Yoshiyuki Hirano

On the contribution of deoxy-hemoglobin to MRI gray-white matter phase contrast at high field.

High field (> or =7 T) MRI studies based on signal phase have been used to improve visualization of the fine structure of the brain, most notably the major white matter fiber bundles, the gray-white matter subdivision, and the laminar cortical architecture. The observed contrast has been attributed in part to local variations in magnetic susceptibility arising from iron in storage proteins and tissue lipid. Another contribution could come from the paramagnetic blood constituent deoxy-hemoglobin, the tissue concentration of which may vary through local variations in vascular density. To investigate this possibility, we examined phase contrast between gray and white matter in rats after intravenous administration of a superparamagnetic contrast agent at various dosages. At the maximum dosage (3 mg Fe/kg), which resulted in an estimated paramagnetic susceptibility shift 4-8 times larger than deoxy-hemoglobin, we observed a negligible increase in phase contrast between gray and white matter. This result suggests that endogenous deoxy-hemoglobin has no significant contribution to phase contrast between gray and white matter.

Direct imaging of macrovascular and microvascular contributions to BOLD fMRI in layers IV-V of the rat whisker-barrel cortex

The spatiotemporal characteristics of the hemodynamic response to increased neural activity were investigated at the level of individual intracortical vessels using BOLD-fMRI in a well-established rodent model of somatosensory stimulation at 11.7 T. Functional maps of the rat barrel cortex were obtained at 150 × 150 × 500 μm spatial resolution every 200 ms. The high spatial resolution allowed separation of active voxels into those containing intracortical macro vessels, mainly vein/venules (referred to as macrovasculature), and those enriched with arteries/capillaries and small venules (referred to as microvasculature) since the macro vessel can be readily mapped due to the fast T2 decay of blood at 11.7 T. The earliest BOLD response was observed within layers IV-V by 0.8s following stimulation and encompassed mainly the voxels containing the microvasculature and some confined macrovasculature voxels. By 1.2s, the BOLD signal propagated to the macrovasculature voxels where the peak BOLD signal was 2-3 times higher than that of the microvasculature voxels. The BOLD response propagated in individual venules/veins far from neuronal sources at later times. This was also observed in layers IV-V of the barrel cortex after specific stimulation of separated whisker rows. These results directly visualized that the earliest hemodynamic changes to increased neural activity occur mainly in the microvasculature and spread toward the macrovasculature. However, at peak response, the BOLD signal is dominated by penetrating venules even at layers IV-V of the cortex.

fMRI in the awake marmoset: somatosensory-evoked responses, functional connectivity, and comparison with propofol anesthesia

Functional neuroimaging in animal models is essential for understanding the principles of neurovascular coupling and the physiological basis of fMRI signals that are widely used to study sensory and cognitive processing in the human brain. While hemodynamic responses to sensory stimuli have been characterized in humans, animal studies are able to combine very high resolution imaging with invasive measurements and pharmacological manipulation. To date, most high-resolution studies of neurovascular coupling in small animals have been carried out in anesthetized rodents. Here we report fMRI experiments in conscious, awake common marmosets (Callithrix jacchus), and compare responses to animals anesthetized with propofol. In conscious marmosets, robust BOLD fMRI responses to somatosensory stimulation of the forearm were found in contralateral and ipsilateral regions of the thalamus, primary (SI) and secondary (SII) somatosensory cortex, and the caudate nucleus. These responses were markedly stronger than those in anesthetized marmosets and showed a monotonic increase in the amplitude of the BOLD response with stimulus frequency. On the other hand, anesthesia significantly attenuated responses in thalamus, SI and SII, and abolished responses in caudate and ipsilateral SI. Moreover, anesthesia influenced several other aspects of the fMRI responses, including the shape of the hemodynamic response function and the interareal (SI-SII) spontaneous functional connectivity. Together, these findings demonstrate the value of the conscious, awake marmoset model for studying physiological responses in the somatosensory pathway, in the absence of anesthesia, so that the data can be compared most directly to fMRI in conscious humans.

Effects of chewing on cognitive processing speed

In recent years, chewing has been discussed as producing effects of maintaining and sustaining cognitive performance. We have reported that chewing may improve or recover the process of working memory; however, the mechanisms underlying these phenomena are still to be elucidated. We investigated the effect of chewing on aspects of attention and cognitive processing speed, testing the hypothesis that this effect induces higher cognitive performance. Seventeen healthy adults (20-34 years old) were studied during attention task with blood oxygenation level-dependent functional (fMRI) at 3.0 T MRI. The attentional network test (ANT) within a single task fMRI containing two cue conditions (no cue and center cue) and two target conditions (congruent and incongruent) was conducted to examine the efficiency of alerting and executive control. Participants were instructed to press a button with the right or left thumb according to the direction of a centrally presented arrow. Each participant underwent two back-to-back ANT sessions with or without chewing gum, odorless and tasteless to remove any effect other than chewing. Behavioral results showed that mean reaction time was significantly decreased during chewing condition, regardless of speed-accuracy trade-off, although there were no significant changes in behavioral effects (both alerting and conflict effects). On the other hand, fMRI analysis revealed higher activations in the anterior cingulate cortex and left frontal gyrus for the executive network and motor-related regions for both attentional networks during chewing condition. These results suggested that chewing induced an increase in the arousal level and alertness in addition to an effect on motor control and, as a consequence, these effects could lead to improvements in cognitive performance.

Longitudinal Functional Magnetic Resonance Imaging in Animal Models

Functional magnetic resonance imaging (fMRI) has had an essential role in furthering our understanding of brain physiology and function. fMRI techniques are nowadays widely applied in neuroscience research, as well as in translational and clinical studies. The use of animal models in fMRI studies has been fundamental in helping elucidate the mechanisms of cerebral blood-flow regulation, and in the exploration of basic neuroscience questions, such as the mechanisms of perception, behavior, and cognition. Because animals are inherently non-compliant, most fMRI performed to date have required the use of anesthesia, which interferes with brain function and compromises interpretability and applicability of results to our understanding of human brain function. An alternative approach that eliminates the need for anesthesia involves training the animal to tolerate physical restraint during the data acquisition. In the present chapter, we review these two different approaches to obtaining fMRI data from animal models, with a specific focus on the acquisition of longitudinal data from the same subjects.

Chewing-induced regional brain activity in edentulous patients who received mandibular implant-supported overdentures: A preliminary report

PURPOSEnWe used functional magnetic resonance imaging (fMRI) to investigate the change in brain regional activity during gum chewing when edentulous subjects switched from mandibular complete dentures to implant-supported removable overdentures.nnnMETHODSnFour edentulous patients (3 males and 1 female, aged 64 to 79 years) participated in the study. All subjects received a set of new maxillary and mandibular complete dentures (CD), followed by a maxillary complete denture and a new mandibular implant-supported removable overdentures (IOD). A 3-T fMRI scanner produced images of the regional brain activity for each subject that showed changes in the blood-oxygenation-level-dependent (BOLD) contrast in the axial orientation during gum-chewing with CD and IOD.nnnRESULTSnRegion-of-interest analysis showed that IOD treatment significantly suppressed chewing-induced brain activity in the prefrontal cortex. The chewing-induced brain activities in the primary sensorimotor cortex and cerebellum tended to decrease with IOD treatment, however they did not reach to significance level. There was no change in brain activity in the supplementary motor area, thalamus and insula between gum chewing with CD and IOD. Group comparison using statistical parametrical mapping further showed that, within the prefrontal cortex, the neural activity of the frontal pole significantly decreased during gum-chewing with IOD when compared to that with CD (P<0.05).nnnCONCLUSIONnDespite the limitation of a small sample size, these results suggest that the gum-chewing task in elderly edentulous patients resulted in differential neural activity in the frontal pole within the prefrontal cortex between the 2 prosthodontic therapies-mandibular CD and IOD.

Chewing and Attention: A Positive Effect on Sustained Attention

Chewing is crushing food not only to aid swallowing and digestion, but also to help stress relief and regulate cognitive function, especially in attention. It is well known that chewing gum is used for sleepiness prevention during work, learning, and driving, suggesting a link between chewing and sustained attention. We hypothesized that chewing elevates attention and/or alertness, leading to improvements in cognitive performance. We carried out a systematic review of the PubMed database. We inspected the attributes of effects on attention in studies investigating the effects of chewing on attention or alertness conducted with pre-post design in healthy subjects, except elderly. We identified 151 references, 22 of which were included: 14 (64%) showed positive attributes of effects on attention, 1 (5%) showed negative attributes of effects on attention, 5 (23%) showed both positive and negative attributes of effects on attention, and 2 (9%) showed no significant attributes of effects on attention. Thus, positive attributes of effects of chewing on attention, especially on sustained attention, were shown in over half of the reports. These effects also appeared with improvement in mood and stress relief and were influenced by time-on-task effect. Further studies are needed, but chewing could be useful for modifying cognitive function.

Activation of dorsolateral prefrontal cortex in a dual neuropsychological screening test: An fMRI approach

BackgroundThe Kana Pick-out Test (KPT), which uses Kana or Japanese symbols that represent syllables, requires parallel processing of discrete (pick-out) and continuous (reading) dual tasks. As a dual task, the KPT is thought to test working memory and executive function, particularly in the prefrontal cortex (PFC), and is widely used in Japan as a clinical screen for dementia. Nevertheless, there has been little neurological investigation into PFC activity during this test.MethodsWe used functional magnetic resonance imaging (fMRI) to evaluate changes in the blood oxygenation level-dependent (BOLD) signal in young healthy adults during performance of a computerized KPT dual task (comprised of reading comprehension and picking out vowels) and compared it to its single task components (reading or vowel pick-out alone).ResultsBehavioral performance of the KPT degraded compared to its single task components. Performance of the KPT markedly increased BOLD signal intensity in the PFC, and also activated sensorimotor, parietal association, and visual cortex areas. In conjunction analyses, bilateral BOLD signal in the dorsolateral PFC (Brodmanns areas 45, 46) was present only in the KPT.ConclusionsOur results support the central bottleneck theory and suggest that the dorsolateral PFC is an important mediator of neural activity for both short-term storage and executive processes. Quantitative evaluation of the KPT with fMRI in healthy adults is the first step towards understanding the effects of aging or cognitive impairment on KPT performance.

Comparison in decision-making between bulimia nervosa, anorexia nervosa, and healthy women: influence of mood status and pathological eating concerns

BackgroundDecision-making is reported to be impaired in anorexia nervosa (AN) and bulimia nervosa (BN), but the influence of mood status, pathophysiological eating, and weight concerns on the performance of decision-making ability between AN and BN is still unclear. The aims of this study were to investigate differential impairments in the decision-making process between AN, BN, and healthy controls (HC), and secondly, to explore the role of mood status, such as anxiety, depression, pathological eating, and weight concerns, in decision-making ability.MethodsPatients suffering from AN (nu2009=u200922), BN (nu2009=u200936) and age-matched HC (nu2009=u200951) were assessed for their decision-making abilities using the Iowa Gambling Task (IGT). Self-reported questionnaires including the Eating Disorder Examination Questionnaire (EDE-Q), the Bulimia Investigatory Test, Edinburgh (BITE), the Eating Disorders Inventory, the Maudsley Obsessive-Compulsive Inventory measuring obsessive-compulsive traits, the Hospital Anxiety and Depression Scale, and the Toronto Alexithymia Scale were used to assess pathological eating concerns and attitude to feelings.ResultsSignificant differences in IGT performance were observed between BN and HC. Significant negative correlation was found between IGT performance and the BITE symptom subscale in AN. In BN, there was a negative correlation between the EDE-Q weight concerns subscale and IGT performance. It was also found that increased anxiety, depression, and eating/weight concerns predicted poorer decision-making.ConclusionDifferent patterns of association between pathological eating concerns/behaviors and performances in decision-making ability were found between AN, BN, and HC. Anxiety, depressive mood status, and eating/weight concerns were related to decision-making ability.

Repetitive Transcranial Magnetic Stimulation Changes Cerebral Oxygenation on the Left Dorsolateral Prefrontal Cortex in Bulimia Nervosa: A Near-Infrared Spectroscopy Pilot Study

Previous studies showed that food craving in eating disorders can be weakened with high-frequency repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC). The aims of this study were to assess cerebral oxygenation change induced with rTMS and to assess the short-term impact of rTMS on food craving and other bulimic symptoms in patients with bulimia nervosa (BN). Eight women diagnosed with BN according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria participated in this study. We measured haemoglobin concentration changes in the DLPFC with near-infrared spectroscopy during cognitive tasks measuring self-regulatory control in response to food photo stimuli, both at baseline and after a single session of rTMS. Subjective ratings for food cravings demonstrated significant reduction. A significant decrease in cerebral oxygenation of the left DLPFC was also observed after a single session of rTMS. Measurement with NIRS after rTMS intervention may be applicable for discussing the mechanisms underlying rTMS modulation in patients with BN.