Portable neuromodulation induces neuroplasticity to re-activate motor function recovery from brain injury: a high-density MEG case study.

BACKGROUND: In a recent high-profile case study, we used functional magnetic resonance imaging (fMRI) to monitor improvements in motor function related to neuroplasticity following rehabilitation for severe traumatic brain injury (TBI). The findings demonstrated that motor function improvements can occur years beyond current established limits. The current study extends the functional imaging investigation to characterize neuromodulation effects on neuroplasticity to further push the limits. METHODS: Canadian Soldier Captain (retired) Trevor Greene (TG) survived a severe open-TBI when attacked with an axe during a 2006 combat tour in Afghanistan. TG has since continued intensive daily rehabilitation to recover motor function, experiencing an extended plateau using conventional physical therapy. To overcome this plateau, we paired translingual neurostimulation (TLNS) with the continuing rehabilitation program. RESULTS: Combining TLNS with rehabilitation resulted in demonstrable clinical improvements along with corresponding changes in movement evoked electro-encephalography (EEG) activity. High-density magneto-encephalography (MEG) characterized cortical activation changes in corresponding beta frequency range (27 Hz). MEG activation changes corresponded with reduced interhemispheric inhibition in the post-central gyri regions together with increased right superior/middle frontal activation suggesting large scale network level changes. CONCLUSIONS: The findings provide valuable insight into the potential importance of non-invasive neuromodulation to enhance neuroplasticity mechanisms for recovery beyond the perceived limits of rehabilitation.

Human translingual neurostimulation alters resting brain activity in high-density EEG.

BACKGROUND: Despite growing evidence of a critical link between neuromodulation technologies and neuroplastic recovery, the underlying mechanisms of these technologies remain elusive. OBJECTIVE: To investigate physiological evidence of central nervous system (CNS) changes in humans during translingual neurostimulation (TLNS). METHODS: We used high-density electroencephalography (EEG) to measure changes in resting brain activity before, during, and after high frequency (HF) and low frequency (LF) TLNS. RESULTS: Wavelet power analysis around Cz and microstate analysis revealed significant changes after 20 min of stimulation compared to baseline. A secondary effect of exposure order was also identified, indicating a differential neuromodulatory influence of HF TLNS relative to LF TLNS on alpha and theta signal power. CONCLUSIONS: These results further our understanding of the effects of TLNS on underlying resting brain activity, which in the long-term may contribute to the critical link between clinical effect and changes in brain activity.

Non-invasive neuromodulation to improve gait in chronic multiple sclerosis: a randomized double blind controlled pilot trial.

BACKGROUND: This study sought to examine the effect of targeted physical therapy with and without cranial nerve non-invasive neuromodulation (CN-NINM), on the walking ability of people with MS who exhibited a dysfunctional gait. We hypothesized that subjects who received electrical stimulation would have greater improvement than those who had a control device after a 14-week intervention. Gait disturbance is a common problem for people with multiple sclerosis (MS). Current management may include exercise, pharmacology, functional electrical stimulation, compensatory strategies, use of assistive devices, and implanted electrical devices. We have developed an effective rehabilitative strategy using neuromodulation of the cranial nerves via electrical stimulation of the tongue to enhance the plasticity of the brain. METHODS: The study is a within-subject blinded randomized control design. Twenty chronic MS subjects with an identified gait disturbance were assigned to either an active or control group. Both groups completed a 14-week intervention program using a standardized combination of exercise and a device that provided electrical stimulation to the tongue. Those in the active group received electrical stimulation on the tongue that they could perceive. Those in the control group used a device that did not provide a physiologically significant stimulus and was not perceivable. Subjects were assessed with the Dynamic Gait Index (DGI). RESULTS: The DGI scores improved for both groups. There were significant between-group differences, with the active group showing statistically greater improvement than the control group mean. CONCLUSION: People with MS demonstrated improved gait with CN-NINM training in a pilot randomized controlled trial. This study suggests that tongue-based neurostimulation may amplify the benefits of exercise for improving gait in people with chronic MS.

Multilayer Epitaxial Heterostructures with Multi-Component III-V:Fe Magnetic Semiconductors.

Three-layer structures based on various multi-component films of III-V semiconductors heavily doped with Fe were grown using the pulsed laser sputtering of InSb, GaSb, InAs, GaAs and Fe solid targets. The structures comprising these InAsSb:Fe, InGaSb:Fe and InSb:Fe layers with Fe concentrations up to 24 at. % and separated by GaAs spacers were deposited on (001) i-GaAs substrates at 200 °C. Transmission electron microscopy showed that the structures have a rather high crystalline quality and do not contain secondary-phase inclusions. X-ray photoelectron spectroscopy investigations revealed a significant diffusion of Ga atoms from the GaAs regions into the InAsSb:Fe layers, which has led to the formation of an InGaAsSb:Fe compound with a Ga content up to 20 at. %. It has been found that the ferromagnetic properties of the InAsSb:Fe magnetic semiconductor improve with an increasing Sb:As ratio. It has been concluded that the indirect ferromagnetic exchange interaction between Fe atoms occurs predominantly via Sb atoms.

Ferromagnetic GaAs structures with single Mn delta-layer fabricated using laser deposition.

The new technique combining metal-organic chemical vapor epitaxy with laser ablation of solid targets was used for fabrication of ferromagnetic GaAs structures with single Mn delta-doped layer. The structures demonstrated anomalous Hall effect, planar Hall effect, negative and anisotropic magnetoresistance in temperature range of 10-35 K. In GaAs structures with only single Mn delta-layer (without additional 2D hole gas channel or quantum well) ferromagnetism was observed for the first time.

Translingual neural stimulation affects resting-state functional connectivity in mild-moderate traumatic brain injury.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) can lead to movement and balance deficits. In addition to physical therapy, brain-based neurorehabilitation efforts have begun to show promise in improving these deficits. The present study investigated the effectiveness of translingual neural stimulation (TLNS) on patients with mild-to-moderate TBI (mmTBI) and related brain connectivity using a resting-state functional connectivity (RSFC) approach. METHODS: Resting-state images with 5-min on GE750 3T scanner were acquired from nine participants with mmTBI. Paired t-test was used for calculating changes in RSFC and behavioral scores before and after the TLNS intervention. The balance and movement performances related to mmTBI were evaluated by Sensory Organization Test (SOT) and Dynamic Gait Index (DGI). RESULTS: Compared to pre-TLNS intervention, significant behavioral changes in SOT and DGI were observed. The analysis revealed increased RSFC between the left postcentral gyrus and left inferior parietal lobule and left Brodmann Area 40, as well as the increased RSFC between the right culmen and right declive, indicating changes due to TLNS treatment. However, there were no correlations between the sensory/somatomotor (or visual or cerebellar) network and SOT/DGI behavioral performance. CONCLUSIONS: Although the limited sample size may have led to lack of significant correlations with functional assessments, these results provide preliminary evidence that TLNS in conjunction with physical therapy can induce brain plasticity in TBI patients with balance and movement deficits.

High-resolution fMRI detects neuromodulation of individual brainstem nuclei by electrical tongue stimulation in balance-impaired individuals.

High-resolution functional magnetic resonance imaging (fMRI) can be used to precisely identify blood oxygen level dependent (BOLD) activation of small structures within the brainstem not accessible with standard fMRI. A previous study identified a region within the pons exhibiting sustained neuromodulation due to electrical tongue stimulation, but was unable to precisely identify the neuronal structure involved. For this study, high-resolution images of neural activity induced by optic flow were acquired in nine healthy controls and nine individuals with balance dysfunction before and after information-free tongue stimulation. Subjects viewed optic flow videos to activate the structures of interest. Sub-millimeter in-plane voxels of structures within the posterior fossa were acquired using a restricted field of view. Whole-brain functional imaging verified that global activation patterns due to optic flow were consistent with previous studies. Optic flow activated the visual association cortices, the vestibular nuclei, and the superior colliculus, as well as multiple regions within the cerebellum. The anterior cingulate cortex showed decreased activity after stimulation, while a region within the pons had increased post-stimulation activity. These observations suggest the pontine region is the trigeminal nucleus and that tongue stimulation interfaces with the balance-processing network within the pons. This high-resolution imaging allows detection of activity within individual brainstem nuclei not possible using standard resolution imaging.

Brain Vital Signs Detect Information Processing Differences When Neuromodulation Is Used During Cognitive Skills Training.

Background: Neuromodulation through translingual neurostimulation (TLNS) has been shown to initiate long-lasting processes of neuronal reorganization with a variety of outcomes (i.e., neuroplasticity). Non-invasive TLNS is increasingly accessible through the Portable Neuromodulation Stimulator (PoNS®), a medical device that delivers electrical stimulation to the tongue to activate the trigeminal (V) and facial (VII) cranial nerves. Anecdotal reports from previous clinical studies have suggested incidental improvements in cognitive function. To objectively explore this observation, we examined TLNS-related effects on the semantic N400 brain vital sign cognitive response during cognitive skills training in healthy individuals. Methods: Thirty-seven healthy volunteers were randomized to receive simultaneous TLNS (treatment) or no TLNS (control) while undergoing cognitive skills training. Cognitive training was conducted for two 20-min sessions (morning and afternoon/evening) over 3 consecutive days. Brain vital signs were evaluated at baseline, Day 1, and Day 3. Analyses focused on cognitive processing as measured by N400 changes in amplitude and latency. Results: Over the 3-day course of cognitive training, the N400 amplitude decreased significantly in the control group due to habituation (p = 0.028). In contrast, there was no significant change in the TLNS treatment group. Conclusion: TLNS led to a sustained N400 response during cognitive skills training, as measured by the brain's vital signs framework. The study findings suggest differential learning effects due to neuromodulation, consistent with increased attention and cognitive vigilance.

Brain Vital Signs Detect Cognitive Improvements During Combined Physical Therapy and Neuromodulation in Rehabilitation From Severe Traumatic Brain Injury: A Case Report.

Using a longitudinal case study design, we have tracked the recovery of motor function following severe traumatic brain injury (TBI) through a multimodal neuroimaging approach. In 2006, Canadian Soldier Captain (retired) Trevor Greene (TG) was attacked with an axe to the head while on tour in Afghanistan. TG continues intensive daily rehabilitation, which recently included the integration of physical therapy (PT) with neuromodulation using translingual neurostimulation (TLNS) to facilitate neuroplasticity. Recent findings with PT + TLNS demonstrated that recovery of motor function occurred beyond conventional time limits, currently extending past 14-years post-injury. To investigate whether PT + TLNS similarly resulted in associated cognitive function improvements, we examined event-related potentials (ERPs) with the brain vital signs framework. In parallel with motor function improvements, brain vital signs detected significant increases in basic attention (as measured by P300 response amplitude) and cognitive processing (as measured by contextual N400 response amplitude). These objective cognitive improvements corresponded with TG's self-reported improvements, including a noteworthy and consistent reduction in ongoing symptoms of post-traumatic stress disorder (PTSD). The findings provide valuable insight into the potential importance of non-invasive neuromodulation in cognitive rehabilitation, in addition to initial indications for physical rehabilitation.

Translingual Neurostimulation for the Treatment of Chronic Symptoms Due to Mild-to-Moderate Traumatic Brain Injury.

OBJECTIVE: To compare the efficacy of high- and low-frequency noninvasive translingual neurostimulation (TLNS) plus targeted physical therapy (PT) for treating chronic balance and gait deficits due to mild-to-moderate traumatic brain injury (mmTBI). DESIGN: Participants were randomized 1:1 in a 26-week double-blind phase 1/2 study (NCT02158494) with 3 consecutive treatment stages: in-clinic, at-home, and no treatment. Arms were high-frequency pulse (HFP) and low-frequency pulse (LFP) TLNS. SETTING: TLNS plus PT training was initiated in-clinic and then continued at home. PARTICIPANTS: Participants (N=44; 18-65y) from across the United States were randomized into the HFP and LFP (each plus PT) arms. Forty-three participants (28 women, 15 men) completed at least 1 stage of the study. Enrollment requirements included an mmTBI ≥1 year prior to screening, balance disorder due to mmTBI, a plateau in recovery with current PT, and a Sensory Organization Test (SOT) score ≥16 points below normal. INTERVENTIONS: Participants received TLNS (HFP or LFP) plus PT for a total of 14 weeks (2 in-clinic and 12 at home), twice daily, followed by 12 weeks without treatment. MAIN OUTCOME MEASURES: The primary endpoint was change in SOT composite score from baseline to week 14. Secondary variables (eg, Dynamic Gait Index [DGI], 6-minute walk test [6MWT]) were also collected. RESULTS: Both arms had a significant (P<.0001) improvement in SOT scores from baseline at weeks 2, 5, 14 (primary endpoint), and 26. DGI scores had significant improvement (P<.001-.01) from baseline at the same test points; 6MWT evaluations after 2 weeks were significant. The SOT, DGI, and 6MWT scores did not significantly differ between arms at any test point. There were no treatment-related serious adverse events. CONCLUSIONS: Both the HFP+PT and LFP+PT groups had significantly improved balance scores, and outcomes were sustained for 12 weeks after discontinuing TLNS treatment. Results between arms did not significantly differ from each other. Whether the 2 dosages are equally effective or whether improvements are because of provision of PT cannot be conclusively established at this time.

Sensory supplementation system based on electrotactile tongue biofeedback of head position for balance control.

The present study aimed at investigating the effects of an artificial head position-based tongue-placed electrotactile biofeedback on postural control during quiet standing under different somatosensory conditions from the support surface. Eight young healthy adults were asked to stand as immobile as possible with their eyes closed on two Firm and Foam support surface conditions executed in two conditions of No-biofeedback and Biofeedback. In the Foam condition, a 6-cm thick foam support surface was placed under the subjects' feet to alter the quality and/or quantity of somatosensory information at the plantar sole and the ankle. The underlying principle of the biofeedback consisted of providing supplementary information about the head orientation with respect to gravitational vertical through electrical stimulation of the tongue. Centre of foot pressure (CoP) displacements were recorded using a force platform. Larger CoP displacements were observed in the Foam than Firm conditions in the two conditions of No-biofeedback and Biofeedback. Interestingly, this destabilizing effect was less accentuated in the Biofeedback than No-biofeedback condition. In accordance with the sensory re-weighting hypothesis for balance control, the present findings evidence that the availability of the central nervous system to integrate an artificial head orientation information delivered through electrical stimulation of the tongue to limit the postural perturbation induced by alteration of somatosensory input from the support surface.

Abnormal muscle activation patterns are associated with chronic gait deficits following traumatic brain injury.

BACKGROUND: Gait and balance disorders are common among individuals who have experienced a mild to moderate traumatic brain injury (TBI). However, little is known about how the neuromuscular control of gait is altered following a TBI. RESEARCH QUESTION: Investigate the relationship between lower limb muscle activation patterns and chronic gait deficits in individuals who previously experienced a mild to moderate TBI. METHODS: Lower extremity electromyographic (EMG) signals were collected bilaterally during treadmill and overground walking in 44 ambulatory individuals with a TBI >1 year prior and 20 unimpaired controls. Activation patterns of TBI muscles were cross-correlated with normative data from control subjects to assess temporal phasing of muscle recruitment. Clinical assessments of gait and balance were performed using dynamic posturography, the dynamic gait index, six-minute walk test, and preferred walking speed. RESULTS: TBI subjects exhibited abnormal activation patterns in the tibialis anterior, medial gastrocnemius, and rectus femoris muscles during both overground and treadmill walking. Activation patterns of the vastus lateralis and soleus muscles did not differ from normal. There was considerable heterogeneity in performance on clinical balance and gait assessments. Abnormal muscle activation patterns were significantly correlated with variations in the dynamic gait index among the TBI subjects. SIGNIFICANCE: Individuals who have experienced a prior TBI do exhibit characteristic changes in the temporal coordination of select lower extremity muscles, which may contribute to impairments during challenging walking tasks.

Brainport: an alternative input to the brain.

Brain Computer Interface (BCI) technology is one of the most rapidly developing areas of modern science; it has created numerous significant crossroads between Neuroscience and Computer Science. The goal of BCI technology is to provide a direct link between the human brain and a computerized environment. The objective of recent BCI approaches and applications have been designed to provide the information flow from the brain to the computerized periphery. The opposite or alternative direction of the flow of information (computer to brain interface, or CBI) remains almost undeveloped. The BrainPort is a CBI that offers a complementary technology designed to support a direct link from a computerized environment to the human brain - and to do so non-invasively. Currently, BrainPort research is pursuing two primary goals. One is the delivery of missing sensory information critical for normal human behavior through an additional artificial sensory channel around the damaged or malfunctioning natural sensory system. The other is to decrease the risk of sensory overload in human-machine interactions by providing a parallel and supplemental channel for information flow to the brain. In contrast, conventional CBI strategies (e.g., Virtual Reality), are usually designed to provide additional or substitution information through pre-existing sensory channels, and unintentionally aggravate the brain overload problem.

Closing an open-loop control system: vestibular substitution through the tongue.

The human postural coordination mechanism is an example of a complex closed-loop control system based on multisensory integration [9,10,13,14]. In models of this process, sensory data from vestibular, visual, tactile and proprioceptive systems are integrated as linearly additive inputs that drive multiple sensory-motor loops to provide effective coordination of body movement, posture and alignment [5-8, 10, 11]. In the absence of normal vestibular (such as from a toxic drug reaction) and other inputs, unstable posture occurs. This instability may be the result of noise in a functionally open-loop control system [9]. Nonetheless, after sensory loss the brain can utilize tactile information from a sensory substitution system for functional compensation [1-4, 12]. Here we have demonstrated that head-body postural coordination can be restored by means of vestibular substitution using a head-mounted accelerometer and a brain-machine interface that employs a unique pattern of electrotactile stimulation on the tongue. Moreover, postural stability persists for a period of time after removing the vestibular substitution, after which the open-loop instability reappears.

Altered connectivity of the balance processing network after tongue stimulation in balance-impaired individuals.

Some individuals with balance impairment have hypersensitivity of the motion-sensitive visual cortices (hMT+) compared to healthy controls. Previous work showed that electrical tongue stimulation can reduce the exaggerated postural sway induced by optic flow in this subject population and decrease the hypersensitive response of hMT+. Additionally, a region within the brainstem (BS), likely containing the vestibular and trigeminal nuclei, showed increased optic flow-induced activity after tongue stimulation. The aim of this study was to understand how the modulation induced by tongue stimulation affects the balance-processing network as a whole and how modulation of BS structures can influence cortical activity. Four volumes of interest, discovered in a general linear model analysis, constitute major contributors to the balance-processing network. These regions were entered into a dynamic causal modeling analysis to map the network and measure any connection or topology changes due to the stimulation. Balance-impaired individuals had downregulated response of the primary visual cortex (V1) to visual stimuli but upregulated modulation of the connection between V1 and hMT+ by visual motion compared to healthy controls (p ≤ 1E-5). This upregulation was decreased to near-normal levels after stimulation. Additionally, the region within the BS showed increased response to visual motion after stimulation compared to both prestimulation and controls. Stimulation to the tongue enters the central nervous system at the BS but likely propagates to the cortex through supramodal information transfer. We present a model to explain these brain responses that utilizes an anatomically present, but functionally dormant pathway of information flow within the processing network.

Electrical tongue stimulation normalizes activity within the motion-sensitive brain network in balance-impaired subjects as revealed by group independent component analysis.

Multivariate analysis of functional magnetic resonance imaging (fMRI) data allows investigations into network behavior beyond simple activations of individual regions. We apply group independent component analysis to fMRI data collected in a previous study looking at the sustained neuromodulatory effects of electrical tongue stimulation in balance-impaired individuals. Twelve subjects with balance disorders viewed optic flow in an fMRI scanner before and after 5 days of electrical tongue stimulation. Nine healthy controls also viewed the visual stimuli but did not receive any stimulation. Multiple regression of the 47 estimated components found two that were modulated by the visual stimuli. Component 7, comprised primarily of the primary visual cortex (V1), responded to all visual stimuli and showed no difference in task-related activity between the healthy controls and the balance-impaired subjects before or after stimulation. Component 11 responded only to motion in the visual field and contained multiple cortical and subcortical regions involved in processing information pertinent to balance. Two-sample t-tests of the calculated signal change revealed that the task-related activity of this network is greater in balance-impaired subjects compared with controls before stimulation (p=0.02), but that this network hypersensitivity decreases after electrical tongue stimulation (p=0.001).

Effects of electrotactile vestibular substitution on rehabilitation of patients with bilateral vestibular loss.

The present study evaluated the effectiveness of electrotactile tongue biofeedback (BrainPort((R))) as a sensory substitute for the vestibular apparatus in patients with bilateral vestibular loss (BVL) who did not have a good response to conventional vestibular rehabilitation (VR). Seven patients with BVL were trained to use the device. Stimulation on the surface of the tongue was created by a dynamic pattern of electrical pulses and the patient was able to adjust the intensity of stimulation and spatially centralize the stimulus on the electrode array. Patients were directed to continuously adjust head orientation and to maintain the stimulus pattern at the center of the array. Postural tasks that present progressive difficulties were given during the use of the device. Pre- and post-treatment distribution of the sensory organization test (SOT) composite score showed an average value of 38.3+/-8.7 and 59.9+/-11.3, respectively, indicating a statistically significant improvement (p=0.01). Electrotactile tongue biofeedback significantly improved the postural control of the study group, even if they had not improved with conventional VR. The electrotactile tongue biofeedback system was able to supply additional information about head position with respect to gravitational vertical orientation in the absence of vestibular input, improving postural control. Patients with BVL can integrate electrotactile information in their postural control in order to improve stability after conventional VR. These results were obtained and verified not only by the subjective questionnaire but also by the SOT composite score. The limitations of the study are the small sample size and short duration of the follow-up. The current findings show that the sensory substitution mediated by electrotactile tongue biofeedback may contribute to the improved balance experienced by these patients compared to VR.

Sustained cortical and subcortical neuromodulation induced by electrical tongue stimulation.

This pilot study aimed to show that information-free stimulation of the tongue can improve behavioral measures and induce sustained neuromodulation of the balance-processing network in individuals with balance dysfunction. Twelve balance-impaired subjects received one week of cranial nerve non-invasive neuromodulation (CN-NINM). Before and after the week of stimulation, postural sway and fMRI activation were measured to monitor susceptibility to optic flow. Nine normal controls also underwent the postural sway and fMRI tests but did not receive CN-NINM. Results showed that before CN-NINM balance-impaired subjects swayed more than normal controls as expected (p ≤ 0.05), and that overall sway and susceptibility to optic flow decreased after CN-NINM (p ≤ 0.005 & p ≤ 0.05). fMRI showed upregulation of visual sensitivity to optic flow in balance-impaired subjects that decreased after CN-NINM. A region of interest analysis indicated that CN-NINM may induce neuromodulation by increasing activity within the dorsal pons (p ≤ 0.01).

Spatial mapping of electrotactile sensation threshold and intensity range on the human tongue: initial results.

We have developed a novel, tongue-based electrotactile brain-machine interface. Variability of the tactile sensation intensity across the stimulated area, however, limits the amount of reliable information transmission. We have conducted an experiment to characterize local sensitivity across the region stimulated by the array. From this data we have constructed an isointensity algorithm to compensate for the variability in electrotactile sensation levels across the stimulated area of the tongue.

Sense of taste in a new world monkey, the common marmoset: recordings from the chorda tympani and glossopharyngeal nerves.

Whole nerve, as well as single fiber, responses in the chorda tympani proper (CT) and glossopharyngeal (NG) nerves of common marmosets were recorded during taste stimulation with three salts, four acids, six bitter compounds and more than 30 sweeteners. We recorded responses of 49 CT and 41 NG taste fibers. The hierarchical cluster analysis distinguished three major clusters in both CT and NG: S, Q, and H. The S(CT) fibers, 38% of all CT fibers, responded only to sweeteners. The S(CT) fibers did not respond during stimulation with salts, acids, and bitter compounds but exhibited OFF responses after citric and ascorbic acids, quinine hydrochloride (QHCl), and salts (in 80% of S(CT) fibers). S(NG) fibers, 50% of all NG fibers, also responded to sweeteners but not to stimuli of other taste qualities (except for citric acid, which stimulated 70% of the S(NG) fibers). Some sweeteners, including natural (the sweet proteins brazzein, monellin) and artificial [cyclamate, neohesperidin dihydrochalcone (NHDHC), N-3,5-dichlorophenyl-N'-(S)-alpha-methylbenzylguanidineacetate (DMGA), N-4-cyanophenylcarbamoyl-(R,S)-3-amino-3-(3,4-methylenedioxyphenyl) propionic acid (CAMPA)] did not elicit responses in the S fibers. In general, the response profiles of the S(CT) and S(NG) clusters were very similar, the correlation coefficient between the responses to sweeteners in these clusters was 0.94. Both the Q(CT) and the Q(NG) fibers (40 and 46% of all fibers) were predominantly responsive to bitter compounds, although their responses to the same set of bitter compounds were quite different. Sweeteners with sweet/bitter taste for humans also stimulated the Q clusters. The H clusters (22 and 3% of all fibers) were predominantly responsive to acids and did not respond to stimuli of other taste qualities. However, bitter stimuli, mainly QHCl, inhibited activity in 70% of H(CT) fibers. Among a total of 90 fibers from both nerves there was only 1 NaCl-best fiber in CT. We found, however, that 35% of the CT fibers reacted to salts with inhibition of activity during stimulation, followed by an OFF response. This OFF response was diminished or eliminated by amiloride. These characteristics indicate that amiloride-sensitive sodium channels are involved in salt transduction in marmosets. In the two NG fibers responding to NaCl, we recorded neither suppression by amiloride nor OFF responses. Comparison of marmoset data with those of other nonhuman primates studied, rhesus and chimpanzee, demonstrates phylogenetic trends in the organization of taste system. This can help to uncover pathways of primate evolution.