Studies of Brain Lesions

We conduct studies in neurological patients who have focal brain lesions.  For the most part, these are patients associated with the Cognitive Neuroscience Lesion Patient Registry at the University of Iowa, where we collaborate with Dr. Daniel Tranel. This resource was established by Antonio Damasio and Hanna Damasio originally.  We study primarily adults with chronic, focal lesions, giving us unique insights into the necessary role of specific brain structures in specific cognitive processes.

Our current work is focused on three themes.

Lesions of the Amygdala

In collaboration with Daniel Tranel at the University of Iowa, Justin Feinstein at the Laureate Institute in Oklahoma, and Rene Hurlemann at the University of Bonn, we have been studied very rare patients who have selective bilateral amygdala lesions due to Urbach-Wiethe Disease.  This is a genetic disease giving rise to developmental amygdala lesions in some patients.  One of the largest groups of these patients is currently being studied by Jack van Honk in South Africa.

amygdala_orangeOur work here has shown that the amygdala is involved in the experience of fear, and in the recognition of fear from facial expressions.

Image on the right: The amygdala is outlined in orange on this photograph of a coronal section of a post-mortem human brain.

 

SM

Image on left: MRI scans of the brain of patient S.M., showing the amygdala lesions. The section numbers (A,B,C) correspond to the planes indicated on the whole brain image shown in the upper left. The lesion can be appreciated in section C. by comparison to the intact orange amygdala on the left, and can also be seen as two symmetrical “holes” in section A.

Amygdala lesions impair the use of information from the eye region of faces.

In our 2005 Nature paper, we showed that patient S.M.’s impaired fear recognition could be traced to an inability to make use of visual information from the eyes in faces. To show this, we used a method called “bubbles” invented by Frederic Gosselin and Philippe Schyns.

The images shown here depict the visual information that viewers make use of in order to classify fear in faces.

Left: information used by healthy control subjects.  Middle: information used by patient S.M.  Right: the difference (information used by controls, but not by S.M.)

Another goal in our lab is to make comparisons across clinical populations, and across techniques.

Shown here are eyetracking data to faces comparing amygdala lesions to autism: the hotter colors indicate that people fixate these regions the most.

Left: Healthy controls.  Middle:  patient S.M.  Right: people with high-functioning autism.

Lesions of the Ventromedial Prefrontal Cortex

Classic work by the group at the University of Iowa (Antonio Damasio, Hanna Damasio, Daniel Tranel) and others had shown that lesions of the ventromedial prefrontal cortex gave rise to severe deficits in social behavior and decision-making.

Our work extended these studies to the realm of moral judgment, and to neuroeconomic quantifications of the decision-making impairment.  These studies continue to provide a powerful complement to fMRI studies of the prefrontal cortex, and are still ongoing in collaboration with Daniel Tranel and John O’Doherty.

Large-Scale Lesion-Symptom Mapping

Finally, in addition to focusing on the specific neuroanatomical regions implicated in emotion and social cognition (amygdala, and ventromedial prefrontal cortex), we have taken a more whole-brain approach and studied larger samples of patients with lesions distributed all over the brain.  Our earlier work did this in a rather crude way, generating overlap images of lesions.  Later, we used nonparametric voxel-based lesion-symptom mapping, which generates voxelwise statistics.

These studies have revealed more distributed neural systems that contribute to cognitive processes like emotion recognition, decision-making, and intelligence.  This work is ongoing, with collaborators Daniel Tranel at the University of Iowa, and Jan Glaescher at the University of Hamburg.

Left: Lesion overlaps in patients from the Iowa patient registry.  In these images the color encodes the density of lesion overlaps in 250 patients.  Note that most of the brain is sampled, but not homogeneously, resulting in a complex anatomical distribution of statistical power to detect potential deficits.

Long-Term Outcomes After Hemispherectomy

Perhaps there is no more remarkable example of brain plasticity and human adaptation than hemispherectomy. Hemispherectomy, surgical removal (or disconnection) of an entire cortical hemisphere, is conducted to treat severe epilepsy. It is a radical procedure, that is typically deemed ‘successful’ if seizures cease. However, very little is known about how the neural system adapts to this change, nor about the long-term impact of this procedure on cognitive and social functioning.

In collaboration with Warren Brown at Travis Research Institute, Fuller Graduate School of Psychology, we are conducting an in-depth examination of cognitive, behavioral and neural functioning in adults who had hemispherectomy during childhood.

Enroll in our Online Study: If you are 18 or older and have had a hemispherectomy, you may be able to participate in our online study. This study involves completing several questionnaires about your current behaviors and your medical history. You will also be asked to provide contact information for someone who can describe your current behaviors and/or history. If you are interested in enrolling, please contact lkpaul@hss.caltech.edu for more information. This work has been supported by the Brain Recovery Project (http://www.brainrecoveryproject.org/).

Right: Brain with surgically removed right hemisphere

Publications

Amygdala Lesions

Khalsa, S.S., Feinstein, J.S., Li, W., Feusner, J.D., Adolphs, R., & Hurlemann, R. (2016). Panic Anxiety in Humans with Bilateral Amygdala Lesions: Pharmacological Induction via Cardiorespiratory Interoceptive Pathways.  J Neurosci. Mar 23;36(12):3559-66. doi: 10.1523/JNEUROSCI.4109-15.2016.

Harrison, R. Hurlemann, R. Adolphs (2015).  An enhanced default approach bias following human amygdala lesions. Psychological Science, 26, 1543-1555.

Spunt, R. P., Elison, J. T., Dufour, N., Hurlemann, R., Saxe, R., & Adolphs, R. (2015). Amygdala lesions do not compromise the cortical network for false-belief reasoning. Proceedings of the National Academy of Sciences of the United States of America, 112(15), 4827-4832. doi: 10.1073/pnas.1422679112

Wang, S., Tsuchiya, N., New, J., Hurlemann, R., & Adolphs, R. (2015). Preferential attention to animals and people is independent of the amygdala. Social Cognitive and Affective Neuroscience, 10(3), 371-380. doi: 10.1093/scan/nsu065

Wang, S., Xu, J., Jiang, M., Zhao, Q., Hurlemann, R., & Adolphs, R. (2014). Autism spectrum disorder, but not amygdala lesions, impairs social attention in visual search. Neuropsychologia, 63, 259-274. doi: 10.1016/j.neuropsychologia.2014.09.002

Birmingham, E., Cerf, M., & Adolphs, R. (2011). Comparing social attention in autism and amygdala lesions: effects of stimulus and task condition. Social Neuroscience, 6(5-6), 420-435. doi: 10.1080/17470919.2011.561547

Boes, A., Mehta, S., Rudrauf, D., Van Der Plas, E., Grabowski, T., Adolphs, R., Nopoulos, P. (2011).  Changes in cortical morphology resulting from long-term amygdala damage.  Social Cognitive and Affective Neuroscience,  7, 588-595.

Feinstein, J. S., Adolphs, R., Damasio, A., & Tranell, D. (2011). The human amygdala and the induction and experience of fear.

Gosselin, F., Spezio, M. L., Tranel, D., & Adolphs, R. (2011). Asymmetrical use of eye information from faces following unilateral amygdala damage. Social Cognitive and Affective Neuroscience, 6(3), 330-337. doi: 10.1093/scan/nsq040

Adolphs, R. (2010). What does the amygdala contribute to social cognition? In A. Kingstone & M. B. Miller (Eds.), Year in Cognitive Neuroscience 2010 (Vol. 1191, pp. 42-61).

De Martino, B., Camerer, C. F., & Adolphs, R. (2010). Amygdala damage eliminates monetary loss aversion. Proceedings of the National Academy of Sciences of the United States of America, 107(8), 3788-3792. doi: 10.1073/pnas.0910230107

Kennedy, D. P., Glaescher, J., Tyszka, J. M., & Adolphs, R. (2009). Personal space regulation by the human amygdala. Nature Neuroscience, 12(10), 1226-1227. doi: 10.1038/nn.2381

Paul, L. K., Corsello, C., Tranel, D., & Adolphs, R. (2010). Does bilateral damage to the human amygdala produce autistic symptoms? Journal of Neurodevelopmental Disorders, 2(3), 165-173. doi: 10.1007/s11689-010-9056-1

Tsuchiya, N., Moradi, F., Felsen, C., Yamazaki, M., & Adolphs, R. (2009). Intact rapid detection of fearful faces in the absence of the amygdala. Nature Neuroscience, 12(10), 1224-1225. doi: 10.1038/nn.2380

Adolphs, R. (2008). Fear, faces, and the human amygdala. Current Opinion in Neurobiology, 18(2), 166-172. doi: 10.1016/j.conb.2008.06.006  [Won Award for most cited paper 2008-2010 from Current Opinion in Neurobiology]

Gosselin, N., Peretz, I., Johnsen, E., & Adolphs, R. (2007). Amygdala damage impairs emotion recognition from music. Neuropsychologia, 45(2), 236-244. doi: 10.1016/j.neuropsychologia.2006.07.012

Hampton, A. N., Adolphs, R., Tyszka, M. J., & O’Doherty, J. P. (2007). Contributions of the amygdala to reward expectancy and choice signals in human prefrontal cortex. Neuron, 55(4), 545-555. doi: 10.1016/j.neuron.2007.07.022

Spezio, M. L., Huang, P.-Y. S., Castelli, F., & Adolphs, R. (2007). Amygdala damage impairs eye contact during conversations with real people. Journal of Neuroscience, 27(15), 3994-3997. doi: 10.1523/jneurosci.3789-06.2007

Tranel, D., Gullickson, G., Koch, M., & Adolphs, R. (2006). Altered experience of emotion following bilateral amygdala damage. Cognitive Neuropsychiatry, 11(3), 219-232. doi: 10.1080/13546800444000281

Adolphs, R., Gosselin, F., Buchanan, T. W., Tranel, D., Schyns, P., & Damasio, A. R. (2005). A mechanism for impaired fear recognition after amygdala damage. Nature, 433(7021), 68-72. doi: 10.1038/nature03086

Adolphs, R., Tranel, D., & Buchanan, T. W. (2005). Amygdala damage impairs emotional memory for gist but not details of complex stimuli. Nature Neuroscience, 8(4), 512-518. doi: 10.1038/nn1413

Heberlein, A. S., & Adolphs, R. (2004). Impaired spontaneous anthropomorphizing despite intact perception and social knowledge. Proceedings of the National Academy of Sciences of the United States of America, 101(19), 7487-7491. doi: 10.1073/pnas.0308220101

Adolphs, R., & Tranel, D. (2003). Amygdala damage impairs emotion recognition from scenes only when they contain facial expressions. Neuropsychologia, 41(10), 1281-1289. doi: 10.1016/s0028-3932(03)00064-2

Adolphs, R., Baron-Cohen, S., & Tranel, D. (2002). Impaired recognition of social emotions following amygdala damage. Journal of Cognitive Neuroscience, 14(8), 1264-1274. doi: 10.1162/089892902760807258

Adolphs, R. & Tranel, D. (1999). Preferences for visual stimuli following amygdala damage. Journal of Cognitive Neuroscience, 11(6), 610-616.

Adolphs, R. & Tranel, D. (1999). Intact recognition of emotional prosody following amygdala damage. Neuropsychologia, 37(11), 1285-1292.

Adolphs, R., Tranel, D., Hamann, S., Young, A. W., Calder, A. J., Phelps, E. A., Anderson, A., Lee, G. P., Damasio, A. R. (1999). Recognition of facial emotion in nine individuals with bilateral amygdala damage. Neuropsychologia, 37(10), 1111-1117.

Hamann, S. B. & Adolphs, R. (1999). Normal recognition of emotional similarity between facial expressions following bilateral amygdala damage. Neuropsychologia, 37(10), 1135-1141.

Adolphs, R., Tranel, D., & Damasio, A. R. (1998). The human amygdala in social judgment. Nature, 393(6684), 470-474.

Adolphs, R., Cahill, L., Schul, R., & Babinsky, R. (1997). Impaired declarative memory for emotional material following bilateral amygdala damage in humans. Learning and Memory, 4(3), 291-300.

Adolphs, R., Tranel, D., Damasio, H., & Damasio, A. R. (1995). Fear and the human amygdala. Journal of Neuroscience, 15(9), 5879-5891.

Bechara, A., Tranel, D., Damasio, H., Adolphs, R., Rockland, C., & Damasio, A. R. (1995). Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. Science, 269(5227), 1115-1118.

Adolphs, R., Tranel, D., Damasio, H., & Damasio A. (1994). Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature, 372(6507), 669-672.

Ventromedial Prefrontal Cortex Lesions

Glaescher, J., Adolphs, R., Damasio, H., Bechara, A., Rudrauf, D., Calamia, M., . . . Tranel, D. (2012). Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex. Proceedings of the National Academy of Sciences of the United States of America, 109(36), 14681-14686. doi: 10.1073/pnas.1206608109

Kovach, C. K., Daw, N. D., Rudrauf, D., Tranel, D., O’Doherty, J. P., & Adolphs, R. (2012). Anterior prefrontal cortex contributes to action selection through tracking of recent reward trends. Journal of Neuroscience, 32(25), 8434-8442. doi: 10.1523/jneurosci.5468-11.2012

Croft, K. E., Duff, M. C., Kovach, C. K., Anderson, S. W., Adolphs, R., & Tranel, D. (2010). Detestable or marvelous?—Neuroanatomical correlates of character judgments. Neuropsychologia, 48(6), 1789-1801. doi: 10.1016/j.neuropsychologia.2010.03.001

Krajbich, I., Adolphs, R., Tranel, D., Denburg, N. L., & Camerer, C. F. (2009). Economic games quantify diminished sense of guilt in patients with damage to the prefrontal cortex. Journal of Neuroscience, 29(7), 2188-2192. doi: 10.1523/jneurosci.5086-08.2009

Koenigs, M., Young, L., Adolphs, R., Tranel, D., Cushman, F., Hauser, M., & Damasio, A. (2008). Do abnormal responses show utilitarian bias? Reply. Nature, 452(7185), E5-E6. doi: Doi 10.1038/Nature06804

Koenigs, M., Young, L., Adolphs, R., Tranel, D., Cushman, F., Hauser, M., & Damasio, A. (2007). Damage to the prefrontal cortex increases utilitarian moral judgements. Nature, 446(7138), 908-911. doi: 10.1038/nature05631

Hsu, M., Bhatt, M., Adolphs, R., Tranel, D., & Camerer, C. F. (2005). Neural systems responding to degrees of uncertainty in human decision-making. Science, 310(5754), 1680-1683. doi: 10.1126/science.1115327

Karafin, M. S., Tranel, D., & Adolphs, R. (2004). Dominance attributions following damage to the ventromedial prefrontal cortex. Journal of Cognitive Neuroscience, 16(10), 1796-1804. doi: 10.1162/0898929042947856

Large Scale Symptom Mapping
Glaescher, J., Adolphs, R., Damasio, H., Bechara, A., Rudrauf, D., Calamia, M., . . . Tranel, D. (2012). Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex. Proceedings of the National Academy of Sciences of the United States of America, 109(36), 14681-14686. doi: 10.1073/pnas.1206608109

Glascher, J., Rudrauf, D., Colom, R., Paul, L. K., Tranel, D., Damasio, H., & Adolphs, R. (2010). Distributed neural system for general intelligence revealed by lesion mapping. Proceedings of the National Academy of Sciences of the United States of America, 107(10), 4705-4709. doi: Doi 10.1073/Pnas.0910397107

Philippi, C. L., Mehta, S., Grabowski, T., Adolphs, R., & Rudrauf, D. (2009). Damage to association fiber tracts impairs recognition of the facial expression of emotion. Journal of Neuroscience, 29(48), 15089-15099. doi: 10.1523/jneurosci.0796-09.2009

Gosselin, N., Samson, S., Adolphs, R., Noulhiane, M., Roy, M., Hasboun, D., . . . Peretz, I. (2006). Emotional responses to unpleasant music correlates with damage to the parahippocampal cortex. Brain, 129, 2585-2592. doi: 10.1093/brain/aw1240

Damasio, H., Tranel, D., Grabowski, T., Adolphs, R., & Damasio, A. (2004). Neural systems behind word and concept retrieval. Cognition, 92(1-2), 179-229.

Heberlein, A. S., Adolphs, R., Tranel, D., & Damasio, H. (2004). Cortical regions for judgments of emotions and personality traits from point-light walkers. Journal of Cognitive Neuroscience, 16(7), 1143-1158. doi: 10.1162/0898929041920423

Tranel, D., Kemmerer, D., Adolphs, R., Damasio, H., & Damasio, A. R. (2003). Neural correlates of conceptual knowledge for actions. Cognitive Neuropsychology, 20(3-6), 409-432. doi: 10.1080/02643290244000248

Adolphs, R., Damasio, H., & Tranel, D. (2002). Neural systems for recognition of emotional prosody: a 3-D lesion study. Emotion, 2(1), 23-51. doi: 10.1037/1528-3542.2.1.23

Single-neuron responses to emotional visual stimuli recorded in human ventral prefrontal cortex. Nature Neuroscience, 4(1), 15-16.

Tranel, D., Adolphs, H., Damasio, H., & Damasio, A.R. (2001). A neural basis for the retrieval of words for actions.  Cognitive Neuropsychology, 18, 655-670.

Adolphs, R., Damasio, H., Tranel, D., Cooper, G., & Damasio, A. R. (2000). A role for somatosensory cortices in the visual recognition of emotion as revealed by three-dimensional lesion mapping. Journal of Neuroscience, 20(7), 2683-2690.