Kosuke Itoh

Object discrimination learning in aged Japanese monkeys.

The authors investigated the behavioral aging effects of Japanese macaques in 3 object discrimination learning tasks: learning-set (LS) formation, go/no-go discrimination learning, and multiple discrimination reversals. Aged monkeys showed deteriorated performance in these tasks compared with younger controls. Hypothesis analysis of LS showed that aged monkeys had difficulty learning the lose-shift component of the hypothesis win-stay-lose-shift with respect to object. Deficits in go/no-go successive discrimination were clear in no-go trials only in the first 2 pairs of 5 tasks. Performance of aged monkeys was severely disturbed from a chance to criterion level in discrimination reversals. These results are attributed not only to increased tendency for perseveration but also to difficulty in associating the reward and the object in aged monkeys and may be related to the decline in the functions of the ventral frontal cortex.

Asymmetry of parietal lobe activation during piano performance : a high field functional magnetic resonance imaging study

Functional asymmetry of the parietal lobes during piano performance was assessed utilizing independent component-cross correlation-sequential epoch analysis of functional magnetic resonance imaging time series. Eight right handed musically trained subjects played the piano with their right hand, left hand, or both hands as cued by visually presented musical scores. The areas activated included the posterior parietal cortex (PPC) and the primary sensorimotor areas (SM1). While unilateral SM1 activation was correlated to motion of the corresponding contralateral hand, PPC activation was correlated to piano performance irrespective of hand modality. Furthermore, PPC activation exhibited significant asymmetry, with left hemisphere dominance. The results indicate that the left parietal lobe plays a significant role in the cortical processes of piano performance.

Electrophysiological correlates of grapheme-phoneme conversion

The cortical processes underlying grapheme-phoneme conversion were investigated by event-related potentials (ERPs). The task consisted of silent reading or vowel-matching of three Japanese hiragana characters, each representing a consonant-vowel syllable. At earlier latencies, typical components of the visual ERP, namely, P1 (110 ms), N1 (170 ms) and P2 (300 ms), were elicited in the temporo-occipital area for both tasks as well as control task (observing the orthographic shapes of three Korean characters). Following these earlier components, two sustained negativities were identified. The earlier sustained negativity, referred here to as SN1, was found in both the silent-reading and vowel-matching task but not in the control task. The scalp distribution of SN1 was over the left occipito-temporal area, with maximum amplitude over O1. The amplitude of SN1 was larger in the vowel-matching task compared to the silent-reading task, consistent with previous reports that ERP amplitude correlates with task difficulty. SN2, the later sustained negativity, was only observed in the vowel-matching task. The scalp distribution of SN2 was over the midsagittal centro-parietal area with maximum amplitude over Cz. Elicitation of SN2 in the vowel-matching task suggested that the vowel-matching task requires a wider range of neural activities exceeding the established conventional area of language processing.

Effects of musical training on the early auditory cortical representation of pitch transitions as indexed by change-N1

The effects of musical training on the early auditory cortical response to pitch transitions in music were investigated by use of the change‐N1 component of auditory event‐related potentials. Musicians and non‐musicians were presented with music stimuli comprising a melody and a harmony under various listening conditions. First, when the subjects played a video game and were instructed to ignore the auditory stimuli, the onset of stimuli elicited a typical, fronto‐central onset‐N1, whereas melodic and harmonic pitch transitions within the stimuli elicited so‐called change‐N1s that were more posterior in scalp distribution. The pitch transition change‐N1s, but not onset‐N1, were enhanced in musicians. Second, when the listeners attended to the same stimuli as above to detect infrequently occurring target stimuli, the change‐N1 elicited by pitch changes (in non‐target stimuli) was augmented, in non‐musicians only when the target was easily detectable, and in both musicians and non‐musicians when it was difficult to detect. Thus, the early, obligatory cortical response to pitch transitions during passive listening was chronically enhanced by training in musicians, and, reflecting this training‐induced enhancement, the task‐related modulation of this response was also different between musicians and non‐musicians. These results are the first to demonstrate the long‐term effects of training, short‐term effects of task and the effects of their interaction on the early (~100‐ms) cortical processing of pitch transitions in music. The scalp distributions of these enhancement effects were generally right dominant at temporal electrode sites, suggesting contributions from the radially oriented subcomponent of change‐N1, namely, the Tb (N1c) wave of the T‐complex.

Ear advantage and consonance of dichotic pitch intervals in absolute-pitch possessors

Left-right asymmetry in the central processing of musical consonance was investigated by dichotic listening tasks. Two piano tones paired at various pitch intervals (1-11 semitones) were presented one note in each ear to twenty absolute-pitch possessors. As a result, a weak overall trend for left ear advantage (LEA) was found, as is characteristic of trained musicians. Second, pitches of dissonant intervals were more difficult to identify than those of consonant intervals. Finally, the LEA was greater with dissonant intervals than with consonant intervals. As the tones were dichotically presented, the results indicated that the central auditory system could distinguish between consonant and dissonant intervals without initial processing of pitch-pitch relations in the cochlea.

Functional asymmetry in primary auditory cortex for processing musical sounds: temporal pattern analysis of fMRI time series

Hemispheric differences in the temporal processing of musical sounds within the primary auditory cortex were investigated using functional magnetic resonance imaging (fMRI) time series analysis on a 3.0 T system in right-handed individuals who had no formal training in music. The two hemispheres exhibited a clear-cut asymmetry in the time pattern of fMRI signals. A large transient signal component was observed in the left primary auditory cortex immediately after the onset of musical sounds, while only sustained activation, without an initial transient component, was seen in the right primary auditory cortex. The observed difference was believed to reflect differential segmentation in primary auditory cortical sound processing. Although the left primary auditory cortex processed the entire 30-s musical sound stimulus as a single event, the right primary auditory cortex had low-level processing of sounds with multiple segmentations of shorter time scales. The study indicated that musical sounds are processed as ‘sounds with contents’, similar to how language is processed in the left primary auditory cortex.

Neural substrates for visual pattern recognition learning in Igo

Different contexts require different visual pattern recognitions even for identical retinal inputs, and acquiring expertise in various visual-cognitive skills requires long-term training to become capable of recognizing relevant visual patterns in otherwise ambiguous stimuli. This 3-Tesla fMRI experiment exploited shikatsu-mondai (life-or-death problems) in the Oriental board game of Igo (Go) to identify the neural substrates supporting this gradual and adaptive learning. In shikatsu-mondai, the player adds stones to the board with the objective of making, or preventing the opponent from making nigan (two eyes), or the topology of figure of eight, with these stones. Without learning the game, passive viewing of shikatsu-mondai activated the occipito-temporal cortices, reflecting visual processing without the recognition of nigan. Several days after two-hour training, passive viewing of the same stimuli additionally activated the premotor area, intraparietal sulcus, and a visual area near the junction of the (left) intraparietal and transverse occipital sulci, demonstrating plastic changes in neuronal responsivity to the stimuli that contained indications of nigan. Behavioral tests confirmed that the participants had successfully learned to recognize nigan and solve the problems. In the newly activated regions, the level of neural activity while viewing the problems correlated positively with the level of achievement in learning. These results conformed to the hypothesis that recognition of a newly learned visual pattern is supported by the activities of fronto-parietal and visual cortical neurons that interact via newly formed functional connections among these regions. These connections would provide the medium by which the fronto-parietal system modulates visual cortical activity to attain behaviorally relevant perceptions.

Assessment of Individual Differences in the Preferred Proximity to a Human Feeder by Partitioned Raisin Test, with Two Species of Macaque Monkeys

All animals must acquire food and mates by approaching them despite possibilities of accompanying risks and thus are frequently encountered with approach-avoidance conflicts in daily lives. Behavioral individual differences in such situations may be considered as one of the most biologically fundamental personality trains. “Partitioned raisin test” was devised to assess this trait with macaque monkeys. It involved throwing raisins into groups of monkeys and observing the preferred distance of each from the human feeder, a source of possible harm. The test was administered to 4 groups of Japanese monkeys (30 total) and 3 groups of rhesus monkeys (19 total), all l-yr-old and matched in history. Individual differences in the preferred proximity to the feeder, as expressed by the Proximity Index (PI), were found in both species.PI was not correlated with a measure of dominance over the raisins. Individual differences inPI were also not due to territorial effects unrelated to the location of the feeder.PI was stable in five of the six monkeys re-tested after one year of interval in a newly organized group, where there supposedly had been a change in their social structure. Partitioned raisin test was shown to be capable of depicting individual differences related to differential approach bias in an approach-avoidance conflict situation. Although possible confounding effects by social factors need to be delineated in the following studies, the method may provide a handy and widely applicable way for the assessment of this trait with monkeys.

Evidence for cerebellar motor functional reorganization in brain tumor patients: An fMRI study

Functional reorganization of the motor system following brain damage has been studied extensively in stroke patients, in which not only the cerebrum but also the cerebellum (Cbll) undergoes substantial reorganization. However, the role of Cbll in motor functional reorganization in brain tumor patients remains poorly investigated. Because brain damages in brain tumor patients occur much more slowly than in stroke patients, the neural mechanisms for motor functional reorganization might differ between these two disease conditions. This functional magnetic resonance imaging (fMRI) study investigated whether Cbll constitutes the neural substrates for motor functional reorganization in eighteen supratentorial brain tumor patients who exhibited no clinical signs of paresis. The patients and normal volunteers underwent a unilateral hand movement task. In the patients, the locus of primary sensory motor (SM1) activation during contralesional hand movement was significantly displaced by the tumor, suggesting functional compromise and/or reorganization in the central sulcus region. In addition, their contralesional Cbll activation during contralesional hand movement was substantially increased as compared to normal controls. The finding represents the first conclusive evidence that Cbll is involved in the motor-related functional reorganization in patients with brain tumor.

Effects of Alda-1, an Aldehyde Dehydrogenase-2 Agonist, on Hypoglycemic Neuronal Death

Hypoglycemic encephalopathy (HE) is caused by a lack of glucose availability to neuronal cells, and no neuroprotective drugs have been developed as yet. Studies on the pathogenesis of HE and the development of new neuroprotective drugs have been conducted using animal models such as the hypoglycemic coma model and non-coma hypoglycemia model. However, both models have inherent problems, and establishment of animal models that mimic clinical situations is desirable. In this study, we first developed a short-term hypoglycemic coma model in which rats could be maintained in an isoelectric electroencephalogram (EEG) state for 2 min and subsequent hyperglycemia without requiring anti-seizure drugs and an artificial ventilation. This condition caused the production of 4-hydroxy-2-nonenal (4-HNE), a cytotoxic aldehyde, in neurons of the hippocampus and cerebral cortex, and a marked increase in neuronal death as evaluated by Fluoro-Jade B (FJB) staining. We also investigated whether N-(1,3-benzodioxole-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1), a small-molecule agonist of aldehyde dehydrogenase-2, could attenuate 4-HNE levels and reduce hypoglycemic neuronal death. After confirming that EEG recordings remained isoelectric for 2 min, Alda-1 (8.5 mg/kg) or vehicle (dimethyl sulfoxide; DMSO) was administered intravenously with glucose to maintain a blood glucose level of 250 to 270 mg/dL. Fewer 4-HNE and FJB-positive cells were observed in the cerebral cortex of Alda-1-treated rats than in DMSO-treated rats 24 h after glucose administration (P = 0.002 and P = 0.020). Thus, activation of the ALDH2 pathway could be a molecular target for HE treatment, and Alda-1 is a potentially neuroprotective agent that exerts a beneficial effect on neurons when intravenously administered simultaneously with glucose.