Hiromasa Sawamura

Default Mode of Brain Function in Monkeys

Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment.

Using Functional Magnetic Resonance Imaging to Assess Adaptation and Size Invariance of Shape Processing by Humans and Monkeys

Functional magnetic resonance imaging in awake monkeys and humans was used to compare object adaptation in shape-sensitive regions of these two species under identical and different size conditions. Object adaptation was similar in humans and monkeys under both conditions. Neither species showed complete size invariance, in agreement with single-cell studies. Both the macaque inferotemporal (IT) complex and human lateral occipital complex (LOC) displayed an anteroposterior gradient in object adaptation and size invariance, with the more anterior regions being more adaptable and size invariant. The results provide additional evidence for the homology between the macaque IT cortex and human LOC but also add to the growing list of differences between human and monkey intraparietal sulcus regions.

Spatial distribution and density of prefrontal cortical cells projecting to three sectors of the premotor cortex.

The spatial distribution of prefrontal cortical cells projecting to three different sectors in the premotor cortex was examined. The cells projecting to the three sectors were distributed in separate regions in the dorsolateral prefrontal cortex with a small overlap. Cells projecting to the ventral sector were distributed in the lower bank of the principal sulcus (PS). Those projecting to the restro-dorsal sector were located near the superior limb of the arcuate sulcus, and in the dorsal convexity and upper bank of the PS. Cells projecting to the caudo-dorsal sector were observed in the upper bank of the PS and in the area 8a. These findings suggest that each of the three sectors of the premotor cortex receive different sets of information from the prefrontal cortex.

Segregated Pathways Carrying Frontally Derived Top-Down Signals to Visual Areas MT and V4 in Macaques

The bottom-up processing of visual information is strongly influenced by top-down signals, at least part of which is thought to be conveyed from the frontal cortex through the frontal eye field (FEF) and the lateral intraparietal area (LIP). Here we investigated the architecture of multisynaptic pathways from the frontal cortex to the middle temporal area (MT) of the dorsal visual stream and visual area 4 (V4) of the ventral visual stream in macaques. In the first series of experiments, the retrograde trans-synaptic tracer, rabies virus, was injected into MT or V4. Three days after rabies injections, the second-order (disynaptically connected) neuron labeling appeared in the ventral part of area 46 (area 46v), along with the first-order (monosynaptically connected) neuron labeling in FEF and LIP. In the MT-injection case, second-order neurons were also observed in the supplementary eye field (SEF). In the next series of experiments, double injections of two fluorescent dyes, fast blue and diamidino yellow, were made into MT and V4 to examine whether the frontal inputs are mediated by distinct or common neuronal populations. Virtually no double-labeled neurons were observed in FEF or LIP, indicating that separate neuronal populations mediate the frontal inputs to MT and V4. The present results define that the multisynaptic frontal input to V4 arises primarily from area 46v, whereas the input to MT arises from not only area 46v but also SEF, through distinct FEF and LIP neurons. Segregated pathways from the frontal cortex possibly carry the functionally diverse top-down signals to each visual stream.

Deficits in action selection based on numerical information after inactivation of the posterior parietal cortex in monkeys.

A previous study identified neuronal activity in area 5 of the monkey posterior parietal cortex that reflects the numerosity of a series of self-performed actions. It is not known, however, whether area 5 is crucially involved in the selection of an action based on numerical information or, instead, merely reflects numerosity-related signals that originate in other brain regions. We transiently and focally inactivated area 5 to test its functional contributions to numerosity-based action selection. Two monkeys were trained to either push or turn a handle in response to a visual trigger signal. The selection of the action was solely based on numerical information from a series of actions performed by the monkey: select A five times, select B five times, and then return to A in a cyclical fashion. When muscimol was applied to a portion of area 5 in which the activity in the numerosity-selective cells was recorded, the error rate in the selection task increased significantly. This transient neural inactivation also caused omission errors that were not observed before the muscimol injection. A control task showed that the errors were not caused by motor deficits or impaired ability to select between two possible actions. Our results indicate that area 5 is crucial for selecting actions on the basis of numerical information about a series of actions performed by the tested individual.

Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type

Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systematic amyloidosis characterized by lattice corneal dystrophy, cranial neuropathy, and cutis laxa. Although FAF has been frequently found in the Finnish population, FAF is a considerably rare disorder in other regions. In this study, we examined the clinical characteristics as well as the haplotypes of six Japanese patients with FAF from five families. They showed the typical clinical presentations of FAF, but we found a broad range of ages at onset of neurological symptoms. All members had the c.654G>A mutation in GSN. To evaluate the disease haplotypes, high-density single-nucleotide polymorphism (SNP) arrays were used and disease-relevant haplotypes were reconstructed. Haplotype analysis in the four apparently unrelated families suggested a common founder haplotype. In a sporadic FAF patient, however, the haplotype was dissimilar to the founder haplotype. The present study demonstrated that a founder mutation in most of the Japanese families with FAF, except for a sporadic patient in whom a de novo mutation event was suggested as the origin of the mutation.

Anti-NMDA receptor encephalitis associated with transient cerebral dyschromatopsia, prosopagnosia, and lack of stereopsis.

A 20-year-old woman suffered from anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and was treated with removal of an ovarian teratoma and retroperitoneal ganglioneuroma in addition to immunotherapy. She was incapable of face recognition, had difficulty with object recognition, and lacked color sensation and stereo perception during recovery. These symptoms were transient and completely resolved over 4 months. Our report documents additional aspects of visual impairment associated with anti-NMDAR encephalitis and suggests that the disease can lead to diffuse cerebral dysfunction including the cortical visual system.

Multisynaptic Inputs from the Medial Temporal Lobe to V4 in Macaques

Retrograde transsynaptic transport of rabies virus was employed to undertake the top-down projections from the medial temporal lobe (MTL) to visual area V4 of the occipitotemporal visual pathway in Japanese monkeys (Macaca fuscata). On day 3 after rabies injections into V4, neuronal labeling was observed prominently in the temporal lobe areas that have direct connections with V4, including area TF of the parahippocampal cortex. Furthermore, conspicuous neuron labeling appeared disynaptically in area TH of the parahippocampal cortex, and areas 35 and 36 of the perirhinal cortex. The labeled neurons were located predominantly in deep layers. On day 4 after the rabies injections, labeled neurons were found in the hippocampal formation, along with massive labeling in the parahippocampal and perirhinal cortices. In the hippocampal formation, the densest neuron labeling was seen in layer 5 of the entorhinal cortex, and a small but certain number of neurons were labeled in other regions, such as the subicular complex and CA1 and CA3 of the hippocampus proper. The present results indicate that V4 receives major input from the hippocampus proper via the entorhinal cortex, as well as “short-cut” pathways that bypass the entorhinal cortex. These multisynaptic pathways may define an anatomical basis for hippocampal-cortical interactions involving lower visual areas. The multisynaptic input from the MTL to V4 is likely to provide mnemonic information about object recognition that is accomplished through the occipitotemporal pathway.

Case of metastatic pulmonary carcinoma in optic disc diagnosed from results of biopsy performed during vitrectomy surgery.

BackgroundMost intraocular metastatic tumors occur in the uveal tract, while isolated metastasis to the optic nerve is rarely found. We report a case of metastasis to the optic disc from primary lung cancer, diagnosed from biopsy findings obtained during a vitrectomy.Patient and methodsA 69-year-old male presented with gradual visual impairment due to a milky white tumour that extended from the optic disc into the vitreous cavity. A systemic examination revealed primary squamous cell lung cancer.ResultsA biopsy specimen was obtained from the optic disc tumor during a vitrectomy, which led to a diagnosis of metastasis from lung cancer. Despite courses of chemotherapy and radiotherapy, the patient died of brain metastasis.DiscussionThere are few reports of secondary optic disc tumors and pathological biopsy findings are rare. When a milky white tumor is observed extending from the optic disc, a possible differential diagnosis is metastatic neoplasm.

Recurrent Optic Neuropathy Caused by a Mucocele of the Anterior Clinoid Process after a 5-Year Remission: A Case Report and Literature Review.

Abstract A 32-year-old male presented with acute left vision loss during a second recurrence of optic neuropathy. Steroid pulse therapy had been effective in both the first episode 9 years previously and the first recurrence 5 years previously. Magnetic resonance imaging demonstrated an anterior clinoid process mucocele compressing the optic nerve. Although surgical treatment was performed, improvement was limited. This report indicates that steroid pulse therapy could be an alternative treatment to obtain temporary remission, but surgical treatment should be considered to prevent irreversible neurological deficits. This paper also presents a review of the literature on anterior clinoid process mucoceles.