Age-Related Decline of Sensorimotor Integration Influences Resting-State Functional Brain Connectivity.

Age-related decline in sensorimotor integration involves both peripheral and central components related to proprioception and kinesthesia. To explore the role of cortical motor networks, we investigated the association between resting-state functional connectivity and a gap-detection angle measured during an arm-reaching task. Four region pairs, namely the left primary sensory area with the left primary motor area (S1left-M1left), the left supplementary motor area with M1left (SMAleft-M1left), the left pre-supplementary motor area with SMAleft (preSMAleft-SMAleft), and the right pre-supplementary motor area with the right premotor area (preSMAright-PMdright), showed significant age-by-gap detection ability interactions in connectivity in the form of opposite-sign correlations with gap detection ability between younger and older participants. Morphometry and tractography analyses did not reveal corresponding structural effects. These results suggest that the impact of aging on sensorimotor integration at the cortical level may be tracked by resting-state brain activity and is primarily functional, rather than structural. From the observation of opposite-sign correlations, we hypothesize that in aging, a "low-level" motor system may hyper-engage unsuccessfully, its dysfunction possibly being compensated by a "high-level" motor system, wherein stronger connectivity predicts higher gap-detection performance. This hypothesis should be tested in future neuroimaging and clinical studies.

Temporal and Force Characteristics of Rapid Single-Finger Tapping in Healthy Older Adults.

The purpose of this study was to examine finger motor function in terms of temporal and force characteristics during rapid single-finger tapping in older adults. Ten older and 10 young males performed maximum frequency tapping by the index, middle, ring, or little finger. Nontapping fingers were maintained in contact with designated keys during tasks. Key-contact force for each of the fingers was monitored using four force transducers. The older subjects had slower tapping rates of all fingers during single-finger tapping than the young subjects. The average forces exerted by the nontapping fingers were larger for the older subjects than for the young subjects during tapping with the ring and little fingers. The ranges of the nontapping finger forces were larger for the older subjects during tapping by the middle, ring, and little fingers than for the young subjects. Thus, the motor abilities of the fingers evaluated by rapid single-finger tapping decline in older adults compared with young adults in terms of both movement speed and finger independence.

Decoding finger movement in humans using synergy of EEG cortical current signals.

The synchronized activity of neuronal populations across multiple distant brain areas may reflect coordinated interactions of large-scale brain networks. Currently, there is no established method to investigate the temporal transitions between these large-scale networks that would allow, for example, to decode finger movements. Here we applied a matrix factorization method employing principal component and temporal independent component analyses to identify brain activity synchronizations. In accordance with previous studies investigating "muscle synergies", we refer to this activity as "brain activity synergy". Using electroencephalography (EEG), we first estimated cortical current sources (CSs) and then identified brain activity synergies within the estimated CS signals. A decoding analysis for finger movement in eight directions showed that such CS synergies provided more information for dissociating between movements than EEG sensor signals, EEG synergy, or CS signals, suggesting that temporal activation patterns of the synchronizing CSs may contain information related to motor control. A quantitative analysis of features selected by the decoders further revealed temporal transitions among the primary motor area, dorsal and ventral premotor areas, pre-supplementary motor area, and supplementary motor area, which may reflect transitions in motor planning and execution. These results provide a proof of concept for brain activity synergy estimation using CSs.

Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells.

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.

Functional brain areas associated with manipulation of a prehensile tool: a PET study.

Using PET, brain areas representing the use of a well-learned tool (chopsticks) were investigated in 10 normal common users. The experimental task was to hold the tool in their right hand and use it to pick up and transport a small pin from a table. Data for the same task performed using only the fingers were also obtained as a control. The results showed an extensive overlap in activated areas with and without the use of the tool. The tool-use prehension, compared to the finger prehension, was associated with higher activities in the caudal-ventral premotor, dorsal premotor, superior parietal, posterior intraparietal, middle temporal gyrus, and primary sensory, occipital cortices, and the cerebellum. These are thus considered to be the human cortical and subcortical substrates representing the use of the tool studied. The activity of the posterior intraparietal area was negatively correlated with the number of drops of the pin, whereas occipital activity was positively correlated with the same error parameter. The caudal-ventral premotor and posterior intraparietal areas are together known to be involved in tool use-related modulation in peripersonal space. The correlation results suggest that this modulation depends on the level of performance. The coactivated left middle temporal gyrus further suggests that familiarity with a tool as well as the knowledge about its usage plays a role in peripersonal space modulation. Superior parietal activation, along with occipital activation, indicates the involvement of visual-spatial attention in the tool use, possibly reflecting the effect of interaction between the prehension (task) and the tool.

The effect of tapping finger and mode differences on cortical and subcortical activities: a PET study.

Using positron emission tomography (PET), the brain regions recruited for the tapping movement by different fingers and different tapping modes were investigated in ten young healthy volunteers without specific finger training. Auditory-paced (2 Hz) tapping movements were performed by the index (I) or ring (R) finger alone (single-finger tapping) and by the alternate use of the I and middle (M) fingers or the R and little (L) fingers (double-finger tapping). Each subject also provided subjective rankings of perceived task difficulty, as well as muscular fatigue, among the tapping tasks. The activated areas of the brain during tapping by the R finger were more extensive in the frontal and temporal areas, as well as the cerebellum, than during tapping by the I finger. A similar result was revealed for the comparison of the RL and IM finger pairs. The perceived task difficulty, as well as muscular fatigue, was also higher for the R finger or RL finger pair than the I finger or IM finger pair. These results indicate that movement of individual fingers or finger pairs with different levels of task difficulty is represented differently in the structures of cortical and subcortical systems. A comparison of the single- and double-finger modes revealed that in addition to the brain areas activated during single-finger mode, the bilateral dorsal premotor and left primary motor/sensory areas and the right anterior cerebellum were also activated during the double-finger mode. These additional areas could be essential structures for the execution and motor sequence operation of the two fingers.