Introduction: The cingulum bundle (CB) has been implicated in the pathophysiology of psychiatric disorders. Anatomic and radiographic CB connectivity analyses suggest that it is heterogeneous in composition, with certain regions, such as the rostral dorsal CB, having greater connectivity than others to cortical and subcortical structures associated with mood and thought, like the anterior cingulate cortex (ACC). Cingulotomy procedures for the treatment of depression, pain, and obsessive-compulsive disorder consist of 1-3 bilateral lesions in a portion of the dorsal ACC (dACC) and underlying CB, yet the exact region responsible for symptom relief is unclear. This study uses tractography to assess the connectivity of standard cingulotomy lesions, as well as of subdivisions of the rostral dorsal CB, to cingulate and non-cingulate structures involved in psychiatric disorders.
Methods: Healthy volunteers underwent T1- and diffusion-weighted MRIs. Region of interest (ROI) masks were created to replicate three cingulotomy lesions commonly used, and to make eight equally-sized subdivisions of the rostral dorsal CB (Figure1). Deterministic tractography was performed, and the connectivity of each ROI to 11 cortical/subcortical brain structures was assessed.
Results: Five subjects were included. All cingulotomy lesions showed greatest connectivity to the dACC, followed closely by the posterior cingulate cortex (PCC) and dorsomedial frontal cortex (dmFC) for lesion 1, and the dmFC for lesions 2 and 3 (Table1). The CB subdivisions with highest connectivity to the dACC were 4-5, and those to the dmFC were 3-4 (Table2). Thus, the antero-rostral-most portion of the CB showed greatest connectivity to key brain structures, including the dACC and dmFC.
Conclusions: Using deterministic tractography, a connectivity analysis of cingulotomy lesions and CB subdivisions was performed. The greatest connectivity between all cingulotomies was to the dACC and dmFC. However, the CB subdivisions with highest connectivity to these regions were located antero-rostrally, possibly suggesting a more effective surgical target for psychiatric diseases.
Patient Care: This study demonstrates, using tractography, the key white matter connections involved in cingulotomy lesions. It also shows other areas of the cingulum bundle that may have greater connections to key regions of the brain, suggesting the possibility of a more effective surgical target for the treatment of psychiatric diseases.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Name brain structures implicated in psychiatric disorders, 2) Discuss in small groups the cingulotomy procedure and its role in treating psychiatric disorders, 3) Understand the value of tractography in assessing connectivity to potentially localize new surgical targets.
References: Jones DK, Christiansen KF, Chapman RJ, Aggleton JP. Distinct subdivisions of the cingulum bundle revealed by diffusion MRI fibre tracking: implications for neuropsychological investigations. Neuropsychologia. 2013;51:67-78.
Wu Y, Sun D, Wang Y, Wang Y, Ou S. Segmentation of the cingulum bundle in the human brain: a new perspective based on DSI tractography and fiber dissection study. Frontiers. 2016;10.
Heilbronner SR, Haber SN. Frontal cortical and subcortical projections provide a basis for segmenting the cingulum bundle: implications for neuroimaging and psychiatric disorders. J. Neurosci. 2014;34(30):10041-10054.
Wang F, Jackowski M, Kalmar JH, et al. Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging. Br J Psychiatry. 2008;193:126-129.
Yang JC, Ginat DT, Dougherty DD, et al. Lesion analysis for cingulotomy and limbic leucotomy: comparison and correlation with clinical outcomes. J Neurosurg. 120: 152-164, 2014.
Boccard SG Prangnell SJ, Pycroft L, et al. Long-term results of deep brain stimulation of the anterior cingulate cortex for neuropathic pain. World Neurosurg. 2017 Jul;20(5):504-513.
Bourne SK, Sheth SA, Neal J, et al. Beneficial effect of subsequent lesion procedures after nonresponse to initial cingulotomy for severe, treatment refractory obsessive-compulsive disorder. Neurosurgery. 72:196–202, 2013.
Mayberg HS, Liotti M, Brannan SK, McGinnis S, et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry. 1999 May;156(5):675-82.
Zhang Y, Schuff N, Jahng G, et al. Diffusion tensor imaging of cingulum fibres in mild cognitive impairment and Alzheimer’s disease. Neurology. 2007;68:13–18.