Atiya Y. Hakeem

The anterior cingulate cortex. The evolution of an interface between emotion and cognition.

Abstract: We propose that the anterior cingulate cortex is a specialization of neocortex rather than a more primitive stage of cortical evolution. Functions central to intelligent behavior, that is, emotional self‐control, focused problem solving, error recognition, and adaptive response to changing conditions, are juxtaposed with the emotions in this structure. Evidence of an important role for the anterior cingulate cortex in these functions has accumulated through single‐neuron recording, electrical stimulation, EEG, PET, fMRI, and lesion studies. The anterior cingulate cortex contains a class of spindle‐shaped neurons that are found only in humans and the great apes, and thus are a recent evolutionary specialization probably related to these functions. The spindle cells appear to be widely connected with diverse parts of the brain and may have a role in the coordination that would be essential in developing the capacity to focus on difficult problems. Furthermore, they emerge postnatally and their survival may be enhanced or reduced by environmental conditions of enrichment or stress, thus potentially influencing adult competence or dysfunction in emotional self‐control and problem‐solving capacity.

Intuition and autism: a possible role for Von Economo neurons

Von Economo neurons (VENs) are a recently evolved cell type which may be involved in the fast intuitive assessment of complex situations. As such, they could be part of the circuitry supporting human social networks. We propose that the VENs relay an output of fronto-insular and anterior cingulate cortex to the parts of frontal and temporal cortex associated with theory-of-mind, where fast intuitions are melded with slower, deliberative judgments. The VENs emerge mainly after birth and increase in number until age 4 yrs. We propose that in autism spectrum disorders the VENs fail to develop normally, and that this failure might be partially responsible for the associated social disabilities that result from faulty intuition.

Von Economo Neurons in the Elephant Brain

Von Economo neurons (VENs), previously found in humans, all of the great ape species, and four cetacean species, are also present in African and Indian elephants. The VENs in the elephant are primarily found in similar locations to those in the other species. They are most abundant in the frontoinsular cortex (area FI) and are also present at lower density in the anterior cingulate cortex. Additionally, they are found in a dorsolateral prefrontal area and less abundantly in the region of the frontal pole. The VEN morphology appears to have arisen independently in hominids, cetaceans, and elephants, and may reflect a specialization for the rapid transmission of crucial social information in very large brains. Anat Rec 2009.

Book Review: Two Phylogenetic Specializations in the Human Brain

In this study, two anatomical specializations of the brain in apes and humans are considered. One of these is a whole cortical area located in the frontal polar cortex (Brodmann’s area 10), and the other is a morphologically distinctive cell type, the spindle neuron of the anterior cingulate cortex. The authors suggest that the spindle cells may relay to other parts of the brain—especially to area 10, the outcome of processing within the anterior cingulate cortex. This relay conveys the motivation to act. It particularly concerns the recognition of having committed an error that leads to the initiation of adaptive responses to these adverse events so as to reduce error commission. This capacity is related to the development of self-control as an individual matures and gains social insight. Although the anterior cingulate deals with the individual’s immediate response to changing conditions, area 10 is involved in the retrieval of memories from the individual’s past experience and the capacity to plan adaptive responses. The authors suggest that these neurobehavioral specializations are crucial aspects of intelligence as defined as the capacity to make adaptive responses to changing conditions. The authors further hypothesize that these specializations facilitated the evolution of the unique capacity for the intergenerational transfer of the food and information characteristic of human extended families.

Total number and volume of Von Economo neurons in the cerebral cortex of cetaceans

Von Economo neurons (VENs) are a type of large, layer V spindle‐shaped neurons that were previously described in humans, great apes, elephants, and some large‐brained cetaceans. Here we report the presence of Von Economo neurons in the anterior cingulate (ACC), anterior insular (AI), and frontopolar (FP) cortices of small odontocetes, including the bottlenose dolphin (Tursiops truncatus), the Rissos dolphin (Grampus griseus), and the beluga whale (Delphinapterus leucas). The total number and volume of VENs and the volume of neighboring layer V pyramidal neurons and layer VI fusiform neurons were obtained by using a design‐based stereologic approach. Two humpback whale (Megaptera novaeangliae) brains were investigated for comparative purposes as representatives of the suborder Mysticeti. Our results show that the distribution of VENs in these cetacean species is comparable to that reported in humans, great apes, and elephants. The number of VENs in these cetaceans is also comparable to data available from great apes, and stereologic estimates indicate that VEN volume follows in these cetacean species a pattern similar to that in hominids, the VENs being larger than neighboring layer V pyramidal cells and conspicuously larger than fusiform neurons of layer VI. The fact that VENs are found in species representative of both cetacean suborders in addition to hominids and elephants suggests that these particular neurons have appeared convergently in phylogenetically unrelated groups of mammals possibly under the influence of comparable selective pressures that influenced specifically the evolution of cortical domains involved in complex cognitive and social/emotional processes. J. Comp. Neurol. 515:243–259, 2009.

The von Economo neurons in the frontoinsular and anterior cingulate cortex

The von Economo neurons (VENs) are large bipolar neurons located in the frontoinsular cortex (FI) and limbic anterior (LA) area in great apes and humans but not in other primates. Our stereological counts of VENs in FI and LA show them to be more numerous in humans than in apes. In humans, small numbers of VENs appear the 36th week postconception, with numbers increasing during the first 8 months after birth. There are significantly more VENs in the right hemisphere in postnatal brains; this may be related to asymmetries in the autonomic nervous system. VENs are also present in elephants and whales and may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI and LA to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of frontotemporal dementia (FTD) implies that they are involved in empathy, social awareness, and self‐control, consistent with evidence from functional imaging.

Selective reduction of Von Economo neuron number in agenesis of the corpus callosum

Von Economo neurons (VENs) are large spindle-shaped neurons localized to anterior cingulate cortex (ACC) and fronto-insular cortex (FI). VENs appear late in development in humans, are a recent phylogenetic specialization, and are selectively destroyed in frontotemporal dementia, a disease which profoundly disrupts social functioning and self-awareness. Agenesis of the corpus callosum (AgCC) is a congenital disorder that can have significant effects on social and emotional behaviors, including alexithymia, difficulty intuiting the emotional states of others, and deficits in self- and social-awareness that can impair humor, comprehension of non-literal or affective language, and social judgment. To test the hypothesis that VEN number is selectively reduced in AgCC, we used stereology to obtain unbiased estimates of total neuron number and VEN number in postmortem brain specimens of four normal adult controls, two adults with isolated callosal dysgenesis, and one adult whose corpus callosum and ACC were severely atrophied due to a non-fatal cerebral arterial infarction. The partial agenesis case had approximately half as many VENs as did the four normal controls, both in ACC and FI. In the complete agenesis case the VENs were almost entirely absent. The percentage of neurons in FI that are VENs was reduced in callosal agenesis, but was actually slightly above normal in the stroke patient. These results indicate that the VEN population is selectively reduced in AgCC, but that the VENs do not depend on having an intact corpus callosum. We conclude that in agenesis of the corpus callosum the reduction in the number of VENs is not the direct result of the failure of this structure to develop, but may instead be another consequence of the genetic disruption that caused the agenesis. The reduction of the VEN population could help to explain some of the social and emotional deficits that are seen in this disorder.

Evolution of Specialized Pyramidal Neurons in Primate Visual and Motor Cortex

The neocortex of primates contains several distinct neuron subtypes. Among these, Betz cells of primary motor cortex and Meynert cells of primary visual cortex are of particular interest for their potential role in specialized sensorimotor adaptations of primates. Betz cells are involved in setting muscle tone prior to fine motor output and Meynert cells participate in the processing of visual motion. We measured the soma volumes of Betz cells, Meynert cells, and adjacent infragranular pyramidal neurons in 23 species of primate and two species of non-primate mammal (Tupaia glis and Pteropus poliocephalus) using unbiased stereological techniques to examine their allometric scaling relationships and socioecological correlations. Results show that Betz somata become proportionally larger with increases in body weight, brain weight, and encephalization whereas Meynert somata remain a constant proportion larger than other visual pyramidal cells. Phylogenetic variance in the volumetric scaling of these neuronal subtypes might be related to species-specific adaptations. Enlargement of Meynert cells in terrestrial anthropoids living in open habitats, for example, might serve as an anatomical substrate for predator detection. Modification of the connectional and physiological properties of these neurons could constitute an important evolutionary mode for species-specific adaptation.

The von economo neurons in apes and humans

The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex (ACC) in great apes and humans but not other primates. We stereologically counted the VENs in FI and the limbic anterior (LA) area of ACC and found them to be more numerous in humans than in apes. In humans, VENs first appear in small numbers in the 36th week postconception are rare at birth and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than the left in FI and LA in postnatal brains; this may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, containing FI, is related to physiological changes in the body, decision‐making, error recognition, and awareness. In a preliminary diffusion tensor imaging study of the connections of FI, we found that the VEN‐containing regions connect with the frontal pole as well as with other parts of frontal and insular cortex, the septum, and the amygdala. The VENs and a related cell population, the fork cells, selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing pepide, which signal satiety. The loss of VENs and fork cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. These cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. Am. J. Hum. Biol., 2011.

The Distribution and Size of Retinal Ganglion Cells in Microcebus murinus, Cheirogaleus medius, and Tarsius syrichta: Implications for the Evolution of Sensory Systems in Primates

Sensory specializations, particularly in the visual system, have been crucial factors in the evolution of brain and behavior in primates (Allman, 1998; Kay and Kirk, 2000; Ross, 2000). The entire output of the retina is channeled through the retinal ganglion cells whose axons form the optic nerve connecting the eye and brain. The patterns of retinal ganglion cell density and size in anthropoids are different from those in strepsirrhines known to date ( Otolemur cmssicaudatus and Galago senegalensis). Anthropoids have higher ganglion cell densities in the central retina than these strepsirrhines, and exhibit a marked gradient in cell soma size across the retina, with larger cells in the periphery of the retina. In the absence of data on these parameters in a wider range of strepsirrhines and haplorhines, it is impossible to determine whether these differences are due to broad ecological differences between the groups, such as activity pattern, or to less tractable suborder differences in visual system anatomy.