Shizuka Horie

Differential roles of spatial frequency on reading processes for ideograms and phonograms: A high-density ERP study

The neural substrate of the dissociation between reading Japanese ideograms (Kanji) and phonograms (Kana) is currently unclear. To test whether spatial frequency (SF) information is responsible for this phenomenon, we recorded high-density event-related potentials (ERPs) with unfiltered or spatially filtered word stimuli in Japanese-speaking subjects. Kanji (early-learned, late-learned), Kana (word, non-word), and scrambled characters served as stimuli. Fourier analysis revealed that Kanji and Kana were characterized by high-SF (HSF) and low-SF (LSF) information, respectively. In ERPs with unfiltered stimuli, bilateral occipital P100, left occipitotemporal N170 and fronto-central N400 were elicited. Scrambled characters did not evoke left-lateralized N170 or clear N400. Under the LSF condition, P100 and N170 latencies for Kanji were significantly longer than those for Kana. In the HSF condition, P100 and N170 latencies for late-learned Kanji were significantly longer than those for early-learned Kanji. There was no significant difference in the N400 between Kanji and Kana in both SF conditions. These results suggest that early visual responses, but not the semantic component, are influenced by SF. This indicates a close link between Kana and LSF information, and between Kanji and HSF information. The differential effects of SF could underlie the neural basis of the differences between Kanji and Kana reading.

Relevance of in vivo neurophysiological biomarkers for mild cognitive impairment and Alzheimer's disease

Visuospatial dysfunction including defects in motion perception in Alzheimers disease (AD) and mild cognitive impairment (MCI) are clues to search for potential in vivo biomarkers. In this review, we focus on the clinical relevance of non-invasive neurophysiological findings in event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) to assess visual dysfunction in AD and MCI. We first summarize the current concept of the parallel visual pathways in primates and humans. Next, we outline the results of previous electrophysiological and fMRI studies on visual function in AD and MCI. Finally, we present the recent findings of our systematic ERP and fMRI approach to visual perception in AD and MCI. Our overview strongly indicates that visual impairments in patients with AD and MCI are mainly caused by dysfunction in higher-level parallel visual pathways. In particular, a deficit in ventro-dorsal stream function related to optic flow perception is responsible for the earliest and most prominent visual symptoms in MCI. Therefore, we conclude that ERP and fMRI measurements for visual perception can be used as in vivo biomarkers for early functional brain changes in MCI and AD patients.

Distinct role of spatial frequency in dissociative reading of ideograms and phonograms: An fMRI study

It has been proposed that distinct neural circuits are activated by reading Japanese ideograms (Kanji) and phonograms (Kana). By measuring high-density event-related potentials, we recently reported that spatial frequency (SF) information is responsible for the dissociation between Kanji and Kana reading. In particular, we found close links between Kana and low SF (LSF) information and between Kanji and high SF (HSF) information. However, it remains unclear which brain regions contribute to this dissociation. To determine this, we performed functional magnetic resonance imaging while presenting unfiltered or spatially filtered Kanji and Kana word stimuli to healthy native Japanese subjects. Fourier analysis revealed that Kanji and Kana stimuli were characterized by HSF and LSF information, respectively. When presented with either type of unfiltered stimulus (Kanji or Kana), the bilateral inferior temporal (IT, BA 37) regions were activated compared to the resting condition. Kana but not Kanji reading also activated the bilateral inferior parietal lobules (IPL, BA 40). When we compared Kanji and Kana reading directly, the left IT region was significantly activated by Kanji reading, while significant activation of the left IPL was observed during Kana reading. In response to filtered HSF stimuli, the Kanji reading minus Kana reading comparison revealed significant activation of the left IT region but not the left IPL. Conversely, significant activation of the left IPL but not the left IT region occurred in the Kana reading minus Kanji reading comparison for filtered LSF stimuli. These results suggest that Kanji and Kana engage a relatively overlapping network, within which the left IT is more involved in Kanji processing, while the left IPL contributes more to Kana processing. The preferential engagements of these brain regions could reflect the close links between Kana and LSF information, and between Kanji and HSF information. Therefore, this study provides further evidence that SF contributes to the dissociation between Kanji and Kana reading.

A Potential VEP Biomarker for Mild Cognitive Impairment: Evidence from Selective Visual Deficit of Higher-Level Dorsal Pathway

Visual dysfunctions are common in Alzheimers disease (AD). Our aim was to establish a neurophysiological biomarker for amnestic mild cognitive impairment (aMCI). Visual evoked potentials (VEPs) were recorded in aMCI patients who later developed AD (nu200a=u200a15) and in healthy older (nu200a=u200a15) and younger controls (nu200a=u200a15). Visual stimuli were optimized to separately activate lower and higher levels of the ventral and dorsal streams. We compared VEP parameters across the three groups of participants and conducted a linear correlation analysis between VEPs and data from neuropsychological tests. We then used a receiver operating characteristic (ROC) analysis to discriminate those with aMCI from those who were healthy older adults. The latency and phase of VEPs to lower-level stimuli (chromatic and achromatic gratings) were significantly affected by age but not by cognitive decline. Conversely, VEP latencies for higher-ventral (faces and kanji-words) and dorsal (kana-words and optic flow motion) stimuli were not affected by age, but they were significantly prolonged in aMCI patients. Interestingly, VEPs for higher-dorsal stimuli were related to outcomes of neuropsychological tests. Furthermore, the ROC analysis showed that the highest areas under the curve were obtained for VEP latencies in response to higher-dorsal stimuli. These results suggest aMCI-related functional impairment specific to higher-level visual processing. Further, dysfunction in the higher-level of the dorsal stream could be an early indicator of cognitive decline. Therefore, we conclude that VEPs associated with higher-level dorsal stream activity can be a sensitive biomarker for early detection of aMCI.

P61: Higher level but not lower level parallel visual pathways are functionally altered in patients with mild cognitive impairment

Objective: Spatial vision and object recognition are processed in parallel by the dorsal (D) and ventral (V) streams. Such visual information is behaviorally impaired in Alzheimer’s disease (AD). We studied how V and D streams are functionally altered in patients with mild cognitive impairment (MCI) who turned out to be AD. Methods: The functions of the Dand V-streams at lower (L) and higher (H) levels were separately evaluated in MCI patients, healthy old and young adults with a 128-ch EEG machine. Each group consisted of 15 subjects. Visual stimuli were optimized to stimulate each stream separately. At L-level, red-green isochromatic gratings were used for V while achromatic gratings for D. At H-level, words [Kanji (ideogram) for V; Kana (phonogram) for D], faces for V, and coherent radial optic flow (OF) motion for D were employed. Results: In all groups, occipital N1 for chromatic stimuli and steady-state responses for achromatic stimuli were major components of VEPs at L-level. In ERPs, occipito-temporal N170 were obtained in both words and faces, and occipito-temporal N170 and parietal P200 were elicited by OF. In comparison between MCI and old adults, there were no significant differences in VEPs for chromatic and achromatic stimuli between the two groups. In contrast, a significant prolongation of N170 latencies for faces and Kana but not Kanji was observed in MCI. N170 and P200 latencies for OF were also significantly prolonged in MCI. N170 amplitude and P200 latency for OF was closely related with the Mini-Mental State Examination score. Similarly, the latency and amplitude of P200 for OF and N170 latency for Kana were most closely correlated with the Wechsler Memory Scale-Revised Logical Memory (delayed recall). Conclusions: These findings suggest that the activities of V and D streams at H-level are impaired with preserved L-level function in MCI patients. Since the high correlation between H-D related ERP and neuropsychological tests was obtained, H-D related ERP can be the most sensitive biomarkers for early detection of MCI.

S8.2 A deficit of dorsal stream function in patients with amnestic mild cognitive impairment

Objectives: To investigate the previously un-studied effect of subthreshold conditioning currents on VRCs of muscle membranes. Methods: Study effects of polarising currents of 100 ms duration presented immediately prior to the test stimulus, ranging in intensity from 0.5 5% of the test stimulus. Studies of the tibialis anterior and biceps brachii muscles in five normal subjects, at rest and during the VRC. Results: Depolarising currents reduce the conduction velocity and early supernormality (SN10) and increase the relative refractory period (RRP) of the following test response. This is similar to the effects reported in ischaemia and hyperkalaemia, supporting the hypothesis that muscle sarcolemma is depolarised in these conditions (2). In contrast, hyperpolarising currents increase the velocity and SN10, as predicted, given the intracellular “depolarising after potential” seen after an action potential. Conclusions: We demonstrate that changes in sarcolemmal excitability can be induced by sub-threshold conditioning currents, akin to nerve excitability testing. Studying sub-threshold excitability changes in muscle may improve our understanding and management of muscle disorders.

P1-14 Facial identity facilitates facial expression recognition: A high-density ERP study

face of 18 persons (8 males and 10 females). Frontal and deviated faces were presented with a fixed gaze direction, followed by an apparent movement of eyes either toward the subject or away from the subject. Furthermore, eyes photographs with the apparent motion cut out from the face were also used as the stimulus. Subjects were eighteen student volunteers (8 males and 9 females). In ‘Direct gaze condition’, gaze direction moved toward the subject either from 30 degrees right or left location, and in ‘Averted gaze condition’, it moved away 30 degrees either right or left direction from the subject. EEG were recorded from Fz, Cz, Pz, C3, C4, T3, T4, T5 and T6 locations referred to nose-tip. The negative ERP component about 170 ms after stimulus onset (N170) were observed to the apparent movement of eyes both for face and eyes stimulus. This component was larger in ‘Direct gaze condition’ than in ‘Averted gaze condition’, suggesting that gaze contact relates to the specific processing different from averted gaze. Furthermore this N170 was interacted with the diretion of face.

17. Neural substrates of reading Kanji and Kana words: A magnetoencephalographic study

direct pathways. We tried to establish a procedure to quantify functions of PNs. Surface electromyogram was recorded from the right or left biceps muscle (Bi) of normal human subjects (n = 13). During weak tonic voluntary contraction of Bi and hand muscles, (1) electric stimulation of the ipsilateral ulnar nerve, (2) transcranial magnetic stimulation (TMS) of the contralateral primary motor cortex, and (3) combined stimulation of both were delivered. Interstimulus intervals for the combined stimulation were set to ensure simultaneous excitatory inputs on PNs, caused by both stimulations. When appropriate stimulus strength was selected, TMS-induced potentials in Bi were facilitated by combined ulnar stimulation. However, the maximum facilitation was observed on the dominant side in righthanded subjects (n = 10). The tendency was not noted in left-handed subjects (n = 3). Thus, the current procedure is useful to evaluate functions of PNs, though stimulus condition and handedness have to be considered. The asymmetry for the right-handed subjects may be explained by differential pyramidal inputs to PNs, because bilateral reflex effects by ulnar stimulation were similarly weak.

P1-28 Aging of the parallel visual pathways in humans

T. Okano1, Y. Terao2, H. Fukuda3, M. Emoto4, R. Hanajima2, K. Takenaka1, H. Ikeda1, Y. Yatomi1, Y. Ugawa5 1Department of Laboratory Medicine, the University of Tokyo Hospital, Japan, 2Department of Neurology, the University of Tokyo, Japan, 3Department of Hazard Assessment, National Institute of Industrial Health, Japan, 4Interfaculty Initiative in Information Studies, Graduate School of Interdisciplinary Information Studies, University of Tokyo, Japan, 5Department of Neurology, Fukushima Medical University, Japan

58. Neural mechanisms of reading Japanese Kanji and Kana words: An fMRI study

abnormality; the age range of the subjects was 11–84 years (mean 51.6). The median, ulnar and tibial nerves were studied. Regression analysis was done to determine normal value. Results: The effect of age on FLM is relatively small, only 0.03– 0.05 ms/year. In contrast, FLM increases with height in arms by 0.12 (median) ms/cm or 0.13 (ulnar) ms/cm and in legs 0.22 (tibial) ms/cm. These effects are around half of the previous reports from Estonia (Puksa et al., 2003) or Brazil (Nobrega et al., 2004). From our database the upper limit of the normal value at 170 cm was 28 ms in median, 29 ms in ulnar and 51 ms in tibial nerve. Conclusion: FWML is highly correlated with height in Japanese. However, the effect is smaller than western people, reflecting the skeletal difference.