Heart Mind

: 2019  |  Volume : 3  |  Issue : 3  |  Page : 107--112

Enhancement of orbitofrontal and insular cortices responses to spicy perception increases high salt sensation: An event-related potentials study

Qiang Li, Qiang Li, Fang Sun, Guoyi Yan, Hongmei Lang, Zhiming Zhu 
 Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Daping Hospital, Third Military Medical University, Chongqing, China

Correspondence Address:
Prof. Zhiming Zhu
Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Daping Hospital, Third Military Medical University, Chongqing


Context: The interplay between taste perception and salt sensation is crucial for salt intake. Our hemodynamic neuroimaging research has shown that the administration of capsaicin (the major spicy component of chili peppers) enhances the metabolic activity of the insula and orbitofrontal cortex (OFC) in response to high salt intake. Aims: The aim is to study how the brain processes underlying salty taste and spicy perception within the first second after stimulation. Settings and Design: This electrophysiological study included 25 participants (10 males) who were recruited by advertisement flyers in Chongqing. Subjects and Methods: The present study investigated the responses of the OFC and insular to the interaction of spicy flavor and salty taste by recording the event-related potentials (ERPs). Two concentrations of sodium chloride solution (150 and 200 mmol/L) with or without 0.5 μM capsaicin were applied to the tongue of the study's participants. Statistical Analysis Used: One-way ANOVA with Games-Howell's multiple comparison post-hoc tests and linear regression analysis. Results: N1 amplitudes were positively correlated with participants' levels of salt intake and their salty preference scores. Source analysis performed on the ERP N1 wave in the 120–180 ms time window showed that the sources were located approximately in the insula and OFC. The amplitudes of the N1 and P2 components in the 200 mmol/L NaCl group were higher than those in 150 mmol/L NaCl group, but not significantly different than the group administered 150 mmol/L of NaCl and 0.5 μmol/L of capsaicin. Conclusions: The present study provides novel insights into the use of flavor or saltiness enhancers for salt reduction in humans through cortical responses to the spicy-salty interaction.

How to cite this article:
Li Q, Li Q, Sun F, Yan G, Lang H, Zhu Z. Enhancement of orbitofrontal and insular cortices responses to spicy perception increases high salt sensation: An event-related potentials study.Heart Mind 2019;3:107-112

How to cite this URL:
Li Q, Li Q, Sun F, Yan G, Lang H, Zhu Z. Enhancement of orbitofrontal and insular cortices responses to spicy perception increases high salt sensation: An event-related potentials study. Heart Mind [serial online] 2019 [cited 2022 Oct 3 ];3:107-112
Available from: http://www.heartmindjournal.org/text.asp?2019/3/3/107/272080

Full Text


High salt intake is associated with the development of hypertension and cardiovascular diseases, whereas reducing salt intake significantly lowers blood pressure and ameliorates cardiovascular diseases related to high salt intake.[1] However, three decades of research have shown that current strategies for salt restriction cannot decrease daily salt intake to an optimal level.[2] Therefore, it is important to identify alternative approaches to reduce excessive salt intake and counter hypertension due to high salt levels. Salt intake is determined by the brain's taste area because the sensory properties of the foods one eats, including taste intensity, influence the processing of taste, and therefore, salt intake.[3] A previous study of ours suggested that the enjoyment of spicy foods could reduce an individual's salt intake and blood pressure.[4] The administration of capsaicin – the major spicy component of chili pepper – was found to enhance the metabolic activity of the insula and orbitofrontal cortex (OFC), which are related to high salt intake. Thus, we speculated that the application of a spicy flavor may be a promising behavioral intervention for reducing high salt intake.

Currently, our understanding of the gustatory cortical areas is mostly derived from hemodynamic neuroimaging studies, including functional neuroimaging studies using either functional magnetic resonance imaging (fMRI) or positron-emission tomography/computed tomography (PET/CT). However, cortical activity is very rapid – within the millisecond range – while the temporal resolution of fMRI and PET/CT is limited by relatively slow metabolic changes that occur within a few seconds.[5] To study how the brain processes salty and spicy sensations within the first second after stimulation in healthy humans, one needs a technique with rapid temporal resolution.

Event-related potentials (ERPs) provide a way to evaluate the timing of cognitive processes by recording electrical activity in the brain that is time-locked to a stimulus or response. The amplitude of an ERP component changes based on how individual processes or response to stimuli. ERP components that reflect initial sensory processes include the P1, N1, P2, and N2. Studies have shown there is “dose-response” relationship between taste intensity and ERP, with increased taste intensity associated with higher amplitudes and shorter latencies for high salt concentrations compared to low salt concentrations.[6],[7] However, it is unclear how cortical responses to gustatory stimuli are associated with the interaction between salty and spicy sensations. We hypothesized that spicy perception would act on the insula's and the OFC's processing of signals related to salty taste. Therefore, the purpose of the present study was to investigate rapid gustatory cortical responses to salty taste, and their changes under the influence of a capsaicin intervention, using ERP measurements. The aim was to identify an alternative strategy for reducing high salt intake.

 Subjects and Methods

Study design and participants

This electrophysiological study included 25 participants (10 males, 15 females; mean age = 53.5 ± 6.1 years old) who were recruited by advertisement flyers in Chongqing. Their mean body mass index (BMI) was 24.4 kg/m2. All the participants signed informed consent forms before the start of the experiment. The protocol was approved by the Ethics Committee of Daping Hospital at the Third Military Medical University.

To be eligible for participation in the study, participants were required to be 18–70 years of age, provide written informed consent, and be able to comply with all study procedures. Participants were excluded if they met any of the following exclusion criteria: Type 1 diabetes; secondary hypertension or a hypertension emergency; hypogeusia or loss due to neural system disease or oral or digestive disease; capsaicin allergy or poor compliance; recent use of oral diuretics or participation in other pharmacological experiments within the past 3 months; acute infection; cancer; serious arrhythmias; drug or alcohol abuse; cigarette consumption (maximum 3/days); currently have a cold, fever, acidosis, dehydration, or diarrhea, or vomiting during the study; unwilling or unable to communicate due to dyskinesia or language disorders; severe neural or psychiatric diseases that would preclude full understanding and cooperation in the study; pregnancy or lactation; a history of taste/smell/neurological disorders; or unwilling to sign the informed consent form.

Stimuli preparation for event-related potential recording

The liquid sodium chloride stimuli were applied in two concentrations (150 and 200 mmol/L) dissolved in deionized water, with or without the addition of 0.5 μM capsaicin. All the participants were asked to evaluate the hedonic value of the salt solutions using a visual analog scale prior to the experiment. On the scale, “very pleasant” was defined as a value of 3, and “very aversive” was defined as-3. The average hedonic value was almost neutral.

Electroencephalography data acquisition

Brain electrical activity was recorded using 64 Ag/AgCl active electrodes mounted in an elastic cap (EasyCap, Brain Products GmbH) with a standard 10/10 system layout. The vertical electro-oculogram was recorded from an electrode placed below the right eye. Electrode impedance was kept below 20 kΩ. FCz was used as the reference electrode and a ground electrode was located at Afz; the sampling rate was 1 kHz.

Participants were seated on a comfortable chair, in a light- and sound-attenuated room, approximately 1 m from a 21-inch computer screen, with electroencephalography (EEG) electrodes attached. The taste stimuli were directly delivered to the center of the tongue by two programmable LSP01–1A syringe pumps (Baoding Longer Precision Pump Co., Ltd., China) through a Teflon tube at a rate of 140 ml/min, in a constant flow to negate any tactile sensations. The tubes were held gently by the participant between the lips and teeth. In order to deliver the taste stimuli quickly, the pump was simultaneously activated under programmed control orders received from the computer during the experiment. The temperature of the taste stimuli and deionized water was maintained at 36°C to match that of the stimulated region of the tongue. During the experiment, the participants listened to background music delivered through headphones to prevent the emergence of auditory ERPs induced by the repetitive sound of the syringe pumps and to prevent the emergence of alpha waves resulting from a boring task. In total, 80 trials (50% of each stimulus) were presented to the participants in a pseudo-random order. Each stimulus was presented for 400 ms with an inter-stimulus interval of 30 s. Each trial consisted of the presentation of the word “Ready” for 1000 ms, which was immediately followed by a fixation cross for 1000 ms. After a random period, during which a blank screen was presented, the stimulus was delivered for 400 ms. Next, the phrase “Please Swallow the fluid” was shown on the screen for 5 s. After that, participants were instructed to select a perceived intensity of saltiness between 0 (not detectable) and 4 (very strong) using their figures on the keyboard within 5 s. This procedure was used to confirm that gustatory adaptation did not occur under repetitive presentation of stimuli. Then, a blank screen was presented again for 20 s [Figure 1]. After every recording experiment, the participants were asked about the stimulus quality and they confirmed there was no difference in temperature between the water and salt solutions.{Figure 1}

Electroencephalography data processing and analysis

The recorded EEG data were processed using a Brain Vision Analyzer (Version 2.0, Brain Products, Munich, Germany). All the data were initially re-referenced to the average of TP9 and TP10 (the electrodes closest to the mastoids). Eye movement artifacts were corrected using ICA and the components that were removed were manually checked. Raw data inspection was performed using a semiautomatic procedure with physiological artifacts identified by the following criteria: A voltage step more than 50 μV, a difference of interval values more than 200 μV, and activity <0.5 μV within 100 ms intervals. After filtering the data with a high cutoff of 40 Hz, the EEG was segmented into epochs, from 200 ms before until 1000 ms after stimulus onset. Baseline correction was performed based on activity during the 200 ms window before stimulus onset. Next, the epochs with residual artifacts were manually rejected, and the remaining segments were averaged. The gustatory ERPs extracted for single electrodes were averaged across experimental conditions and patients. To detect peaks, we defined the P1 wave as the mean activity in the 80–120 ms time window, the N1 wave as activity in the 120–180 ms time window, and the P2 wave as activity in the 160–250 ms window. The amplitudes at the individual level were exported for the statistical analysis.

Dipole source analysis was applied to the grand-averaged gustatory ERPs in BESA (Version 5.3, MEGIS Software GmbH, Gräfelfing, Germany). Principal component analysis was performed to determine the number of sources, which has been shown to significantly improve the accuracy of source localization.[8] When the dipole points were determined, standardized low-resolution brain electromagnetic tomography (sLORETA) was used to identify the location of the source dipoles. The relevant residual variance criterion was used to evaluate whether the current model explained the data the best and accounted for most of the variance.

Statistical analysis

Baseline characteristics of the participants are presented as the mean ± standard deviation for continuous variables. We performed one-way ANOVA, using Games-Howell's multiple comparison post-hoc tests to analyze the differences between the peak amplitudes of the N1 and P2 components under different concentrations of salt solutions with or without capsaicin added. Linear regression analysis was performed to assess the relationships among salt intake, salt preference, and the amplitude of the ERP waves of all the participants. A two-tailed P value < 0.05 was considered to be statistically significant. All the statistical analyses were conducted using the SPSS software, version 13.0 (SPSS Inc.), or GraphPad Prism software, version 5.0 (GraphPad Software, San Diego, CA, USA).


Baseline characteristics of the study participants

Twenty-eight healthy participants were enrolled in this study, but three of them were subsequently excluded because of the lower quality of the recorded signals. The baseline characteristics of the participants are presented in [Table 1]. The 25 participants included 10 males and 15 females, with a mean age of 53.5 ± 6.1 years, and a mean BMI of 24.4 kg/m2.{Table 1}

Effect of high salt intake on the activity of the insula and orbitofrontal cortex

First, we examined how salt intake and salty taste affect neuronal activity in the participants. Recording gustatory ERPs is a direct measure of neuronal activity in response to taste input signals. The grand averaged gustatory ERP waveform at the electrode Cz is presented in [Figure 2]a (left panel). The topographical distribution maps showed the frontocentral distributions of both the N1 and P2 components [Figure 2]a, right panel]. Electrodes at the Fpz, Fz, and Cz were chosen for correlation analysis. The N1 amplitudes of those electrodes were positively correlated with both individual levels of salt intake and their salty preference scores [Figure 2]b. Source analysis using SPM and BESA software was performed on the N1 wave in the 120–180 ms time window [Figure 2]c. The analyzed sources were approximately located in the insula and OFC, which closely matched our previous PET/CT results. This indicated that increased neuronal activity was closely associated with high salt intake and high salty preference scores.{Figure 2}

Spicy perception increased insular and orbitofrontal cortex responses to salty taste

Next, we asked whether high salt-induced neuronal activity can be modified by the spicy sensation induced by capsaicin, the major pungent ingredient in hot peppers. A human study showed that the administration of <0.7 μmol/L of capsaicin does not produce a spicy taste, but it can increase the perception of saltiness.[9] Our previous study showed that 0.5 μmol/L of capsaicin significantly increased insula and OFC activity in response to high salt stimulation.[4] In this study, we further examined neuronal activity differences in response to spicy perception, by comparing the ERP waveforms to water and capsaicin stimuli at electrodes Fpz, Fz, and Cz [Figure 3]a. There were no significant differences in ERP waveforms between the water and capsaicin stimuli. Neuronal responses of the insula were correlated with the subjective intensity of taste.[10] The ERP electrophysiological results also confirmed that the amplitudes of the N1 and P2 components in the 200 mmol/L NaCl group were higher than those in 150 mmol/L NaCl group, but they were not significantly different than those in the 150 mmol/L NaCl plus 0.5 μmol/L capsaicin group [Figure 3]b and c]. These results indicate that the spicy sensation induced by capsaicin can modify the sensation of salty intensity by activating brain regions that are involved in hedonic experiences.{Figure 3}


The major findings of this study demonstrated that high salt intake and salty preference were closely correlated with increased brain activity in the insula and OFC of the participants. Administration of capsaicin at a concentration that does not produce a spicy taste enhanced the insula and OFC neuronal activity in response to highly salty stimuli. Furthermore, these spicy perception effects reversed salt intensity-dependent differences in insula and OFC activity.

Flavor or saltiness enhancers have been proposed as a promising strategy for salt reduction.[11] Both the insula and OFC are responsible for the taste enhancement effect.[12],[13],[14],[15] Two studies showed that capsaicin, a major pungent ingredient in chili pepper, can enhance saltiness in humans,[9],[16] and a recent study of ours further confirmed that spicy flavor can enhance salt sensitivity, reduce the salty preference, and lower salt intake.[4] Several neuroimaging studies showed there are overlapping representations of taste and somatosensory information at the cortical level,[13],[17] but there are little data on the interaction of the sensations of salty taste and spicy flavor. Importantly, an fMRI study by Rudenga et al. reported that a region of the anterior insula responds to both salt and capsaicin stimuli, which suggests a potential role of spicy sensation on central salty taste processing.[18] Our recent study showed that the administration of capsaicin enhanced insula and OFC metabolic activity in response to a salt stimulus.[4] However, functional neuroimaging has some limitations. For example, such up-to-date methods only mirror neuronal blood flow or metabolic changes in the brain; they do not reflect neuronal electrophysiological activity because of their slow responses to stimuli. The current study explored the time-locked activity of central cortical responses to the presence of both spicy flavor and salty stimuli. We did not find the significant differences in ERP waveforms between water and capsaicin stimuli in participants, although Rudenga et al. showed insula activity in response to capsaicin administration. This discrepancy might be due to the relatively lower concentration of capsaicin (0.5 μmol/L) used in our study, which can affect salty taste, whereas Rudenga et al. applied a higher concentration of capsaicin (44 μmol/L). A higher concentration of capsaicin can cause burning and painful sensations.

Similar to other's studies,[6],[19],[20] we confirmed that high salt solutions, as peripheral sensory stimuli, trigger higher activity in both the insula and OFC regions. Furthermore, we revealed that these changes in neuronal activity were associated with an individual's salt intake levels and salty preference scores. Thus, our results are consistent with previous studies, which suggested that the OFC is particularly associated with hedonic experiences, and therefore, the subjective pleasantness of taste in humans, whereas the response of the insula appears to be more sensitive to the intensity of taste.[10],[21],[22] In addition, we found that capsaicin increased neural activity in both the insula and the OFC in response to highly salty stimuli. Notably, the capsaicin-mediated increase in brain activity was able to reverse intensity-dependent activity differences in these brain regions that are induced by highly salty stimuli. What is the clinical relevance of this study? Hot or spicy foods are very popular worldwide, and our study indicates that capsaicin enhances the activity of the insula and OFC in response to highly salty stimuli. Thus, accompanied with our previous neuroimaging findings, the enjoyment of a spicy food can significantly reduce the salt preference, daily salt consumption, and the blood pressure of individuals by modifying the neural processing of salty perception. This study provides insights into using the enjoyment of spicy flavors as a promising behavioral intervention for reducing high salt intake and salt-sensitive hypertension. Our study certainly has several limitations needed further elusive: To verify our findings in a larger population, and to explore the underlying mechanisms.


We report electrophysiological results on the cortical processing of salt taste and spicy flavor perception. The results demonstrate that the insula and OFC are key brain areas for gustatory processing. The present study provides novel insights into using flavor or saltiness enhancers for salt reduction in populations who are exposed to a risk of high salt intake.

Financial support and sponsorship

This work was supported by grants from the National Natural Science Foundation of China (81721001, 81630015, 31701023, and 91839000).

Conflicts of interest

There are no conflicts of interest.


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