ELectron microscopic abnormality and therapeutic efficacy in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin155 immunoglobulin G4 antibody.

INTRODUCTION: Neurofascin155 (NF155) is a target antigen for autoantibodies in a subset of chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We report the cases of 4 patients with anti-NF155 immunoglobulin G4 (IgG4) antibody-positive CIDP who underwent sural nerve biopsies. RESULTS: All patients were relatively young at onset. Three patients experienced tremors, and 2 patients had severe ataxia. Although the response to intravenous immunoglobulin was poor in all patients, plasma exchange and corticosteroids were at least partially effective. Immunoadsorption plasmapheresis was performed in 1 patient but was ineffective. Electron microscopic examination of sural nerve biopsies revealed loss of paranodal transverse bands in all patients. DISCUSSION: Anti-NF155 IgG4 antibody-positive CIDP shows distinctive clinicopathological features, indicating that the IgG4 antibody is directly associated with the pathogenic mechanisms of anti-NF155 IgG4 antibody-positive CIDP. Muscle Nerve 57: 498-502, 2018.

Spatiotemporal Organization and Cross-Frequency Coupling of Sleep Spindles in Primate Cerebral Cortex.

STUDY OBJECTIVES: The sleep spindle has been implicated in thalamic sensory gating, cortical development, and memory consolidation. These multiple functions may depend on specific spatiotemporal emergence and interactions with other spindles and other forms of brain activity. Therefore, we measured sleep spindle cortical distribution, regional heterogeneity, synchronization, and phase relationships with other electroencephalographic components in freely moving primates. METHODS: Transcortical field potentials were recorded from Japanese monkeys via telemetry and were analyzed using the Hilbert-Huang transform. RESULTS: Spindle (12-20 Hz) current sources were identified over a wide region of the frontoparietal cortex. Most spindles occurred independently in their own frequency, but some appeared concordant between cortical areas with frequency interdependence, particularly in nearby regions and bilaterally symmetrical regions. Spindles in the dorsolateral prefrontal cortex appeared around the surface-positive and depth-negative phase of transcortically recorded slow oscillations (< 1 Hz), whereas centroparietal spindles emerged around the opposite phase. The slow-oscillation phase reversed between the prefrontal and central regions. Gamma activities increased before spindle onset. Several regional heterogeneities in properties of human spindles were replicated in the monkeys, including frequency, density, and inter-cortical time lags, although their topographic patterns were different from those of humans. The phase-amplitude coupling between spindle and gamma activity was also replicated. CONCLUSIONS: Spindles in widespread cortical regions are possibly driven by independent rhythm generators, but are temporally associated to spindles in other regions and to slow and gamma oscillations by corticocortical and thalamocortical pathways.

Gamma Oscillations and Their Cross-frequency Coupling in the Primate Hippocampus during Sleep.

STUDY OBJECTIVES: The mechanism by which sleep consolidates memory is unclear. Based on the two-stage model of memory consolidation, different functions for slow wave sleep (SWS) and rapid eye movement (REM) sleep have been proposed; thus, state-dependent changes of neural oscillations in the hippocampus might clarify this fundamental question. METHODS: We recorded hippocampal local field potentials from freely behaving monkeys via telemetry and analyzed their nonstationary oscillations using Hilbert-Huang transform. RESULTS: By applying a recently developed empirical mode decomposition analysis, we found strong cross-frequency coupling between high-frequency and slow wave oscillations during SWS and a prominent increase of gamma band activity in short bursts during REM sleep in unanesthetized primates' hippocampus. CONCLUSION: Spatiotemporal integration through coupled oscillations during slow wave sleep might be a physiological basis of system consolidation, whereas gamma bursts during rapid eye movement sleep might be related to synaptic consolidation in the local hippocampal neural circuit.

Theta oscillations in primate prefrontal and anterior cingulate cortices in forewarned reaction time tasks.

Previously, we introduced a monkey model for human frontal midline theta oscillations as a possible neural correlate of attention. It was based on homologous theta oscillations found in the monkey's prefrontal and anterior cingulate cortices (areas 9 and 32) in a self-initiated hand-movement task. However, it has not been confirmed whether theta activity in the monkey model consistently appears in other situations demanding attention. Here, we examined the detailed properties of theta oscillations in four variations of forewarned reaction time tasks with warning (S1) and imperative (S2) stimuli. We characterized the theta oscillations generated exclusively in areas 9 and 32, as follows: 1) in the S1-S2 interval where movement preparation and reward expectation were presumably involved, the theta power was higher than in the pre-S1 period; 2) in the no-go trials of go/no-go tasks instructed by S1, the theta power in the S1-S2 interval was lower than in the pre-S1 period in an asymmetrical reward condition, whereas it was moderately higher in a symmetrical condition; 3) the theta power after reward delivery was higher than in the unrewarded trials; 4) the theta power in the pre-S1 period was higher than in the resting condition; and 5) when the monkey had to guess the S1-S2 duration internally without seeing S2, the theta power in the pre-S1 period was higher than in the original S1-S2 experiment. These findings suggest that attentional loads associated with different causes can induce the same theta activity, thereby supporting the consistency of attention-dependent theta oscillations in our model.

Directional organization of sensorimotor oscillatory activity related to the electromyogram in the monkey.

OBJECTIVE: To investigate cortical control of the electromyogram (EMG). METHODS: We examined the directed transfer function (DTF) between the EMG and local field potential oscillations in the monkey sensorimotor area during both an isotonic muscle contraction task and the rest condition with EMG silence. DTF computation based on a multivariate model is suitable for analyzing the directional structure of a reciprocally interconnected system. RESULTS: We found that DTF between the cortex and EMG in the beta band is predominantly centrifugal and largest at the anterior bank of the central sulcus. As for the cortico-cortical DTF within the sensorimotor area, the effective connectivity in the beta band was reciprocal across the central sulcus but was dominated by a posterior-to-anterior direction, especially during the muscle contraction task. The asymmetry of the DTF during the rest condition was inconsistent across the monkeys. CONCLUSIONS: These findings indicate the functional relevance of field potential oscillations in the post- as well as pre-central gyri in generating EMG rhythmicity. SIGNIFICANCE: This supports the idea that information flow from the post- to pre-central gyri is a key element in volitional muscle contraction.

Direct recording of theta oscillations in primate prefrontal and anterior cingulate cortices.

Recent evidence has suggested that theta-frequency (4-7 Hz) oscillations around the human anterior cingulate cortex (ACC) and frontal cortex--that is, frontal midline theta (Fm theta) oscillations--may be involved in attentional processes in the brain. However, little is known about the physiological basis of Fm theta oscillations because invasive study in the human is allowed in only limited cases. In the present study, we developed a monkey model for Fm theta oscillations and located the generators of theta waves using electrodes implanted in various cortical areas. Monkeys were engaged in a self-initiated hand-movement task with a waiting period. The theta power in area 9 (the medial prefrontal cortex) and area 32 (the rostral ACC) was gradually increased from a few seconds before the movement and reached a peak immediately after the movement. When the movement was rewarded, the theta power attained a second peak, whereas it swiftly decreased in the unrewarded trials. Theta oscillations in areas 9 and 32 were coherent and phase locked together. This theta activity may be associated with "executive attention" including self-control, internal timing, and assessment of reward. It is probably a homologue of human Fm theta oscillations, as judged from the similar localization, corresponding frequency, and dependency on attentional processes. The monkey model would be useful for studying executive functions in the frontal cortex.

Reactive and anticipatory control of posture and bipedal locomotion in a nonhuman primate.

Bipedal locomotion is a common daily activity. Despite its apparent simplicity, it is a complex set of movements that requires the integrated neural control of multiple body segments. We have recently shown that the juvenile Japanese monkey, M. fuscata, can be operant-trained to walk bipedally on moving treadmill. It can control the body axis and lower limb movements when confronted by a change in treadmill speed. M. fuscata can also walk bipedally on a slanted treadmill. Furthermore, it can learn to clear an obstacle attached to the treadmill's belt. When failing to clear the obstacle, the monkey stumbles but quickly corrects its posture and the associated movements of multiple motor segments to again resume smooth bipedal walking. These results give indication that in learning to walk bipedally, M. fuscata transforms relevant visual, vestibular, proprioceptive, and exteroceptive sensory inputs into commands that engage both anticipatory and reactive motor mechanisms. Both mechanisms are essential for meeting external demands imposed upon posture and locomotion.

Prefrontal theta oscillations associated with hand movements triggered by warning and imperative stimuli in the monkey.

In order to investigate the functional significance of theta oscillations in the brain, we recorded the cortical field potential in monkeys engaged in a visually-initiated hand movement task. In each trial a warning signal (S1) was followed 3 s later by an imperative signal (S2) to which the monkey had to respond to get a reward. The theta power in the prefrontal area 9 and the prelimbic area 32 was higher in the S1-S2 interval than in the pre-S1 period. This theta activity may be related to attentional processes and is probably a homologue of the human frontal midline theta (Fm theta) rhythms.