Separate neural correlates for the mnemonic components of successive discrimination and working memory tasks

We have used positron emission tomography to map the mnemonic components of two tasks at the extremes of the visual short-term/ working memory spectrum. The successive discrimination task requires only storage of a single item for very short time (ultra-short- term memory), while the 2back task requires both maintenance (i.e. storage and rehearsal) and manipulation of several items (working memory). We tested whether or not the storage component, common to the two tasks, engaged the same cerebral regions. To remove unnecessary confounds, we reduced the cues available to the subjects to a single elementary attribute, the orientation of a grating presented in central vision. This prevented subjects from using verbal strategies or vestibular cues and allowed equating of difficulty among tasks. Ultra-short-term memory for orientation engaged a large expanse of occipito-temporal cortex with a rate-dependent antero-posterior gradient: a fast trial rate engaged posterior regions, a slow trial rate anterior regions. On the other hand, working memory for orientation involved the left inferior parietal cortex, left dorsolateral prefrontal cortex and a left superior frontal sulcus region, and to a lesser degree the symmetrical right superior frontal region and a left superior parietal region. Direct comparison of the two orientation memory networks confirmed their functional segregation. We conclude that at least the storage of orientation information engages distinct regions depending on whether or not short-term memory/working memory involves rehearsal and/or manipulative processes.     

Dissociation of verbal working memory system components using a delayed serial recall task

Functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of component processes in verbal working memory. Based on behavioral research using manipulations of verbal stimulus type to dissociate storage, rehearsal, and executive components of verbal working memory, we designed a delayed serial recall task requiring subjects to encode, maintain, and overtly recall sets of verbal items for which phonological similarity, articulatory length, and lexical status were manipulated. By using a task with temporally extended trials, we were able to exploit the temporal resolution afforded by fMRI to partially isolate neural contributions to encoding, maintenance, and retrieval stages of task performance. Several regions commonly associated with maintenance, including supplementary motor, premotor, and inferior frontal areas, were found to be active across all three trial stages. Additionally, we found that left inferior frontal and supplementary motor regions showed patterns of stimulus and temporal sensitivity implicating them in distinct aspects of articulatory rehearsal, while no regions showed a pattern of sensitivity consistent with a role in phonological storage. Regional modulation by task difficulty was further investigated as a measure of executive processing. We interpret our findings as they relate to notions about the cognitive architecture underlying verbal working memory performance.     

Reduced functional connectivity during working memory in Turner syndrome

Turner syndrome (TS) is a genetic disorder affecting females, resulting from the complete or partial absence of an X chromosome. The cognitive profile of TS shows relative strengths in the verbal domain and weaknesses in the procedural domain, including working memory. Neuroimaging studies have identified differences in the morphology of the parietal lobes, and white matter pathways linking frontal and parietal regions, as well as abnormal activation in dorsal frontal and parietal regions. Taken together these findings suggest that abnormal functional connectivity between frontal and parietal regions may be related to working memory impairments in TS, a hypothesis we tested in the present study. We scanned TS and typically developing participants with functional magnetic resonance imaging while they performed visuospatial and phonological working memory tasks. We generated a seed region in parietal cortex based on structural differences in TS and found that functional connectivity with dorsal frontal regions was reduced during working memory in TS. Finally, we found that connectivity was correlated with task performance in TS. These findings suggest that structural brain abnormalities in TS affect not only regional activity but also the functional interactions between regions and that this has important consequences for behavior.     

Separable neuronal circuitries for manipulable and non-manipulable objects in working memory

Previous work using single-cell recordings in monkeys and neuro-imaging studies in humans has shown that perceiving an object or imaging the action associated with the object recruits the same brain regions in the ventral premotor cortex as performing an action with the object. We used functional magnetic resonance imaging (fMRI) for examining whether similar brain regions are also activated while maintaining information about manipulable objects in working memory. Holding information about manipulable objects in working memory activated the left ventral premotor cortex and the left inferior frontal gyrus (Broca's area). Conversely, non-manipulable objects to be held in working memory co-activated Broca's area and the left angular gyrus. When contrasted directly, manipulable relative to non-manipulable objects activated the left ventral premotor cortex and the anterior intraparietal sulcus, a circuitry that is assumed to mediate the transformation of movement-relevant object properties into hand actions. These results indicate that visual working memory for manipulable objects is based on motor programmes associated with their use. Similar to speech motor programmes in verbal memory tasks, hand motor programmes may allow the maintenance of objects in working memory over short intervals.     

Right prefrontal activation during encoding, but not during retrieval, in a non-verbal paired-associates task

Brain imaging studies have shown that episodic encoding into long-term memory preferentially activates the left prefrontal cortex and retrieval activates the right prefrontal cortex. However, it is unclear to what degree verbal analysis contributes to the left prefrontal activation during encoding. The present study was designed to avoid verbal analysis during encoding by using abstract pictures and computer- generated sounds which were difficult to code verbally. Sounds and pictures were grouped into six stimulus-stimulus pairs. When the sound from a pair was presented, the subjects were instructed to recall and visualize the associated picture. After 2.0 s the associated picture and another picture appeared on the screen and the subjects were required to identify the associated picture. Feedback about the choice was then given. Regional cerebral blood flow (rCBF) was measured with [15O]butanol and positron emission tomography (PET) in 10 subjects during initial training on the paired-associates task (encoding scan) and after 35 min of training (retrieval scan). Performance during the encoding scan was 59% correct and during the retrieval scan 98% correct, with a mean reaction time of 709 ms during retrieval. The rCBF was also measured during a control condition without any instruction to encode or retrieve. Compared with retrieval, encoding showed significant activation of the posterior part of the right middle frontal gyrus, the right inferior parietal cortex, the cingulate cortex, the left inferior parietal cortex and the left inferior and middle temporal gyri. The rCBF increase during encoding was strongly correlated with the rate of encoding. Retrieval was compared with both encoding and control. In none of these comparisons was there any prefrontal activation. The lack of prefrontal activation during near- perfect performance of the retrieval task suggests that the prefrontal cortex is not necessarily active when retrieval is fast and accurate, or what might be called automatic. Encoding was not associated with more activation of the left than the right prefrontal cortex. This result presents a limitation to the generality of left prefrontal activation during episodic encoding, which has been found in several previous brain imaging studies. Differences between studies in the relative activation of left and right prefrontal cortex during encoding and retrieval might be due to differences in paradigms, the type of stimulus used, and the demand for working memory and verbal analysis.      

Interindividual differences in functional interactions among prefrontal, parietal and parahippocampal regions during working memory

To clarify the neural systems deployed by individual subjects during working memory (WM), we collected functional neuroimaging data from healthy subjects, and constructed a model of 2-back WM using structural equation modeling (SEM). A group model was constructed, and models for each subject were validated against it. The group model consisted principally of regions in the prefrontal and parietal cortex, with considerable interindividual variance in the single-subject models. To explore this variance, subjects were split into two groups based on performance. Performance level and self-reported strategy scores were used in a correlation analysis against path weights between nodes of individual models. High performers utilized a left hemisphere sub-network involving inferior parietal lobule and Broca's area, whereas lower performers utilized a right hemisphere sub-network with interactions between inferior parietal lobule and dorsolateral prefrontal cortex. Further, we observed an interaction between the parahippocampal formation and the inferior parietal lobule that was related to the different strategies used by the individuals to perform the task. Strategy and performance level appear to be intricately related in this task, with neural systems supporting verbal processing producing better performance than those associated with spatial processing. These results demonstrate that individual behavioral characteristics are reflected in specific neurofunctional patterns at the system level and that these can be captured by analytical techniques such as SEM.     

Neural correlates of availability and accessibility in memory

Failure to remember can be due to not having information available in memory or to an inability to access information that is available. We used functional magnetic resonance imaging to examine brain responses during encoding and successive cued recall and associative recognition tests of paired associates. Items were classified into 3 categories based on performance on the 2 retrieval tests: 1) successfully remembered (both recalled and recognized), 2) inaccessible (not recalled but later recognized), and 3) forgotten (neither recalled nor recognized). During cued recall, availability in memory was signaled in a network of regions including bilateral medial temporal lobe, left middle temporal cortex, and the parietal cortex. Memory access resulted in heightened activity in these regions as well as in left inferior frontal cortex. Encoding-related activity in hippocampus and inferior temporal cortex predicted subsequent availability and left inferior frontal activity predicted subsequent access. These results suggest that failure to access information that is available in memory may reflect weaker memory representations.     

Anatomical correlates of foreign speech sound production

Previous work has shown a relationship between brain anatomy and how quickly adults learn to perceive foreign speech sounds. Faster learners have greater asymmetry (left>right) in parietal lobe white matter (WM) volumes and larger WM volumes of left Heschl's gyrus than slower learners. Here, we tested native French speakers who were previously scanned using high-resolution anatomical magnetic resonance imaging. We asked them to pronounce a Persian consonant that does not exist in French but which can easily be distinguished from French speech sounds, the voiced uvular stop. Two judges scored the goodness of the utterances. Voxel-based morphometry revealed that individuals who more accurately pronounce the foreign sound have higher WM density in the left insula/prefrontal cortex and in the inferior parietal cortices bilaterally compared with poorer producers. Results suggest that WM anatomy in brain regions previously implicated in articulation and phonological working memory, or the size/shape of these or adjacent regions, is in part predictive of the accuracy of speech sound pronunciation.     

Repetition suppression and reactivation in auditory-verbal short-term recognition memory

The neural response to stimulus repetition is not uniform across brain regions, stimulus modalities, or task contexts. For instance, it has been observed in many functional magnetic resonance imaging (fMRI) studies that sometimes stimulus repetition leads to a relative reduction in neural activity (repetition suppression), whereas in other cases repetition results in a relative increase in activity (repetition enhancement). In the present study, we hypothesized that in the context of a verbal short-term recognition memory task, repetition-related "increases" should be observed in the same posterior temporal regions that have been previously associated with "persistent activity" in working memory rehearsal paradigms. We used fMRI and a continuous recognition memory paradigm with short lags to examine repetition effects in the posterior and anterior regions of the superior temporal cortex. Results showed that, consistent with our hypothesis, the 2 posterior temporal regions consistently associated with working memory maintenance, also show repetition increases during short-term recognition memory. In contrast, a region in the anterior superior temporal lobe showed repetition suppression effects, consistent with previous research work on perceptual adaptation in the auditory-verbal domain. We interpret these results in light of recent theories of the functional specialization along the anterior and posterior axes of the superior temporal lobe.     

Distribution of cortical activation during visuospatial n-back tasks as revealed by functional magnetic resonance imaging

Human neuroimaging studies conducted during visuospatial working memory tasks have inconsistently detected activation in the prefrontal cortical areas depending presumably on the type of memory and control tasks employed. We used functional magnetic resonance imaging to study brain activation related to the performance of a visuospatial n-back task with different memory loads (0-back, 1-back and 2-back tasks). Comparison of the 2-back versus 0-back tasks revealed consistent, bilateral activation in the medial frontal gyrus (MFG), superior frontal sulcus and adjacent cortical tissue (SFS/SFG) in all subjects and in six out of seven subjects in the intraparietal sulcus (IPS). Activation was also detected in the inferior frontal gyrus, medially in the superior frontal gyrus, precentral gyrus, superior and inferior parietal lobuli, occipital visual association areas, anterior and posterior cingulate areas and in the insula. Comparison between the 1- back versus 0-back tasks revealed activation only in a few brain areas. Activation in the MFG, SFS/SFG and IPS appeared dependent on memory load. The results suggest that the performance of a visuospatial working memory task engages a network of distributed brain areas and that areas in the dorsal visual pathway are engaged in mnemonic processing of visuospatial information.      

Working memory of auditory localization

To investigate brain mechanisms of sound location memory, we studied the distribution of brain activation with functional magnetic resonance imaging (fMRI) in subjects performing an audiospatial n-back task with three memory load levels. Working memory processing of audiospatial information activated areas in the superior, middle and inferior frontal gyri, and in the posterior parietal and middle temporal cortices. In a control experiment, fMRI during audio- and visuospatial 2-back task performances revealed only few differentially activated subregions between the two tasks. These results demonstrate that working memory processing of auditory locations involves a distributed network of brain areas and suggest that mnemonic processing of audio- and visuospatial information is directed along a common neural pathway in the posterior parietal and prefrontal cortices.     

Language learning under working memory constraints correlates with microstructural differences in the ventral language pathway

The present study combined behavioral measures and diffusion tensor imaging to investigate the neuroanatomical basis of language learning in relation to phonological working memory (WM). Participants were exposed to simplified artificial languages under WM constraints. The results underscore the role of the rehearsal subcomponent of WM in successful speech segmentation and rule learning. Moreover, when rehearsal was blocked task performance was correlated to the white matter microstructure of the left ventral pathway connecting frontal and temporal language-related cortical areas through the extreme/external capsule. This ventral pathway may therefore play an important additional role in language learning when the main dorsal pathway-dependent rehearsal mechanisms are not available.     

Developmental changes in mental arithmetic: evidence for increased functional specialization in the left inferior parietal cortex

Arithmetic reasoning is arguably one of the most important cognitive skills a child must master. Here we examine neurodevelopmental changes in mental arithmetic. Subjects (ages 8-19 years) viewed arithmetic equations and were asked to judge whether the results were correct or incorrect. During two-operand addition or subtraction trials, for which accuracy was comparable across age, older subjects showed greater activation in the left parietal cortex, along the supramarginal gyrus and adjoining anterior intra-parietal sulcus as well as the left lateral occipital temporal cortex. These age-related changes were not associated with alterations in gray matter density, and provide novel evidence for increased functional maturation with age. By contrast, younger subjects showed greater activation in the prefrontal cortex, including the dorsolateral and ventrolateral prefrontal cortex and the anterior cingulate cortex, suggesting that they require comparatively more working memory and attentional resources to achieve similar levels of mental arithmetic performance. Younger subjects also showed greater activation of the hippocampus and dorsal basal ganglia, reflecting the greater demands placed on both declarative and procedural memory systems. Our findings provide evidence for a process of increased functional specialization of the left inferior parietal cortex in mental arithmetic, a process that is accompanied by decreased dependence on memory and attentional resources with development.     

fMRI investigation of working memory for faces in autism: visual coding and underconnectivity with frontal areas

Brain activation and functional connectivity were investigated in high functioning autism using functional magnetic resonance imaging in an n-back working memory task involving photographic face stimuli. The autism group showed reliably lower activation compared with controls in the inferior left prefrontal area (involved in verbal processing and working memory maintenance) and the right posterior temporal area (associated with theory of mind processing). The participants with autism also showed activation in a somewhat different location in the fusiform area than the control participants. These results suggest that the neural circuitry of the brain for face processing in autism may be analyzing the features of the face more as objects and less in terms of their human significance. The functional connectivity results revealed that the abnormal fusiform activation was embedded in a larger context of smaller and less synchronized networks, particularly indicating lower functional connectivity with frontal areas. In contrast to the underconnectivity with frontal areas, the autism group showed no underconnectivity among posterior cortical regions. These results extend previous findings of abnormal face perception in autism by demonstrating that the abnormalities are embedded in an abnormal cortical network that manages to perform the working memory task proficiently, using a visually oriented, asocial processing style that minimizes reliance on prefrontal areas.     

The contributions of prefrontal cortex and executive control to deception: evidence from activation likelihood estimate meta-analyses

Previous neuroimaging studies have implicated the prefrontal cortex (PFC) and nearby brain regions in deception. This is consistent with the hypothesis that lying involves the executive control system. To date, the nature of the contribution of different aspects of executive control to deception, however, remains unclear. In the present study, we utilized an activation likelihood estimate (ALE) method of meta-analysis to quantitatively identify brain regions that are consistently more active for deceptive responses relative to truthful responses across past studies. We then contrasted the results with additional ALE maps generated for 3 different aspects of executive control: working memory, inhibitory control, and task switching. Deception-related regions in dorsolateral PFC and posterior parietal cortex were selectively associated with working memory. Additional deception regions in ventrolateral PFC, anterior insula, and anterior cingulate cortex were associated with multiple aspects of executive control. In contrast, deception-related regions in bilateral inferior parietal lobule were not associated with any of the 3 executive control constructs. Our findings support the notion that executive control processes, particularly working memory, and their associated neural substrates play an integral role in deception. This work provides a foundation for future research on the neurocognitive basis of deception.     

Positron emission tomography study of letter and object processing: empirical findings and methodological considerations.

The study of functional-anatomical correlations of higher-order cognitive processing has benefited from recent advances in brain imaging techniques such as positron emission tomography (PET) measurements of regional cerebral blood flow (CBF). Comparisons of CBF changes by paired image subtraction provide the opportunity to isolate cerebral areas participating in the realization of the processes that differentiate two tasks. However, the subtraction method is based on assumptions that are not entirely compatible with cerebral cognitive processing, and the derived pattern of activation specifically associated with the processes that differentiate two tasks is relative to the activation associated with the subtracted task and may therefore vary as a function of the processes actually performed in this subtracted task. To examine the implications of this procedure, a PET study with the 15O water bolus technique was carried out on normal adults. Subjects performed three tasks that made nonoverlapping cognitive processing demands: a semantic categorization of visual objects, a spatial discrimination of visually presented letters, and a phonological decision on visually presented single letters. Each task produced distinct patterns of activation consistent with evidence from neurological patients, specifically in the left occipital cortex in the semantic categorization of objects, in the parietal cortex of both hemispheres in the letter-spatial task, and in the left frontal and superior temporal cortex in the letter-sound task. However, the comparisons between the two letter tasks did not result in the expected CBF changes even though these two tasks make distinct processing requirements and are dissociable by brain injury. In addition, the phonological task resulted in activation of areas of the frontal cortex that earlier PET studies had identified as participating in semantic operations, whereas letters have no semantic property. These results suggest that the interpretation of patterns of activation is confronted with difficulties due to the automatic, and uncontrolled, processing of verbal stimuli that raises the threshold for significant CBF changes between two conditions that use the same stimuli but different task demands.     

The compassionate brain: humans detect intensity of pain from another's face

Understanding another person's experience draws on "mirroring systems," brain circuitries shared by the subject's own actions/feelings and by similar states observed in others. Lately, also the experience of pain has been shown to activate partly the same brain areas in the subjects' own and in the observer's brain. Recent studies show remarkable overlap between brain areas activated when a subject undergoes painful sensory stimulation and when he/she observes others suffering from pain. Using functional magnetic resonance imaging, we show that not only the presence of pain but also the intensity of the observed pain is encoded in the observer's brain-as occurs during the observer's own pain experience. When subjects observed pain from the faces of chronic pain patients, activations in bilateral anterior insula (AI), left anterior cingulate cortex, and left inferior parietal lobe in the observer's brain correlated with their estimates of the intensity of observed pain. Furthermore, the strengths of activation in the left AI and left inferior frontal gyrus during observation of intensified pain correlated with subjects' self-rated empathy. These findings imply that the intersubjective representation of pain in the human brain is more detailed than has been previously thought.     

Neurophysiological measures of working memory and individual differences in cognitive ability and cognitive style

The capacity to deliberately control attention in order to hold and manipulate information in working memory is critical to higher cognitive functions. This suggests that between-subject differences in general cognitive ability might be related to observable differences in the activity of brain systems that support working memory and attention control. To test this notion, electroencephalograms were recorded from 80 healthy young adults during spatial working memory tasks. Measures of task-related neurophysiological and behavioral variables were derived from these data and compared to scores on a test battery commonly used to assess general cognitive ability (the WAIS-R). Subjects who scored high on the psychometric test also tended to respond faster in the experimental tasks without any loss of accuracy. The amplitude of the late positive component of the event-related potential was larger in high-ability subjects, and the frontal midline theta component of the EEG signal was also selectively enhanced in this group under conditions of sustained performance and high working memory load. These results suggest that subjects who scored high on the WAIS-R were better able to focus and sustain attention to task performance. Changes in the EEG alpha rhythm in response to manipulations of task practice and load were also examined and compared between frontal and parietal regions. The results indicated that high-ability subjects developed strategies that made relatively greater use of parietal regions, whereas low-ability subjects relied more exclusively on frontal regions. Other analyses indicated that hemispheric asymmetries in alpha band measures distinguish between individuals with relatively high verbal aptitude and those with relatively high nonverbal aptitude. In particular, subjects with a verbal cognitive style tended to make greater use of the left parietal region during task performance, and subjects with a nonverbal style tended to make greater use of the right parietal region. These results help clarify relationships between task-related brain activity and individual differences in cognitive ability and style.     

Time modulated prefrontal and parietal activity during the maintenance of integrated information as revealed by magnetoencephalography

Using magnetoencephalography, we investigated the spatiotemporal patterns of brain magnetic activity responsible for maintaining verbal and spatial information in either an integrated or an unintegrated fashion. Considering time dimension, we noted a greater activation of a fronto-parietal network in early latencies during the maintenance of integrated information, and a different pattern during the maintenance of unintegrated material, showing a greater activation in a fronto-posterior network in late latencies. The greater activation found in certain areas which are traditionally reported as being engaged in spatial working memory (i.e. superior frontal gyri, dorsolateral prefrontal cortex, superior and inferior parietal lobes) when subjects maintained integrated information could be explained by a greater weight of the spatial dimension. It is as if words somehow acquired a spatial attribute, thus exerting a greater load in a neural network specialized in spatial working memory. Alternatively, and not mutually exclusive, we also propose that during the maintenance of integrated information the allocation of cognitive resources is less interfering than during the maintenance of unintegrated information, making it easier.     

Dorsal cortical regions subserving visually guided saccades in humans: an fMRI study

Neurophysiological studies in non-human primates have identified saccade-related neuronal activity in cortical regions including frontal (FEF), supplementary (SEF) and parietal eye fields. Lesion and neuroimaging studies suggest a generally homologous mapping of the oculomotor system in humans; however, a detailed mapping of the precise anatomical location of these functional regions has not yet been achieved. We investigated dorsal frontal and parietal cortex during a saccade task vs. central fixation in 10 adult subjects using functional magnetic resonance imaging (fMRI). The FEF were restricted to the precentral sulcus, and did not extend anteriorly into Brodmann area 8, which has traditionally been viewed as their location in humans. The SEF were located in cortex along the interhemispheric fissure and extended minimally onto the dorsal cortical surface. Parietal activation was seen in precuneus and along the intraparietal sulcus, extending into both superior and inferior parietal lobules. These findings localize areas in frontal and parietal cortex involved in saccade generation in humans, and indicate significant differences from the macaque monkey in both frontal and parietal cortex. These differences may have functional implications for the roles these areas play in visuomotor processes.