The long-term goal of the proposed research program is to understand the role of prefrontal limbic cortices in cognitive, mnemonic and emotional processes. Regionally distinct limbic and eulaminate prefrontal cortices have a different role in these functions. The objective of the proposed studies is to investigate the anatomic organization of a massive feedback system issued from prefrontal limbic and adjacent eulaminate cortices and distributed to the mediodorsal and midline thalamic nuclei and the amygdala. Our previous work indicates that prefrontal limbic and eulaminate cortices can be distinguished by their structure and pattern of interconnections: Eulaminate cortices project to limbic cortices primarily through their upper layers. In contrast, limbic cortices project to all eulaminate cortices primarily through their deep layers, suggesting a predominant role in feedback communication. Our working hypothesis is that feedback projections from the functionally distinct prefrontal limbic and eulaminate cortices to the thalamus and the amygdala have specific roles in mnemonic, emotional and cognitive processes associated with these structures. We will test this hypothesis by investigating: 1 - how prefrontal limbic cortices, in comparison with the eulaminate, parcel feedback projection neurons destined for the mediodorsal thalamic nucleus and those destined for neighboring cortices. 2- whether the organization of projection neurons from prefrontal cortices to the thalamus follows a general plan, or if it varies depending on the particular thalamic destination or cortical origin. 3- If prefrontal limbic and eulaminate cortices have a different anatomic relationship with the amygdala based on their respective roles in emotion and cognition. Populations of feedback projection neurons will be identified by different tracers and will be considered anatomically distinct if they are segregated in different layers or modules, or by their differential expression of a cytoskeletal marker. The proposed studies have important implications for understanding the dissociation of emotional from cognitive processes in mental diseases which affect the prefrontal cortices, in general, and their limbic component, in particular.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-8 (01))
Program Officer
Baughman, Robert W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
Other Health Professions
Schools of Allied Health Profes
United States
Zip Code
García-Cabezas, Miguel Á; Barbas, Helen; Zikopoulos, Basilis (2018) Parallel Development of Chromatin Patterns, Neuron Morphology, and Connections: Potential for Disruption in Autism. Front Neuroanat 12:70
Barbas, Helen; Wang, Jingyi; Joyce, Mary Kate P et al. (2018) Pathway mechanism for excitatory and inhibitory control in working memory. J Neurophysiol :
Wang, Jingyi; Barbas, Helen (2018) Specificity of Primate Amygdalar Pathways to Hippocampus. J Neurosci 38:10019-10041
Joyce, Mary Kate P; Barbas, Helen (2018) Cortical Connections Position Primate Area 25 as a Keystone for Interoception, Emotion, and Memory. J Neurosci 38:1677-1698
García-Cabezas, Miguel Á; Joyce, Mary Kate P; John, Yohan J et al. (2017) Mirror trends of plasticity and stability indicators in primate prefrontal cortex. Eur J Neurosci 46:2392-2405
Zikopoulos, Basilis; Höistad, Malin; John, Yohan et al. (2017) Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions. J Neurosci 37:5051-5064
García-Cabezas, Miguel Á; Barbas, Helen (2017) Anterior Cingulate Pathways May Affect Emotions Through Orbitofrontal Cortex. Cereb Cortex 27:4891-4910
Beul, Sarah F; Barbas, Helen; Hilgetag, Claus C (2017) A Predictive Structural Model of the Primate Connectome. Sci Rep 7:43176
Hilgetag, Claus C; Medalla, Maria; Beul, Sarah F et al. (2016) The primate connectome in context: Principles of connections of the cortical visual system. Neuroimage 134:685-702
Anderson, Michael C; Bunce, Jamie G; Barbas, Helen (2016) Prefrontal-hippocampal pathways underlying inhibitory control over memory. Neurobiol Learn Mem 134 Pt A:145-161

Showing the most recent 10 out of 39 publications