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The Wisconsin Card Sorting Test (WCST) is the standard task paradigm to detect human frontal lobe dysfunction. In this test, subjects sort card stimuli with respect to one of three possible dimensions (color, form and number). These dimensions are changed intermittently, whereupon subjects are required to identify by trial and error a new correct dimension and flexibly shift cognitive set. We decomposed the cognitive requirements at the time of the dimensional changes of the WCST, using functional magnetic resonance imaging (fMRI). By explicitly informing subjects of a new correct dimension, the working memory load for the trial-and-error identification of the new dimensional was removed. Event-related fMRI still revealed transient activation time-locked to the dimensional changes in areas in the posterior part of the inferior frontal sulci. However, the activation was significantly smaller than in the original WCST in which subjects had to use working memory to identify the new dimension by trial and error. Furthermore, these areas were found to spatially overlap the areas activated by a working memory task. These results suggest that working memory and set-shifting act cooperatively in the same areas of prefrontal cortex to adapt us to changing environments. [ABSTRACT FROM AUTHOR]

Background and Purpose: Pure midbrain stroke can cause isolated unilateral oculomotor paresis. We attempted to determine whether there is a difference in the oculomotor paresis pattern between pure midbrain infarction and midbrain hemorrhage., Methods: Pure midbrain stroke patients who presented with isolated unilateral oculomotor paresis were identified from a group of 2447 consecutive patients hospitalized for acute cerebral infarction or hemorrhage during the period May 2008 through April 2014. Detailed oculomotor findings were evaluated in the identified patients per the cause of the stroke., Results: Five patients with infarct and 1 with hemorrhage became our study subjects. Lesions were located in the paramedian area of the midbrain involving the oculomotor fascicles. The pupillary sphincter and inferior rectus muscles were selectively spared in the infarct patients, whereas these muscles were selectively affected in the hemorrhage patient., Conclusion: Fibers in the oculomotor fascicle that innervate the levator palpebrae, superior rectus, and inferior oblique muscles appear to be more susceptible to ischemic damage than those that innervate the pupillary sphincter and inferior rectus muscles. Isolated impairment of the pupillary sphincter and inferior rectus muscles may be suggestive of a non-ischemic process., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Purpose: Unilateral gaze palsy associated with internuclear ophthalmoplegia (INO), i.e., one-and-a-half syndrome, is well known. Exotropia can also be associated with INO, but it has been reported only rarely. We sought to determine the frequencies and courses of gaze palsy and exotropia in INO., Methods: Patients hospitalized with acute-onset INO during the period January 2009 through December 2013 were identified from our clinical registry. Associated gaze palsy and exotropia were evaluated in the identified patients., Results: Twenty-five patients with unilateral INO and 7 patients with bilateral INO were included in this study. Of the 25 patients with unilateral INO, 4 (16.0.0%) had ipsilateral gaze palsy (one-and-a-half syndrome), 8 (32.0%) had exotropia (non-paralytic pontine exotropia), and 6 (24.0%) had both ipsilateral gaze palsy and exotropia (paralytic pontine exotropia). Six (85.7%) of the 7 patients with bilateral INO had exotropia. The gaze palsy persisted more than 1 week in 40.0% of patients, whereas the exotropia disappeared within 1 week in 92.9% of patients when the INO was unilateral., Conclusion: Exotropia is not uncommon in the acute stage of INO. However, it is often overlooked because of its short duration., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Several animal studies have demonstrated functional roles of dopamine (DA) D1 and D2 receptors in amygdala activity. However, the contribution of DA D1 and D2 receptors to amygdala response induced by affective stimuli in human is unknown. To investigate the contribution of DA receptor subtypes to amygdala reactivity in human, we conducted a multimodal in vivo neuroimaging study in which DA D1 and D2 receptor bindings in the amygdala were measured with positron emission tomography (PET), and amygdala response induced by fearful faces was assessed by functional magnetic resonance imaging (fMRI) in healthy volunteers. We used multimodality voxelwise correlation analysis between fMRI signal and DA receptor binding measured by PET. DA D1 binding in the amygdala was positively correlated with amygdala signal change in response to fearful faces, but DA D2 binding in the amygdala was not related to amygdala signal change. DA D1 receptors might play a major role in enhancing amygdala response when sensory inputs are affective.

When we cannot recall the name of a well-known person despite preserved access to his/her semantic knowledge, a phonological hint such as his/her initials sometimes helps us to recall the name. This type of recall failure appeared to occur by the transmission deficit from the lexical-semantic stage to the lexical-phonological stage in name recall processes, and the phonological cue appeared to activate this transmission, which leads to successful recall. We hypothesized that the brain regions responsible for the transmission would respond to the phonological cue that facilitates name recall, and would also respond to successful recall. A famous face image was presented with a phonological cue, and the subjects were required to recall and overtly pronounce the name during fMRI scanning. The behavioral results showed that the first syllable cue induced greater number of successful recall trials than both the non-verbal sound of the chime and the non-first syllable cue, suggesting that the first syllable facilitated name recall. The fMRI results demonstrated that two regions in the left superior temporal gyrus responded more strongly to the first syllable than both to the non-verbal sound of the chime and to the non-first syllable. In addition, these two regions were activated when the name recall was successful. These results suggest that two regions in the left superior temporal gyrus may play a crucial role in the transmission from the lexical-semantic to the lexical-phonological stage in the name recall processes.

We investigated neural correlates of retrieval success for music memory using event-related functional magnetic resonance imaging. To minimize the interference from MRI scan noise, we used sparse temporal sampling technique. Newly composed music materials were employed as stimuli, which enabled us to detect regions in absence of effects of experience with the music stimuli in this study. Whole brain analyses demonstrated significant retrieval success activities in the right hippocampus, bilateral lateral temporal regions, left inferior frontal gyrus and left precuneus. Anatomically defined region-of-interests analyses showed that the activity of the right hippocampus was stronger than that of the left, while the activities of the inferior frontal gyri showed the reverse pattern. Furthermore, performance-based analyses demonstrated that the retrieval success activity of the right hippocampus was positively correlated with the corrected recognition rate, suggesting that the right hippocampus contributes to the accuracy of music retrieval outcome.

"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.

The "feeling-of-knowing" (FOK) is a subjective sense of knowing a word before recalling it, and the FOK provides us clues to understanding the mechanisms of human metamemory systems. We investigated neural correlates for the FOK based on the recall-judgment-recognition paradigm. Event-related functional magnetic resonance imaging with a parametric analysis was used. We found activations in left dorsolateral, left anterior, bilateral inferior, and medial prefrontal cortices that significantly increased as the FOK became greater, and the activations remained significant even when the potentially confounding factor of the response latency was removed. Furthermore, we demonstrated that the FOK region in the right inferior frontal gyrus and a subset of the FOK region in the left inferior frontal gyrus are not recruited for successful recall processes, suggesting their particular role in metamemory processing.

Functional organization of human cerebral hemispheres is asymmetrically specialized, most typically along a verbal/nonverbal axis. In this event-related functional MRI study, we report another example of the asymmetrical specialization. Set-shifting paradigms derived from the Wisconsin card sorting test were used, where subjects update one behavior to another on the basis of environmental feedback. The cognitive requirements constituting the paradigms were decomposed into two components according to temporal stages of task events. Double dissociation of the component brain activity was found in the three bilateral pairs of regions in the lateral frontal cortex, the right regions being activated during exposure to negative feedback and the corresponding left regions being activated during updating of behavior, to suggest that both hemispheres contribute to cognitive set shifting but in different ways. The asymmetrical hemispheric specialization within the same paradigms further implies an interhemispheric interaction of these task components that achieve a common goal.

"Tip of the tongue" (TOT) is a natural phenomenon in which people cannot retrieve a target word immediately, even though they feel confident that they know the target. This provides us an opportunity to understand the human memory system, because cognitive components of memory retrieval such as retrieval effort and successful retrieval are temporally dissociated from each other during the TOT states. The purpose of the present study was to reveal the neural correlates of the cognitive components of the retrieval process by separating cognitive phases of the TOT phenomenon using event-related functional magnetic resonance imaging with multiple regression analysis. We demonstrated that the left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex were activated at the time of successful retrieval, and the left DLPFC also showed activation when the subjects successfully retrieved the target names as compared to when they gave up. This result suggests that the left DLPFC is specific to the successful retrieval process. During the TOT state, a number of regions were activated, and this suggests that widely distributed brain regions are engaged when people make a hard effort to retrieve a proper name in the TOT state. Our new approach employing temporal resolution of the TOT phenomenon may contribute to the understanding of the mechanisms of the human memory system.

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

We investigated the early orthographic processing in the occipital cortex using Japanese morphogram by functional magnetic resonance imaging. Kanji (Japanese morphogram) is one system of character used in the Japanese language, each character of which has a specific meaning and pronunciations. To ensure that the effects of the general visual properties of Kanji were excluded from Kanji-related activation, we created strict control stimuli, the "scrambled Kanji" that had the same luminance, contrast, and retinotopical size as those of the original Kanji. In the Kanji vs scrambled Kanji task, we found significant activation in the left inferior occipital gyrus. However, we found no activation in earlier visual cortices, including the primary visual cortex, indicating that the scrambled Kanji served as an effective control stimulus for this task. In the Kanji vs blank screen task, much more areas, including earlier visual cortices, were activated. The activation that we found in the Kanji vs scrambled Kanji task was compatible with the results of previous studies of English letter strings by other groups, suggesting that the left inferior occipital gyrus plays an essential role in orthographic processing common to these two different writing systems., (Copyright 1999 Academic Press.)