Anatomizing the “King of Neurosciences”

Abstract

The human nucleus accumbens (NA), a major part of the ventral striatum, is the area of continuity between the putamen and head of the caudate nucleus. It consists of two parts, a shell laterally and a core medially. The first is mainly connected to the limbic system and the second to the extrapyramidal motor system. The NA, a major pleasure center of the human brain, acts as a limbic-motor interface and is involved in several cognitive, emotional and psychomotor functions. It has a modulating function in the amygdala-basal ganglia-prefrontal cortex circuit. It is considered as the neural interface between motivation and action. Further, it is a principal modulator of the reward circuits and supplies motor expression to emotional responses. Such a clinical significance could easily explain the intense work taking place in the respective field of basic research. Its exceptional clinical importance justifies the title of the “King of Neurosciences” for this nucleus. Purpose of this editorial is to review the “informational paths” left behind by the few researchers who tried to explore the architecture (gross anatomy) of this ‘kingdom’. The first anatomical study focused on this nucleus came from Neto et al. The most extensive study of the NA gross, imaging, stereotactic and neurosurgical anatomy so far, came from the research efforts of Mavridis et al.

Key Words: Gross anatomy; Neurosciences; Neurosurgical anatomy; Nucleus accumbens; Stereotactic anatomy

Core tip: The human nucleus accumbens (NA), a major pleasure center of the brain, is a limbic-motor interface involved in several neurological and psychiatric disorders. It became recently a deep brain stimulation target for selected patients. Its exceptional clinical significance justifies its title as the “King of Neurosciences”. Purpose of this editorial is to review the few studies who explored the NA gross anatomy. The first anatomical study focused on this nucleus came from Neto et al. The most extensive study of the NA gross, imaging, stereotactic and neurosurgical anatomy came from the research of Mavridis et al.

Core tip: The human nucleus accumbens (NA), a major pleasure center of the brain, is a limbic-motor interface involved in several neurological and psychiatric disorders. It became recently a deep brain stimulation target for selected patients. Its exceptional clinical significance justifies its title as the “King of Neurosciences”. Purpose of this editorial is to review the few studies who explored the NA gross anatomy. The first anatomical study focused on this nucleus came from Neto et al. The most extensive study of the NA gross, imaging, stereotactic and neurosurgical anatomy came from the research of Mavridis et al.

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THE HUMAN NUCLEUS ACCUMBENS

The human nucleus accumbens (NA), a major part of the ventral striatum, is the area of continuity between the putamen and head of the caudate nucleus[1]. It consists of two parts, a shell laterally and a core medially. The first is mainly connected to the limbic system and the second to the extrapyramidal motor system (Figure 1). NA’s afferent connections include: hippocampus, frontal cortex, entorhinal cortex, amygdala, cingulate gyrus and thalamus. Its efferent connections include: striatum, globus pallidus, hypothalamus, prefrontal cortex, ventral tegmental area and substantia nigra. The principal neurotransmitters in NA circuits are glutamic acid, dopamine and γ-aminobutyric acid (GABA)[2].

Figure 1 Nucleus accumbens connections. Schematic representation of the nucleus accumbens afferent and efferent connections within the human brain (modified from Mavridis[2]).

The NA, a major pleasure center of the human brain[2], acts as a limbic-motor interface and is involved in several cognitive, emotional and psychomotor functions[1]. It has a modulating function in the amygdala-basal ganglia-prefrontal cortex circuit. It is considered as the neural interface between motivation and action. Further, it is a principal modulator of the reward circuits and supplies motor expression to emotional responses[2]. The NA anatomical architecture and pathways, as well as the effect of different drugs on the NA have been studied on experimental animals.

"KING OF NEUROSCIENCES"

The human NA is involved in several neurological disorders including epilepsy, Parkinson’s disease, Huntington’s chorea, frontotemporal dementia, narcolepsy and spinocerebellar ataxia[2]. Given its great functional importance, it is not surprising that this nucleus is also involved in several psychiatric disorders such as obsessive-compulsive disorder, depression, Tourette syndrome, addiction, schizophrenia, bipolar disorder, attention-deficit/ hyperactivity disorder, post-traumatic stress disorder and apathy[2]. Latest decade’s advancements in Stereotactic Neurosurgery made the NA a deep brain stimulation target for selected patients mainly suffering from obsessive-compulsive disorder, depression and Tourette syndrome[2].

Such a clinical significance could easily explain the intense work taking place in the respective field of basic research. There are numerous neurochemical and neurobiological studies of the NA in the literature, usually focusing on neurons and neurotransmitters of this nucleus and its crucial connections. Moreover, there are several neuroimaging and some neuroanatomical studies of the human NA. The first are mainly magnetic resonance imaging (MRI) or functional MRI studies.

According to the above physiological and clinical data which aimed to light just the peak of the amazing iceberg, of the “Arctic Ocean of Neurosciences”, called “human NA”, I think that this exceptional nucleus rightfully deserves the crown of the “King of Neurosciences”. Purpose of this editorial is to review the ‘informational paths’ left behind by the few researchers who tried to explore the architecture (gross anatomy) of this “kingdom”.

GROSS ANATOMICAL STUDIES

Several animal studies have investigated the anatomy and physiology of the NA[1]. There are some studies that provided morphometric data of the human NA[1,3-7]. Methodologically, Yelnik et al[6] and Bardinet et al[7] used post-mortem brain MRIs (as well as dissections with cryomacrotome) for three-dimensional studying of the human basal ganglia. Xia et al[3] used T1-weighted high-resolution MRIs for studying the caudate nucleus (including findings about the NA). Ahsan et al[5] also used high-resolution MRIs for their volumetric study of the human basal ganglia and thalamus. Brabec et al[4] used anatomical dissections and MRIs for their volumetric study of the striatum. Neto et al[1] applied MRIs as well as coronal anatomical slices into cadaveric brains for their NA-focused study. Mavridis et al[8-11] used formalin-fixated cerebral hemispheres for studying NA stereotactic anatomy and morphometry and specific details of the NA deep brain stimulation (DBS) operative technique. They also used cerebral MRIs for studying NA stereotactic anatomy and morphometry[8,9], as well as MRIs from patients with Parkinson’s disease[12].

Neto et al[1] studied the location, limits and size of the human NA and found the right NA to be wider than the left one. They reported that the precise limits of the NA were only possible to delimitate in the anatomical study and that the NA does not have a distinct signal intensity imaging, as well as no evidence of NA width or height variations along age and that this nucleus does not suffer any age-related atrophy as other brain structures. Brabec et al[4] reported absence of significant difference of the absolute volume of the caudate-accumbens complex between sides and gender. In contrast, Ahsan et al[5] found greater left NA.

Mavridis et al[9] found the definition of the NA limits with the caudate nucleus and putamen easier by MRI than by anatomical technique, specifically on T2-weighted MRIs due to the slightly more intense MR signal (remarkably similar to those of the cerebral cortex) that this nucleus presents compared to the caudate nucleus and putamen (and also compared to other nuclei such as the red or subthalamic nucleus). They also agreed with Neto et al[1] about the difficulty in establishing the rostral end of the NA relative to the caudate nucleus and putamen but found no such difficulty in transverse MRI sections.

They also found no statistically significant difference among side regarding the NA stereotactic coordinates and dimensions[8,9] and that the human NA extended superiorly above the intercommissural plane[11] and was paradoxically longer in the elderly[9]. Further, its maximum transverse dimension was greater in individuals with putamen microcysts (dilated perivascular spaces)[9] and the absolute value of its y΄ coordinate was greater in males[8]. The NA was morphometrically correlated neither with the striatum[9] nor with its cortical connections. However, they found significant correlations of the thickness of NA cortical connections, specifically: the orbitofrontal with the entorhinal cortex, the cingulate with the orbitofrontal cortex, the piriform with the orbitofrontal and entorhinal cortices[2].

In addition, Mavridis et al[8] found stereotactically standard areas in the NA (e.g., G, H, M). Standard area M (Mavridis’ area), based on a combined study of anatomic specimens and MRIs, which is defined by coordinates x = 6.0 mm, x΄ = 9.0 mm, y = 2.0 mm, y΄ = 2.0 mm, z = -0.8 mm, z΄ = -2.0 mm and has a 3.6 mm² surface, always consisted a NA part regardless of side (right-left) or gender (male-female). They also found that the human NA is smaller in patients with advanced Parkinson’s disease (Mavridis’ atrophy). The mean percentage reduction of its size was 11.77%[12].

Finally, Mavridis et al[2] studied anatomical details of the NA DBS surgical technique on cadavers, they found that the today used electrode target point for NA DBS missed the target in 8% of cases[11] and they proposed a safe navigation model (‘port’ model) for NA DBS[10] as well as new surgical approaches and anatomic landmarks for NA surgery[2].

CONCLUSION

In conclusion, the human NA, a major pleasure center of the human brain, is a limbic-motor interface involved in several neurological and psychiatric disorders. During the last decade, this nucleus is also a DBS target for selected patients. Its exceptional clinical significance justifies the title of the “King of Neurosciences” for this nucleus. There are few researchers who tried to explore the gross anatomy of this nucleus. The first anatomical study focused on this nucleus came from Neto et al[1]. The most extensive study of the NA gross, imaging, stereotactic and neurosurgical anatomy so far, came from the research efforts of Mavridis et al[2,8-12].