Retrieval of relational information: a role for the left inferior prefrontal cortex

Neuroimaging studies have implicated different areas of prefrontal cortex and medial temporal lobe structures (MTL) in episodic retrieval tasks. However, the role of specific regions in particular aspects of episodic memory is still unclear. In this experiment we studied changes in regional cerebral blood flow (rCBF) associated with relational and nonrelational retrieval of studied pairs of words. For relational retrieval, a list of either studied or rearranged pairs was presented and subjects (n = 8) were asked to indicate whether pairs had appeared on the study list. Under the nonrelational retrieval condition they indicated whether one or both words of the pair had appeared on the study list. As compared to the baseline condition (looking at a cross-mark), increased rCBF was observed in the left inferior prefrontal cortex (LIPFC) for both studied pairs and rearranged pairs under the relational retrieval condition. Under the nonrelational condition, an increase was observed in right inferior frontal gyrus. The MTL showed a trend for increased rCBF in the rearranged-pair condition. This increase was probably associated with the encoding that accompanies retrieval of novel stimuli. Results suggest that the lateralized activation of prefrontal cortex observed in episodic memory tasks may be related to the degree of relational processing involved. The LIPFC appears to be associated with relational retrieval and the right prefrontal cortex with nonrelational retrieval.     

Age-Related Changes in Regional Cerebral Blood Flow during Working Memory for Faces

Young and old adults underwent positron emission tomography during the performance of a working memory task for faces (delayed match-to-sample), in which the delay between the sample and choice faces was varied from 1 to 21 s. Reaction time was slower and accuracy lower in the old group, but not markedly so. Values of regional cerebral blood flow (rCBF) were analyzed for sustained activity across delay conditions, as well as for changes as delay increased. Many brain regions showed similar activity during these tasks in both young and old adults, including left anterior prefrontal cortex, which had increased rCBF with delay, and ventral extrastriate cortex, which showed decreased rCBF with delay. However, old adults had less activation overall and less modulation of rCBF across delay in right ventrolateral prefrontal cortex than did the young adults. Old adults also showed greater rCBF activation in left dorsolateral prefrontal cortex across all WM delays and increased rCBF at short delays in left occipitoparietal cortex compared to young adults. Activity in many of these regions was differentially related to performance in that it was associated with decreasing response times in the young group and increasing response times in the older individuals. Thus despite the finding that performance on these memory tasks and associated activity in a number of brain areas are relatively preserved in old adults, differences elsewhere in the brain suggest that different strategies or cognitive processes are used by the elderly to maintain memory representations over short periods of time.     

Transperceptual encoding and retrieval processes in memory: a PET study of visual and haptic objects

An important objective of functional neuroimaging research is to identify neuroanatomical correlates of memory processes such as encoding and retrieval. In typical studies directed at this goal, however, the to-be-remembered information has been presented in a single perceptual modality. Under these conditions it is not known whether the observed brain activity reflects the studied memory process as such or only the memory process in the given modality. The positron emission tomography (PET) study reported here was designed to identify brain regions involved in encoding and retrieval processes specific to visual and haptic modalities, as well as those common to the two modalities. These latter, common regions, were assumed to be associated with "transperceptual" encoding and retrieval processes. Abstract three-dimensional objects, difficult to describe verbally, served as to-be-remembered materials. A multivariate partial least squares analysis of the PET data revealed that transperceptual encoding processes activated right medial temporal lobe, superior prefrontal cortex bilaterally, and posterior inferior temporal gyrus bilaterally. Transperceptual recognition activations were observed in two right orbitofrontal regions and in anterior cingulate. These results provide initial evidence that some processes involved in memory encoding and retrieval operate beyond perceptual processes and in that sense are transperceptual.     

An examination of the effects of stimulus type, encoding task, and functional connectivity on the role of right prefrontal cortex in recognition memory

Right anterior prefrontal cortex and other brain areas are active during memory retrieval but the role of prefrontal cortex and how it interacts with these other regions to mediate memory function remain unclear. To explore these issues we used positron emission tomography to examine the effects of stimulus material and encoding task on brain activity during visual recognition, assessing both task-related changes and functional connectivity. Words and pictures of objects were encoded using perceptual and semantic strategies, resulting in better memory for semantically encoded items. There was no significant effect of prior encoding strategy on brain activity during recognition. Right anterior prefrontal cortex was equally active during recognition of both types of stimuli irrespective of initial encoding strategy. Regions whose activity was positively correlated with activity in right anterior prefrontal cortex included widespread areas of prefrontal and inferior temporal cortices bilaterally. Activity in this entire network of regions was negatively correlated with recognition accuracy of semantically encoded items. These results suggest that initial encoding task has little impact on the set of brain regions that is active during subsequent recognition. Right anterior prefrontal cortex appears to be involved in retrieval mode, reflected in its equivalent activity across conditions differing in both stimulus type and encoding task, and also in retrieval effort, shown by the negative correlation between its functional connectivity and individual differences in recognition accuracy.     

汉字情景记忆时皮层定位的fMRI研究

目的探讨用功能磁共振成像(fMRI)检测汉字情景记忆时皮层定位的价值及皮层定位的双侧不对称性.方法 10名健康右利手成人,以高频双字汉字作为刺激任务,行全脑fMRI,确定激活皮层的定位.结果汉字情景记忆时双侧多个脑区有激活,但两侧激活脑区不完全对称,编码加工时主要激活脑区为左侧纹外区和左侧颞叶梭状回,而提取加工时左侧顶叶楔前叶、左侧前额叶背外侧显著激活.结论汉字情景记忆时左右大脑半球激活区存在不对称性,fMRI可对此种功能皮层进行准确定位.     

Isolating the retrieval of imagined pictures during episodic memory: activation of the left precuneus and left prefrontal cortex

The posterior medial parietal cortex and the left prefrontal cortex have both been implicated in the recollection of past episodes. In order to clarify their functional significance, we performed this functional magnetic resonance imaging study, which employed event-related source memory and item recognition retrieval of words paired with corresponding imagined or viewed pictures. Our results suggest that episodic source memory is related to a functional network including the posterior precuneus and the left lateral prefrontal cortex. This network is activated during explicit retrieval of imagined pictures and results from the retrieval of item-context associations. This suggests that previously imagined pictures provide a context with which encoded words can be more strongly associated.     

Distributed self in episodic memory: neural correlates of successful retrieval of self-encoded positive and negative personality traits

Words processed with reference to the self are generally better remembered than words processed in semantic terms. An account of this phenomenon, labeled the Self Reference Effect (SRE), is that the self promotes elaboration and organization of encoded information. Although a few neuroimaging studies associated self-referential encoding with activations of the medial prefrontal cortex, no previous study has investigated the neural correlates of remembering emotional words encoded in an SRE paradigm. The main goal of this study was to define with fMRI the neural correlates of the successful retrieval of negative and positive personality traits encoded in a self-referential mode. Functional MRI scans were acquired for 11 subjects as they recognized positive and negative emotional personality traits adjectives encoded in a self-referential condition, a semantic condition and in a phonemic condition. The correct recognition of self-encoded personality traits engaged dorso-medial prefrontal cortex and lateral prefrontal regions, premotor cortex, parietal and occipital cortex, caudate and cerebellum. The specific recognition of self-encoded negative personality traits involved greater neural activation in the right extra-striate region than the recognition of positive personality traits. Our fMRI findings suggest that specific processes may operate at both encoding and retrieval to subserve the SRE. Unlike self-encoding, the retrieval of personality traits is modulated by the valence of the stimuli with greater activation for negative words. Our results indicate that personally relevant words may signal important emotional clues and support the notion of a widely distributed set of brain regions involved in maintaining the concepts of self.     

Working memory effects on semantic processing: priming differences in pars orbitalis

Both working memory (WM) and controlled (attention-mediated) semantic processing functions have been thought to operate as limited capacity systems, but the possible link between these processes has not been investigated. We found that increased WM load attenuated semantic priming (i.e., reduced the response time advantage for semantically primed relative to unprimed items) and changed fMRI signal intensities in brain regions usually associated with both WM (dorsolateral prefrontal cortex) and controlled semantic retrieval (inferior frontal gyrus [IFG], pars orbitalis). fMRI signal changes in dorsolateral prefrontal cortex were negatively correlated with signal changes in pars orbitalis. The findings suggest that controlled semantic processing and working memory share neural system resources.     

Dissociable contributions of the mid-ventrolateral frontal cortex and the medial temporal lobe system to human memory

Although the prefrontal cortex and regions of the medial temporal lobe are commonly co-activated in neuroimaging studies, their precise respective contributions to human memory remain unclear. In this event-related fMRI study, conditions requiring volunteers to simply look at pictures of abstract art were compared with conditions in which they were explicitly instructed to remember similar stimuli for later recognition. Looking, with no explicit instruction to remember, was associated with significant increases in signal intensity in the medial temporal lobe in 19 of the 20 volunteers scanned, but not in a region of the mid-ventrolateral prefrontal cortex that has previously been implicated in memory encoding and retrieval. Behavioral data collected outside the scanner on the same task revealed that recognition of these stimuli was, however, above chance. When the task instructions were changed to encourage the volunteers to remember the stimuli, significant increases in signal intensity were observed bilaterally, in the mid-ventrolateral frontal cortex, but there was no concomitant increase within the medial temporal lobe region. Moreover, behavioral data collected outside the scanner confirmed that recognition of these stimuli was significantly improved relative to the 'just look' trials. These results suggest that the mid-ventrolateral frontal cortex and the medial temporal lobe region make dissociable contributions to human memory that correspond closely to 'top-down' and 'bottom-up' notions of cognitive control, respectively.     

Reactivation of motor brain areas during explicit memory for actions

Recent functional brain imaging studies have shown that sensory-specific brain regions that are activated during perception/encoding of sensory-specific information are reactivated during memory retrieval of the same information. Here we used PET to examine whether verbal retrieval of action phrases is associated with reactivation of motor brain regions if the actions were overtly or covertly performed during encoding. Compared to a verbal condition, encoding by means of overt as well as covert activity was associated with differential activity in regions in contralateral somatosensory and motor cortex. Several of these regions were reactivated during retrieval. Common to both the overt and covert conditions was reactivation of regions in left ventral motor cortex and left inferior parietal cortex. A direct comparison of the overt and covert activity conditions showed that activation and reactivation of left dorsal parietal cortex and right cerebellum was specific to the overt condition. These results support the reactivation hypothesis by showing that verbal-explicit memory of actions involves areas that are engaged during overt and covert motor activity.     

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

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

The role of the right anterior prefrontal cortex in episodic retrieval

Regional brain activity was measured with H(2) (15)O PET while participants attempted to complete word-stem and word-fragment retrieval cues with previously studied words. The retrieval cue manipulation was employed to gain control over the monitoring operations associated with evaluating the episodic status of alternative cue completions. These operations were more constrained for fragments, which had fewer possible completions than each corresponding stem. In one condition (zero target), during the scanning interval none of the cues could be completed with studied items, whereas in another condition (high target), 80% of cues belonged to studied items. Relative to baseline tasks, right anterior prefrontal activity was greater for stems than for fragments in the zero target condition. The target density manipulation did not modulate right anterior prefrontal activity, but was associated with increased activity in right dorsolateral prefrontal cortex. These findings are consistent with the proposal that the right anterior prefrontal cortex supports monitoring operations during episodic retrieval tasks. In addition, the findings add to evidence suggesting that the dorsolateral and anterior right prefrontal cortex make functionally distinct contributions to episodic retrieval.     

Neural correlates of regional EEG power change

To clarify the physiological significance of task-related change of the regional electroencephalogram (EEG) rhythm, we quantitatively evaluated the correlation between regional cerebral blood flow (rCBF) and EEG power. Eight subjects underwent H2 15O positron emission tomography scans simultaneously with EEG recording during the following tasks: rest condition with eyes closed and open, self-paced movements of the right and left thumb and right ankle. EEG signals were recorded from the occipital and bilateral sensorimotor areas. Cortical activation associated with EEG rhythm generation was studied by the correlation between rCBF and EEG power. There were significant negative correlations between the sensorimotor EEG rhythm at 10-20 Hz on each side and the ipsilateral sensorimotor rCBF and between the occipital EEG rhythm at 10-20 Hz and the occipital rCBF. The occipital EEG rhythm showed a positive correlation with the bilateral medial prefrontal rCBF, while the right sensorimotor EEG rhythm showed a positive correlation with the left prefrontal rCBF. In conclusion, decrease in the regional EEG rhythm at 10-20 Hz might represent the neuronal activation of the cortex underlying the electrodes, at least for the visual and sensorimotor areas. The neural network including the prefrontal cortex could play an important role to generate the EEG rhythm.     

Brain correlates of negative and positive visuospatial priming in adults

A balance of inhibitory and facilitatory mechanisms is essential for efficient and goal-directed behaviors. These mechanisms may go awry in several neuropsychiatric disorders characterized by uncontrolled, repetitive behaviors. The visuospatial priming paradigm is a well-established probe of inhibition and facilitation that has been used to demonstrate behavioral deficits in patients with Tourette syndrome and obsessive-compulsive disorder. However, the brain correlates of this visuospatial priming paradigm are not yet well established. In the present study, we used a visuospatial priming paradigm and event-related functional MRI, to probe inhibitory and facilitatory brain mechanisms in healthy adult women. When subjects performed the negative priming (i.e., inhibitory) task, several regions of the prefrontal cortex were selectively activated relative to the neutral condition. Non-overlapping regions of the prefrontal cortex were deactivated in the positive priming condition. These results support the notion that the prefrontal cortex is involved in both inhibitory and facilitatory processing and demonstrate that this visuospatial priming task shares brain correlates with other positive and negative priming tasks. In conjunction with functional MRI, this visuospatial priming task may be useful for studying the pathophysiology of neuropsychiatric disorders in which deficient inhibitory processing or excessive facilitation is a feature.     

Human cortical EEG rhythms during long-term episodic memory task. A high-resolution EEG study of the HERA model

Many recent neuroimaging studies of episodic memory have indicated an asymmetry in prefrontal involvement, with the left prefrontal cortex more involved than the right in encoding, the right more than the left in retrieval (hemispheric encoding and retrieval asymmetry, or HERA model). In this electroencephalographic (EEG) high-resolution study, we studied brain rhythmicity during a visual episodic memory (recognition) task. The theta (4-6 Hz), alpha (6-12 Hz) and gamma (28-48 Hz) oscillations were investigated during a visuospatial long-term episodic memory task including an encoding (ENC) and retrieval (RET) phases. During the ENC phase, 25 figures representing interiors of buildings ("indoor") were randomly intermingled with 25 figures representing landscapes ("landscapes"). Subject's response was given at left ("indoor") or right ("landscapes") mouse button. During the RET phase (1 h later), 25 figures representing previously presented "indoor" pictures ("tests") were randomly intermingled with 25 figures representing novel "indoor" ("distractors"). Again, a mouse response was required. Theta and alpha EEG results showed no change of frontal rhythmicity. In contrast, the HERA prediction of asymmetry was fitted only by EEG gamma responses, but only in the posterior parietal areas. The ENC phase was associated with gamma EEG oscillations over left parietal cortex. Afterward, the RET phase was associated with gamma EEG oscillations predominantly over right parietal cortex. The predicted HERA asymmetry was thus observed in an unexpected location. This discrepancy may be due to the differential sensitivity of neuroimaging methods to selected components of cognitive processing. The strict relation between gamma response and perception suggests that retrieval processes of long-term memory deeply impinged upon sensory representation of the stored material.     

Hemispheric Activation of Anterior and Inferior Prefrontal Cortex during Verbal Encoding and Recognition: A PET Study of Healthy Volunteers

Evidence of bilateral prefrontal activation during memory encoding and retrieval has increased attention given to anatomical subdivisions within the prefrontal cortex. The current study examined anterior and inferior aspects of the prefrontal cortex to determine their degree of functional and hemispheric overlap during encoding and recognition. Cerebral blood flow of 25 healthy volunteers was measured using PET ¹⁵O-water methods during four conditions: resting baseline, sequential finger movement, word encoding, and word recognition. Resting and motor images were averaged to provide a single reference that was subtracted from encoding and recognition using statistical parametric mapping (SPM96). Memory conditions were also subtracted from each other to identify differences in regional activity. Subjects performed well (86% correct) and had a slightly conservative response bias. Baseline subtraction from encoding revealed focal activation of left inferior prefrontal cortex (area 45) without significant contralateral activation. Recognition minus baseline subtraction produced a focal right anterior prefrontal activation (areas 9 and 10) that was not present in the left hemisphere. Bilateral effects were seen in area 45 during recognition. Subtraction of memory tasks from each other did not reveal any areas of greater activity during encoding. However, the recognition task produced greater activation in right area 9 extending into the anterior cingulate. Greater activity during recognition was also observed in left insula and bilateral visual integration areas. These results are discussed in relation to the prevailing model of prefrontal hemispheric asymmetry during episodic memory.     

Positron emission tomography study of a chronic pain patient successfully treated with somatosensory thalamic stimulation

Previous neuroimaging studies suggested that the neuronal network underlying the perception of chronic pain may differ from that underlying acute pain. To further map the neural network associated with chronic pain, we used positron emission tomography (PET) to determine significant regional cerebral blood flow (rCBF) changes in a patient with chronic facial pain. The patient is implanted with a chronic stimulation electrode in the left ventroposterior medial thalamic nucleus with which he can completely suppress his chronic pain. The patient was scanned in the following conditions: before thalamic stimulation (pain, no stimulation), during thalamic stimulation (no pain, stimulation) and after successful thalamic stimulation (no pain, no stimulation). Comparing baseline scans during pain with scans taken after stimulation, when the patient had become pain-free, revealed significant rCBF increases in the prefrontal (Brodmann areas (BA) 9, 10, 11 and 47) and anterior insular cortices, hypothalamus and periaqueductal gray associated with the presence of chronic pain. No significant rCBF changes occurred in thalamus, primary and secondary somatosensory cortex and anterior cingulate cortex, BA 24'. Significant rCBF decreases were observed in the substantia nigra/nucleus ruber and in the anterior pulvinar nucleus. During thalamic stimulation, blood flow significantly increased in the amygdala and anterior insular cortex. These data further support that there are important differences in the cerebral processing of acute and chronic pain.     

Hippocampal activations during encoding and retrieval in a verbal working memory paradigm

Though the hippocampus has been associated with encoding and retrieval processes in episodic memory, the precise nature of its involvement in working memory has yet to be determined. This functional magnetic resonance imaging (fMRI) study employed a verbal working memory paradigm that allows for the within-subject comparison of functional activations during encoding, maintenance, and retrieval. In each trial, participants were shown 5 target words and, after an 8 s delay, a series of probe words. Probe words consisted of target matches, phonetically or semantically related foils, or foils unrelated to the target words. Both the left and right hippocampi showed higher mean activation amplitudes during encoding than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC) showed greater activation during maintenance than encoding. Both hippocampal and DLPFC regions were more active during retrieval than maintenance. Furthermore, an analysis of retrieval activation separated by probe type showed a trend toward greater bilateral hippocampal activation for probes related (both semantically and phonetically) to the target than for unrelated probes and still greater activation for target matches. This pattern suggests that there may be roles for the hippocampus and DLPFC in working memory that change as function of information processing stage. Additionally, the trend towards increased involvement of the hippocampus with the increase in relatedness of the probe stimuli to the information maintained is interpreted to be consistent with the role of the hippocampus in recollection-based retrieval in long-term memory and may indicate that this role extends to working memory processes.     

Late Onset of Anterior Prefrontal Activity during True and False Recognition: An Event-Related fMRI Study

Previous studies using PET and fMRI to examine memory retrieval have been limited by the requirement to test different types of items in separate blocks and to average data across items and response types within blocks. We used recently developed procedures for analyzing event-related mixed trial data from fMRI experiments to compare brain activity during true recognition of previously studied words and false recognition of semantic associates. A previous PET study using blocked testing procedures reported similarities and differences in rCBF patterns associated with true and false recognition (Schacteret al.,1996a). We examined brain activity during blocked testing of studied words and nonstudied semantic associates (similar to PET), and also during event-related mixed trials, where studied words and nonstudied semantic associates are intermixed. Six subjects initially heard lists of semantically related words and were later tested for old/new recognition with studied words and nonstudied semantic associates, either in separate blocks or intermixed randomly for the event-related analysis. Compared to a fixation control condition, a variety of regions previously reported in the PET study showed significant activation for both true and false recognition, including anterior prefrontal, frontal opercular, medial parietal, and visual cortex extending into hippocampal/parahippocampal regions. Differences across trial types were not clearly present. Event-related analyses of time course data show a relatively late onset and sustained duration for anterior prefrontal signal changes compared to signal changes in other activated regions. Further study is needed to resolve whether this late onset originates from variance in hemodynamic response properties or is attributable to delayed neural activity. The delayed onset is consistent with the idea that anterior prefrontal regions participate in postretrieval monitoring processes.     

Functional anatomy and differential time courses of neural processing for explicit,inferred, and illusory contours. An event-related fMRI study

The perception of shape does not necessarily require viewing an explicit outline figure. Using event-related functional magnetic resonance imaging we examined the time courses of neural activations provoked by shapes defined by (1) lines, (2) illusory contour inducers, and (3) reversed inducers. SPM99 was used to analyze the common and differential neural responses associated with the stimuli and their temporal derivatives. Illusory figures versus reversed inducers activated extrastriate cortex. Reversed inducers versus illusory figures activated the right parietal cortex. For both illusory and line contours versus reversed inducers, analysis of the temporal derivatives showed earlier activations in extrastriate and left parietal cortex and for line contours also in the extrastriate cortex bilaterally and in the right parietal cortex; these earlier activations were mirrored by differences in reaction times with subjects responding more slowly to shapes defined by reversed inducers. The results show substantial bottom-up effects (in occipital cortex) in the recognition of illusory and explicit shapes. By contrast, in stimuli where the shape must be inferred, there is greater reliance on right parietal cortex, consistent with increased attentional demands and top-down processing. The temporal derivatives provide useful information on the differential timing of the associated hemodynamic responses in occipital, parietal, and motor cortex.