Functional Near-infrared Spectroscopy Measures Research Articles

FNIRS as a biomarker for individuals with subjective memory complaints and MCI.

Identifying individuals at risk of developing dementia is crucial for early intervention. Mild cognitive impairment (MCI) and subjective memory complaints (SMCs) are considered its preceding stages. This study aimed to assess the utility of functional near-infrared spectroscopy (fNIRS) in identifying individuals with MCI and SMC. One hundred fifty-one participants were categorized into normal cognition (NC); amnestic MCI (aMCI); non-amnestic MCI (naMCI); and mild, moderate, and severe SMC groups. Task-related prefrontal hemodynamics were measured using fNIRS during a visual memory span task. Results showed significantly lower oxyhemoglobin (HbO) levels in aMCI, but not in naMCI, compared to the NC. In addition, severe SMC had lower HbO levels than the NC, mild, and moderate SMC. Receiver operating characteristic analysis demonstrated 69.23% and 69.70% accuracy in differentiating aMCI and severe SMC from NC, respectively. FNIRS may serve as a potential non-invasive biomarker for early detection of dementia. Only amnestic mild cognitive impairment (aMCI), but not non-amnestic MCI, showed lower oxyhemoglobin (HbO) than normal individuals. Reduced HbO was observed in those with severe subjective memory complaints (SMCs) compared to normal cognition (NC), mild, and moderate SMCs. Functional near-infrared spectroscopy measures were associated with performance in memory assessments. Prefrontal hemodynamics could distinguish aMCI and severe SMC from NC.

The efficacy and safety of MARS-PD: Meridian activation remedy system for Parkinson's disease-A single-center, assessor and statistician-blinded, parallel-group randomized, controlled trial protocol.

Parkinson's disease (PD) patients face a substantial unmet need for disease-modifying interventions. Potential approaches such as exercise and acupuncture have been investigated to slow PD progression. To address this unmet need, we developed a novel therapeutic approach that integrates acupuncture and exercise: the Meridian Activation Remedy System for PD patients (MARS-PD). Building upon promising outcomes observed in our preliminary pilot study, where MARS-PD exhibited a large clinically important difference on the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III), we embark on a randomized controlled trial with the primary objective of examining the efficacy, safety, and economic impact of MARS-PD. In this single-center, assessor and statistician-blinded, parallel-group randomized controlled trial, we aim to investigate the clinical efficacy of MARS-PD through 16 interventions administered over 8 weeks in 88 PD patients. Participants will be randomly assigned to the experimental (n = 44) or control (n = 44) groups. The experimental group will receive MARS-PD intervention alongside standard care, while the control group will solely receive standard care. The intervention period spans 8 weeks, followed by a 12-week post-intervention follow-up. The primary endpoint is the change in MDS-UPDRS Part III score from baseline to the conclusion of the 8-week intervention. Secondary outcomes encompass various assessments, including MDS-UPDRS, International Physical Activity Questionnaire Short Form, Parkinson Self Questionnaire, Parkinson's Disease Sleep Scale, Timed Up and Go test, GAITRite metrics, Functional Near-Infrared Spectroscopy measurements, smart band outcomes, gut microbiome analysis results, and iris connective tissue texture. Previous studies by the authors have indicated MARS-PD's safety and benefits for PD patients. Building upon this foundation, our current study aims to provide a more comprehensive and detailed confirmation of the efficacy of MARS-PD. cris.nih.go.kr KCT0006646 -First posted on 7 October 2021; ClinicalTrials.gov NCT05621772 -First posted on 11 November 2022.

Functional near-infrared spectroscopy measures of frontal hemodynamic responses in Parkinson's patients and controls performing the Timed-Up-and-Go test

Using functional near-infrared spectroscopy (fNIRS), hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) were measured while participants with Parkinson’s disease (PD) and healthy controls performed the Timed-Up-and-Go test (TUGT), and differences in cortical activity at baseline and three different intervals were examined between the two groups. Seventeen PD patients and twenty-two controls participated in the study, but two PD patients were excluded from statistical analysis due to the presence of freezing of gait and using walking aids during the TUGT. During the TUGT, activity in the front, left, right and total frontal cortices initially decreased significantly, then significantly increased in PD participants and low-risk faller PD participants, compared to when in a sitting position. ΔHbO (HbO change from baseline) over the front, left and total frontal cortices in the PD group was significantly lower than the control group in interval 1 (P = 0.019, P = 0.014 and P = 0.031, respectively), while significantly higher than the control group in interval 2 over the left frontal cortex (P = 0.010). No significant differences were observed between the high-risk faller and low-risk faller subgroups of PD participants in ΔHbO and ΔHbR in the three intervals (P > 0.05). In the high-risk faller subgroup, ΔHbO over the left frontal cortex was significantly higher than the right frontal cortex in interval 2 and interval 3 (P = 0.015, P = 0.030, respectively). There was a strong positive correlation between education and HbR concentration over the right frontal cortex in PD participants (rho = 0.557, P = 0.031), while there were strong negative correlations between PD duration and HbR concentration over the right and total frontal cortices in the high-risk faller subgroup of PD participants (rho = −0.854, P = 0.014 for the right; rho = −0.784, P = 0.037 for the total). The falls prediction cutoff TUGT time for PD participants was 14.2 s. These results suggest that frontal cognition training, along with exercise training, could be used as an effective training method to improve motor performance in PD patients, especially for those at high-risk for falls.

Human creativity escapes in the struggle against threat: Evidence from neural mechanisms

The damaging effect of threat on creativity has been confirmed by many studies. However, the neural mechanism underlying this effect has not been clarified. We designed an experiment to explore changes in brain activation when creativity is threatened. Specifically, participants performed the Chinese Remote Associates Test (RAT) under three conditions. The control condition was accompanied by no sound, the neutral condition was accompanied by unpredictable neutral sounds, and the threat condition was manipulated through unpredictable aversive sounds. We used functional near-infrared spectroscopy measurements to collect cognitive neurological data. The results showed that the threat condition reduced the accuracy and response time of the RAT and led to individual negative emotions. Participants’ prefrontal cortex and supramarginal gyrus activation decreased under threat. These results provide a reference for clarifying the negative impact of threat on creativity and highlight its cognitive neural mechanisms.

Hybrid motion artifact detection and correction approach for functional near-infrared spectroscopy measurements.

.SignificanceFunctional near-infrared spectroscopy (fNIRS) is a promising optical neuroimaging technique, measuring the hemodynamic signals from the cortex. However, improving signal quality and reducing artifacts arising from oscillation and baseline shift (BS) are still challenging up to now for fNIRS applications.AimConsidering the advantages and weaknesses of the different algorithms to reduce the artifact effect in fNIRS signals, we propose a hybrid artifact detection and correction approach.ApproachFirst, distinct artifact detection was realized through an fNIRS detection strategy. Then the artifacts were divided into three categories: BS, slight oscillation, and severe oscillation. A comprehensive correction was applied through three main steps: severe artifact correction by cubic spline interpolation, BS removal by spline interpolation, and slight oscillation reduction by dual-threshold wavelet-based method.ResultsUsing fNIRS data acquired during whole night sleep monitoring, we compared the performance of our approach with existing algorithms in signal-to-noise ratio (SNR) and Pearson’s correlation coefficient (). We found that the proposed method showed improvements in performance in SNR and with strong stability.ConclusionsThese results suggest that the new hybrid artifact detection and correction method enhances the viability of fNIRS as a functional neuroimaging modality.

Decoding a Music-Modulated Cognitive Arousal State using Electrodermal Activity and Functional Near-infrared Spectroscopy Measurements.

Biofeedback systems sense different physiological activities and help with gaining self-awareness. Understanding music's impact on the arousal state is of great importance for biofeedback stress management systems. In this study, we investigate a cognitive-stress-related arousal state modulated by different types of music. During our experiments, each subject was presented with neurological stimuli that elicit a cognitive-stress-related arousal response in a working memory experiment. Moreover, this cognitive-stress-related arousal was modulated by calming and vexing music played in the background. Electrodermal activity and functional near-infrared spectroscopy (fNIRS) measurements both contain information related to cognitive arousal and were collected in our study. By considering various fNIRS features, we selected three features based on variance, root mean square, and local fNIRS peaks as the most informative fNIRS observations in terms of cognitive arousal. The rate of neural impulse occurrence underlying EDA was taken as a binary observation. To retain a low computational complexity for our decoder and select the best fNIRS-based observations, two features were chosen as fNIRS-based observations at a time. A decoder based on one binary and two continuous observations was utilized to estimate the hidden cognitive-stress-related arousal state. This was done by using a Bayesian filtering approach within an expectation-maximization framework. Our results indicate that the decoded cognitive arousal modulated by vexing music was higher than calming music. Among the three fNIRS observations selected, a combination of observations based on root mean square and local fNIRS peaks resulted in the best decoded states for our experimental settings. This study serves as a proof of concept for utilizing fNIRS and EDA measurements to develop a low-dimensional decoder for tracking cognitive-stress-related arousal levels.

Altered complexity in resting-state fNIRS signal in autism: a multiscale entropy approach

Objective. Feature extraction and recognition in brain signal processing is of great significance for understanding the neurological mechanism of autism spectrum disorder (ASD). Resting-state (RS) functional near-infrared spectroscopy measurement provides a way to investigate the possible alteration in ASD-related complexity of resting-state (RS) functional near-infrared spectroscopy (fNIRS) signals and to explore the relationship between brain functional connectivity and complexity. Approach. Using the multiscale entropy (MSE) of fNIRS signals recorded from the bilateral temporal lobes (TLs) on 25 children with ASD and 22 typical development (TD) children, the pattern of brain complexity was assessed for both the ASD and TD groups. Main results. The quantitative analysis of MSE revealed the increased complexity in RS-fNIRS in children with ASD, particularly in the left temporal lobe. The complexity in the RS signal and resting state functional connectivity (RSFC) were also observed to exhibit negative correlation in the medium magnitude. Significance. These results indicated that the MSE might serve as a novel measure for RS-fNIRS signals in characterizing and understanding ASD.

Neural basis for egalitarian sharing in five-to six-year-old children

Preferring fair resource distribution reflects human cooperative nature, but its neural correlates in young children are not well known. We investigated the neural mechanism of egalitarian resource sharing in five-to six-year-old children to examine the possibility that early egalitarianism requires behavioral control to inhibit selfish impulses. In Study 1, children participated in a behavioral control task in which they either needed or did not need to inhibit their impulsive behavioral responses in order to quickly press a key. They subsequently allocated their resources to strangers by choosing a 2:2, 3:1, or 4:0 distribution. The activation of the dorsolateral prefrontal (dlpfc) regions was recorded by functional near-infrared spectroscopy measurements. We found that dlpfc regions were activated during cognitive tasks involving behavioral control and also during the equal, but not the more selfish, allocations. There was no difference among these allocations. The results did not show evidence of an ego depletion effect on children's sharing behavior, which predicts that children will share less after their behavioral control is taxed in a cognitive task (i.e., their self-control resource depleted). Study 2 showed no activation of the dlpfc regions during third-party equal allocations in which there was no conflict between fairness and self-interest in the distribution of resources. Overall, we showed that costly equal sharing in young children relates to the activation of dlpfc regions. These results suggest that costly equal allocation has a common neural basis with behavioral control in five-to six-year-old children, implying that early egalitarian sharing requires dealing with conflicts between maximizing self-interest and following moral norms.

Effective Connectivity Study Guiding the Neuromodulation Intervention in Figurative Language Comprehension Using Optical Neuroimaging.

The current study is aimed at establishing links between brain network examination and neural plasticity studies measured by optical neuroimaging. Sixteen healthy subjects were recruited from the University of Macau to test the Granger Prediction Estimation (GPE) method to investigate brain network connectivity during figurative language comprehension. The method is aimed at mapping significant causal relationships across language brain networks, captured by functional near-infrared spectroscopy measurements (fNIRS): (i) definition of regions of interest (ROIs) based on significant channels extracted from spatial activation maps; (ii) inspection of significant causal relationships in temporal resolution, exploring the experimental task agreement; and (iii) early identification of stronger causal relationships that guide neuromodulation intervention, targeting impaired connectivity pathways. Our results propose top-down mechanisms responsible for perceptive-attention engagement in the left anterior frontal cortex and bottom-up mechanism in the right hemispheres during the semantic integration of figurative language. Moreover, the interhemispheric directional flow suggests a right hemisphere engagement in decoding unfamiliar literal sentences and fine-grained integration guided by the left hemisphere to reduce ambiguity in meaningless words. Finally, bottom-up mechanisms seem activated by logographic-semantic processing in literal meanings and memory storage centres in meaningless comprehension. To sum up, our main findings reveal that the Granger Prediction Estimation (GPE) integrated strategy proposes an effective link between assessment and intervention, capable of enhancing the efficiency of the treatment in language disorders and reducing the neuromodulation side effects.

58 Monte Carlo modelling of photon propagation in a human head model containing an enhanced-absorbing target

Introduction. Modelling the light propagation inside brain tissue structures is still a challenging task which requires the use of complex computational schemes often based on Monte Carlo method [ 1 Vaudelle F. and L’Huillier J.P. Time-resolved optical fluorescence spectroscopy of heterogeneous turbid media with special emphasis on brain tissue structures including diseased regions: a sensitivity analysis. Opt Comm. 304 161–168 (2013). Google Scholar , 2 Mansouri C, L’Huillier JP, Kashou NH, Humeau A. Depth sensitivity analysis of functional near-infrared spectroscopy measurement using three-dimensional Monte Carlo modelling based magnetic resonance imaging. Lasers Med Sci. 25, 431-438 (2010). Google Scholar , 3 Fang Q. Mesh-based Monte Carlo method using fast ray tracing in Plücker coordinates. Biomed Opt Exp. 1 165–175 (2010). Google Scholar ]. Because of strong tissue-scattering process (NIR infrared range: 600–900 nm), deep probed structures receive much less light amount than the superficial tissues. This has the effect to impede optical measurements and efficient planning treatments. In this paper, we take an interest in noninvasive tissue arrangements for which a NIR light source strikes a human head model, and thus investigate how photons penetrate and interact with an enhanced-absorbing target located close to the CSF layer. The study especially aims at displaying the effects of tissue structure, optical properties, location and size of the inclusion, dye concentration and light source parameters on optical diagnostic and therapeutic treatment.

Evaluating Working Memory Capacity with Functional Near-Infrared Spectroscopy Measurement of Brain Activity

The present study investigated the relationship between working memory capacity and brain activity in the dorsolateral prefrontal cortex (DLPFC) and the left ventrolateral prefrontal cortex (VLPFC) using functional near-infrared spectroscopy. We administered the reading span test language task to measure linguistic working memory, while we assessed brain activity reflected in the cerebral blood flow change during the task. The cerebral blood flow change in the DLPFC had a negative correlation with the reading span test score. Both focused regions exhibited different patterns of cerebral blood flow changes during the first and second halves of the task period in the high- and low-score groups. Our findings suggest that the brain activity correlates with the reading span test score, which is associated with linguistic working memory capacity. Therefore, brain activity measurement in the DLPFC with the functional near-infrared spectroscopy can be used to indirectly assess working memory capacity.

Frontal Lobe Hemodynamic Responses to Painful Stimulation: A Potential Brain Marker of Nociception.

The purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to examine patterns of both activation and deactivation that occur in the frontal lobe in response to noxious stimuli. The frontal lobe was selected because it has been shown to be activated by noxious stimuli in functional magnetic resonance imaging studies. The brain region is located behind the forehead which is devoid of hair, providing a relative ease of placement for fNIRS probes on this area of the head. Based on functional magnetic resonance imaging studies showing blood-oxygenation-level dependent changes in the frontal lobes, we evaluated functional near-infrared spectroscopy measures in response to two levels of electrical pain in awake, healthy human subjects (n = 10; male = 10). Each subject underwent two recording sessions separated by a 30-minute resting period. Data collected from 7 subjects were analyzed, containing a total of 38/36 low/high intensity pain stimuli for the first recording session and 27/31 pain stimuli for the second session. Our results show that there is a robust and significant deactivation in sections of the frontal cortices. Further development and definition of the specificity and sensitivity of the approach may provide an objective measure of nociceptive activity in the brain that can be easily applied in the surgical setting.

Removal of motion artifacts originating from optode fluctuations during functional near-infrared spectroscopy measurements.

Functional near-infrared spectroscopy (fNIRS) has been increasingly utilized for detecting human cerebral activity in many disciplines because of the potential for less-restraining conditions. However, users often suffer from motion artifacts originating from optode fluctuation during task execution when the task includes motion. In such cases, the optode fluctuation induces changes both in the reflection by hair and in the transmission between the optode and scalp. If part of the reflected light is directly received by the detector optode (short-circuited light), it will contaminate the fNIRS signal. The transmittance change at the optode-scalp gap will also contaminate the signal. In this study, we proposed an optical model on the influence of optode fluctuation on the fNIRS signal and a method for removing the influence. The model revealed the following: (1) the received short-circuited light and the gap transmittance change generated a baseline change in the detected light intensity, and (2) the signal from the tissues was downscaled with increases in the receiving intensity of short-circuited light. To avoid erroneous detection of short-circuited light, we developed a method that optically eliminated hair-reflected light from the detection using linearly polarized light sources and an orthogonally polarized analyzer. The method was validated with an optical phantom possessing a haired surface. The optical absorbance change of a close source-detector (S-D) pair equipped with polarizers was very similar to that of distant S-D pairs, even though these optodes were artificially fluctuated. By combining the multidistance optode arrangement technique with the short-circuited light elimination method, the measurement could effectively eliminate motion artifacts originating from optode fluctuation.

Frontal cerebral oxygen response as an indicator of initial attention effort during perceptual learning

Perceptual learning is critical in many settings. In the present study, we investigated the role of individual differences in attention effort in perceptual learning by having participants learn to detect rare cryptic figures. We employed both functional near-infrared spectroscopy measures of frontal cortical activity and self-reports of pre-task motivation in order to assess individual differences in attention effort. We also manipulated performance feedback and the amount of background information provided to the participants regarding the task. Twelve men and 28 women participated in the experiment. Performance metrics were indicative of perceptual learning occurring. Overall performance on the task was correlated significantly with pre-task levels of self-reported motivation and the rate of learning was correlated with initial oxygen response in the frontal cortex. The initial spike in frontal oxygen response declined with time on task, perhaps due to shifts towards automaticity. The results suggest perceptual learning is influenced by individual differences in attention effort.

Detection of an unstable and/or a weak probe contact in a multichannel functional near-infrared spectroscopy measurement

Multichannel functional near-infrared spectroscopy measurements involve the placement of many probes on a subject's head. A stable close contact between the probe and head surface is essential. We propose a way to detect two types of problematic probe contacts from the measurement data: an unstable contact whose light transmission easily fluctuates with body motion, and a weak contact whose light transmission is constantly small. An unstable contact causes large baseline fluctuation, whereas a weak contact causes large noise. Because absorbance changes caused by body motion and noise show different spectroscopic properties from the tissue hemoglobin absorption, they have a component orthogonal to the plane spanned by hemoglobin molar extinction coefficient vectors. We use this information to detect unstable and/or weak contacts. Probes are shared by different channels, and this sharing configuration is determined by the probe arrangement. Thus, the baseline fluctuation and noise of the channels are related to contact instability and weakness of the probe according to the probe arrangement. Unstable and/or weak probes are determined by solving an inverse problem of this relation. Problematic probes can be effectively determined using the proposed method.

Quantitative assessment of diffuse optical tomography sensitivity to the cerebral cortex using a whole-head probe

We quantify the variability in diffuse optical tomography (DOT) sensitivity over the cortical surface in eight young adult subjects. We use the 10/5 electroencephalography system as a basis for our whole-head optical high-density probe design. The contrast-to-noise ratio (CNR) is calculated along with the percentage of the cortex that is above a CNR = 0 dB threshold. We also quantify the effect of including vasculature on the forward model and list our assumptions that allow us to estimate light penetration depth in the head. We show that using the 10/5 system for the optical probe design allows for the measurement of 37% of the cortical surface on average, with a mean CNR in the visible region of 5.5 dB. Certain anatomical regions, such as the lateral occipital cortex, had a very high percentage above the CNR threshold, while other regions such as the cingulate cortex were not measurable. Vasculature blocked optical sensitivity over 1% of the cortex. Cortical coverage was positively correlated with intracranial volume and relative cerebrospinal fluid volume, and negatively correlated with relative scalp volume and skull volume. These contributions allow experimenters to understand how anatomical variation in a subject population may impact DOT or functional near-infrared spectroscopy measurements.

Decoding what one likes or dislikes from single-trial fNIRS measurements

Recent functional neuroimaging studies have shown the possibility of decoding human mental states from their brain activity using noninvasive neuroimaging techniques. In this study, we applied multivariate pattern classification, in conjunction with a short interval of functional near-infrared spectroscopy measurements of the anterior frontal cortex, to decode whether a human likes or dislikes a presented visual object; an ability that is quite beneficial for a number of clinical and technological applications. A variety of objects comprising sceneries, cars, foods, and animals were used as the stimuli. The results showed the possibility of predicting subjective preference from a short interval of functional near-infrared spectroscopy measurements of the anterior frontal regions. In addition, the pattern localization results showed the neuroscientific validity of the constructed classifier.

In vivo functional near-infrared spectroscopy measures mood-modulated cerebral responses to a positive emotional stimulus in sheep

The affective state of an animal, which is thought to reflect its welfare, consists of both short-term emotional reactions and long-term general mood. Because this state is generated and processed by the brain, we used non-invasive measurement of such brain activity as a novel indicator variable and investigated the interplay of mood and short-term emotional reactions in animals. We developed a wireless sensor for functional near-infrared spectroscopy (fNIRS), which assesses cortical perfusion changes, and consequently neuronal activity. Mood differences were induced by barren and enriched housing in a total of nine sheep and we observed their brain reaction in response to the positive situation of being groomed. We detected a decrease in cerebral oxyhaemoglobin concentration ([O2Hb]) which persisted during grooming. The localisation of the decrease in the brain did not depend on the site where the stimulus was applied. Also, the intensity of the response did not depend on the intensity of the grooming stimulus and a sham stimulus did not evoke an [O2Hb] response as seen with a grooming stimulus. Thus, we conclude that the observed haemodynamic brain response was unlikely to reflect pure somato-sensory information. We then found that the amplitude of the [O2Hb] response was larger if sheep were in a supposedly more negative mood. This contradicts the common assumption that negative mood generally taints reactions to emotional stimuli. Our results also demonstrate the potential of fNIRS for assessing affective states in freely moving animals.

Depth sensitivity analysis of functional near-infrared spectroscopy measurement using three-dimensional Monte Carlo modelling-based magnetic resonance imaging

Theoretical analysis of spatial distribution of near-infrared light propagation in head tissues is very important in brain function measurement, since it is impossible to measure the effective optical path length of the detected signal or the effect of optical fibre arrangement on the regions of measurement or its sensitivity. In this study a realistic head model generated from structure data from magnetic resonance imaging (MRI) was introduced into a three-dimensional Monte Carlo code and the sensitivity of functional near-infrared measurement was analysed. The effects of the distance between source and detector, and of the optical properties of the probed tissues, on the sensitivity of the optical measurement to deep layers of the adult head were investigated. The spatial sensitivity profiles of photons in the head, the so-called banana shape, and the partial mean optical path lengths in the skin-scalp and brain tissues were calculated, so that the contribution of different parts of the head to near-infrared spectroscopy signals could be examined. It was shown that the signal detected in brain function measurements was greatly affected by the heterogeneity of the head tissue and its scattering properties, particularly for the shorter interfibre distances.

Face pictures reduce behavioural, autonomic, endocrine and neural indices of stress and fear in sheep.

Faces are highly emotive stimuli and we find smiling or familiar faces both attractive and comforting, even as young babies. Do other species with sophisticated face recognition skills, such as sheep, also respond to the emotional significance of familiar faces? We report that when sheep experience social isolation, the sight of familiar sheep face pictures compared with those of goats or inverted triangles significantly reduces behavioural (activity and protest vocalizations), autonomic (heart rate) and endocrine (cortisol and adrenaline) indices of stress. They also increase mRNA expression of activity-dependent genes (c-fos and zif/268) in brain regions specialized for processing faces (temporal and medial frontal cortices and basolateral amygdala) and for emotional control (orbitofrontal and cingulate cortex), and reduce their expression in regions associated with stress responses (hypothalamic paraventricular nucleus) and fear (central and lateral amygdala). Effects on face recognition, emotional control and fear centres are restricted to the right brain hemisphere. Results provide evidence that face pictures may be useful for relieving stress caused by unavoidable social isolation in sheep, and possibly other animal species, including humans. The finding that sheep, like humans, appear to have a right brain hemisphere involvement in the control of negative emotional experiences also suggests that functional lateralization of brain emotion systems may be a general feature in mammals.