Methods of the Week
MOTW #1: Human Behavior
Article:
Jensen, Jimmy, Willeit, Matthäus, Zipursky, Robert B., Savina, Loulia, Smith, Andrew J., Menon, Mahesh, Crawley, Adrian P., and Kapur, Shitij, The Formation of Abnormal Associations in Schizophrenia: Neural and Behavioral Evidence, 2008, Neuropsychopharmacology, 33, 473-479
New associations are normally formed by through dopamine firing during a new event forming a new association in that context. However, people with schizophrenia have an abnormal way of forming new associations causing their delusions. It has been proposed that a heightened firing of dopamine during an event causing inappropriate and false associations. In this article, Jensen et al. investigated whether patients with schizophrenia showed abnormal learning when exposed to aversive stimuli. The experiment consisted of thirteen patients with schizophrenia and thirteen patients without schizophrenia who were exposed to aversive events of an 800ms long loud fire-truck horn burst as the unconditioned stimulus and colored circles which were presented five seconds after as the controlled stimulus. In addition, circles of another color followed by a start were shown as neutral comparators during the trials. During the aversive stimuli, MRI scans of the patients were taken to scan the whole brain. As a result, the patients with schizophrenia could not distinguish between the controlled stimulus and the neutral comparators showing evidence of abnormal learning. In the MRI scans, the patients with schizophrenia showed more arousal in their brains to the neutral comparators than the controlled stimulus. These results showed that people with schizophrenia have an abnormal way of forming new associations which can be a reason for their delusions.
MOTW #2: Human Imaging
Article:
Agartz, Ingrid, Andersson, Jesper L.R, and Skare, Stefan, Abnormal Brain and White Matter in Schizophrenia: a diffusion tensor imaging study, 2001, Neuroreport, 12:10, 2251-2254
Agartz et al. researched on a possible biological cause of schizophrenia in the brain. Their objective was to investigate the brain in schizophrenic patients and healthy subjects by mapping their brain white matter structure. They used diffusion tensor imaging (DTI) which is a measure of the thermal motion of water in gray matter in the brain. The DTI allowed for the analysis of fractional analysis to evaluate the white matter fiber tracts in the brain. Their hypothesis was that the mean diffusion of water in the brains of schizophrenic patients more than the diffusion of healthy individuals due to the loss of grey matter in the schizophrenic patients. The study consisted of 20 white patients with chronic schizophrenia and 24 healthy individuals. All of the subjects were examined using 1.5 T General Electric Signa Echospeed MRI scanner and a single shot diffusion spin echo EPI sequence. During the study, they found a significant reduction in the splenium of the corpus callosum and the occipital white matter corresponding to the forceps major and an increase of diffusion in the grey and white matter of schizophrenia patients. These abnormalities can be an explanation for an altered visual perception in schizophrenia patients. Although the mean diffusion of water was increased in schizophrenia patients due to a loss of white and grey matter, Agartz et al. reassures that more research should be conducted to ultimately evaluate the white matter’s role in causing schizophrenic symptoms.
MOTW #3: Neuroanatomy
Article:
D. Sussman, E.W. Pang, R. Jetly, B.T. Dunkley, and M.J Taylor, Neuroanatomical features in soldier with post-traumatic stress disorder, 2016, BMC Neuroscience, 17
D. Sussman et. al researched the neuroanatomical features of posttraumatic stress disorder (PTSD). Their objective was to analyze different brain structures of soldiers that have been diagnosed with PTSD to compare their neuroanatomy with soldiers who do not have PTSD. 47 active Canadian soldiers who served in the Afghanistan participated in the study. 23 of the soldiers had a diagnosis of PTSD while the other 24 soldiers did not have PTSD and were used as the control group. An MRI scanner was used to get brain images from the participants. Cortical surface rea, cortical thickness, white and grey matter volume, and volumes of the hippocampus, caudate, globus pallidus, putamen, thalamus, and cerebellum were analyzed in each of the soldiers. In addition, IQ scores of the soldiers were taken to compare them to the cerebral parameters. During the study, IQ scores were found to be lowers in the soldiers with PTSD than the soldiers without PTSD. However, grey and white matter volume were found to be increased in soldiers with PTSD. The cortical thickness in soldiers with PTSD was found to be thinner than the control group. The research did not find any significant difference between the volumes of the soldier’s hippocampus, globus pallidus, putamen, thalamus, and cerebellum but they did find a decreased volume of the caudate in the soldiers with PTSD. The researchers were able to connect the decreased volume of the cerebral and cortical structures with symptoms of PTSD, such as heightened anxiety, a decrease in their attention system, and depression.
MOTW #4: Tract Tracing
Article:
Choi, Jeewook, Jeong, Bumseok, Rohan, Michael L., Polcari, Ann M., and Teicher, Martin H., Preliminary Evidence for White Matter Tract Abnormalities in Young Adults Exposed to Parental Verbal Abuse, 2009, Biological Psychiatry, 65:3, 227-234
To understand the effect of parental verbal abuse (PVA) on brain development, Choi et al. analyzed the white matter tract on young adults with and without exposure to parental verbal abuse. They hypothesized that exposure to parental verbal abuse would affect the connectivity of the left hemisphere pathways. They reasoned that this exposure would affect the development of language and linguistic skills. Parental verbal abuse was defined as verbal humiliation, ridicule, and neglect towards a child from their parent. 32 total adolescents between 18 and 25 years old participated in the study. 16 of the participants have experienced PVA and the 16 ither participants have not experienced any PVA and were used a control group. An MRI was used to get scans of the participant’s brain. Diffusion tensor imaging (DTI) was used to calculate tract-based differences between the PVA participants and the control group. White matter tracts were projected as black on the images to trace them. Disrupted fiber tracts of white matter were found in the left superior temporal gyrus, the left fusiform gyrus, and the left body of the fornix. These regions are correlated with verbal IQ in the left temporal gyrus, depression and dissociation in the left fusiform gyrus, and anxiety in the fornix. Overall, these results supported the researcher’s hypothesis that PVA would affect the neural connectivity of the left hemisphere pathways, which would lead to developmental verbal delays, depression, and anxiety.
Article:
Koenigs M., Huey E.D., Raymont V., Cheon B., Solomon J., Wassermann E.M., and Grafman J., Focal Brain Damage Protects Against Post-Traumatic Stress Disorder In Combat Veterans, 2008, Nature Neuroscience, 11:2, 232-237
Micheal Koenigs and other researchers wanted to examine the casual contribution of specific brain areas to PTSD. Specifically, they wanted to see if damage to the amygdala, hippocampus, and ventromedial prefrontal cortex changes the likelihood of developing PTSD. They looked at Vietnam War veterans who suffered brain lesions located in the ventromedial prefrontal cortex(40 participants), lesions located in the amygdala in either hemisphere(15 participants), veterans who did not have any brain lesions in either region(133 participants), and a control group with no brain damage at all(52 participants). They found that PTSD symptoms were more prevalent in the groups that had no lesions in either brain regions and no brain damage at all. This shows that the amygdala and ventromedial prefrontal cortex are casually involved in the formation of PTSD. The groups with the brain lesions located in the amygdala showed the most reduction in PTSD symptoms. No evidence was found that hippocampal damage affected the development of PTSD.
MOTW #6: Animal Behavior
Article:
Jackowski A., Perera T.D., Abdallah C.G., Garrido G., Tang C.Y., Martinez J., Matthew S.J., Gorman J.M., Rosenblum L.A., Smith E.L.P., Dwork A.J., Shungu D.C, Kaffman A., Gelernter J., Coplan J.D., and Kaufman J., Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates, 2011, Psychiatry Res., 192:1, 37-44
Andrea Jackowski and other researchers sought to examine the behavioral effects of corpus callosum structure in male bonnet macaques that were subjected to variable foraging demand rearing. VDF was defined as an early life model where infant bonnet macaques are raised by mothers who were undergoing a perception of food uncertainty. They hypothesized that VFD raising would be associated with a smaller corpus callosum and hippocampus and that these brain changes would be related to behavioral differences in emotional reactivity. 14 bonnet macaques that were VDF raised and 9 normally raised bonnet macaques were subjects in the study. Once the bonnet macaques were fully matured, MRI of the bonnet macaques were taken to measure their corpus callosum. 12 of the bonnet macaques were subjected to behavioral testing in which they were exposed to an intruder as a fear-stimulus test. As a result, the researchers found that the bonnet macaques that were subjected to VDF had a smaller mid-sagittal corpus callosum area. In addition, the bonnet macaques that were subjected to VDF showed greater emotional responsivity during the fear test than the bonnet macaques that were not exposed to VDF.