Masato Taira

Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B–null mice

Cyclic nucleotide phosphodiesterase 3B (PDE3B) has been suggested to be critical for mediating insulin/IGF-1 inhibition of cAMP signaling in adipocytes, liver, and pancreatic beta cells. In Pde3b-KO adipocytes we found decreased adipocyte size, unchanged insulin-stimulated phosphorylation of protein kinase B and activation of glucose uptake, enhanced catecholamine-stimulated lipolysis and insulin-stimulated lipogenesis, and blocked insulin inhibition of catecholamine-stimulated lipolysis. Glucose, alone or in combination with glucagon-like peptide-1, increased insulin secretion more in isolated pancreatic KO islets, although islet size and morphology and immunoreactive insulin and glucagon levels were unchanged. The beta(3)-adrenergic agonist CL 316,243 (CL) increased lipolysis and serum insulin more in KO mice, but blood glucose reduction was less in CL-treated KO mice. Insulin resistance was observed in KO mice, with liver an important site of alterations in insulin-sensitive glucose production. In KO mice, liver triglyceride and cAMP contents were increased, and the liver content and phosphorylation states of several insulin signaling, gluconeogenic, and inflammation- and stress-related components were altered. Thus, PDE3B may be important in regulating certain cAMP signaling pathways, including lipolysis, insulin-induced antilipolysis, and cAMP-mediated insulin secretion. Altered expression and/or regulation of PDE3B may contribute to metabolic dysregulation, including systemic insulin resistance.

Relating Neuronal Firing Patterns to Functional Differentiation of Cerebral Cortex

It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

Segregated and Integrated Coding of Reward and Punishment in the Cingulate Cortex

Reward and punishment have opposite affective value but are both processed by the cingulate cortex. However, it is unclear whether the positive and negative affective values of monetary reward and punishment are processed by separate or common subregions of the cingulate cortex. We performed a functional magnetic resonance imaging study using a free-choice task and compared cingulate activations for different levels of monetary gain and loss. Gain-specific activation (increasing activation for increasing gain, but no activation change in relation to loss) occurred mainly in the anterior part of the anterior cingulate and in the posterior cingulate cortex. Conversely, loss-specific activation (increasing activation for increasing loss, but no activation change in relation to gain) occurred between these areas, in the middle and posterior part of the anterior cingulate. Integrated coding of gain and loss (increasing activation throughout the full range, from biggest loss to biggest gain) occurred in the dorsal part of the anterior cingulate, at the border with the medial prefrontal cortex. Finally, unspecific activation increases to both gains and losses (increasing activation to increasing gains and increasing losses, possibly reflecting attention) occurred in dorsal and middle regions of the cingulate cortex. Together, these results suggest separate and common coding of monetary reward and punishment in distinct subregions of the cingulate cortex. Further meta-analysis suggested that the presently found reward- and punishment-specific areas overlapped with those processing positive and negative emotions, respectively.

Navigation-associated medial parietal neurons in monkeys

To examine the neural basis of route knowledge by which one can reach ones destination, we recorded the activity of 580 neurons in the monkey medial parietal region (MPR) while monkeys actively navigated through a virtual environment. One hundred eighty of these neurons (31%) showed significant responses to the monkeys movements in the virtual environment. Of these responsive neurons, 77% (139/180) showed responses associated with a specific movement at a specific location (navigation neurons), 8% (14/180) showed responses associated with a specific movement (movement-selective neurons), and the remaining 27 neurons (15%) were nonselective. We found navigation neurons whose responses to the same movement at the same location were modulated depending on the route that the monkey was currently taking, that is, in a route-selective manner (32 of 59 tested neurons among 139 navigation neurons, route-selective navigation neurons). The reversible inactivation of MPR neurons by muscimol resulted in a monkey becoming lost during the navigation task trial. These results suggest that MPR plays a critical role in route-based navigation by integrating location information and self-movement information.

Disclosing concealed information on the basis of cortical activations

Concealed information, which is information only known to oneself is sometimes crucial for criminal investigation. In this study, we examined cortical activations related to incidental responses to concealed information. We found that cortical responses to stimuli related to concealed information were different from those to other stimuli; the bilateral ventrolateral prefrontal (VLPF) areas, left inferior frontal gyrus, right middle frontal gyrus and right inferior parietal lobule were activated, and among those activated areas, the right VLPF was found to be crucial. Furthermore, we examined by discriminant analysis which cortical areas contribute to the determination of whether the subjects had concealed information. On the basis of the activity in the right VLPF, we were able to correctly identify 32 of the 38 subjects (84.21%) as who had concealed information. These results suggest that the right VLPF may play a crucial role in the incidental processing of concealed information, and we were able to determine whether a subject had concealed information without the need for deceptive responses.

Functional and histological properties of caudal intraparietal area of macaque monkey

In our previous studies, we found that cells in the caudal intraparietal (CIP) area of the macaque monkey selectively responded to three-dimensional (3D) features, such as the axis and surface orientations, and we suggested that this area played a crucial role in 3D vision. In this study, we investigated (1) whether cells in CIP respond to other 3D features, such as curvature, and (2) whether CIP has any histological property to distinguish it from neighboring areas. Curvatures defined by a random-dot stereogram were presented on a display while the monkey performed a fixation task. The shape and amount of curvature were manipulated by two independent variables, shape index and curvedness, respectively. Two-way ANOVA showed that 19 out of 56 visually responsive cells (34.0%) showed the main effect of shape index. We tentatively designated these cells as 3D curvature-selective (3DCS). Of these, six 3DCS cells showed the main effects of shape index and curvedness, whereas 13 showed the main effect of shape index only. In both types of 3DCS cells, preferred shape indices calculated from tuning curves at two levels of curvedness matched well. These results indicate that the majority of 3DCS cells responded equally to a particular shape of curvatures with different curvedness levels. An immunohistochemical study showed that the recording sites of 3DCS cells were in a cortical region characterized by a dense SMI-32 immunoreactivity in the caudal portion of the lateral intraparietal sulcus (IPS), which suggests that this region is comparable to the lateral occipital parietal (LOP) designated in the caudal IPS previously. Further investigations showed that this region was separated from LIPv, the ventral subdivision of lateral intraparietal (LIP) located rostral to CIP/LOP. These results suggest that CIP is a cortical area distinct from LIP histologically as well as functionally.

A parametric relief signal in human ventrolateral prefrontal cortex

People experience relief whenever outcomes are better than they would have been, had an alternative course of action been chosen. Here we investigated the neuronal basis of relief with functional resonance imaging in a choice task in which the outcome of the chosen option and that of the unchosen option were revealed sequentially. We found parametric activation increases in anterior ventrolateral prefrontal cortex with increasing relief (chosen outcomes better than unchosen outcomes). Conversely, anterior ventrolateral prefrontal activation was unrelated to the opposite of relief, increasing regret (chosen outcomes worse than unchosen outcomes). Furthermore, the anterior ventrolateral prefrontal activation was unrelated to primary gains and increased with relief irrespective of whether the chosen outcome was a loss or a gain. These results suggest that the anterior ventrolateral prefrontal cortex encodes a higher-order reward signal that lies at the core of current theories of emotion.

Information processing of geometrical features of a surface based on binocular disparity cues: an fMRI study

Cortical areas related to the information processing of binocular disparity-defined geometrical features of a surface, such as depth, orientation and shape are examined by functional magnetic resonance imaging while subjects discriminated these three types of geometrical feature in random dot stereograms. Results indicate that disparity-defined information of depth and that of orientation are processed in the parietal area. Furthermore, the visual system for 3D vision in the parietal area may be organized in a hierarchical manner and the posterior part of the right intraparietal sulcus may be involved in cognitive process of 3D vision. On the other hand, disparity-defined shape information seems to be processed in the occipital visual areas and the crucial involvement of human LOS for this process is suggested.

Inhibition of the primary motor cortex can alter one's "sense of effort": effects of low-frequency rTMS.

Studies using force-matching tasks have suggested that when we feel a sense of effort, cortical regions may act to increase motor commands, and thus recruit additional motor units, in order to compensate for the exerted force. We hypothesized that suppressing activity in the primary motor cortex (M1), which is the source of the motor commands, would initiate the same process, and induce the same sense of effort. In a force-matching task, grip force was applied to right hand and 10 healthy participants were asked to try to exert the same amount by using left hand, with no visual feedback. On some trials, low-frequency, repetitive transcranial magnetic stimulation (lf-rTMS) was used to suppress the M1 and the primary somatosensory cortex (SI) in the left hemisphere, separately. Results showed that participants tended to overestimate the level of exerted force by up to 24%. In contrast, sham stimulation of the M1 and lf-rTMS over the SI did not significantly affect participants estimations. Further, the M1 suppression resulted in a 42% reduction in motor-evoked potentials. Thus, the M1 suppression can affect our sense of effort, suggesting that compensatory neural mechanisms that increase the MI activity may play an important role in producing senses of effort.

Personality-dependent dissociation of absolute and relative loss processing in orbitofrontal cortex

A negative outcome can have motivational and emotional consequences on its own (absolute loss) or in comparison to alternative, better, outcomes (relative loss). The consequences of incurring a loss are moderated by personality factors such as neuroticism and introversion. However, the neuronal basis of this moderation is unknown. Here we investigated the neuronal basis of loss processing and personality with functional magnetic resonance imaging in a choice task. We separated absolute and relative financial loss by sequentially revealing the chosen and unchosen outcomes. With increasing neuroticism, activity in the left lateral orbitofrontal cortex (OFC) preferentially reflected relative rather than absolute losses. Conversely, with increasing introversion, activity in the right lateral OFC preferentially reflected absolute rather than relative losses. These results suggest that personality affects loss‐related processing through the lateral OFC, and propose a dissociation of personality dimension and loss type on the neuronal level.