Different Food Preferences in Patients with Gastrointestinal Disorders.

Objective Gastrointestinal (GI) disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and inflammatory bowel disease (IBD) can exhibit overlapping GI symptoms, including abdominal pain and alterations in bowel habits. The symptoms of GI disorders are commonly considered to be triggered and exacerbated by fatty food intake. Therefore, this study aimed to compare the food preferences of patients with GI disorders. Methods Forty food images (including fatty and light foods) and 20 animal images were selected to evaluate food preferences. The preference score was assessed using a visual analog scale ranging from 1 to 100. GI symptoms were evaluated using the GI Symptom Rating Scale (GSRS), and correlations between the GSRS and preference scores were investigated. Results Overall, 22 healthy controls and 23, 29, 27, and 20 patients with FD, IBS, GERD, and IBD, respectively, were enrolled. The preference score for all foods in patients with FD was significantly lower than that in healthy controls and those with IBS, GERD, and IBD (52.9 vs. 66.5 vs. 68.5 vs. 69.1 vs. 70.7, p<0.01). The score of fatty foods was lower in patients with FD than in healthy controls and those with IBS, GERD, and IBD (43.8 vs. 72.3 vs. 77.5 vs. 77.4 vs. 80.7, p<0.01), whereas that of light foods and animal images was not different among the groups. No significant correlation was found between the preference score and symptom severity. Conclusions Patients with FD had a negative preference for foods, particularly fatty foods, independent of the severity of GI symptoms.

Contribution of default mode network to game and delayed-response task performance: Power and connectivity analyses of theta oscillation in the monkey.

Neuroimaging studies have demonstrated the presence of a default mode network (DMN) which shows greater activity during rest, and an executive network (EN) which is activated during cognitive tasks. DMN and EN are thought to have competing functions. However, recent studies reported that the two networks show coactivation during some cognitive tasks. To clarify how DMN works and how DMN interacts with EN for cognitive control, we recorded EEG activities in the medial prefrontal (anterior DMN: aDMN), posterior cingulate/precuneus (posterior DMN: pDMN), and lateral prefrontal (EN) areas in the monkey. As cognitive tasks, we employed a monkey-monkey competitive video game (GAME) and a delayed-response (DR) task. We focused on theta oscillation because of its importance in cognitive control. We also examined theta band connectivity among the three network areas using the Granger causality analysis. DMN and EN were found to work cooperatively in both tasks. In all the three network areas, we found GAME-task-related, but no DR-task-related, increase in theta power from the resting level, maybe because of the higher cognitive demand associated with the GAME task performance. The information flow conveyed by the theta oscillation was directed more to aDMN than from aDMN for both tasks. The GAME-task-related increase in theta power in aDMN is supposed to be supported by more information flow conveyed by the theta oscillation from EN and pDMN.

Brain activity in response to food images in patients with irritable bowel syndrome and functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are caused and exacerbated by consumption of fatty foods. However, no study has evaluated brain activity in response to food images in patients with disorders of gut-brain interaction (DGBI). This study aimed to compare food preference and brain activity when viewing food images between patients with DGBI and healthy controls. METHODS: FD and IBS were diagnosed using the ROME IV criteria. Food preference was assessed using a visual analog scale (VAS). Brain activity in the prefrontal cortex (PFC) in response to food images was investigated using functional near-infrared spectroscopy (fNIRS). RESULTS: Forty-one patients were enrolled, including 25 with DGBI. The mean VAS scores for all foods (controls vs. FD vs. IBS: 69.1 ± 3.3 vs. 54.8 ± 3.8 vs. 62.8 ± 3.7, p = 0.02), including fatty foods (78.1 ± 5.4 vs. 43.4 ± 6.3 vs. 64.7 ± 6.1, p < 0.01), were the lowest in patients with FD among all groups. Patients with FD had significantly higher brain activity in the left PFC than those with IBS and healthy controls (mean z-scores in controls vs. FD vs. IBS: - 0.077 ± 0.03 vs. 0.125 ± 0.04 vs. - 0.002 ± 0.03, p < 0.001). CONCLUSIONS: Patients with DGBI, particularly those with FD, disliked fatty foods. The brain activity in patients with DGBI differed from that in healthy controls. Increased activity in the PFC of patients with FD was confirmed.

Artificial Intelligence-Based Diagnostic Support System for Functional Dyspepsia Based on Brain Activity and Food Preference.

Background and aim Disorders of gut-brain interaction (DGBI) are disorders where no organic clinical abnormalities are detected such as functional dyspepsia (FD) and irritable bowel syndrome (IBS). The brain activity of individuals with FD and IBS differs from that of healthy controls. Artificial intelligence can distinguish healthy controls from individuals with DGBI using several biomarkers. This study aimed to establish an artificial intelligence-based diagnostic support system using food preferences and brain activity in patients with DGBI. Methods ROME IV criteria were used to diagnose patients with FD and IBS. Their food preference was scored using a visual analog scale, and brain activity in the prefrontal cortex was investigated using functional near-infrared spectroscopy (fNIRS). The diagnostic model was developed based on the brain activity and visual analog scale scores for food using an artificial neural network model. Results Forty-one participants, including 25 patients with DGBI were enrolled in the study. The accuracy of the artificial intelligence-based diagnostic model using an artificial neural network in differentiating between healthy controls and patients with DGBI and between healthy controls and those with FD were 72.3% and 77.1%, respectively. Conclusions The artificial intelligence-based diagnostic model using brain activity and preference to food images showed sufficiently high accuracy in distinguishing patients with DGBI from healthy controls, and those with FD from healthy controls. Therefore, the fNIRS system provides objective evidence for diagnosing DGBI.

Individual differences in processing ability to transform visual stimuli during the mental rotation task are closely related to individual motor adaptation ability.

Mental rotation (MR) is a well-established experimental paradigm for exploring human spatial ability. Although MR tasks are assumed to be involved in several cognitive processes, it remains unclear which cognitive processes are related to the individual ability of motor adaptation. Therefore, we aimed to elucidate the relationship between the response time (RT) of MR using body parts and the adaptive motor learning capability of gait. In the MR task, dorsal hand, palmar plane, dorsal foot, and plantar plane images rotated in 45° increments were utilized to measure the RTs required for judging hand/foot laterality. A split-belt treadmill paradigm was applied, and the number of strides until the value of the asymmetrical ground reaction force reached a steady state was calculated to evaluate the individual motor adaptation ability. No significant relationship was found between the mean RT of the egocentric perspectives (0°, 45°, and 315°) or allocentric perspectives (135°, 180°, and 225°) and adaptive learning ability of gait, irrespective of body parts or image planes. Contrarily, the change rate of RTs obtained by subtracting the RT of the egocentric perspective from that of the allocentric perspective in dorsal hand/foot images that reflect the time to mentally transform a rotated visual stimulus correlated only with adaptive learning ability. Interestingly, the change rate of RTs calculated using the palmar and plantar images, assumed to reflect the three-dimensional transformation process, was not correlated. These findings suggest that individual differences in the processing capability of visual stimuli during the transformation process involved in the pure motor simulation of MR tasks are precisely related to individual motor adaptation ability.

Monkey Prefrontal Single-Unit Activity Reflecting Category-Based Logical Thinking Process and Its Neural Network Model.

Category-based thinking is a fundamental form of logical thinking. Here, we aimed to investigate its neural process at the local circuit level in the prefrontal cortex (PFC). We recorded single-unit PFC activity while male monkeys (Macaca fuscata) performed a task in which the category and rule were prerequisites of logical thinking and the outcome contingency was its consequence. Different groups of neurons coded a single type of information discretely or multiple types in a transitional form. Results of time-by-time analysis of neuronal activity suggest an information flow from category-coding and rule-coding neurons to transitional intermediate neurons, and then to contingency-coding neurons. Category-coding, rule-coding, and contingency-coding neurons showed stable coding of information, whereas intermediate neurons showed dynamic coding, as if it integrated category and rule to derive contingency. A similar process was confirmed by using a spiking neural network model that consisted of subnetworks coding category and rule on the input layer and those coding contingency on the output layer, with a subnetwork for integration in the intermediate layer. These results suggest that category-based logical thinking is realized in the PFC by separated neural populations organized for working in a feedforward manner.SIGNIFICANCE STATEMENT To elucidate the neural process for logical thinking, we combined an in-depth analysis of single-unit activity data with a biologically plausible computational model. Results of time-by-time analysis of prefrontal neuronal activity suggest an information flow from category-coding and rule-coding neurons to transitional intermediate neurons, and then to contingency-coding neurons. Category-coding, rule-coding, and contingency-coding neurons showed stable coding, whereas intermediate neurons showed dynamic coding, as if they integrated category and rule to derive contingency. A spiking neural network model reproduced similar temporal changes of information as the recorded neuronal data. Our results suggest that the prefrontal cortex (PFC) is critically involved in category-based thought process, and this process may be produced by separated neural populations organized for working in a feedforward manner.

Effects of different exercise intensities on prefrontal activity during a dual task.

The effects of physical exercise on cognitive tasks have been investigated. However, it is unclear how different exercise intensities affect the neural activity. In this study, we investigated the neural activity in the prefrontal cortex (PFC) by varying the exercise intensity while participants performed a dual task (DT). Twenty healthy young adults performed serial subtraction while driving a cycle ergometer. Exercise intensity was set to one of three levels: low, moderate, or high intensity. We did not find any significant change in PFC activity during DT under either the control (no exercise) or low-intensity conditions. In contrast, we observed a significant increase in PFC activity during DT under moderate- and high-intensity conditions. In addition, we observed complex hemodynamics after DT. PFC activity decreased from baseline after DT under the control condition, while it increased under the low-intensity condition. PFC activity remained higher than the baseline level after DT under the moderate-intensity condition but returned to baseline under the high-intensity condition. The results suggest that moderate-intensity exercise with a cognitive load effectively increases PFC activity, and low-intensity exercise may increase PFC activity when combined with a cognitive load.

Utilization of Anion-exchange Guard Column as an Ion Chromatographic Column of Anions Including Application to Simultaneous Separation of Anions and Cations.

This study demonstrated that a guard column containing anion-exchange resin has the potential for use as a separation column for acid eluent. Specifically, a 1-cm long anion-exchange guard column with a 4.6-mm internal diameter provided good separation of monovalent inorganic anions, by elution of 8 mM tartaric acid or 4 mM malic acid. Using the guard column with acid eluent could be applied to evaluation of nitrite and nitrate ions in mountain and urban river water samples. When the guard column was connected in front of a cation-exchange separation column (15 cm long × 4.6 mm internal diameter) in a series, the system provided simultaneous separation of anions and cations in eluent of 8 mM tartaric acid and 0.5 mM 18-crown-6 ether by a single injection.

Behavioral evidence for the use of functional categories during group reversal task performance in monkeys.

A functional category is a set of stimuli that are regarded as equivalent independently of their physical properties and elicit the same behavioral responses. Major psychological theories suggest the ability to form and utilize functional categories as a basis of higher cognition that markedly increases behavioral flexibility. Vaughan claimed the category use in pigeons on the basis of partition, a mathematical criterion for equivalence, however, there have been some criticisms that the evidence he showed was insufficient. In this study, by using a group reversal task, a procedure originally used by Vaughan, we aimed to gather further evidence to prove the category use in animals. Macaque monkeys, which served as subjects in our study, could efficiently perform the task not only with familiar stimulus sets as Vaughan demonstrated but also with novel sets, and furthermore the task performance was stable even when the number of stimuli in a set was increased, which we consider as further evidence for the category use in animals. In addition, by varying the timing of the reversal, we found that a category formation takes place soon after encountering new stimuli, i.e. in a few blocks of trial after a novel stimulus set was introduced.

Oral Administration of Methylphenidate (Ritalin) Affects Dopamine Release Differentially Between the Prefrontal Cortex and Striatum: A Microdialysis Study in the Monkey.

Methylphenidate (MPH; trade name Ritalin) is a widely used drug for the treatment of attention deficit hyperactivity disorder (ADHD) and is often used as a cognitive enhancer. Because MPH increases dopamine (DA) release by blocking the DA transporter in the human striatum, MPH is supposed to work on attention and cognition through a DA increase in the striatum. However, ADHD patients show impaired prefrontal cortex (PFC) function and MPH administration is associated with increased neural activity in the PFC. Although MPH is indicated to increase DA release in the rat PFC, there has been no study to examine MPH-induced DA changes in the human PFC because of technical difficulties associated with the low level of PFC DA receptors. Using the microdialysis technique, we examined the effects of oral administration of MPH on DA release in both the PFC and striatum in the monkey. We also tested the effect of MPH on cognitive task performance. As in human studies, in the striatum, both high and low doses of MPH induced consistent increases in DA release ∼30 min after their administrations. In the PFC, a consistent increase in DA release was observed 1 h after a high dose, but not low doses, of MPH. Low doses of MPH improved cognitive task performance, but a high dose of MPH made the monkey drowsy. Therefore, low-dose MPH-induced cognitive enhancement is supported by striatum DA increase.SIGNIFICANCE STATEMENT Methylphenidate (MPH) is a widely used drug for the treatment of attention deficit hyperactivity disorder and is often used as a cognitive enhancer. Although human positron emission tomography studies suggest that MPH works on attention and cognition through dopamine (DA) changes in the striatum, there has been no study to examine MPH-induced DA changes in the human prefrontal cortex (PFC). Using the microdialysis technique in monkeys, we found, for the first time, that low doses of MPH consistently increased DA release in the striatum but did not in the PFC. Cognitive enhancement effects of low doses of MPH are supposed to be supported by the striatum DA increase.

Representation of Functional Category in the Monkey Prefrontal Cortex and Its Rule-Dependent Use for Behavioral Selection.

Humans, monkeys, and other animals are considered to have the cognitive ability to use functional categories--that is, stimulus groups based on functional equivalence independent of physical properties. To investigate the underlying neural mechanisms of the use of functional categories, we recorded single-unit activity in the prefrontal cortex of monkeys performing a behavioral task in which the rule-dependent usage of functional category was needed to select an appropriate response. We found a neural correlate of functional categories on the single-neuron level and found that category information is coded independently of other task-relevant information such as rule and contingency information. Analysis of the time course of the information activation suggested that contingency information used for action selection is derived by integrating incoming category information with rule information maintained throughout a session. Such neural computation can be considered as the neural background of flexible behavioral control based on category and rule.

Capturing the temporal evolution of choice across prefrontal cortex.

Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making.

Egalitarian reward contingency in competitive games and primate prefrontal neuronal activity.

How people work to obtain a reward depends on the context of the reward delivery, such as the presence/absence of competition and the contingency of reward delivery. Since resources are limited, winning a competition is critically important for organisms' obtaining a reward. People usually expect ordinary performance-reward contingency, with better performers obtaining better rewards. Unordinary reward contingency, such as egalitarianism (equal rewards/no-rewards to both good and poor performers), dampens people's motivation. We previously reported that monkeys were more motivated, and neurons in the lateral prefrontal cortex (LPFC) showed higher outcome-related activity in a competitive than in a noncompetitive game (Hosokawa and Watanabe, 2012). However, monkey's behavior and LPFC neuronal activity have not been examined in a competitive situation with an unordinary performance-reward contingency. Also, the fixed performance-reward contingency in the previous study did not allow us to examine effects of win/loss separately from those of reward/no-reward on prefrontal neuronal activity. Here, we employed the egalitarian competitive situation in which both the winner and loser, or neither of them, got a reward as well as the normal competitive situation in which only the winner got a reward. Monkey's behavioral performance greatly deteriorated in trials with the egalitarian outcome conditions. LPFC neurons showed activities that reflected the normal or egalitarian outcome condition while very few neurons coded win/loss independent of reward/no-reward. Importantly, we found neurons that showed reward-related activity in the normal, but not in the egalitarian outcome conditions, even though the same reward was given to the animal. These results indicate that LPFC may play an important role in monitoring the current reward contingency and integrating it with the performance outcome (win-loss) for better performing the competitive game, and thus for better survival.

Single-neuron mechanisms underlying cost-benefit analysis in frontal cortex.

Effective decision-making requires consideration of costs and benefits. Previous studies have implicated orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC) in cost-benefit decision-making. Yet controversy remains about whether different decision costs are encoded by different brain areas, and whether single neurons integrate costs and benefits to derive a subjective value estimate for each choice alternative. To address these issues, we trained four subjects to perform delay- and effort-based cost-benefit decisions and recorded neuronal activity in OFC, ACC, DLPFC, and the cingulate motor area (CMA). Although some neurons, mainly in ACC, did exhibit integrated value signals as if performing cost-benefit computations, they were relatively few in number. Instead, the majority of neurons in all areas encoded the decision type; that is whether the subject was required to perform a delay- or effort-based decision. OFC and DLPFC neurons tended to show the largest changes in firing rate for delay- but not effort-based decisions; whereas, the reverse was true for CMA neurons. Only ACC contained neurons modulated by both effort- and delay-based decisions. These findings challenge the idea that OFC calculates an abstract value signal to guide decision-making. Instead, our results suggest that an important function of single PFC neurons is to categorize sensory stimuli based on the consequences predicted by those stimuli.

Prefrontal neurons represent winning and losing during competitive video shooting games between monkeys.

Humans and animals must work to support their survival and reproductive needs. Because resources are limited in the natural environment, competition is inevitable, and competing successfully is vitally important. However, the neuronal mechanisms of competitive behavior are poorly studied. We examined whether neurons in the lateral prefrontal cortex (LPFC) showed response sensitivity related to a competitive game. In this study, monkeys played a video shooting game, either competing with another monkey or the computer, or playing alone without a rival. Monkeys performed more quickly and more accurately in the competitive than in the noncompetitive games, indicating that they were more motivated in the competitive than in the noncompetitive games. LPFC neurons showed differential activity between the competitive and noncompetitive games showing winning- and losing-related activity. Furthermore, activities of prefrontal neurons differed depending on whether the competition was between monkeys or between the monkey and the computer. These results indicate that LPFC neurons may play an important role in monitoring the outcome of competition and enabling animals to adapt their behavior to increase their chances of obtaining a reward in a socially interactive environment.

Context-dependent representation of reinforcement in monkey amygdala.

It has been reported that neurons in the amygdala respond to visual cues that predict reward and aversive outcomes. However, it remains unclear whether the representation of reinforcement in the amygdala depends on the relative preference for an outcome compared with another simultaneously available outcome. In this study, we introduced three reinforcements (juice, water, and electrical stimulus) and used two of them in one experimental block. Of 52 neurons that showed cue responses reflecting the outcome information, 23% of amygdala neurons coded preferred outcomes, whereas only one neuron coded nonpreferred outcomes. These proportions of amygdala were significantly different from those of the orbitofrontal cortex, which had both types of neurons.

Neurons in the macaque orbitofrontal cortex code relative preference of both rewarding and aversive outcomes.

Many studies have shown that the orbitofrontal cortex (OFC) is involved in the processing of emotional information. However, although some lines of study showed that the OFC is also involved in negative emotions, few electrophysiological studies have focused on the characteristics of OFC neuronal responses to aversive information at the individual neuron level. On the other hand, a previous study has shown that many OFC neurons code relative preference of available rewards. In this study, we aimed to elucidate how reward information and aversive information are coded in the OFC at the individual neuron level. To achieve this aim, we introduced the electrical stimulus (ES) as an aversive stimulus, and compared the neuronal responses to the ES-predicting stimulus with those to reward-predicting stimuli. We found that many OFC neurons showed responses to both the ES-predicting stimulus and the reward-predicting stimulus, and they code relative preference of not only the reward outcome but also the aversive outcome. This result suggests that the same group of OFC neurons code both reward and aversive information in the form of relative preference.

Advantage of dichromats over trichromats in discrimination of color-camouflaged stimuli in humans.

This study investigated whether 12 participants with color-vision deficiency had superior visual discrimination of color-camouflaged stimuli shown on a computer screen compared with 12 participants with normal trichromatic vision. Participants were asked to distinguish a circular pattern from other patterns in which textural elements differed from the background in orientation and thickness. In one condition, stimuli were single-colored, green or red; in the other condition, stimuli were color camouflaged with a green and red mosaic overlaid onto the pattern. Color-vision deficient participants selected the correct stimuli in the color-camouflaged condition as quickly as they did in the single-colored condition. However, normal color-vision participants took longer to select the correct choice in the color-camouflaged condition than in the single-colored condition. These results suggest that participants with color-vision deficiency may have a superior visual ability to discriminate the color-camouflaged stimuli.

Correspondence of cue activity to reward activity in the macaque orbitofrontal cortex.

It has been reported that neurons in the orbitofrontal cortex (OFC) respond to emotionally significant events such as reward-predicting cues and/or the reward itself. The responses to reward-predicting cues are considered to carry the information of the predicted reward. However, few studies have focused on the relationship of the neuronal activity during a cue period with that during a reward period. We can infer that the cue responses of OFC neurons are correlated to the reward responses if they carry the information of the predicted reward. In this study, we focused on neurons that showed responses during both the cue and reward periods, and compared the response characteristics between these periods. We found 94 of 369 OFC neurons showed significant responses during both the cue and reward periods, and 43 of which preserved their selectivity between these periods. Furthermore, population analysis showed that stronger cue responses corresponded to stronger reward responses, and stronger reward responses corresponded to stronger cue responses. These results suggest that individual neurons in the OFC associate visual information with reward information, and contribute to the prediction of future rewards by forming reward representations.

Neurons in the orbitofrontal cortex code both visual shapes and reward types.

It has been reported that neurons in the orbitofrontal cortex respond to visual cues that predict reward; however, few studies have focused on the neuronal correlates with the predicted reward type and the cue stimulus. In this study, we used a paired association task and introduced a reversal condition, in which cue stimuli that usually predict water were switched to predict juice, and vice versa. Of 111 cue-responsive neurons, 60 neurons (54.1%) depended on both the cue stimulus and the predicted reward type. The results suggest that neurons in the orbitofrontal cortex can code both visual and reward information, and contribute to the association between these two pieces of information according to the current combination of a cue stimulus and a reward type.