces amyloid deposition and preserves synaptic function in AD mouse models. In tau mouse models, manipulation of neural activity also controls tau propagation and pathology in the medial temporal lobe/hippocampus. Heightened neural activity as a condition associated with aging may contribute to the risk conferred by aging in driving the pathophysiology of late-onset sporadic AD. A demonstrated translation for the efficacy of targeting hippocampal hyperactivity in clinical investigations may extend to the additional cortical components of an AD vulnerable network in patients.

Functional dedifferentiation and reduced task-related deactivations underlie the age-related decline of prospective memory.

Prospective memory (PM) refers to the ability to remember to execute an intention at the appropriate moment in the future, which can be performed either at the appearance of an event (event-based, EBPM) or after a certain amount of time (time-based, TBPM). PM is generally impaired during aging but the cerebral substrates of this decline have been little investigated. Using functional Magnetic Resonance Imaging (fMRI), we investigated the neural bases of PM in 20 young and 20 healthy older adults. They were proposed a task of semantic categorisation of pictures (ongoing task). For some blocks, participants only had to perform this ongoing task while, for others, a PM instruction was added. In this case, a supplementary answer in response to a specific colour of border for EBPM or at specific time intervals for TBPM was expected. PM, and more particularly TBPM, declined in older adults. For both PM conditions, older adults recruited additional brain areas, but also showed reduced deactivations of other regions. These results are discussed in light of models of the aging brain.

Dysfunctional organization of default mode network before memory impairments in type 2 diabetes

AimsEpisodic memory depends on the maintenance of an intact default mode network (DMN), and is one of the earliest cognitive domains to become impaired in type 2 diabetes mellitus (T2DM). Therefore, exploring the alterations in task-related DMN deactivation and functional connectivity that affect episodic memory in T2DM will help to enhance our understanding of the allocation patterns underlying memory function in T2DM. MethodsThe current study assessed changes in DMN activation and architecture during the encoding of a functional magnetic resonance imaging task in 39 patients with T2DM and 41 healthy controls which were recruited from local communities in Beijing, China. ResultsWe found that patients with T2DM and intact episodic memory performance exhibited reduced deactivation in the right precuneus and the middle temporal gyrus during the episodic memory task. Furthermore, an anterior-posterior disconnection phenotype and altered topological configuration of the DMN were observed in patients with T2DM using graph-theoretical approaches. Correlation analysis showed that altered deactivation during the episodic memory task was closely related to connectivity dysfunction and topological properties in the DMN. ConclusionsOur findings demonstrate that the maintenance of memory in patients with T2DM involves reduced deactivation and impaired anterior-posterior connections in the DMN during encoding.

The modifying effect of the BDNF Val66Met polymorphism on the neurophysiological characteristics of verbal information processing

Human functional MRI studies frequently reveal the joint activation of parietal and of lateral and mesial frontal areas during various cognitive tasks. To analyze the geometrical organization of those networks, we used an automatized clustering algorithm that parcels out sets of areas based on their similar profile of task-related activations or deactivations. This algorithm allowed us to reanalyze published fMRI data (Simon, O., Mangin, J.F., Cohen, L., Le Bihan, D., Dehaene, S., 2002. Topographical layout of hand, eye, calculation, and language-related areas in the human parietal lobe. Neuron 33, 475–487) and to reproduce the previously observed geometrical organization of activations for saccades, attention, grasping, pointing, calculation, and language processing in the parietal lobe. Further, we show that this organization extends to lateral and mesial prefrontal regions. Relative to the parietal lobe, the prefrontal functional geometry is characterized by a partially symmetrical anteroposterior ordering of activations, a decreased representation of effector-specific tasks, and a greater emphasis on higher cognitive functions of attention, higher-order spatial representation, calculation, and language. Anatomically, our results in humans are closely homologous to the known connectivity of parietal and frontal regions in the macaque monkey.