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1.  A volumetric comparison of the insular cortex and its subregions in primates 
Journal of human evolution  2013;64(4):263-279.
The neuronal composition of the insula in primates displays a gradient, transitioning from granular neocortex in the posterior-dorsal insula to agranular neocortex in the anterior-ventral insula with an intermediate zone of dysgranularity. Additionally, apes and humans exhibit a distinctive subdomain in the agranular insula, the frontoinsular cortex (FI), defined by the presence of clusters of von Economo neurons (VENs). Studies in humans indicate that the ventral anterior insula, including agranular insular cortex and FI, is involved in social awareness, and that the posterodorsal insula, including granular and dysgranular cortices, produces an internal representation of the body’s homeostatic state. We examined the volumes of these cytoarchitectural areas of insular cortex in 30 primate species, including the volume of FI in apes and humans. Results indicate that the whole insula scales hyperallometrically (exponent = 1.13) relative to total brain mass, and the agranular insula (including FI) scales against total brain mass with even greater positive allometry (exponent = 1.23), providing a potential neural basis for enhancement of social cognition in association with increased brain size. The relative volumes of the subdivisions of the insular cortex, after controlling for total brain volume, are not correlated with species typical social group size. Although its size is predicted by primate-wide allometric scaling patterns, we found that the absolute volume of the left and right agranular insula and left FI are among the most differentially expanded of the human cerebral cortex compared to our closest living relative, the chimpanzee.
doi:10.1016/j.jhevol.2012.12.003
PMCID: PMC3756831  PMID: 23466178
Allometry; Brain; Evolution; Frontoinsular cortex; Hominoids
2.  Human Ecstasy Use is Associated with Increased Cortical Excitability: An fMRI Study 
Neuropsychopharmacology  2011;36(6):1127-1141.
The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popular recreational drug. Human recreational MDMA users have neurocognitive and neuropsychiatric impairments, and human neuroimaging data are consistent with animal reports of serotonin neurotoxicity. However, functional neuroimaging studies have not found consistent effects of MDMA on brain neurophysiology in human users. Several lines of evidence suggest that studying MDMA effects in visual system might reveal the general cortical and subcortical neurophysiological consequences of MDMA use. We used 3 T functional magnetic resonance imaging during visual stimulation to compare visual system lateral geniculate nucleus (LGN) and Brodmann Area (BA) 17 and BA 18 activation in 20 long abstinent (479.95±580.65 days) MDMA users and 20 non-MDMA user controls. Lifetime quantity of MDMA use was strongly positively correlated with blood oxygenation level-dependent (BOLD) signal intensity in bilateral LGN (rs=0.59; p=0.007), BA 17 (rs=0.50; p=0.027), and BA 18 (rs=0.48; p=0.031), and with the spatial extent of activation in BA 17 (rs=0.059; p=0.007) and BA 18 (rs=0.55; p=0.013). There were no between-group differences in brain activation in any region, but the heaviest MDMA users showed a significantly greater spatial extent of activation than controls in BA 17 (p=0.031) and BA 18 (p=0.049). These results suggest that human recreational MDMA use may be associated with a long-lasting increase in cortical excitability, possibly through loss of serotonin input to cortical and subcortical regions. When considered in the context of previous results, cortical hyper-excitability may be a biomarker for MDMA-induced serotonin neurotoxicity.
doi:10.1038/npp.2010.244
PMCID: PMC3079831  PMID: 21326196
neurotoxicity; amphetamine; cortical excitability; serotonin; drug abuse; addiction and substance abuse; neurophysiology; imaging, clinical, or preclinical; serotonin; neurotoxicity; amphetamine; cortical excitability; epilepsy
3.  MDMA (Ecstasy) use is associated with reduced BOLD signal change during semantic recognition in abstinent human polydrug users: a preliminary fMRI study 
Objectives
MDMA users have impaired verbal memory, and voxel-based morphometry has demonstrated decreased gray matter in Brodmann area (BA) 18, 21 and 45. Because these regions play a role in verbal memory, we hypothesized that MDMA users would show altered brain activation in these areas during performance of an fMRI task that probed semantic verbal memory.
Methods
Polysubstance users enriched for MDMA exposure participated in a semantic memory encoding and recognition fMRI task that activated left BA 9, 18, 21/22 and 45. Primary outcomes were percent BOLD signal change in left BA 9, 18, 21/22 and 45, accuracy and response time.
Results
During semantic recognition, lifetime MDMA use was associated with decreased activation in left BA 9, 18 and 21/22 but not 45. This was partly influenced by contributions from cannabis and cocaine use. MDMA exposure was not associated with accuracy or response time during the semantic recognition task.
Conclusions
During semantic recognition, MDMA exposure is associated with reduced regional brain activation in regions mediating verbal memory. These findings partially overlap with prior structural evidence for reduced gray matter in MDMA users and may, in part, explain the consistent verbal memory impairments observed in other studies of MDMA users.
doi:10.1177/0269881109103203
PMCID: PMC3198867  PMID: 19304866
Ecstasy (MDMA); drug abuse; semantic memory; verbal memory; fMRI; neuroimaging
4.  Wernicke's area homologue in chimpanzees (Pan troglodytes) and its relation to the appearance of modern human language 
Human language is distinctive compared with the communication systems of other species. Yet, several questions concerning its emergence and evolution remain unresolved. As a means of evaluating the neuroanatomical changes relevant to language that accompanied divergence from the last common ancestor of chimpanzees, bonobos and humans, we defined the cytoarchitectonic boundaries of area Tpt, a component of Wernicke's area, in 12 common chimpanzee brains and used design-based stereologic methods to estimate regional volumes, total neuron number and neuron density. In addition, we created a probabilistic map of the location of area Tpt in a template chimpanzee brain coordinate space. Our results show that chimpanzees display significant population-level leftward asymmetry of area Tpt in terms of neuron number, with volume asymmetry approaching significance. Furthermore, asymmetry in the number of neurons in area Tpt was positively correlated with asymmetry of neuron numbers in Brodmann's area 45, a component of Broca's frontal language region. Our findings support the conclusion that leftward asymmetry of Wernicke's area originated prior to the appearance of modern human language and before our divergence from the last common ancestor. Moreover, this study provides the first evidence of covariance between asymmetry of anterior and posterior cortical regions that in humans are important to language and other higher order cognitive functions.
doi:10.1098/rspb.2010.0011
PMCID: PMC2880147  PMID: 20236975
cytoarchitecture; chimpanzee; evolution; Wernicke's area; asymmetry

Results 1-4 (4)