Pyramidal cells in prefrontal cortex: comparative observations reveal unparalleled specializations in neuronal structure among primate species

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.

Pyramidal neurons of granular prefrontal cortex of the galago: Complexity in evolution of the psychic cell in primates

Typically, cognitive abilities of humans have been attributed to their greatly expanded cortical mantle, granular prefrontal cortex (gPFC) in particular. Recently we have demonstrated systematic differences in microstructure of gPFC in different species. Specifically, pyramidal cells in adult human gPFC are considerably more spinous than those in the gPFC of the macaque monkey, which are more spinous than those in the gPFC of marmoset and owl monkeys. As most cortical dendritic spines receive at least one excitatory input, pyramidal cells in these different species putatively receive different numbers of inputs. These differences in the gPFC pyramidal cell phenotype may be of fundamental importance in determining the functional characteristics of prefrontal circuitry and hence the cognitive styles of the different species. However, it remains unknown as to why the gPFC pyramidal cell phenotype differs between species. Differences could be attributed to, among other things, brain size, relative size of gPFC, or the lineage to which the species belong. Here we investigated pyramidal cells in the dorsolateral gPFC of the prosimian galago to extend the basis for comparison. We found these cells to be less spinous than those in human, macaque, and marmoset. (c) 2005 Wiley-Liss, Inc.

Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear

Although the endocannabinoid system (ECS) has been implicated in brain development and various psychiatric disorders, precise mechanisms of the ECS on mood and anxiety disorders remain unclear. Here, we have investigated developmental and disease-related expression pattern of the cannabinoid receptor 1 (CB1) and the cannabinoid receptor 2 (CB2) genes in the dorsolateral prefrontal cortex (PFC) of humans. Using mice selectively bred for high and low fear, we further investigated potential association between fear memory and the cannabinoid receptor expression in the brain. The CB1, not the CB2, mRNA levels in the PFC gradually decrease during postnatal development ranging in age from birth to 50 years (r 2 > 0.6 & adj. p < 0.05). The CB1 levels in the PFC of major depression patients were higher when compared to the age-matched controls (adj. p < 0.05). In mice, the CB1, not the CB2, levels in the PFC were positively correlated with freezing behavior in classical fear conditioning (p < 0.05). These results suggest that the CB1 in the PFC may play a significant role in regulating mood and anxiety symptoms. Our study demonstrates the advantage of utilizing data from postmortem brain tissue and a mouse model of fear to enhance our understanding of the role of the cannabinoid receptors in mood and anxiety disorders

Metabolic changes in rat prefrontal cortex and hippocampus induced by chronic morphine treatment studied ex vivo by high resolution H-1 NMR spectroscopy

Ex vivo H-1 NMR spectroscopy was used to measure changes in the concentrations of cerebral metabolites in the prefrontal cortex (PFC) and hippocampus of rats subjected to repeated morphine treatment known to cause tolerance/dependence. The results show th

Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions

Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement t

Distracters Impair and Create Working Memory-Related Neuronal Activity in the Prefrontal Cortex

The prefrontal cortex (PFC) has a central role in working memory (WM). Resistance to distraction is considered a fundamental feature of WM and PFC neuronal activity. However, although unexpected stimuli often disrupt our work, little is known about the un

Increasing top-down suppression from prefrontal cortex facilitates tactile working memory

Navigated transcranial magnetic stimulation (TMS) combined with diffusion-weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM. (C) 2009 Elsevier Inc. All rights reserved.

Schizophrenia patients and their healthy siblings share disruption of white matter integrity in the left prefrontal cortex and the hippocampus but not the anterior cingulate cortex

Healthy siblings of schizophrenia patients have an almost 9-fold higher risk for developing the illness than the general population. Disruption of white matter (WM) integrity as indicated by reduced fractional anisotropy (FA) derived from diffusion tensor

Resolving response, decision, and strategic control: evidence for a functional topography in dorsomedial prefrontal cortex.

The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of cognitive control and decision making. Here, we provide evidence for an anterior-to-posterior topography within the DMPFC using tasks that evoke three distinct forms of control demands--response, decision, and strategic--each of which could be mapped onto independent behavioral data. Specifically, we identify three spatially distinct regions within the DMPFC: a posterior region associated with control demands evoked by multiple incompatible responses, a middle region associated with control demands evoked by the relative desirability of decision options, and an anterior region that predicts control demands related to deviations from an individual's preferred decision-making strategy. These results provide new insight into the functional organization of DMPFC and suggest how recent controversies about its role in complex decision making and response mapping can be reconciled.

Neuronal correlates of metacognition in primate frontal cortex.

Humans are metacognitive: they monitor and control their cognition. Our hypothesis was that neuronal correlates of metacognition reside in the same brain areas responsible for cognition, including frontal cortex. Recent work demonstrated that nonhuman primates are capable of metacognition, so we recorded from single neurons in the frontal eye field, dorsolateral prefrontal cortex, and supplementary eye field of monkeys (Macaca mulatta) that performed a metacognitive visual-oculomotor task. The animals made a decision and reported it with a saccade, but received no immediate reward or feedback. Instead, they had to monitor their decision and bet whether it was correct. Activity was correlated with decisions and bets in all three brain areas, but putative metacognitive activity that linked decisions to appropriate bets occurred exclusively in the SEF. Our results offer a survey of neuronal correlates of metacognition and implicate the SEF in linking cognitive functions over short periods of time.

The Impact of Prenatal Nicotine Exposure on Impulsivity and Neural Firing in the Medial Prefrontal Cortex

Prenatal nicotine exposure (PNE) is linked to a large number of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD). Current literature suggests that core deficits observed in ADHD reflect abnormal inhibitory control governed by the prefrontal cortex (PFC) of the brain. The PFC is structurally altered by PNE, but it is still unclear how neural firing is affected during tasks that test behavioral inhibition, such as the stop-signal task, or if neural correlates related to inhibitory control are affected after PNE in awake behaving animals. To address these questions, we recorded from single medial PFC (mPFC) neurons in control rats and PNE rats as they performed our stopsignal task. We found that PNE rats were faster for all trial types and were less likely to inhibit the behavioral response on STOP trials. Neurons in mPFC fired more strongly on STOP trials and were correlated with accuracy and reaction time. Although the number of neurons exhibiting significant modulation during task performance did not differ between groups, overall activity in PNE was reduced. We conclude that PNE makes rats impulsive and reduces firing in mPFC neurons that carry signals related to response inhibition.

Hot cognition and activation of the medial prefrontal cortex: Self-regulating in contexts involving motivational pressures

The medial prefrontal cortex (mPFC) is involved in performance-monitoring and has been implicated in the generation of several electrocortical responses associated with self-regulation. The error-related negativity (ERN), the inhibitory Nogo N2 (N2), and the feedback-related negativity (FRN) are event-related potential (ERP) components which reflect mPFC activity associated with feedback to behavioural (ERN, N2) and environmental (FRN) consequences. Our main goal was to determine whether or not rnPFC activation varies as a function of motivational context (e.g., those involving performance-related incentives) or the use of internally versus externally generated feedback signals (i.e., errors). Additionally, we assessed medial prefrontal activity in relation to individual differences in personality and temperament. Participants completed a combination of tasks in which performance-related incentives were associated with task performance and feedback generated from internal versus external responses. MPFC activity was indexed using both ERP scalp voltage peaks and intracerebral current source density (CSD) of dorsal and ventral regions. Additionally, participants completed several questionnaires assessing personality and temperament styles. Given previous studies have shown that enhanced mPFC activity to loss (or negative) feedback, we expected that activity in the mPFC would generally be greater during the Loss condition relative to the Win condition for both the ERN and N2. Also, due to the evidence that the (vmPFC) is engaged in arousing contexts, we hypothesized that activity in the ventromedial prefrontal cortex (vmPFC) would be greater than activity in the dorsomedial prefrontal cortex (dmPFC), especially in the Loss condition of the GoNogo task (ERN). Similarly, loss feedback in the BART (FRN) was expected to engage the vmPFC more than the dmPFC. Finally, we predicted that persons rating themselves as more willing to engage in approach-related behaviours or to exhibit rigid cognitive styles would show reduced activity of the mPFC. Overall, our results emphasize the role of affective evaluations of behavioural and environmental consequences when self-regulating. Although there were no effects of context on brain activity, our data indicate that, during the time of the ERN and N2 on the MW Go-Nogo task and the FRN on the BART, the vrnPFC was more active compared to the dmPFC. Moreover, regional recruitment in the mPFC was similar across internally (ERN) and externally (FRN) generated errors signals associated with loss feedback, as reflected by relatively greater activity in the vmPFC than the dmPFC. Our data also suggest that greater activity in the mPFC is associated with better inhibitory control, as reflected by both scalp and CSD measures. Additionally, deactivation of the subgenual anterior cingulate cortex (sgACC) and lower levels of self-reported positive affect were both related to increased voluntary risk-taking on the BART. Finally, persons reporting higher levels of approach-related behaviour or cognitive rigidity showed reduced activity of the mPFC. These results are in line with previous research emphasizing that affect/motivation is central to the processes reflected by mediofrontal negativities (MFNs), that the vmPFC is involved in regulating demands on motivational/affective systems, and that the underlying mechanisms driving these functions vary across both individuals and contexts.

Disambiguating the Effects of Social Instability Stress in Adolescence on Learning and Memory Tasks that Involve the Medial Prefrontal Cortex and Hippocampus

Exposure to chronic stress can alter the structure and function of brain regions involved in learning and memory, and these effects are typically long-lasting if the stress occurs during sensitive periods of development. Until recently, adolescence has received relatively little attention as a sensitive period of development, despite marked changes in behaviour, heightened reactivity to stressors, and cognitive and neural maturation. Therefore, the purpose of the present study was to investigate the long-term effects of chronic stress in adolescence on two spatial learning and memory tasks (Morris water maze and Spatial Object Location test) and on a working memory task (Delayed Alternation task). Male rats were randomly assigned to chronic social instability stress (SS; daily 1 hour isolation and subsequent change of cage partner between postnatal days 30 and 45) or to a no-stress control group (CTL). During acquisition learning in the Morris water maze task, SS rats demonstrated impaired long-term memory for the location of the hidden escape platform compared to CTL rats, although the impairment was only seen after the first day of training. Similarly, SS rats had impaired long-term memory in the Spatial Object Location test after a long delay (240 minutes), but not after shorter delays (15 or 60 minutes) compared to CTL rats. On the Delayed Alternation task, which assessed working memory across delays ranging from 5 to 90 seconds, no group differences were observed. These results are partially in line with previous research that revealed adult impairment on spatial learning and memory tasks after exposure to chronic social instability stress in adolescence. The observed deficits, however, appear to be limited to long-term memory as no group differences were observed during brief periods of retention.