Internal and external information in error processing

The use of self-generated and externally provided information in performance monitoring is reflected by the appearance of error-related and feedback-related negativities (ERN and FRN), respectively. Several authors proposed that ERN and FRN are supported by similar neural mechanisms residing in the anterior cingulate cortex (ACC) and the mesolimbic dopaminergic system. The present study is aimed to test the functional relationship between ERN and FRN. Using an Eriksen-Flanker task with a moving response deadline we tested 17 young healthy subjects. Subjects received feedback with respect to their response accuracy and response speed. To fulfill both requirements of the task, they had to press the correct button and had to respond in time to give a valid response.

Results

When performance monitoring based on self-generated information was sufficient to detect a criterion violation an ERN was released, while the subsequent feedback became redundant and therefore failed to trigger an FRN. In contrast, an FRN was released if the feedback contained information which was not available before and action monitoring processes based on self-generated information failed to detect an error.

Conclusions

The described pattern of results indicates a functional interrelationship of response and feedback related negativities in performance monitoring.

Internal and external information in error processing.
Marcus Heldmann, Jascha Ruesseler and Thomas F Muente.
BMC Neuroscience 2008, 9:33doi:10.1186/1471-2202-9-33

http://www.biomedcentral.com/1471-2202/9/33/abstract

Cortical Connections of Area V4 in the Macaque

To determine the locus, full extent, and topographic organization of cortical connections of area V4 (visual area 4), we injected anterograde and retrograde tracers under electrophysiological guidance into 21 sites in 9 macaques. Injection sites included representations ranging from central to far peripheral eccentricities in the upper and lower fields. Our results indicated that all parts of V4 are connected with occipital areas V2 (visual area 2), V3 (visual area 3), and V3A (visual complex V3, part A), superior temporal areas V4t (V4 transition zone), MT (medial temporal area), and FST (fundus of the superior temporal sulcus [STS] area), inferior temporal areas TEO (cytoarchitectonic area TEO in posterior inferior temporal cortex) and TE (cytoarchitectonic area TE in anterior temporal cortex), and the frontal eye field (FEF). By contrast, mainly peripheral field representations of V4 are connected with occipitoparietal areas DP (dorsal prelunate area), VIP (ventral intraparietal area), LIP (lateral intraparietal area), PIP (posterior intraparietal area), parieto-occipital area, and MST (medial STS area), and parahippocampal area TF (cytoarchitectonic area TF on the parahippocampal gyrus). Based on the distribution of labeled cells and terminals, projections from V4 to V2 and V3 are feedback, those to V3A, V4t, MT, DP, VIP, PIP, and FEF are the intermediate type, and those to FST, MST, LIP, TEO, TE, and TF are feedforward. Peripheral field projections from V4 to parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention. By contrast, the predominance of central field projections from V4 to inferior temporal areas is consistent with the need for detailed form analysis for object vision.






Cortical Connections of Area V4 in the Macaque.
Leslie G. Ungerleider, Thelma W. Galkin, Robert Desimone, and Ricardo Gattass.
Cerebral Cortex 2008 18(3):477-499; doi:10.1093/cercor/bhm061

Lateralized Anterior Cingulate Function during Error Processing and Conflict Monitoring as Revealed by High-Resolution fMRI

Recent studies have reported that functional subdivisions of anterior cingulate cortex (ACC) may be selectively responsible for conflict and error-related processing. We examined this claim by imaging ACC activation to correct and erroneous response inhibitions in a GoNogo task. After localizing the ACC cluster in individual subjects using functional magnetic resonance imaging (fMRI) at standard resolution (2 x 2 x 4 mm3), high-resolution fMRI (1.5 x 1.5 x 1.5 mm3) of the ACC was performed in a second session to investigate its precise functional anatomy. At standard resolution, and in agreement with previous studies, ACC was activated for correct and incorrect responses, albeit more so for errors. High-resolution maps of activated ACC clusters revealed localized and reproducible foci in 9 out of 10 volunteers. Multisubject analysis suggested a bilateral distribution of error-related processes in ACC, whereas correct inhibitions only seemed to activate ACC in the right hemisphere. Subsequent region of interest analysis largely confirmed the activation maps. Our results contribute toward a better understanding of the microanatomy of ACC and demonstrate the potential of fMRI for mapping the functional architecture of brain regions involved in cognitive tasks at a previously unaccomplished spatial scale.

Lateralized Anterior Cingulate Function during Error Processing and Conflict Monitoring as Revealed by High-Resolution fMRI.
Henry Lütcke and Jens Frahm.
Cerebral Cortex 2008 18(3):508-515; doi:10.1093/cercor/bhm090

The Effect of Prior Visual Information on Recognition of Speech and Sounds

To identify and categorize complex stimuli such as familiar objects or speech, the human brain integrates information that is abstracted at multiple levels from its sensory inputs. Using cross-modal priming for spoken words and sounds, this functional magnetic resonance imaging study identified 3 distinct classes of visuoauditory incongruency effects: visuoauditory incongruency effects were selective for 1) spoken words in the left superior temporal sulcus (STS), 2) environmental sounds in the left angular gyrus (AG), and 3) both words and sounds in the lateral and medial prefrontal cortices (IFS/mPFC). From a cognitive perspective, these incongruency effects suggest that prior visual information influences the neural processes underlying speech and sound recognition at multiple levels, with the STS being involved in phonological, AG in semantic, and mPFC/IFS in higher conceptual processing. In terms of neural mechanisms, effective connectivity analyses (dynamic causal modeling) suggest that these incongruency effects may emerge via greater bottom-up effects from early auditory regions to intermediate multisensory integration areas (i.e., STS and AG). This is consistent with a predictive coding perspective on hierarchical Bayesian inference in the cortex where the domain of the prediction error (phonological vs. semantic) determines its regional expression (middle temporal gyrus/STS vs. AG/intraparietal sulcus).

The Effect of Prior Visual Information on Recognition of Speech and Sounds.
Uta Noppeney, Oliver Josephs, Julia Hocking, Cathy J. Price and Karl J. Friston.
Cerebral Cortex 2008 18(3):598-609; doi:10.1093/cercor/bhm091

Forgetting as an Active Process: An fMRI Investigation of Item-Method–Directed Forgetting

Using event-related functional magnetic resonance imaging (fMRI), we examined the blood oxygen level–dependent response associated with intentional remembering and forgetting. In an item-method directed forgetting paradigm, participants were presented with words, one at a time, each of which was followed after a brief delay by an instruction to Remember or Forget. Behavioral data revealed a directed forgetting effect: greater recognition of to-be-remembered than to-be-forgotten words. We used this behavioral recognition data to sort the fMRI data into 4 conditions based on the combination of memory instruction and behavioral outcome. When contrasted with unintentional forgetting, intentional forgetting was associated with increased activity in hippocampus (Broadmann area [BA] 35) and superior frontal gyrus (BA10/11); when contrasted with intentional remembering, intentional forgetting was associated with activity in medial frontal gyrus (BA10), middle temporal gyrus (BA21), parahippocampal gyrus (BA34 and 35), and cingulate gyrus (BA31). Thus, intentional forgetting depends on neural structures distinct from those involved in unintentional forgetting and intentional remembering. These results challenge the standard selective rehearsal account of item-method directed forgetting and suggest that frontal control processes may be critical for directed forgetting.

Forgetting as an Active Process: An fMRI Investigation of Item-Method–Directed Forgetting.
Glenn R. Wylie, John J. Foxe, Tracy L. Taylor.
Cerebral Cortex 2008 18(3):670-682; doi:10.1093/cercor/bhm101

Perceived causality influences brain activity evoked by biological motion

Using functional magnetic resonance imaging (fMRI), we investigated brain activity in an observer who watched the hand and arm motions of an individual when that individual was, or was not, the cause of the motion. Subjects viewed a realistic animated 3D character who sat at a table containing four pistons. On Intended Motion trials, the character raised his hand and arm upwards. On Unintended Motion trials, the piston under one of the character's hands pushed the hand and arm upward with the same motion. Finally, during Non-Biological Motion control trials, a piston pushed a coffee mug upward in the same smooth motion. Hand and arm motions, regardless of intention, evoked significantly more activity than control trials in a bilateral region that extended ventrally from the posterior superior temporal sulcus (pSTS) region and which was more spatially extensive in the right hemisphere. The left pSTS near the temporal-parietal junction, robustly differentiated between the Intended Motion and Unintended Motion conditions. Here, strong activity was observed for Intended Motion trials, while Unintended Motion trials evoked similar activity as the coffee mug trials. Our results demonstrate a strong hemispheric bias in the role of the pSTS in the perception of causality of biological motion.

Perceived causality influences brain activity evoked by biological motion.
James P. Morris a; Kevin A. Pelphrey a; Gregory McCarthy.
Social Neuroscience 17 July 2007.

http://www.informaworld.com/smpp/content~content=a780679116~db=all~jumptype=rss

Neural activity in the frontal eye fields modulated by the number of alternatives in target choice

Selection of identical responses may not use the same neural mechanisms when the number of alternatives (NA) for the selection changes, as suggested by Hick's law. For elucidating the choice mechanisms, frontal eye field (FEF) neurons were monitored during a color-to-location choice saccade task as the number of potential targets was varied. Visual responses to alternative targets decreased as NA increased, whereas perisaccade activities increased with NA. These modulations of FEF activities seem closely related to the choice process because the activity enhancements coincided with the timing of target selection, and the neural modulation was greater as NA increased, features expected of neural correlates for a choice process from the perspective of Hick's law. Our current observations suggest two novel notions of FEF neuronal behavior that have not been reported previously: (1) cells called "phasic visual" that do not discharge in the perisaccade interval in a delayed-saccade paradigm show such activity in a choice response task at the time of the saccade; and (2) the activity in FEF visuomotor cells display an inverse relationship between perisaccadic activity and the time of saccade triggering with higher levels of activity leading to longer saccade reaction times. These findings support the area's involvement in sensory-motor translation for target selection through coactivation and competitive interaction of neural populations that code for alternative action sets.

Neural activity in the frontal eye fields modulated by the number of alternatives in target choice.
Lee KM, Keller EL.
J Neurosci. 2008 Feb 27;28(9):2242-51.

The cerebellum predicts the timing of perceptual events

Prospective (forward) temporal-spatial models are essential for both action and perception, but the literature on perceptual prediction has primarily been limited to the spatial domain. In this study we asked how the neural systems of perceptual prediction change, when change-over-time must be modeled. We used a naturalistic paradigm in which observers had to extrapolate the trajectory of an occluded moving object to make perceptual judgments based on the spatial (direction) or temporal-spatial (velocity) characteristics of object motion. Using functional magnetic resonance imaging we found that a region in posterior cerebellum (lobule VII crus 1) was engaged specifically when a temporal-spatial model was required (velocity judgment task), suggesting that circuitry involved in motor forward-modeling may also be engaged in perceptual prediction when a model of change-over-time is required. This cerebellar region appears to supply a temporal signal to cortical networks involved in spatial orienting: a frontal-parietal network associated with attentional orienting was engaged in both (spatial and temporal-spatial) tasks, but functional connectivity between these regions and the posterior cerebellum was enhanced in the temporal-spatial prediction task. In addition to the oculomotor spatial orienting network, regions involved in hand movements (aIP and PMv) were recruited in the temporal-spatial task, suggesting that the nature of perceptual prediction may bias the recruitment of sensory-motor networks in orienting. Finally, in temporal-spatial prediction, functional connectivity was enhanced between the cerebellum and the putamen, a structure which has been proposed to supply the brain's metric of time, in the temporal-spatial prediction task.

The cerebellum predicts the timing of perceptual events.
O'Reilly JX, Mesulam MM, Nobre AC.
J Neurosci. 2008 Feb 27;28(9):2252-60.

http://www.ncbi.nlm.nih.gov/pubmed/18305258?dopt=Abstract

Brain Activity Evoked by the Perception of Human Walking:Controlling for Meaningful Coherent Motion

Manyfunctional neuroimaging studies of biological motion have used as stimuli point-light displays of walking figures and compared the resulting activations with those evoked by the same display elements moving in arandomor noncoherent manner. Although these studies have established that biological motion activates the superior temporal sulcus (STS), the use of random motion controls has left open the possibility that coordinated and meaningful nonbiological motion might activate these same brain regions and thus call into question their specificity for processing biological motion. Here we used functional magnetic resonance imaging and an anatomical region-ofinterest approach to test a hierarchy of three questions regarding activity within the STS. First, by comparing responses in the STS with animations of human and robot walking figures, we determined (1) that the STS is sensitive to biological motion itself, not merely to the superficial characteristics of the stimulus. Then we determined that the STS responds more strongly to biological motion (as conveyed by the walking robot) than to (2) a nonmeaningful but complex nonbiological motion (a disjointed mechanical figure) and (3) a complex and meaningful nonbiological motion (the movements of a grandfather clock). In subsequent whole-brain voxel-based analyses, we confirmed robust STS activity that was strongly right lateralized. In addition, we observed significant deactivations in the STS that differentiated biological and nonbiological motion. These voxel-based analyses also revealed regions of motion-related positive activity in other brain regions, including MT or V5, fusiform gyri, right premotor cortex, and the intraparietal sulci.

Brain Activity Evoked by the Perception of Human Walking:Controlling for Meaningful Coherent Motion.
Kevin A. Pelphrey, Teresa V. Mitchell, Martin J. McKeown, Jeremy Goldstein, Truett Allison, and Gregory McCarthy.
The Journal of Neuroscience, July 30, 2003 • 23(17):6819–6825 • 6819.

Perceived causality influences brain activity evoked by biological motion

Using functional magnetic resonance imaging (fMRI), we investigated brain activity in an observer who watched the hand and arm motions of an individual when that individual was, or was not, the cause of the motion. Subjects viewed a realistic animated 3D character who sat at a table containing four pistons. On Intended Motion trials, the character raised his hand and arm upwards. On Unintended Motion trials, the piston under one of the character's hands pushed the hand and arm upward with the same motion. Finally, during Non-Biological Motion control trials, a piston pushed a coffee mug upward in the same smooth motion. Hand and arm motions, regardless of intention, evoked significantly more activity than control trials in a bilateral region that extended ventrally from the posterior superior temporal sulcus (pSTS) region and which was more spatially extensive in the right hemisphere. The left pSTS near the temporal-parietal junction, robustly differentiated between the Intended Motion and Unintended Motion conditions. Here, strong activity was observed for Intended Motion trials, while Unintended Motion trials evoked similar activity as the coffee mug trials. Our results demonstrate a strong hemispheric bias in the role of the pSTS in the perception of causality of biological motion.

James P. Morris a; Kevin A. Pelphrey a; Gregory McCarthy bc.
Perceived causality influences brain activity evoked by biological motion.
journal of Social Neuroscience 17 July 2007.

Distinct visual perspective-taking strategies involve the left and right medial temporal lobe structures differently

This study assesses the role of the human medial temporal lobe (MTL) structures in the coordination of spatial information across perspective change and, in particular, in visual perspective taking—namely the capacity to know what another individual is seeing on the visual scene. Fourteen patients with unilateral temporal lobe resection and 21 control subjects performed two tasks, called ‘object location memory’ and ‘viewpoint recognition’, respectively. In the object location memory task, subjects had to memorize the position of a target object in the environment from an initial viewpoint. They were then shown the same environment from a new viewpoint and had to indicate whether or not the target object had moved. In the viewpoint recognition task, subjects had to imagine the perspective of an avatar from the initial viewpoint and then decide whether or not the new viewpoint was that of the avatar. The results showed a double dissociation, with left MTL patients being impaired in the object location memory task but not in the viewpoint recognition task and right MTL patients being impaired in the viewpoint recognition task but not in the object location memory task. Furthermore, based on multiple regression analyses between performance and the volumes of the different MTL structures, we discuss the specific involvement of the left temporopolar cortex and of the right hippocampus in different kinds of visual perspective taking.

S. Lambrey , M.-A. Amorim , S. Samson , M. Noulhiane , D. Hasboun , S. Dupont , M. Baulac , and A. Berthoz.
Distinct visual perspective-taking strategies involve the left and right medial temporal lobe structures differently.
Brain Advance Access published on February 1, 2008, DOI 10.1093/brain/awm317. Brain 131: 523-534.

http://brain.oxfordjournals.org/cgi/content/abstract/131/2/523

Reward Timing in the Primary Visual Cortex

We discovered that when adult rats experience an association between visual stimuli and subsequent rewards, the responses of a substantial fraction of neurons in the primary visual cortex evolve from those that relate solely to the physical attributes of the stimuli to those that accurately predict the timing of reward. In addition to revealing a remarkable type of response plasticity in adult V1, these data demonstrate that reward-timing activity—a "higher" brain function—can occur very early in sensory-processing paths. These findings challenge the traditional interpretation of activity in the primary visual cortex.

Reward Timing in the Primary Visual Cortex
Marshall G. Shuler and Mark F. Bear (17 March 2006)
Science 311 (5767), 1606. [DOI: 10.1126/science.1123513]

http://www.sciencemag.org/cgi/citmgr?gca=sci;311/5767/1606

Pathways for emotions and memory II. Afferent input to the anterior thalamic nuclei from PF, temporal, hypothalamic areas and the BG in the rhesus ...

The anterior thalamic nuclei are a key link in pathways associated with emotions and memory. In the preceding study we found that one of the anterior nuclei, the anterior medial (AM), had particularly robust connections with specific medial prefrontal and orbitofrontal cortices and moderate connections with frontal polar cortices. The goal of this study was to use a direct approach to determine the sources of projections to the AM nucleus from all prefrontal cortices, as well as from temporal structures and the hypothalamic mammillary body, known for their role in distinct aspects of memory and emotion. We addressed this issue with targeted injections of retrograde fluorescent tracers in the AM nucleus to determine its sources of input. Projection neurons directed to the AM nucleus were found in the deep layers of most prefrontal cortices (layers V and VI), and were most densely distributed in medial areas 24, 32 and 25, orbitofrontal areas 13 and 25, and lateral areas 10 and 46. Most projection neurons were found in layer VI, though in medial prefrontal cortices and dorsal area 9 about a third were found in layer V, a significantly higher proportion than in lateral and orbitofrontal cortices. In the temporal lobe, projection neurons originated mostly from the hippocampal formation (ammonic field CA3 and subicular complex), and the amygdala (basolateral, lateral, and basomedial nuclei). In the hypothalamus, a significant number of neurons in the ipsilateral medial mammillary body projected to the AM nucleus, some of which were positive for calbindin (CB) or parvalbumin (PV), markers expressed, respectively, in “diffuse” and “specific” pathways in the thalamus [Adv. Neurol. 77 (1998a) 49]. As recipient of diverse signals, the AM nucleus is in a key position to link pathways associated with emotions, and may be an important interface for systems associated with retrieval of information from long-term memory in the process of solving problems within working memory. Finally, the internal segment of the globus pallidus (GPi) issued projections to AM, suggesting direct linkage with executive systems through the basal ganglia. The diverse connections of the AM nucleus may help explain the varied deficits in memory and emotions seen in neurodegenerative and psychiatric diseases affecting the anterior thalamic nuclei.



Fig. 12. Summary of the connections of the anterior medial nucleus with prefrontal and temporal structures, the hypothalamic mammillary body and the internal segment of the globus pallidus. The bi-directional arrows for connections of prefrontal cortices with AM summarize findings obtained from this and the preceding study, and are shown on the lateral (top, left), medial (top, right) and basal surfaces (bottom) of the cerebral hemisphere. The projections from temporal cortex, the amygdala, the hippocampus, the hypothalamic mammillary body, and the basal ganglia to AM are according to the findings from this study. Density variations of prefrontal projections to AM are depicted in pseudocolor denoting dense (red) to light (blue) projections, as reconstructed from serial coronal sections (this paper). cal outputs of the AM nucleus, the cingulate cortex (Gaffan and Harrison, 1989; Gaffan, 1993, 2002; Parker and Gaffan, 1997a,b; Gaffan et al., 2001). In humans, infarction of the AM nucleus dramatically impaired episodic and recognition memory resulting in anterograde amnesia (Parkin et al., 1994; Ghika-Schmid and Bogousslavsky, 2000; Nolan et al.,

Pathways for emotions and memory II. Afferent input to the anterior thalamic nuclei from prefrontal, temporal, hypothalamic areas and the basal ganglia in the rhesus monkey.
D. Xiao b, H. Barbas.
Thalamus & Related Systems 2 (2002) 33–48.

http://www.bu.edu/neural/Final/Publications/2002/Thalamus%20&%20Related%20Systems,%20Volume%202,%20Issue%201,%20December%202002,%20Pages%2033-48.PDF

Cortical Structure Predicts the Pattern of Corticocortical Connections

Cortical areas are linked through pathways which originate and terminate in specific layers. The factors underlying which layers are involved in specific connections are not well understood. Here we tested whether cortical structure can predict the pattern as well as the relative distribution of projection neurons and axonal terminals in cortical layers, studied with retrograde and anterograde tracers. We used the prefrontal cortices in the rhesus monkey as a model system because their laminar organization varies systematically, ranging from areas that have only three identifiable layers, to those that have six layers. We rated each prefrontal area based on the number and definition of its cortical layers (level 1, lowest; level 5, highest). The structural model accurately predicted the laminar pattern of connections in ~80% of the cases. Thus, projection neurons from a higher-level cortex originated mostly in the upper layers and their axons terminated predominantly in the deep layers (4–6) of a lower-level cortex. Conversely, most projection neurons from a lower-level area originated in the deep layers and their axons terminated predominantly in the upper layers (1–3) of a higher-level area. In addition, the structural model accurately predicted that the proportion of projection neurons or axonal terminals in the upper to the deep layers would vary as a function of the number of levels between the connected cortices. The power of this structural model lies in its potential to predict patterns of connections in the human cortex, where invasive procedures are precluded.



Figure 11. Summary of the pattern of connections predicted by the structural model. (A) Connections between cortices with large differences in laminar definition show a readily distinguishable pattern. (Top) Projection neurons originate predominantly in the deep layers of cortices with low laminar definition and their axons terminate predominantly in the upper layers of cortices with high laminar definition. (Bottom) The opposite pattern is seen for the reciprocal connections. (B) A less extreme version of the above pattern is predicted in the interconnections of cortices with moderate differences in laminar definition. (Top) Most neurons (though fewer than in A) originate in the deep layers of the cortex with comparatively lower laminar definition, and their axons terminate primarily in the upper layers of the cortex with comparatively higher laminar definition. (Bottom) The opposite pattern is predicted for the reciprocal connections.

Cortical Structure Predicts the Pattern of Corticocortical Connections.
H. Barbas and N. Rempel-Clower.
Cerebral Cortex Oct/Nov 1997;7:635–646; 1047–3211/97/

http://www.bu.edu/neural/Final/Publications/1997/Cereb%20Cortex.%201997%20Oct-Nov.%207(7)635-46.pdf

Circuits through prefrontal cortex, basal ganglia, and ventral anterior nucleus map pathways beyond motor control

The ventral anterior (VA) nucleus of the thalamus is connected with prefrontal and premotor cortices and with the basal ganglia. Although classically associated with motor functions, recent evidence implicates the basal ganglia in cognition and emotion as well. Here, we used two complementary approaches to investigate whether the VA is a key link for pathways underlying cognitive and emotional processes through prefrontal cortices and the basal ganglia. After application of bidirectional tracers in functionally distinct lateral, medial, and orbitofrontal cortices, we found that projection neurons were embedded in much larger patches of axonal terminations found in the magnocellular part of VA (VAmc), and in the principal part of VA. Connections from medial prefrontal cortices occupied the dorsomedial and ventromedial VA, and orbitofrontal connections were found in ventrolateral VAmc. Moreover, about half of all projection neurons in orbitofrontal areas directed to the VA or VAmc were positive for calbindin but not parvalbumin, even though comparable populations of neurons were positive for each marker in the VA.We then applied tracers in VA and investigated simultaneously projections from all prefrontal areas, the internal segment of the globus pallidus (GPi), the substantia nigra reticulata (SNr), and the thalamic reticular nucleus. Projection neurons were most densely distributed in anterior cingulate areas 24 and 32, and dorsolateral areas 9 and 8, innervating the same VA sites that received projections from a large part of GPi and dorsal SNr. Nearly as many projection neurons originated from cortical layer V as from layer VI. There is evidence that cortical layer VI neurons innervate thalamic neurons that project focally to the middle cortical layers, whereas layer V neurons synapse with thalamic neurons projecting widely to cortical layer I. Projections from layer V to the VA may facilitate cortical recruitment for executive functions within a cognitive context through lateral prefrontal areas, and autonomic responses within an emotional context through anterior cingulate areas.

Circuits through prefrontal cortex, basal ganglia, and ventral anterior nucleus map pathways beyond motor control.
Danqing Xiao, Helen Barbas.
Thalamus & Related Systems 2 (2004) 325–343.

http://www.bu.edu/neural/Final/Publications/2004/Thalamus%20&%20Related%20Systems,%20Volume%202,%20Issue%204,%20July%202004,%20Pages%20325-343.pdf

Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left–right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems—e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

Daniel Tranel , Hanna Damasio , Natalie L. Denburg , and Antoine Bechara
Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?
Brain Advance Access published on December 1, 2005, DOI 10.1093/brain/awh643.
Brain 128: 2872-2881.

http://brain.oxfordjournals.org/cgi/content/full/128/12/2872

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7 s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Seiki Konishi , Kyoichi Nakajima , Idai Uchida , Hideyuki Kikyo , Masashi Kameyama , and Yasushi Miyashita
Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI
Bain 122: 981-991.

http://brain.oxfordjournals.org/cgi/content/full/122/5/981

Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli

Ventromedial prefrontal cortex (VMPFC) lesions can alter emotional and autonomic responses. In animals, VMPFC activation results in cardiovascular sympathetic inhibition. In humans, VMPFC modulates emotional processing and autonomic response to arousal (e.g. accompanying decision-making). The specific role of the left or right VMPFC in mediating somatic responses to non-arousing, daily-life pleasant or unpleasant stimuli is unclear. To further evaluate VMPFC interaction with autonomic processing of non-stressful emotional stimuli and assess the effects of stimulus valence, we studied patients with unilateral VMPFC lesions and assessed autonomic modulation at rest and during physical challenge, and heart rate (HR) and blood pressure (BP) responses to non-stressful neutral, pleasant and unpleasant visual stimulation (VES) via emotionally laden slides. In 6 patients (54.0 ± 7.2 years) with left-sided VMPFC lesions (VMPFC-L), 7 patients (43.3 ± 11.6 years) with right-sided VMPFC lesions (VMPFC-R) and 13 healthy volunteers (44.7 ± 11.6 years), we monitored HR as R–R interval (RRI), BP, respiration, end-tidal carbon dioxide levels, and oxygen saturation at rest, during autonomic challenge by metronomic breathing, a Valsalva manoeuvre and active standing, and in response to non-stressful pleasant, unpleasant and neutral VES. Pleasantness versus unpleasantness of slides was rated on a 7-point Likert scale. At rest, during physical autonomic challenge, and during neutral VES, parameters did not differ between the patient groups and volunteers. During VES, Likert scores also were similar across the three groups. During pleasant and unpleasant VES, HR decreased (i.e. RRI increased) significantly whereas BP remained unchanged in volunteers. In VMPFC-L patients, HR decrease was insignificant with pleasant and unpleasant VES. BP slightly increased (P = 0.06) with pleasant VES but was stable with unpleasant VES. In contrast, VMPFC-R patients had significant increases in HR and BP during pleasant and not quite significant HR increases (P = 0.06) with only slight BP increase during unpleasant VES. Other biosignals remained unchanged during VES in all groups. Our results show that VMPFC has no major influence on autonomic modulation at rest and during non-emotional, physical stimulation. The paradoxical HR and BP responses in VMPFC-R patients suggest hemispheric specialization for VMPFC interaction with predominant parasympathetic activation by the left, but sympathetic inhibition by the right VMPFC. Valence of non-stressful stimuli has a limited effect with more prominent left VMPFC modulation of pleasant and more right VMPFC modulation of unpleasant stimuli. The paradoxical sympathetic disinhibition in VMPFC-R patients may increase their risk of sympathetic hyperexcitability with negative consequences such as anxiety, hypertension or cardiac arrhythmias.

Max J. Hilz , Orrin Devinsky , Hanna Szczepanska , Joan C. Borod , Harald Marthol , and Marcin Tutaj
Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli
Brain Advance Access published on December 1, 2006, DOI 10.1093/brain/awl299.
Brain 129: 3343-3355.

http://brain.oxfordjournals.org/cgi/content/full/129/12/3343

Prefrontal regions involved in keeping information in and out of mind

Goal-directed behaviour depends on keeping relevant information in mind (working memory) and irrelevant information out of mind (behavioural inhibition or interference resolution). Prefrontal cortex is essential for working memory and for interference resolution, but it is unknown whether these two mental abilities are mediated by common or distinct prefrontal regions. To address this question, functional MRI was used to identify brain regions activated by separate manipulations of working memory load and interference within a single task (the Sternberg item recognition paradigm). Both load and interference manipulations were associated with performance decrements. Subjects were unaware of the interference manipulation. There was a high degree of overlap between the regions activated by load and interference, which included bilateral ventrolateral and dorsolateral prefrontal cortex, anterior insula, anterior cingulate and parietal cortex. Critically, no region was activated exclusively by interference. Several regions within this common network exhibited a brain–behaviour correlation across subjects for the load or interference manipulation. Activation within the right middle frontal gyrus and left inferior frontal gyrus was correlated with the ability to resolve interference efficiently, but not the ability to manage an increased working memory load efficiently. Conversely, activation of the anterior cingulate was correlated with load susceptibility, but was not correlated with interference susceptibility. These findings suggest that, within the circuitry engaged by this task, some regions are more critically involved in the resolution of interference whereas others are more involved in the resolution of an increase in load. The anterior cingulate was engaged to a greater extent by the load than interference manipulation, suggesting that this region, which is thought to be involved in detecting the need for greater allocation of attentional resources, may be particularly implicated during awareness of the need for cognitive control. In the present study, interference resolution did not involve recruitment of additional inhibitory circuitry, but was instead mediated by a subset of the neural system supporting working memory.



Fig. 3 Rendering of group-averaged brain activations. (A) Load-related activations identified by the contrast Load 4 > Load 1 (P <>B) Load-related activations identified by the contrast Load 6 > Load 4 (P <>P <>C) Interference-related activations identified by the contrast Load 4 High Recency > Load 4 (P <>P < 0.05). Liberal thresholds were chosen to illustrate the overlap between regions activated by each contrast. The level of significance of activation at each voxel (T value) is colour-coded according to the scale on the right of each figure. Silvia A. Bunge , Kevin N. Ochsner , John E. Desmond , Gary H. Glover , and John D. E. Gabrieli Prefrontal regions involved in keeping information in and out of mind Brain 124: 2074-2086. Silvia A. Bunge , Kevin N. Ochsner , John E. Desmond , Gary H. Glover , and John D. E. Gabrieli Prefrontal regions involved in keeping information in and out of mind Brain 124: 2074-2086.

Silvia A. Bunge , Kevin N. Ochsner , John E. Desmond , Gary H. Glover , and John D. E. Gabrieli
Prefrontal regions involved in keeping information in and out of mind
Brain 124: 2074-2086.

http://brain.oxfordjournals.org/cgi/content/full/124/10/2074

Right prefrontal cortex and episodic memory retrieval: a functional MRI test of the monitoring hypothesis

Though the right prefrontal cortex is often activated in neuroimaging studies of episodic memory retrieval, the functional significance of this activation remains unresolved. In this functional MRI study of 12 healthy volunteers, we tested the hypothesis that one role of the right prefrontal cortex is to monitor the information retrieved from episodic memory in order to make an appropriate response. The critical comparison was between two word recognition tasks that differed only in whether correct responses did or did not require reference to the spatiotemporal context of words presented during a previous study episode. Activation in a dorsal midlateral region of the right prefrontal cortex was associated with increased contextual monitoring demands, whereas a more ventral region of the right prefrontal cortex showed retrieval-related activation that was independent of task instructions. This functional dissociation of dorsal and ventral right prefrontal regions is discussed in relation to a theoretical framework for the control of episodic memory retrieval.



Fig. 2 Lateral areas showing BOLD signal increases (red) and decreases (blue) in comparisons of (A) the Encoding condition relative to the Control condition, (B) the Inclusion condition relative to the Control condition, (C) the Exclusion condition relative to the Control condition and (D) the Exclusion condition relative to the Inclusion condition. For the purpose of illustration the threshold is slightly lower (P < 0.0001 uncorrected) than in Tables 2–5.

R. N. A. Henson , T. Shallice , and R. J. Dolan
Right prefrontal cortex and episodic memory retrieval: a functional MRI test of the monitoring hypothesis
Brain 122: 1367-1381.

http://brain.oxfordjournals.org/cgi/content/full/122/7/1367