Abstract
Surgical candidates for epilepsy need more information pertaining to possible side effects of surgical resection impacting emotional recognition of people and experiences. Specifically, for an individual what degree of lateralization is present in a brain’s ability to recognize, respond to, and experience an emotion? Olfaction is processed in brain structures excised during surgery, but it overlays networks involved in other sensory modalities. Its connection to emotional memory is long established. Recognition tests of emotion evoking substances should be explored for use in Wada exams to predict the resected brain’s ability to respond to stimuli for emotions such as pleasure, disgust, or affection. Whereas odor processing in the brain is largely ipsilateral to the nostril, it may further prove useful to compare a Wada evaluation to a test done simply by alternately blocking nostrils and screening for changes in perceived quality of substances. If successful, such an approach would obviate the need to involve a Wada exam.
Key words
emotional recognition, olfaction, epilepsy, Wada exam
Abbreviations
ATL – anterior temporal lobectomy
Introduction
Anterior temporal lobectomy (ATL) is a common approach to seizure control with a proven therapeutic track record. However, as many as 7% of patients experience postoperative psychiatric disorders [1]. For a patient who experiences preoperative emotional impairment (such as can be the case following status epilepticus), even on the scale of minutes, and comes to recognize it as such, the experience can inspire an obsessive yet warranted desire for information pertaining to the possible postoperative side effects of ATL. By impairment I generally mean a deficit of response to a stimuli such as feeling a profound indifference towards a loved one following a medical trauma [2] rather than a miss-assignment of emotion to a stimulus (a greater impairment but not one I address). In personal experience in an American hospital (the author has left mesial temporal sclerosis), preoperative assessment for vulnerability to emotional impairment is not evaluated nor is information drawn from research on others discussed with the patient (see [3] for an example of ideal procedures in France)
For a resection candidate, functional redundancy across cerebral hemispheres is valuable. Thus, a key question for decision making becomes whether or not the ability to recognize or express emotions differs between hemispheres and with much person-to-person variation. If so, is making a personal profile a source of novel and useful data for the doctor and patient to use in decision making regarding surgical resection?
Emotional recognition functions in the brain are more complex and region specific than has been previously assumed [4]. Discernment of the valence of other’s response to stimuli is lateralized across hemispheres but the extent of this lateralization for different emotions varies between individuals [5]. Patients suffering from amygdala damage can have inconsistent patterns of recognition deficits [6]. Particular attention should be paid to the amygdala in preoperative assessment of risks, as it is especially important in linking affect (esp. negative affect) to stimuli from the environment or from individuals, and it has strong connections to sensory cortex [7].
In addition to recognition of external displays of emotion (such as from music or the facial expressions of others) internal perceptions of fear, happiness, and other emotions have been mapped with direct electrical stimulus to brain areas and found to originate in the amygdala with perceptions varying between the left and right hemisphere [3]. Thus the potential side effects of an ATL, both in accuracy of recognition and/or intensity of personal feeling can vary by the side of the brain operated on and from patient to patient thereby justifying a patient’s desire for more information.
How then can more preoperative knowledge be gained? From the outset, let me acknowledge that no specific test can be comprehensive in any sense. I take the view that any knowledge is good and incremental gain is useful.
The Wada exam is a common part of preoperative evaluation for epilepsy surgery and could play a role in assessing a degree of emotional lateralization in an individual’s brain. During its usage for localizing eloquent cortex, can it serve dual purposes? Stabell et al. [8] looked at how the Wada exam, itself, might affect emotional state. They found that the exam could trigger both euphoric and, less commonly, dysphoric changes in mood. The former occurred for one in five persons and the latter one tenth as frequently. They analyzed age, gender, amobarbital dosage, its side and sequence of its injection, and language laterality. They found no statistical differences in these variables between patients with and without emotional changes under anesthesia. Emotional responses appeared immediately and abated long before testing ended. The responses never hindered a subject’s ability to follow instructions. Their results suggest that using a Wada exam in a test of emotional recognition, and even internal emotional feeling, cannot be dismissed out of hand.
In light of the effects of anesthesia on eloquent cortex (and thus communicative ability) and in light of any time concerns, a system for evaluating emotional cognition that has a quick response, high reliability, and one which may reflect trends toward other sensory systems should be useful. Something which has fast associative training capability would also be welcome. Naturally, such a system should connect closely to the hippocampus and amygdala which are removed in surgery.
Olfaction is more influential to emotional cognition [9] than other senses – the sense of smell is appetitive i.e. central to seeking food, sexually receptive mates, and other things associated to joy or pleasure. Smell also warns of dangers and triggers fear response. It is superior to other senses in cuing emotional memories far back into time [10]. Emotion may have a fundamental relationship to olfaction to a considerably greater degree than to other senses ([11]; reviewed in [12]) and the two systems share extensive parts of neural networking (reviewed in [12]).
Olfaction is processed through the hippocampus and amygdala (reviewed in [9]). It may also be a more potent stimulus of activity in the amygdala than are hearing and vision [13]. Olfactory and visual input stimulate activity in the hypothalamus, whereas auditory input does not [13]. Olfaction, as a trigger, is very rapid – two to three neurons lie between the olfactory epithelium and the memory and emotional structures in the brain [14]. Importantly, primary olfactory cortical functional connectivity within a hemisphere does not statistically differ between hemispheres [11].
A key concern to a method for assessing emotion in the brain is the possible influence of cultural and personal differences in relation to stimulant effects which can be quite substantial [15]. Surstromming (months – old fermented fish) is perceived differently by a Scandinavian than by persons of other cultures. Age and gender related life histories also influence the emotional response to odor. A veteran is expected to have a dampened response to any negative emotional stimulus than would an adolescent. A faint smell of horse manure will simply offend some people but bring up pleasant memories of grandpa’s farm to others.
A training procedure that would impart stimulus – response patterns de novo might ameliorate concerns about response variations across cultures, ages, or other demographic parameters. Temporal lobe epilepsy, itself, can cause deficits in olfactory perception of pleasantness, familiarity, and other parameters [16]. Training de novo might address this problem. Emotional associations to odors are not innate, but rather, learned and new associations with novel odors can be trained in situ and remain stable for a week [15] if not longer.
One example of what training can entail is the work of Herz et al. [17] who manipulated research participants’ associations to odor using culturally relevant entertaining and funny films of 15 minutes in duration. They also used gambling games that were secretly biased in favor of the subject. All the while, the individual was selectively exposed to ambient odors to be used as emotional stimulants in later research.
Emotional connections to odors already have a broad study base (reviewed in [18] and extensively in [19]). In addition to established test methodologies, an extensive amount of research results exists for a broad catalog of odors and feelings linked to them (e.g. [10, 18, 20, 21]; see Appendices A & B in [15] for detailed examples used in verbal assessments). Hence, experiments in clinical usage do not need to break new ground in materials used.
Given that the Wada test attempts to impair language, responses to stimulated feelings (or the lack thereof) need to be conveyed non-verbally. Research methods involving an assessment of affect have also used non-verbal methodologies. An affect grid allows an individual to rate pleasantness and arousal from a stimulus simply by placing a mark on a grid. The technique is reviewed extensively by Toet et al. [22] who further describe an approach for testing children that uses emojis (the cartoon faces employed in such web sites as Facebook to convey sentiment). No language is involved, ameliorating at least some concern regarding the left side bias of language. Of course heart rate and skin conductance have long been used to such ends. Skin conductance correlates to emotional arousal, though heart rate may be less predictable [18].
As a side note, a visionary yet feasible approach to training the olfactory system outside of a clinical setting hypothetically requires only essential oils, disposable masks to conduct odors, a room fan (for purging the environment) and an internet connection. Movie clips or games can readily be tailored to stimulate to any set of emotions, be viewed via the internet, and procedure adherence recorded remotely. Likewise, olfactory cues can be self administered with the use of blindly labeled vials with a single use disposable mask (blind methodologies are critical [20]). Intervals between training for different stimulants can be indicated remotely with or without close human supervision. In – home olfactory training also has a familiar and relaxed environment. Remote patient monitoring of a simpler nature is already used pre- and postoperatively in cardiac surgery and also pace-maker monitoring (personal experience).
While my thoughts generally assume the administration of a Wada exam, one exciting characteristic of the olfactory system is that smells are primarily processed ipsilaterally to the individual receiving nostril with much reduced contralateral processing, though this pattern is by no means absolute (reviewed in [23]). Sensory cells project exclusively to the ipsilateral olfactory bulb which connects exclusively to the ipsilateral olfactory cortex [24] The ramifications for anesthesiology are that it might be possible to forgo it in favor of a simple nostril plug. EEG results provide useful information and have a huge study base to draw upon [19]. In the time interval between ipsilateral and contralateral responses to stimulation, an EEG might provide pertinent information regarding response locations and intensities thereby providing some information about the response regions of the brain for a stimulus without needing to anesthetize half of the brain and coping with artificially induced euphoria / dysphoria. Nevertheless, the issue of predominant ipsilateral processing is not completely resolved [25], and any optimism for such an approach must remain guarded.
Conclusion
There are deeper concerns to temporal lobe resection than just the preservation of eloquent cortex. Preserving a full range of emotional faculties can be a patient’s main concern. Sensory systems that offer direct insight into how we associate emotions to our physical and social environment under artificial brain impairment are valuable to judging the impact of ATL on such faculties. Associations include recognizing expressions in or from others via sensory cues, feeling emotions stimulated within ourselves, and combinations of each. Of further value is a sensory system that surrogates other senses to a great extent. The olfactory system is such a system, and relevant psychological background research is quite substantial thus facilitating rapid optimization of methodologies, e.g. choosing odors to use or defining time intervals of interest on EEG results. Olfactory responses to stimuli can readily be trained – calibrated – to preclude cultural and other artifacts between people from distorting results. As such, it warrants deeper attention for a role in preoperative patient evaluation for ATL.
References
[1] Brotis A, Giannis T, Kapsalaki E, Dardiotis E, and Fountas K (2019) Complications after anterior temporal lobectomy for medically intractable epilepsy: a systematic review and meta-analysis. Stereot Funct Neuros 97: 69-82
[2] Hatcher J (2015) Tacking on the Styx: an Epileptic Sails the Facts, Fiction, and Philosophy of a Mental Illness. AuthorHouse Press. Bloomington: Indiana.
[3] Lanteaume L, Khalfa S, Regis J, Marquis P, and Bartolomei F (2007) Emotion induction after direct intracerebral stimulations of human amygdala. Cerebral Cortex 17: 1307-1313.
[4] Wager TD, Phan KL, Liberzon I, and Taylor SF (2003) Valence, gender, and lateralization of functional brain anatomy in emotion: a meta-analysis of findings from neuroimaging. NeuroImage 19: 513-531.
[5] Schiffer F, Teicher MH, Anderson C, Tomoda A, Polcari A, et al. (2007) Determination of hemispheric emotional valence in individual subjects: a new approach with research and therapeutic implications. Behav Brain Func 3: 13.
[6] Fowler HL, Baker GA, Tipples J, Hare DJ, Keller S, et al. (2006) Recognition of emotion with temporal lobe epilepsy and asymmetrical amygdala damage. Epilepsy & Behav 9: 164-172.
[7] Cristinzio C and Vuilleumier P (2007) The role of amygdala in emotional and social functions for temporal lobe epilepsy. Epileptologie 24:78-89.
[8] Stabell KE, Andresen S, Bakke SJ, Bjornaes H, Borchgrevink HM, et al. (2004) Emotional responses during unilateral amobarbital anesthesia: differential hemisphere contributions? Acta Neurol Scand 110: 313-321.
[9] Krusemark EA, Novak LR, Gitelman DR, and Li, W (2013) When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry. J Neurosci 33: 15324-15332. https://www.jneurosci.org/content/jneuro/33/39/15324.full.pdf
[10] Chu S and Downes JJ (2002) Proust nose best: odors are better cues of autobiographical memory. Mem Cognition 30: 511-518.
[11] Zhou G, Lane G, Cooper SL, Kahnt T, and Zelano C. (2019) Characterizing functional pathways of the human olfactory system. eLife 2019;8:e47177 DOI: 10.7554/eLife.47177
[12] Chrea C, Grandjean D, Delplanque S, Cayeux I, Le Calve B, et al (2009) Mapping the semantic space for the subjective experience of emotional responses to odors. Chem Senses 34: 49-62.
[13] Royet JP and Plailly J (2004) Lateralization of olfactory processes. Chem. Senses 29:731-745.
[14] Saive A, Royet JP, Ravel N, Thevenet M, Garcia S, et al. (2014) A unique memory process modulated by emotion underpins successful odor recognition and episodic retrieval in humans. Front Behav Neurosci 8: 1-11.
[15] Ferdenzi C, Roberts SC, Schirmer A, Delplanque S, Cekic S, et al. (2013) Variability of affective responses to odors: culture, gender, and olfactory knowledge. Chem. Senses 38: 175-186.
[16] Hudry J, Ryvlin P, Saive AL, Ravel N, Plailly J and Royet, JP (2014) Lateralization of olfactory processing: differential impact of right and left temporal lobe epilepsies. Epilepsy & Behav 37: 184-190.
[17] Herz RS, Beland SL and Hellerstein M (2004) Changing odor hedonic perception through emotional associations in humans. Int J Comp Psychol 17: 315-338.
[18] Bensafi M, Rouby C, Farget V, Bertrand B, Vigouroux M, et al. (2002) Autonomic nervous system responses to odours: the role of pleasantness and arousal. Chem. Senses 27: 703-709.
[19] Sowndhararajan K and Kim S (2016) Influence of fragrances on human psychophysiological activity: with special reference to human electroenchephalographic response. Sci. Pharm. 2016, 84, 724–751.
[20] Herz RS, von Clef J. (2001) The influence of verbal labeling on the perception of odors: evidence for olfactory illusions? Perception. 30(3):381–391.
[21] Moskowitz HR, Dravnieks A, and Klarman, LA (1976) Odor intensity and pleasantness for a diverse set of odorants. Percept Psychophys 19: 122-128.
[22] Toet A, Kaneko D, Ushiama S, Hoving S, de Kruijf I, et al. (2018) EmojiGrid: a 2D pictorial scale for the assessment of food elicited emotions. Front Psychol 9: 2396.
[23] Olsson MJ and Cain WS (2003) Implicit and explicit memory for odors: hemispheric differences. Mem Cognition 31: 44-50.
[24] Cohen Y, Putrino D and Wilson DA (2015) Dynamic cortical lateralization during olfactory discrimination learning. J Physiol 593.7: 1701-1714.
[25] Savic I and Gulyas B (2000) PET shows that odors are processed both ipsilaterall and contralaterally to the stimulated nostril. NeuroReport 11: 2861-2866.
对于任何用中文阅读的人来说，如果我有任何混乱或措辞不当的句子，请允许我道歉。 这个翻译是用https://www.deepl.com/en/translator 的程序编写的，我认为这个程序对大多数主题都很有效。 我不懂任何亚洲语言，但我认为我的主题值得关注，即使我的语言技能有限，也足以翻译。
手术切除大脑颞叶前部的一部分是停止癫痫发作的常见手术，因为很多癫痫发作都是从颞叶开始的。然而，每一百个病人中，有多达七个人在做完手术后出现精神问题[1]。作为一名患者，我只经历过几次非常严重的癫痫发作后的情感识别障碍。所谓情感识别，是指看到家人，感受到对他们的爱。 它也可能意味着看到一个孩子受到伤害而对造成伤害的人感到愤怒。当我在癫痫发作一小时后住院时，我认出了我家里的一个人，当我恢复意识时，他和我在一起，但他们的存在对我来说没有什么特别的意义。我对他们的感情，与对照顾我的护士和医生的感情是完全一样的。 由于我所遭受的创伤，这种缺乏情感反应的情况令人困惑。 这种不能正确地把认识的面孔和感情联系起来的感觉，使我觉得自己不是人。 雖然我的辨認能力在幾分鐘後就恢復了，但這個經驗，加上患了癲癇的抑鬱，使我考慮自殺[2]。
几年后，当我在哥伦比亚大学攻读博士学位时，我的癫痫病再次变得很严重。 我的神经科医生开始测试是否可以通过做手术来阻止我的癫痫发作。 然而，我已经知道大脑的颞叶会产生情绪。 我也知道如果我表现情绪的能力受到手术的伤害，我可能会有自杀倾向。 我的焦虑影响了我的学校工作，这让我更加焦虑。 焦虑的增加使我的癫痫病更加严重。 在这段时间里，我想知道更多关于手术对自己大脑的后果的信息，但医生根本没有给我任何信息。
根据个人在美国医院的经验(我患有左颞部中层硬化症)，术前并没有评估易受情绪损伤的程度，也没有向患者提供从他人研究中得出的信息(参见[3]法国理想程序的例子)
对于要手术的病人来说，跨大脑半球的功能冗余是非常有价值的。因此，对于决策来说，一个重要的问题就变成了患者大脑左半边和右半边的识别或表达情绪的能力是否不同。如果是这样，那么制作个人档案是否可以为医生和患者提供新颖而有用的数据来源，用于决定是否进行手术？
大脑识别情绪的能力比以前所认为的要复杂得多[4]。一个人识别他人对特定刺激的情绪反应的能力，对于特定的情绪，其大脑的左右两边是不同的。 但两侧之间的差异量取决于所关注的特定情绪。 此外，也是很重要的一点，不同患者之间的量也是不同的[5]。杏仁核受损的患者会有不一致的识别困难模式[6]。医生在评估手术风险时需要特别关注杏仁核，因为杏仁核在将情绪，尤其是负面情绪与来自环境或其他个体的刺激联系起来方面特别重要。 杏仁核与处理感觉信息的脑区有很强的神经联系[7]。
除了识别外部的情绪显示（如来自音乐或他人的面部表情），对恐惧、快乐等情绪的内部感知也用直接的电刺激绘制了脑区图谱，发现其起源于杏仁核，左右大脑半球的感知有所不同[4]。因此，手术的潜在副作用既会影响识别的准确性，也会影响个人反应的强度。 这些手术的副作用会随着不同患者所手术的大脑一侧而不同从而证明了患者对更多个人信息的渴望。
那么如何在手术前获得更多的知识呢？让我承认，没有任何具体的测试可以回答患者可能有的所有问题，但哪怕是一点额外的知识也是好的。
和田创造的阿莫巴比妥试验是癫痫手术常用的评估程序，可以起到评估个体大脑情感侧化程度的作用。在其用于定位大脑中的语言处理中心的过程中，能否起到双重作用呢？Stabell等人[8]研究了和田检查，本身如何影响情绪。他们发现，考试过程既可能引起好的情绪变化，也可能引起坏的情绪变化。好的情绪变化发生在五分之一的人身上，坏的情绪变化发生在2%的人身上。他们分析了年龄、性别、阿莫巴比妥剂量、注射阿莫巴比妥的副作用和顺序以及语言位置。他们发现，在麻醉下，经历和未经历情绪变化的患者在这些变量上没有统计学差异。情绪反应立即出现，并在测试结束前很长时间停止。这些反应从未妨碍受试者遵循指令的能力。他们的结果表明，Wada检查可以被调整以探索特定患者的情绪。
由于麻醉对语言皮层的影响，从而对交际能力的影响，一种用于评价情感认知的感觉系统应该是有用的，这种系统具有快速反应、高可靠性，并且可以反映其他感觉系统的趋势。 显然，这种系统应该与手术中被切除的海马体和杏仁核紧密相连。
与其他感官相比，嗅觉对情感认知的影响更大[9]–嗅觉是寻求食物、性接受伴侣以及其他与快乐或愉悦相关的事物的核心。嗅觉还能警告危险并引发恐惧反应。它在提示远古的情感记忆方面优于其他感官[10]。情绪与嗅觉的基本关系可能比其他感官的关系大得多([11]；综述于[12])。 情绪和嗅觉共享神经网络的广泛部分（在[12]中回顾）。 嗅觉是通过海马体和杏仁核处理的（在[9]中回顾）。它也可能比听觉和视觉更有效地刺激杏仁核的活动[13]。嗅觉和视觉输入会刺激下丘脑的活动，而听觉输入则不会[13]。嗅觉作为一个触发器，是非常迅速的–两到三个神经元位于嗅觉上皮和大脑中的记忆和情感结构之间[14]。重要的是，一个半球内的嗅觉网络在两个大脑半球中的程度是相似的[11]。
评估大脑中情感的方法的一个关键问题是文化和个人差异对气味感知方式的可能影响。文化差异可能是相当大的[15]。斯堪的纳维亚人对老发酵鱼的感知与来自其他文化的人不同。年龄和性别也会影响对气味的情绪反应。一个退伍军人对任何负面情绪刺激的反应会比一个年轻学生的反应要小。一股淡淡的马粪味会让一些人反感，但对其他人来说，却会带来祖父母农场的愉快回忆。
一个训练程序，将传授新的刺激–反应模式可能会减少对不同文化、年龄或因素的反应变化的关注。颞叶癫痫，本身就可以导致嗅觉感知的愉悦性、熟悉性和其他情感参数的缺陷[16]。新颖的情绪训练或许可以解决这个问题。对气味的情感联想不是天生的。 它们是习得的，可以为一项研究训练新的与新气味的关联，并且这种关联保持稳定一周或更长时间[15]。
Herz等人[17]的工作就是训练的一个例子，他们使用文化相关的娱乐性和有趣的电影来操纵研究参与者对气味的联想。他们还使用了暗中偏向被试者的赌博游戏。同时，将个体有选择地暴露在环境气味中，作为以后研究中的情绪刺激物。
情感与气味的联系这一主题已被广泛研究（在[18]和[19]中广泛回顾）。除了既定的测试方法，大量的研究结果存在于众多的气味和与气味相关联的情感（例如[10，18，20，21]；参见[15]中附录A和B中用于口头评估的详细例子）。因此，临床使用中的实验不需要对所用材料进行大量的调查。
鉴于和田测试试图损害语言，对刺激感情的反应（或没有反应）需要以非语言方式传达。涉及情绪影响评估的研究方法也使用了非语言方法。一个人可以简单地通过在格子上做标记，对刺激的愉悦性和兴奋性进行评分。Toet等人[22]对该技术进行了广泛的评述，他们进一步描述了一种测试儿童的方法，该方法使用Facebook等网站上的卡通面孔来传达情感。不涉及语言，消除了人们对左右大脑半球之间语言功能不对称的一些担忧。当然，心率和皮肤电导早已被用来测量对刺激的情绪反应。皮肤电导与情绪唤醒相关，尽管心率可能不太可预测[18]。
附带一提的是，在临床环境之外训练嗅觉系统的一个有远见但可行的方法，假设只需要有明确气味的油、一次性口罩来传导气味、一个房间风扇（用于净化环境）和一个计算机网络连接。电影片段或游戏可以很容易地刺激到任何一组情绪，通过互联网查看，并远程记录程序的坚持。同样，嗅觉提示也可以通过使用病人不知道内容的标签小瓶进行自我管理。小瓶的内容被应用到一次性口罩（保持患者未知的内容是至关重要的[20]）。不同的刺激物的训练之间的时间间隔，可以远程指示有或没有密切的人类监督。在患者自己的家中进行嗅觉训练，也能提供一个熟悉和轻松的环境。在病人自己家中进行电子监测，已经被用于心脏手术前后，也用于监测心脏病人的起搏器（个人观察）。
虽然我的想法一般都是假设使用和田检查，但嗅觉系统的一个令人兴奋的特点是，气味主要是在个人鼻孔吸入气味的同侧进行处理，而对侧的处理要少得多，尽管这种模式绝不是绝对的（在[23]中回顾）。感觉细胞只投射到同侧的嗅球，而嗅球只连接到同侧的嗅皮层[24]，这对麻醉学的影响是，可能完全放弃阿莫巴比妥而采用简单的鼻孔塞。脑电图结果提供了有用的信息，并有庞大的研究基础可以借鉴[19]。在同侧和对侧对刺激反应的时间间隔内，脑电图可能会提供有关反应位置和强度的相关信息，从而提供一些关于大脑对刺激的反应区域的信息，而不需要麻醉半边大脑和应付麻醉引起的感觉。尽管如此，同侧处理为主的问题还没有完全解决[25]，对这种方法的任何乐观态度必须保持谨慎。
结语
颞叶切除术除了保留语言功能外，还有更深层次的关注。保留全方位的情感精神功能可以成为患者的主要关注点。感官系统可以直接洞察我们在人工脑损伤下如何将情绪与物理和社会环境联系起来，这对判断脑部手术对这种精神官能的影响很有价值。联想包括通过感觉线索识别他人的表情或来自他人的表情，感受自己内心的情绪，以及两者的组合。更有价值的是一种感觉系统，它在很大程度上代偿了其他感觉。嗅觉系统就是这样一个系统，相关的心理学背景研究相当丰富，从而有利于快速优化方法，例如选择使用的气味或在脑电图结果上定义感兴趣的时间间隔。嗅觉对刺激的反应可以很容易地被训练或校准，以排除文化和其他文物扭曲结果的病人。嗅觉值得更多的关注，用于颞叶脑手术前的患者评估。
Tacking on the Styx 