Medial Prefrontal Cortical Areas Research Articles

Optogenetic activation of basal forebrain cholinergic neurons improves interval timing performance in rodents (P1-6.009)

<h3>Objective:</h3> To study the effect of basal forebrain optogenetic cholinergic activation in an interval timing task in freely behaving animals. <h3>Background:</h3> Cholinergic deficit is a major feature in patients with Alzheimer’s disease, Parkinson’s disease dementia and dementia with Lewy bodies. Parkinson’s and Alzheimer’s patients can have impairments in interval timing, or the ability to control movements in time. Timing is preserved across mammalian species, and timing tasks require subjects to estimate an interval of several seconds. These tasks require attention to time and working memory for temporal rules. Mice receiving scopolamine, a cholinergic inhibitor, perform poorly during timing tasks. Interval timing involves medial prefrontal cortical areas that receive prominent cholinergic input; our recent work showed that scopolamine impairs interval timing through disrupting stimulus-processing rather than temporal processing in the medial prefrontal cortex. However, it is unclear whether basal forebrain cholinergic neuron activation could improve timing performance. <h3>Design/Methods:</h3> ChAT-Cre transgenic mice were trained on a 12s interval timing task before bilateral basal forebrain stereotactic AAV-DIO-ChR2 injection and optic canulae implantation (AP −0.7, ML +/−1.8, DV AAV injection at −4.0 and −5.0, with optic canulae at −3.5). Laser (473nm) stimulation was assigned on/off randomly across trials, and interval timing tasks were performed 30 min after intraperitoneal scopolamine (1mg/kg) or normal saline injections. <h3>Results:</h3> Scopolamine induced interval-timing deficits were partially reversed by optogenetic activation of basal forebrain cholinergic neurons with 20Hz stimulation but not 4 Hz. <h3>Conclusions:</h3> Optogenetic activation of the basal forebrain cholinergic neurons improves interval timing performance. These data may have relevance for our understanding of cholinergic function in human diseases such as Parkinson’s disease and Alzheimer’s disease. <b>Disclosure:</b> Dr. Zhang has nothing to disclose. Mr. Kirkpatrick has nothing to disclose. Dr. Narayanan has nothing to disclose.

The Theta Paradox: 4-8 Hz EEG Oscillations Reflect Both Sleep Pressure and Cognitive Control.

Human electroencephalographic (EEG) oscillations characterize specific behavioral and vigilance states. The frequency of these oscillations is typically sufficient to distinguish a given state; however, theta oscillations (4-8 Hz) have instead been found in near-opposite conditions of drowsiness during sleep deprivation and alert cognitive control. While the latter has been extensively studied and is often referred to as "frontal midline theta," (fmTheta) the former has been investigated far less but is considered a marker for sleep pressure during wake. In this study we investigated to what extent theta oscillations differed during cognitive tasks and sleep deprivation. We measured high-density EEG in 18 young healthy adults (nine female) performing six tasks under three levels of sleep deprivation. We found both cognitive load and sleep deprivation increased theta power in medial prefrontal cortical areas; however, sleep deprivation caused additional increases in theta in many other, predominantly frontal, areas. The sources of sleep deprivation theta (sdTheta) were task dependent, with a visual-spatial task and short-term memory (STM) task showing the most widespread effects. Notably, theta was highest in supplementary motor areas during passive music listening, and highest in the inferior temporal cortex (responsible for object recognition) during a spatial game. Furthermore, while changes in task performance were correlated with increases in theta during sleep deprivation, this relationship was not specific to the EEG of the same task and did not survive correction for multiple comparisons. Altogether, these results suggest that both during sleep deprivation and cognition theta oscillations may preferentially occur in cortical areas not involved in ongoing behavior.SIGNIFICANCE STATEMENT Electroencephalographic (EEG) research in sleep has often remained separate from research in cognition. This has led to two incompatible interpretations of the function of theta brain oscillations (4-8 Hz): that they reflect local sleep events during sleep deprivation, or that they reflect cognitive processing during tasks. With this study, we found no fundamental differences between theta oscillations during cognition and theta during sleep deprivation that would suggest different functions. Instead, our results indicate that in both cases, theta oscillations are generated by cortical areas not required for ongoing behavior. Therefore, at least in humans, theta may reflect either cortical disengagement or inhibition.

The Function of Paraventricular Thalamic Circuitry in Adaptive Control of Feeding Behavior.

The paraventricular nucleus of the thalamus (PVT) is a complex area that is uniquely embedded across the core feeding, reward, arousal, and stress circuits. The PVT role in the control of feeding behavior is discussed here within a framework of adaptive behavioral guidance based on the body’s energy state and competing drives. The survival of an organism depends on bodily energy resources and promotion of feeding over other behaviors is adaptive except when in danger or sated. The PVT is structurally set up to respond to homeostatic and hedonic needs to feed, and to integrate those signals with physiological and environmental stress, as well as anticipatory needs and other cognitive inputs. It can regulate both food foraging (seeking) and consumption and may balance their expression. The PVT is proposed to accomplish these functions through a network of connections with the brainstem, hypothalamic, striatal, and cortical areas. The connectivity of the PVT further indicates that it could broadcast the information about energy use/gain and behavioral choice to impact cognitive processes—learning, memory, and decision-making—through connections with the medial and lateral prefrontal cortical areas, the hippocampal formation, and the amygdala. The PVT is structurally complex and recent evidence for specific PVT pathways in different aspects of feeding behavior will be discussed.

Cortico-Hippocampal Brain Connectivity-Guided Repetitive Transcranial Magnetic Stimulation Enhances Face-Cued Word-Based Associative Memory in the Short Term.

Repetitive transcranial magnetic stimulation (rTMS) can be used to enhance the associative memory of healthy subjects and patients with Alzheimer’s disease (AD). However, the question of where the stimulation should be applied is still unresolved. In a preliminary survey for an effective and feasible solution to this problem, we identified three representative rTMS targets using cortico-hippocampal connectivity, calculated using resting-state fMRI (rs-fMRI) data from 80 young, healthy subjects: (1) the cortical area with the strongest connectivity across the whole cerebral cortical area; (2) the whole lateral parietal cortical area; and (3) the whole medial prefrontal cortical area. We then compared the short-term effects on associative memory, which was tested using face-cued word recall by applying rTMS to three identified targets in a single population of eight healthy adults. Each treatment lasted for 2 days. Associative memory performance was measured at four time points: before and after stimulation on the first day (baseline and post 1) and before and after stimulation on the second day (post 2 and post 3). Compared with baseline levels, 20 min of high-frequency rTMS delivered to target 2 or target 3 produced a significant increase in the mean accuracy of associative memory performance at the post 3 time point alone (target 2, P = 0.0035; target 3, P = 0.0012). Compared with the sham conditions, significant increases in the mean associative memory performance were observed when high-frequency rTMS was delivered to target 2 (P = 0.02) and target 3 (P = 0.012), but not when delivered to target 1 (P = 0.1). Compared with baseline levels, 20 min of high-frequency rTMS delivered to target 3 produced a significant reduction in the mean reaction time of associative memory only at time points post 1 (P = 0.0464) and post 3 (P = 0.0477). Compared with the sham conditions, significant reductions in the mean reaction time of associative memory were observed when high-frequency rTMS was delivered to target 3 (P = 0.006), but not when delivered to target 1 (P = 0.471) or target 2 (P = 0.365). Our findings indicate that stimulation of the locations with the strongest cortico-hippocampal connectivity within the lateral parietal cortical or medial prefrontal cortical areas is effective in enhancing face–word recall-based associative memory in the short term.

Robust encoding of scene anticipation during human spatial navigation.

In a familiar city, people can recall scene views (e.g., a particular street corner scene) they could encounter again in the future. Complex objects with multiple features are represented by multiple neural units (channels) in the brain, but when anticipating a scene view, the kind of feature that is assigned to a specific channel is unknown. Here, we studied neural encoding of scene view anticipation during spatial navigation, using a novel data-driven analysis to evaluate encoding channels. Our encoding models, based on functional magnetic resonance imaging (fMRI) activity, provided channel error correction via redundant channel assignments that reflected the navigation environment. We also found that our encoding models strongly reflected brain activity in the inferior parietal gyrus and precuneus, and that details of future scenes were locally represented in the superior prefrontal gyrus and temporal pole. Furthermore, a decoder associated with the encoding models accurately predicted future scene views in both passive and active navigation. These results suggest that the human brain uses scene anticipation, mediated especially by parietal and medial prefrontal cortical areas, as a robust and effective navigation processing.

Neural correlates of emotion perception depending on culture and gaze direction

A person’s cultural background as well as their gaze direction have been identified as relevant factors that influence the behavioural and neural processing of emotional expressions. However, research on their combined influence is sparse. Here, we manipulated the cultural background and gaze direction of emotion-encoders to investigate the interaction of both factors during the neural processing of emotions. Stimuli consisted of short video sequences showing faces that displayed either direct or averted gaze, expressed either anger or happiness, and represented either cultural in-group (European faces) or cultural out-group members (Asian faces). While undergoing functional magnetic resonance imaging, a group of German participants rated the stimuli with respect to their valence. Results revealed that when anger was expressed with direct gaze, more activation was found in the dorsomedial and dorsolateral prefrontal cortices in response to cultural out-group compared to in-group members. However, when anger was expressed with averted gaze, activity increased in the amygdala and the striatum in response to cultural in-group compared to out-group members. With respect to happiness, enhanced neural activation in medial and lateral prefrontal cortical areas was associated with the processing of cultural in-group compared to out-group members expressing happiness with direct gaze. These findings indicate a complex interplay between culture, gaze direction and the valence of emotions.

Default Mode Network Connectivity in Stroke Patients

The pathophysiology of episodic memory dysfunction after infarction is not completely understood. It has been suggested that infarctions located anywhere in the brain can induce widespread effects causing disruption of functional networks of the cortical regions. The default mode network, which includes the medial temporal lobe, is a functional network that is associated with episodic memory processing. We investigated whether the default mode network activity is reduced in stroke patients compared to healthy control subjects in the resting state condition. We assessed the whole brain network properties during resting state functional MRI in 21 control subjects and 20 ‘first-ever’ stroke patients. Patients were scanned 9–12 weeks after stroke onset. Stroke lesions were located in various parts of the brain. Independent component analyses were conducted to identify the default mode network and to compare the group differences of the default mode network. Furthermore, region-of-interest based analysis was performed to explore the functional connectivity between the regions of the default mode network. Stroke patients performed significantly worse than control subjects on the delayed recall score on California verbal learning test. We found decreased functional connectivity in the left medial temporal lobe, posterior cingulate and medial prefrontal cortical areas within the default mode network and reduced functional connectivity between these regions in stroke patients compared with controls. There were no significant volumetric differences between the groups. These results demonstrate that connectivity within the default mode network is reduced in ‘first-ever’ stroke patients compared to control subjects. This phenomenon might explain the occurrence of post-stroke cognitive dysfunction in stroke patients.

The rat prefrontostriatal system analyzed in 3D: evidence for multiple interacting functional units.

Previous studies in monkeys disclosed a specific arrangement of corticostriatal projections. Prefrontal and premotor areas form dense projection fields surrounded by diffuse terminal areas extending outside the densely innervated region and overlapping with projections from other areas. In this study, the mode of prefrontostriatal innervation was analyzed in rats using a 3D approach. Following injections of tracers in defined cortical areas, 3D maps from individual cases were elaborated and combined into a global 3D map allowing us to define putative overlaps between projection territories. In addition to providing a detailed 3D mapping of the topographic representation of prefrontal cortical areas in the rat striatum, the results stress important similarities between the rodent and primate prefrontostriatal projections. They share the dual pattern of focal and diffuse corticostriatal projections. Moreover, besides segregated projections consistent with parallel processing, the interweaving of projection territories establishes specific patterns of overlaps spatially organized along the dorsoventral, mediolateral, and anteroposterior striatal axis. In particular, the extensive striatal projection fields from the prelimbic and anterior cingulate areas, which partly overlap the terminal fields from medial, orbital, and lateral prefrontal cortical areas, provide putative domains of convergence for integration between reward, cognitive, and motor processes.

Recent advances in sleep physiology of interest to psychoanalysis

Evidence from recent electroencephalographic and magnetoencephalographic sleep studies is reviewed in relation to consciousness and dreams, two fundamental issues in psychoanalytic theory and practice. The rich dynamics of the macro- and microstructure of human sleep indicate specific brain disintegrating mechanisms as underlying the loss and alteration of consciousness in non-rapid eye movement (NREM) and REM sleep, respectively. Transient state changes and dynamic interactions between elements of sleep graphoelements (i.e. K-complexes and spindles) are described; these, beyond their involvement in controlling consciousness level, may support the consolidation or modification of therapeutic experiences. Higher powers than in awake-state gamma-band electrographic activity (known to underlie cognitive processes), which we observed in specific medial prefrontal cortical areas, are proposed to support content in dreaming (REM) and mentation (NREM). These areas lie in remarkably close proximity to the “default system” and “theory of mind” areas, which may be parts of the neural correlates of intrapsychic and intersubjective processes. Specific activations of limbic circuits were observed in REM sleep in consistency with the emotional content of dreams. Current brain imaging technology in sleep studies offers new opportunities to explore the mechanisms underlying consciousness and dreaming, a unique area of convergence between biology and psychology.

Altered Processing of Contextual Information during Fear Extinction in PTSD: An fMRI Study

Medial prefrontal cortical areas have been hypothesized to underlie altered contextual processing in posttraumatic stress disorder (PTSD). We investigated brain signaling of contextual information in this disorder. Eighteen PTSD subjects and 16 healthy trauma-exposed subjects underwent a two-day fear conditioning and extinction paradigm. On day 1, within visual context A, a conditioned stimulus (CS) was followed 60% of the time by an electric shock (conditioning). The conditioned response was then extinguished (extinction learning) in context B. On day 2, recall of the extinction memory was tested in context B. Skin conductance response (SCR) and functional magnetic resonance imaging (fMRI) data were collected during context presentations. There were no SCR group differences in any context presentation. Concerning fMRI data, during late conditioning, when context A signaled danger, PTSD subjects showed dorsal anterior cingulate cortical (dACC) hyperactivation. During early extinction, when context B had not yet fully acquired signal value for safety, PTSD subjects still showed dACC hyperactivation. During late extinction, when context B had come to signal safety, they showed ventromedial prefrontal cortex (vmPFC) hypoactivation. During early extinction recall, when context B signaled safety, they showed both vmPFC hypoactivation and dACC hyperactivation. These findings suggest that PTSD subjects show alterations in the processing of contextual information related to danger and safety. This impairment is manifest even prior to a physiologically-measured, cue-elicited fear response, and characterized by hypoactivation in vmPFC and hyperactivation in dACC.

Distinct patterns of brain activity in young carriers of the APOE -ε4 allele

The APOE epsilon4 allele is a risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE epsilon4-carriers and 18 matched noncarriers (age range: 20-35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased "default mode network" (involving retrosplenial, medial temporal, and medial-prefrontal cortical areas) coactivation in epsilon4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in epsilon4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE epsilon4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.

Resection of the Medial Temporal Lobe Disconnects the Rostral Superior Temporal Gyrus from Some of its Projection Targets in the Frontal Lobe and Thalamus

Auditory memory in the monkey does not appear to extend beyond the limits of working memory. It is therefore surprising that this ability is impaired by medial temporal lobe (MTL) resections, because such lesions spare working memory in other sensory modalities. To determine whether MTL ablations might have caused the auditory deficit through inadvertent transection of superior temporal gyrus (STG) projections to its downstream targets, and, if so, which targets might have been compromised, we injected anterograde tracer (biotinylated dextran amine) in the STG of both the normal and MTL-lesioned hemispheres of split-brain monkeys. Interhemispheric comparison of label failed to show any effect of the MTL ablation on efferents from caudal STG, which projects to the inferior prefrontal convexity. However, the ablation did consistently interrupt the normally dense projections from rostral STG to both the ventral medial prefrontal cortex and medial thalamic nuclei. The findings support the possibility that the auditory working memory deficit after MTL ablation is due to transection of downstream auditory projections, and indicate that the candidate structures for mediating auditory working memory are the ventral medial prefrontal cortical areas, the medial thalamus, or both.

Afferent Connections to the Rostrolateral Part of the Periaqueductal Gray: A Critical Region Influencing the Motivation Drive to Hunt and Forage

Previous studies have shown that a particular site in the periaqueductal gray (PAG), the rostrolateral PAG, influences the motivation drive to forage or hunt. To have a deeper understanding on the putative paths involved in the decision-making process between foraging, hunting, and other behavioral responses, in the present investigation, we carried out a systematic analysis of the neural inputs to the rostrolateral PAG (rlPAG), using Fluorogold as a retrograde tracer. According to the present findings, the rlPAG appears to be importantly driven by medial prefrontal cortical areas involved in controlling attention-related and decision-making processes. Moreover, the rlPAG also receives a wealth of information from different amygdalar, hypothalamic, and brainstem sites related to feeding, drinking, or hunting behavioral responses. Therefore, this unique combination of afferent connections puts the rlPAG in a privileged position to influence the motivation drive to choose whether hunting and foraging would be the most appropriate adaptive responses.

Medial prefrontal cortex supports recollection, but not familiarity, in the rat.

There is continuing controversy about the extent to which the rodent medial prefrontal cortical area (mPFC) is functionally homologous to the dorsolateral prefrontal cortex in humans and nonhuman primates. Previous studies have compared the effects of mPFC lesions in rats to those of dorsolateral prefrontal lesions in working memory, strategy switching, and temporal ordering. None, however, has examined the role of the rodent mPFC in recognition memory, wherein, in humans, dorsolateral prefrontal damage results in a deficit in source monitoring resulting in impaired recollection. In the present study, we examined recognition memory in rats with bilateral mPFC lesions (prelimbic/infralimbic regions; ibotenic acid) using a variant of a non-match-to-sample task with manipulations of response bias that allowed for a signal detection analysis that distinguishes recollection and familiarity contributions to recognition memory. Animals with medial prefrontal lesions had a modest overall deficit in recognition with no general change in their tendency to elicit "old" or "new" responses. Signal detection analyses indicated that rats with mPFC damage had a curvilinear and symmetrical receiver operating characteristic (ROC) curve, compared with a curvilinear and asymmetrical ROC curve in control subjects, indicating that mPFC damage severely reduced recollection-based performance, while sparing familiarity. The recollection failure was associated with an impaired ability to reject new items (increased false alarm rate), whereas the identification of old items (hit rate) was normal. This pattern of findings is similar to that observed in humans with dorsolateral prefrontal damage and is complementary to the selective deficit in hit rate observed after hippocampal damage.

Double Dissociation of the Effects of Medial and Orbital Prefrontal Cortical Lesions on Attentional and Affective Shifts in Mice

Many neuropsychiatric diseases are associated with cognitive rigidity linked to prefrontal dysfunction. For example, schizophrenia and Parkinson's disease are associated with performance deficits on the Wisconsin Card Sorting Test, which evaluates attentional set shifting. Although the genetic underpinnings of these disorders can be reproduced in mice, there are few models for testing the functional consequences. Here, we demonstrate that an analog of the Wisconsin Card Sorting Test, developed in marmosets and recently adapted to rats, is a behavioral model of prefrontal function in mice. Systematic analysis demonstrated that formation of the attentional set in mice is dependent on the number of problem sets. We found that mice, like rats and primates, exhibit both affective and attentional sets, and these functions are disrupted by neurotoxic damage to orbitofrontal and medial prefrontal cortical areas, respectively. These data are identical to studies in rats and similar to the deficits reported after prefrontal damage in a comparable task in marmosets. These results provide a behavioral model to assess prefrontal function in mice.

Prefrontal Hypoactivation and Recovery in Insomnia

Although subjective complaints about daytime cognitive functioning are an essential symptom of chronic insomnia, abnormalities in functional brain activation have not previously been investigated. This study was designed to investigate functional brain activation differences as a possible result of chronic insomnia, and the reversibility of these differences after nonmedicated sleep therapy. Insomniacs and carefully matched controls underwent functional magnetic resonance imaging (fMRI) scanning during the performance of a category and a letter fluency task. Insomniacs were randomly assigned to either a 6-week period of nonpharmacological sleep therapy or a wait list period, after which fMRI scanning was repeated using parallel tasks. Task-related brain activation and number of generated words were considered as outcome measures. The outpatient sleep clinic of the VU University Medical Center, Department of Clinical Neurophysiology; fMRI was performed at the Department of Radiology. Twenty-one patients suffering from chronic insomnia and 12 matched controls. Nonpharmacological sleep therapy for 6 weeks, consisting of cognitive behavioral therapy, body temperature and bright light interventions, sleep hygiene, and physical activity counseling. Compared to controls, insomnia patients showed hypoactivation of the medial and inferior prefrontal cortical areas (Brodmann Area 9, 44-45), which recovered after sleep therapy but not after a wait list period. Insomnia interferes in a reversible fashion with activation of the prefrontal cortical system during daytime task performance.

Recent advances in compulsive hoarding

Compulsive hoarding is a common and often disabling neuropsychiatric disorder. This article reviews the conceptualization, phenomenology, diagnosis, etiology, neurobiology, and treatment of compulsive hoarding. Compulsive hoarding is part of a discrete clinical syndrome that includes difficulty discarding, urges to save, excessive acquisition, indecisiveness, perfectionism, procrastination, disorganization, and avoidance. It was thought to be part of obsessive-compulsive disorder or obsessive-compulsive personality disorder, but recent evidence indicates that it should be classified as a separate disorder with its own diagnostic criteria. Compulsive hoarding is a genetically discrete, strongly heritable phenotype. Neuroimaging and neuropsychological studies are elucidating its neurobiology, implicating dysfunction of ventral and medial prefrontal cortical areas that mediate decision-making, attention, and emotional regulation. Effective treatments include pharmacotherapy and cognitive-behavioral therapy. More research will be required to determine the prevalence, etiology, and pathophysiology of compulsive hoarding and to develop better treatments.

Neurobiology and Treatment of Compulsive Hoarding

Compulsive hoarding is a common and often disabling neuropsychiatric disorder. This article reviews the phenomenology, etiology, neurobiology, and treatment of compulsive hoarding. Compulsive hoarding is part of a discrete clinical syndrome that includes difficulty discarding, urges to save, clutter, excessive acquisition, indecisiveness, perfectionism, procrastination, disorganization, and avoidance. Epidemiological and taxometric studies indicate that compulsive hoarding is a separate but related obsessive-compulsive spectrum disorder that is frequently comorbid with obsessive-compulsive disorder (OCD). Compulsive hoarding is a genetically discrete, strongly heritable phenotype. Neuroimaging and neuropsychological studies indicate that compulsive hoarding is neurobiologically distinct from OCD and implicate dysfunction of the anterior cingulate cortex and other ventral and medial prefrontal cortical areas that mediate decision-making, attention, and emotional regulation. Effective treatments for compulsive hoarding include pharmacotherapy and cognitive-behavioral therapy. More research will be required to determine the etiology and pathophysiology of compulsive hoarding, and to develop better treatments for this disorder.

Positron emission tomography study of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without comorbid lifetime alcohol dependence

This is the first study contrasting regional glucose metabolic rate (rCMRglu) responses to a serotonergic challenge in major depressive disorder (MDD) with and without comorbid alcohol dependence. In a university hospital, patients with MDD without a history of alcohol dependence (MDD only) and patients with MDD and comorbid alcohol dependence (MDD/ALC) were enrolled in this study. Subjects with comorbid borderline personality disorder were excluded. A bolus injection of approximately 5 mCi of 18fluorodeoxyglucose was administered 3 h after the administration of placebo or fenfluramine. We found an anterior medial prefrontal cortical area where MDD/ALC subjects had more severe hypofrontality than MDD only patients. This area encompassed the left medial frontal and left and right anterior cingulate gyri. This group difference disappeared after fenfluramine administration. The fact that the observed group difference disappeared after the fenfluramine challenge suggests that serotonergic mechanisms play a role in the observed differences between the groups.

Face memory and its disorders.

Face recognition is an essential biologic and social skill. Accurate recognition depends on the ability to encode, store, and retrieve distinct memory representations for the faces of countless individuals encountered in everyday life. In addition, face memory records must be integrated with specific biographic and name information in order to allow the recognition of each person's unique identity. Converging evidence from functional imaging, cortical electrical recording, and neuropsychologic studies suggests that face memory operations in the human brain are mediated by a distributed neural system. Components of this network include specialized memory storage sites within temporal neocortex that interact with medial temporal lobe and prefrontal cortical areas during face memory encoding and retrieval. Selective damage to these neuroanatomic regions gives rise to face recognition disorders characterized by memory loss or memory distortion.