The neural basis of visual skill learning: an fMRI study of mirror reading

The learning of perceptual skills is thought to rely upon multiple regions in the cerebral cortex, but imaging studies have not yet provided evidence about the changes in neural activity that accompany visual skill learning. Functional magnetic resonance imaging (fMRI) was used to examine changes in activation of posterior brain regions associated with the acquisition of mirror-reading skill for novel and practiced stimuli. Multiple regions in the occipital lobe, inferior temporal cortex, superior parietal cortex and cerebellum were involved in the reading of mirror-reversed compared to normally oriented text. For novel stimuli, skilled mirror-reading was associated with decreased activation in the right superior parietal cortex and posterior occipital regions and increased activation in the left inferior temporal lobe. These results suggest that learning to read mirror- reversed text involves a progression from visuospatial transformation to direct recognition of transformed letters. Reading practiced, relative to unpracticed, stimuli was associated with decreased activation in occipital visual cortices, inferior temporal cortex and superior parietal cortex and increased activation in occipito-parietal and lateral temporal regions. By examining skill learning and item- specific repetition priming in the same task, this study demonstrates that both of these forms of learning exhibit shifts in the set of neural structures that contribute to performance.      

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.     

Regional specificity of format-specific priming effects in mirror word reading using functional magnetic resonance imaging

The speed and accuracy with which subjects can read words is enhanced or "primed" by a prior presentation of the same words. Moreover, priming effects are generally larger when the physical form of the words is maintained from the first to the second presentation. We investigated the neural basis of format-specific priming in a mirror word-reading task using event-related functional magnetic resonance imaging (fMRI). Participants read words that were presented either in mirror-image (M) orientation or in normal (N) orientation and were repeated either in the same or the alternate orientation, creating 4 study-test conditions, N-N, M-N, N-M, and M-M. Priming of N words resulted in reductions in fMRI signal in multiple brain regions, even though reading times (RTs) were unchanged. Priming of M words showed a pattern of RTs consistent with format-specific priming, with greater reductions when the prime matched the form of the test word. Priming-related reductions in fMRI activity were evident in all regions involved in mirror-image reading, regardless of the orientation of the prime. Importantly, reductions in several posterior regions, including fusiform, superior parietal, and superior temporal regions were also format specific. That is, signal reductions in these regions were greatest when the visual form of the prime and target matched (M-M compared with N-M). The results indicate that, although there are global neural priming effects due to stimulus repetition, it is also possible to identify regional brain changes that are sensitive to the specific perceptual overlap of primes and targets.     

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.     

Increased neural efficiency with repeated performance of a working memory task is information-type dependent

Unlike tasks in which practice leads to an automatic stimulus-response association, it is thought working memory (WM) tasks continue to require cognitive control processes after repeated performance. Previous studies investigating WM task repetition are in accord with this. However, it is unclear whether changes in neural activity after repetition imply alterations in general control processes common to all WM tasks or are specific to the selection, encoding and maintenance of the relevant information. In the present study, functional magnetic resonance imaging (fMRI) was used to examine changes during sample, delay and test periods during repetition of both object and spatial delayed recognition tasks. We found decreases in fMRI activation in both spatial and object-selective areas after spatial WM task repetition, independent of behavioral performance. Few areas showed changed activity after object WM task repetition. These results indicate that spatial task repetition leads to increased efficiency of maintaining task-relevant information and improved ability to filter out task-irrelevant information. The specificity of this repetition effect to the spatial task suggests a difference exists in the nature of the representation of object and spatial information and that their maintenance in WM is likely subserved by different neural systems.     

Nonvisual codes and nonvisual brain areas support visual working memory

Systems models hold working memory to depend on specialized, domain-specific storage buffers. Here, however, we demonstrate that short-term retention of the identity or location of visually presented stimuli is disrupted by nonvisual secondary tasks performed in the dark-passive listening to nouns or endogenous generation of saccades, respectively. This indicates that the short-term retention of visual information relies on multiple mental codes, some of them nonvisual. Event-related functional magnetic resonance imaging (fMRI) reveals the neural correlates of these interference effects to be more complex and more regionally specific than previously described. Although nonspecific dual-task effects produce a generalized decrease of task-evoked fMRI response across many brain regions, the interference-specific effect is a relative increase of activity localized to regions associated with the secondary task in question: left hemisphere perisylvian cortex in the case of passive listening distraction and frontal oculomotor regions in the case of saccadic distraction. Within these regions, the neural interference effects are specific to voxels that show delay-period activity on unfilled memory trials. They also predict individual differences in the magnitude of the behavioral interference effect. These results indicate that nonvisual processes supported by nonvisual brain areas contribute importantly to "visual" working memory performance.     

Neural basis for priming of pop-out during visual search revealed with fMRI

Maljkovic and Nakayama first showed that visual search efficiency can be influenced by priming effects. Even "pop-out" targets (defined by unique color) are judged quicker if they appear at the same location and/or in the same color as on the preceding trial, in an unpredictable sequence. Here, we studied the potential neural correlates of such priming in human visual search using functional magnetic resonance imaging (fMRI). We found that repeating either the location or the color of a singleton target led to repetition suppression of blood oxygen level-dependent (BOLD) activity in brain regions traditionally linked with attentional control, including bilateral intraparietal sulci. This indicates that the attention system of the human brain can be "primed," in apparent analogy to repetition-suppression effects on activity in other neural systems. For repetition of target color but not location, we also found repetition suppression in inferior temporal areas that may be associated with color processing, whereas repetition of target location led to greater reduction of activation in contralateral inferior parietal and frontal areas, relative to color repetition. The frontal eye fields were also implicated, notably when both target properties (color and location) were repeated together, which also led to further BOLD decreases in anterior fusiform cortex not seen when either property was repeated alone. These findings reveal the neural correlates for priming of pop-out search, including commonalities, differences, and interactions between location and color repetition. fMRI repetition-suppression effects may arise in components of the attention network because these settle into a stable "attractor state" more readily when the same target property is repeated than when a different attentional state is required.     

Frontoparietal network involved in successful retrieval from episodic memory. Spatial and temporal analyses using fMRI and ERP

The neural basis for successful recognition of previously studied items, referred to as "retrieval success," has been investigated using either neuroimaging or brain potentials; however, few studies have used both modalities. Our study combined event-related functional magnetic resonance imaging (fMRI) and event-related potential (ERP) in separate groups of subjects. The neural responses were measured while the subjects performed an old/new recognition task with pictures that had been previously studied in either a deep- or shallow-encoding condition. The fMRI experiment showed that among the frontoparietal regions involved in retrieval success, the inferior frontal gyrus and intraparietal sulcus were crucial to conscious recollection because the activity of these regions was influenced by the depth of memory at encoding. The activity of the right parietal region in response to a repeated item was modulated by the repetition lag, indicating that this area would be critical to familiarity-based judgment. The results of structural equation modeling revealed that the functional connectivity among the regions in the left hemisphere was more significant than that in the right hemisphere. The results of the ERP experiment and independent component analysis paralleled those of the fMRI experiment and demonstrated that the repeated item produced an earlier peak than the hit item by approximately 50 ms.     

Neural correlates of true memory, false memory, and deception

We used functional magnetic resonance imaging (fMRI) to determine whether neural activity can differentiate between true memory, false memory, and deception. Subjects heard a series of semantically related words and were later asked to make a recognition judgment of old words, semantically related nonstudied words (lures for false recognition), and unrelated new words. They were also asked to make a deceptive response to half of the old and unrelated new words. There were 3 main findings. First, consistent with the notion that executive function supports deception, 2 types of deception (pretending to know and pretending not to know) recruited prefrontal activity. Second, consistent with the sensory reactivation hypothesis, the difference between true recognition and false recognition was found in the left temporoparietal regions probably engaged in the encoding of auditorily presented words. Third, the left prefrontal cortex was activated during pretending to know relative to correct rejection and false recognition, whereas the right anterior hippocampus was activated during false recognition relative to correct rejection and pretending to know. These findings indicate that fMRI can detect the difference in brain activity between deception and false memory despite the fact that subjects respond with "I know" to novel events in both processes.     

Face repetition effects in implicit and explicit memory tests as measured by fMRI.

Recent parallels between neurophysiological and neuroimaging findings suggest that repeated stimulus processing produces decreased responses in brain regions associated with that processing--a 'repetition suppression' effect. In the present study, volunteers performed two tasks on repeated presentation of famous and unfamiliar faces during functional magnetic resonance imaging (fMRI). In the implicit task, they made fame-judgements (regardless of repetition); in the explicit task, they made episodic recognition judgements (regardless of familiarity). Only in the implicit task was repetition suppression observed: for famous faces in a right lateral fusiform region, and for both famous and unfamiliar faces in a left inferior occipital region. Repetition suppression is therefore not an automatic consequence of repeated perceptual processing of stimuli.     

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.     

Disturbing visual working memory: electrophysiological evidence for a role of the prefrontal cortex in recovery from interference

Single cell recordings in monkeys support the notion that the lateral prefrontal cortex (PFC) controls reactivation of visual working memory representations when rehearsal is disrupted. In contrast, recent fMRI findings yielded a double dissociation for PFC and the medial temporal lobe (MTL) in a letter working memory task. PFC was engaged in interference protection during reactivation while MTL was prominently involved in the retrieval of the letter representations. We present event-related potential data (ERP) that support PFC involvement in the top-down control of reactivation during a visual working memory task with endogenously triggered recovery after visual interference. A differentiating view is proposed for the role of PFC in working memory with respect to endogenous/exogenous control and to stimulus type. General implications for binding and retention mechanisms are discussed.     

Temporal and cerebellar brain regions that support both declarative memory formation and retrieval

Using event-related fMRI, we scanned young healthy subjects while they memorized real-world photographs and subsequently tried to recognize them within a series of new photographs. We confirmed that activity in the medial temporal lobe (MTL) and inferior prefrontal cortex correlates with declarative memory formation as defined by the subsequent memory effect, stronger responses to subsequently remembered than forgotten items. Additionally, we confirmed that activity in specific regions within the parietal lobe, anterior prefrontal cortex, anterior cingulate and cerebellum correlate with recognition memory as measured by the conventional old/new effect, stronger responses for recognized old items (hits) than correctly identified new items (correct rejections). To obtain a purer measure of recognition success, we introduced two recognition effects by comparing brain responses to hits and old items misclassified as new (misses). The positive recognition effect (hits > misses) revealed prefrontal, parietal and cerebellar contributions to recognition, and in line with electrophysiological findings, the negative recognition effect (hits < misses) revealed an anterior medial temporal contribution. Finally, by inclusive masking, we identified temporal and cerebellar brain areas that support both declarative memory formation and retrieval. For matching operations during recognition, these areas may re-use representations formed and stored locally during encoding.     

Task-specific repetition priming in left inferior prefrontal cortex

Previous neuroimaging studies have shown that activation in left inferior prefrontal cortices (LIPC) is reduced during repeated (primed) relative to initial (unprimed) stimulus processing. These reductions in anterior (approximately BA 45/47) and posterior (approximately BA 44/6) LIPC activation have been interpreted as reflecting implicit memory for initial semantic or phonological processing. However, prior studies do not unambiguously indicate that LIPC priming effects are specific to the recapitulation of higher-level (semantic and/or phonological), rather than lower-level (perceptual), processes. Moreover, no prior study has shown that the patterns of priming in anterior and posterior LIPC regions are dissociable. To address these issues, the present fMRI study examined the nature of priming in LIPC by examining the task-specificity of these effects. Participants initially processed words in either a semantic or a nonsemantic manner. Subsequently, participants were scanned while they made semantic decisions about words that had been previously processed in a semantic manner (within-task repetition), words that had been previously processed in a nonsemantic manner (across-task repetition), and words that had not been previously processed (novel words). Behaviorally, task-specific priming was observed: reaction times to make the semantic decision declined following prior semantic processing but not following prior nonsemantic processing of a word. Priming in anterior LIPC paralleled these results with signal reductions being observed following within-task, but not following across-task, repetition. Importantly, neural priming in posterior LIPC demonstrated a different pattern: priming was observed following both within-task and across-task repetition, with the magnitude of priming tending to be greater in the within-task condition. Direct comparison between anterior and posterior LIPC regions revealed a significant interaction. These findings indicate that anterior and posterior LIPC demonstrate distinct patterns of priming, with priming in the anterior region being task-specific, suggesting that this facilitation derives from repeated semantic processing of a stimulus.     

Controlling emotional expression: behavioral and neural correlates of nonimitative emotional responses

Emotional facial expressions can engender similar expressions in others. However, adaptive social and motivational behavior can require individuals to suppress, conceal, or override prepotent imitative responses. We predicted, in line with a theory of "emotion contagion," that when viewing a facial expression, expressing a different emotion would manifest as behavioral conflict and interference. We employed facial electromyography (EMG) and functional magnetic resonance imaging (fMRI) to investigate brain activity related to this emotion expression interference (EEI) effect, where the expressed response was either concordant or discordant with the observed emotion. The Simon task was included as a nonemotional comparison for the fMRI study. Facilitation and interference effects were observed in the latency of facial EMG responses. Neuroimaging revealed activation of distributed brain regions including anterior right inferior frontal gyrus (brain area [BA] 47), supplementary motor area (facial area), posterior superior temporal sulcus (STS), and right anterior insula during emotion expression-associated interference. In contrast, nonemotional response conflict (Simon task) engaged a distinct frontostriatal network. Individual differences in empathy and emotion regulatory tendency predicted the magnitude of EEI-evoked regional activity with BA 47 and STS. Our findings point to these regions as providing a putative neural substrate underpinning a crucial adaptive aspect of social/emotional behavior.     

Functional neuroimaging evidence for high cognitive effort on the Word Memory Test in the absence of external incentives

PRIMARY OBJECTIVE: This study presents data from a functional neuroimaging experiment which brings into question whether poor performance on the Word Memory Test (WMT) can be construed as straightforward evidence for 'poor effort' in the context of cognitive assessment, as asserted in a recent report in this journal. METHODS AND PROCEDURES: Functional magnetic resonance image (fMRI) data were acquired from four participants without brain injury who engaged in the delayed recognition (DR) portion of Green's WMT protocol. OUTCOMES AND RESULTS: Compared to a simple perceptual identification control task, this study found a highly reliable activation pattern across all participants which was restricted almost exclusively to cortical areas most commonly associated with task difficulty, memory load, concentration and other forms of cognitive effort These areas include dorsolateral prefrontal cortex, anterior insula, superior parietal cortex and the dorsal anterior cingulate. CONCLUSIONS: These findings demonstrate that the WMT activates numerous cortical regions that are critical for cognitive effort. Given the extensive neural network necessary to perform the WMT, this study raises important questions about what WMT 'failure' truly means in patients with traumatic brain injury, who have increased likelihood of disruption within this neural network of vision, language, attention, effort and working memory.     

Dissociable functional cortical topographies for working memory maintenance of voice identity and location

In order to ascertain whether the neural system for auditory working memory exhibits a functional dissociation for spatial and nonspatial information, we used functional magnetic resonance imaging and a single set of auditory stimuli to study working memory for the location and identity of human voices. The subjects performed a delayed recognition task for human voices and voice locations and an auditory sensorimotor control task. Several temporal, parietal, and frontal areas were activated by both memory tasks in comparison with the control task. However, during the delay periods, activation was greater for the location than for the voice identity task in dorsal prefrontal (SFS/PreCG) and parietal regions and, conversely, greater for voices than locations in ventral prefrontal cortex and the anterior portion of the insula. This preferential response to the voice identity task in ventral prefrontal cortex continued during the recognition test period, but the double dissociation was observed only during maintenance, not during encoding or recognition. Together, the present findings suggest that, during auditory working memory, maintenance of spatial and nonspatial information modulates activity preferentially in a dorsal and a ventral auditory pathway, respectively. Furthermore, the magnitude of this dissociation seems to be dependent on the cognitive operations required at different times during task performance.     

Task-dependency of the neural correlates of episodic encoding as measured by fMRI.

Using event-related functional magnetic resonance imaging (fMRI), the neural correlates of memory encoding can be studied by contrasting item-related activity elicited in a study task according to whether the items are remembered or forgotten in a subsequent memory test. Previous studies using this approach have implicated the left prefrontal cortex in the successful encoding of verbal material into episodic memory when the study task is semantic in nature. In the current study, we asked whether the neural correlates of episodic encoding differ depending on type of study task. Seventeen volunteers participated in an event-related fMRI experiment in which at study, volunteers were cued to make either animacy or syllable judgements about words. A recognition memory test followed after a delay of approximately 15 min. For the animacy task, words that were subsequently remembered showed greater activation in left and medial prefrontal regions. For the syllable task, by contrast, successful memory for words was associated with activations in bilateral intraparietal sulcus, bilateral fusiform gyrus, right prefrontal cortex and left superior occipital gyrus. These findings suggest that the brain networks supporting episodic encoding differ according to study task.     

Emotional voice areas: anatomic location, functional properties, and structural connections revealed by combined fMRI/DTI

We determined the location, functional response profile, and structural fiber connections of auditory areas with voice- and emotion-sensitive activity using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging. Bilateral regions responding to emotional voices were consistently found in the superior temporal gyrus, posterolateral to the primary auditory cortex. Event-related fMRI showed stronger responses in these areas to voices-expressing anger, sadness, joy, and relief, relative to voices with neutral prosody. Their neural responses were primarily driven by prosodic arousal, irrespective of valence. Probabilistic fiber tracking revealed direct structural connections of these "emotional voice areas" (EVA) with ipsilateral medial geniculate body, which is the major input source of early auditory cortex, as well as with the ipsilateral inferior frontal gyrus (IFG) and inferior parietal lobe (IPL). In addition, vocal emotions (compared with neutral prosody) increased the functional coupling of EVA with the ipsilateral IFG but not IPL. These results provide new insights into the neural architecture of the human voice processing system and support a crucial involvement of IFG in the recognition of vocal emotions, whereas IPL may subserve distinct auditory spatial functions, consistent with distinct anatomical substrates for the processing of "how" and "where" information within the auditory pathways.     

Oscillatory synchrony in the monkey temporal lobe correlates with performance in a visual short-term memory task

Oscillatory synchrony has been proposed to dynamically coordinate distributed neural ensembles, but whether this mechanism is effectively used in neural processing remains controversial. We trained two monkeys to perform a delayed matching-to-sample task using new visual shapes at each trial. Measures of population-activity patterns (cortical field potentials) were obtained from a chronically implanted array of electrodes placed over area V4 and posterior infero-temporal cortex. In correct trials, oscillatory phase synchrony in the beta range (15-20 Hz) was observed between two focal sites in the inferior temporal cortex while holding the sample in short-term memory. Error trials were characterized by an absence of oscillatory synchrony during memory maintenance. Errors did not seem to be due to an impaired stimulus encoding, since various parameters of neural activity in sensory area V4 did not differ in correct and incorrect trials during sample presentation. Our findings suggest that the successful performance of a visual short-term memory task depends on the strength of oscillatory synchrony during the maintenance of the object in short-term memory. The strength of oscillatory synchrony thus seems to be a relevant parameter of the neural population dynamics that matches behavioral performance.