Todd M. Preuss

The evolution of the arcuate fasciculus revealed with comparative DTI.

The arcuate fasciculus is a white-matter fiber tract that is involved in human language. Here we compared cortical connectivity in humans, chimpanzees and macaques (Macaca mulatta) and found a prominent temporal lobe projection of the human arcuate fasciculus that is much smaller or absent in nonhuman primates. This human specialization may be relevant to the evolution of language.

Do rats have prefrontal cortex? the rose-woolsey-akert program reconsidered

Primates are unique among mammals in possessing a region of dorsolateral prefrontal cortex with a well-developed internal granular layer. This region is commonly implicated in higher cognitive functions. Despite the histological distinctiveness of primate dorsolateral prefrontal cortex, the work of Rose, Woolsey, and Akert produced a broad consensus among neuroscientists that homologues of primate granular frontal cortex exist in nonprimates and can be recognized by their dense innervation from the mediodorsal thalamic nucleus (MD). Additional characteristics have come to be identified with dorsolateral prefrontal cortex, including rich dopaminergic innervation and involvement in spatial delayed-reaction tasks. However, recent studies reveal that these characteristics are not distinctive of the dorsolateral prefrontal region in primates: MD and dopaminergic projections are widespread in the frontal lobe, and medial and orbital frontal areas may play a role in delay tasks. A reevaluation of rat frontal cortex suggests that the medial frontal cortex, usually considered to be homologous to the dorsolateral prefrontal cortex of primates, actually consists of cortex homologous to primate premotor and anterior cin-date cortex. The lateral MD-projection cortex of rats resembles portions of primate orbital cortex. If prefrontal cortex is construed broadly enough to include orbital and cingulate cortex, rats can be said to have prefrontal cortex. However, they evidently lack homologues of the dorsolateral prefrontal areas of primates. This assessment suggests that rats probably do not provide useful models of human dorsolateral frontal lobe function and dysfunction, although they might prove valuable for understanding other regions of frontal cortex.

Elevated gene expression levels distinguish human from non-human primate brains

Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee cortex, and 91 were ascribed to the human lineage by using macaques as an outgroup. Surprisingly, most differences between the brains of humans and non-human primates involved up-regulation, with ≈90% of the genes being more highly expressed in humans. By contrast, in the comparison of human and chimpanzee heart and liver, the numbers of up- and down-regulated genes were nearly identical. Our results indicate that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans and suggests that the human brain is characterized by elevated levels of neuronal activity.

Architectonic identification of the core region in auditory cortex of macaques, chimpanzees, and humans

The goal of the present study was to determine whether the architectonic criteria used to identify the core region in macaque monkeys (Macaca mulatta, M. nemestrina) could be used to identify a homologous region in chimpanzees (Pan troglodytes) and humans (Homo sapiens). Current models of auditory cortical organization in primates describe a centrally located core region containing two or three subdivisions including the primary auditory area (AI), a surrounding belt of cortex with perhaps seven divisions, and a lateral parabelt region comprised of at least two fields. In monkeys the core region can be identified on the basis of specific anatomical and physiological features. In this study, the core was identified from serial sets of adjacent sections processed for cytoarchitecture, myeloarchitecture, acetylcholinesterase, and cytochrome oxidase. Qualitative and quantitative criteria were used to identify the borders of the core region in individual sections. Serial reconstructions of each brain were made showing the location of the core with respect to gross anatomical landmarks. The position of the core with respect to major sulci and gyri in the superior temporal region varied most in the chimpanzee and human specimens. Although the architectonic appearance of the core areas did vary in certain respects across taxonomic groups, the numerous similarities made it possible to identify unambiguously a homologous cortical region in macaques, chimpanzees, and humans. J. Comp. Neurol. 441:197–222, 2001.

Human-Specific Transcriptional Regulation of CNS Development Genes by FOXP2

The signalling pathways controlling both the evolution and development of language in the human brain remain unknown. So far, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction. It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans. However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans.

Movement representation in the dorsal and ventral premotor areas of owl monkeys: A microstimulation study

We used intracortical microstimulation to investigate the lateral premotor cortex and neighboring areas in 14 hemispheres of owl monkeys, focusing on the somatotopic distribution of evoked movements, thresholds for forelimb movements, and the relative representation of proximal and distal forelimb movements. We elicited movements from the dorsal and ventral premotor areas (PMD, PMV), the caudal and rostral divisions of primary motor cortex (Mlc, Mlr), the frontal eye field (FEF), the dorsal oculomotor area (OMD; area 8b), the supplementary motor area (SMA), and somatosensory cortex (areas 3a and 3b). Area PMD was composed of architectonically distinguishable caudal and rostral subdivisions (PMDc, PMDr). Stimulation of PMD elicited movements of the hindlimb, forelimb, neck and upper trunk, face, and eyes. Hindlimb and forelimb movements were represented in the caudalmost part of PMDc. Face, neck, and eye movements were represented in the lateral and rostral parts of PMDc and in PMDr. Stimulation of PMV elicited forelimb and orofacial movements, but not hindlimb movements. Both proximal and distal forelimb movements were elicited from PMDc and PMV, although PMD stimulation elicited mainly shoulder and elbow movements, while PMV stimulation evoked primarily wrist and digit movements. Distal movements were evoked more frequently from PMV than from Mlr or Mlc. Across cases, the median forelimb thresholds for PMDc and PMV were 60 and 36 μA, respectively, values that differ significantly from each other and from the value of 11 μA obtained for Mlr. Our observations indicate that premotor cortex is much more responsive to electrical stimulation than commonly thought, and contains a large territory from which eye movements can be elicited. These results suggest that in humans, much of the electrically excitable cortex located on the precentral gyrus, including cortex sometimes considered part of the frontal eye field, is probably homologous to the premotor cortex of nonhuman primates.

Human brain evolution: insights from microarrays.

Several recent microarray studies have compared gene-expression patterns n humans, chimpanzees and other non-human primates to identify evolutionary changes that contribute to the distinctive cognitive and behavioural characteristics of humans. These studies support the surprising conclusion that the evolution of the human brain involved an upregulation of gene expression relative to non-human primates, a finding that could be relevant to understanding human cerebral physiology and function. These results show how genetic and genomic methods can shed light on the basis of human neural and cognitive specializations, and have important implications for neuroscience, anthropology and medicine.

Theory of mind: evolutionary history of a cognitive specialization

Traditional analyses of the evolution of intelligence have emphasized commonality and continuity among species. However, recent research suggests that humans might have specialized in a particular kind of intelligence that is related to understanding mental states such as desires, intentions and beliefs. Data indicate that the ability to reflect on ones own mental states, as well as those of others, might be the result of evolutionary changes in the prefrontal cortex. Behavioral studies in children and chimpanzees reveal both similarities and striking differences in the developmental pathways that lead to theory-of-mind capacities. Humans and great apes share many ancient patterns of social behavior, but it is too early to be certain if they interpret them in the same manner. Humans might have evolved a cognitive specialization in theory of mind, forever altering their view of the social universe.

A comparison of resting-state brain activity in humans and chimpanzees

In humans, the wakeful resting condition is characterized by a default mode of brain function involving high levels of activity within a functionally connected network of brain regions. This network has recently been implicated in mental self-projection into the past, the future, or another individuals perspective. Here we use [18F]-fluorodeoxyglucose positron emission tomography imaging to assess resting-state brain activity in our closest living relative, the chimpanzee, as a potential window onto their mental world and compare these results with those of a human sample. We find that, like humans, chimpanzees show high levels of activity within default mode areas, including medial prefrontal and medial parietal cortex. Chimpanzees differ from our human sample in showing higher levels of activity in ventromedial prefrontal cortex and lower levels of activity in left-sided cortical areas involved in language and conceptual processing in humans. Our results raise the possibility that the resting state of chimpanzees involves emotionally laden episodic memory retrieval and some level of mental self-projection, albeit in the absence of language and conceptual processing.

Human-specific transcriptional networks in the brain

Understanding human-specific patterns of brain gene expression and regulation can provide key insights into human brain evolution and speciation. Here, we use next-generation sequencing, and Illumina and Affymetrix microarray platforms, to compare the transcriptome of human, chimpanzee, and macaque telencephalon. Our analysis reveals a predominance of genes differentially expressed within human frontal lobe and a striking increase in transcriptional complexity specific to the human lineage in the frontal lobe. In contrast, caudate nucleus gene expression is highly conserved. We also identify gene coexpression signatures related to either neuronal processes or neuropsychiatric diseases, including a human-specific module with CLOCK as its hub gene and another module enriched for neuronal morphological processes and genes coexpressed with FOXP2, a gene important for language evolution. These data demonstrate that transcriptional networks have undergone evolutionary remodeling even within a given brain region, providing a window through which to view the foundation of uniquely human cognitive capacities.