Contribution of the Neuroanatomy of the Cingulate Gyrus to the Neuroscientific Approach to Depression

Introduction: Numerous studies show the involvement of the cingulate gyrus in affective disorders, particularly in depression. With a preventive and curative aim, the authors raise questions leading to therapeutic applications such as focal brain stimulation. The cingulate gyrus is the primary target of these brain stimulation therapies for the treatment of depression. The objective of this work is to establish anatomoclinical correlations and to deduce the therapeutic implications. Methodology: Our work is a review of the literature. The inventory of the cingulate gyrus and depression was based on the development of a critical synthesis of bibliographic knowledge. Results: We found a bipartite Brodmann subdivision which evolved into a subdivision into four regions of the cingulate gyrus. Descriptions of the cingulate gyrus boundaries are imprecise and divergent. The anterior end of the anterior cingulate cortex is a confirmed target of stimulation in the treatment of major and resistant depression, thus requiring the authors, a consensus in its delineation. Brodmann’s area 25 has been described as the main target of brain stimulation therapies. Dysfunction by local lesion or by alteration of the connectivity of Brodmann’s area has repercussions on these different structures to which it is interconnected. These disturbances when they are in the direction of collapse paint a picture similar to major depression. Conclusion: The anterior cingulate cortex is involved in depression. The functional system organization of affectivity will allow new brain stimulation techniques to act on the entire functional system or on one of its components.


Introduction
The cingulate gyrus is a part of the limbic lobe located on the medial aspect of the cerebral hemispheres, above the corpus callosum. It corresponds to Brodmann areas (AB) 23,24,25,26,29,30,31,32 and 33 [1]. Many studies have shown the involvement of the cingulate gyrus in affective or mood disturbances [2] [3] [4] [5] [6]. These disturbances in affectivity can point in the direction of collapse or exaggeration.
Depression is a mood disorder or affective disorder [7] characterized by an unpleasant feeling that can reach pain. There are several clinical forms of depression. They all have a common core, which is the depressive syndrome consisting of: depressed mood (sadness, crying, apathy), psychomotor slowing and physical signs [8].
Symptoms of depressive syndrome are complete in severe forms such as major depression, resistant depression and chronic depression. For curative purposes, authors have raised questions which currently lead to therapeutic applications such as focal brain stimulation. The cingulate gyrus is at the forefront of the targets of these brain stimulation therapies including "Deep Brain Stimulation" (DBS) and "Transcranial Magnetic Stimulation" (TMS). The brilliant results obtained reinforce the involvement of the neuro-anatomo-functional dimension in the diagnostic and therapeutic processes of depression, especially in its severe forms. Therefore, the identification of neuroanatomical structures involved in the control of affectivity is of increasing interest day by day in the field of research. Indeed, this interest is noted at several levels. First in the clinic, this update will allow us to understand the mechanism by which the various symptoms of major depression occur. This suggests that practitioners and researchers take into account the biological dimension of mood disorders. Then, this work is also of interest in anatomy in the sense that the development of a recent synthesis on the descriptive and functional aspects of the anatomy of the cingulate gyrus is necessary. This synthesis will complete the first anatomical descriptions of the cingulate gyrus which are certainly existing but rather disparate. She is also contributing to the development of new Atlases of Anatomy of the Central Nervous System. Finally, in imaging, the precise anatomical descriptions produced are of capital interest because they will constitute a descriptive and functional database of this part of the central nervous system. These data will serve as a reference for new image acquisition techniques. This will allow the latter to be close to reality and to keep all their coherence.
Thus, the objective of our work is: -To establish correlations between the anatomical abnormalities (morphological and functional) of the cingulate gyrus and the clinical aspects occurring during major depression and; -To deduce the therapeutic implications.

Type of Study
Our work is a bibliographic study.

Materials
The material used was both physical and electronic works of Anatomy and Psychiatry. The articles were available in the various databases and journals offered by the Jubil entry portal.
We used Excel and World for entering and representing some data in tabular form. The diagram was drawn by hand then scanned and captioned.
The Zotero software allowed the construction of a bibliographic database and the automatic insertion of bibliographic references.
Also, drawing material on paper consisting of colored pencils and felt-tip pens was used to produce a synthesis diagram of the anatomical data.

Method
The review of the literature was based on the development of a critical synthesis of bibliographic knowledge on Cingulate Gyrus and Depression.
We first carried out a well-organized documentary search using the funnel method. This method consists in making a broad then restrictive search.
Through the Jubil entry portal we searched library catalogs and databases according to the type of document sought. The search keywords taken from the title "Cingulate Gyrus and Depression" were translated into Medical Subject Headings (MeSH) terms using the Pubmed database. The same terms were searched directly in Direct Science.
As we went along, we recorded the bibliographic references in Zotero.
From the full texts of the articles that best answered our topic, we assessed the extent, form, and depth of work on the cingulate gyrus and depression. The neuroanatomical data found were synthesized and represented on a diagram produced by freehand.
Also, the analysis of the various consensual aspects and controversies of the subject, led to the formulation of hypotheses that could later be the subject of in-depth research.

Summary of Studies on the Subdivision of the Cingulate Gyrus
We found a bipartite Brodmann subdivision which evolved into a subdivision into four regions of the cingulate gyrus [ Table 1].

Synthesis Diagram
The synthesis diagram shows the limits and subdivision of the cingulate gyrus on a medial view of a left cerebral hemisphere [ Figure 1].

Subdivision
The controversies noted in the literature are partly underpinned by the lack of consensus in the delineation of brain regions. The involvement of Brodmann's area 25 in the regulation of affectivity is confirmed by several works [9] [10] [11]. However, some authors consider it to be part of the ACC while others consider it to be part of the ventromedial prefrontal cortex [12]. This leads to divergent conclusions concerning the areas of the brain involved in the affective process.

Semiological Limits
Psychiatry is a medical discipline that is not without subtlety when it comes to defining criteria for a given syndrome. The depressive syndrome which is the nucleus of depression is no exception to this criterion. In the literature, patients suffering from major depression are included according to the DSM-IV-TR [9] [13] [14] [15] and DSM-V criteria. On the other hand, those suffering from resistant depression are included according to the criteria of different scales of apathy or depression [9] [10]. Also, the authors used different indicators including apathy and emotion. Tribolet (2000) defines emotion as a usually transient, important variation of the thymic experience. It is a component of affec-Open Journal of Psychiatry tivity. It also defines affectivity which corresponds to a thymia refined, orchestrated and often amplified by intelligence and higher psychic functions which constitute the terminal stage of the personality. Affectivity therefore appears as the system which synchronizes both cognitive functions and higher psychic functions such as thought, attention, memory, judgment and mood. The latter is influenced by emotions and instinctual functions [16]. Thus the system organization of the affectivity register comes very close to the new neurobiological approach based on connectivity.

Subdivision of the Cingulate Gyrus
The

Synthesis Diagram
The  [22]. The synthesis of the various neuroanatomical descriptions allowed us to specify its limits on the diagram. Brodmann's area 25 is bounded in front and below by Brodmann's area 11, behind the paraterminal gyrus from which it is separated by the posterior para-olfactory sulcus. Above and in front it is limited by the cranial part of the subcallous gyrus and a short vertical groove called the anterior para-olfactory groove. However, for some authors, it belongs to the prefrontal cortex. This partly explains the divergent conclusions found in the literature. The proponents for the membership of Brodmann's area 25 to the pre-frontal cortex used a methodology based on imaging (PET, CT, MRI) and the proponents for the membership of this Brodmann area 25 to the cingulate cortex have used in addition to imagery arguably more precise cyto-architectonics. Moreover, this anterior extremity (Brodmann's area 25) is arousing much interest with new focal brain stimulation therapies applied to neurological and psychiatric pathologies [10] [25] [26] [27]. It constitutes a confirmed target of stimulation in the treatment of major and resistant depression.
Faced with these innovative therapeutic perspectives and the disagreements described above, it is necessary to carry out work whose main objective would be to find a consensus in the delimitation and nomenclature of this region. Also, this would make it possible to make the data from the literature that already exist better usable. Part of our work is a start.

Cingulate Gyrus and Depression
The first experimental studies in animals linked emotional behavior to the cingulate gyrus. Lesions of the cingulate gyrus in monkeys have led to the disappearance of their aggressiveness, an exaggerated taming and a disinterest in the face of danger [28] [29]. These animal experiments paved the way for cingulectomy as a psychosurgical method. Patients with mental disorders whose depression improved rapidly after cingulectomy. Also, thanks to neuroimaging, abnormalities in brain activity of ACC were found in patients suffering from depression [13]. From then on, researchers were interested in the identification of neuroanatomical structures involved in the control of affectivity. The first results showed that only the anterior part of the ACC is involved in the emotion, the posterior part being activated during pain responses. The second results obtained incriminated the subcallous gyrus of ACC and more precisely Brodmann's area [5] [9] as the control center of the affectivity system. In fact, abnormalities in the brain activity of Brodmann's area have been found in depressive patients. Also in a stimulation experiment in humans (thoughts of sad events) the results showed significant brain activity at Brodmann's area. -Psychomotor slowing down with bradypsychia (slowing down of thought), rare movements which may be due to a loss of movement initiation; -Physical signs: Ey (1989) in his book describes digestive signs such as anorexia, nausea, saburral state of the digestive tract, constipation or diarrheal debacles. Cardiovascular examination shows disturbances in pulse and blood pressure with hypotension in the stuporous form and hypertension in the anxious form. Amenorrhea is common. The neuro-vegetative signs lead to vagotonic syndrome in the stuporous form and suggest a stressful adrenergic reaction in the anxious form [8]. -Amnesia; -Hypoprosexia (decreased attention); -A decrease in libido; -Insomnia.
These anatomo-clinical correlations justify the application of new therapeutic approaches to focal brain stimulation. "Deep Brain Stimulation" (DBS) and "Transcranial Magnetic Stimulation" (TMS) have been shown to be effective in the treatment of major depression and resistant depression [10] [31]. The focal stimulation of the primary center of the emotion will propagate to the levels of the other structures to which it is interconnected [5]. Thus it will raise their level of activity and give a state of basal emotional tone. This stimulation can also concern the white matter fibers which connect these different structures.
In addition, other authors inspired by the work of Papez, organize the representation of emotion at the level of the brain, into two components [32]:

Recommendations
This work carried out on depression and the cingulate gyrus suggests that we push our reflection on the following points: -The precise delimitation of a psychic cortical area and the knowledge of the trajectory of the fibers which connects it to other structures, will make it possible to act on the entire functional system or on one of its components.
Thus, we recommend focal stimulation on white matter fibers to act on a dominant component of depression. This is an example of a clinical form of anxiety depression. The stimulation will target the white fibers originating from the cingulate cortical area and which are in connection with the structures that govern anxiety. On the other hand for a complete depressive syndrome in a context of major, resistant or chronic depression, we indicate a cortical stimulation which will diffuse at the level of the other interconnected structures thanks to the fibrous projections; -The integration of anatomical data obtained in neuro-navigation systems; which will help in pinpointing the exact site during brain stimulation; -The establishment of a mapping of psychic brain areas which also takes into account the connectivity between the different brain structures; -The revision of the anatomical nomenclature of the different regions of the Open Journal of Psychiatry cingulate gyrus in order to eliminate the many synonymies without topographical or functional correspondence. This revision will also make the much research work on the cingulate gyrus and depression more useful.

Conclusion
Emotion is a primitive instance that humans share with other mammals. Affection involves highly differentiated structures including the prefrontal cortex. Its system organization responds to the new neurobiological approach based on the connectivity of neuro-anatomical structures. Brodmann's area of the anterior cingulate cortex (ACC) is implicated in depression despite the complexity of the neuroanatomical and psychiatric aspects noted in the various studies. This complexity opens the way for fundamental, clinical and synthetic studies.