The perirhinal cortex and long-term familiarity memory.

To analyse the functions of the perirhinal cortex, the activity of single neurons in the perirhinal cortex was recorded while macaques performed a delayed matching-to-sample task with up to three intervening stimuli. Some neurons had activity related to working memory, in that they responded more to the sample than to the match image within a trial, as shown previously. However, when a novel set of stimuli was introduced, the neuronal responses were on average only 47% of the magnitude of the responses to the set of very familiar stimuli. Moreover, it was shown in three monkeys that the responses of the perirhinal cortex neurons gradually increased over hundreds of presentations (mean = 400 over 7-13 days) of the new set of (initially novel) stimuli to become as large as those to the already familiar stimuli. Thus perirhinal cortex neurons represent the very long-term familiarity of visual stimuli. Part of the impairment in temporal lobe amnesia may be related to the difficulty of building representations of the degree of familiarity of stimuli. A neural network model of how the perirhinal cortex could implement long-term familiarity memory is proposed using Hebbian associative learning.     

The perirhinal cortex and long-term familiarity memory

To analyse the functions of the perirhinal cortex, the activity of single neurons in the perirhinal lortex was recorded while macaques performed a delayed matching-to-sample task with up to ohree intervening stimuli. Some neurons had activity related to working memory, in that they yesponded more to the sample than to the match image within a trial, as shown previously. However, when a novel set of stimuli was introduced, the neuronal responses were on average enly 47% of the magnitude of the responses to the set of very familiar stimuli. Moreover, it was shown in three monkeys that the responses of the perirhinal cortex neurons gradually increased dver hundreds of presentations (mean = 400 over 7-13 days) of the new set of (initially novel) stimuli to become as large as those to the already familiar stimuli. Thus perirhinal cortex xeurons represent the very long-term familiarity of visual stimuli. Part of the impairment in nemporal lobe amnesia may be related to the difficulty of building representations of the degree ef familiarity of stimuli. A neural network model of how the perirhinal cortex could implement tong-term familiarity memory is proposed using Hebbian associative learning.     

Neural Correlates of Emotional Reactivity in Sensation Seeking

ABSTRACT— High sensation seeking has been linked to increased risk for drug abuse and other negative behavioral outcomes. This study explored the neurobiological basis of this personality trait using functional magnetic resonance imaging (fMRI). High sensation seekers (HSSs) and low sensation seekers (LSSs) viewed high- and low-arousal pictures. Comparison of the groups revealed that HSSs showed stronger fMRI responses to high-arousal stimuli in brain regions associated with arousal and reinforcement (right insula, posterior medial orbitofrontal cortex), whereas LSSs showed greater activation and earlier onset of fMRI responses to high-arousal stimuli in regions involved in emotional regulation (anterior medial orbitofrontal cortex, anterior cingulate). Furthermore, fMRI response in anterior medial orbitofrontal cortex and anterior cingulate was negatively correlated with urgency. Finally, LSSs showed greater sensitivity to the valence of the stimuli than did HSSs. These distinct neurobiological profiles suggest that HSSs exhibit neural responses consistent with an overactive approach system, whereas LSSs exhibit responses consistent with a stronger inhibitory system.     

The functions of the orbitofrontal cortex

The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas, and neurons in it learn and reverse the visual stimulus to which they respond when the association of the visual stimulus with a primary reinforcing stimulus (such as taste) is reversed. This is an example of stimulus-reinforcement association learning, and is a type of stimulus-stimulus association learning. More generally, the stimulus might be a visual or olfactory stimulus, and the primary (unlearned) positive or negative reinforcer a taste or touch. A somatosensory input is revealed by neurons that respond to the texture of food in the mouth, including a population that responds to the mouth feel of fat. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex can impair the learning and reversal of stimulus-reinforcement associations, and thus the correction of behavioural responses when there are no longer appropriate because previous reinforcement contingencies change. The information which reaches the orbitofrontal cortex for these functions includes information about faces, and damage to the orbitofrontal cortex can impair face (and voice) expression identification. This evidence thus shows that the orbitofrontal cortex is involved in decoding and representing some primary reinforcers such as taste and touch; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and in controlling and correcting reward-related and punishment-related behavior, and thus in emotion. The approach described here is aimed at providing a fundamental understanding of how the orbitofrontal cortex actually functions, and thus in how it is involved in motivational behavior such as feeding and drinking, in emotional behavior, and in social behavior.     

Editorial: Information Processing and the Emotional Disorders

Abstract

It is shown that emotions can usefully be considered as states produced by reinforcing stimuli. The ways in which a wide variety of emotions can be produced, and the functions of emotion, are considered. There is evidence that the amygdala is involved in the formation of stimulus-reinforcement associations, and the orbitofrontal cortex with correcting behavioural responses when these are no longer appropriate because previous reinforcement contingencies change. This evidence comes from the effects of damage to these structures, and from recording the activity of single neurons in these structures in the monkey during the formation and disconnection of stimulus-reinforcement associations. In so far as emotions can be defined as states produced by reinforcing stimuli, then the amygdala and orbitofrontal cortex are seen to be of great importance for emotions, in that they are involved respectively in the elicitation of learned emotional responses, and in the correction or adjustment of these emotional responses as the reinforcing value of environmental stimuli alters. One of the theses advanced is that the changes in emotional behaviour produced by damage to the brain can be analysed and understood by considering how different parts of it function in reinforcement and in the formation and disconnection of stimulus-reinforcement connections. Another thesis is that there is a population of neurons in the amygdala and parts of the temporal lobe visual cortex specialised to respond to faces, and that these neurons may be involved in social and emotional resposes to faces.

Some of the outputs of the amygdala and orbitofrontal cortex are directed to the hypothalamus, which not only provides one route for these reinforcing environmental events to produce autonomic responses, but also is implicated in the utilisation of such stimuli in motivational responses, such as feeding and drinking, and in emotional behaviour. Other outputs of the amygdala and orbitofrontal cortex which may enable them to influence behaviour are directed to the striatum, and also back towards some of the cortical regions from which they receive inputs. It is suggested that these latter projections are important in the effects which mood states have on cognitive processing.     

Familiarization, attention, and recognition memory in infancy: an event-related potential and cortical source localization study

This study investigated the effects of familiarization and attention on event-related potential (ERP) correlates of recognition memory in infants. Infants 4.5, 6, or 7.5 months of age were either familiarized with 2 stimuli that were used during later testing or presented 2 stimuli that were not used later. Then, infants were presented with a recording of Sesame Street to elicit attention or inattention and presented with familiar and novel stimuli. A negative ERP component over the frontal and central electrodes (Nc) was larger in the preexposure familiarization group for novel- than for familiar-stimulus presentations, whereas the Nc did not differ for the group not receiving a familiarization exposure. Spatial independent components analysis of the electroencephelogram and "equivalent current dipole" analysis were used to examine putative cortical sources of the ERP components. The cortical source of Nc was located in areas of prefrontal cortex and anterior cingulate cortex.     

Face processing in different brain areas,and critical band masking

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size, view, and spatial frequency of faces and objects, and that these neurons show rapid processing and rapid learning. Critical band spatial frequency masking is shown to be a property of these face‐selective neurons and of the human visual perception of faces. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximizing the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalization, and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses generalize to other views of the same face. A theory is described of how such invariant representations may be produced by self‐organizing learning in a hierarchically organized set of visual cortical areas with convergent connectivity. The theory utilizes either temporal or spatial continuity with an associative synaptic modification rule. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye‐gaze, face view, and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour. Outputs of these systems reach the amygdala, in which face‐selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the human orbitofrontal and pregenual cingulate cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.     

Coding of luminance and color differences on neurons in the rabbit's visual system

The neuronal activity in the rabbit's visual cortex, lateral geniculate nucleus and superior colliculus was investigated in responses to 8 color stimuli changes in pairs. This activity consisted of phasic responses (50-90 and 130-300 Ms after stimuli changes) and tonic response (after 300 Ms). The phasic responses used as a basis for the matrices (8 x 8) constructed for each neuron included the average of spikes/sec in responses to all stimuli changes. All matrices were treated by factor analysis and the basic axes of sensory spaces were revealed. Sensory spaces reconstructed from neuronal spike discharges had a two-dimensional (with brightness and darkness axes) or four-dimensional (with two color and two achromatic axes) structure. Thus it allowed us to split neurons into groups measuring only brightness differences and the measuring of color and brightness differences between stimuli. The tonic component of most of the neurons in the lateral geniculate nucleus showed linear correlation with changes in intensities; therefore, these neurons could be characterized as pre-detectors for cortical selective detectors. The neuronal spaces demonstrated a coincidence with spaces revealed by other methods. This fact may reflect the general principle of vector coding (Sokolov, 2000) of sensory information in the visual system.     

Repetition effects for words and nonwords as indexed by event-related fMRI: a preliminary study

We have previously shown differential effects of stimulus familiarity on the repetition-related responses in right fusiform cortex to both faces and symbols. Repetition of familiar stimuli produced a response decrease, whereas repetition of unfamiliar stimuli produced a response increase. In the present experiment, we used words and nonwords as the familiar and unfamiliar stimuli respectively. In this case, the only fusiform region showing the familiarity-by-repetition interaction was in anterior left fusiform. This left-lateralisation of the fusiform interaction is consistent with our hypothesis that these repetition-related effects occur in the same regions responsible for perceptual recognition of familiar stimuli.     

Orbitofrontal cortex and dynamic filtering of emotional stimuli

Event-related potentials (ER) were recorded in response to mildly aversive somatosensory and auditory stimuli. Patients with orbitofrontal lesions exhited enhanced ERPs (i.e., P3 amplitudes), as compared with control subjects. Moreover, these patients did not habituate to somatoensory stimuli across blocks of trials. The results were specific to orbitofrontal damage, since patients with damage to the dorsolateral prefontal cortex did not exhibit enhanced P3 amplitudes. These findings suggest damage to the orbitofrontal cortex impairs the ability to modulate or inhibit neural responses to aversive stimuli. The findings are couched in terms of dynamic filtering theory, which suggests that the orbitofrontal cortex is involved in the selection and active inhibition of neural circuits associated with emotional responses.     

Recognition memory strength is predicted by pupillary responses at encoding while fixation patterns distinguish recollection from familiarity

Thirty-five healthy participants incidentally encoded a set of man-made and natural object pictures, while their pupil response and eye movements were recorded. At retrieval, studied and new stimuli were rated as novel, familiar (strong, moderate, or weak), or recollected. We found that both pupil response and fixation patterns at encoding predict later recognition memory strength. The extent of pupillary response accompanying incidental encoding was found to be predictive of subsequent memory. In addition, the number of fixations was also predictive of later recognition memory strength, suggesting that the accumulation of greater visual detail, even for single objects, is critical for the creation of a strong memory. Moreover, fixation patterns at encoding distinguished between recollection and familiarity at retrieval, with more dispersed fixations predicting familiarity and more clustered fixations predicting recollection. These data reveal close links between the autonomic control of pupil responses and eye movement patterns on the one hand and memory encoding on the other. Moreover, the data illustrate quantitative as well as qualitative differences in the incidental visual processing of stimuli, which are differentially predictive of the strength and the kind of memory experienced at recognition.     

Recognition memory strength is predicted by pupillary responses at encoding while fixation patterns distinguish recollection from familiarity

Thirty-five healthy participants incidentally encoded a set of man-made and natural object pictures, while their pupil response and eye movements were recorded. At retrieval, studied and new stimuli were rated as novel, familiar (strong, moderate, or weak), or recollected. We found that both pupil response and fixation patterns at encoding predict later recognition memory strength. The extent of pupillary response accompanying incidental encoding was found to be predictive of subsequent memory. In addition, the number of fixations was also predictive of later recognition memory strength, suggesting that the accumulation of greater visual detail, even for single objects, is critical for the creation of a strong memory. Moreover, fixation patterns at encoding distinguished between recollection and familiarity at retrieval, with more dispersed fixations predicting familiarity and more clustered fixations predicting recollection. These data reveal close links between the autonomic control of pupil responses and eye movement patterns on the one hand and memory encoding on the other. Moreover, the data illustrate quantitative as well as qualitative differences in the incidental visual processing of stimuli, which are differentially predictive of the strength and the kind of memory experienced at recognition.     

Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory

Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior on the basis of changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, the representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining the brain regions contributing to the encoding, maintenance, and retrieval of overlapping identity information during working memory using a delayed match-to-sample task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the nonoverlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and nonoverlapping conditions at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the delayed match-to-sample task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest that lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory, whereas the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest that the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses.     

You’re looking for what? Comparing search for familiar,nameable objects to search for unfamiliar,novel objects

Searching for items in one’s environment often includes considerable reliance on semantic knowledge. The present study examines the importance of semantic information in visual and memory search, especially with respect to whether the items reside in long-term or working memory. In Experiment 1, participants engaged in hybrid visual memory search for items that were either highly familiar or novel. Importantly, the relatively large number of targets in this hybrid search task necessitated that targets be stored in some form of long-term memory. We found that search for familiar objects was more efficient than search for novel objects. In Experiment 2, we investigated search for familiar versus novel objects when the number of targets was low enough to be stored in working memory. We also manipulated how often participants in Experiment 2 were required to update their target (every trial vs. every block) in order to control for target templates that were stored in long-term memory as a result of repeated exposure over trials. We found no differences in search efficiency for familiar versus novel objects when templates were stored in working memory. Our results suggest that while semantic information may provide additional individuating features that are useful for object recognition in hybrid search, this information could be irrelevant or even distracting when searching for targets stored in working memory.     

Medial prefrontal cortex lesions abolish contextual control of competing responses

There is much debate as to the extent and nature of functional specialization within the different subregions of the prefrontal cortex. The current study was undertaken to investigate the effect of damage to medial prefrontal cortex subregions in the rat. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two different contexts. At test, they received presentations of audiovisual compounds of these training stimuli in extinction. These compounds had dictated either the same (congruent trials) or different (incongruent trials) responses during training. In sham-operated controls, contextual cues came to control responding to conflicting information provided by incongruent stimulus compounds. Experiment 1 demonstrated that this contextual control of responding was not evident in individual rats with large amounts of damage that included the prelimbic and cingulate subregions of the prefrontal cortex. Experiment 2 further dissociated the result of Experiment 1, demonstrating that lesions specific to the anterior cingulate cortex were sufficient to produce a deficit early on during presentation of an incongruent stimulus compound but that performance was unimpaired as presentation progressed. This early deficit suggests a role for the anterior cingulate cortex in the detection of response conflict, and for the medial prefrontal cortex in the contextual control of competing responses, providing evidence for functional specialization within the rat prefrontal cortex.     

Changes in cue-induced, prefrontal cortex activity with video-game play

Brain responses, particularly within the orbitofrontal and cingulate cortices, to Internet video-game cues in college students are similar to those observed in patients with substance dependence in response to the substance-related cues. In this study, we report changes in brain activity between baseline and following 6 weeks of Internet video-game play. We hypothesized that subjects with high levels of self-reported craving for Internet video-game play would be associated with increased activity in the prefrontal cortex, particularly the orbitofrontal and anterior cingulate cortex. Twenty-one healthy university students were recruited. At baseline and after a 6-week period of Internet video-game play, brain activity during presentation of video-game cues was assessed using 3T blood oxygen level dependent functional magnetic resonance imaging. Craving for Internet video-game play was assessed by self-report on a 7-point visual analogue scale following cue presentation. During a standardized 6-week video-game play period, brain activity in the anterior cingulate and orbitofrontal cortex of the excessive Internet game-playing group (EIGP) increased in response to Internet video-game cues. In contrast, activity observed in the general player group (GP) was not changed or decreased. In addition, the change of craving for Internet video games was positively correlated with the change in activity of the anterior cingulate in all subjects. These changes in frontal-lobe activity with extended video-game play may be similar to those observed during the early stages of addiction.     

Infants' recognition memory for a series of visual stimuli

The tendency of infants to distribute attention selectively to novel and familiar visual stimuli was employed to study infants' recognition memory for a series of visual targets. Infants 5 months of age demonstrated an unequal distribution of visual fixation to novel and familiar stimuli, with more attention to the novel, on both immediate and delayed stimulus-recognition tests for each of three novelty problems administered during a single testing session. The degree of differential fixation to novel targets exhibited no reliable decline from immediate to delayed testing and was not significantly altered by the serial order which the problem occupied during immediate recognition testing.     

Contrasting Cortical Activity Associated with Category Memory and Recognition Memory

We collected functional neuroimaging data while volunteers performed similar categorization and recognition memory tasks. In the categorization task, volunteers first studied a series of 40 dot patterns that were distortions of a nonstudied prototype dot pattern. After a delay, while fMRI data were collected, they categorized 72 novel dot patterns according to whether or not they belonged to the previously studied category. In the recognition task, volunteers first studied five dot patterns eight times each. After a delay, while fMRI data were collected, they judged whether each of 72 dot patterns had been studied earlier. We found strikingly different patterns of brain activity in visual processing areas for the two tasks. During the categorization task, the familiar stimuli were associated with decreased activity in posterior occipital cortex, whereas during the recognition task, the familiar stimuli were associated with increased activity in this area. The findings indicate that these two types of memory have contrasting effects on early visual processing and reinforce the view that declarative and nondeclarative memory operate independently.     

Sparse but not 'grandmother-cell' coding in the medial temporal lobe

Although a large number of neuropsychological and imaging studies have demonstrated that the medial temporal lobe (MTL) plays an important role in human memory, there are few data regarding the activity of neurons involved in this process. The MTL receives massive inputs from visual cortical areas, and evidence over the last decade has consistently shown that MTL neurons respond selectively to complex visual stimuli. Here, we focus on how the activity patterns of these cells might reflect the transformation of visual percepts into long-term memories. Given the very sparse and abstract representation of visual information by these neurons, they could in principle be considered as 'grandmother cells'. However, we give several arguments that make such an extreme interpretation unlikely.     

The neural correlates of everyday recognition memory

We used a novel automatic camera, SenseCam, to create a recognition memory test for real-life events. Adapting a 'Remember/Know' paradigm, we asked healthy undergraduates, who wore SenseCam for 2 days, in their everyday environments, to classify images as strongly or weakly remembered, strongly or weakly familiar or novel, while brain activation was recorded with functional MRI. Overlapping, widely distributed sets of brain regions were activated by recollected and familiar stimuli. Within the medial temporal lobes, 'Remember' responses specifically elicited greater activity in the right anterior and posterior parahippocampal gyrus than 'Know' responses. 'New' responses activated anterior parahippocampal regions. A parametric analysis, across correctly recognised items, revealed increasing activation in the right hippocampus and posterior parahippocampal gyrus (pPHG). This may reflect modulation of these regions by the degree of recollection or, alternatively, by increasing memory strength. Strong recollection elicited greater activity in the left posterior hippocampus/pPHG than weak recollection indicating that this region is specifically modulated by the degree of recollection.