Evidence for quantitative domain dominance for verbal and spatial working memory in frontal and parietal cortex

Neuroimaging studies in humans have shown that different working memory (WM) tasks recruit a common bilateral fronto-parietal cortical network. Animal studies as well as neuroimaging studies in humans have suggested that this network, in particular the prefrontal cortex, is preferentially recruited when material from different domains (e.g. spatial information or verbal/object information) has to be memorized. Early imaging studies have suggested qualitative dissociations in the prefrontal cortex for spatial and object/verbal WM, either in a left-right or a ventral-dorsal dimension. However, results from different studies are inconsistent. Moreover, recent fMRI studies have failed to find evidence for domain dependent dissociations of WM-related activity in prefrontal cortex. Here we present evidence from two independent fMRI studies using physically identical stimuli in a verbal and spatial WM task showing that domain dominance for WM does indeed exist, although only in the form of quantitative differences in activation and not in the form of a dissociation with different prefrontal regions showing mutually exclusive activation in different domains. Our results support a mixed dimension model of domain dominance for WM within the prefrontal cortex, with left ventral prefrontal cortex (PFC) supporting preferentially verbal WM and right dorsal PFC supporting preferentially spatial WM. The concept of domain dominance is discussed in the light of recent theories of prefrontal cortex function.     

Cooperative processing in primary somatosensory cortex and posterior parietal cortex during tactile working memory

In the present study, causal roles of both the primary somatosensory cortex (SI) and the posterior parietal cortex (PPC) were investigated in a tactile unimodal working memory (WM) task. Individual magnetic resonance imaging‐based single‐pulse transcranial magnetic stimulation (spTMS) was applied, respectively, to the left SI (ipsilateral to tactile stimuli), right SI (contralateral to tactile stimuli) and right PPC (contralateral to tactile stimuli), while human participants were performing a tactile‐tactile unimodal delayed matching‐to‐sample task. The time points of spTMS were 300, 600 and 900 ms after the onset of the tactile sample stimulus (duration: 200 ms). Compared with ipsilateral SI, application of spTMS over either contralateral SI or contralateral PPC at those time points significantly impaired the accuracy of task performance. Meanwhile, the deterioration in accuracy did not vary with the stimulating time points. Together, these results indicate that the tactile information is processed cooperatively by SI and PPC in the same hemisphere, starting from the early delay of the tactile unimodal WM task. This pattern of processing of tactile information is different from the pattern in tactile‐visual cross‐modal WM. In a tactile‐visual cross‐modal WM task, SI and PPC contribute to the processing sequentially, suggesting a process of sensory information transfer during the early delay between modalities.     

Patterned firing of parietal cells in a haptic working memory task

Abstract Cells in the somatosensory cortex of the monkey are known to exhibit sustained elevations of firing frequency during the short-term mnemonic retention of tactile information in a haptic delay task. In this study, we examine the possibility that those firing elevations are accompanied by changes in firing pattern. Patterns are identified by the application of a pattern-searching algorithm to the interspike intervals of spike trains. By sequential use of sets of pattern templates with a range of temporal resolutions, we find patterned activity in the majority of the cells investigated. In general, the degree of patterning significantly increases during active memory. Surrogate analysis suggests that the observed patterns may not be simple linear stochastic functions of instantaneous or average firing frequency. Therefore, during the active retention of a memorandum, the activity of a 'memory cell' may be characterized not only by changes in frequency but also by changes in pattern.     

Load effects on spatial working memory performance are linked to distributed alpha and beta oscillations

Increasing spatial working memory (SWM) load is generally associated with declines in behavioral performance, but the neural correlates of load‐related behavioral effects remain poorly understood. Herein, we examine the alterations in oscillatory activity that accompany such performance changes in 22 healthy adults who performed a two‐ and four‐load SWM task during magnetoencephalography (MEG). All MEG data were transformed into the time‐frequency domain and significant oscillatory responses were imaged separately per load using a beamformer. Whole‐brain correlation maps were computed using the load‐related beamformer difference images and load‐related accuracy effects on the SWM task. The results indicated that load‐related differences in left inferior frontal alpha activity during encoding and maintenance were negatively correlated with load‐related accuracy differences on the SWM task. That is, individuals who had more substantial decreases in prefrontal alpha during high‐relative to low‐load SWM trials tended to have smaller performance decrements on the high‐load condition (i.e., they performed more accurately). The same pattern of neurobehavioral correlations was observed during the maintenance period for right superior temporal alpha activity and right superior parietal beta activity. Importantly, this is the first study to employ a voxel‐wise whole‐brain approach to significantly link load‐related oscillatory differences and load‐related SWM performance differences.     

Intermittent theta burst stimulation over the parietal cortex has a significant neural effect on working memory

The crucial role of the parietal cortex in working memory (WM) storage has been identified by fMRI studies. However, it remains unknown whether repeated parietal intermittent theta‐burst stimulation (iTBS) can improve WM. In this within‐subject randomized controlled study, under the guidance of fMRI‐identified parietal activation in the left hemisphere, 22 healthy adults received real and sham iTBS sessions (five consecutive days, 600 pulses per day for each session) with an interval of 9 months between the two sessions. Electroencephalography signals of each subject before and after both iTBS sessions were collected during a change detection task. Changes in contralateral delay activity (CDA) and K‐score were then calculated to reflect neural and behavioral WM improvement. Repeated‐measures ANOVA suggested that real iTBS increased CDA more than the sham one (p = .011 for iTBS effect). Further analysis showed that this effect was more significant in the left hemisphere than in the right hemisphere (p = .029 for the hemisphere‐by‐iTBS interaction effect). Pearson correlation analyses showed significant correlations for two conditions between CDA changes in the left hemisphere and K score changes (ps <.05). In terms of the behavioral results, significant K score changes after real iTBS were observed for two conditions, but a repeated‐measures ANOVA showed a nonsignificant main effect of iTBS (p = .826). These results indicate that the current iTBS protocol is a promising way to improve WM capability based on the neural indicator (CDA) but further optimization is needed to produce a behavioral effect.     

Brain areas involved in spatial working memory

Spatial working memory entails the ability to keep spatial information active in working memory over a short period of time. To study the areas of the brain that are involved in spatial working memory, a group of stroke patients was tested with a spatial search task. Patients and healthy controls were asked to search through a number of boxes shown at different locations on a touch-sensitive computer screen in order to find a target object. In subsequent trials, new target objects were hidden in boxes that were previously empty. Within-search errors were made if a participant returned to an already searched box; between-search errors occurred if a participant returned to a box that was already known to contain a target item. The use of a strategy to remember the locations of the target objects was calculated as well. Damage to the right posterior parietal and right dorsolateral prefrontal cortex impaired the ability to keep spatial information 'on-line', as was indicated by performance on the Corsi Block-Tapping task and the within-search errors. Moreover, patients with damage to the right posterior parietal cortex, the right dorsolateral prefrontal cortex and the hippocampal formation bilaterally made more between-search errors, indicating the importance of these areas in maintaining spatial information in working memory over an extended time period.     

Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI

Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways. Hum. Brain Mapping 6:14–32, 1998. © 1998 Wiley-Liss, Inc.     

Functional neuroanatomy of sustained attention in schizophrenia: contribution of parietal cortices

Deficits in sustained attention have been frequently described in schizophrenia. The neuroanatomical basis reported previously have included altered levels of activation in cingulate and prefrontal cortex, but the contribution of further regions remains unclear. We explored the full neuroanatomy underlying the sustained attentional deficits observed in naïve schizophrenics compared with controls. Participants included 10 controls and 11 patients. The experimental design included rest, auditory stimulation using clicks, and two counting tasks. Subjects were instructed to mentally count the clicks, and then to count forward at the same frequency they heard previously when listening to the clicks. Relative cerebral blood flow (relCBF) was measured by means of PET ¹⁵O‐water. Differences were observed between both groups at superior temporal cortex, superior parietal gyrus, and cerebellum during tasks requiring listening. During all counting conditions, additionally to supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPCF), precentral gyrus, cingulate, cerebellum, and inferior parietal (IP) gyrus, patients engaged other frontal structures including inferior, medial, and superior frontal areas. When counting with no auditory stimulation (C; requires components of working memory and time estimation), significant differences were observed in the level of activation of frontal and IP regions. Our naïve patients presented abnormal activation of auditory associative pathways. They failed to activate prefrontal and parietal regions at a similar level during tasks requiring increased cognitive effort, and they required a higher activation of inferior frontal regions to properly respond to cognitive demands. Hum. Brain Mapping 17:116–130, 2002. © 2002 Wiley‐Liss, Inc.     

Modulation of working memory function by motivation through loss‐aversion

Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top‐down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss‐threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g., stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to nonincentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to nonincentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top‐down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered. Hum Brain Mapp , 2013. © 2011 Wiley Periodicals, Inc.     

Representations of visual proportions in the primate posterior parietal and prefrontal cortices

The primate prefrontal (PFC) and posterior parietal cortices (PPC) have been shown to be cardinal structures in processing abstract absolute magnitudes, such as numerosity or length. The neuronal representation of quantity relations, however, remained largely elusive. Recent functional imaging studies in humans showed that blood flow changes systematically both in the PFC and the PPC as a function of relational distance between proportions. We investigated the response properties of single neurons in the lateral PFC and the inferior parietal lobule (IPL, area 7) in rhesus monkeys performing a lengths-proportion-discrimination task. Neurons in both areas shared many characteristics and showed peaked tuning functions with preferred proportions. However, a significantly higher percentage of neurons coding proportions was found in the PFC compared with the IPL. In agreement with human studies, our study shows that proportions are represented in the fronto-parietal network that has already been implicated for absolute magnitude processing.     

Anterior cingulate cortex differently modulates frontoparietal functional connectivity between resting‐state and working memory tasks

The brain frontoparietal regions and the functional communications between them are critical in supporting working memory and other executive functions. The functional connectivity between frontoparietal regions are modulated by working memory loads, and are shown to be modulated by a third brain region in resting‐state. However, it is largely unknown whether the third‐region modulations remain the same during working memory tasks or were largely modulated by task demands. In the current study, we collected functional MRI (fMRI) data when the subjects were performing n‐back tasks and in resting‐state. We first used a block‐designed localizer to define the frontoparietal regions that showed higher activations in the 2‐back than the 1‐back condition. Next, we performed physiophysiological interaction (PPI) analysis using left and right middle frontal gyrus (MFG) and superior parietal lobule (SPL) regions, respectively, in three continuous‐designed runs of resting‐state, 1‐back, and 2‐back conditions. No regions showed consistent modulatory interactions with the seed pairs in the three conditions. Instead, the anterior cingulate cortex (ACC) showed different modulatory interactions with the right MFG and SPL among the three conditions. While the increased activity of the ACC was associated with decreased functional coupling between the right MFG and SPL in resting‐state, it was associated with increased functional coupling in the 2‐back condition. The observed task modulations support the functional significance of the modulations of the ACC on frontoparietal connectivity.     

A systematic fMRI investigation of the brain systems subserving different working memory components in schizophrenia

Working memory impairment is one of the cardinal cognitive disturbances in schizophrenia and considerable evidence suggests that it can be traced to functional alterations in the brain. The exact allocation of specific deficits to regional specific dysfunctions, however, remains elusive. The aim of this study was to examine the functional integrity of three distinguishable brain systems underlying maintenance-related subprocesses of working memory (articulatory rehearsal, non-articulatory maintenance of phonological information, maintenance of visuospatial information) in patients with schizophrenia. Using an experimental paradigm, which had been designed to selectively activate these different brain systems, we assessed the brain activation of patients and controls with functional magnetic resonance imaging. Compared with controls, patients showed reduced activation of the fronto-opercular, intraparietal and anterior cingulate cortex during the non-articulatory maintenance of phonological information, as well as attenuated deactivation of the hippocampus. Additionally, we found prefrontal activation to depend critically on the patients' current symptom status. During visuospatial maintenance, patients showed impaired activation of the superior parietal, temporal and occipital cortex, combined with enhanced activation of the frontal eye field and the inferior parietal cortex. No abnormal activations were observed during the articulatory rehearsal task. All activation differences were independent of group differences in task performance. Our fine-grained analysis of dysfunctions in particular aspects of working memory circuitry provides evidence for a differential impairment of the brain systems supporting working memory subcomponents in schizophrenia and extends knowledge of the relationship between cognitive deficits, brain activation abnormalities and symptoms in schizophrenia.     

Default network connectivity during a working memory task

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task‐related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task‐related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task‐positive networks at rest. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Neural correlates underlying the attentional spotlight in human parietal cortex independent of task difficulty

Changes in the size of the attentional focus and task difficulty often co‐vary. Nevertheless, the neural processes underlying the attentional spotlight process and task difficulty are likely to differ from each other. To differentiate between the two, we parametrically varied the size of the attentional focus in a novel behavioral paradigm while keeping visual processing difficulty either constant or not. A behavioral control experiment proved that the present behavioral paradigm could indeed effectively manipulate the size of the attentional focus per se, rather than affecting purely perceptual processes or surface processing. Imaging results showed that neural activity in a dorsal frontoparietal network, including right superior parietal cortex (SPL), was positively correlated with the size of the attentional spotlight, irrespective of whether task difficulty was constant or varied across different sizes of attentional focus. In contrast, neural activity in the ventral frontoparietal network, including the right inferior parietal cortex (IPL), was positively correlated with increasing task difficulty. Data suggest that sub‐regions in parietal cortex are differentially involved in the attentional spotlight process and task difficulty: while SPL was involved in the attentional spotlight process independent of task difficulty, IPL was involved in the effect of task difficulty independent of the attentional spotlight process. Hum Brain Mapp 38:4996–5018, 2017. © 2017 Wiley Periodicals, Inc.     

Parietal cortex integrates contextual and saliency signals during the encoding of natural scenes in working memory

The Brief presentation of a complex scene entails that only a few objects can be selected, processed indepth, and stored in memory. Both low‐level sensory salience and high‐level context‐related factors (e.g., the conceptual match/mismatch between objects and scene context) contribute to this selection process, but how the interplay between these factors affects memory encoding is largely unexplored. Here, during fMRI we presented participants with pictures of everyday scenes. After a short retention interval, participants judged the position of a target object extracted from the initial scene. The target object could be either congruent or incongruent with the context of the scene, and could be located in a region of the image with maximal or minimal salience. Behaviourally, we found a reduced impact of saliency on visuospatial working memory performance when the target was out‐of‐context. Encoding‐related fMRI results showed that context–congruent targets activated dorsoparietal regions, while context–incongruent targets de‐activated the ventroparietal cortex. Saliency modulated activity both in dorsal and ventral regions, with larger context‐related effects for salient targets. These findings demonstrate the joint contribution of knowledge‐based and saliency‐driven attention for memory encoding, highlighting a dissociation between dorsal and ventral parietal regions. Hum Brain Mapp 36:5003–5017, 2015. © 2015 Wiley Periodicals, Inc .     

Changes in effective connectivity of human superior parietal lobule under multisensory and unisensory stimulation

Previous event-related potential (ERP) studies have identified the superior parietal lobule (SPL) as actively multisensory. This study compares effective, or contextually active, connections to this region under unisensory and multisensory conditions. Effective connectivity, the influence of one brain region over another, during unisensory visual, unisensory auditory and multisensory audiovisual stimulation was investigated. ERPs were recorded from subdural electrodes placed over the parietal lobe of three patients while they conducted a rapid reaction-time task. A generative model of interacting neuronal ensembles for ERPs was inverted in a scheme allowing investigation of the connections from and to the SPL, a multisensory processing area. Important features of the ensemble model include inhibitory and excitatory feedback connections to pyramidal cells and extrinsic input to the stellate cell pool, with extrinsic forward and backward connections delineated by laminar connection differences between ensembles. The framework embeds the SPL in a plausible connection of distinct neuronal ensembles mirroring the integrated brain regions involved in the response task. Bayesian model comparison was used to test competing feed-forward and feed-backward models of how the electrophysiological data were generated. Comparisons were performed between multisensory and unisensory data. Findings from three patients show differences in summed unisensory and multisensory ERPs that can be accounted for by a mediation of both forward and backward connections to the SPL. In particular, a negative gain in all forward and backward connections to the SPL from other regions was observed during the period of multisensory integration, while a positive gain was observed for forward projections that arise from the SPL.     

Modulation of neural oscillations during working memory update,maintenance, and readout: An hdEEG study

Working memory (WM) performance is very often measured using the n‐back task, in which the participant is presented with a sequence of stimuli, and required to indicate whether the current stimulus matches the one presented n steps earlier. In this study, we used high‐density electroencephalography (hdEEG) coupled to source localization to obtain information on spatial distribution and temporal dynamics of neural oscillations associated with WM update, maintenance and readout. Specifically, we a priori selected regions from a large fronto‐parietal network, including also the insula and the cerebellum, and we analyzed modulation of neural oscillations by event‐related desynchronization and synchronization (ERD/ERS). During update and readout, we found larger θ ERS and smaller β ERS respect to maintenance in all the selected areas. γ_LOW and γ_HIGH bands oscillations decreased in the frontal and insular cortices of the left hemisphere. In the maintenance phase we observed decreased θ oscillations and increased β oscillations (ERS) in most of the selected posterior areas and focally increased oscillations in γ_LOW and γ_HIGH bands in the frontal and insular cortices of the left hemisphere. Finally, during WM readout, we also found a focal modulation of the γ_LOW band in the left fusiform cortex and cerebellum, depending on the response trial type (true positive vs. true negative). Overall, our study demonstrated specific spectral signatures associated with updating of memory information, WM maintenance, and readout, with relatively high spatial resolution.     

Relationship between prefrontal task-related activity and information flow during spatial working memory performance

While monkeys performed spatial working memory tasks, cue- (C), delay- (D), and response-period (R) activities or their combinations (CD, CR, DR, CDR) were observed in prefrontal neurons. In the present study, we tried to understand information flow during spatial working memory performances and how each task-related neuron contributed to this process. We first characterized each neuron based on which task-related activity was exhibited and which information (cue location or saccade direction) each task-related activity represented, then classified these neurons into 9 groups (C, Dcue, Dsac, CDcue, DcueRcue, DsacRsac, DcueRsac, CDcueRcue and CDcueRsac). Preferred directions were similar between cue- and delay-period activities in CDcue, CDcueRcue, and CDcueRsac, indicating that the directional selectivity of delay-period activity is affected by the directional selectivity of cue-period activity, all of which represented visual information. Preferred directions were also similar between delay- and response-period activities in DcueRcue, CDcueRcue, and DsacRsac, indicating that the directional selectivity of delay-period activity affects the directional selectivity of response-period activity in these neurons. By the comparison of temporal profiles of delay-period activity among these groups, we found (1) cue-period activity could affect directional selectivity of delay-period activity of CDcue and CDcueRcue, (2) cue-period activity of C, CDcue, and CDcueRcue might contribute to the initiation and the maintenance of delay-period activity of CDcue, CDcueRcue, Dcue, and DcueRcue, and (3) saccade-related activity of DsacRsac could be affected by delay-period activity of Dsac and DsacRsac. These results suggest that the combination of task-related activities, the information represented by each activity, and the temporal profile of delay-period activity are important factors to consider information flow and processing and integration of the information in the prefrontal cortex during spatial working memory processes.     

Motor deficits and beta oscillations are dissociable in an alpha‐synuclein model of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder characterised by progressive motor symptoms resulting from chronic loss of dopaminergic neurons in the nigrostriatal pathway. The over expression of the protein alpha‐synuclein in the substantia nigra has been used to induce progressive dopaminergic neuronal loss and to reproduce key histopathological and temporal features of PD in animal models. However, the neurophysiological aspects of the alpha‐synuclein PD model have been poorly characterised. Hereby, we performed chronic in vivo electrophysiological recordings in the corticostriatal circuit of rats injected with viral vector to over express alpha‐synuclein in the right substantia nigra. Our model, previously shown to exhibit mild motor deficits, presented moderate dopaminergic cell loss but did not present prominent local field potential oscillations in the beta frequency range (11–30 Hz), considered a hallmark of PD, during the 9 weeks after onset of alpha‐synuclein over expression. Spinal cord stimulation, a potential PD symptomatic therapy, was applied regularly from sixth to ninth week after alpha‐synuclein over expression onset and had an inhibitory effect on the firing rate of corticostriatal neurons in both control and alpha‐synuclein hemispheres. Dopamine synthesis inhibition at the end of the experiment resulted in severe parkinsonian symptoms such as akinesia and increased beta and high‐frequency (>90 Hz) oscillations. These results suggest that the alpha‐synuclein PD model with moderate level of dopaminergic depletion does not reproduce the prominent corticostriatal beta oscillatory activity associated to parkinsonian conditions.     

Modulation of medial prefrontal and inferior parietal cortices when thinking about past,present, and future selves

Abstract

Recent functional neuroimaging studies have shown that reflecting on representations of the present self versus temporally distant selves is associated with higher activity in the medial prefrontal cortex (MPFC). In the current fMRI study, we investigated whether this effect of temporal perspective is symmetrical between the past and future. The main results revealed that the MPFC showed higher activity when reflecting on the present self than when reflecting on past and future selves, with no difference between past and future selves. Temporal perspective also modulated activity in the right inferior parietal cortex but in the opposite direction, activity in this brain region being higher when reflecting on past and future selves relative to the present self (with again no difference between past and future selves). These findings show that differences in brain activity when thinking about current versus temporally distant selves are symmetrical between the past and the future. It is suggested that by processing degrees of self-relatedness, the MPFC might sustain the process of identifying oneself with current representations of the self, whereas the right inferior parietal cortex might be involved in distinguishing the present self from temporally distant selves.