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

Prefrontal cortex and recognition memory. Functional-MRI evidence for context-dependent retrieval processes

Functional neuroimaging studies of episodic recognition memory consistently demonstrate retrieval-associated activation in right prefrontal regions, including the right anterior and right dorsolateral prefrontal cortices. In theory, these activations could reflect processes associated with retrieval success, retrieval effort or retrieval attempt; each of these hypotheses has some support from previous studies. In Experiment 1, we examined these functional interpretations using functional MRI to measure prefrontal activation across multiple levels of recognition performance. Results revealed similar patterns of right prefrontal activation across varying levels of retrieval success and retrieval effort, suggesting that these activations reflect retrieval attempt. Retrieval attempt may include initiation of retrieval search or evaluation of the products of retrieval, such as scrutiny of specific attributes of the test item in an effort to determine whether it was encountered previously. In Experiment 2, we examined whether engagement of retrieval attempt is context-dependent by varying the context in which retrieval was performed; this was done by changing test instructions. Importantly, study and test stimuli were held constant, with only the test instructions varying across conditions. Results revealed that the pattern of right prefrontal activation varied across retrieval contexts. Collectively, these experiments suggest that right prefrontal regions mediate processes associated with retrieval attempt, with the probability of engaging these regions depending upon the retrieval context. Conflicting results across previous studies may be reconciled if the influence of retrieval context on the adopted retrieval strategy is considered. Finally, these results suggest that right prefrontal regions activated during recognition are not critical for successful performance as similar magnitudes of activation were present across multiple levels of performance. These findings reconcile imaging results with the selective effects of prefrontal lesions on retrieval- intensive episodic memory tests.

AD Wagner , JE Desmond , GH Glover , and JD Gabrieli.
Prefrontal cortex and recognition memory. Functional-MRI evidence for context-dependent retrieval processes.
Brain 121: 1985-2002.

http://brain.oxfordjournals.org/cgi/content/abstract/121/10/1985

Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour

Three patients with a unilateral cortical lesion affecting the dorsolateral prefrontal cortex (DLPFC), i.e. Brodmann area 46, were tested using different paradigms of reflexive saccades (gap and overlap tasks), intentional saccades (antisaccades, memory-guided and predictive saccades) and smooth pursuit movements. Visually guided saccades with gap and overlap, latency of correct antisaccades and memory-guided saccades and the gain of smooth pursuit were normal, compared with controls. These results confirm our anatomical data showing that the adjacent frontal eye field (FEF) was unimpaired in these patients. The specific pattern of abnormalities after a unilateral DLPFC lesion, compared with that of the FEF lesions previously reported, consists mainly of: (i) a bilateral increase in the percentage of errors in the antisaccade task (misdirected reflexive saccades); (ii) a bilateral increase in the variable error in amplitude, without significant decrease in the gain, in the memory-guided saccade task; and (iii) a bilateral decrease in the percentage of anticipatory saccades in the predictive task. Taken together, these results suggest that the DLPFC plays a crucial role in the decisional processes, preparing saccades by inhibiting unwanted reflexive saccades (inhibition), maintaining memorized information for ongoing intentional saccades (short-term spatial memory) or facilitating anticipatory saccades (prediction), depending upon current external environmental and internal circumstances.




Fig. 6 Cortical areas involved in saccades. After receiving visual information in the occipital lobe and after visuospatial integration in the PPC, a saccade may be either triggered reflexively, mainly by the PEF, or triggered intentionally by the FEF, an area which also appears to be involved in active visual fixation. If a reflexive saccade must be inhibited, the DLPFC appears to play a crucial role (1). This area is also involved in short-term spatial memory (2) and prediction (3) when anticipatory saccades must be performed. With these three different actions, the DLPFC could play an important role in the decisional processes controlling ocular motor behaviour. The SEF could be involved in motor programmes including several successive saccades, or saccades combined with other body movements, whereas the CEF appears to activate all the areas controlling intentional saccades via a motivation process. ACC = anterior cingulate cortex; CEF = cingulate eye field; cs = central sulcus; DLPFC = dorsolateral prefrontal cortex; FEF = frontal eye field; ips = intraparietal sulcus; ls = lateral sulcus; pcs = precentral sulcus; PEF = parietal eye field; PPC = posterior parietal cortex; RF = brainstem reticular formation; SC = superior colliculus; SEF = supplementary eye field; 1, 2, 3 = the main actions of the DLPFC; + = saccade triggering; – = saccade inhibition.

C. Pierrot-Deseilligny , R. M. Müri , C. J. Ploner , B. Gaymard , S. Demeret , and S. Rivaud-Pechoux .
Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour.
Brain Advance Access published on June 1, 2003, DOI 10.1093/brain/awg148.
Brain 126: 1460-1473.

http://brain.oxfordjournals.org/cgi/content/full/126/6/1460

Functional Internal Complexity of Amygdala: Focus on Gene Activity Mapping After Behavioral Training and Drugs of Abuse

The amygdala is a heterogeneous brain structure implicated in processing of emotions and storing the emotional aspects of memories. Gene activity markers such as c-Fos have been shown to reflect both neuronal activation and neuronal plasticity. Herein, we analyze the expression patterns of gene activity markers in the amygdala in response to either behavioral training or treatment with drugs of abuse and then we confront the results with data on other approaches to internal complexity of the amygdala. c-Fos has been the most often studied in the amygdala, showing specific expression patterns in response to various treatments, most probably reflecting functional specializations among amygdala subdivisions. In the basolateral amygdala, c-Fos expression appears to be consistent with the proposed role of this nucleus in a plasticity of the current stimulus-value associations. Within the medial part of the central amygdala, c-Fos correlates with acquisition of alimentary/gustatory behaviors. On the other hand, in the lateral subdivision of the central amygdala, c-Fos expression relates to attention and vigilance. In the medial amygdala, c-Fos appears to be evoked by emotional novelty of the experimental situation. The data on the other major subdivisions of the amygdala are scarce. In conclusion, the studies on the gene activity markers, confronted with other approaches involving neuroanatomy, physiology, and the lesion method, have revealed novel aspects of the amygdala, especially pointing to functional heterogeneity of this brain region that does not fit very well into contemporarily active debate on serial versus parallel information processing within the amygdala.

Ewelina Knapska, Kasia Radwanska, Tomasz Werka, and Leszek Kaczmarek.
Functional Internal Complexity of Amygdala: Focus on Gene Activity Mapping After Behavioral Training and Drugs of Abuse.
Physiol. Rev. 87: 1113-1173, 2007. doi:10.1152/physrev.00037.2006.

http://physrev.physiology.org/cgi/content/abstract/87/4/1113

Lesions of the Basal Amygdala Block Expression of Conditioned Fear But Not Extinction

Although the role of the amygdala in acquisition of conditioned fear is well established, there is debate concerning the intra-amygdala circuits involved. The lateral nucleus of the amygdala (LA) is thought to be an essential site of plasticity in fear conditioning. The LA has both direct and indirect [via the basal nuclei; basal amygdala (BA)] projections to the central nucleus (Ce) of the amygdala, an essential output for fear behaviors. Lesions of the LA or Ce prevent acquisition of conditioned freezing to a conditioned stimulus, but BA lesions do not, suggesting that the BA is not normally involved in fear conditioning. If true, posttraining BA lesions should also have no effect. Replicating previous studies, we found that rats given electrolytic BA lesions before training acquired conditioned fear normally. They also showed normal long-term retention and extinction of conditioned fear. Unexpectedly, BA lesions made after training completely blocked expression of conditioned fear. Despite this deficit, lesioned rats were able to learn a new tone-shock association. Thus, although the LA-Ce system is sufficient for fear acquisition in the absence of the BA, it is not sufficient when the BA is present, suggesting that the BA is an important site of plasticity in fear conditioning. The pattern of lesion deficits we observed (after but not before training) might be explained by homeostatic mechanisms that balance plasticity over multiple inputs, regulating the influence of the BA and LA onto Ce output neurons.



Figure 5. Model to account for deficits with posttraining, but not pretraining, lesions. We suggest that homeostatic mechanisms that balance plasticity over multiple inputs could regulate the influence of the BA, LA, and MGm onto CeM neurons. 1, The CeM receives inputs from the MGm, BA, and LA via ITC cells (dashed line). 2, After fear conditioning, BA inputs gain a large proportion of the total plasticity, inhibiting the development of plasticity in neighboring inputs. 3, Posttraining lesions of the BA remove this plasticity, leaving the system subthreshold for producing a fear response. 4, With pretraining removal of the BA, however, increased plasticity in the LA and MGm supports fear learning. For simplicity, projections from the MGm to the LA and from the LA to the BA are not shown.

David Anglada-Figueroa, and Gregory J. Quirk
Lesions of the Basal Amygdala Block Expression of Conditioned Fear But Not Extinction
J. Neurosci. 25: 9680-9685; doi:10.1523/JNEUROSCI.2600-05.2005

http://www.jneurosci.org/cgi/content/full/25/42/9680

Cortical Connections of the Insular and Adjacent Parieto-temporal Fields in the Cat

We present a comprehensive analysis of the cortical connections of the insular and adjacent cortical areas in the domestic cat by using microinjections of wheat-germ agglutinin conjugated to horseradish peroxidase. We examined the identity and extent of the cortical fields connected to each area, the relative anatomical weights of the various connections, their laminar origin, and their paths across the cerebral commissures. Our main finding is that despite their relatively small size and close apposition, the connections of the insular and adjacent areas are far more widespread and more specific to each area than previously realized, suggesting that each area is involved in disparate aspects of cortical integration. The granular insular area is linked to a constellation of somatosensory, motor, premotor and prefrontal districts. The dysgranular insular area is chiefly associated with lateral prefrontal and premotor, lateral somatosensory and perirhinal cortices. The dorsal agranular insular area is connected with limbic neocortical fields, while the ventral agranular insular area is associated with an array of olfactory allocortical fields. The anterior sylvian area is associated with visual, auditory and multimodal areas, with the dorsolateral prefrontal cortex, and with perirhinal area 36. The parainsular area is linked to non-tonotopic auditory and ventromedial frontal areas. Trajectories followed by the callosal axons of each of the investigated areas are extremely divergent. As a whole, the picture of the insular region that emerges from this and a parallel study (Clascá et al., J Comp Neurol 384:456–482, 1997) is that of an extreme heterogeneity, both in terms of histological architecture and neural connections. Comparison with earlier published reports on primates suggests that most, but not all, of the areas we investigated in cats may have an direct counterpart within the insula of Old World monkeys.



Figure 1



Figure 17. Summary of cortical and thalamic relationships of the areas under study. Each panel represents the connections of an area on standard medial and lateral views of the hemisphere. Outlined letters identify the area of interest. Thicker lines and bold case highlight heavier connections, while thin or dashed lines indicate less numerous connections. Thalamic input is represented by the ellipsoids and arrow at the bottom of each panel. Connections of (A) GI, (B) DI, (C) AId, (D) AIv, (E) Pi, (F) AS. Abbreviations for thalamic nuclei (n): CeM, centralis medialis n.; LM, lateralis medialis n.; M(D), mediodorsal nucleus; MGm, medial geniculate n., medial division; MGvl, medial geniculate n., ventrolateral subnucleus; Pf, parafascicular n.; PoM, posterior thalamic n., medial division; Re, reuniens n.; Rh, rhomboid n.; VL, ventrolateral n.; VM, ventromedial n.; VPi, ventralis posteroinferior n.; VPmP, ventralis posteromedialis n., peripheral subnucleus. For other abbreviations see Table 1.

Francisco Clascá , Alfonso Llamas , and Fernando Reinoso-Suárez
Cortical Connections of the Insular and Adjacent Parieto-temporal Fields in the Cat.
Cereb. Cortex 10: 371-399.

http://cercor.oxfordjournals.org/cgi/content/full/10/4/371

Superior temporal gyrus and insula provide response and outcome-dependent information during assessment and action selection in a decision-making ...

Decision-making is a complex process that comprises the assessment of a situation, the selection of an action, and the evaluation of an outcome. Distinct neural systems may contribute differentially during various stages within a decision-making situation. This study investigated whether neural activation during assessment or action selection is critically dependent on previous outcomes or actions. Twelve healthy, right-handed subjects (6 females) played a Rock Paper Scissors (RPS) computer game during functional magnetic resonance imaging. Bilateral insula and medial prefrontal cortex (including the anterior cingulate) were specifically engaged during the assessment and action selection stages of decision-making, whereas bilateral superior frontal gyrus and right inferior parietal lobule activated more during the outcome. Two regions of activation within the bilateral superior temporal gyrus activated only when the previous outcome was a win. Moreover, right insula and superior temporal gyrus were active more when the subject switched responses relative to staying with the same choice made on the previous trial. These findings support the hypothesis that distinct neural systems underlie different stages of the decision-making process. Furthermore, the superior temporal gyrus may play an important role in integrating previous actions and successful outcomes into one's decision-making strategy.

Paulus MP, Feinstein JS, Leland D, Simmons AN.
Superior temporal gyrus and insula provide response and outcome-dependent information during assessment and action selection in a decision-making situation.
Neuroimage. 2005 Apr 1;25(2):607-15.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15784440