Interactions between the Orbitofrontal Cortex and the Hippocampal Memory System during the Storage of Long-Term Memory

It has been proposed that long-term declarative memories are ultimately stored through interactions between the hippocampal memory system and the neocortical association areas that initially processed the to-be-stored information. One association neocortex, the orbitofrontal cortex (OFC) is strongly and reciprocally connected with the hippocampal memory system and plays an important role in odor recognition memory in rats. We will report data from two studies: one that examined the firing of neurons in a task dependent on the parahippocampal region (PHR; including the perirhinal, postrhinal, and entrorhinal cortices), and one examined the firing of OFC neurons performing a task that is presumably dependent on the hippocampus. In the first study, we examined the role of OFC neurons in the continuous odor-guided nonmatching to sample task. While the firing of neurons in the PHR and OFC are similar in this task, there are several notable differences that are consistent with the idea that OFC is a high-order association cortex which interacts extensively with the PHR to store declarative memories. In the second study, we characterized the firing patterns of neurons in the OFC rats performing a passive, 8-odor-sequence memory task. Most interesting were neurons that fired selectively in anticipation of specific odors. We found that hippocampal lesions abolished the anticipatory firing in OFC, suggesting that these anticipatory responses (memory) were in fact dependent on the hippocampus, further supporting the view that the OFC interacts with the hippocampal memory system to store long-term, declarative memories.

SETH J. RAMUS, JENA B DAVIS, RACHEL J DONAHUE, CLAIRE B DISCENZA, and ALISSA A. WAITE.
Interactions between the Orbitofrontal Cortex and the Hippocampal Memory System during the Storage of Long-Term Memory.
Ann NY Acad Sci 2007 1121: 216-231.

http://www.annalsnyas.org/cgi/content/abstract/1121/1/216

Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task

The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural activity was recorded during an olfactory discrimination "go"/"no-go" task in which five different odor stimuli were predictive for various amounts of reward or an aversive reinforcer. Neural correlates related to both actual and expected reward magnitude were observed. Responses related to reward expectation occurred during the execution of the behavioral response toward the reward site and within a waiting period prior to reinforcement delivery. About one-half of these neurons demonstrated differential firing toward the different reward sizes. These data provide new and strong evidence that reward expectancy, regardless of reward magnitude, is coded by neurons of the rat OBFc, and are indicative for representation of quantitative information concerning expected reward. Moreover, neural correlates of reward expectancy appear to be distributed across both motor and nonmotor phases of the task.

van Duuren, Esther, Escamez, Francisco A. Nieto, Joosten, Ruud N.J.M.A., Visser, Rein, Mulder, Antonius B., Pennartz, Cyriel M.A.
Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task.
Learn. Mem. 2007 14: 446-456.

http://www.learnmem.org/cgi/content/abstract/14/6/446

Associative Encoding in Anterior Piriform Cortex versus Orbitofrontal Cortex during Odor Discrimination and Reversal Learning

Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex (OFC). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. To test this hypothesis, we recorded from neurons in OFC and anatomically related parts of the anterior piriform cortex (APC) in rats, learning and reversing novel odor discriminations. Findings in OFC were similar to what we have reported previously, with nearly all the cue-selective neurons exhibiting substantial plasticity during learning and reversal. Also, many of the cue-selective neurons were originally responsive in anticipation of the outcomes early in learning, thereby providing a single-unit representation of the cue-outcome associations. Some of these features were also evident in firing activity in APC, including some plasticity across learning and reversal. However, APC neurons failed to reverse cue selectivity when the associated outcome was changed, and the cue-selective population did not include neurons that were active prior to outcome delivery. Thus, although representations in APC are substantially more associative than expected in a purely sensory region, they do appear to be somewhat more constrained by the sensory features of the odor cues than representations in downstream areas of OFC.

Matthew R. Roesch , Thomas A. Stalnaker , and Geoffrey Schoenbaum.
Associative Encoding in Anterior Piriform Cortex versus Orbitofrontal Cortex during Odor Discrimination and Reversal Learning.
Cerebral Cortex Advance Access published on March 1, 2007, DOI 10.1093/cercor/bhk009. Cereb. Cortex 17: 643-652.

http://cercor.oxfordjournals.org/cgi/content/abstract/17/3/643

From Rule to Response: Neuronal Processes in the Premotor and Prefrontal Cortex

The ability to use abstract rules or principles allows behavior to generalize from specific circumstances (e.g., rules learned in a specific restaurant can subsequently be applied to any dining experience). Neurons in the prefrontal cortex (PFC) encode such rules. However, to guide behavior, rules must be linked to motor responses. We investigated the neuronal mechanisms underlying this process by recording from the PFC and the premotor cortex (PMC) of monkeys trained to use two abstract rules: "same" or "different." The monkeys had to either hold or release a lever, depending on whether two successively presented pictures were the same or different, and depending on which rule was in effect. The abstract rules were represented in both regions, although they were more prevalent and were encoded earlier and more strongly in the PMC. There was a perceptual bias in the PFC, relative to the PMC, with more PFC neurons encoding the presented pictures. In contrast, neurons encoding the behavioral response were more prevalent in the PMC, and the selectivity was stronger and appeared earlier in the PMC than in the PFC.

Jonathan D. Wallis, and Earl K. Miller.
From Rule to Response: Neuronal Processes in the Premotor and Prefrontal Cortex.
Neurophysiol 90: 1790-1806, 2003. First published doi:10.1152/jn.00086.2003.

http://jn.physiology.org/cgi/content/full/90/3/1790/

Integrating Orbitofrontal Cortex into Prefrontal Theory: Common Processing Themes across Species and Subdivisions

Currently, many theories highlight either representational memory or rule representation as the hallmark of prefrontal function. Neurophysiological findings in the primate dorsolateral prefrontal cortex indicate that both features may characterize prefrontal processing. Neurons in the dorsolateral prefrontal cortex encode information in working memory, and this information is represented when relevant to the rules governing performance in a task. In this review, we discuss recent reports of encoding in primate and rat orbitofrontal regions indicating that these features also characterize activity in the orbitofrontal subdivision of the prefrontal cortex. These data indicate that (1) neural activity in the orbitofrontal cortex links the current incentive value of reinforcers to cues, rather than representing the physical features of cues or associated reinforcers; (2) this incentive-based information is represented in the orbitofrontal cortex when it is relevant to the rules guiding performance in a task; and (3) incentive information is also represented in the orbitofrontal cortex in working memory during delays when neither the cues nor reinforcers are present. Therefore, although the orbitofrontal cortex appears to be uniquely specialized to process incentive or motivational information, it may be integrated into a more global framework of prefrontal function characterized by representational encoding of performance-relevant information.

Schoenbaum, Geoffrey, Setlow, Barry
Integrating Orbitofrontal Cortex into Prefrontal Theory: Common Processing Themes across Species and Subdivisions
Learn. Mem. 2001 8: 134-147

http://www.learnmem.org/cgi/content/full/8/3/134

An attractor network in the hippocampus: Theory and neurophysiology

A quantitative computational theory of the operation of the CA3 system as an attractor or autoassociation network is described. Based on the proposal that CA3–CA3 autoassociative networks are important for episodic or event memory in which space is a component (place in rodents and spatial view in primates), it has been shown behaviorally that the CA3 supports spatial rapid one-trial learning and learning of arbitrary associations and pattern completion where space is a component. Consistent with the theory, single neurons in the primate CA3 respond to combinations of spatial view and object, and spatial view and reward. Furthermore, single CA3 neurons reflect the recall of a place from an object in a one-trial object-place event memory task. CA3 neurons also reflect in their firing a memory of spatial view that is retained and updated by idiothetic information to implement path integration when the spatial view is obscured. Based on the computational proposal that the dentate gyrus produces sparse representations by competitive learning and via the mossy fiber pathway forces new representations on the CA3 during learning (encoding), it has been shown behaviorally that the dentate gyrus supports spatial pattern separation during learning, and that the mossy fiber system to CA3 connections are involved in learning but not in recall. The perforant path input to CA3 is quantitatively appropriate to provide the cue for recall in CA3. The concept that the CA1 recodes information from CA3 and sets up associatively learned back-projections to neocortex to allow subsequent retrieval of information to neocortex provides a quantitative account of the large number of hippocampo–neocortical back-projections.

Rolls, Edmund T.
An attractor network in the hippocampus: Theory and neurophysiology
Learn. Mem. 2007 14: 714-731.

http://www.learnmem.org/cgi/content/abstract/14/11/714

Specific Involvement of Human Parietal Systems and the Amygdala in the Perception of Biological Motion

To explore the extent to which functional systems within the human posterior parietal cortex and the superior temporal sulcus are involved in the perception of action, we measured cerebral metabolic activity in human subjects by positron emission tomography during the perception of simulations of biological motion with point-light displays. The experimental design involved comparisons of activity during the perception of goal-directed hand action, whole body motion, object motion, and random motion. The results demonstrated that the perception of scripts of goal-directed hand action implicates the cortex in the intraparietal sulcus and the caudal part of the superior temporal sulcus, both in the left hemisphere. By contrast, the rostrocaudal part of the right superior temporal sulcus and adjacent temporal cortex, and limbic structures such as the amygdala, are involved in the perception of signs conveyed by expressive body movements.

Eva Bonda, Michael Petrides, David Ostry, and Alan Evans
Specific Involvement of Human Parietal Systems and the Amygdala in the Perception of Biological Motion
J. Neurosci. 16: 3737-3744; doi:

http://www.jneurosci.org/cgi/content/full/16/11/3737

Orbitofrontal Cortex Encodes Willingness to Pay in Everyday Economic Transactions

An essential component of every economic transaction is a willingness-to-pay (WTP) computation in which buyers calculate the maximum amount of financial resources that they are willing to give up in exchange for the object being sold. Despite its pervasiveness, little is known about how the brain makes this computation. We investigated the neural basis of the WTP computation by scanning hungry subjects' brains using functional magnetic resonance imaging while they placed real bids for the right to eat different foods. We found that activity in the medial orbitofrontal cortex and in the dorsolateral prefrontal cortex encodes subjects' WTP for the items. Our results support the hypothesis that the medial orbitofrontal cortex encodes the value of goals in decision making.

Hilke Plassmann, John O'Doherty, and Antonio Rangel
Orbitofrontal Cortex Encodes Willingness to Pay in Everyday Economic Transactions
J. Neurosci. 27: 9984-9988; doi:10.1523/JNEUROSCI.2131-07.2007

http://www.jneurosci.org/cgi/content/abstract/27/37/9984

Learning-Related Facilitation of Rhinal Interactions by Medial Prefrontal Inputs

Much data suggests that hippocampal–medial prefrontal cortex (mPFC) interactions support memory consolidation. This process is thought to involve the gradual transfer of transient hippocampal-dependent memories to distributed neocortical sites for long-term storage. However, hippocampal projections to the neocortex involve a multisynaptic pathway that sequentially progresses through the entorhinal and perirhinal regions before reaching the neocortex. Similarly, the mPFC influences the hippocampus via the rhinal cortices, suggesting that the rhinal cortices occupy a strategic position in this network. The present study thus tested the idea that the mPFC supports memory by facilitating the transfer of hippocampal activity to the neocortex via an enhancement of entorhinal to perirhinal communication. To this end, we simultaneously recorded mPFC, perirhinal, and entorhinal neurons during the acquisition of a trace-conditioning task in which a visual conditioned stimulus (CS) was followed by a delay period after which a liquid reward was administered. At learning onset, correlated perirhinal-entorhinal firing increased in relation to mPFC activity, but with no preferential directionality, and only after reward delivery. However, as learning progressed across days, mPFC activity gradually enhanced rhinal correlations in relation to the CS as well, and did so in a specific direction: from entorhinal to perirhinal neurons. This suggests that, at late stages of learning, mPFC activity facilitates entorhinal to perirhinal communication. Because this connection is a necessary step for the transfer of hippocampal activity to the neocortex, our results suggest that the mPFC is involved in the slow iterative process supporting the integration of hippocampal-dependent memories into neocortical networks.

Rony Paz, Elizabeth P. Bauer, and Denis Paré
Learning-Related Facilitation of Rhinal Interactions by Medial Prefrontal Inputs
J. Neurosci. 27: 6542-6551; doi:10.1523/JNEUROSCI.1077-07.2007

http://www.jneurosci.org/cgi/content/full/27/24/6542

Interaction between Perirhinal and Medial Prefrontal Cortex Is Required for Temporal Order But Not Recognition Memory for Objects in Rats

The present study investigated the roles of the perirhinal cortex, medial prefrontal cortex, and intrahemispheric interactions between them in recognition and temporal order memory for objects. Experiment 1 assessed the effects of bilateral microinfusions of the sodium channel blocker lidocaine into either the anterior perirhinal or medial prefrontal cortex immediately before memory testing in a familiarity discrimination task and a recency discrimination task, both of which involved spontaneous exploration of objects. Inactivation of the perirhinal cortex disrupted performance in both tasks, whereas inactivation of the medial prefrontal cortex disrupted performance in the recency, but not the familiarity, discrimination task. In a second experiment, the importance of intrahemispheric interactions between these structures in temporal order memory were assessed by comparing the effects of unilateral inactivation of either structure alone with those of crossed unilateral inactivation of both structures on the recency discrimination task. Crossed unilateral inactivation of both structures produced a significant impairment, whereas inactivation of either structure alone produced little or no impairment. Collectively, these findings suggest that the perirhinal cortex, but not the medial prefrontal cortex, contributes to retrieval of information necessary for long-term object recognition, whereas both structures, via intrahemispheric interactions between them, contribute to retrieval of information necessary for long-term object temporal order memory. These data are consistent with models in which attributed information is stored in posterior cortical sites and supports lower-order mnemonic functions (e.g., recognition memory) but can also be retrieved and further processed via interactions with the prefrontal cortex to support higher-order mnemonic functions (e.g., temporal order memory).

Darren K. Hannesson, John G. Howland, and Anthony G.
Interaction between Perirhinal and Medial Prefrontal Cortex Is Required for Temporal Order But Not Recognition Memory for Objects in Rats.
J. Neurosci. 24: 4596-4604; doi:10.1523/JNEUROSCI.5517-03.2004

http://www.jneurosci.org/cgi/content/abstract/24/19/4596

Cytoarchitecture of the canine perirhinal and postrhinal cortex

The perirhinal cortex in the dog’s brain is composed of two traditional Brodmann’s areas: 35 and 36. Area 35 is situated along the entire rostro-caudal extent of the fundus of the posterior rhinal sulcus, whereas area 36 occupies its lateral bank. In this study, four subdivisions were distinguished in area 35 based on cytoarchitectonic differentiation. Area 36 is poorly developed in the dog’s brain and was divided into two subdivisions. The most characteristic features of area 35 are: a wide layer I, scattered cell clusters in layer II, and a prominent layer V containing a distinct population of large multiform neurons. Area 36 can be recognized by the presence of numerous cell clusters in layer II and increasing radial arrangement of neurons in deep layers of the area. Two fields of the postrhinal cortex were identified in the additional postrhinal gyrus, which is found in the fundus of the most caudal extent of the posterior rhinal sulcus.

Agnieszka WoŸnicka and Anna Kosmal
Cytoarchitecture of the canine perirhinal and postrhinal cortex.
Acta Neurobiol. Exp. 2003, 63: 197-209.

http://www.nencki.gov.pl/pdf/an/vol63/woznicka.pdf

Response Differences in Monkey TE and Perirhinal Cortex: Stimulus Association Related to Reward Schedules

Anatomic and behavioral evidence shows that TE and perirhinal cortices are two
directly connected but distinct inferior temporal areas. Despite this distinctness, physiological properties of neurons in these two areas generally have been similar with neurons in both areas showing selectivity for complex visual patterns and showing response modulations
related to behavioral context in the sequential delayed matchto-sample (DMS) trials, attention, and stimulus familiarity. Here we identify physiological differences in the neuronal activity of these two areas. We recorded single neurons from area TE and perirhinal cortex while the monkeys performed a simple behavioral task using randomly interleaved visually cued reward schedules of one, two, or three DMS trials. The monkeys used the cue’s relation to the reward schedule (indicated by the brightness) to adjust their behavioral performance. They performed most quickly and most accurately in trials in which reward was immediately forthcoming and progressively less well as more intermediate trials remained. Thus the monkeys appeared more motivated as they progressed through the trial schedule. Neurons in both TE and perirhinal cortex responded to both the visual cues related to the reward schedules and the stimulus patterns used in the DMS trials. As expected, neurons in both areas showed response selectivity to the DMS patterns, and significant, but small, modulations related to the behavioral context in the DMS trial. However, TE and perirhinal neurons showed strikingly different response properties. The latency distribution of perirhinal responses was centered 66 ms later than the distribution of TE responses, a larger difference than the 10–15 ms usually found in sequentially connected visual cortical areas. In TE, cue-related responses were related to the cue’s brightness. In perirhinal cortex, cue-related responses were related to the trial schedules independently of the cue’s brightness. For example, some perirhinal neurons responded in the first trial of any reward schedule including the one trial schedule, whereas other neurons
failed to respond in the first trial but respond in the last trial of any schedule. The majority of perirhinal neurons had more complicated relations to the schedule. The cue-related activity of TE neurons is interpreted most parsimoniously as a response to the stimulus brightness,
whereas the cue-related activity of perirhinal neurons is interpreted most parsimoniously as carrying associative information about the animal’s progress through the reward schedule. Perirhinal cortex may be part of a system gauging the relation between work schedules
and rewards.

Liu, Zheng and Barry J. Richmond.
Response differences in monkey TE and perirhinal cortex: stimulus association related to reward schedules.
J. Neurophysiol. 83: 1677–1692, 2000.

http://neuron.nimh.nih.gov/richmond/docs/TE_perirhinal_reward_schedules.pdf

Collateral projection from the amygdalo–hippocampal transition area and CA1 to the hypothalamus and medial prefrontal cortex in the rat

Amygdaloid and hippocampal neurons projecting to both the medial prefrontal cortex and hypothalamus by way of axon collaterals were examined in the rat by double labeling method using fluorescence retrograde tracers. Fluoro-gold was injected in the medial prefrontal cortex, while Fluoro-red was injected into the ventromedial and ventral premammillary nuclei of the hypothalamus. The results indicated that neurons which sent axon collaterals to both the medial prefrontal cortex and hypothalamus constituted 50 or 30% of populations of medial prefrontal cortex-projecting neurons in the amygdalo–hippocampal transition area or in CA1, respectively. Possible roles of the neurons with axon collaterals in sexually related aggressive and/or defensive behavior were discussed.

Tanemichi Chiba
Collateral projection from the amygdalo–hippocampal transition area and CA1 to the hypothalamus and medial prefrontal cortex in the rat.
Neuroscience Research Volume 38, Issue 4, December 2000, Pages 373-383.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0H-426XXND-7&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=7dfba4ddd462ea5905d7bef0ad3ecea4

Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus accumbens: Combined anterograde and retrograde tracing study in the ...

A combination of anterograde and retrograde tracing techniques was used to study the projections to the nucleus accumbens from the amygdala, the hippocampal formation (including the entorhinal cortex), and the perirhinal cortex in two species of macaque monkey. To help identify possible subregions within the nucleus accumbens, the distribution of calbindin was examined in two additional monkeys. Although this revealed evidence of core- and shell-like regions within the accumbens, these different regions could not consistently be related to cytoarchitectonic features. The rostral amygdala sent nearly equivalent projections to both the medial and the lateral portions of nucleus accumbens, whereas projections arising from the middle and caudal amygdala terminated preferentially in the medial division of nucleus accumbens. The basal nucleus was the major source of these amygdala efferents, and there was a crude topography as parts of the basal and accessory basal nuclei terminated in different parts of nucleus accumbens. The subiculum was the major source of hippocampal projections to the nucleus accumbens, but some hippocampal efferents also originated in the parasubiculum, the prosubiculum, the adjacent portion of CA1, and the uncal portion of CA3. These hippocampal projections, which coursed through the fornix, showed a rostrocaudal gradient as more arose in the rostral hippocampus. Hippocampal efferents terminated most densely in the medial and ventral portions of nucleus accumbens, along with light label in the adjacent olfactory tubercle. The entorhinal projections were more evenly distributed between the medial nucleus accumbens and the olfactory tubercle, whereas the perirhinal projections were primarily to the olfactory tubercle. These cortical inputs were less reliant on the fornix. Amygdala and subicular (hippocampal) projections overlapped most completely in the medial division of nucleus accumbens.

David P. Friedman, John P. Aggleton, Richard C. Saunders.
Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus accumbens: Combined anterograde and retrograde tracing study in the Macaque brain.
J. Comp. Neurol. 450:345-365, 2002.

http://www3.interscience.wiley.com/cgi-bin/abstract/97515953/

An extrahippocampal projection from the dentate gyrus to the olfactory tubercle

Background:

The dentate gyrus is well known for its mossy fiber projection to the hippocampal field 3 (CA3) and its extensive associational and commissural connections. The dentate gyrus, on the other hand, has only few projections to the CA1 and the subiculum, and none have clearly been shown to extrahippocampal target regions.

Results:

Using anterograde and retrograde tracer techniques in the Madagascan lesser hedgehog tenrec (Afrosoricidae, Afrotheria) it was shown in this study that the dentate hilar region gave rise to a faint, but distinct, bilateral projection to the most rostromedial portion of the olfactory tubercle, particularly its molecular layer. Unlike the CA1 and the subiculum the dentate gyrus did not project to the accumbens nucleus. A control injection into the medial septum-diagonal band complex also retrogradely labeled cells in the dentate hilus, but these neurons were found immediately adjacent to the heavily labeled CA3, while the tracer injections into the rostromedial tubercle did not reveal any labeling in CA3.

Conclusion:

The dentate hilar neurons projecting to the olfactory tubercle cannot be considered displaced cells of CA3 but represent true dentato-tubercular projection neurons. This projection supplements the subiculo-tubercular projection. Both terminal fields overlap among one another as well as with the fiber terminations arising in the anteromedial frontal cortex. The rostromedial olfactory tubercle might represent a distinct ventral striatal target area worth investigating in studies of the parallel processing of cortico-limbic information in tenrec as well as in cat and monkey.

Figure 3

Retrograde labeling in DtHi and HCt following tracer injections into the olfactory tubercle. Tracer injections into the rostromedial Tu (A) consistently labeled a few dentate hilar neurons (D-H; arrows point to labeled cells), but failed to label the CA3 (D-F). A-E are from Et03-58W, F-H from Et01-47W. Some labeled neurons are also noted in the ipsilateral, anterior HCt (B, C) confirming previous anterograde data [28]. Remarkably, both the HCt and the DtHi project to the rostromedial Tu, but not to the Acb. Arrow heads point to similar location. OfB, olfactory bulb; PCx, paleocortex. Scale bars = 0.8 mm in A, 0.4 mm in B and D, 0.3 mm in F, 0.2 mm in C, E and H (as G).

Heinz Künzle.
An extrahippocampal projection from the dentate gyrus to the olfactory tubercle.
BMC Neurosci. 2005; 6: 38.


http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1180450&rendertype=figure&id=F3

The Orbitofrontal Cortex and Reward

The primate 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 odors is represented. The orbitofrontal cortex also receives information about the sight of objects and faces 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 a taste reward) is reversed. However, the orbitofrontal cortex is involved in representing negative reinforcers (punishers) too, such as aversive taste, and in rapid stimulus–reinforcement association learning for both positive and negative primary reinforcers. In complementary neuroimaging studies in humans it is being found that areas of the orbitofrontal cortex (and connected subgenual cingulate cortex) are activated by pleasant touch, by painful touch, by rewarding and aversive taste, and by odor. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus– reinforcement associations, and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. 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.




Figure 1. Schematic diagram showing some of the gustatory, olfactory, visual and somatosensory pathways to the orbitofrontal cortex, and some of the outputs of the orbitofrontal cortex. The secondary taste cortex and the secondary olfactory cortex are within the orbitofrontal cortex. V1, primary visual cortex. V4, visual cortical area V4. Abbreviations: as, arcuate sulcus; cc, corpus callosum; cf, calcarine fissure; cgs, cingulate sulcus; cs, central sulcus; ls, lunate sulcus; ios, inferior occipital sulcus; mos, medial orbital sulcus; os, orbital sulcus; ots, occipito-temporal sulcus; ps, principal sulcus; rhs, rhinal sulcus; sts, superior temporal sulcus; lf, lateral (or Sylvian) fissure (which has been opened to reveal the insula); A, amygdala; INS, insula; T, thalamus; TE (21), inferior temporal visual cortex; TA (22), superior temporal auditory association cortex; TF and TH, parahippocampal cortex; TG, temporal pole cortex; 12, 13, 11, orbitofrontal cortex; 35, perirhinal cortex; 51, olfactory (prepyriform and periamygdaloid) cortex. Most of the forward projections shown in this diagram have corresponding backprojections (Rolls and Treves, 1998).

Edmund T. Rolls
The Orbitofrontal Cortex and Reward
Cereb. Cortex 10: 284-294.

http://cercor.oxfordjournals.org/cgi/content/full/10/3/284

Neurogenesis in adult dentate gyrus: Evidence of mitosis in differentiated granule cells following spatial learning

An increasing body of evidence has been presented to demonstrate the idea that neurogenesis occurs only during development and ends before puberty is erroneous. In adult vertebrate brain, neurogenesis persists throughout life mainly in two discrete regions – the dentate gyrus of the hippocampus (DG) and the olfactory bulb. Neurogenesis has been shown by detection of tagged thymidine analogues which are incorporated into the S phase of the cell cycle, but these
may also detect repaired DNA in post-mitotic neurons and/or an abortive cell cycle. Recent retroviral labelling has shown that neuronal progenitors/neuroblasts divide and produce functional neurons. However, it is unclear whether differentiated granule cells (GC) in the DG can divide and give rise to another GC. We have used three-dimensional (3D) reconstructions of serial ultrathin sections to identify and reconstruct GC, thereby illustrating individual mitotic elements and phases. We report that functional GC with clear synaptic specializations re-enter the cell cycle demonstrating for the first time that newly generated neurons within the DG can arise not only from stem cell precursors, but also from differentiated GC.

Neurogenesis in adult dentate gyrus: Evidence of mitosis in differentiated granule cells following spatial learning
V.Popov, J.J.Rodriguez, H.A.Davies, I.V.Kraev, D.Banks, M.I.Cordero, C.Sandi and M.G.Stewart
18TH NATIONAL MEETING OF THE BRITISH NEUROSCIENCE ASSOCIATION 2005

Functional Heterogeneity in Human Olfactory Cortex: An Event-Related Functional Magnetic Resonance Imaging Study

Studies of patients with focal brain injury indicate that smell perception involves caudal orbitofrontal and medial temporal cortices, but a more precise functional organization has not been characterized. In addition, although it is believed that odors are potent triggers of emotion, support for an anatomical association is scant. We sought to define the neural substrates of human olfactory information processing and determine how these are modulated by affective properties of odors. We used event-related functional magnetic resonance imaging (fMRI) in an olfactory version of a classical conditioning paradigm, whereby neutral faces were paired with pleasant, neutral, or unpleasant odors, under 50% reinforcement. By comparing paired (odor/face) and unpaired (face only) conditions, odor-evoked neural activations could be isolated specifically. In primary olfactory (piriform) cortex, spatially and temporally dissociable responses were identified along a rostrocaudal axis. A nonhabituating response in posterior piriform cortex was tuned to all odors, whereas activity in anterior piriform cortex reflected sensitivity to odor affect. Bilateral amygdala activation was elicited by all odors, regardless of valence. In posterior orbitofrontal cortex, neural responses evoked by pleasant and unpleasant odors were segregated within medial and lateral segments, respectively. The results indicate functional heterogeneity in areas critical to human olfaction. They also show that brain regions mediating emotional processing are differentially activated by odor valence, providing evidence for a close anatomical coupling between olfactory and emotional processes.

Jay A. Gottfried, Ralf Deichmann, Joel S. Winston, and Raymond J. Dolan
Functional Heterogeneity in Human Olfactory Cortex: An Event-Related Functional Magnetic Resonance Imaging Study
J. Neurosci. 22: 10819-10828; doi:

http://www.jneurosci.org/cgi/content/full/22/24/10819

The Amygdaloid Complex: Anatomy and Physiology

A converging body of literature over the last 50 years has implicated the amygdala in assigning emotional significance or value to sensory information. In particular, the amygdala has been shown to be an essential component of the circuitry underlying fear-related responses. Disorders in the processing of fear-related information are likely to be the underlying cause of some anxiety disorders in humans such as posttraumatic stress. The amygdaloid complex is a group of more than 10 nuclei that are located in the midtemporal lobe. These nuclei can be distinguished both on cytoarchitectonic and connectional grounds. Anatomical tract tracing studies have shown that these nuclei have extensive intranuclear and internuclear connections. The afferent and efferent connections of the amygdala have also been mapped in detail, showing that the amygdaloid complex has extensive connections with cortical and subcortical regions. Analysis of fear conditioning in rats has suggested that long-term synaptic plasticity of inputs to the amygdala underlies the acquisition and perhaps storage of the fear memory. In agreement with this proposal, synaptic plasticity has been demonstrated at synapses in the amygdala in both in vitro and in vivo studies. In this review, we examine the anatomical and physiological substrates proposed to underlie amygdala function.




FIG. 1. Nuclei of the rat amygdaloid complex. Coronal sections are drawn from rostral (A) to caudal (D). The different nuclei are divided into three groups as described in text. Areas in blue form part of the basolateral group, areas in yellow are the cortical group, and areas in green form the centromedial group. ABmc, accessory basal magnocellular subdivision; ABpc, accessory basal parvicellular subdivision; Bpc, basal nucleus magnocellular subdivision; e.c., external capsule; Ladl, lateral amygdala medial subdivision; Lam, lateral amygdala medial subdivision; Lavl, lateral amygdala ventrolateral subdivision; Mcd, medial amygdala dorsal subdivision; Mcv, medial amygdala ventral subdivision; Mr, medial amygdala rostral subdivision; Pir, piriform cortex; s.t., stria terminalis. See text for other definitions.




Sah, P., E. S. L. Faber, M. Lopez de Armentia, and J. Power.
The Amygdaloid Complex: Anatomy and Physiology.
Physiol Rev 83: 803–834, 2003; 10.1152/physrev.00002.2003.

http://physrev.physiology.org/cgi/content/full/83/3/803

Central Olfactory Connections in the Microsmatic Marmoset Monkey (Callithrix jacchus)

The mammalian primary olfactory system consists of a set of different telencephalic structures, including paleo-, archi-, periarchi- and mesocortical components. We present the first characterisation of the normal and connectional anatomy of the primary olfactory cortex of the common marmoset, a microsmatic simian species increasingly used in primate research. The centrifugal and centripetal bulbar projections were determined by injections of the anterograde and retrograde tracer wheat germ agglutinin-conjugated horseradish peroxidase and fluorescent dyes into the ipsilateral main olfactory bulb. The efferent projections of the marmoset bulb are organised entirely ipsilaterally and are established via a rudimentary medial olfactory tract and the dominant lateral olfactory tract. Target areas are the anterior olfactory nucleus, the entire prepiriform cortex, ventral tenia tecta, periamygdaloid cortex and the rostral part of the entorhinal cortex. The bulbar axons predominantly terminate in the outer part of layer I. The anterior olfactory nucleus receives a weak additional input within layer II and III, which is not found in macrosmatic rodents. Further anterograde labelling was found in the endopiriform nucleus deep under the prepiriform cortex and within an anterolateral strip of the olfactory tubercle. However, control injections into the olfactory tubercle suggest that the marmoset olfactory tubercle receives a bisynaptic olfactory input only. Retrograde labelling after bulb injections revealed that, except for the olfactory tubercle, all primary olfactory cortices contributed to an ipsilateral bulbopetal feedback projection. Like in rodents, the only bulbopetal projection organised bilaterally in the marmoset is maintained by the anterior olfactory nucleus. With few exceptions, the projections of the marmoset olfactory brain are organised similarly to that of the macaque monkey or those of macrosmatic species.

David Liebetanz, Michael Andreas Nitsche, Christoph Fromm, Christian Karl Hermann Reyher
Central Olfactory Connections in the Microsmatic Marmoset Monkey (Callithrix jacchus)
Cells Tissues Organs 2002;172:53-69 (DOI: 10.1159/000064386)

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ProduktNr=224197&Ausgabe=228534&ArtikelNr=64386

New Features of Connectivity in Piriform Cortex Visualized by Intracellular Injection of Pyramidal Cells Suggest that "Primary" Olfactory Cortex ...

Associational connections of pyramidal cells in rat posterior piriform cortex were studied by direct visualization of axons stained by intracellular injection in vivo. The results revealed that individual cells have widespread axonal arbors that extend over nearly the full length of the cerebral hemisphere. Within piriform cortex these arbors are highly distributed with no regularly arranged patchy concentrations like those associated with the columnar organization in other primary sensory areas (i.e., where periodically arranged sets of cells have common response properties, inputs, and outputs). A lack of columnar organization was also indicated by a marked disparity in the intrinsic projection patterns of neighboring injected cells. Analysis of axonal branching patterns, bouton distributions, and dendritic arbors suggested that each pyramidal cell makes a small number of synaptic contacts on a large number (>1000) of other cells in piriform cortex at disparate locations. Axons from individual pyramidal cells also arborize extensively within many neighboring cortical areas, most of which send strong projections back to piriform cortex. These include areas involved in high-order functions in prefrontal, amygdaloid, entorhinal, and perirhinal cortex, to which there are few projections from other primary sensory areas. Our results suggest that piriform cortex performs correlative functions analogous to those in association areas of neocortex rather than those typical of primary sensory areas with which it has been traditionally classed. Findings from other studies suggest that the olfactory bulb subserves functions performed by primary areas in other sensory systems.






Figure 1. Axon from a single pyramidal cell in layer II of rat piriform cortex. Note that axon branches extend over nearly the entire length of the cerebral hemisphere and are widely distributed within piriform cortex and other olfactory and nonolfactory areas. The SP cell in posterior piriform cortex was stained by intracellular injection of biotinylated dextran amine in vivo, and the axon was reconstructed through serial sections with a computer microscope system. A, Spatial distribution of axon branches in surface view. The inset at top right shows the illustrated portion of the rat brain (dashed rectangle) and orientation (45° upward rotation); the hatched area is piriform cortex, and the shaded area is lateral olfactory tract. APC, Anterior piriform cortex; PPC, posterior piriform cortex. B, Depth distribution of same axon within PPC. View is parallel to layers after 90° rotation; rostral is at left as in A; branches outside PPC have been removed; size scale is expanded relative to that in A. Roman numerals indicate layers: Ib, association fiber zone in layer I (molecular layer); IIIs, IIId, superficial and deep portions of layer III; dotted lines, superficial and deep borders of layer II (compact cell body layer). Open arrowheads mark branch points for axon collaterals that ascend to layer I. Open arrows in A and B indicate cell body; dendritic tree is not illustrated (Fig. 3). Ant, Anterior; ctx, cortex; nuc, nucleus; olfac, olfactory.

Dawn M. G. Johnson, Kurt R. Illig, Mary Behan, and Lewis B. Haberly
New Features of Connectivity in Piriform Cortex Visualized by Intracellular Injection of Pyramidal Cells Suggest that "Primary" Olfactory Cortex Functions Like "Association" Cortex in Other Sensory Systems
J. Neurosci. 20: 6974-6982; doi:

http://www.jneurosci.org/cgi/content/full/20/18/6974

Central olfactory connections in the macaque monkey

The connections between the olfactory bulb, primary olfactory cortex, and olfactory related areas of the orbital cortex were defined in macaque monkeys with a combination of anterograde and retrograde axonal tracers and electrophysiological recording. Anterograde tracers placed into the olfactory bulb labeled axons in eight primary olfactory cortical areas: the anterior olfactory nucleus, piriform cortex, ventral tenia tecta, olfactory tubercle, anterior cortical nucleus of the amygdala, periamygdaloid cortex, and olfactory division of the entorhinal cortex. The bulbar axons terminate in the outer part of layer I throughout these areas and are most dense in areas that are close to the lateral olfactory tract. Labeled axons also were found in the superficial part of nucleus of the horizontal diagonal band. Retrograde tracers injected into the olfactory bulb labeled cells in the nucleus of the diagonal band and in all of the primary olfactory cortical areas except the olfactory tubercle. Electrical stimulation of the olfactory bulb evoked short-latency unit responses and a characteristic field wave in the primary olfactory cortex. Multiunit activity in layer II tended to be of shorter latency than that in layer III and the endopiriform nucleus. Associational connections within the primary olfactory cortex were demonstrated with anterograde tracer injections into the piriform cortex and the entorhinal cortex. Injections into the piriform cortex near the lateral olfactory tract labeled axons in the deep part of layer I of many primary olfactory areas, but especially in areas near the tract. An injection into the rostral entorhinal cortex, distant to the lateral olfactory tract, labeled a complementary distribution of axons in deep layer I of olfactory areas medial and caudoventral to the tract. This organization resembles that reported in the primary olfactory cortex of the rat [Luskin and Price (1983) J. Comp. Neurol. 216:264-291]. The anterograde tracer injections into the piriform cortex and retrograde tracer injections into the orbital and medial prefrontal cortex and rostral insula label connections from the primary olfactory cortex to nine areas in the caudal orbital cortex, including the agranular insula areas Iam, Iai, Ial, Iapm, and Iapl and areas 14c, 25, 13a, and 13m. The piriform cortex projects most heavily to layer I of these areas. Only Iam, Iapm, and 13a receive a substantial projection to the deeper layers. Areas Iam, Iapm, and 13a were also the only areas that responded with multiunit action potentials to olfactory bulb stimulation in anesthetized animals.

Central olfactory connections in the macaque monkey
Carmichael ST, Clugnet MC, Price JL.
J Comp Neurol 1994 Aug 15;346(3):403-34

http://brainmeta.com/neuroanat/a16.html

Parallel-distributed Processing in Olfactory Cortex: New Insights from Morphological and Physiological Analysis of Neuronal Circuitry

A working hypothesis is proposed for piriform cortex (PC) and other olfactory cortical areas that redefines the traditional functional roles as follows: the olfactory bulb serves as the primary olfactory cortex by virtue of encoding ‘molecular features’ (structural components common to many odorant molecules) as a patchy mosaic reminiscent of the representation of simple features in primary visual cortex. The anterior olfactory cortex (that has been inappropriately termed the anterior olfactory nucleus) detects and stores correlations between olfactory features, creating representations (gestalts) for particular odorants and odorant mixtures. This function places anterior olfactory cortex at the level of secondary visual cortex. PC carries out functions that have traditionally defined association cortex—it detects and learns correlations between olfactory gestalts formed in anterior olfactory cortex and a large repertoire of behavioral, cognitive and contextual information to which it has access through reciprocal connections with prefrontal, entorhinal, perirhinal and amygdaloid areas. Using principles derived from artificial networks with biologically plausible parallel-distributed architectures and Hebbian synaptic plasticity (i.e. adjustments in synaptic strength based on locally convergent activity), functional proposals are made for PC and related cortical areas. Architectural features incorporated include extensive recurrent connectivity in anterior PC, predominantly feedforward connectivity in posterior PC and backprojections that connect distal to proximal structures in the cascade of olfactory cortical areas. Capabilities of the ‘reciprocal feedforward correlation’ architecture that characterizes PC and adjoining higher-order areas are discussed in some detail. The working hypothesis is preceded by a review of relevant anatomy and physiology, and a non-quantitative account of parallel-distributed principles. To increase the accessibility of findings for PC and to advertise its substantial potential as a model for experimental and modeling analysis of associative processes, parallels are described between PC and the hippocampal formation, inferotemporal visual cortex and prefrontal cortex.

Lewis B. Haberly
Parallel-distributed Processing in Olfactory Cortex: New Insights from Morphological and Physiological Analysis of Neuronal Circuitry
Chem. Senses 26: 551-576.

http://chemse.oxfordjournals.org/cgi/content/full/26/5/551

Multisensory and Secondary Somatosensory Cortex in the Rat

The function of secondary somatosensory (SII) cortex is poorly understood, but there is evidence to suggest that one of its roles may be in multisensory integration. This study used high-resolution field potential mapping coupled with laminar field potential and multiunit recording to examine the association between SII and multisensory (auditory–somatosensory) cortex in the rat. We demonstrate that while there is spatial overlap between unisensory areas of SII and multisensory regions, particularly for representations of the trunk and hind limbs, they form distinct somatotopic maps. We propose that multisensory cortex be considered functionally distinct from SII, and that SII may be more concerned with unisensory processing tasks.

Richard R. Menzel , and Daniel S. Barth
Multisensory and Secondary Somatosensory Cortex in the Rat
Cerebral Cortex Advance Access published on November 1, 2005, DOI 10.1093/cercor/bhi045.
Cereb. Cortex 15: 1690-1696.

http://cercor.oxfordjournals.org/cgi/content/full/15/11/1690

Insular Cortical Projections to Functional Regions of the Striatum Correlate with Cortical Cytoarchitectonic Organization in the Primate

We examined the striatal projections from different cytoarchitectonic regions of the insular cortex using anterograde and retrograde techniques. The shell and medial ventral striatum receive inputs primarily from the agranular and ventral dysgranular insula. The central ventral striatum receives inputs primarily from the dorsal agranular and dysgranular insula. Projections to the central ventral striatum originate from more posterior and dorsal insular regions than projections to the medial ventral striatum. The dorsolateral striatum receives projections primarily from the dorsal dysgranular and granular insula.

These results show that cytoarchitectonically less differentiated (agranular) insular regions project to the ventromedial "limbic" part of the ventral striatum, whereas more differentiated (granular) insular regions project to the dorsolateral "sensorimotor" part of the striatum. The finding that the ventral "limbic" striatum receives inputs from less differentiated regions of the insula is consistent with the general principle that less differentiated cortical regions project primarily to the "limbic" striatum. Functionally, the ventral striatum receives insular projections primarily related to integrating feeding behavior with rewards and memory, whereas the dorsolateral striatum receives insular inputs related to the somatosensation. Information regarding food acquisition in the insula may be sent to the intermediate area of the striatum.

Masanori Chikama, Nikolaus R. McFarland, David G. Amaral, and Suzanne N. Haber
Insular Cortical Projections to Functional Regions of the Striatum Correlate with Cortical Cytoarchitectonic Organization in the Primate
J. Neurosci. 17: 9686-9705; doi:

http://www.jneurosci.org/cgi/content/full/17/24/9686

Changes in brain activity related to eating chocolate

We performed successive H215O-PET scans on volunteers as they ate chocolate to beyond satiety. Thus, the sensory stimulus and act (eating) were held constant while the reward value of the chocolate and motivation of the subject to eat were manipulated by feeding. Non-specific effects of satiety (such as feelings of fullness and autonomic changes) were also present and probably contributed to the modulation of brain activity. After eating each piece of chocolate, subjects gave ratings of how pleasant/unpleasant the chocolate was and of how much they did or did not want another piece of chocolate. Regional cerebral blood flow was then regressed against subjects' ratings. Different groups of structures were recruited selectively depending on whether subjects were eating chocolate when they were highly motivated to eat and rated the chocolate as very pleasant [subcallosal region, caudomedial orbitofrontal cortex (OFC), insula/operculum, striatum and midbrain] or whether they ate chocolate despite being satiated (parahippocampal gyrus, caudolateral OFC and prefrontal regions). As predicted, modulation was observed in cortical chemosensory areas, including the insula and caudomedial and caudolateral OFC, suggesting that the reward value of food is represented here. Of particular interest, the medial and lateral caudal OFC showed opposite patterns of activity. This pattern of activity indicates that there may be a functional segregation of the neural representation of reward and punishment within this region. The only brain region that was active during both positive and negative compared with neutral conditions was the posterior cingulate cortex. Therefore, these results support the hypothesis that there are two separate motivational systems: one orchestrating approach and another avoidance behaviours.

Dana M. Small , Robert J. Zatorre , Alain Dagher , Alan C. Evans , and Marilyn Jones-Gotman
Changes in brain activity related to eating chocolate: From pleasure to aversion
Brain 124: 1720-1733.

http://brain.oxfordjournals.org/cgi/content/full/124/9/1720

A Specific Role for the Thalamus in Mediating the Interaction of Attention and Arousal in Humans

The physiological basis for the interaction of selective attention and arousal is not clearly understood. Here we present evidence in humans that specifically implicates the thalamus in this interaction. We used functional magnetic resonance imaging to measure brain activity during the performance of an attentional task under different levels of arousal. Activity evoked in the ventrolateral thalamus by the attentional task changed as a function of arousal. The highest level of attention-related thalamic activity is seen under conditions of low arousal (secondary to sleep deprivation) compared with high arousal (secondary to caffeine administration). Other brain regions were also active during the attentional task, but these areas did not change their activity as a function of arousal. Control experiments establish that this pattern of changes in thalamic activity cannot be accounted for by nonspecific effects of arousal on cerebral hemodynamics. We conclude that the thalamus is involved in mediating the interaction of attention and arousal in humans.

C. M. Portas, G. Rees, A. M. Howseman, O. Josephs, R. Turner, and C. D. Frith
A Specific Role for the Thalamus in Mediating the Interaction of Attention and Arousal in Humans
J. Neurosci. 18: 8979-8989; doi:

http://www.jneurosci.org/cgi/content/full/18/21/8979

The Connectional Organization of the Cortico-thalamic System of the Cat

Data on connections between the areas of the cerebral cortex and nuclei of the thalamus are too complicated to analyse with naked intuition. Indeed, the complexity of connection data is one of the major challenges facing neuroanatomy. Recently, systematic methods have been developed and applied to the analysis of the connectivity in the cerebral cortex. These approaches have shed light on the gross organization of the cortical network, have made it possible to test systematically theories of cortical organization, and have guided new electrophysiological studies. This paper extends the approach to investigate the organization of the entire corticothalamic network. An extensive collation of connection tracing studies revealed ~1500 extrinsic connections between the cortical areas and thalamic nuclei of the cat cerebral hemisphere. Around 850 connections linked 53 cortical areas with each other, and around 650 connections linked the cortical areas with 42 thalamic nuclei. Non-metric multidimensional scaling, optimal set analysis and non-parametric cluster analysis were used to study global connectivity and the `place' of individual structures within the overall scheme. Thalamic nuclei and cortical areas were in intimate connectional association. Connectivity defined four major thalamocortical systems. These included three broadly hierarchical sensory or sensory/motor systems (visual and auditory systems and a single system containing both somatosensory and motor structures). The highest stations of these sensory/motor systems were associated with a fourth processing system composed of prefrontal, cingulate, insular and parahippocampal cortex and associated thalamic nuclei (the `fronto-limbic system'). The association between fronto-limbic and somato-motor systems was particularly close.

J.W. Scannell , G.A.P.C. Burns , C.C. Hilgetag , M.A. O'Neil , and M.P. Young
The Connectional Organization of the Cortico-thalamic System of the Cat
Cereb. Cortex 9: 277-299.

http://cercor.oxfordjournals.org/cgi/content/full/9/3/277

Pathways for emotions and memory I. Input and output zones linking the anterior thalamic nuclei with prefrontal cortices in the rhesus monkey

The anterior thalamic nuclei occupy a central position in pathways associated with emotions and memory. The goal of this study was to determine the anatomic interaction of the anterior nuclei with distinct prefrontal cortices that have been implicated in emotion and specific aspects of memory. To address this issue, we investigated the relationship of input and output zones in the anterior thalamic nuclei linking them with functionally distinct orbitofrontal, medial, and lateral prefrontal cortices. We identified input zones by mapping the pattern and topography of terminations of prefrontal axons, and the output zones by mapping projection neurons in the anterior nuclei, after injection of anterograde and bidirectional tracers in distinct prefrontal cortices. The results showed that the anterior nuclei were preferentially connected with some orbitofrontal and medial prefrontal areas. In contrast, the anterior nuclei had comparatively sparse connections with most lateral prefrontal cortices, with the notable exception of frontal polar cortex, which had moderate but consistent connections with the anterior nuclei. Prefrontal cortices were connected mostly with the anterior medial nucleus, though medial areas 32 and 25 as well as the frontal polar cortex were also connected with the anterior ventral nucleus.
The zones of axonal terminations were more expansive than the sites with projection neurons in the anterior nuclei, suggesting extensive influence of feedback projections from prefrontal cortices. The results suggest that the anterior thalamic nuclei may act in concert with
orbitofrontal and medial prefrontal cortices in processes underlying emotions and long-term memory, and with the frontal polar cortex in prospective aspects of working memory.


D. Xiao, H. Barbas
Pathways for emotions and memory I. Input and output zones linking the anterior thalamic nuclei with prefrontal cortices in the rhesus monkey
Thalamus & Related Systems 2 (2002) 21–32

http://www.bu.edu/neural/Final/Publications/2002/Thalamus%20&%20Related%20Systems,%20Volume%202,%20Issue%201,%20December%202002,%20Pages%2021-32.pdf

Involvement of the Superior Temporal Cortex and the Occipital Cortex in Spatial Hearing: Evidence from Repetitive Transcranial Magnetic Stimulation

The processing of auditory spatial information in cortical areas of the human brain outside of the primary auditory cortex remains poorly understood. Here we investigated the role of the superior temporal gyrus (STG) and the occipital cortex (OC) in spatial hearing using repetitive transcranial magnetic stimulation (rTMS). The right STG is known to be of crucial importance for visual spatial awareness, and has been suggested to be involved in auditory spatial perception. We found that rTMS of the right STG induced a systematic error in the perception of interaural time differences (a primary cue for sound localization in the azimuthal plane). This is in accordance with the recent view, based on both neurophysiological data obtained in monkeys and human neuroimaging studies, that information on sound location is processed within a dorsolateral "where" stream including the caudal STG. A similar, but opposite, auditory shift was obtained after rTMS of secondary visual areas of the right OC. Processing of auditory information in the OC has previously been shown to exist only in blind persons. Thus, the latter finding provides the first evidence of an involvement of the visual cortex in spatial hearing in sighted human subjects, and suggests a close interconnection of the neural representation of auditory and visual space. Because rTMS induced systematic shifts in auditory lateralization, but not a general deterioration, we propose that rTMS of STG or OC specifically affected neuronal circuits transforming auditory spatial coordinates in order to maintain alignment with vision.

Lewald, Jorg, Meister, Ingo G., Weidemann, Jurgen, Topper, Rudolf
Involvement of the Superior Temporal Cortex and the Occipital Cortex in Spatial Hearing: Evidence from Repetitive Transcranial Magnetic Stimulation
J. Cogn. Neurosci. 2004 16: 828-838

http://jocn.mitpress.org/cgi/citmgr?gca=jocn;16/5/828

Social concepts are represented in the superior anterior temporal cortex

Social concepts such as "tactless" or "honorable" enable us to describe our own as well as others' social behaviors. The prevailing view is that this abstract social semantic knowledge is mainly subserved by the same medial prefrontal regions that are considered essential for mental state attribution and self-reflection. Nevertheless, neurodegeneration of the anterior temporal cortex typically leads to impairments of social behavior as well as general conceptual knowledge. By using functional MRI, we demonstrate that the anterior temporal lobe represents abstract social semantic knowledge in agreement with this patient evidence. The bilateral superior anterior temporal lobes (Brodmann's area 38) are selectively activated when participants judge the meaning relatedness of social concepts (e.g., honor–brave) as compared with concepts describing general animal functions (e.g., nutritious–useful). Remarkably, only activity in the superior anterior temporal cortex, but not the medial prefrontal cortex, correlates with the richness of detail with which social concepts describe social behavior. Furthermore, this anterior temporal lobe activation is independent of emotional valence, whereas medial prefrontal regions show enhanced activation for positive social concepts. Our results demonstrate that the superior anterior temporal cortex plays a key role in social cognition by providing abstract conceptual knowledge of social behaviors. We further speculate that these abstract conceptual representations can be associated with different contexts of social actions and emotions through integration with frontolimbic circuits to enable flexible evaluations of social behavior.

Roland Zahn, Jorge Moll, Frank Krueger, Edward D. Huey, Griselda Garrido, and Jordan Grafman
Social concepts are represented in the superior anterior temporal cortex
Proceedings of the National Academy of Sciences 104: 6430-6435; published online before print as 10.1073/pnas.0607061104

http://www.pnas.org/cgi/content/full/104/15/6430

Neural connections of the posteromedial cortex in the macaque

The posterior cingulate and the medial parietal cortices constitute an ensemble known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29, 30, 31, and 7m. To understand the neural relationship of the PMC with the rest of the brain, we injected its component areas with four different anterograde and retrograde tracers in the cynomolgus monkey and found that all PMC areas are interconnected with each other and with the anterior cingulate, the mid-dorsolateral prefrontal, the lateral parietal cortices, and area TPO, as well as the thalamus, where projections from some of the PMC areas traverse in an uninterrupted bar-like manner, the dorsum of this structure from the posteriormost nuclei to its rostralmost tip. All PMC regions also receive projections from the claustrum and the basal forebrain and project to the caudate, the basis pontis, and the zona incerta. Moreover, the posterior cingulate areas are interconnected with the parahippocampal regions, whereas the medial parietal cortex projects only sparsely to the presubiculum. Although local interconnections and shared remote connections of all PMC components suggest a functional relationship among them, the distinct connections of each area with different neural structures suggests that distinct functional modules may be operating within the PMC. Our study provides a large-scale map of the PMC connections with the rest of the brain, which may serve as a useful tool for future studies of this cortical region and may contribute to elucidating its intriguing pattern of activity seen in recent functional imaging studies.

Josef Parvizi, Gary W. Van Hoesen, Joseph Buckwalter, and Antonio Damasio
Neural connections of the posteromedial cortex in the macaque Proceedings of the National Academy of Sciences 103: 1563-1568; published online before print as 10.1073/pnas.0507729103


ttp://www.pnas.org/cgi/content/full/103/5/1563

Amygdala contribution to selective dimensions of emotion

The amygdala has been implicated in emotional processes, although the precise nature of the emotional deficits following amygdala lesions remains to be fully elucidated. Cognitive disturbances in the perception, recognition or memory of emotional stimuli have been suggested by some, whereas others have proposed changes in emotional arousal. To address this issue, measures of emotional arousal and valence (positivity and negativity) to a graded series of emotional pictures were obtained from patients with lesions of the amygdala and from a clinical contrast group with lesions that spared this structure. Relative to the contrast group, patients with damage to the amygdala evidenced a complete lack of an arousal gradient across negative stimuli, although they displayed a typical arousal gradient to positive stimuli. These results were not attributable to the inability of amygdala patients to process the hostile or hospitable nature of the stimuli, as the amygdala group accurately recognized and categorized both positive and negative features of the stimuli. The relative lack of emotional arousal to negative stimuli may account for many of the clinical features of amygdala lesions.

Gary G. Berntson , Antoine Bechara , Hanna Damasio , Daniel Tranel , and John T. Cacioppo
Amygdala contribution to selective dimensions of emotion Social Cognitive and Affective Neuroscience Advance Access published on June 1, 2007, DOI 10.1093/scan/nsm008.Soc Cogn Affect Neurosci 2: 123-129.

http://scan.oxfordjournals.org/cgi/content/abstract/2/2/123

Cingulate cortex: a closer look at its gut-related functional topography

Earlier studies have documented activation of the cingulate cortex during gut related sensory-motor function. However, topography of the cingulate cortex in relationship to various levels of visceromotor sensory stimuli and gender is not completely elucidated. The aim was to characterize and compare the activation topography of the cingulate cortex in response to 1) subliminal, 2) perceived rectal distensions, and 3) external anal sphincter contraction (EASC) in males and females. We studied 18 healthy volunteers (ages 18–35 yr; 10 women, 8 men) using functional MRI blood-oxygenation-level-dependent technique. We obtained 11 axial slices (voxel vol. 2.5–6.0 x 2.5 x 2.5 mm3) through the cingulate cortex during barostat-controlled subliminal, liminal, and supraliminal nonpainful rectal distensions as well as EASC. Overall, for viscerosensation, the anterior cingulate cortex exhibited significantly more numbers of activated cortical voxels for all levels of stimulations compared with the posterior cingulate cortex (P < 0.05). In contrast, during EASC, activity in the posterior cingulate was larger than in the anterior cingulate cortex (P < 0.05). Cingulate activation was similar during EASC in males and females (P = 0.58), whereas there was a gender difference in anterior cingulate activation during liminal and supraliminal stimulations (P < 0.05). In females, viscerosensory cortical activity response was stimulus-intensity dependent. Intestinal viscerosensation and EASC induce different patterns of cingulate cortical activation. There may be gender differences in cingulate cortical activation during viscerosensation. In contrast to male subjects, females exhibit increased activity in response to liminal nonpainful stimulation compared with subliminal stimulation suggesting differences in cognition-related recruitment.
functional magnetic resonance imaging; rectal distension; external anal sphincter contraction.

Adeyemi Lawal, Mark Kern, Arthi Sanjeevi, Candy Hofmann, and Reza Shaker
Cingulate cortex: a closer look at its gut-related functional topography Am J Physiol Gastrointest Liver Physiol 289: G722-G730, 2005.

http://ajpgi.physiology.org/cgi/content/full/289/4/G722

Dissociating medial frontal and posterior cingulate activity during self-reflection

Motivationally significant agendas guide perception, thought and behaviour, helping one to define a ‘self’ and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus.

Marcia K. Johnson , Carol L. Raye , Karen J. Mitchell , Sharon R. Touryan , Erich J. Greene , and Susan Nolen-Hoeksema
Dissociating medial frontal and posterior cingulate activity during self-reflection Soc Cogn Affect Neurosci 1: 56-64.

http://scan.oxfordjournals.org/cgi/content/full/1/1/56