A04 Alteration of brain dynamics as underlying mechanisms of hyper-adaptability in neurotransmitter disorders

Research Outline


Our daily activities consist of continuous and parallel multi-tasking, which requires integration of executive functions (attention, prediction, working memory, etc.) and motor functions. This cognitive-motor linkage is impaired by neurodegenerative disorders as well as aging in which dysfunctions of neurotransmitter systems co-exist with neural degeneration. Here we hypothesize that the “hyper-adaptation” compensates for the functional decline in aging and neurodegenerative diseases, which involve abnormality in neurotransmitters such as dopamine (DA) and acetylcholine (ACh). Specifically, the present research project is designed to test the hypothesis that the alteration of neural dynamics following abnormal DA or ACh neurotransmissions may lead to the change of “rule of the conduct” as an underlying mechanism of “hyper-adaptation”.
To test this hypothesis, we will conduct both clinical (Hanakawa et al.) and animal (Takakusaki et al.) studies. In the clinical study, we will focus on decline of the midbrain DA system in aging and Parkinson’s disease. We will use brain imaging and brain stimulation techniques to know the causal relationship between the changes in DA-dependent neural dynamics and executive functions involved in action selection. We aim to identify “parameters of altered neural dynamics associated with aging”. In the animal experimentation, we will focus on the ACh system, which is deteriorated in Alzheimer-type dementia, in addition to the DA system. In multi-tasks of posture control during walking and forelimb reaching in the cat, we will try to identify the alteration of dynamics in the cortical and subcortical neural network before and after damages to subcortical ACh and DA systems, which will be induced by molecular genetics procedures.
We will collaborate with Model Research Group (B04) to elucidate the specific functions of each neurotransmitter, which affects the alteration of action rules that lead to hyper-adaptation. Our findings will be also shared with the A01 and B01 research groups, which will contribute to “elucidation of motivation of behavior (A01)” and “construction of mathematical models for posture control (B01)”


Principal investigator Kaoru TAKAKUSAKI Professor, Asahikawa Medical University
Funded co-investigator Takashi HANAKAWA Professor, Graduate School of Medicine, Kyoto University
Co-investigators Tomohiro NOGUCHI Lecturer, Asahikawa Medical University
Toshi NAKAJIMA Assistant Professor, Asahikawa Medical University
Mirai TAKAHASHI Visiting Assistant Professor, Asahikawa Medical University
Syusei HUKUYAMA Assistant Professor, Asahikawa Medical University
Toshikatsu OKUMURA Professor, Asahikawa Medical University
Tsukasa NOZU Professor, Asahikawa Medical University
Seiji MATSUMOTO Professor, Asahikawa Medical University
Hitoshi SASAJIMA Lecturer, Asahikawa Medical University
Sadaharu MIYAZONO Lecturer, Asahikawa Medical University
Kenji YOSHINAGA Postdoctoral fellow, NCNP
Hiroki TOGO Postdoctoral fellow, NCNP
Toma MATSUSHIMA Undergraduate Student, Tokyo University of Agriculture and Technology (Research Student, NCNP)