c o r t e x 5 0 ( 2 0 1 4 ) 2 0 4 e2 0 7
Available online at www.sciencedirect.com
ScienceDirect Journal homepage: www.elsevier.com/locate/cortex
Letter to the Editor
Visualeolfactory hallucinatory synesthesia: The Charles Bonnet Syndrome with olfactory hallucinations David Gubernick a, Pouya Ameli b, Qingshan Teng a, Arnaldo Velez a, Kenneth M. Heilman a and Vishnumurthy Shushrutha Hedna a,* a b
Departments of Neurology, University of Florida College of Medicine, Gainesville, FL, USA University of Central Florida College of Medicine, Orlando, FL, USA
article info Article history: Received 8 August 2013 Reviewed 17 September 2013 Revised 29 September 2013 Accepted 14 October 2013 Published online 31 October 2013
1.
Introduction
In the year 1760, Charles Bonnet noted that his 89-year old grandfather, who was blind from cataracts, was having visual hallucinations. The Charles Bonnet Syndrome (CBS)1 is now a well-documented condition where patients have intricate visual hallucinations, in the absence of psychosis, after a severe decrease or complete loss of vision. The most widely accepted mechanism of CBS is the concept of denervation hypersensitivity. This phenomena describes how internally generated electrical impulses become “released” or disinhibited within the brain following the loss of neuronal inputs from normal external visual stimuli. These released electrical signals then synapse at sites in the visual cortex and can produce complex visual hallucinations (Burke, 2002). Similarly, sensory deprivation in other modalities can lead to hallucinations in that modality. The occurrence of olfactory hallucinations, or phantom smells, following damage to the olfactory system has been previously reported and believed to be induced by a similar denervation hypersensitivity mechanism (Henkin,
Levy, & Lin, 2000). Here we report a 74-year old woman with a right posterior cerebral artery infarction who developed both visual and olfactory hallucinations, which were related to each other both temporally and in content. A search of the literature revealed no reports describing the CBS occurring in conjunction with olfactory hallucinations.
2.
Case report
A 74-year old woman, who was blind in her left eye from a childhood injury to the optic nerve, was transferred to our hospital from an outside facility for stroke management. Two days previously she had gone to this outside hospital complaining of a severe bilateral posterior headache as well as a 1 h episode of vertigo. A brain MRI at this hospital, and later verified by our institution, revealed a large right posterior cerebral artery (PCA) territory infarction affecting the right mesial inferior temporal and occipital lobes (see Fig. 1). Further neurologic exam revealed a left hemianopia. The
* Corresponding author. Department of Neurology, Room L3-100, McKnight Brain Institute, 1149 Newell Drive, Gainesville, FL 32611, USA. E-mail address: [email protected] (V.S. Hedna). 1 CBS ¼ Charles Bonnet Syndrome. 0010-9452/$ e see front matter ª 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.cortex.2013.10.002
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205
Fig. 1 e Proposed model for visualeolfactory hallucinatory synesthesia. 1 & 2: Coronal T2w MRI showing right occipital lobe infarct (circles) consistent with right posterior cerebral artery occlusion. 3: Coronal T2w MRI showing infarction involves inferior mesial temporal lobe (blue) and spares entorhinal cortex (red). 4: Axial T1 MRI showing that the infarction spares anterior parahippocampal-entorhinal cortex (circle). 5: Sagittal T1 showing damage to inferior mesial temporal lobe but sparing the anterior parahippocampal-entorhinal cortex. 6: Sagittal T1 MRI showing damage to visual cortex (circle). Note: arrow depict the relayed hyperactive signaling from the visual cortex to anterior parahippocampal-entorhinal cortex which the arrowhead pointing in the direction of the relay.
morning after our initial evaluation, she started experiencing visual and olfactory hallucinations. She repeatedly described seeing miniature sized people and animals in full color and vivid detail (please see video interview link goes here). She saw these images throughout the day but they most often occurred in the morning when she first awakened from sleep. She also described the people as smelling of a strong “spice”, or the “smoke from a burning stick of incense”. Since olfactory hallucinations had not been reported to be associated with visual hallucinations in the CBS and seizure-like activity from the region of the uncus, so-called uncal fits, can cause olfactory hallucinations (Kiernan, 2012), an electroencephalogram (EEG) was performed while these olfactory hallucinations were present. However, this EEG revealed only mild generalized slowing of brain wave activity over the right temporal lobe without any features of seizure activity. Since, decrements in olfactory sensation can induce olfactory hallucinations we assessed the function of the olfactory nerve in our patient using the Unirhinal Peanut Butter Odor Detection Test (UPBODT).2 The UPBODT is a modified form of the Alcohol Sniff Test, an odorant detection test originally developed by Davidson, Freed, Healy, and Murphy (1998) as a tool to evaluate anosmia clinically. Stamps, Bartoshuk, and Heilman 2
UPBODT ¼ Unirhinal Peanut Butter Odor Detection Test.
(2013) developed the modified form of this test, the UPBODT, to assess olfaction in patients with Alzheimer’s disease. They chose to use peanut butter instead of ammonia to avoid irritating the trigeminal nerve. Consequently, the test proved to have a low cognitive load and good test retest reliability. By testing each nostril separately with the eyes closed, we found that our patient could identify the presence of the odorant at the same distance with each nostril, but could only correctly identify the odor as peanut butter with the left nostril. She reported detecting a variety of odors including coffee with the right nostril. Thus, these results suggest our patient had developed a right-sided troposmia, with intact detection but perceived distortion of odorant stimuli. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.cortex.2013.10.002.
3.
Discussion
The reason why this woman had olfactory hallucinations, together with her visual hallucinations is not entirely clear. According to Leopold (2002) troposmia is often associated with a decreased number of functioning olfactory neurons so that an incomplete characterization of the odorant is made. Greenberg (1992) would argue that this is an example of an
206
c o r t e x 5 0 ( 2 0 1 4 ) 2 0 4 e2 0 7
olfactory distortion rather than a hallucination, since the olfactory experience occurred in the presence of an actual odorant stimulus. In contrast, true olfactory hallucinations occur spontaneously in the absence of any such stimulus. However, Greenberg also would argue that decreased afferent olfactory information could plausibly trigger both true olfactory hallucinations as well as olfactory distortions. It is important to consider that this woman’s right PCA territory infarct injured the right mesial inferior temporal lobe and occipital lobe and did not involve the more anteriorly situated parts of the brain important in olfaction; and thus, olfactory denervation cannot fully explain her olfactory hallucinations. This suggests that if our patient’s troposmia was caused by a decreased number of functioning olfactory neurons, this deficit must have been present prior to her stroke. Although it is possible that she did indeed have a prior undetected troposmia, her denial of previous olfactory deficits, distortions, or hallucinations suggest decreased olfactory nerve function is an unlikely mechanism to explain these new olfactory sensations. Since at least some of her olfactory sensations were always tied to distinct and reproducible visual hallucinations in the absence of any odorant stimulus, we believe that these olfactory sensations represented true olfactory hallucinations and mechanistically were triggered in conjunction with her visual hallucinations. Thus, the challenge of explaining this presentation of CBS is therefore to explore how denervation hypersensitivity in the visual system could result in cross-modal sensory hallucinations. The visual system is highly integrated with the auditory system and in some people this strong integration may be associated with the phenomenon of synesthesia. For example, when people with auditoryevisual synesthesia hear a certain musical note they may see a corresponding color (Cytowic & Eagleman, 2009). Synesthesia is thought to be related to an increase in cross activation between the different modality specific areas of association cortex and recent studies of patients with synesthesia have revealed increased connectivity between the regions of the brain that mediate these perceptions (Rouw & Scholte, 2007). Kinoshita, Tsuchiya, Kawakami, Furukawa, and Kingdon (2009) reported that some patients with the CBS had auditory hallucinations along with their visual hallucinations and this could be an example of ‘hallucinatory synesthesia’. Thus, it is possible that the woman we report had a visualeolfactory hallucinatory synesthesia. Normally, there is evidence of interaction between vision and audition in the brain. For example, the musician who sees written music will often hear the melody in his/her head, but what about smell and vision. In a 2001 French study, four wine professionals were presented glasses of red and white wine, which were artificially colored the opposite of their true color. Researchers found that these professionals were extremely poor at distinguishing the odor of red and white wine in the absence of visual cues, using descriptors widely reserved for red wine to describe white wine and vice versa (Morrot, Brochet, & Dubourdieu, 2001). A 2003 study by Gottfried and Dolan gives strong support for a model of visual processing that facilitates olfactory perception. They presented a series of odors and pictures to participants, recording brain activity upon odorepicture presentation using functional MRI (f-MRI).
Odors presented with congruent pictures led to enhancement of neural activity in the anterior hippocampus and rostromedial orbitofrontal cortex. This enhancement was not seen when incongruent odorepicture pairs were presented. Thus, it can reasonably be argued that one or both of these structures is responsible for the integration of vision and olfactory perception. Further support for this model of olfactory and visual integration, comes from primate studies which have demonstrated that the perirhinal and parahippocampal cortices including the entorhinal cortex, which is a portion of the “smell brain”, gets input from the visual association areas such as V4 (Ninomiya, Sawamura, Inoue, & Takada, 2012; Suzuki & Amaral, 1994). Based on the material we have reviewed, we propose a model of integrative cross-modal hallucinations as a result of hyperactive signaling from the visual cortex cross-activating with areas of association cortex related to the olfactory system. Thus, in our patient, we believe that abnormal activity of the visual cortex, induced by ischemic denervation, produced visual hallucinations and this activity was relayed to the anterior parahippocampal-entorhinal cortex which helped to produce her olfactory hallucinations.
Conflict of interest/funding source There are no conflicts of interest associated with this work. We have no potential financial interests in this manuscript.
Acknowledgments This report was generated from clinical observation and therefore no funding was necessary for its production.
references
Burke, W. (2002). The neural basis of Charles Bonnet hallucinations: a hypothesis. Journal of Neurology, Neurosurgery and Psychiatry, 73(5), 535e554. http://dx.doi.org/10.1136/ jnnp.73.5.535. Cytowic, R. E., & Eagleman, D. M. (2009). Wednesday is Indigo Blue: Discovering the brain of synesthesia (pp. 309). Cambridge: MIT Press. Davidson, T. M., Freed, C., Healy, M. P., & Murphy, C. (1998). Rapid clinical evaluation of anosmia in children: the Alcohol Sniff Test. Annals of New York Academy of Science, 855, 787e792. http://dx.doi.org/10.1111/j.1749-6632.1998.tb10659.x. Greenberg, M. S. (1992). Olfactory hallucinations. In K. L. Chobor, & M. J. Serby (Eds.), Science of olfaction (pp. 470e480). New York: Springer-Verlag. Gottfried, J., & Dolan, R. (2003). The nose smells what the eye sees: crossmodal visual facilitation of human olfactory perception. Neuron, 39(2), 375e386. http://dx.doi.org/10.1016/S08966273(03)00392-1. Henkin, R., Levy, L., & Lin, C. (2000). Taste and smell phantoms revealed by brain functional MRI. Journal of Computer Assisted Tomography, 2(1), 106e123. PMID:10667670.
c o r t e x 5 0 ( 2 0 1 4 ) 2 0 4 e2 0 7
Kiernan, J. (2012). Anatomy of the temporal lobe. Epilepsy Research and Treatment. http://dx.doi.org/10.1155/2012/176157. Article ID 176157. Kinoshita, Y., Tsuchiya, M., Kawakami, N., Furukawa, T. A., & Kingdon, D. (2009). Hallucinations in visually impaired individuals: an analysis of the National Comorbidity Survey Replication. Society Psychiatry and Psychiatric Epidemiology, 44(2), 104e108. http://dx.doi.org/10.1007/s00127-008-0417. Leopold, D. (2002). Distortion of olfactory perception: diagnosis and treatment. Chemical Sense, 27(7), 611e615. http:// dx.doi.org/10.1093/chemse/27.7.611. Morrot, G., Brochet, F., & Dubourdieu, D. (2001). The color of odors. Brain and Language, 79(2), 309e320. http://dx.doi.org/ 10.1006/brln.2001.2493.
207
Ninomiya, T., Sawamura, H., Inoue, K., & Takada, M. (2012). Multisynaptic inputs from the medial temporal lobe to V4 in macaques. PLoS One, 7(12), e52115. http://dx.doi.org/10.1371/ journal.pone.0052115. Rouw, R., & Scholte, H. S. (2007). Increased structural connectivity in grapheme-color synesthesia. Nature Neuroscience, 10(6), 792e797. http://dx.doi.org/10.1038/nn1906. Stamps, J. J., Bartoshuk, L. M., & Heilman, K. M. (2013). A brief olfactory test for Alzheimer’s disease. Journal of the Neurological Sciences [Epub ahead of print]. doi:pii: S0022e510X(13)003110.10.1016/j.jns.2013.06.033. Suzuki, W., & Amaral, D. (1994). Perirhinal and parahippocampal cortices of the Macaque monkey: cortical afferents. Journal of Comparative Neurology, 350, 497e533. PMID:7890828.
Available online at www.sciencedirect.com
ScienceDirect Journal homepage: www.elsevier.com/locate/cortex
Letter to the Editor
Visualeolfactory hallucinatory synesthesia: The Charles Bonnet Syndrome with olfactory hallucinations David Gubernick a, Pouya Ameli b, Qingshan Teng a, Arnaldo Velez a, Kenneth M. Heilman a and Vishnumurthy Shushrutha Hedna a,* a b
Departments of Neurology, University of Florida College of Medicine, Gainesville, FL, USA University of Central Florida College of Medicine, Orlando, FL, USA
article info Article history: Received 8 August 2013 Reviewed 17 September 2013 Revised 29 September 2013 Accepted 14 October 2013 Published online 31 October 2013
1.
Introduction
In the year 1760, Charles Bonnet noted that his 89-year old grandfather, who was blind from cataracts, was having visual hallucinations. The Charles Bonnet Syndrome (CBS)1 is now a well-documented condition where patients have intricate visual hallucinations, in the absence of psychosis, after a severe decrease or complete loss of vision. The most widely accepted mechanism of CBS is the concept of denervation hypersensitivity. This phenomena describes how internally generated electrical impulses become “released” or disinhibited within the brain following the loss of neuronal inputs from normal external visual stimuli. These released electrical signals then synapse at sites in the visual cortex and can produce complex visual hallucinations (Burke, 2002). Similarly, sensory deprivation in other modalities can lead to hallucinations in that modality. The occurrence of olfactory hallucinations, or phantom smells, following damage to the olfactory system has been previously reported and believed to be induced by a similar denervation hypersensitivity mechanism (Henkin,
Levy, & Lin, 2000). Here we report a 74-year old woman with a right posterior cerebral artery infarction who developed both visual and olfactory hallucinations, which were related to each other both temporally and in content. A search of the literature revealed no reports describing the CBS occurring in conjunction with olfactory hallucinations.
2.
Case report
A 74-year old woman, who was blind in her left eye from a childhood injury to the optic nerve, was transferred to our hospital from an outside facility for stroke management. Two days previously she had gone to this outside hospital complaining of a severe bilateral posterior headache as well as a 1 h episode of vertigo. A brain MRI at this hospital, and later verified by our institution, revealed a large right posterior cerebral artery (PCA) territory infarction affecting the right mesial inferior temporal and occipital lobes (see Fig. 1). Further neurologic exam revealed a left hemianopia. The
* Corresponding author. Department of Neurology, Room L3-100, McKnight Brain Institute, 1149 Newell Drive, Gainesville, FL 32611, USA. E-mail address: [email protected] (V.S. Hedna). 1 CBS ¼ Charles Bonnet Syndrome. 0010-9452/$ e see front matter ª 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.cortex.2013.10.002
c o r t e x 5 0 ( 2 0 1 4 ) 2 0 4 e2 0 7
205
Fig. 1 e Proposed model for visualeolfactory hallucinatory synesthesia. 1 & 2: Coronal T2w MRI showing right occipital lobe infarct (circles) consistent with right posterior cerebral artery occlusion. 3: Coronal T2w MRI showing infarction involves inferior mesial temporal lobe (blue) and spares entorhinal cortex (red). 4: Axial T1 MRI showing that the infarction spares anterior parahippocampal-entorhinal cortex (circle). 5: Sagittal T1 showing damage to inferior mesial temporal lobe but sparing the anterior parahippocampal-entorhinal cortex. 6: Sagittal T1 MRI showing damage to visual cortex (circle). Note: arrow depict the relayed hyperactive signaling from the visual cortex to anterior parahippocampal-entorhinal cortex which the arrowhead pointing in the direction of the relay.
morning after our initial evaluation, she started experiencing visual and olfactory hallucinations. She repeatedly described seeing miniature sized people and animals in full color and vivid detail (please see video interview link goes here). She saw these images throughout the day but they most often occurred in the morning when she first awakened from sleep. She also described the people as smelling of a strong “spice”, or the “smoke from a burning stick of incense”. Since olfactory hallucinations had not been reported to be associated with visual hallucinations in the CBS and seizure-like activity from the region of the uncus, so-called uncal fits, can cause olfactory hallucinations (Kiernan, 2012), an electroencephalogram (EEG) was performed while these olfactory hallucinations were present. However, this EEG revealed only mild generalized slowing of brain wave activity over the right temporal lobe without any features of seizure activity. Since, decrements in olfactory sensation can induce olfactory hallucinations we assessed the function of the olfactory nerve in our patient using the Unirhinal Peanut Butter Odor Detection Test (UPBODT).2 The UPBODT is a modified form of the Alcohol Sniff Test, an odorant detection test originally developed by Davidson, Freed, Healy, and Murphy (1998) as a tool to evaluate anosmia clinically. Stamps, Bartoshuk, and Heilman 2
UPBODT ¼ Unirhinal Peanut Butter Odor Detection Test.
(2013) developed the modified form of this test, the UPBODT, to assess olfaction in patients with Alzheimer’s disease. They chose to use peanut butter instead of ammonia to avoid irritating the trigeminal nerve. Consequently, the test proved to have a low cognitive load and good test retest reliability. By testing each nostril separately with the eyes closed, we found that our patient could identify the presence of the odorant at the same distance with each nostril, but could only correctly identify the odor as peanut butter with the left nostril. She reported detecting a variety of odors including coffee with the right nostril. Thus, these results suggest our patient had developed a right-sided troposmia, with intact detection but perceived distortion of odorant stimuli. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.cortex.2013.10.002.
3.
Discussion
The reason why this woman had olfactory hallucinations, together with her visual hallucinations is not entirely clear. According to Leopold (2002) troposmia is often associated with a decreased number of functioning olfactory neurons so that an incomplete characterization of the odorant is made. Greenberg (1992) would argue that this is an example of an
206
c o r t e x 5 0 ( 2 0 1 4 ) 2 0 4 e2 0 7
olfactory distortion rather than a hallucination, since the olfactory experience occurred in the presence of an actual odorant stimulus. In contrast, true olfactory hallucinations occur spontaneously in the absence of any such stimulus. However, Greenberg also would argue that decreased afferent olfactory information could plausibly trigger both true olfactory hallucinations as well as olfactory distortions. It is important to consider that this woman’s right PCA territory infarct injured the right mesial inferior temporal lobe and occipital lobe and did not involve the more anteriorly situated parts of the brain important in olfaction; and thus, olfactory denervation cannot fully explain her olfactory hallucinations. This suggests that if our patient’s troposmia was caused by a decreased number of functioning olfactory neurons, this deficit must have been present prior to her stroke. Although it is possible that she did indeed have a prior undetected troposmia, her denial of previous olfactory deficits, distortions, or hallucinations suggest decreased olfactory nerve function is an unlikely mechanism to explain these new olfactory sensations. Since at least some of her olfactory sensations were always tied to distinct and reproducible visual hallucinations in the absence of any odorant stimulus, we believe that these olfactory sensations represented true olfactory hallucinations and mechanistically were triggered in conjunction with her visual hallucinations. Thus, the challenge of explaining this presentation of CBS is therefore to explore how denervation hypersensitivity in the visual system could result in cross-modal sensory hallucinations. The visual system is highly integrated with the auditory system and in some people this strong integration may be associated with the phenomenon of synesthesia. For example, when people with auditoryevisual synesthesia hear a certain musical note they may see a corresponding color (Cytowic & Eagleman, 2009). Synesthesia is thought to be related to an increase in cross activation between the different modality specific areas of association cortex and recent studies of patients with synesthesia have revealed increased connectivity between the regions of the brain that mediate these perceptions (Rouw & Scholte, 2007). Kinoshita, Tsuchiya, Kawakami, Furukawa, and Kingdon (2009) reported that some patients with the CBS had auditory hallucinations along with their visual hallucinations and this could be an example of ‘hallucinatory synesthesia’. Thus, it is possible that the woman we report had a visualeolfactory hallucinatory synesthesia. Normally, there is evidence of interaction between vision and audition in the brain. For example, the musician who sees written music will often hear the melody in his/her head, but what about smell and vision. In a 2001 French study, four wine professionals were presented glasses of red and white wine, which were artificially colored the opposite of their true color. Researchers found that these professionals were extremely poor at distinguishing the odor of red and white wine in the absence of visual cues, using descriptors widely reserved for red wine to describe white wine and vice versa (Morrot, Brochet, & Dubourdieu, 2001). A 2003 study by Gottfried and Dolan gives strong support for a model of visual processing that facilitates olfactory perception. They presented a series of odors and pictures to participants, recording brain activity upon odorepicture presentation using functional MRI (f-MRI).
Odors presented with congruent pictures led to enhancement of neural activity in the anterior hippocampus and rostromedial orbitofrontal cortex. This enhancement was not seen when incongruent odorepicture pairs were presented. Thus, it can reasonably be argued that one or both of these structures is responsible for the integration of vision and olfactory perception. Further support for this model of olfactory and visual integration, comes from primate studies which have demonstrated that the perirhinal and parahippocampal cortices including the entorhinal cortex, which is a portion of the “smell brain”, gets input from the visual association areas such as V4 (Ninomiya, Sawamura, Inoue, & Takada, 2012; Suzuki & Amaral, 1994). Based on the material we have reviewed, we propose a model of integrative cross-modal hallucinations as a result of hyperactive signaling from the visual cortex cross-activating with areas of association cortex related to the olfactory system. Thus, in our patient, we believe that abnormal activity of the visual cortex, induced by ischemic denervation, produced visual hallucinations and this activity was relayed to the anterior parahippocampal-entorhinal cortex which helped to produce her olfactory hallucinations.
Conflict of interest/funding source There are no conflicts of interest associated with this work. We have no potential financial interests in this manuscript.
Acknowledgments This report was generated from clinical observation and therefore no funding was necessary for its production.
references
Burke, W. (2002). The neural basis of Charles Bonnet hallucinations: a hypothesis. Journal of Neurology, Neurosurgery and Psychiatry, 73(5), 535e554. http://dx.doi.org/10.1136/ jnnp.73.5.535. Cytowic, R. E., & Eagleman, D. M. (2009). Wednesday is Indigo Blue: Discovering the brain of synesthesia (pp. 309). Cambridge: MIT Press. Davidson, T. M., Freed, C., Healy, M. P., & Murphy, C. (1998). Rapid clinical evaluation of anosmia in children: the Alcohol Sniff Test. Annals of New York Academy of Science, 855, 787e792. http://dx.doi.org/10.1111/j.1749-6632.1998.tb10659.x. Greenberg, M. S. (1992). Olfactory hallucinations. In K. L. Chobor, & M. J. Serby (Eds.), Science of olfaction (pp. 470e480). New York: Springer-Verlag. Gottfried, J., & Dolan, R. (2003). The nose smells what the eye sees: crossmodal visual facilitation of human olfactory perception. Neuron, 39(2), 375e386. http://dx.doi.org/10.1016/S08966273(03)00392-1. Henkin, R., Levy, L., & Lin, C. (2000). Taste and smell phantoms revealed by brain functional MRI. Journal of Computer Assisted Tomography, 2(1), 106e123. PMID:10667670.
c o r t e x 5 0 ( 2 0 1 4 ) 2 0 4 e2 0 7
Kiernan, J. (2012). Anatomy of the temporal lobe. Epilepsy Research and Treatment. http://dx.doi.org/10.1155/2012/176157. Article ID 176157. Kinoshita, Y., Tsuchiya, M., Kawakami, N., Furukawa, T. A., & Kingdon, D. (2009). Hallucinations in visually impaired individuals: an analysis of the National Comorbidity Survey Replication. Society Psychiatry and Psychiatric Epidemiology, 44(2), 104e108. http://dx.doi.org/10.1007/s00127-008-0417. Leopold, D. (2002). Distortion of olfactory perception: diagnosis and treatment. Chemical Sense, 27(7), 611e615. http:// dx.doi.org/10.1093/chemse/27.7.611. Morrot, G., Brochet, F., & Dubourdieu, D. (2001). The color of odors. Brain and Language, 79(2), 309e320. http://dx.doi.org/ 10.1006/brln.2001.2493.
207
Ninomiya, T., Sawamura, H., Inoue, K., & Takada, M. (2012). Multisynaptic inputs from the medial temporal lobe to V4 in macaques. PLoS One, 7(12), e52115. http://dx.doi.org/10.1371/ journal.pone.0052115. Rouw, R., & Scholte, H. S. (2007). Increased structural connectivity in grapheme-color synesthesia. Nature Neuroscience, 10(6), 792e797. http://dx.doi.org/10.1038/nn1906. Stamps, J. J., Bartoshuk, L. M., & Heilman, K. M. (2013). A brief olfactory test for Alzheimer’s disease. Journal of the Neurological Sciences [Epub ahead of print]. doi:pii: S0022e510X(13)003110.10.1016/j.jns.2013.06.033. Suzuki, W., & Amaral, D. (1994). Perirhinal and parahippocampal cortices of the Macaque monkey: cortical afferents. Journal of Comparative Neurology, 350, 497e533. PMID:7890828.
