Prefrontal cortex asymmetry for memory encoding of words and abstract shapes

Previous work suggested a differential contribution of prefrontal cortex (PFC) to successful encoding depending on the stimulus material. Here, we tested the hypothesis that encoding of words preferentially involves the left PFC, while encoding of nonverbal items (abstract shapes) relies on the right PFC. We used an experimental design that evaluated encoding of both words and abstract shapes in the same healthy volunteers. A transient virtual lesion of the left or the right PFC was elicited with transcranial magnetic stimulation (TMS) while subjects memorized verbal and nonverbal items. We found that encoding of verbal material was disrupted by left PFC stimulation, whereas encoding of nonverbal material was disrupted by right PFC stimulation. These results demonstrate a functionally relevant lateralization of prefrontal contribution for verbal and nonverbal memory encoding.     

FMRI evidence for an organization of prefrontal cortex by both type of process and type of information

Neuroimaging evidence is conflicting regarding whether human prefrontal cortex (PFC) shows functional organization by type of processes engaged or type of information processed. Most studies use complex working or long-term memory tasks requiring multiple processes and the combinations of processes recruited for different materials may vary. Using functional magnetic resonance imaging (fMRI) and simple tasks suggested by a component process approach, we found activity in left PFC when participants thought about (refreshed) a just-seen item and in right PFC when participants noted whether an item had been presented previously. Furthermore, the distribution of activation in left or right PFC varied with type of information. Thus, at the component process level, PFC shows functional organization by both process and type of information.     

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.     

When planning fails: individual differences and error-related brain activity in problem solving

The neuronal processes underlying correct and erroneous problem solving were studied in strong and weak problem-solvers using functional magnetic resonance imaging (fMRI). During planning, the right dorsolateral prefrontal cortex was activated, and showed a linear relationship with the participants' performance level. A similar pattern emerged in right inferior parietal regions for all trials, and in anterior cingulate cortex for erroneously solved trials only. In the performance phase, when the pre-planned moves had to be executed by means of an fMRI-compatible computer mouse, the right dorsolateral prefrontal cortex was again activated jointly with right parahippocampal cortex, and displayed a similar positive relationship with the participants' performance level. Incorrectly solved problems elicited stronger bilateral prefrontal and left inferior parietal activations than correctly solved trials. For both individual ability and trial-specific performance, our results thus demonstrate the crucial involvement of right prefrontal cortex in efficient visuospatial planning.     

Domain-general and domain-sensitive prefrontal mechanisms for recollecting events and detecting novelty

Recollecting the past and discriminating novel from familiar memoranda depend on poorly understood prefrontal cortical (PFC) mechanisms hypothesized to vary according to memory task (e.g. recollection versus novelty detection) and domain of targeted memories (e.g. perceptual versus conceptual). Using event-related fMRI, we demonstrate that recollecting conceptual or perceptual details surrounding object encounters similarly recruits left frontopolar and posterior PFC compared with detecting novel stimuli, suggesting that a domain-general control network is engaged during contextual remembering. In contrast, left anterior ventrolateral PFC coactivated with a left middle temporal region associated with semantic representation, and right ventrolateral PFC with bilateral occipito-temporal cortices associated with representing object form, depending on whether recollections were conceptual or perceptual. These PFC/posterior cortical dissociations suggest that during recollection, lateralized ventrolateral PFC mechanisms bias posterior conceptual or perceptual feature representations as a function of memory relevance, potentially improving the gain of bottom-up memory signals. Supporting this domain-sensitive biasing hypothesis, novelty detection also recruited right ventrolateral PFC and bilateral occipito-temporal cortices compared with conceptual recollection, suggesting that searching for novel objects heavily relies upon perceptual feature processing. Collectively, these data isolate task- from domain-sensitive PFC control processes strategically recruited in the service of episodic memory.     

Concurrent multiple left atrial focal activations with fibrillatory conduction and right atrial focal or reentrant activation as the mechanism in atrial fibrillation

OBJECTIVE: We examined the atrial activation during atrial fibrillation to validate the rationale behind simplified surgical procedures. METHODS: Intraoperative mapping of the entire atrial epicardium was performed in 21 patients with permanent atrial fibrillation and mitral valve disease using a 256-channel, 3-dimensional dynamic mapping system. RESULTS: Concurrent multiple repetitive activations arose from the posterior left atrium adjacent to the pulmonary veins or the left atrial appendage in all patients. The fastest activation propagated toward the right atrium conducting through Bachmann's bundle, leaving the other activations confined to a small atrial region. As the activation propagated toward the right atrium, there was a progressive conduction delay or block in the pathway. As a result, the activation in the right atrium desynchronized with the left atrial activation and became irregular and complex. The average cycle length measured at the right atrial appendage was significantly longer than that at the left atrial foci (206 +/- 32 milliseconds vs 175 +/- 23 milliseconds, P <.001). In addition to the passive activation, a focal activation and reentrant activation were also observed in the right atrium in 5 and 6 patients, respectively. The number of wave fronts in the right atrium was significantly greater than that in the left atrium (2.9 +/- 0.8 vs 0.6 +/- 0.7, P <.001). CONCLUSIONS: Multiple left atrial focal activations with fibrillatory conduction and right atrial focal or reentrant activations are the mechanism in permanent atrial fibrillation associated with mitral valve disease. Intraoperative mapping would facilitate the indication for simplified procedures confined to the left atrium or the pulmonary veins.     

The role of the lateral frontal cortex in causal associative learning: exploring preventative and super-learning

Prediction error--a mismatch between expected and actual outcome--is critical to associative accounts of inferential learning. However, it has proven difficult to explore the effects of prediction error using functional magnetic resonance imaging (fMRI) while excluding the confounding effects of stimulus novelty and incorrect responses. In this event-related fMRI study we used a three-stage experiment generating preventative- and super-learning conditions. In both cases, it was possible to generate prediction error within a causal associative learning experiment while subtracting the effects of novelty and error. We show that right lateral prefrontal cortex (PFC) activation is sensitive to the magnitude of prediction error. Furthermore, super-learning activation in this region of PFC correlates, across subjects, with the amount learned. We thus provide direct evidence for a brain correlate of the surprise-dependent mechanisms proposed by associative accounts of causal learning. We show that activity in right lateral PFC is sensitive to the magnitude, though not the direction, of the prediction error. Furthermore, its activity is not directly explicable in terms of novelty or response errors and appears directly related to the learning that arises out of prediction error.     

Possibility of focal activation around the left upper pulmonary vein during chronic atrial fibrillation with mitral valve disease.

Focal regular activations were sometimes observed during chronic atrial fibrillation (AF) associated with mitral valve disease. We present a 58 year-old male diagnosed with mitral valvular stenosis and regurgitation with chronic atrial fibrillation. Intraoperative mapping of both atria was performed during mitral valvular surgery. Regular and repetitive activations around the left superior pulmonary vein were observed, in contrast to irregular and chaotic activations of the right atrium. This regular activation was supposed to be the focus of chronic AF. Surgical ablation of the posterior left atrium was successfully performed and eliminated the chronic AF, concomitant with mitral valve replacement.     

Hemispheric specialization in human prefrontal cortex for resolving certain and uncertain inferences

Uncertainty is a fact of life that must be accommodated in real-world decision making. Although it has been suggested that the right prefrontal cortex (PFC) has a special role to play in decision making under uncertainty, there is very little hard data to support this hypothesis. To better understand the roles of left and right PFCs in reasoning and decision making in situations with complete and incomplete information, we administered simple inference problems to 18 patients with lateralized focal lesions to PFC (9 right hemisphere, 9 left hemisphere) and 22 age- and education-matched normal controls. The stimuli were systematically manipulated for completeness of information regarding the status of the conclusion. Our results demonstrated a 2-way interaction such that patients with left PFC lesions were selectively impaired in trials with complete information, whereas patients with right PFC lesions were selectively impaired in trials with incomplete information. These results provide compelling evidence for hemispheric specialization for reasoning in PFC and suggest that the right PFC has a critical role to play in reasoning about incompletely specified situations. We postulate this role involves the maintenance of ambiguous mental representations that temper premature overinterpretation by the left hemisphere.     

Isolating rule- versus evidence-based prefrontal activity during episodic and lexical discrimination: a functional magnetic resonance imaging investigation of detection theory distinctions

Dorsolateral and frontopolar prefrontal cortices (PFCs) are often implicated in neuroimaging studies of memory retrieval, with this activity ascribed to controlled monitoring processes indicative of difficult or demanding retrieval. Difficulty, however, is multiply determined, with success rates governed both by the available evidence and by the nature of decision rules applied to that evidence. Using event-related functional magnetic resonance imaging, we isolated these factors by 1) contrasting different decision rules across matched evidence and 2) manipulating the level of evidence within a fixed decision rule. For identically constructed retrieval probes (1 old and 1 new item), same-different (are these different?) compared with forced-choice (which one is old?) decision rules yielded bilateral dorsolateral and right frontopolar PFC increases. However, these regions were unaffected when the available evidence was greatly lowered within forced-choice decisions. Thus, the regions were simultaneously sensitive to the type of decision rule and yet insensitive to the level of evidence supporting those decisions. Analogous lexical tasks yielded similar patterns, demonstrating that the PFC responses were not episodic memory specific. We discuss the mechanistic differences between same-different versus forced-choice decisions and the implications of these data for current theories of PFC activity during episodic remembering and executive control.     

Learning the exception to the rule: model-based FMRI reveals specialized representations for surprising category members

Category knowledge can be explicit, yet not conform to a perfect rule. For example, a child may acquire the rule "If it has wings, then it is a bird," but then must account for exceptions to this rule, such as bats. The current study explored the neurobiological basis of rule-plus-exception learning by using quantitative predictions from a category learning model, SUSTAIN, to analyze behavioral and functional magnetic resonance imaging (fMRI) data. SUSTAIN predicts that exceptions require formation of specialized representations to distinguish exceptions from rule-following items in memory. By incorporating quantitative trial-by-trial predictions from SUSTAIN directly into fMRI analyses, we observed medial temporal lobe (MTL) activation consistent with 2 predicted psychological processes that enable exception learning: item recognition and error correction. SUSTAIN explains how these processes vary in the MTL across learning trials as category knowledge is acquired. Importantly, MTL engagement during exception learning was not captured by an alternate exemplar-based model of category learning or by standard contrasts comparing exception and rule-following items. The current findings thus provide a well-specified theory for the role of the MTL in category learning, where the MTL plays an important role in forming specialized category representations appropriate for the learning context.     

Motor "dexterity"?: Evidence that left hemisphere lateralization of motor circuit connectivity is associated with better motor performance in children

Motor control relies on well-established motor circuits, which are critical for typical child development. Although many imaging studies have examined task activation during motor performance, none have examined the relationship between functional intrinsic connectivity and motor ability. The current study investigated the relationship between resting state functional connectivity within the motor network and motor performance assessment outside of the scanner in 40 typically developing right-handed children. Better motor performance correlated with greater left-lateralized (mean left hemisphere-mean right hemisphere) motor circuit connectivity. Speed, rhythmicity, and control of movements were associated with connectivity within different individual region pairs: faster speed was associated with more left-lateralized putamen-thalamus connectivity, less overflow with more left-lateralized supplementary motor-primary motor connectivity, and less dysrhythmia with more left-lateralized supplementary motor-anterior cerebellar connectivity. These findings suggest that for right-handed children, superior motor development depends on the establishment of left-hemisphere dominance in intrinsic motor network connectivity.     

Laterality of temporoparietal causal connectivity during the prestimulus period correlates with phonological decoding task performance in dyslexic and typical readers

We examined how effective connectivity into and out of the left and right temporoparietal areas (TPAs) to/from other key cortical areas affected phonological decoding in 7 dyslexic readers (DRs) and 10 typical readers (TRs) who were young adults. Granger causality was used to compute the effective connectivity of the preparatory network 500 ms prior to presentation of nonwords that required phonological decoding. Neuromagnetic activity was analyzed within the low, medium, and high beta and gamma subbands. A mixed-model analysis determined whether connectivity to or from the left and right TPAs differed across connectivity direction (in vs. out), brain areas (right and left inferior frontal and ventral occipital-temporal and the contralateral TPA), reading group (DR vs. TR), and/or task performance. Within the low beta subband, better performance was associated with increased influence of the left TPA on other brain areas across both reading groups and poorer performance was associated with increased influence of the right TPA on other brain areas for DRs only. DRs were also found to have an increase in high gamma connectivity between the left TPA and other brain areas. This study suggests that hierarchal network structure rather than connectivity per se is important in determining phonological decoding performance.     

Modulation of ventral prefrontal cortex functional connections reflects the interplay of cognitive processes and stimulus characteristics

Emerging ideas of brain function emphasize the context-dependency of regional contributions to cognitive operations, where the function of a particular region is constrained by its pattern of functional connectivity. We used functional magnetic resonance imaging to examine how modality of input (auditory or visual) affects prefrontal cortex (PFC) functional connectivity for simple working memory tasks. The hypothesis was that PFC would show contextually dependent changes in functional connectivity in relation to the modality of input despite similar cognitive demands. Participants were presented with auditory or visual bandpass-filtered noise stimuli, and performed 2 simple short-term memory tasks. Brain activation patterns independently mapped onto modality and task demands. Analysis of right ventral PFC functional connectivity, however, suggested these activity patterns interact. One functional connectivity pattern showed task differences independent of stimulus modality and involved ventromedial and dorsolateral prefrontal and occipitoparietal cortices. A second pattern showed task differences that varied with modality, engaging superior temporal and occipital association regions. Importantly, these association regions showed nonzero functional connectivity in all conditions, rather than showing a zero connectivity in one modality and nonzero in the other. These results underscore the interactive nature of brain processing, where modality-specific and process-specific networks interact for normal cognitive operations.     

Dissociating the roles of right ventral lateral and dorsal lateral prefrontal cortex in generation and maintenance of hypotheses in set-shift problems

Although patient data have traditionally implicated the left prefrontal cortex (PFC) in hypothesis generation, recent lesion data implicate right PFC in hypothesis generation tasks that involve set shifts (lateral transformations). To test the involvement of the right prefrontal cortex in a hypothesis generation task involving set shifts, we scanned 13 normal subjects with fMRI as they completed Match Problems (a classic divergent thinking task) and a baseline task. In Match Problems subjects determined the number of possible solutions for each trial. Successful solutions are indicative of set shifts. In the baseline condition subjects evaluated the accuracy of hypothetical solutions to match problems. A comparison of Match Problems versus baseline trials revealed activation in right ventral lateral PFC (BA 47) and left dorsal lateral PFC (BA 46). A further comparison of successfully versus unsuccessfully completed Match Problems revealed activation in right ventral lateral PFC (BA 47), left middle frontal gyrus (BA 9) and left frontal pole (BA 10), thus identifying the former as a critical component of the neural mechanisms of set-shift transformation. By contrast, activation in right dorsal lateral PFC (BA 46) covaried as a function of the number of solutions generated in Match Problems, possibly due to increased working memory demands to maintain multiple solutions 'on-line', conflict resolution, or progress monitoring. These results go beyond the patient data by identifying the ventral lateral (BA 47) aspect of right PFC as being a critical component of the neural systems underlying lateral transformations, and demonstrate a dissociation between right VLPFC and DLPFC in hypotheses generation and maintenance.     

Differential functions of lateral and medial rostral prefrontal cortex (area 10) revealed by brain-behavior associations

We analyzed the behavioral data from 104 neuroimaging studies using positron emission tomography or functional magnetic resonance imaging that reported activation peaks in rostral prefrontal cortex (PFC), approximating Brodmann's area 10. The distribution of absolute x coordinates of activation peaks (i.e., x coordinate regardless of hemisphere) differed significantly from a unimodal normal distribution, reflecting distinct clusters of activation in lateral and medial subregions. These 2 clusters were associated with different patterns of behavioral data. Lateral activations were associated with contrasts between experimental and control conditions where response times (RTs) were slower in the experimental condition. Medial activations were associated with contrasts where RTs were, if anything, faster in experimental than control conditions. These findings place important constraints on theories of rostral PFC functions.     

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.     

Anterior prefrontal cortex mediates rule learning in humans

Despite a need for rule learning in everyday life, the brain regions involved in explicit rule induction remain undetermined. Here we use event-related functional magnetic resonance imaging to measure learning-dependent neuronal responses during an explicit categorization task. Subjects made category decisions, with feedback, to exemplar letter strings for which the rule governing category membership was periodically changed. Bilateral fronto-polar prefrontal cortices were selectively engaged following rule change. This activation pattern declined with improving task performance reflecting rule acquisition. The vocabulary of letters comprising the exemplars was also periodically changed, independently of rule changes. This exemplar change modulated activation in left anterior hippocampus. Our finding that fronto-polar cortex mediates rule learning supports a functional contribution of this region to generic reasoning and problem-solving behaviours.     

Multifocal glioma of the brain--an autopsy case

This is an autopsy case report of a 76 year old woman with multifocal glioblastoma multiforme. CT scan revealed three separate mass lesions in the left temporal lobe, left parietal lobe and right fronto-parietal lobes. CT-guided needle biopsy of the right fronto-parietal mass revealed glioblastoma multiforme. At autopsy, serial horizontal sections of the brain confirmed the CT scan findings and demonstrated extension of the tumor in the left parietal lobe to the subarachnoid space. The lesion in the right fronto-parietal region infiltrated a large area and was not demarcated. Microscopic examination of all three lesions revealed glioblastoma multiforme. The left temporal lobe tumor consisted of gemistocytic astrocytes predominantly. Reaction of the tumor to glial fibrillary acid protein (GFAP) antibody ranged from markedly positive in the gemistocytic astrocytes to negative in the anaplastic cells. The reported incidence of multifocal glioma is about 2-10%. The main pathophysiologic mechanisms invoked for this phenomenon are simultaneous neoplastic transformation and seeding from one tumor. The pathophysiology of this particular case is discussed in reference to the differences in the histopathology of the 3 separate foci of glioblastoma multiforme.     

Functional specializations in lateral prefrontal cortex associated with the integration and segregation of information in working memory

Control processes are thought to play an important role in working memory (WM), by enabling the coordination, transformation, and integration of stored information. Yet little is known about the neural mechanisms that subserve such control processes. This study examined whether integration operations within WM involve the activation of distinct neural mechanisms within lateral prefrontal cortex (PFC). Event-related functional magnetic resonance imaging was used to monitor brain activity while participants performed a mental arithmetic task. In the integration (IN) condition, a WM preload item had to be mentally inserted into the last step of the math problem. This contrasted with the segregation (SG) condition, which also required maintenance of the WM preload while performing mental arithmetic but had no integration requirement. Two additional control conditions involved either ignoring the preload (math only condition) or ignoring the math problem (recall only condition). Left anterior PFC (Brodmann's Area [BA] 46/10) was selectively engaged by integration demands, with activation increasing prior to, as well as during the integration period. A homologous right anterior PFC region showed selectively increased activity in the SG condition during the period in which the math problem and preload digit were reported. Left middorsolateral PFC regions (BA 9/46) showed increased, but equivalent, activity in both the SG and IN conditions relative to both control conditions. These results provide support for the selective role of lateral PFC in cognitive control over WM and suggest more specific hypotheses regarding dissociable PFC mechanisms involved during the integration and segregation of stored WM items.