Abstract

Introduction: The nucleus accumbens (NAc) is one of the principal components of the ventral striatum and serves as a functional interface between limbic, cognitive, and motor systems. Although it is a clinical target for stereotactic surgery and neuromodulation procedures, precise delineation of its boundaries remains challenging due to its anatomical continuity with adjacent gray and white matter structures. The aim of this study was to evaluate the anatomical boundaries of the NAc based on white matter fiber dissection.

Materials and Methods: This study was conducted on three formalin-fixed human brain cadavers using the white matter fiber dissection technique under microscopic magnification. The spatial relationships of the NAc were evaluated through stepwise dissections performed in lateral to medial, medial to lateral, and superior to inferior orientations.

Results: The dissections demonstrated that the NAc represents a transitional zone within the ventral striatum rather than an isolated nucleus with distinct and sharp boundaries. Superiorly, the NAc showed continuity with the head of the caudate nucleus without a clear demarcation, while laterally and inferolaterally it merged with the substantia innominata. In contrast, the body and limbs of the anterior commissure, the anterior segment of the internal capsule, the fornix, the cingulum, and the ventromedial fibers of the uncinate fasciculus provided reliable and reproducible reference planes for defining the relative anatomical boundaries of the NAc. In particular, sagittal and vertical reference lines defined based on the anterior commissure were found to be decisive in the three-dimensional assessment of the superior and posterior extent of the NAc.

Conclusion: This study demonstrates that the anatomical boundaries of the NAc can be evaluated more consistently using a topographic approach based on white matter fiber dissection rather than relying on classical gray matter–based absolute definitions. A reference framework centered on white matter structures enables a more accurate interpretation of the anatomical organization of the NAc and may facilitate anatomical orientation in stereotactic, functional surgical, and neuromodulation procedures targeting this region.

Keywords: nucleus accumbens, ventral striatum, white matter fiber dissection, anatomical boundaries

References

  1. Nieuwenhuys R, Voogd J, Van Huijzen C. The human central nervous system. Berlin Heidelberg: Springer; 2008. https://doi.org/10.1007/978-3-540-34686-9
  2. Humphries MD, Prescott TJ. The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Prog Neurobiol 2010; 90: 385-417. https://doi.org/10.1016/j.pneurobio.2009.11.003
  3. Sesack SR, Grace AA. Cortico-Basal Ganglia reward network: microcircuitry. Neuropsychopharmacology 2010; 35: 27-47. https://doi.org/10.1038/npp.2009.93
  4. Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 1990; 13: 266-271. https://doi.org/10.1016/0166-2236(90)90107-l
  5. Middleton FA, Strick PL. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Brain Res Rev 2000; 31: 236-250. https://doi.org/10.1016/s0165-0173(99)00040-5
  6. Haber SN. The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat 2003; 26: 317-330. https://doi.org/10.1016/j.jchemneu.2003.10.003
  7. Heimer L, Switzer RD, Van Hoesen GW. Ventral striatum and ventral pallidum: components of the motor system? Trends in Neurosciences 1982;5:83-87. https://doi.org/10.1016/0166-2236(82)90037-6
  8. de Olmos JS, Heimer L. The concepts of the ventral striatopallidal system and extended amygdala. Ann N Y Acad Sci 1999; 877: 1-32. https://doi.org/10.1111/j.1749-6632.1999.tb09258.x
  9. Groenewegen HJ, Berendse HW, Haber SN. Organization of the output of the ventral striatopallidal system in the rat: ventral pallidal efferents. Neuroscience 1993; 57: 113-142. https://doi.org/10.1016/0306-4522(93)90115-v
  10. Mogenson GJ, Jones DL, Yim CY. From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 1980; 14: 69-97. https://doi.org/10.1016/0301-0082(80)90018-0
  11. Baydin S, Yagmurlu K, Tanriover N, Gungor A, Rhoton AL. Microsurgical and fiber tract anatomy of the nucleus accumbens. Oper Neurosurg 2016; 12: 269-288. https://doi.org/10.1227/NEU.0000000000001133
  12. Baydin S, Gungor A, Tanriover N, Baran O, Middlebrooks EH, Rhoton AL. Fiber tracts of the medial and inferior surfaces of the cerebrum. World Neurosurg 2017; 98: 34-49. https://doi.org/10.1016/j.wneu.2016.05.016
  13. Powell EW, Leman RB. Connections of the nucleus accumbens. Brain Res 1976; 105: 389-403. https://doi.org/10.1016/0006-8993(76)90589-8
  14. Sturm V, Lenartz D, Koulousakis A, et al. The nucleus accumbens: a target for deep brain stimulation in obsessive-compulsive- and anxiety-disorders. J Chem Neuroanat 2003; 26: 293-299. https://doi.org/10.1016/j.jchemneu.2003.09.003
  15. Mayberg HS, Lozano AM, Voon V, et al. Deep brain stimulation for treatment-resistant depression. Neuron 2005; 45: 651-660. https://doi.org/10.1016/j.neuron.2005.02.014
  16. Bewernick BH, Hurlemann R, Matusch A, et al. Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry 2010; 67: 110-116. https://doi.org/10.1016/j.biopsych.2009.09.013
  17. Denys D, Mantione M, Figee M, et al. Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 2010; 67: 1061-1068. https://doi.org/10.1001/archgenpsychiatry.2010.122
  18. Bewernick BH, Kayser S, Sturm V, Schlaepfer TE. Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. Neuropsychopharmacology 2012; 37: 1975-1985. https://doi.org/10.1038/npp.2012.44
  19. Müller UJ, Voges J, Steiner J, et al. Deep brain stimulation of the nucleus accumbens for the treatment of addiction. Ann N Y Acad Sci 2013; 1282: 119-128. https://doi.org/10.1111/j.1749-6632.2012.06834.x
  20. Kuhn J, Möller M, Treppmann JF, et al. Deep brain stimulation of the nucleus accumbens and its usefulness in severe opioid addiction. Mol Psychiatry 2014; 19: 145-146. https://doi.org/10.1038/mp.2012.196
  21. Müller UJ, Sturm V, Voges J, et al. Nucleus accumbens deep brain stimulation for alcohol addiction - safety and clinical long-term results of a pilot trial. Pharmacopsychiatry 2016; 49: 170-173. https://doi.org/10.1055/s-0042-104507
  22. Li MCH, Cook MJ. Deep brain stimulation for drug-resistant epilepsy. Epilepsia 2018; 59: 273-290. https://doi.org/10.1111/epi.13964
  23. Shivacharan RS, Rolle CE, Barbosa DAN, et al. Pilot study of responsive nucleus accumbens deep brain stimulation for loss-of-control eating. Nat Med 2022; 28: 1791-1796. https://doi.org/10.1038/s41591-022-01941-w
  24. Davidson B, Giacobbe P, George TP, et al. Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial. Mol Psychiatry 2022; 27: 3992-4000. https://doi.org/10.1038/s41380-022-01677-6
  25. Bach P, Luderer M, Müller UJ, et al. Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial. Transl Psychiatry 2023; 13: 49. https://doi.org/10.1038/s41398-023-02337-1
  26. Rezai AR, Mahoney JJ, Ranjan M, et al. Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder. J Neurosurg 2023; 140: 231-239. https://doi.org/10.3171/2023.4.JNS23114
  27. Neto LL, Oliveira E, Correia F, Ferreira AG. The human nucleus accumbens: where is it? A stereotactic, anatomical and magnetic resonance imaging study. Neuromodulation 2008; 11: 13-22. https://doi.org/10.1111/j.1525-1403.2007.00138.x
  28. Lucas-Neto L, Neto D, Oliveira E, et al. Three dimensional anatomy of the human nucleus accumbens. Acta Neurochir (Wien) 2013; 155: 2389-2398. https://doi.org/10.1007/s00701-013-1820-z
  29. Salgado S, Kaplitt MG. The nucleus accumbens: a comprehensive review. Stereotact Funct Neurosurg 2015; 93: 75-93. https://doi.org/10.1159/000368279
  30. Yagmurlu K, Vlasak AL, Rhoton AL. Three-dimensional topographic fiber tract anatomy of the cerebrum. Neurosurgery 2015; 11(Suppl 2): 274-305; discussion 305. https://doi.org/10.1227/NEU.0000000000000704
  31. Fernández-Miranda JC, Rhoton AL, Alvarez-Linera J, Kakizawa Y, Choi C, de Oliveira EP. Three-dimensional microsurgical and tractographic anatomy of the white matter of the human brain. Neurosurgery 2008; 62: 989-1026; discussion 1026-8. https://doi.org/10.1227/01.neu.0000333767.05328.49
  32. Baydin SS, Barut O, Kucukyuruk B, Hasimoglu O, Tanriover N. Anatomical segmentation and connectivity of the uncinate fasciculus. Turk Neurosurg 2025; 35: 652-660. https://doi.org/10.5137/1019-5149.JTN.49120-25.2
  33. Barut O, Durmus YE, Cevik OM, Baydin SS, Cokluk C, Tanriover N. Three-dimensional dissection of the bed nucleus of the stria terminalis and its white matter connections: a surgical and neuropsychiatric perspective. Turk Neurosurg 2025; 35: 791-800. https://doi.org/10.5137/1019-5149.JTN.49121-25.1
  34. Erkan B, Hergünsel B, Barut O, et al. Ventral amygdalofugal pathway as an integrated surgically important network: microsurgical anatomy and segmentation based on fiber dissection. J Neurosurg 2024; 141: 540-554. https://doi.org/10.3171/2024.1.JNS231541
  35. Mavridis I, Boviatsis E, Anagnostopoulou S. Anatomy of the human nucleus accumbens: a combined morphometric study. Surg Radiol Anat 2011; 33: 405-414. https://doi.org/10.1007/s00276-010-0766-6
  36. Mavridis I, Boviatsis E, Anagnostopoulou S. Stereotactic anatomy of the human nucleus accumbens: from applied mathematics to microsurgical accuracy. Surg Radiol Anat 2011; 33: 583-594. https://doi.org/10.1007/s00276-011-0804-z
  37. Mavridis IN. Stereotactic neurosurgical anatomy of the nucleus accumbens: four-year outcomes. Surg Radiol Anat 2013; 35: 637-638. https://doi.org/10.1007/s00276-013-1121-5
  38. Rhoton AL. The cerebrum. Anatomy. Neurosurgery 2007; 61: 37-118; discussion 118-9. https://doi.org/10.1227/01.NEU.0000255490.88321.CE

Copyright and license

Copyright © 2025 The Author(s). This is an open access article distributed under the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

How to cite

1.
Erbaş MA, Barut O, Marangoz AH, Aras M, Aydın K, Baydın ŞS. A white matter–based topographic evaluation of the anatomical boundaries of the nucleus accumbens. Sinir Sistemi Cerrahisi Derg 2025;10(3):101-110. https://doi.org/10.54306/SSCD.2025.231