Insights into Human Behavior from Lesions to the Prefrontal Cortex

Learning Substrates in the Primate Prefrontal Cortex and Striatum: Sustained Activity Related to Successful Actions

Distributed Coding of Actual and Hypothetical Outcomes in the Orbital and Dorsolateral Prefrontal Cortex

Dynamics and Hierarchical Encoding of Non-compact Acoustic Categories in Auditory and Frontal Cortex.

Prefrontal cortical unit activity and delayed alternation performance in monkeys.

Pieces of the Schizophrenia Puzzle Fall into Place

Anterior Cingulate Cortex: Unique Role in Cognition and Emotion

Top-Down Control-Signal Dynamics in Anterior Cingulate and Prefrontal Cortex Neurons following Task Switching

Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices

It is often assumed that the massive expansion of the prefrontal cortex (PFC) in humans and nonhuman primates was a pivotal determinant of evolutionary success. Whereas dorsolateral prefrontal cortical areas in macaque monkeys and humans share multiple characteristics with regard to cytoarchitecture, hodology (Petrides and Pandya, 1999), and DA innervation (Lewis and Sesack, 1997), the organization of the frontal cortex and its dopaminergic innervation are vastly different in rats and primates (Berger et al., 1991; Preuss, 1995; Williams and Goldman-Rakic, 1998; Uylings et al., 2003). This raises the question of whether certain properties of the primate PFC are not present, or only represented in a rudimentary fashion in other species. Seminal findings from brain lesion and behavioral electrophysiology studies determined that different subregions of the PFC engage in distinct cognitive functions. Among these findings is the observation that cells in the dorsolateral PFC regions exhibit persistent activity in response to external stimuli, after the stimuli have ceased. This activity may reflect the ability to temporarily hold items in working memory (WM), a cognitive function required for the temporal organization of behavior (Fuster, 1997). Persistent activity is believed to be maintained through recurrent excitation in assemblies of PFC neurons. In the primate PFC, such cell assemblies may be organized into interconnected stripe-like clusters, similar to the columns in primary sensory cortex. By means of persistent firing, the PFC is thought to transiently store stimulus-related information that is task-relevant, for example, “what” an object is, or “where” it is located. Thus, primate PFC neurons are said to

Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.

Cognitive impairments that accompany aging, even in the absence of neurodegenerative diseases, include deficits in executive function and memory mediated by the prefrontal cortex. Because of the unique differentiation and expansion of the prefrontal cortex in primates, investigations of the neurobiological basis of cognitive aging in nonhuman primates have been particularly informative about the potential basis for age-related cognitive decline in humans. We review the cognitive functions mediated by specific subregions of prefrontal cortex, and their corresponding connections, as well as the evidence for age-related alterations in specific regions of prefrontal cortex. We also discuss evidence for similarities and differences in the effects of aging on prefrontal cortex across species.

INTERFERENCE FACTORS IN DELAYED RESPONSE IN MONKEYS AFTER REMOVAL OF FRONTAL LOBES

A recurring debate concerns whether regions of primate prefrontal cortex (PFC) support domain-flexible or domain-specific processes. Here we tested the hypothesis with functional MRI (fMRI) that side-by-side PFC regions, within distinct parallel association networks, differentially support domain-flexible and domain-specialized processing. Individuals (N = 9) were intensively sampled, and all effects were estimated within their own idiosyncratic anatomy. Within each individual, we identified PFC regions linked to distinct networks, including a dorsolateral PFC (DLPFC) region coupled to the medial temporal lobe (MTL) and an extended region associated with the canonical multiple-demand network. We further identified an inferior PFC region coupled to the language network. Exploration in separate task data, collected within the same individuals, revealed a robust functional triple dissociation. The DLPFC region linked to the MTL was recruited during remembering and imagining the future, distinct from juxtaposed regions that were modulated in a domain-flexible manner during working memory. The inferior PFC region linked to the language network was recruited during sentence processing. Detailed analysis of the trial-level responses further revealed that the DLPFC region linked to the MTL specifically tracked processes associated with scene construction. These results suggest that the DLPFC possesses a domain-specialized region that is small and easily confused with nearby (larger) regions associated with cognitive control. The newly described region is domain specialized for functions traditionally associated with the MTL. We discuss the implications of these findings in relation to convergent anatomical analysis in the monkey.NEW & NOTEWORTHY Competing hypotheses link regions of prefrontal cortex (PFC) to domain-flexible or domain-specific processes. Here, using a precision neuroimaging approach, we identify a domain-specialized region in dorsolateral PFC, coupled to the medial temporal lobe and recruited for scene construction. This region is juxtaposed to, but distinct from, broader PFC regions recruited flexibly for cognitive control. Region distinctions align with broader network differences, suggesting that PFC regions gain dissociable processing properties via segregated anatomical projections.

The most ubiquitous neuron in the cerebral cortex, the pyramidal cell, is characterized by markedly different dendritic structure among different cortical areas. The complex pyramidal cell phenotype in granular prefrontal cortex (gPFC) of higher primates endows specific biophysical properties and patterns of connectivity, which differ from those in other cortical regions. However, within the gPFC, data have been sampled from only a select few cortical areas. The gPFC of species such as human and macaque monkey includes more than 10 cortical areas. It remains unknown as to what degree pyramidal cell structure may vary among these cortical areas. Here we undertook a survey of pyramidal cells in the dorsolateral, medial, and orbital gPFC of cercopithecid primates. We found marked heterogeneity in pyramidal cell structure within and between these regions. Moreover, trends for gradients in neuronal complexity varied among species. As the structure of neurons determines their computational abilities, memory storage capacity and connectivity, we propose that these specializations in the pyramidal cell phenotype are an important determinant of species-specific executive cortical functions in primates.

The evolution of human language has been discussed for centuries from different perspectives. Linguistic theory has proposed grammar as a core part of human language that has to be considered in this context. Recent advances in neurosciences have allowed us to take a new neurobiological look on the similarities and dissimilarities of cognitive capacities and their neural basis across both closely and distantly related species. A couple of decades ago, the comparisons were mainly drawn between human and non-human primates, investigating the cytoarchitecture of particular brain areas and their structural connectivity. Moreover, comparative studies were conducted with respect to their ability to process grammars of different complexity. So far the available data suggest that non-human primates are able to learn simple probabilistic grammars, but not hierarchically structured complex grammars. The human brain, which easily learns both grammars, differs from the non-human brain (among others) in how two language-relevant brain regions (Broca's area in the inferior frontal cortex and the superior temporal cortex) are connected structurally by fiber tracts which run dorsally and ventrally in the primate brain. Whether the more dominant dorsal pathway in humans compared to non-human primates is causally related to this behavioral difference is an issue of current debate. Ontogenetic findings suggest at least a correlation between the maturation of the dorsal pathway and the behavior to process syntactically complex structures, although the ultimate causal prove is still not available. Thus, the neural basis of complex grammar processing in humans remains to be defined. More recently it has been reported that songbirds are also able to distinguish between sound sequences reflecting complex grammar. Interestingly, songbirds learn to sing by imitating adult song in a process not unlike language development in children. Moreover, the neural circuits supporting this behavior in songbirds bear anatomical and functional similarities to those in humans. In adult humans the fiber tract connecting the auditory cortex and motor cortex dorsally is known to be involved in the repetition of spoken language. This pathway is present already at birth and is taken to play a major role during language acquisition. In songbirds, detailed information exist concerning the interaction of auditory, motor, and cortical-basal ganglia processing during song learning, and present a rich substrate for comparative studies. The scope of the Research Topic was to bring together contributions of researchers from different fields, who investigate grammar processing in humans, non-human primates, and songbirds with the aim to find answers to the question of what constitutes the neurobiological basis of language and language learning. A number of contributions discuss the ventral and dorsal pathways in human and non-human primates considering their functional roles in speech and language. Some of these take an evolutionary perspective comparing non-human and human primates (Rauschecker, 2012; Rilling et al., 2012), whereas other takes an ontogenetic perspective (Friederici, 2012). The functional roles of the ventral and dorsal pathways in language and other modalities in particular action including articulatory and hand gestures are discussed in further articles (Fitch, 2011; Aboitiz, 2012; Rijntjes et al., 2012). Two articles consider the language system at the interface of two other human specific abilities, namely number processing (Heim et al., 2012) and reading (Lachmann et al., 2012). A couple of contributions take the evolutionary perspective even further by including song birds into their comparative approach (Berwick et al., 2012; Kiggins et al., 2012; Petkov and Jarvis, 2012). The selection of the articles provides a picture of the current views on the evolutionary and neurobiological basis of the language and language learning.