Drink alcohol and dim the lights: The impact of cognitive deficits on medial frontal cortex function

Scalp electroencephalogram (EEG) recordings indicate that regions in the medial frontal cortex (MFC) are active following errors. Alcohol consumption reduces this error-related activity, perhaps suggesting that alcohol disrupts the operation of an error-monitoring system in the MFC. However, it could also be that alcohol consumption affects the MFC only indirectly, by impairing stimulus processing and thus making errors harder to detect. This interpretation leads to the prediction that stimulus degradation should likewise reduce error-related activity in the MFC. To test this hypothesis, behavioral and EEG data were collected as participants performed a speeded response task with either bright or very dim stimuli. The results using dim stimuli replicated the observed effects of alcohol consumption—with slowed responses accompanied by reduced error-related MFC activity. The sensitivity of the MFC to disrupted processing elsewhere in the brain suggests complications in interpreting evidence of disturbed MFC function. This research was supported by the National Institutes of Health Conte Center for Neuroscience Research (Grant P50-MH62196 to N.Y.) and by the Netherlands Organization for Scientific Research (to S.N.).     

Cognitive functioning after medial frontal lobe damage including the anterior cingulate cortex: a preliminary investigation

Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was compared with age and education matched healthy controls. Both patients showed intact intellectual, memory, and language abilities. No clear-cut abnormalities were noted in visuoperceptual functions. Speed of information processing was mildly reduced only in Patient 2 (bilateral ACC lesion). The patients demonstrated weak or impaired performance only on selective executive function tests. Performance on anterior attention tasks was satisfactory. We tentatively suggest that our findings are inconsistent with anterior attention theories of ACC function based on neuroimaging findings. We propose that the data may imply that the ACC does not have a central role in cognition. We speculate that our findings may be compatible with the view that the ACC integrates cognitive processing with autonomic functioning to guide behaviour.     

Integrating rewards and cognition in the frontal cortex

Research indicates that the dorsolateral prefrontal cortex (DLPFC) contributes to working memory and executive control, whereas the ventral frontal cortex (VFC) contributes to affective and motivational processing. Few studies have examined both the functional specificity and the integration of these regions. We did so using fMRI and a verbal working memory task in which visual cues indicated whether recall performance on an upcoming trial would be linked to a monetary reward. On the basis of prior findings obtained in delayed response tasks performed by nonhuman primates, we hypothesized that (1) VFC would show an increase only in response to a cue indicating potential for a monetary reward; (2) DLPFC would show sustained activity across a delay interval for all trials, though activity in rewarded trials would be enhanced; and (3) regions engaged in speech-based rehearsal would be relatively insensitive to monetary incentive. Our hypotheses about DLPFC and rehearsal-related regions were confirmed. In VFC regions, we failed to observe statistically significant effects of reward when the cue or delay epochs of the task were examined in isolation. However, an unexpected and significant deactivation was observed in VFC during the delay epoch; furthermore, a post hoc voxelwise analysis indicated a complex interaction between (1) the cue and delay epochs of the task and (2) the reward value of the trials. The pattern of activation and deactivation across trial types suggests that VFC is sensitive to reward cues, and that portions of DLPFC and VFC may work in opposition during the delay epoch of a working memory task in order to facilitate task performance.     

Inhibition and the right inferior frontal cortex

It is controversial whether different cognitive functions can be mapped to discrete regions of the prefrontal cortex (PFC). The localisationist tradition has associated one cognitive function - inhibition - by turns with dorsolateral prefrontal cortex (DLPFC), inferior frontal cortex (IFC), or orbital frontal cortex (OFC). Inhibition is postulated to be a mechanism by which PFC exerts its effects on subcortical and posterior-cortical regions to implement executive control. We review evidence concerning inhibition of responses and task-sets. Whereas neuroimaging implicates diverse PFC foci, advances in human lesion-mapping support the functional localization of such inhibition to right IFC alone. Future research should investigate the generality of this proposed inhibitory function to other task domains, and its interaction within a wider network.     

At your own peril: An ERP study of voluntary task set selection processes in the medial frontal cortex

A tool that is commonly used to investigate selection among different alternatives in a changing environment is the task-switching paradigm. Functional neuroimaging has pointed out a role for the posterior medial frontal cortex and the posterior parietal cortex in the voluntary selection of task sets. In the present study, we set out to investigate the temporal dynamics of these agency-related processes (in task choice vs. no-choice conditions) using event-related brain potentials (ERPs). The results revealed agency-related modulations of a series of ERP components, including (1) an early parieto-occipital activation, taken to reflect the evaluation of choice versus no choice; (2) a subsequent medial frontal expression of the voluntary selection between task sets; (3) a CNV-like sustained negativity in preparation for the target; (4) a target-induced N210—P210 complex, taken to reflect early sensory-perceptual processing; and (5) a target-induced P3, associated with the evaluation of the stimulus and its designated response vis-à-vis the chosen versus competing task sets. Together, these results indicate that the opportunity to choose between tasks invokes activity originating from the medial frontal cortex, associated with voluntary task set selection, but also activation at different time points in a number of other brain areas, not necessarily captured by functional neuroimaging.     

Left inferior frontal cortex can compensate the inhibitory functions of right inferior frontal cortex and pre-supplementary motor area

Right-IFG and pre-SMA are associated with inhibitory responses. We used functional Magnetic Resonance Imaging to explore whether the contralateral homotopic regions can functionally replace them. An adolescent, with an extensive traumatic lesion of the right cerebral hemisphere having occurred 5 years earlier, performed a motor response inhibition task (Go/Nogo), which was properly accomplished and associated to activations in the left-IFC, precuneus and occipital cortex. Such functional remodelling is in line with the theory of ‘near equipotentiality’ of the cerebral hemispheres.     

Aged rats are impaired on an attentional set-shifting task sensitive to medial frontal cortex damage in young rats

Normal aging is associated with disruption of neural systems that subserve different aspects of cognitive function, particularly in the hippocampus and frontal cortex. Abnormalities in hippocampal function have been well investigated in rodent models of aging, but studies of frontal cortex function in aged rodents are few. We tested young (4–5 mo old) and aged (27–28 mo old) male Long-Evans rats on an attentional set-shifting task modified slightly from previous publication. After training on two problems in which the reward was consistently associated with the same stimulus dimension, and a reversal of one problem, a new problem was presented in which the reward was consistently associated with the previously irrelevant stimulus dimension (extradimensional shift [EDS]). Aged rats as a group were significantly impaired on the EDS, although some individual aged rats performed as well as young rats on this phase. In addition, some aged rats were impaired on the reversal, although a group effect did not reach significance in this phase. Impairment in neither reversal nor EDS was associated with impairments in spatial learning in the Morris water maze. Young rats with neurotoxic lesions of medial frontal cortex are also selectively impaired on the EDS. These results indicate that normal aging in rats is associated with impaired medial frontal cortex function. Furthermore, age-related declines in frontal cortex function are independent of those in hippocampal function. These results provide a possible basis for correlating age-related changes in neurobiological markers in frontal cortex with cognitive decline.     

Plasticity and functions of the orbital frontal cortex

We compare the effects of psychoactive drugs such as morphine and amphetamine on the synaptic organization of neurons in the orbital frontal (OFC) and medial frontal (mPFC) regions in the rat. Both regions are altered chronically by exposure to intermittent doses of either drug but the effects are area-dependent. For example, whereas morphine produces increased spine density in OFC but decreased spine density in mPFC. The differential response of the OFC and mPFC to drugs is paralleled by an areal-dependent effect of gonadal hormones on these regions as well: males have greater dendritic arborization in the mPFC whereas females have a greater arborization in the OFC. We also compared the effects of neonatal injury to the OFC and mPFC on cognitive, motor, and social behaviors as well as on the anatomical organization of the remaining brain. Again, there were differential effects of the treatments to the OFC and mPFC. Neonatal OFC lesions allowed virtually complete functional recovery of cognitive and motor behaviors, which was correlated with mild abnormalities in cerebral development compared to the more severe deficits and morphological sequelae following mPFC lesions at the same ages. One exception was the effect of OFC on social behavior, which was severe regardless of whether the injury was in infancy or adulthood. It is proposed that both drug-induced and developmental abnormalities in the integrity of OFC neurons may lead to deficits in social behavior or other behavioral pathologies, possibly including depression.     

Fear conditioning-induced alterations of phospholipase C-beta1a protein level and enzyme activity in rat hippocampal formation and medial frontal cortex

We investigated the effects of one-trial fear conditioning on phospholipase C-beta1a catalytic activity and protein level in hippocampal formation and medial frontal cortex of untreated control rats and rats prenatally exposed to ethanol. One hour following fear conditioning of untreated control rats, phospholipase C-beta1a protein level was increased in the hippocampal cytosolic fraction and decreased in the hippocampal membrane and cortical cytosolic and cortical membrane fractions. Twenty-four hours after fear conditioning, phospholipase C-beta1a protein level was reduced in the hippocampal cytosolic fraction and elevated in the cortical nuclear fraction; in addition, 24 h after conditioning, phospholipase C-beta1a activity in the cortical cytosolic fraction was increased. Rats that were exposed prenatally to ethanol displayed attenuated contextual fear conditioning, whereas conditioning to the acoustic-conditioned stimulus was not different from controls. In behavioral control (unconditioned) rats, fetal ethanol exposure was associated with reduced phospholipase C-beta1a enzyme activity in the hippocampal nuclear, cortical cytosolic, and cortical membrane fractions and increased phospholipase C-beta1a protein level in the hippocampal membrane and cortical cytosolic fractions. In certain cases, prenatal ethanol exposure modified the relationship between fear conditioning and changes in phospholipase C-beta1a protein level and/or activity. The majority of these effects occurred 1 h, rather than 24 h, after fear conditioning. Multivariate analysis of variance revealed interactions between fear conditioning, subcellular fraction, and prenatal ethanol exposure for measures of phospholipase C-beta1a protein level in hippocampal formation and phospholipase C-beta1a enzyme activity in medial frontal cortex. In the majority of cases, fear conditioning-induced changes in hippocampal phospholipase C-beta1a protein level were augmented in rats prenatally exposed to ethanol. In contrast, fear conditioning-induced changes in cortical phospholipase C-beta1a activity were, often, in opposite directions in prenatal ethanol-exposed compared to diet control rats. We speculate that alterations in subcellular phospholipase C-beta1a catalytic activity and protein level contribute to contextual fear conditioning and that learning deficits observed in rats exposed prenatally to ethanol result, in part, from dysfunctions in phospholipase C-beta1a signal transduction.     

Affective aprosodia from a medial frontal stroke

BACKGROUND AND OBJECTIVES: Whereas injury to the left hemisphere induces aphasia, injury to the right hemisphere's perisylvian region induces an impairment of emotional speech prosody (affective aprosodia). Left-sided medial frontal lesions are associated with reduced verbal fluency with relatively intact comprehension and repetition (transcortical motor aphasia), but persistent affective prosodic defects associated with right medial frontal lesions have not been described. METHODS: We assessed the prosody of a man who sustained a right medial frontal cerebral infarction seven years prior. RESULTS: While propositional speech expression was normal including syntactic prosody, the patient was impaired at expressing emotions using prosody. His comprehension and repetition of prosody were also impaired but less so than expression. CONCLUSIONS: Right medial frontal lesions can induce an affective aprosodia that primarily impairs expression.     

Emotional processing in anterior cingulate and medial prefrontal cortex

Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal-caudal cognitive and ventral-rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal-caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral-rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions.     

Data on the role of the frontal cortex in vegetative behavior

A homeostatic conditional reflex (CR) was elaborated to the effect of repeated inhalations in rats of a gas mixture containing 8 per cent oxygen. The effect of the conditional response was opposite to that of the unconditional one. After ablation of the frontal cortex, the conditional reaction disappeared. The repeated administration of 40 mg/kg of histamine resulted in a tolerance to the temperature lowering effect of histamine similar to the habituation. An injection of distilled water brought about dishabituation. Tolerance was not influenced by the ablation of the frontal cortex, but the dishabituating effect of distilled water was absent.     

The medial prefrontal cortex and memory of cue location in the rat

We developed a single-trial cue-location memory task in which rats experienced an auditory cue while exploring an environment. They then recalled and avoided the sound origination point after the cue was paired with shock in a separate context. Subjects with medial prefrontal cortical (mPFC) lesions made no such avoidance response, but both lesioned and control subjects avoided the cue itself when presented at test. A follow up assessment revealed no spatial learning impairment in either group. These findings suggest that the rodent mPFC is required for incidental learning or recollection of the location at which a discrete cue occurred, but is not required for cue recognition or for allocentric spatial memory.     

Medial frontal cortex function: An introduction and overview

The growing attention being given to medial frontal cortex (MFC) in cognitive neuroscience studies has fostered a number of theoretical and paradigmatic perspectives that diverge in important ways. This has led to a great deal of research fractionation, with investigators studying domains and issues in MFC function that sometimes bear (at least at the surface) little relation to the questions addressed by others studying the same brain region. The present issue of Cognitive, Affective, & Behavioral Neuroscience presents articles inspired by a conference bringing together views from across this diversity of research, highlighting both the richness and vibrancy of the field and the challenges to be faced in terms of integration, synthesis, and precision among the theoretical accounts. The present article presents a brief introduction, overview, and road map to the field and to the special issue devoted to MFC function.     

The role of inferior frontal cortex in phonological processing

Recent neuroimaging studies of language processing are examining the neural substrate of phonology because of its critical role in mapping sound information onto higher levels of language processing (e.g., words) as well as providing codes in which verbal information can be temporarily stored in working memory. However, the precise role of the inferior frontal cortex in spoken and written phonological tasks has remained elusive. Although lesion studies have indicated the presence of selective deficits in phonological processing, the location of lesions underlying these impairments has not revealed a consistent pattern. Despite efforts to refine methods and tasks, functional neuroimaging studies have also revealed variability in activation patterns. Reanalysis of evidence from these neuroimaging studies suggests that there are functional subregions within the inferior frontal gyrus that correspond to specific components of phonological processing (e.g., orthographic to phonological conversion in reading, and segmentation in speech).