Katsuya Ogata

Functional network of the basal ganglia and cerebellar motor loops in vivo: Different activation patterns between self-initiated and externally triggered movements

The basal ganglia and cerebellar loops are known to participate differently in self-initiated (SI) and externally triggered (ET) movements. However, no previous neuroimaging studies have illustrated functional organization of these loops in vivo. Here, we aimed to functionally visualize these loops during motor execution using functional magnetic resonance imaging (fMRI) with structural equation modeling (SEM). Twelve normal subjects (24-29 years old) were scanned while performing five different frequencies of sequential left finger movements using either SI or ET movements. Random effect analysis combined with a parametric approach revealed a significant positive linear dependence of cerebral activation upon movement rate in the right Put, GPi, VL, SMC and SMA during SI tasks. During ET tasks, significant positive linear relationships were found in the right SMC, VPL, left CB and DN, whereas tendency for linear relationships was seen in the right PMv. SEM further showed significant interactions within the right basal ganglia-thalamo-motor loop during SI tasks. In contrast, there were significant interactions within the entire right cerebral hemisphere-left cerebellar loop involving CB, DN, VPL, PMv and SMC during ET tasks. Therefore, our modeling approach enabled identification of different contributions of the motor loops of basal ganglia and cerebellum to SI and ET tasks during motor execution.

Age-related alterations of the functional interactions within the basal ganglia and cerebellar motor loops in vivo

Aging may alter the motor functions of the basal ganglia and cerebellum; however, no previous neuroimaging study has investigated the effect of aging on the functional connectivity of the motor loops involving these structures. Recently, using fMRI with a parametric approach and structural equation modeling (SEM), we demonstrated a significant functional interaction within the basal ganglia-thalamo-motor (BGTM) loop during self-initiated (SI) finger movement in young normal subjects, whereas cerebro-cerebellar (CC) loop was mainly involved during externally triggered (ET) movement. We applied this method to 12 normal aged subjects (53-72 years old) in order to study the effect of age on BGTM and CC loops. Compared with the functional connectivity seen in young subjects, SEM showed decreased connectivity in BGTM loops during SI task, decreased interaction in the CC loop during ET task, and increased connectivity within motor cortices and between hemispheres during both types of tasks. These results suggest an age-related decline of cortico-subcortical connectivity with increased interactions between motor cortices. Aging effects on SI and ET movements are probably caused by functional alterations within BGTM and CC loops.

Early ERP components differentially extract facial features: evidence for spatial frequency-and-contrast detectors.

It is generally accepted that the N170 component of an event-related potential (ERP) reflects the structural encoding of faces and is specialized for face processing. Recent neuroimaging and ERP studies have demonstrated that spatial frequency is a crucial factor for face recognition. To clarify which early ERP components reflect either coarse (low spatial frequency, LSF) or fine (high spatial frequency, HSF) processing of faces, we recorded ERPs induced by manipulated face stimuli. By filtering the original grayscale faces (broadband spatial frequency) spatially, we created LSF and HSF face stimuli. Next, we created physically equiluminant (PEL) face stimuli to eliminate the effects of lower order information, such as luminance and contrast. The P1 amplitude at the occipital region was augmented by LSF faces, while the N170 amplitude increased for HSF faces. The occipital P1 amplitude for PEL faces was relatively unaffected compared with that for PEL houses. In addition, the occipital N2 for PEL faces was spatiotemporally separable from N170 in a time-window between P1 and N170. These results indicate that P1 reflects coarse processing of faces, and that the face robustness further assures face-specific processing in the early component. Moreover, N2 reflects the early contrast processing of faces whereas N170 analyzes the fine facial features. Our findings suggest the presence of spatial frequency-and-contrast detectors for face processing.

Spatiotemporal signatures of an abnormal auditory system in stuttering.

People who stutter (PWS) can reduce their stuttering rates under masking noise and altered auditory feedback; such a response can be attributed to altered auditory input, which suggests that abnormal speech processing in PWS results from abnormal processing of auditory input. However, the details of this abnormal processing of basic auditory information remain unclear. In order to characterize such abnormalities, we examined the functional and structural changes in the auditory cortices of PWS by using a 306-channel magnetoencephalography system to assess auditory sensory gating (P50m suppression) and tonotopic organization. Additionally, we employed voxel-based morphometry to compare cortical gray matter (GM) volumes on structural MR images. PWS exhibited impaired left auditory sensory gating. The tonotopic organization in the right hemisphere of PWS is expanded compared with that of the controls. Furthermore, PWS showed a significant increase in the GM volume of the right superior temporal gyrus, consistent with the right tonotopic expansion. Accordingly, we suggest that PWS have impaired left auditory sensory gating during basic auditory input processing and that some error signals in the auditory cortex could result in abnormal speech processing. Functional and structural reorganization of the right auditory cortex appears to be a compensatory mechanism for impaired left auditory cortex function in PWS.

Oscillatory gamma synchronization binds the primary and secondary somatosensory areas in humans

Induced gamma activity has a key role in the temporal binding of distributed cortico-cortical processing. To elucidate the neural synchronization in the early-stage somatosensory processing, we studied the functional connectivity between the primary and secondary somatosensory cortices (SI and SII) in healthy subjects using magnetoencephalography (MEG) with excellent spatiotemporal resolution. First, somatosensory-evoked magnetic fields were recorded to determine the locations of each cortical activity. Then we analyzed the phase-locking values (PLVs) of the induced gamma activity to assess neural synchrony within the somatosensory cortical network. We also assessed PLVs in patients with multiple sclerosis (MS) to validate our PLV analysis in evaluating the inter-areal functional connectivity, which can often be impaired in MS. The PLVs of the induced gamma activity were calculated for each pair of unaveraged MEG signals that represented the activities of the contralateral SI and bilateral SII areas. Analysis of PLVs between the SI and SII areas showed significantly increased PLVs for gamma-band activities, starting at an early post-stimulus stage in normal controls, whereas this increase in PLVs was apparently diminished in MS. The PLV analysis provided evidence for early-latency, gamma-band neuronal synchronization between the SI and SII areas in normal controls. Our study first demonstrates the gamma-band synchrony in the early-stage human somatosensory processing.

Transcranial direct current stimulation over the motor association cortex induces plastic changes in ipsilateral primary motor and somatosensory cortices

OBJECTIVE This study was performed to elucidate whether transcranial direct current stimulation (tDCS) over the motor association cortex modifies the excitability of primary motor (M1) and somatosensory (S1) cortices via neuronal connectivity. METHODS Anodal, cathodal, and sham tDCS (1 mA) over the left motor association cortex was applied to 10 subjects for 15 min using electrodes of two sizes (9 and 18 cm(2)). Both motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) were recorded before, immediately after, and 15 min after tDCS. Electrode positions were confirmed by overlaying them on MRI anatomical surface images of two individuals. RESULTS After applying anodal tDCS using the large electrode, amplitudes of MEP components significantly decreased, whereas those of early SEP components (N20 and P25) increase. Opposite effects were observed on MEPs and SEPs after cathodal tDCS. However, a small electrode did not significantly influence either MEPs or SEPs, irrespective of polarity. The small electrode covered mainly the dorsal premotor cortex (PMd) while the large electrode involved the supplementary motor area (SMA) in addition to PMd. CONCLUSIONS These results suggest that anodal tDCS over PMd together with SMA enhanced the inhibitory input to M1 and excitatory input to S1, and that cathodal tDCS might lead to an opposite effect. SIGNIFICANCE The finding that only the large electrode modulated M1 and S1 implies that activation of PMd together with SMA by tDCS can induce plastic changes in primary sensorimotor areas.

Preattentive visual change detection as reflected by the mismatch negativity (MMN)--evidence for a memory-based process.

The aim of this study was to test the hypothesis that visual mismatch negativity (vMMN) is based on memory trace formation. Special care was taken to distinguish between memory mismatch and rareness effect. Subjects were seated in front of a monitor and asked to listen to a story. The standard sequence block consisted of nine consecutive 24-vane windmill patterns with an 800-ms inter-stimulus interval. The deviant sequence block consisted of one 24-vane pattern with eight six-vane patterns. Inter-train intervals (ITIs) varied among 1, 6, and 12s in the changing ITI experiment, while the deviant stimulus occupied the eighth position in the sequence. In the changing order experiment, the position of the deviant stimulus was varied among the second, fourth and eighth position with a 12-s constant ITI. vMMN was ascertained from the difference in responses to standard and deviant stimulus. vMMN appeared in the occipital region 150-300 ms after stimulus onset. It was significantly modulated by the ITI, and more than four preceding stimuli were needed to reinstate the implicit memory trace. These results suggest that memory-based change detection underlies vMMN. Therefore, vMMN is useful to study visual sensory memory function.

A distinct subgroup of chronic inflammatory demyelinating polyneuropathy with CNS demyelination and a favorable response to immunotherapy

To explore subclinical central nervous system (CNS) involvement in chronic inflammatory demyelinating polyneuropathy (CIDP), we recorded somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) using transcranial magnetic stimulation, to measure central sensory conduction time (CSCT) and central motor conduction time (CMCT) and examined brain and spinal cord MRI in patients with probable CIDP based on the American Academy of Neurology AIDS Task Force criteria. Eighteen patients with probable CIDP (12 males and 6 females; mean age at examination+/-SD, 45.8+/-17.0 years; range, 17-72) were included in the study. Of the 13 patients who underwent SEPs, one had prolonged CSCT (8%) and of the 13 who underwent MEPs, four had abnormal CMCT (31%). Cranial MRI revealed five of 18 patients had abnormal scans, only one of which showed multiple ovoid periventricular lesions suggestive of demyelination while none showed any intramedullary lesion on spinal cord MRI. Thus, 6 of the 18 patients were considered to have subclinical demyelinative CNS involvement which had lower disability on Global Neurological Disability Score (GNDS) (p=0.0061), a male preponderance (0.0537) and a larger compound muscle action potential (CMAP) amplitude in the median nerve (p=0.005) than those without. The decrease of GNDS with immunologic therapies was nearly significant in the former (p=0.0556) but not in the latter. The results of the present study suggest that subclinical CNS involvement in CIDP is not uncommon in Japanese patients and that CIDP with subclinical CNS involvement is more demyelinative thus responsive to immunotherapies while those without have more axonal damage and less responsive to immunotherapies.

Altered visual information processing systems in bipolar disorder: evidence from visual MMN and P3

Objective: Mismatch negativity (MMN) and P3 are unique ERP components that provide objective indices of human cognitive functions such as short-term memory and prediction. Bipolar disorder (BD) is an endogenous psychiatric disorder characterized by extreme shifts in mood, energy, and ability to function socially. BD patients usually show cognitive dysfunction, and the goal of this study was to access their altered visual information processing via visual MMN (vMMN) and P3 using windmill pattern stimuli. Methods: Twenty patients with BD and 20 healthy controls matched for age, gender, and handedness participated in this study. Subjects were seated in front of a monitor and listened to a story via earphones. Two types of windmill patterns (standard and deviant) and white circle (target) stimuli were randomly presented on the monitor. All stimuli were presented in random order at 200-ms durations with an 800-ms inter-stimulus interval. Stimuli were presented at 80% (standard), 10% (deviant), and 10% (target) probabilities. The participants were instructed to attend to the story and press a button as soon as possible when the target stimuli were presented. Event-related potentials (ERPs) were recorded throughout the experiment using 128-channel EEG equipment. vMMN was obtained by subtracting standard from deviant stimuli responses, and P3 was evoked from the target stimulus. Results: Mean reaction times for target stimuli in the BD group were significantly higher than those in the control group. Additionally, mean vMMN-amplitudes and peak P3-amplitudes were significantly lower in the BD group than in controls. Conclusions: Abnormal vMMN and P3 in patients indicate a deficit of visual information processing in BD, which is consistent with their increased reaction time to visual target stimuli. Significance: Both bottom-up and top-down visual information processing are likely altered in BD.

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.