Contents 1 Goal 2 Plans 2.1 The Strategy of Linking Brain and Mind (SLBM) 2.2 step 1 Identification of key Cognitive & Brain mechanisms 2.3 step 2 Integration of key Neurometric & Psychometric tools 2.4 step 3 Linking Neural Activities to Cognitive Functions 3 Research Units 3.1 Three Core Research Units 4 Research overview 5 Publication 5.1 WCU Publication

Goal

To understand how the mind, behavior and brain are interrelated by linking key cognitive & emotional functions to neural activities at multiple levels of brain systems.

Plans

The Strategy of Linking Brain and Mind (SLBM)

First, we have identified a set of comprehensive but focused set of cognitive functions and targeted brain mechanisms with an aim to achieve breadth while insuring that our studies fall squarely within the areas of expertise of our associated faculty (Fig 1A, 1B). Second, to address the 'linking' questions around those key cognitive and brain mechanisms, we intend to integrate cutting-edge ‘neurometric' techniques to probe neural activities/structures at multiple levels spanning the depth of genetic, molecular, synaptic, neuronal, local/global network-level measurements (Fig 1C). These brain measurements will be paralleled by state-of-the-art 'psychometric' tools to capture mind in action, with behavioral tasks spanning the breadth of behavioral genetics, rodent memory tasks, visual perception tasks, eye movements, reverse correlation and social perception tasks (Fig 1D). Third, based on the neurometric and psychometric data, we will build tight linkages between brain activity/structure and mind. In doing so, computational approaches will help us to build comprehensive neural models constrained by data from empirical studies (Fig 1E). Computational models of complex brain systems allow us to put to test, via simulation, predictions that cannot be tested in empirical situations and to guide empirical studies by generating testable predictions about behaviors in the domains of both brain and mind. In addition, we will study brains and minds in abnormal states by specifying the roles of neural circuits underlying cognitive deficits in patients with psychiatric disorders and in individuals with remarkable cognitive abilities that fall outside the range of normal (Fig 1F). Our multi-level approach, transpiring through 'gene', 'protein', 'neuron', 'system', 'behavior', 'abnormality' and 'computation', can lead to fundamental cure for mental diseases in the future.

step 1 Identification of key Cognitive & Brain mechanisms

Perirhinal cortex / Entorhinal cortex / Parietal cortex / Hippocampus / Amygdala / Visual cortex / Prefrontal cortex / Corpus callosum / Orbitofrontal cortex / Longrange cortical circuitry

step 2 Integration of key Neurometric & Psychometric tools

step 3 Linking Neural Activities to Cognitive Functions

Research Units

Three Core Research Units

Research overview

I. Introduction and overview of research plans Our research aim is to use biological, behavioral and computational methods to understand how the mind, brain and behavior are interrelated. Studying humans and animals, our research will link key cognitive and emotional functions to neural activities at multiple levels of brain systems. To establish these linkages, we set forth a research strategy, named 'SLBM (Strategy of Linking Brain and Mind)', the major steps and components of which are summarized in the following three sections. Target mechanisms A Brain B Mind Synaptic plasticity     Calcium sensors Perirhinal cortex Entorhinal cortex Auditory cortex Somatosensory cortex Parietal cortex Prefrontal cortex Hippocampus Amygdala Visual cortex Anterior cingulatu cortex Basal ganglia Superior temporal cortex Long-range cortical circuitry Orbitofrontal cortex Ventromedial frontal cortex Corpus callosum Episodic Memory Contextual Memory Place Memory Association Memory Working Memory Emotion Pain and Pleasure Attention Anxiety Motion and form perception Perceptual organization Decision making Multistable perception Adaptation Cross-modal sensory integration Social interaction Measurements C Neurometric D Psychometric Transgenic animals     Protein-protein interaction Patch-clamp recording In vitro electrophysiology in vivo electrophysiology Two-photon imaging Multi-unit parallel recording Chronic eletrophysiology Lesion/inactivation study (F)MRI/DTI/PET/MEG Classification of cortical activity Functional connectivity analysis Transcranial magnetic stim Brain Segmentation Near-Infrared Optical Imaging Tractography Maze learning tasks   Fear conditioning Anxiety and depression test Test of genetic mutant mice Behavioral genetics Bistable perception task Signal detection task 2-alternative force choice task Motion discrimination task Reverse correlation Biological motion task Visual search task Eye movements Face recognition task Neuropsychological testing Theory-of-Mind task Social cue Perception task Imitation task E Brain/Mind, Simulated F Abnormal Brain/Mind Neural modeling of dynamic vs resting state network/ Hippocampal network of memory/Propagation of cortical excitability/Motion perception/Oscillations in brain or percept/Cortical hippocampal interaction Neurocognitive deficits in Schizophrenia/Depression/Amnesia/Autism/ Alzheimer's Disease/Epilepsy/Synesthesia/Phantom pain/ Anxiety/Fragile X disease Protein to Cognition unit System & Cognitive unit Clinical & Computational unit Figure 1. Structure of SLBM

Publication

WCU Publication

Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of hte perforant path

The after-effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro-electrodes in rabbits anaesthetized with urethane.
In fifteen out of eighteen rabbits the population response recordedfrom granule cells in the dentate area to single perforant path volleys was potentiated for periods ranging from 30 min to 10 hr after one or more conditioning trains at 10-20/sec for 10-15 sec, or 100/sec for 3-4 sec.
The population response was analysed in terms of three parameters: the amplitude of the population excitatory post-synaptic potential (e.p.s.p.), signalling the depolarization of the granule cells, and the amplitude and latency of the population spike, signalling the discharge of the granule cells.
All three parameters were potentiated in 29% of the experiments; in other experiments in which long term changes occurred, potentiation was confined to one or two of the three parameters. A reduction in the latency of the population spike was the commonest sign of potentiation, occurring in 57 % of all experiments. The amplitude of the population e.p.s.p. was increased in 43 %, and of the population spike in 40 %, of all experiments.
During conditioning at 10-20/sec there was massive potentiation of the population spike ('frequency potentiation'). The spike was suppressed during stimulation at 100/sec. Both frequencies produced long-term potentiation.
The results suggest that two independent mechanisms are responsiblefor long-lasting potentiation: (a) an increase in the efficiency of synaptic transmission at the perforant path synapses; (b) an increase in the excitability of the granule cell population.

An Animal Model of a Behavioral Intervention for Depression

Although conditioned inhibition of fear (or learned safety) is a learning process critical for preventing chronic stress, a predisposing factor for depression and other psychopathologies, tittle is known about its functional purposes or molecular mechanisms. To obtain better insight into learned safety, we investigated its behavioral and molecular characteristics and found that it acts as a behavioral antidepressant in two animal models. Learned safety promotes the survival of newborn cells in the dentate gyrus of the hippocampus, while its antidepressant effect is abolished in mice with ablated hippocampal neurogenesis. Learned safety also increases the expression of BDNF in the hippocampus and leads to downregulation of genes involved in the dopaminergic and neuropeptidergic but not the serotonergic system in the basolateral amygdala. These data suggest that learned safety is an animal model of a behavioral antidepressant that shares some neuronal hallmarks of pharmacological antidepressants but is mediated by different molecular pathways.

Distinct Neural Bases of Route Following and Wayfinding in Humans An Animal Model of a Behavioral Intervention for Depression

Finding one's way in a large-scale environment may engage different cognitive processes than following a familiar route. The neural bases of these processes were investigated using functional MRI (fMRI). Subjects found their way in one virtual-reality town and followed a well-learned route in another. In a control condition, subjects followed a visible trail.Within subjects, accurate wayfinding activated the right posterior hippocampus. Between-subjects correlations with performance showed that good navigators (i.e., accurate wayfinders) activated the anterior hippocampus during wayfinding and head of caudate during route following. These results coincidewith neurophysiological evidence for distinct response (caudate) and place (hippocampal) representations supporting navigation. We argue that the type of representation used influences both performance and concomitant fMRI activation patterns.