Subregions of DLPFC Display Graded yet Distinct Structural and Functional Connectivity

Abstract

The human dorsolateral prefrontal cortex (DLPFC; approximately corresponding to Brodmann areas 9 and 46) has demonstrable roles in diverse executive functions such as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning. However, it remains unclear whether this is the result of one functionally homogeneous region or whether there are functional subdivisions within the DLPFC. Here, we divided the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically and explored their respective patterns of structural and functional connectivity. In vivo probabilistic tractography (11 females and 13 males) and resting-state functional magnetic resonance imaging (fMRI; 57 females and 21 males) were employed to map out the patterns of connectivity from each DLPFC subregion. Structural connectivity demonstrated graded intraregional connectivity within the DLPFC. The patterns of structural connectivity between the DLPFC subregions and other cortical areas revealed that the dorsal-rostral subregions connections were restricted to other frontal and limbic areas, whereas the ventral-caudal region was widely connected to frontal, parietal, and limbic cortex. Functional connectivity analyses demonstrated that subregions of DLPFC were strongly interconnected to each other. The dorsal subregions were associated with the default mode network (DMN), while middle dorsal-rostral subregions were linked with the multiple demand network (MDN). The ventral-caudal subregion showed increased functional coupling with both DMN and MDN. Our results suggest that the connectivity of the DLPFC may be subdivided along a dorsorostral-ventrocaudal axis with differing (albeit graded) patterns of connectivity reflecting the integrative executive function of the DLPFC. SIGNIFICANCE STATEMENT Research has shown that the dorsolateral prefrontal cortex (DLPFC) plays a role in various executive functions. By dividing the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically, we explored their patterns of structural and functional connectivity. The patterns of connectivity within DLPFC subregions demonstrated graded intraregional connectivity. There were distinctive patterns of connectivity with other cortical areas in dorsal-rostral and ventral-caudal DLPFC subregions. Divisions across DLPFC subregions seem to align with their structural and functional connectivity. Our results suggest that DLPFC may be subdivided by the diagonal axis of the dorsal-ventral axis and rostral-caudal axis, supporting the framework of a functional organization along the anterior-posterior axis in the lateral PFC.

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References 77

1. 1.

   Alexander GE, DeLong MR, Strick PL (1986 ) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381.

   Not in our library10.1146/annurev.ne.09.030186.002041

2. 2.
   An improved neuroanatomical model of the default-mode network reconciles previous neuroimaging and neuropathological findings · 2019

   No notice
3. 3.

   Andrews-Hanna JR, Smallwood J, Spreng RN (2014 ) The default network and self-generated thought: component processes, dynamic control, and clinical relevance. Ann N Y Acad Sci 1316:29–52.

   Not in our library10.1111/nyas.12360

4. 4.

   Ashburner J (2007 ) A fast diffeomorphic image registration algorithm. Neuroimage 38:95–113.

   Not in our library10.1016/j.neuroimage.2007.07.007

5. 5.

   Bahlmann J, Blumenfeld RS, D'Esposito M (2015 ) The rostro-caudal axis of frontal cortex is sensitive to the domain of stimulus information. Cereb Cortex 25:1815–1826.

   Not in our library10.1093/cercor/bht419

6. 6.

   Bajada CJ, Haroon HA, Azadbakht H, Parker GJ, Lambon Ralph MA, Cloutman LL (2017a ) The tract terminations in the temporal lobe: their location and associated functions. Cortex 97:277–290.

   Not in our library10.1016/j.cortex.2016.03.013

7. 7.

   Bajada CJ, Jackson RL, Haroon HA, Azadbakht H, Parker GJM, Lambon Ralph MA, Cloutman LL (2017b ) A graded tractographic parcellation of the temporal lobe. Neuroimage 155:503–512.

   Not in our library10.1016/j.neuroimage.2017.04.016

8. 8.
   Default and Executive Network Coupling Supports Creative Idea Production · 2015

   No notice
9. 9.

   Binney RJ, Parker GJ, Lambon Ralph MA (2012 ) Convergent connectivity and graded specialization in the rostral human temporal lobe as revealed by diffusion-weighted imaging probabilistic tractography. J Cogn Neurosci 24:1998–2014.

   Not in our library10.1162/jocn_a_00263

10. 10.

    Brass M, Derrfuss J, Forstmann B, von Cramon DY (2005 ) The role of the inferior frontal junction area in cognitive control. Trends Cogn Sci 9:314–316.

    Not in our library10.1016/j.tics.2005.05.001

11. 11.

    Brodmann K (1908 ) Contributions to the histological localisation of the cerebral cortex VI Announcement The arrangement of the cortex in humans. J Psychol Neurol 10:229–244.

    Not in our library

12. 12.

    Buckner RL, Andrews-Hanna JR, Schacter DL (2008 ) The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38.

    Not in our library10.1196/annals.1440.011

13. 13.

    Camilleri JA, Müller VI, Fox P, Laird AR, Hoffstaedter F, Kalenscher T, Eickhoff SB (2018 ) Definition and characterization of an extended multiple-demand network. Neuroimage 165:138–147.

    Not in our library10.1016/j.neuroimage.2017.10.020

14. 14.

    Catani M, Dell'Acqua F, Vergani F, Malik F, Hodge H, Roy P, Valabregue R, Thiebaut de Schotten M (2012 ) Short frontal lobe connections of the human brain. Cortex 48:273–291.

    Not in our library10.1016/j.cortex.2011.12.001

15. 15.

    Christoff K, Irving ZC, Fox KC, Spreng RN, Andrews-Hanna JR (2016 ) Mind-wandering as spontaneous thought: a dynamic framework. Nat Rev Neurosci 17:718–731.

    Not in our library10.1038/nrn.2016.113

16. 16.

    Cieslik EC, Zilles K, Caspers S, Roski C, Kellermann TS, Jakobs O, Langner R, Laird AR, Fox PT, Eickhoff SB (2013 ) Is there one DLPFC in cognitive action control? Evidence for heterogeneity from co-activation-based parcellation. Cereb Cortex 23:2677–2689.

    Not in our library10.1093/cercor/bhs256

17. 17.

    Cloutman LL, Binney RJ, Drakesmith M, Parker GJ, Lambon Ralph MA (2012 ) The variation of function across the human insula mirrors its patterns of structural connectivity: evidence from in vivo probabilistic tractography. Neuroimage 59:3514–3521.

    Not in our library10.1016/j.neuroimage.2011.11.016

18. 18.

    Damoiseaux JS, Greicius MD (2009 ) Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity. Brain Struct Funct 213:525–533.

    Not in our library10.1007/s00429-009-0208-6

19. 19.

    Duncan J (2010 ) The multiple-demand (MD) system of the primate brain: mental programs for intelligent behaviour. Trends Cogn Sci 14:172–179.

    Not in our library10.1016/j.tics.2010.01.004

20. 20.

    Duncan J, Owen AM (2000 ) Common regions of the human frontal lobe recruited by diverse cognitive demands. Trends Neurosci 23:475–483.

    Not in our library10.1016/s0166-2236(00)01633-7

21. 21.

    Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, Zilles K (2005 ) A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. Neuroimage 25:1325–1335.

    Not in our library10.1016/j.neuroimage.2004.12.034

22. 22.

    Embleton KV, Haroon HA, Morris DM, Ralph MA, Parker GJ (2010 ) Distortion correction for diffusion-weighted MRI tractography and fMRI in the temporal lobes. Hum Brain Mapp 31:1570–1587.

    Not in our library10.1002/hbm.20959

23. 23.

    Farah MJ, McClelland JL (1991 ) A computational model of semantic memory impairment: modality specificity and emergent category specificity. J Exp Psychol Gen 120:339–357.

    Not in our library

24. 24.

    Friston K (2002 ) Functional integration and inference in the brain. Prog Neurobiol 68:113–143.

    Not in our library10.1016/s0301-0082(02)00076-x

25. 25.

    Friston KJ, Williams S, Howard R, Frackowiak RS, Turner R (1996 ) Movement-related effects in fMRI time-series. Magn Reson Med 35:346–355.

    Not in our library10.1002/mrm.1910350312

26. 26.

    Gerlach KD, Spreng RN, Madore KP, Schacter DL (2014 ) Future planning: default network activity couples with frontoparietal control network and reward-processing regions during process and outcome simulations. Soc Cogn Affect Neurosci 9:1942–1951.

    Not in our library10.1093/scan/nsu001

27. 27.

    Gottlieb J (2007 ) From thought to action: the parietal cortex as a bridge between perception, action, and cognition. Neuron 53:9–16.

    Not in our library10.1016/j.neuron.2006.12.009

28. 28.

    Haber SN (2003 ) The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat 26:317–330.

    Not in our library10.1016/j.jchemneu.2003.10.003

29. 29.

    Halai AD, Welbourne SR, Embleton K, Parkes LM (2014 ) A comparison of dual gradient-echo and spin-echo fMRI of the inferior temporal lobe. Hum Brain Mapp 35:4118–4128.

    Not in our library10.1002/hbm.22463

30. 30.

    Haroon HA, Morris DM, Embleton KV, Alexander DC, Parker GJ (2009 ) Using the model-based residual bootstrap to quantify uncertainty in fiber orientations from Q-ball analysis. IEEE Trans Med Imaging 28:535–550.

    Not in our library10.1109/tmi.2008.2006528

31. 31.

    Hoshi E (2006 ) Functional specialization within the dorsolateral prefrontal cortex: a review of anatomical and physiological studies of non-human primates. Neurosci Res 54:73–84.

    Not in our library10.1016/j.neures.2005.10.013

32. 32.

    Jackson RL, Hoffman P, Pobric G, Lambon Ralph MA (2016 ) The semantic network at work and rest: differential connectivity of anterior temporal lobe subregions. J Neurosci 36:1490–1501.

    Not in our library10.1523/jneurosci.2999-15.2016

33. 33.

    Jackson RL, Bajada CJ, Rice GE, Cloutman LL, Lambon Ralph MA (2018 ) An emergent functional parcellation of the temporal cortex. Neuroimage 170:385–399.

    Not in our library10.1016/j.neuroimage.2017.04.024

34. 34.

    Jackson RL, Bajada CJ, Lambon Ralph MA, Cloutman LL (2020 ) The graded change in connectivity across the ventromedial prefrontal cortex reveals distinct subregions. Cereb Cortex 30:165–180.

    Not in our library10.1093/cercor/bhz079

35. 35.

    Jarbo K, Verstynen TD (2015 ) Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum. J Neurosci 35:3865–3878.

    Not in our library10.1523/jneurosci.2636-14.2015

36. 36.

    Jeurissen B, Leemans A, Jones DK, Tournier JD, Sijbers J (2011 ) Probabilistic fiber tracking using the residual bootstrap with constrained spherical deconvolution. Hum Brain Mapp 32:461–479.

    Not in our library10.1002/hbm.21032

37. 37.

    Jones DK (2008 ) Studying connections in the living human brain with diffusion MRI. Cortex 44:936–952.

    Not in our library10.1016/j.cortex.2008.05.002

38. 38.

    Jung J, Cloutman LL, Binney RJ, Lambon Ralph MA (2017 ) The structural connectivity of higher order association cortices reflects human functional brain networks. Cortex 97:221–239.

    Not in our library10.1016/j.cortex.2016.08.011

39. 39.

    Jung J, Visser M, Binney RJ, Lambon Ralph MA (2018 ) Establishing the cognitive signature of human brain networks derived from structural and functional connectivity. Brain Struct Funct 223:4023–4038.

    Not in our library10.1007/s00429-018-1734-x

40. 40.

    Koechlin E, Ody C, Kouneiher F (2003 ) The architecture of cognitive control in the human prefrontal cortex. Science 302:1181–1185.

    Not in our library10.1126/science.1088545

41. 41.

    Kohn N, Eickhoff SB, Scheller M, Laird AR, Fox PT, Habel U (2014 ) Neural network of cognitive emotion regulation–an ALE meta-analysis and MACM analysis. Neuroimage 87:345–355.

    Not in our library10.1016/j.neuroimage.2013.11.001

42. 42.

    Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH (2003 ) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19:1233–1239.

    Not in our library10.1016/s1053-8119(03)00169-1

43. 43.

    Martino J, Brogna C, Robles SG, Vergani F, Duffau H (2010 ) Anatomic dissection of the inferior fronto-occipital fasciculus revisited in the lights of brain stimulation data. Cortex 46:691–699.

    Not in our library10.1016/j.cortex.2009.07.015

44. 44.

    Menon V, Uddin LQ (2010 ) Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct 214:655–667.

    Not in our library10.1007/s00429-010-0262-0

45. 45.

    Miller BL, Cummings JL (2007 ) The human frontal lobes: functions and disorders, Ed 2. New York: Guilford Press.

    Not in our library

46. 46.

    Moayedi M, Salomons TV, Dunlop KA, Downar J, Davis KD (2015 ) Connectivity-based parcellation of the human frontal polar cortex. Brain Struct Funct 220:2603–2616.

    Not in our library10.1007/s00429-014-0809-6

47. 47.

    Morecraft RJ, Cipolloni PB, Stilwell-Morecraft KS, Gedney MT, Pandya DN (2004 ) Cytoarchitecture and cortical connections of the posterior cingulate and adjacent somatosensory fields in the rhesus monkey. J Comp Neurol 469:37–69.

    Not in our library10.1002/cne.10980

48. 48.

    Morris DM, Embleton KV, Parker GJ (2008 ) Probabilistic fibre tracking: differentiation of connections from chance events. Neuroimage 42:1329–1339.

    Not in our library10.1016/j.neuroimage.2008.06.012

49. 49.

    Morris R, Pandya DN, Petrides M (1999 ) Fiber system linking the mid-dorsolateral frontal cortex with the retrosplenial/presubicular region in the rhesus monkey. J Comp Neurol 407:183–192.

    Not in our library10.1002/(sici)1096-9861(19990503)407:2<183::aid-cne3>3.0.co;2-n

50. 50.

    Nee DE, Wager TD, Jonides J (2007 ) Interference resolution: insights from a meta-analysis of neuroimaging tasks. Cogn Affect Behav Neurosci 7:1–17.

    Not in our library10.3758/cabn.7.1.1

51. 51.

    Parker GJ, Alexander DC (2005 ) Probabilistic anatomical connectivity derived from the microscopic persistent angular structure of cerebral tissue. Philos Trans R Soc Lond B Biol Sci 360:893–902.

    Not in our library10.1098/rstb.2005.1639

52. 52.

    Parker GJ, Luzzi S, Alexander DC, Wheeler-Kingshott CA, Ciccarelli O, Lambon Ralph MA (2005 ) Lateralization of ventral and dorsal auditory-language pathways in the human brain. Neuroimage 24:656–666.

    Not in our library10.1016/j.neuroimage.2004.08.047

53. 53.

    Petrides M (1985 ) Deficits in non-spatial conditional associative learning after periarcuate lesions in the monkey. Behav Brain Res 16:95–101.

    Not in our library10.1016/0166-4328(85)90085-3

54. 54.

    Petrides M (2005a ) The rostral–caudal axis of cognitive control within the lateral frontal cortex. In: From monkey brain to human brain. Cambridge: The MIT Press.

    Not in our library

55. 55.

    Petrides M (2005b ) Lateral prefrontal cortex: architectonic and functional organization. Philos Trans R Soc Lond B Biol Sci 360:781–795.

    Not in our library10.1098/rstb.2005.1631

56. 56.

    Petrides M, Pandya DN (1984 ) Projections to the frontal cortex from the posterior parietal region in the rhesus monkey. J Comp Neurol 228:105–116.

    Not in our library10.1002/cne.902280110

57. 57.

    Petrides M, Pandya DN (1999 ) Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns. Eur J Neurosci 11:1011–1036.

    Not in our library10.1046/j.1460-9568.1999.00518.x

58. 58.

    Poser BA, Versluis MJ, Hoogduin JM, Norris DG (2006 ) BOLD contrast sensitivity enhancement and artifact reduction with multiecho EPI: parallel-acquired inhomogeneity-desensitized fMRI. Magn Reson Med 55:1227–1235.

    Not in our library10.1002/mrm.20900

59. 59.

    Power JD, Mitra A, Laumann TO, Snyder AZ, Schlaggar BL, Petersen SE (2014 ) Methods to detect, characterize, and remove motion artifact in resting state fMRI. NeuroImage 84:320–341.

    Not in our library10.1016/j.neuroimage.2013.08.048

60. 60.
    A default mode of brain function · 2001

    Not checked
61. 61.

    Ramnani N, Owen AM (2004 ) Anterior prefrontal cortex: insights into function from anatomy and neuroimaging. Nat Rev Neurosci 5:184–194.

    Not in our library10.1038/nrn1343

62. 62.

    Rottschy C, Langner R, Dogan I, Reetz K, Laird AR, Schulz JB, Fox PT, Eickhoff SB (2012 ) Modelling neural correlates of working memory: a coordinate-based meta-analysis. Neuroimage 60:830–846.

    Not in our library10.1016/j.neuroimage.2011.11.050

63. 63.

    Schmahmann JD, Pandya DN, Wang R, Dai G, D'Arceuil HE, de Crespigny AJ, Wedeen VJ (2007 ) Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 130:630–653.

    Not in our library10.1093/brain/awl359

64. 64.

    Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, Reiss AL, Greicius MD (2007 ) Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27:2349–2356.

    Not in our library10.1523/jneurosci.5587-06.2007

65. 65.

    Sormaz M, Murphy C, Wang HT, Hymers M, Karapanagiotidis T, Poerio G, Margulies DS, Jefferies E, Smallwood J (2018 ) Default mode network can support the level of detail in experience during active task states. Proc Natl Acad Sci U S A 115:9318–9323.

    Not in our library10.1073/pnas.1721259115

66. 66.

    Spreng NR, Grady CL (2010 ) Patterns of brain activity supporting autobiographical memory, prospection, and theory of mind, and their relationship to the default mode network. J Cogn Neurosci 22:1112–1123.

    Not in our library10.1162/jocn.2009.21282

67. 67.

    Spreng RN, Sepulcre J, Turner GR, Stevens WD, Schacter DL (2013 ) Intrinsic architecture underlying the relations among the default, dorsal attention, and frontoparietal control networks of the human brain. J Cogn Neurosci 25:74–86.

    Not in our library10.1162/jocn_a_00281

68. 68.

    Spreng RN, DuPre E, Selarka D, Garcia J, Gojkovic S, Mildner J, Luh WM, Turner GR (2014 ) Goal-congruent default network activity facilitates cognitive control. J Neurosci 34:14108–14114.

    Not in our library10.1523/jneurosci.2815-14.2014

69. 69.

    Spreng RN, Lockrow AW, DuPre E, Setton R, Spreng KAP, Turner GR (2018 ) Semanticized autobiographical memory and the default - executive coupling hypothesis of aging. Neuropsychologia 110:37–43.

    Not in our library10.1016/j.neuropsychologia.2017.06.009

70. 70.

    Thiebaut de Schotten M, Dell'Acqua F, Valabregue R, Catani M (2012 ) Monkey to human comparative anatomy of the frontal lobe association tracts. Cortex 48:82–96.

    Not in our library10.1016/j.cortex.2011.10.001

71. 71.

    Tournier JD, Yeh CH, Calamante F, Cho KH, Connelly A, Lin CP (2008 ) Resolving crossing fibres using constrained spherical deconvolution: validation using diffusion-weighted imaging phantom data. Neuroimage 42:617–625.

    Not in our library10.1016/j.neuroimage.2008.05.002

72. 72.
    Left dorsolateral prefrontal cortex supports context-dependent prioritisation of off-task thought · 2019

    No notice
73. 73.

    Walker AE (1940 ) A cytoarchitectural study of the prefrontal area of the macaque monkey. J Comp Neurol 73:59–86.

    Not in our library10.1002/cne.900730106

74. 74.

    Woolgar A, Hampshire A, Thompson R, Duncan J (2011 ) Adaptive coding of task-relevant information in human frontoparietal cortex. J Neurosci 31:14592–14599.

    Not in our library10.1523/jneurosci.2616-11.2011

75. 75.

    Yan CG, Craddock CR, Zuo XN, Zang YF, Milham MP (2013 ) Standardizing the intrinsic brain: Towards robust measurement of inter-individual variation in 1000 functional connectomes. NeuroImage 80:246–262.

    Not in our library10.1016/j.neuroimage.2013.04.081

76. 76.

    Yeterian EH, Pandya DN, Tomaiuolo F, Petrides M (2012 ) The cortical connectivity of the prefrontal cortex in the monkey brain. Cortex 48:58–81.

    Not in our library10.1016/j.cortex.2011.03.004

77. 77.

    Zheng D, Oka T, Bokura H, Yamaguchi S (2008 ) The key locus of common response inhibition network for no-go and stop signals. J Cogn Neurosci 20:1434–1442.

    Not in our library10.1162/jocn.2008.20100

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