Anatomical variability, multi-modal coordinate systems, and precision targeting in the marmoset brain.

Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses.

Oral hypofunction and its relation to frailty and sarcopenia in community-dwelling older people.

OBJECTIVE: The purpose of this study was to examine the frequency of oral hypofunction in community-dwelling older people and determine its relationship with frailty and sarcopenia. BACKGROUND: Previous studies have shown that frailty and sarcopenia are associated with decreased oral function. However, these studies have only evaluated frailty or sarcopenia alone and have not evaluated their relationship with each other. MATERIALS AND METHODS: The participants were community-dwelling independent older people in Kyoto. Their oral function evaluation included seven items (oral hygiene, oral dryness, occlusal force, tongue-lip motor function, tongue pressure, masticatory function and swallowing function). Oral hypofunction was defined as abnormalities in at least three of these items. The frailty status was classified into three categories (robust, pre-frail and frail) according to the frailty phenotype and deficit-accumulation models. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) Consensus. The relationships between oral function and frailty were analysed using logistic regression analyses, after adjusting for sarcopenia. RESULTS: Among the 340 participants that were analysed (69 men, 271 women; average age: 75.0 years), 182 (53.5%) had oral hypofunction (40 men, 142 women; average age: 76.8 years). There was a significant relationship between oral hypofunction and deficit-accumulation model-assessed frailty, after adjusting for sarcopenia. CONCLUSION: Almost half of the community-dwelling older people have oral hypofunction, which is significantly related to comprehensive frailty and sarcopenia.

Delayed Swallowing Reflex is Overlooked in Swallowing Screening Among Acute Stroke Patients.

BACKGROUND AND PURPOSE: Dysphagia in the acute phase of stroke contributes significantly to poor outcomes and is associated with the development of aspiration pneumonia and malnutrition. Therefore, an accurate evaluation of swallowing is necessary before initiating oral food intake. The modified water swallow test (MWST) and the repetitive saliva swallow test (RSST) are commonly used as bedside screening methods for swallowing dysfunction, but it is unclear whether other factors contribute to dysphagia and consequent aspiration. The purpose of this study was to identify characteristics that might be overlooked in screening tests. METHODS: Participants were prospectively selected from patients hospitalized for stroke at the Suiseikai Kajikawa Hospital between August 1, 2016 and June 30, 2018. Inclusion criteria were conscious and stable medical condition, and patients who were diagnosed with dementia were excluded. A videofluoroscopic (VF) swallowing study was carried out on all patients who met the inclusion/exclusion criteria and who passed both the MWST and the RSST. RESULTS: Aspiration was observed in 16 of 172 patients (9.3%) when swallowing 3 ml of water. These aspirated patients showed significantly delayed swallowing reflex on VF. CONCLUSIONS: Swallowing evaluation using a combination of the MWST and the RSST is reasonably effective. However, patients who show a delayed swallowing reflex might be overlooked by this screening procedure.

Individual identity and affective valence in marmoset calls: in vivo brain imaging with vocal sound playback.

As with humans, vocal communication is an important social tool for nonhuman primates. Common marmosets (Callithrix jacchus) often produce whistle-like 'phee' calls when they are visually separated from conspecifics. The neural processes specific to phee call perception, however, are largely unknown, despite the possibility that these processes involve social information. Here, we examined behavioral and whole-brain mapping evidence regarding the detection of individual conspecific phee calls using an audio playback procedure. Phee calls evoked sound exploratory responses when the caller changed, indicating that marmosets can discriminate between caller identities. Positron emission tomography with [18F] fluorodeoxyglucose revealed that perception of phee calls from a single subject was associated with activity in the dorsolateral prefrontal, medial prefrontal, orbitofrontal cortices, and the amygdala. These findings suggest that these regions are implicated in cognitive and affective processing of salient social information. However, phee calls from multiple subjects induced brain activation in only some of these regions, such as the dorsolateral prefrontal cortex. We also found distinctive brain deactivation and functional connectivity associated with phee call perception depending on the caller change. According to changes in pupillary size, phee calls from a single subject induced a higher arousal level compared with those from multiple subjects. These results suggest that marmoset phee calls convey information about individual identity and affective valence depending on the consistency or variability of the caller. Based on the flexible perception of the call based on individual recognition, humans and marmosets may share some neural mechanisms underlying conspecific vocal perception.

Marmoset Serotonin 5-HT1A Receptor Mapping with a Biased Agonist PET Probe 18F-F13714: Comparison with an Antagonist Tracer 18F-MPPF in Awake and Anesthetized States.

BACKGROUND: In vivo mapping by positron emission tomography of the serotonin 1A receptors has been hindered by the lack of suitable agonist positron emission tomography probes. 18F-labeled F13714 is a recently developed biased agonist positron emission tomography probe that preferentially targets subpopulations of serotonin 1A receptors in their "active state," but its brain labeling pattern in nonhuman primate has not been described. In addition, a potential confound in the translatability of PET data between nonhuman animal and human arise from the use of anesthetics that may modify the binding profiles of target receptors. METHODS: Positron emission tomography scans were conducted in a cohort of common marmosets (n=4) using the serotonin 1A receptor biased agonist radiotracer, 18F-F13714, compared with a well-characterized 18F-labeled antagonist radiotracer, 18F-MPPF. Experiments on each animal were performed under both consciousness and isoflurane-anesthesia conditions. RESULTS: 18F-F13714 binding distribution in marmosets by positron emission tomography differs markedly from that of the 18F-MPPF. Whereas 18F-MPPF showed highest binding in hippocampus and amygdala, 18F-F13714 showed highest labeling in other regions, including insular and cingulate cortex, thalamus, raphe, caudate nucleus, and putamen. The binding potential values of 18F-F13714 were about one-third of those observed with 18F-MPPF, with marked individual- and region-specific differences under isoflurane-anesthetized vs conscious conditions. CONCLUSIONS: These findings highlight the importance of investigating the brain imaging of serotonin 1A receptors using agonist probes such as 18F-F13714, which may preferentially target subpopulations of serotonin 1A receptors in specific brain regions of nonhuman primate as a biased agonist.

Cortical adaptation of the night monkey to a nocturnal niche environment: a comparative non-invasive T1w/T2w myelin study.

Night monkeys (Aotus) are the only genus of monkeys within the Simian lineage that successfully occupy a nocturnal environmental niche. Their behavior is supported by their sensory organs' distinctive morphological features; however, little is known about their evolutionary adaptations in sensory regions of the cerebral cortex. Here, we investigate this question by exploring the cortical organization of night monkeys using high-resolution in-vivo brain MRI and comparative cortical-surface T1w/T2w myeloarchitectonic mapping. Our results show that the night monkey cerebral cortex has a qualitatively similar but quantitatively different pattern of cortical myelin compared to the diurnal macaque and marmoset monkeys. T1w/T2w myelin and its gradient allowed us to parcellate high myelin areas, including the middle temporal complex (MT +) and auditory cortex, and a low-myelin area, Brodmann area 7 (BA7) in the three species, despite species differences in cortical convolutions. Relative to the total cortical-surface area, those of MT + and the auditory cortex are significantly larger in night monkeys than diurnal monkeys, whereas area BA7 occupies a similar fraction of the cortical sheet in all three species. We propose that the selective expansion of sensory areas dedicated to visual motion and auditory processing in night monkeys may reflect cortical adaptations to a nocturnal environment.

Relationship between Food Crushing and Oral Function in Older Adults Requiring Nursing Home Care: A Pilot Study.

We investigated how jelly is crushed and examined the relationship between tongue pressure and tongue food crushing ability among older adults requiring nursing home care. Seventy-two participants were instructed to freely crush the test foods soft jelly (SJ) and hard jelly (HJ). We visually evaluated the crushability of the test food and identified the intraoral tissues (active sites) used to crush the test food. The active sites were consistent for all participants for both SJ and HJ, and they included the maxillary and mandibular teeth in 41 participants, teeth and residual ridges in 15 participants, maxillary and mandibular residual ridges in 10 participants, and tongue and palate in six participants. Two participants failed to crush the SJ; the active sites in both participants were the tongue and palate. No participant using the tongue and palate as active sites could crush the HJ. Furthermore, 64 participants could crush the SJ and 23 could crush the HJ using the tongue and palate. The cutoff value of the tongue pressure for crushability of the HJ was 22.0 kPa. Assessing tongue pressure and intraoral active sites involved in food crushing could help determine an appropriate diet for older adults requiring nursing home care.

Comparison of the Iowa Oral Performance Instrument and JMS tongue pressure measurement device.

BACKGROUND/PURPOSE: Tongue pressure measurement conveys important information about eating and swallowing function. The Iowa Oral Performance Instrument® (IOPI) and KAY Swallowing Workstation® are internationally used for tongue pressure measurement, but for legal reasons cannot be used in Japan; rather the JMS tongue pressure measurement device® has been approved for use in Japan. However, it is not clear whether measurement obtained with these devices are directly comparable. MATERIALS AND METHODS: This study investigated the correlation between the maximum tongue pressure data measured by the IOPI and the JMS tongue pressure measurement device in young healthy participants (34 males; 23.2 ±â€¯2.0 years old, and 40 females; 21.4 ±â€¯1.3 years old). RESULTS: Measurements obtained with these two devices showed significant correlations in the total cohort, and in male and female participants, separately (P < 0.05). CONCLUSION: These findings demonstrate that the measurements obtained with the JMS device is comparable to those obtained with the IOPI. In Japan, JMS tongue pressure measurement device is used not only in dysphagia research field, but also geriatrics field, and extensive and detailed investigations has been carried out.

Association between stroke lesions and videofluoroscopic findings in acute stroke patients.

BACKGROUND AND PURPOSE: We aimed to assess stroke lesions, which play a key role in determining swallowing dysfunction, and findings of videofluoroscopy (VF), which provides the most accurate instrumental assessment for evaluating swallowing function, in patients with acute stroke. METHODS: We enrolled 342 patients with first-time acute stroke (age 70.4 ± 12.6 years, 142 female). Patients with dementia and altered mental status due to severe stroke were excluded. All patients underwent cranial magnetic resonance imaging to identify the location of stroke lesion, VF, and tongue pressure measurement. RESULTS: Aspiration was detected in 45 (13.2%) patients. Multivariate analysis identified parietal lobe lesion and the National Institutes of Health Stroke Scale (NIHSS) score as independent significant factors for aspiration (odds ratio 6.33, 95% confidence interval [CI] 2.25-17.84, p < 0.001; odds ratio 1.12, 95% CI 1.03-1.20, p = 0.004, respectively). Swallowing reflex delay was detected in 58 (17.0%) patients. Multivariate analysis identified habitual drinking, basal ganglia lesion, and the NIHSS score as independent significant factors for swallowing reflex delay (odds ratio 0.51, 95% CI 0.26-0.99, p = 0.047; odds ratio 1.91, 95% CI 1.09-3.67, p = 0.041; odds ratio 1.12, 95% CI 1.05-1.20, p < 0.001, respectively). Additionally, oral cavity and pharyngeal residues were independently associated with tongue pressure. CONCLUSION: Parietal lobe lesions are associated with aspiration and basal ganglia lesions with swallowing reflex delay.

Five-year change in maximum tongue pressure and physical function in community-dwelling elderly adults.

BACKGROUND/PURPOSE: To identify age-related changes in maximum tongue pressure (MTP), it is necessary to determine individual biological age. The fitness age score (FAS) is used to calculate the biological age, based on the one-leg standing time with eyes open, vertical jump height, grip strength, functional reach, and 10-m walk time. MATERIALS AND METHODS: The study included 112 community-dwelling elderly adults (42 males and 70 females). We investigated MTP, FAS, and body mass index (BMI) at baseline and 5 years later. MTP was determined with a pressure measurement device. RESULTS: A significant reduction in MTP, FAS, and BMI in both male and female subjects was observed at 5 years. A negative correlation between change in MTP and baseline MTP was observed, but there was no correlation between MTP change and baseline FAS, BMI, and change in FAS and BMI. CONCLUSION: Age-related decline in MTP might be associated with high MTP, reflecting decreased reserve. Additionally, age-related decline in tongue function might be different from that of physical function.

The mechanisms by which latanoprost free acid inhibits human carbonic anhydrase I and II.

Latanoprost, a prostaglandin F2 alpha analogue, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. Carbonic anhydrase (CA) inhibitors are also used to reduce ocular hypertension by decreasing aqueous humor secretion, and are given in combination with prostaglandin F2 alpha analogue. It has been shown that prostaglandin F2 alpha, Minprostin F2 alpha, has been shown to increase the carbonic anhydrase (CA) activity and blood pressure. However, the effects of latanoprost on CA have not been clarified. Therefore, we studied the effects of latanoprost free acid on human carbonic anhydrase (HCA) I and II using the stopped flow method. Latanoprost free acid inhibited the hydration activity of HCA I or II by a noncompetitive mechanism. The inhibition constants (Ki) of latanoprost free acid for HCA I and II were 0.22 and 2.3 mM, respectively. Therefore, latanoprost free acid is a weak inhibitor of HCA I or II. AutoDock simulation of the latanoprost free acid-HCA I or II complex showed that the carboxylic moiety of latanoprost free acid, which is located at the end of the molecule, binds to the zinc ion of the active site by stretching of the chain of latanoprost free acid through the narrow and deep active site cavity of HCA I or II. In the active site cavity of HCA I or II, one side is hydrophilic and the other is hydrophobic. AutoDock simulation results clearly showed that latanoprost free acids lie down on the hydrophobic sides of the active site cavities in HCA I and II. The noncompetitive inhibition mechanism and the binding mode of latanoprost free acid indicate that the behavior of latanoprost free acid is very similar to that of simple anions.