Microsurgical anatomy of the anterior cerebral artery and the arterial supply of the cingulate gyrus

The cingulate gyrus is a potential surgical area to treat tumours, psychiatric diseases, intractable pain and vascular malformations. The aim of the study was to define the topographic anatomy and arterial supply of the cingulate gyrus located on the medial surface of the cerebral hemisphere. We studied thirty-six hemispheres, each hemisected in the midsagittal plane. The vertical thickness of the cingulate gyrus was measured at the anterior commissure (AC), posterior commissure (PC), and genu levels of the corpus callosum. The branches of the anterior and posterior cerebral arteries supplying each zone were noted separately. The arterial pathways were transformed to digital data in AutoCAD to identify the condensation and reduction areas. The mean AC-PC distance was 27.17 ± 1.63 mm. The thinnest region was the genu level of the corpus callosum (10.29 mm). The superior internal parietal artery (SIPA), inferior internal parietal artery (IIPA) and pericallosal artery (PrCA) supplied all zones of the cingulate gyrus. The anterior zone received the greatest supply. The arterial condensation and reduction areas on both sides of cingulate gyrus and its x, y, and z coordinates specified. The target cingulotomy (TC) area was determined for anterior cingulotomy. The properties of the TC area are that the thinnest region of the cingulate gyrus is supplied relatively less than other areas and is close to the anterior cingulotomy areas in the literature. The arterial reduction area (ARA) was found to be suitable for corpus callosotomy in terms of avoiding haemorrhage.


Introduction
According to Brodmann, the cingulate gyrus is divided into two areas: the anterior (Brodmann 24) and posterior (Brodmann 23) regions. Functionally, the cingulate gyrus consists of three main regions with a similar cytoarchitectural motif and neuronal circuits [3,12,25]. These regions are the anterior cingulate cortex (ACC), midcingulate or middle cingulate cortex (MCC), and posterior cingulate cortex (PCC). The cingulate gyrus is supplied by the anterior and posterior cerebral arteries. While the branches of the anterior cerebral artery spread across all three regions, the posterior cerebral artery only contributes to the arterial supply of the posterior cingulate cortex. There have been numerous studies on the microanatomy of the cingulate gyrus [4,6,13,14,21,24]. Nevertheless, a detailed portrayal of the distribution of the anterior cerebral artery over the cingulate gyrus is still lacking. The aim of this study was to identify the condensation and reduction areas of the arteries on the cingulate gyrus. Thus, we think that this study contributes especially to cingulotomy surgery.

Materials and methods
Thirty-six cerebral hemispheres from 20 adult cadaveric brains were obtained. We excluded four cerebral hemispheres from the study due to signs of trauma or disease. After the cerebral arteries were cannulated separately and filled with red-coloured latex and opaque material, the brains were fixed in formaldehyde. Brains were dissected with microsurgical instruments under a surgical microscope (OPMI 99; Carl Zeiss, Göttingen, Germany). All measurements were obtained by a digital calliper (Digimatic calliper, model no: CD-15APXR, Mituyoto Corporation R ). Each brain was hemisected sagittally at a distance of 4 mm from the midsagittal plane. After removing the cranial arachnoid and pia mater over the anterior and posterior cerebral arteries, the branches of these cerebral arteries supplying the cingulate cortex were determined.
The anterior (AC) and posterior commissure (PC) were pinpointed, and the needle was used to prick the mid-commissural point (MCP). The y-axis (AC-PC line) was determined in the anterior-posterior direction by passing a thread over these three needles. The z-axis was oriented vertically over the mid-commissural point ( Figs. 1 and 2).
The medial surface of the cingulate gyrus was divided vertically into three parts, the anterior, middle, and posterior zones, according to the AC and PC. The branches passing over the cingulate gyrus were recorded. These branches were classified according to the zones that supplied them (Figs. 1 and 2).
The following measurements and parameters were assessed: 1. The distance between the AC and the PC was measured; 2. The vertical thicknesses of the cingulate gyrus at the AC, PC, and genu levels of the corpus callosum (perpendicular to the AC-PC line) were measured; The arterial traces and the border of the cingulate gyrus were determined using an acetate sheet. Then, these arterial traces on the acetate sheet were analysed on Auto-CAD 2020 (Autodesk R ). Traces of arterial lines on the virtual plane were labelled with a fixed AC-PC distance of 26 mm, and all lines were combined. In each specimen, the coordinates of the branches were rearranged according to the ratio of the AC-PC distance to 26 mm.
We used the International Business Machines Statistical Package for the Social Sciences (IBM SPSS) version 20 programme for statistical analysis of data in a digital environment.

Results
This study focussed on three anatomic landmarks on the cingulate gyrus: AC, PC, and MCP. The mean AC-PC distance was 27.17 ± 1.63 mm (range 24.06-29.56 mm, median 27.61 mm). The vertical thicknesses of the corpus callosum at the AC, PC, and genu levels were 11.90 ± 2.68 mm, 15.65 ± 3.33 mm, and 10.29 ± 2.68 mm, respectively. In thirty specimens, the vertical thickness at the genu level of the corpus callosum was narrower than at other levels.
The anterior and posterior cerebral arteries and their branches supplied the cingulate gyrus. We divided the cingulate gyrus vertically into three zones. The anterior zone was separated at the anterior commissure. The middle zone was located between anterior and posterior commissures. The posterior zone was split at the PC. Table 1 indicates the number of cases in which the arteries supplied these zones. SIPA, IIPA, and PrCA contributed to the arterial supply of the whole cingulate gyrus. The anterior zone had the most arterial diversity. Moreover, the callosal branches of the anterior cerebral artery particularly supplied the middle (7 specimens) and posterior zones (11 specimens). The posterior zone was supplied by the dorsal callosal (24 specimens) and cingulocallosal branches (8 specimens) of the posterior cerebral artery. There was no artery passing over the middle zone in four cases and the posterior zone in one case.
After the anterior cerebral artery gave rise to the anterior communicating artery, it traversed over the sulcus of the corpus callosum. The anterior cerebral artery gave rise to the branches passing across and supplied the cingulate gyrus. The coordinates of the branches feeding the cingulate gyrus are listed in Table 2. Furthermore, the coordinates of the branches were rearranged according to the ratio of the AC-PC distance to 26 mm in each specimen. The arterial traces on the rearranged plane were depicted on a fixed AC-PC distance of 26 mm and are illustrated in Figs. 3 and   4. The regions where the arteries were most and least dense were detected in the common cingulate gyrus. The focus of this study was to determine the effective zone coordinates of the cingulate gyrus with a fixed coefficient. This study shows that variations in the cingulate gyrus can be studied with a constant AC-PC distance of 26 mm, and these variations in the common base can help locate the unique coordinates of the effective zones of the cingulate gyrus. The coefficient (k) is determined as the division of the calculated AC-PC distance and 26 (k: measured AC-PC distance/26) (fixed the AC-PC distance at 26 mm space). The arterial traces and the border of the cingulate gyrus were analysed on AutoCAD. According to the results of this analysis, the mean x, y, and z coordinates of the arterial condensation area were + 4.00 mm, + 39.29 mm, and − 2.16 mm on the right side and − 4.00 mm, + 36.44 mm, and − 3.28 mm on the left side, respectively. The mean x, y, and z coordinates of the arterial reduction area were + 4.00 mm, − 27.07 mm, and 22.20 mm on the right side and − 4.00 mm, − 32.34 mm, and 16.71 mm on the left side, respectively. Finally, the mean x, y, and z coordinates of the target cingulotomy were + 4.00 mm, + 25.54 mm, and + 27.06 mm on the right side and − 4.00 mm, + 23.26 mm, and + 27.36 mm on the left side, respectively.

Discussion
The cingulate gyrus is a surgical area targeted to treat intractable pain, schizophrenia, tumours, and vascular pathologies. The best reason this region is associated with these diseases is that the cingulate gyrus has numerous connections with adjacent brain areas, such as the basal nuclei, hippocampus, paracentral lobule, superior frontal gyrus, supplementary motor area, and precuneus.
The subgenual cingulate gyrus has connectivity with the nucleus accumbens, amygdala, hypothalamus, and orbitofrontal cortex. This is why subgenual cingulotomy has been performed for psychiatric disorders, such as major depression, obsessive compulsive disorder, and anxiety [7,11,12,16]. The subgenual cingulotomy was popularized by Laitinen in the 1970s [15]. It was observed that the subgenual cingulotomy area was close to the arterial condensation area in this study (Figs. 3 and 4). Arteries are thought to Anterior cingulotomy is performed for patients with chronic intractable pain disorders [2,10,17,20,27]. The recommended anterior cingulotomy area is determined according to the frontal horn of the lateral ventricle. The target cingulotomy areas in the literature range from 10 to 40 mm [8,9,17,26]. We identified three criteria for deciding the anterior cingulotomy area, quite independent of the frontal horn. The area should be the thinnest region of the cingulate gyrus, which is supplied relatively less than other parts of the cingulate gyrus and close to the anterior cingulotomy areas in the literature. In this study, the vertical thickness of the cingulate gyrus at the genu level of the corpus callosum (10.29 mm) was thinner than that at the anterior and posterior commissures. The mean x, y, and z coordinates of the target cingulotomy were + 4.00 mm, 25.54 mm, and 27.06 mm on the right side and − 4.00 mm, + 23.26 mm, and + 27.36 mm on the left side, respectively (Figs. 3 and  4). The reason for including the thinnest and less supplied region as part of the criteria is to decrease the cingulotomy surface and the risk of bleeding. We believe that if the whole white matter of the cingulum bundles were included in the lesioning procedure, the effect of the cingulotomy would have greater success.
There are numerous articles in the literature studying corpus callosotomy as a treatment modality for drugresistant psychiatric disorders. Taghipour and Ghaffarpasand [22] drew attention to functional magnetic resonance imaging (fMRI) showing functional and structural changes in the brain in those with schizophrenia. The interhemispheric connectivity through corpus callosotomy differs in those with schizophrenia, which may lead to hallucinations and altered perception of reality. Julian Janes' controversial hypothesis of the "bicameral mind" also suggests that the corpus callosum plays a key role in consciousness [5]. All these findings would be presumed as corpus callosotomy could be a choice of treatment for psychiatric patients who are refractory to medical and behavioural therapy. Corpus callosotomy is also used for the treatment of some refractory epilepsies, especially for those with atonic seizures [1,23]. The course of atonic seizures is mostly drug resistant and is difficult to control and predict; therefore, atonic seizures may have serious consequences for patients and result in disabilities. Callosal irradiation with stereotactic radiosurgery is an alternate method for open callosotomy procedures [19]. Cautious preprocedural planning is a necessity for these operations. Understanding the white matter tracts of cingulum fibres will improve the effectiveness of these operations and decrease complications. Rolston [18] compared vagus nerve stimulation with corpus callosotomy in terms of effectiveness and complication rates. According to seizure freedom from atonic seizures, significantly more patients were seizure-free after undergoing corpus callosotomy than after undergoing vagus nerve stimulation. Documented adverse events were far more common with vagus nerve stimulation, such as hoarseness and voice changes, than with corpus callosotomy.
Due to the widespread use of corpus callosotomy, it is crucial to know the detailed anatomy of the posterior zone of the cingulate gyrus. In this study, we identified an appropriate area for corpus callosotomy. In our opinion, the arterial reduction area will reduce the risk of bleeding in patients with schizophrenia and refractory epilepsy surgery (Figs. 3 and 4).
Detailed mapping of the corpus callosum and cingulum with advanced diffusion tensor imaging (DTI) tractography images fused with knowledge of white matter dissection in anatomical studies will increase the functional understanding of neurological and neuropsychiatric impairments.

Conclusion
Knowledge of the arterial supply emphasized in this study may reduce morbidity in pursuit of operative approaches near or through the corpus callosum. The connectivity of the arterial reduction area, arterial condensation area, and target cingulotomy with the adjacent anatomical structures should be verified using diffusion tensor imaging.
Author contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by YEG, ACK, TMG, YES, YG, AC, GK, and AS. The first draft of the manuscript was written by YEG and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding No funding was received for conducting this study.

Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Conflict of interest
The authors have no competing interests to declare that are relevant to the content of this article.
Ethics approval This study includes no use of live subjects or animals in any way. This was a cadaveric study, and all cadavers were supplied from a donated institution. All the procedures performed in this study involving cadavers followed the ethical standards of the Institutional Review Board and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The authors sincerely thank those who donated their bodies to science so that anatomical research could be performed. Results from such research can potentially increase mankind's overall knowledge that can then improve patient care. Therefore, these donors and their families deserve our highest gratitude.
Consent to participate Informed consent was obtained from all individual participants included in the study.

Consent to publish
The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1a-c.