Introduction
Described for the first time by Johann Christian Reil in 1796,[1] the insular lobe was considered “hidden” by several anatomists and physiologists,
earning this name for its Latin meaning: insula = island. Sometimes, it is completely hidden, surrounded by various brain lobes, including
the frontal, the temporal, and the parietal operculum. Actually, it composes the most
lateral part of the central core of the brain, which we will discuss later in the
present paper. Macroscopically, the lobe is composed of a central sulcus of the insula,
dividing it into two long (posterior) gyri and three short (anterior) gyri, as well
as an accessory gyrus in its most ventral portion, described by Brodmann in 1909.
Currently, the concept of central core of the brain corresponds to several deep regions of the cerebral cortex, present in the two hemispheres,
constituting a block between the brainstem and the cerebral cortex. The central core
of the brain is composed of the insular surface (insular lobe), the basal ganglia,
and the thalamus, thus connecting the brainstem to all of the supratentorial structures,
including the extreme, external, and internal capsule. In this topography, the central
core of the brain functions as a true station integrating the motor, sensorial, emotional
and cognitive information. The understanding of the anatomy and of the physiology
of the insula also includes its correlations with these other structures that compose
the central core of the brain, elucidating a little more of its neurophysiology.[2]
[3]
According to studies performed on monkeys, the insular lobe receives afferents from
the amygdaloid complex, from the dorsal thalamus, and from various regions of the
cerebral lobes, particularly from the auditory areas of the parietal lobes. These
afferents predominantly connect to the posterior portions of the insula, whereas the
limbic afferents (the entorhinal, the perirhinal, and the posterior orbitofrontal
cortexes) and cingulate gyrus connect with the anterior portions of the insular lobe.
The anterior portions of the insula have reciprocal efferent pathways to the afferents;
however, the same does not occur for the posterior portions of the insular lobe. Current
knowledge of the human neurophysiology of the insular lobe is based on the clinical
aspects observed in patients with epilepsy, tumors, and sequelae of cerebrovascular
diseases that affect this region. Studies have shown that these patients often have
a pattern of epilepsy that is extremely resistant to pharmacological treatment, with
paresthesia (electric shock sensation, pharyngolaryngeal constriction), dysphonia,
and dysarthria. In patients submitted to intraoperative cortical stimulation, stimuli
to the anterior portions of the insula induced viscerosensitive symptoms (abdominal
and thoracic discomfort as well as nausea), motor and somatosensitive, without specific
topographic characteristics, only diffuse and nonspecific sensations.[4]
[5] More recently, in addition to the symptoms mentioned above, there are descriptions
of olfactory-gustatory responses, especially to the sensation of disgust. In general,
the somatosensory responses were attributed to the posterior portions of the insular
lobe, whereas the viscerosensitive responses were attributed to the anterior portions.
Nguyen et al also report, but to a lesser extent, vestibular symptoms and aphasia
in those patients with epilepsy refractory to medications.[6] Pollatos et al describe, through neuroimaging, patients with autonomic symptoms,
involving, among other things, changes in thermoregulation, also placing the insula
in the center of homeostasis regulation.[7]
Discussion
Central core of the brain
The central core stands as a block on the top of the brainstem, at the morphological
center of the supratentorial compartment. This solid block includes, from lateral
to medial, the insular surface, the extreme capsule, the claustrum, the external capsule,
the putamen, the globus pallidus, the internal capsule, the caudate nucleus, the stria
terminalis, the septal region, and the thalamus.[8] Also included in the concept of the central core is the medial portion of the anterior
commissure and structures above and posterior to the anterior perforated substance,
including the nucleus accumbens (ventral striatum), the Meynert basal nuclei, the
ventral amygdalofugal pathways, and the innominate substance, corresponding to the
ventral globus pallidus. Superiorly, the central core connects almost to the entire
cerebral cortex through the cerebral isthmus and, inferiorly, through white projecting
fibers that descend to the brainstem. There is no natural division between the central
core and the brainstem.[9]
In the region of the cerebral isthmus, the white fibers arise from the central core
radiating to all of the cerebral lobes. The isthmus is composed of the continuation
of the extreme, of the external, and of the internal capsule, as well as of the extension
of the anterior commissure and of the ventral amygdalofugal pathways. The cerebral
isthmus is best visualized deep in the limiting sulci of the insula, where the fibers
pass through a narrow space between the limiting sulci of the insula and the lateral
ventricle cavity ([Fig. 1]).
Fig. 1 Insular lobe anatomy, and the concept of central core of the brain, with neurological
and neurosurgical relevance.1. Precentral sulcus of the insula; 2. Postcentral sulcus
of the insula. Abbreviations: aILG, anterior insular long gyrus; aISG, anterior insular
short gyrus; mISG, middle insular short gyrus; pILG, posterior insular long gyrus;
pISG, posterior insular short gyrus.
The insular surface is the most lateral portion of the central core, seen through
the Sylvian fissure, removing the frontal, parietal and temporal operculum. The insular
lobe is limited anteriorly, posteriorly and superiorly by the anterior, posterior
and superior limiting sulci of the insula.[3]
[10]
[11] The third ventricle, the hypothalamus, and the epithalamus are grouped together
in the midline, between the central cores of the left and right hemispheres.[8]
Insular Lobe
The insular surface is the most lateral part of the central core and is observed by
splitting the sylvian fissure and retracting the frontotemporoparietal opercula. It
is limited by the anterior, superior, and posterior insular limiting sulci (also referred
to all together as the circular sulcus of the insula). The limits of the central core
were first defined by 3 planes, each drawn from one of the limiting sulci toward the
lateral ventricle, marking the anterior, the superior, and the posteroinferior limits.
Each of these planes passes through the cerebral isthmus, transecting the connections
that link the central core to the other cerebral lobes. The insular surface is the
most lateral aspect of the central core and is encircled by the insular limiting sulci.
The limen insula is a hook-like structure found at the antero-inferior vertex of the
insula and is connected to the anterior limiting sulci (ALS) and to the inferior limiting
sulci (ILS). The point where the limen joins the ALS, at the frontal lobe, we refer
to as the frontal limen point (FLP) and consider the beginning of the ALS. This sulcus
ends at its meeting point with the superior limiting sulcus (SLS), which is referred
to as the anterior insular point (AIP), which is also the superior anterior limit
of the SLS.[8]
[9]
[12] The central sulcus of the insula is visualized on the surface of the insular lobe,
dividing the insular lobe into anterior and posterior areas. This sulcus is continuous
and runs in the direction of the limen of the insula to the upper limiting sulcus
of the insula. The anterior portion of the insula is composed of three short insular
gyri most of the time. However, in some specimens, a fourth short gyrus or anterior
accessory gyrus of the insula is found. A transverse gyrus of the insula is also present
and communicates the anterior lower portion of the lobe with the posterior orbital
gyrus and, in some cases, the accessory gyrus lies above this transverse gyrus, running
along with the anterior limiting sulcus to the orbitofrontal operculum. The posterior
portion of the insular lobe is composed of two long gyri, located posterior to the
central sulcus of the insula.[8]
Deep Structures
After removing the cortical surface of the insular lobe, there will be exposure of
the extreme capsule and, more medially, of the claustrum, consisting of a thin layer
of gray matter present between the extreme and the external capsules, subdivided into
the ventral and dorsal portion of the claustrum. The ventral claustrum runs the depth
of the anteroinferior region of the insular surface, surrounded by white matter. Its
continuation in the lower sense enters the amygdaloid complex. The dorsal claustrum
is located superiorly and posteriorly, and its gray layer is organized in a thin and
more compact form.[3]
[10]
[11]
[13]
[14]
Insular Vasculature
The insula receives its blood supply predominantly from the M2 (insular) segment of the middle cerebral artery. The middle cerebral artery, first
running under the anterior perforated substance and sending lenticulostriate branches,
reaches the limen insula and bends posteriorly over the insular surface. At the limen,
or close to it, the middle cerebral artery bifurcates (or trifurcates) into trunks;
the inferior trunk is frequently located along the ILS, while the superior one courses
in a posterosuperior direction toward the SLS. These trunks, as well as their several
main branches, send small arteries into the insular surface to supply its cortex.
These small penetrating branches do not seem to reach too deep into the insular subcortical
white matter, mostly stopping before the claustrum. The venous drainage of the insular
region can be defined by cisternal drainage. The cisternal vessels are composed of
the insular veins that drain the insular cortical surface and are directed to the
limen insula, where they join the deep sylvian vein or the deep middle cerebral vein
to later empty into the anterior part of the basal vein of Rosenthal. Occasionally,
this group terminates at the sphenoparietal or cavernous sinuses.[8]
[12]
[14] It is well known that chronic hypertension induces pathological changes in cerebral
vessels, resulting in either their occlusion or rupture, which leads to lacunar infarctions
or intracerebral hemorrhages, respectively. Some striate arteriovenous malformations
have been observed to receive their blood supply from these two groups of arteries:
the middle cerebral artery (M2 segment) and the lateral lenticulostriate artery, which indicates the potential existence
of microcommunicaton.[12]
Functional Studies of the Insular Lobe
The vast majority of information about insular functions comes from studies following
cortical lesions (in animals and humans) or even through cortical electric stimulation.
Since the first studies performed by Penfield in 1955, with electric corticostimulation,
the insular surface seems to provide visceroception and somatosensory symptoms ([Figs. 2] and [3]).
Fig. 2 Some afferent pathways related to the insular lobe. The three main systems that deserve
attention: autonomic sensitivity pathways; trigeminal sensitivity, and vestibular
sensitivity pathways. Abbreviation: STN, solitary tract nucleus. Modified from Borsook
D et al.[22]
Fig. 3 Some efferent pathways related to the insular lobe. Abbreviations: BA, Brodmann Area;
STN, solitary tract nucleus. Modified from Borsook D et al.[22]
Thermoception and Nociception
Painful stimuli appear to be triggered by electrical stimuli in the posterosuperior
portion of the insular lobe, predominantly in the right hemisphere. In the most posterosuperior
portions, the presence of the thermoception associated with somatosensitivity is described.
The somatotopic distribution of sensitivity is as follows: upper limbs in the dorsal
part, while lower limbs are more ventral. The facial sensitivity is also found in
the more ventral portions.[2]
[15]
[16] The anterior and lateral spinothalamic pathway, after projecting to the thalamus
(posterior ventromedial nucleus), is directed to the postcentral gyrus, and some fibers,
such as the spinoreticular pathway (positioned closely to the lateral spinothalamic
tract), pass through the posterior cortical surface of the insula and the cingulum
after connections to the medullary laminae of the thalamus. The anterior and lateral
spinothalamic tract is an important projection of the main somatosensory pathway (protopathic
touch, nociception, and thermoception), thus differentiating itself from the dorsal
column lemniscal pathways responsible for the epicritic and vibratory sensitivity.[16]
Somatosensitivity
Since 1955, Penfield and Faulk have associated somatosensitivity to the insular lobe.
Currently, with functional neuroimaging studies, Eickhoff et al, using studies on
cerebral cytoarchitecture, question the actual existence of a specific insular somatosensory
area, proposing that this region would consist only of the extension of the parietal
operculum (post-central gyrus).[17]
[18] In a postmortem study in 10 human specimens, Kurth et al separated three cytoarchitectonically
distinct area regions in the posterior insular lobe: two granular cortical regions
in the posterior dorsal insula, called Ig1 and Ig2, respectively, and a dysgranular
cortical area, named Idg1, located in the ventral posterior insula, associated with
a great variety of cortical somatosensory electrical stimuli. The presence of the
granular cortex is predominantly associated with afferent fibers, associating with
somatosensitivity, thermosensitivity, and nociception. Projections of these granular
and dysgranular cortices are observed and come from the limbic areas, including the
amygdaloid complex and the entorhinal cortex, suggesting the presence of an important
limbic-cortical connection in this location, which is associated with motor learning
and with the mechanisms of memory consolidation. Thus, the regions of the granular
insular cortex represent secondary somatosensory and tertiary areas.[5] Kahane et al[19] describe vestibular phenomena associated with electrical stimuli of the posterior
insula, such as dizziness, nausea, vomiting and vertigo. The posterior dorsal region
of the insula receives thalamic afferents (upper and lower posterior ventral nuclei
of the thalamus), projecting into the parietal insular vestibular cortex, justifying
these symptoms.[19]
Visceroception
Visceral symptoms are extremely relevant when electrically stimulating the insular
cortex. Some authors further propose that the ventral insula could be an extension
of the gustatory cortex. Stimuli to these regions give rise to gastrointestinal motor
activity, transmitted by vagal nerves bilaterally; once both vague nerves have been
damaged, complete suppression of insular gastrointestinal motility control is observed.
In addition, the gastrointestinal afferent pathways ascend to the thalamus (medial
and parvocellular ventroposterior nuclei), projecting to the granular and dysgranular
cortices. Functional neuroimaging studies revealed that after feeding, healthy volunteers
had increased metabolic activity in their cortexes. Ischemic insular lesions in the
regions attributed to visceroception commonly occur with dysphagia alone, producing
evidence for the hypothesis that the solitary tract nucleus (vagal afferent) protrudes
mainly to the insular cortex.[2]
[19]
[20]
Taste
The gustatory pathway begins in the chord tympani nerve projecting from the solitary
tract nucleus (STN), located in the brainstem, to the hypothalamus and to the ventromedial
parvocellular nucleus of the thalamus. It is anatomically accepted that the gustatory
area is not part of the primary somatosensitive cortex, where the tongue is included.
Taste appears to be situated in the central portion of the insula (being more posterior
in humans compared with primates, for example), receiving ventromedial thalamic afferences
as well as afferent frontal and parietal operculum.[21] Epileptic seizures involving these regions of the insula commonly occur with unpleasant
sensations involving taste, often described as a “disgust” sensation, also associated
with facial expression. However, insular lesions cause gustatory phenomena in the
ipsilateral hemitongue to the injured cortex; however, complete deficits (in both
hemitongues), with an inability to recognize the food, can be triggered by involvement
of the left insular lobe.[2]
Anterior Part of the Insular Lobe
Initially, we must consider that the central sulcus of the insula does not divide
it functionally, only anatomically. The central sulcus of the insula does not coincide
with microscopic alterations that justify its functional modification.[22] In animals, the anterior agranular insula seems to have relevant connections with
the limbic and paralimbic cortexes, especially the connections between the anterior
insula and the cingulate gyrus. However, Craig et al[23] propose that the anterior insula would participate in important integrative functions
related to self-recognition or interoception (“self-circuit,” like a neural map of
body states), attention, emotion, subjective sensations such as joy, sadness, pleasure,
and pain beyond their own perception. The anterior part of the insular lobe also seems
to be able to codify pleasurable behaviors, justified by their connections to the
nucleus accumbens, as part of the reward circuitry.[1] In general, the anterior portion of the insula can be considered as an associative
area between homeostatic functions (including autonomic control) and emotional processing.[23] Disconnections between the brainstem and the cortex of the anterior insula, or even
between the anterior insula and the claustrum, can severely compromise the level of
consciousness.[24] Atypical cytoarchitectural presentations of the anterior insula are observed in
individuals diagnosed with autism spectrum disorder (ASD), thus showing the importance
of this anterior region also in social interaction.[25] Thus, the empathy circuit was attributed to the connections between the anterior
insula and the medial portion of the cingulate gyrus: individuals considered as being
more empathic have a higher density of neurons in this circuit, whereas individuals
with ASD, for example, have a marked reduction in the cellularity of this region.[15]
Social Behavior and Mirror-neurons Circuit
Empathy is defined as the ability to understand the other, associated with visceral
emotional reactions, correlated to the various situations in which the other is living;
it is literally the situation of understanding another person by putting oneself in
the “skin of the other.” Trying to understand the neural circuitry correlated to empathy,
Rizzolatti et al described in 1992 the circuit of mirror-neurons, initially observing
primates. Rizzolatti et al reported that when they visualized motor acts performed
by their peers, monkeys activated brain circuits, as if they were performing the motor
act themselves. Besides the motor aspect, this neurocircuit brought to the neurosciences
the idea that socialization depends on one's own perception of the situation of the
other, being able to put oneself in the place of the other. This circuit has great
activation only in the fact of imagining the pain that the other could be feeling,
anticipating it only by imagination itself.[26]
[27] As already mentioned, the insula is strategically located in a region where it facilitates
the interconnection between the limbic system and the thalamus. The bodily representation
itself, that is, the “self-circuit”, is present in the insula, including unpleasant
sensations like disgust. The circuits of mirror-neurons also have associative areas
in the insular lobe, being intensely activated at the moment of imitation of a movement
only initially visualized. Singer et al observed that personally experienced pain
sensation activates the insular lobe, as well as the observation of someone experiencing
the painful sensation, with only the imagination of the pain sensation.[28]
[29]
Clinical Aspects Related to the Insular Lobe
Several neurological and psychiatric diseases present involvement of the insular lobe,
given its behavioral, motivational and cognitive functions. Patients with depression,
anxiety and schizophrenia have a significant reduction of gray matter present in the
insular lobe. Psychopathy and eating disorders such as anorexia (autoimage disorder)
also find correlation with functional insular abnormalities. In neurology, the involvement
of facial expression of emotions can be found in Huntington chorea and in multiple
sclerosis, whereas in Alzheimer dementia, the impairment of the “self-circuit” becomes
more evident.[1] Neuroimaging studies associate dysfunctions of the insular cortex with motivational
deficits, as well as with the behavior of addiction. Substance abuse appears to directly
activate the insular cortex, thereby modulating its behavioral aspect involved in
the reward circuit. Injuries in these regions often occur with anhedonia.[30] Currently, transcranial magnetic stimulation has been performed and maybe will reveal
new aspects of the insular neurophysiology.[31]
[32]
