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Biomedical subjects

Yasushi Miyashita

Publications and source records attributed to Yasushi Miyashita.

At least 19 recordsLinked to original sources

Activation of right inferior frontal gyrus during response inhibition across response modalities.

The go/no-go task, which effectively taps the ability to inhibit prepotent response tendency, has consistently activated the lateral prefrontal cortex, particularly the right inferior frontal gyrus (rIFG). On the other hand, rIFG activation has rarely been reported in the antisaccade task, seemingly an oculomotor version of the manual go/no-go task. One possible explanation for the variable IFG activation is the modality difference of the two tasks: The go/no-go task is performed manually, whereas the antisaccade task is performed in the oculomotor modality. Another explanation is that these two tasks have different task structures that require different cognitive processes: The traditional antisaccade task requires (i) configuration of a preparatory set prior to antisaccade execution and (ii) response inhibition at the time of antisaccade execution, whereas the go/no-go task requires heightened response inhibition under a minimal preparatory set. To test these possibilities, the traditional antisaccade task was modified in the present functional magnetic resonance imaging study such that it required heightened response inhibition at the time of antisaccade execution under a minimal preparatory set. Prominent activation related to response inhibition was observed in multiple frontoparietal regions, including the rIFG. Moreover, meta-analyses revealed that the rIFG activation in the present study was observed in the go/no-go tasks but not in the traditional antisaccade task, indicating that the rIFG activation was sensitive to the task structure difference, but not to the response modality difference. These results suggest that the rIFG is part of a network active during response inhibition across different response modalities.

Adult↗

Exploring the neural basis of cognition: multi-modal links between human fMRI and macaque neurophysiology.

Although functional magnetic resonance imaging (fMRI) with sophisticated behavioral paradigms has enabled the investigation of increasingly higher-level cognitive functions in humans, these studies seem to lose touch with neurophysiological studies in macaque monkeys. The application of fMRI and other MRI-based techniques to macaque brains allows studies in the two species to be linked. fMRI in human and macaque subjects using equivalent cognitive tasks enables direct comparisons of the functional brain architecture, even for high-level cognitive functions. Combinations of functional or structural MRI and microelectrode techniques provide ways to explore functional brain networks at multiple spatiotemporal scales. These approaches would illuminate the neurophysiological underpinnings of human cognitive functions by integrating human functional neuroimaging with macaque single-unit recordings.

Animals↗

MRI-based localization of electrophysiological recording sites within the cerebral cortex at single-voxel accuracy.

The localization of microelectrode recording sites in the layers of primate cerebral cortex permits the analysis of relationships between recorded neuronal activities and underlying anatomical connections. We present a magnetic resonance imaging method for precise in vivo localization of cortical recording sites. In this method, the susceptibility-induced effect thickens the appearance of the microelectrode and enhances the detectability of the microelectrode tip, which usually occupies less than a few percent of the volume of an image voxel. In a phantom study, the optimized susceptibility-induced effect allowed tip detection with single-voxel accuracy (in-plane resolution, 50 mum). We applied this method to recording microelectrodes inserted into the brains of macaque monkeys, and localized the microelectrode tip at an in-plane resolution of 150 mum within the cortex of 2-3 mm in thickness. Subsequent histological analyses validated the single-voxel accuracy of the in vivo tip localization. This method opens up a way to investigate information flow during cognitive processes in the brain.

Animals↗

Ventricular fibrillation due to severe hypokalemia induced by steroid treatment in a patient with thyrotoxic periodic paralysis.

We report a 25-year-old Japanese man with ventricular fibrillation associated with severe hypokalemia. He developed arm and leg paralysis. He had received 2 g of methylprednisolone because thoracic epidural hematoma had been suspected in another hospital. His serum potassium was 0.8 mEq/l on arrival at our hospital. Half an hour after arrival ventricular fibrillation occurred. Treatment with electric defibrillation 8 times was successful. Afterward Graves' disease was diagnosed, therefore, his clinical symptom was diagnosed as thyrotoxic periodic paralysis. We considered that the unusual condition of hyperthyroid-related hypokalemia worsened by steroid therapy induced the ventricular fibrillation.

Adult↗

Active maintenance of associative mnemonic signal in monkey inferior temporal cortex.

We investigated the contribution of the inferior temporal (IT) cortical neurons to the active maintenance of internal representations. The activity of single neurons in the IT cortex was recorded while the monkeys performed a sequential-type associative memory task in which distractor stimuli interrupted the delay epoch between the cue and target (paired-associate) stimuli. For each neuron, information about each stimulus conveyed by the delay activity was estimated as a coefficient of multiple regression analysis. We found that target information derived from long-term memory (LTM) persisted despite the distractors. By contrast, cue information derived from the visual system was attenuated and frequently replaced by distractor information. These results suggest that LTM-derived information required for upcoming behavior is actively maintained in the IT neurons, whereas visually derived information tends to be updated irrespective of behavioral relevance.

Animals↗

Dynamically modulated spike correlation in monkey inferior temporal cortex depending on the feature configuration within a whole object.

The mechanism underlying the processing of spatially separated multiple local features to form a unique whole object is an important issue in visual object recognition. We tested whether, in behaving monkeys, the spike correlation between pairs of inferior temporal (IT) neurons dynamically changes depending on the spatial configuration of the local features within a whole object. We prepared more than 60,000 face-like objects (FOs) and their corresponding non-face-like objects (NFOs) that consisted of random arrangements of the same set of local features as those in FOs. The spike correlation between a pair of neurons was quantified by the peak height of the shift predictor-subtracted cross-correlogram. For both neurons of the pair, the local features in a whole object were determined so that they elicited as high a response as possible to enable a reliable cross-correlation analysis. We found that the FOs thus constructed elicited neuronal activities that were more strongly correlated than the corresponding NFOs. Firing rates of the same neurons did not show such a consistent bias depending on the feature configuration. Furthermore, receiver operating characteristic analysis revealed that this FO dominance of spike correlation was robust enough to discriminate between different feature configurations at the population level. Spike correlation of the cell pairs exhibited significant FO dominance within 300 ms after stimulus onset. The present results suggest that feature configuration within a unique whole object can be reflected in the rapid modulation of spike correlation among a population of neurons in the IT cortex.

Action Potentials↗

Neural mechanism in anterior prefrontal cortex for inhibition of prolonged set interference.

Once one cognitive set dominates our behavior, it continues to influence subsequent behavior for a while even after a task to be performed is changed to another. Despite abundant knowledge of the inhibitory mechanisms that are recruited at the first trial after the change (the first inhibition trial), little is known about the inhibition of prolonged proactive interference from a previous set that lingers for several trials after the first inhibition trial. The present functional MRI study explored the neural mechanisms for inhibition of a previous set that were recruited after the first inhibition trial. A modified Wisconsin Card Sorting Test was used where "dual-match stimuli" were intermittently presented and allowed subjects to perform correctly based on previously appropriate, now inappropriate, responses. In response to the dual-match stimulus at "release" trials presented after the first inhibition trials, the subjects were transiently exempted from inhibiting the prolonged previous set. As expected from the exempted inhibitory demands, significant reaction time decrease was revealed in the release trials. Consistent with the behavioral results, transient signal decrease time-locked to the release trials was revealed in the left anterior part of the superior frontal sulcus. Moreover, the anterior prefrontal region was not sensitive to the task change, which exhibited a marked contrast to the left posterior inferior prefrontal region that showed significant signal changes in both events. These results revealed multiple inhibitory mechanisms in the lateral prefrontal cortex that are recruited in different temporal contexts of the interference from a previous cognitive set.

Adult↗

Activation shift from medial to lateral temporal cortex associated with recency judgements following impoverished encoding.

Recency judgements can be performed on the basis of across-event relational information that directly provides temporal order among past events. Non-relational item-based information internal to individual past events, such as information retrieved through familiarity, may also contribute to recency judgements. The present functional magnetic resonance imaging study examined neural substrates for item-based processing during recency judgements as an alternative to relational recency judgements. One half of word stimuli were encoded relationally prior to recency judgements, and the relational encoding of the other half was hampered such that the words were processed relatively in an item-based manner. Brain activity in the medial temporal lobe was observed during recency judgements for words studied with relational memory processing, whereas brain activity in the lateral temporal cortex was observed during recency judgements for words studied relatively in an item-based manner. It was revealed further that recognition of individual words per se, which can also be regarded as familiarity/recency judgements but is non-relational in nature, also activated the lateral temporal region. These results indicate multiple routes for recency judgements within the temporal lobe that are recruited depending on how past episodes are represented and retrieved for judgements of their temporal order.

Adult↗

Multiple components of lateral posterior parietal activation associated with cognitive set shifting.

Posterior parietal activation has commonly been observed in previous neuroimaging studies in association with flexible shifting of cognitive set. However, it is not clear whether the parietal activation reflects cognitive processes intrinsic to the shifting itself or other confounding factors such as spatial attention. To address this issue, the Wisconsin Card Sorting Task (WCST) was modified such that spatial components were eliminated from the sensory and motor aspects of the task. Moreover, a visual instruction of a next dimension was introduced to eliminate cognitive processes related to trial and error identification of a next rule, and a control null-instruction was also introduced to eliminate perceptual/oddball effects of the instruction cue. Localizer scans using a visually guided saccade task were also conducted to identify eye movement/spatial attention-related areas. Activity related to set shifting with trial and error was revealed in the lateral parts of the intraparietal regions, while activity related to eye movements/spatial attention was revealed in the medial parts of the intraparietal regions, confirming little spatial contribution to the modified WCST as indexed by the double dissociation. The lateral intraparietal activity was bilateral, but when the instructed shifting was contrasted with the null-instructed shifting to purify the shift-related activity further, the left intraparietal activation was significantly greater than that in the right hemisphere. These results reveal the left hemisphere dominance of purified shifting-related activity in the lateral posterior parietal cortex that may cooperate with the lateral prefrontal cortex whose left hemisphere dominance has already been reported.

Adult↗

Cognitive memory: cellular and network machineries and their top-down control.

A brain-wide distributed network orchestrates cognitive memorizing and remembering of explicit memory (i.e., memory of facts and events). The network was initially identified in humans and is being systematically investigated in molecular/genetic, single-unit, lesion, and imaging studies in animals. The types of memory identified in humans are extended into animals as episodic-like (event) memory or semantic-like (fact) memory. The unique configurational association between environmental stimuli and behavioral context, which is likely the basis of episodic-like memory, depends on neural circuits in the medial temporal lobe, whereas memory traces representing repeated associations, which is likely the basis of semantic-like memory, are consolidated in the domain-specific regions in the temporal cortex. These regions are reactivated during remembering and contribute to the contents of a memory. Two types of retrieval signal reach the cortical representations. One runs from the frontal cortex for active (or effortful) retrieval (top-down signal), and the other spreads backward from the medial temporal lobe for automatic retrieval. By sending the top-down signal to the temporal cortex, frontal regions manipulate and organize to-be-remembered information, devise strategies for retrieval, and also monitor the outcome, with dissociated frontal regions making functionally separate contributions. The challenge is to understand the hierarchical interactions between these multiple cortical areas, not only with a correlational analysis but also with an interventional study demonstrating the causal necessity and the direction of the causality.

Animals↗

Functional magnetic resonance imaging of macaque monkeys performing visually guided saccade tasks: comparison of cortical eye fields with humans.

The frontal and parietal eye fields serve as functional landmarks of the primate brain, although their correspondences between humans and macaque monkeys remain unclear. We conducted fMRI at 4.7 T in monkeys performing visually-guided saccade tasks and compared brain activations with those in humans using identical paradigms. Among multiple parietal activations, the dorsal lateral intraparietal area in monkeys and an area in the posterior superior parietal lobule in humans exhibited the highest selectivity to saccade directions. In the frontal cortex, the selectivity was highest at the junction of the precentral and superior frontal sulci in humans and in the frontal eye field (FEF) in monkeys. BOLD activation peaks were also found in premotor areas (BA6) in monkeys, which suggests that the apparent discrepancy in location between putative human FEF (BA6, suggested by imaging studies) and monkey FEF (BA8, identified by microstimulation studies) partly arose from methodological differences.

Analysis of Variance↗

Dissociable concurrent activity of lateral and medial frontal lobe during negative feedback processing.

External feedback on results of one's behavior guides flexible adaptation to changing environments. It has been suggested that the lateral and medial parts of the frontal lobe are responsible for cognitive and emotional functions, respectively. In the present fMRI study, multiple mental components evoked by the presentation of negative feedback were dissociated along the cognitive-emotional axis in set-shifting paradigms. The double dissociation of the concurrent feedback-related activity was observed in the right frontal lobe: the lateral frontal lobe was associated with the inferential component, whereas the medial frontal lobe was associated with the emotional component. However, among the multiple right lateral frontal regions, a region of interest (ROI) analysis indicated that the inferential component was not dominant in the region near the inferior frontal junction. The medial frontal activations were observed ventral and anterior to the presupplementary motor area, and dorsal and posterior to the anterior cingulate cortex. The double dissociation in the right frontal lobe suggests that the lateral and medial frontal lobe cooperatively but differentially contributes to the negative feedback processing, demonstrating the lateral-medial dichotomy of the frontal lobe functions suggested by previous neuropsychological studies. At the same time, the functional heterogeneity in the lateral and medial frontal lobe demands modifications of the traditional view of the functional organization of the frontal lobe.

Adult↗

Temporal lobe activations of "feeling-of-knowing" induced by face-name associations.

"Feeling-of-Knowing" (FOK) refers to the sense of what one knows and is a component of the human metamemory system. We investigated the neural correlates of the FOK induced by face-name associations using the Recall-Judgment-Recognition paradigm. Data were gathered using event-related functional magnetic resonance imaging (fMRI). We analyzed the fMRI data with parametric analyses of six FOK ratings while compensating for the effects of unbalanced response latencies among trials ("variable duration parametric analysis"). Regions showing a significant linear relationships with the FOK ratings (FOK regions) were the bilateral ventral, dorsal, and anterior prefrontal regions; the medial frontal regions; the medial surface regions; the left parietal regions; the bilateral superior temporal and nearby regions; the right anterior temporal region; and the bilateral thalami/basal ganglia. Most of the active areas in the prefrontal regions were common to those found in our previous FOK studies of general knowledge (Kikyo, H., Ohki, K., Miyashita, Y., 2002. Neural correlates for feeling-of-knowing: an fMRI parametric analysis. Neuron 36, 177-186). However, in this study, we found robust activations of the temporal regions near to the regions that were related to the higher-order information processing of face images or semantic information processing of the to-be-recalled person. Those results suggest that the information related to the higher-order visual features of a face, which was represented in the temporal cortex, was activated by the top-down signal from the prefrontal cortex, and that this cooperation between the temporal and prefrontal cortices may contribute to the FOK.

Adult↗

Prefrontal neuronal activity encodes spatial target representations sequentially updated after nonspatial target-shift cues.

We examined prefrontal neuronal activity while monkeys performed a sequential target-shift task, in which, after a positional cue indicated the initial saccade target among 8 peripheral positions, the monkeys were required to internally shift the target by one position on every flash of a target-shift cue. The target-shift cue appeared in the center 0 to 3 times within a single trial and was always the same in shape, size, and color. We found selective neuronal activity related to the target position: when the target-shift cue implied the target shift to particular peripheral positions, neurons exhibited early-dominant and late-dominant activity during the following delay period. The early-dominant target-selective activity emerged early in the delay just after the presentation of the target-shift cue, whereas the late-dominant activity gradually built up toward the end of the delay. Because the target-shift cue was not related to any specific target location, the early-dominant target-selective activity could not be a mere visual response to the target-shift cue. We suggest that the early-dominant activity reflects the transitory representation for the saccade target that was triggered by the nonspatial target-shift cue, whereas the late-dominant activity reflects the target representation in the spatial working memory or the preparatory set for the possible impending saccade, being repeatedly updated during sequential target shifts.

Animals↗

Transient activation of superior prefrontal cortex during inhibition of cognitive set.

The prefrontal cortex implements a set-shifting function that includes inhibition of a previously acquired cognitive set. The impairment of the inhibitory function results in perseverative behavior that forms one characteristic feature of frontal lobe dysfunction. Previous neuroimaging studies have revealed inhibitory mechanisms in the inferior prefrontal cortex. The present functional magnetic resonance imaging study devised "dual-match" stimuli in a set-shifting paradigm that allowed us to temporally isolate the inhibitory processes recruited during exposure to a previously acquired set. Transient activation time-locked to the isolated inhibition was revealed in the left middle frontal gyrus near the superior frontal sulcus. In a control experiment conducted after subjects had been informed and made aware of the exposure, however, the superior prefrontal activation disappeared, and prominent activation was revealed in a set of brain regions that included the left posterior inferior frontal sulcus. These double dissociation results indicate inhibitory mechanisms in the superior prefrontal cortex, alternative to the inferior prefrontal ones, that are activated depending on the subjects' strategy for inhibition of cognitive set.

Adult↗

Conversion of working memory to motor sequence in the monkey premotor cortex.

To plan a serial order behavior, we hold serial sensory information in our minds and convert it to a movement program. We trained monkeys to memorize a sequence of positional cues and to reproduce it by making saccades in either the original or reverse order. The order was determined in the middle of a trial on the basis of an instruction stimulus. Triggered by the instruction stimulus, single neurons in the dorsal premotor cortex became transiently active only when the order needed to be determined. These transient neurons, together with nearby sustained neurons that hold information on cue or movement sequences, appear to mediate the generation of a motor program from the maintained information.

Animals↗