The limbic system has always been considered as a complex arrangement of transitional structures situated between a visceral ‘primitive’ subcortical brain and a more evolved cortical one (Yakovlev, 1948; MacLean, 1952). The subcortical limbic structures include the amygdala, mammillary bodies, hypothalamus, some thalamic nuclei (i.e. anterior, intralaminar, and medial dorsal groups) and the ventral striatum (i.e. nucleus accumbens). The neurons and fibres composing the subcortical limbic structures present a simple arrangement, not dissimilar to other subcortical nuclei of the brainstem regulating basic metabolism, respiration, and circulation. The cortical components of the limbic system include areas of increasing complexity separated into limbic and paralimbic zones (Mesulam, 2000). At the lower level the corticoid areas of the amygdaloid complex, substantia innominata, together with septal and olfactory nuclei display an anatomical organization that lacks consistent lamination and dendritic orientation. These structures are in part subcortical and in part situated on the ventral and medial surfaces of the cerebral hemispheres. The next level of organization is the allocortex of the olfactory regions and hippocampal complex, where the neurons are well differentiated into layers and their dendrites show an orderly pattern of orientation. The corticoid and allocortical regions are grouped together into the limbic zone of the cerebral cortex as distinct from the paralimbic zone. The latter is mainly composed of ’mesocortex’, whose progressive level of structural complexity ranges from a simplified arrangement similar to the allocortex, to the most complex six-layered isocortex.
The Iimbic and paralimbic zones can also be divided into olfactocentric and hippocampocentric groups (Figure 11.4) (Mega et al., 1997; Mesulam, 2000). Each division is organized around a central core of allocortex. The olfactocentric division is organized around the primary olfactory piriform cortex and includes the orbitofrontal, insular and temporopolar region. The hippocampocentric division is organized around the hippocampus and includes the parahippocampal and cingulate cortex. Both divisions have reciprocal connections with subcortical Iimbic structures and surrounding isocortical regions (Figure 11.4). The two divisions overlap in the anterior cingulate cortex.
Functionally the paralimbic areas contribute to the activity of three distinct networks (Figure 11.5). The network composed of the hippocampal-diencephalic structures (connected through the fornix and mammillo-thalamic tract) and the parahippocampal-retrosplenial circuit (ventral cingulum) is dedicated to memory and spatial orientation (Aggleton, 2008; Vann et al., 2009). Some of the structures composing the network are particularly vulnerable to damage caused by viral infections (e.g. encephalitis) or alcohol (e.g. Korsakoff’s syndrome) (Figure 11.5). Imaging studies have documented altered metabolism and reduced functional activation of this network also in age-related neurodegenerative disorders, such as mild cognitive impairment (Nestor et al., 2003; Minoshima et al., 1997) and Alzheimer’s disease (Buckner et al., 2005).
The temporo-amygdala-orbitofrontal network (connected through the uncinate fasciculus) is dedicated to the integration of visceral and emotional states, cognition, and behaviour (Mesulam, 2000). In animal studies, disconnection of the uncinate fasciculus causes impairment of object-reward association learning and reduced performances in memory tasks involving temporally complex visual information (Gaffan and Wilson, 2008). Tasks involving the monitoring of outcomes activate the medial orbital cortex (Amodio and Frith, 2006). Damage to this network manifests with cognitive and behavioural symptoms characteristic of temporal lobe epilepsy, mood disorders, traumatic brain injury, and neurodegenerative dementias, including advanced Alzheimer’s disease and semantic dementia (Figure 11.5).
The default-mode network consists of a group of medial and lateral regions whose activity decreases during goal-directed tasks (Raichle et al., 2001; Raichle and Snyder, 2007). The anterior cinguIate-medial prefrontal cortex and the posterior cingulate-precuneus form the medial portion of the default-mode network and are inter-connected through the dorsal cingulum. In functional imaging studies the default-mode network is active during the ‘resting state’, a condition in which the majority of the subjects engage in an introspective, self-directed stream of thought (i.e. similar to daydreaming). A synchronous deactivation of the default network is observed in the transition between the ‘resting state’ and the execution of goal directed tasks, irrespective of the nature of the task. The deactivation of the default-mode network has been linked to a number of functions including working memory, focusing attention to sensorially driven activities, understanding other people’s intention (mentalizing or theory of mind), prospective thinking (envisioning the future) and memory for personal events (autobiographic memory) (Amodio and Frith, 2006). Altered activation of the default network has been reported in functional imaging studies of patients with neuropsychiatric disorders (Broyd et al., 2009) (Figure 11.5).
The hypothalamus is a part of the limbic system, which is a group of forebrain structures that has the hypothalamus, the amygdala, and the hippocampus. These are involved in motivation, emotion, learning, and memory. The limbic system is where the subcortical structures meet the cerebral cortex. The limbic system operates by influencing the endocrine system and the autonomic nervous system. It is highly interconnected with the nucleus accumbens, the brain’s pleasure center, which plays a role in sexual arousal and the “high” derived from certain recreational drugs. These responses are heavily modulated by dopaminergic projections from the limbic system. In 1954, Olds and Milner found that rats with metal electrodes implanted into their nucleus accumbens, as well as their septal nuclei, repeatedly pressed a lever activating this region, and did so in preference to eating and drinking, eventually dying of exhaustion. The limbic system also includes the basal ganglia. The basal ganglia are a set of subcortical structures that directs intentional movements. The basal ganglia are located near the thalamus and hypothalamus. They receive input from the cerebral cortex, which sends outputs to the motor centers in the brain stem. A part of the basal ganglia called the striatum controls posture and movement. Recent studies indicate that, if there is an inadequate supply of dopamine, the striatum is affected, which can lead to visible behavioral symptoms of Parkinson’s. The limbic system is also tightly connected to the prefrontal cortex. Some scientists contend that this connection is related to the pleasure obtained from solving problems. To cure severe emotional disorders, this connection was sometimes surgically severed, a procedure of psychosurgery, called a prefrontal lobotomy (this is actually a misnomer). Patients having undergone this procedure often became passive and lacked all motivation. The limbic system is often classified as a “cerebral structure”. This structure is closely linked to olfaction, emotions, drives, autonomic regulation, memory, and pathologically to encephalopathy, epilepsy, psychotic symptoms, cognitive defects. The functional relevance of the limbic system has proven to serve many different functions such as affects/emotions, memory, sensory processing, time perception, attention, consciousness, instincts, autonomic/vegetative control, and actions/motor behavior. Some of the disorders associated with the limbic system are epilepsy and schizophrenia.
The hippocampus has been demonstrated to be involved in various processes of cognition. The first and most widely researched area concerns memory, spatial memory in particular. Spatial memory was found to have many sub-regions in the hippocampus, such as the dentate gyrus (DG) in the dorsal hippocampus, the left hippocampus, and the parahippocampal region. The dorsal hippocampus was found to be an important component for the generation of new neurons, called adult-born granules (GC), in adolescence and adulthood. These new neurons contribute to pattern separation in spatial memory, increasing the firing in cell networks, and overall causing stronger memory formations. While the dorsal hippocampus is involved in spatial memory formation, the left hippocampus is a participant in the recall of these spatial memories. Eichenbaum and his team found, when studying the hippocampal lesions in rats, that the left hippocampus is “critical for effectively combining the ‘what, ‘when,’ and ‘where’ qualities of each experience to compose the retrieved memory.” This makes the left hippocampus a key component in the retrieval of spatial memory. However, Spreng found that the left hippocampus is, in fact, a general concentrated region for binding together bits and pieces of memory composed not only by the hippocampus, but also by other areas of the brain to be recalled at a later time. Eichenbaum’s research in 2007 also demonstrates that the parahippocampal area of the hippocampus is another specialized region for the retrieval of memories just like the left hippocampus.
The hippocampus, over the decades, has also been found to have a huge impact in learning. CurlikShors examined the effects of neurogenesis in the hippocampus and its effects on learning. This researcher and his team employed many different types of mental and physical training on their subjects, and found that the hippocampus is highly responsive to these latter tasks. Thus, they discovered an upsurge of new neurons and neural circuits in the hippocampus as a result of the training, causing an overall improvement in the learning of the task. This neurogenesis contributes to the creation of adult-born granules cells (GC), cells also described by Eichenbaum in his own research on neurogenesis and its contributions to learning. The creation of these cells exhibited “enhanced excitability” in the dentate gyrus (DG) of the dorsal hippocampus, impacting the hippocampus and its contribution to the learning process.
Damage relayed to the hippocampal region of the brain has reported vast effects on overall cognitive functioning, particularly memory such as spatial memory. As previously mentioned, spatial memory is a cognitive function greatly intertwined with the hippocampus. While damage to the hippocampus may be a result of a brain injury or other injuries of that sort, researchers particularly investigated the effects that high emotional arousal and certain types of drugs had on the recall ability in this specific memory type. In particular, in a study performed by Parkard, rats were given the task of correctly making their way through a maze. In the first condition, rats were stressed by shock or restraint which caused a high emotional arousal. When completing the maze task, these rats had an impaired effect on their hippocampal-dependent memory when compared to the control group,. Then, in a second condition, a group of rats were injected with anxiogenic drugs. Like the former these results reported similar outcomes, in that hippocampal-memory was also impaired. Studies such as these reinforce the impact that the hippocampus has on memory processing, in particular the recall function of spatial memory. Furthermore, impairment to the hippocampus can occur from prolonged exposure to stress hormones such as Glucocorticoids (GCs), which target the hippocampus and cause disruption in explicit memory.
In an attempt to curtail life threatening epileptic seizures, 27-year-old Henry Gustave Molaison underwent bilateral removal of almost all of his hippocampus in 1953. Over the course of fifty years he participated in thousands of tests and research projects that provided specific information on exactly what he had lost. Semantic and episodic events faded within minutes, having never reached his long term memory, yet emotions, unconnected from the details of causation, were often retained. Dr. Suzanne Corkin who worked with him for 46 years until his death described the contribution of this tragic “experiment” in her 2013 book.
Episodic-autobiographical memory (EAM) networks
The amygdala, another integrative part of the limbic system, is also involved in many cognitive processes. Just as in the hippocampus, memory seems to be impacted by processes in the amygdale; however, it is not spatial memory as in the hippocampus, but episodic-autobiographical memory (EAM) networks. The amygdala, as researched by Markowitsch, was found to be responsible for the encoding, storage, and retrieval of these types of memories. To delve deeper into these types of processes by the amygdala, Markowitsch and his team provided extensive evidence through investigations that the “amygdala’s main function is to charge cues so that mnemonic events of a specific emotional significance can be successfully searched within the appropriate neural nets and re-activated.” These cues for emotional events created by the amygdala encompass the EAM networks previously mentioned.
Attentional and emotional processes
Besides memory, the amygdala also seems to be an important brain region involved in attentional and emotional processes. First, to define attention in cognitive terms, attention is the ability to hone in on some stimuli while ignoring others. Thus, the amygdala seems to be an important structure in this ability. Foremost, however, this structure was historically thought to be linked to fear, allowing the individual to take action to rid that fear in some sort. However, as time has gone by, researchers such as Pessoa, generalized this concept with help from evidence of EEG recordings, and concluded that the amygdala helps an organism to define a stimulus and therefore respond accordingly. However, when the amygdala was initially thought to be linked to fear, this gave way for research in the amygdala for emotional processes. Kheirbek demonstrated research that the amygdala is involved in emotional processes, in particular the ventral hippocampus. He described the ventral hippocampus as having a role in neurogenesis and the creation of adult-born granule cells (GC). These cells not only were a crucial part of neurogenesis and the strengthening of spatial memory and learning in the hippocampus but also appear to be an essential component in the amygdala. A deficit of these cells, as Pessoa (2009) predicted in his studies, would result in low emotional functioning, leading to high retention rate of mental diseases, such as anxiety disorders.
Social processing is an area of cognition specific to the amygdala. To be specific, the evaluation of faces in social processing is of particular importance. In a study done by Todorov, fMRI tasks were performed with participants to evaluate whether the amygdala was involved in the general evaluation of faces. After the study, Todorov concluded from his fMRI results that the amygdala did indeed play a key role in the general evaluation of faces. However, in a study performed by researchers Koscik and his team, the trait of truthworthiness was particularly examined in the evaluation of faces. They investigated how brain damage to the amygdala played a role in truthworthiness, and found that individuals that suffered damage tended to confuse trust and betrayal, and thus placed trust in those having done them wrong. So Koscik demonstrated that the amygdala was involved in evaluating the truthworthiness of an individual. Yet, a man named Rule, along with his colleagues, expanded on the idea of the amygdala in its critique of truthworthiness in others and performed a study in 2009 in which he examined the amygdala in its role of evaluating general first impressions and relating them to real-world outcomes with his study involving first impressions of CEOs. Rule demonstrated that while the amygdala did play a role in the evaluation of truthworthiness, as observed by Koscik in his own research two years later in 2011, the amygdala played a generalized role in the overall evaluation of first impression of faces. This latter conclusion, along with Todorov’s study on the amygdala’s role in general evaluations of faces and Koscik’s research on truthworthiness and the amygdala, further solidified evidence that the amygdala plays a role in overall social processing.
Paul D. MacLean, as part of his triune brain theory, hypothesized that the limbic system is older than other parts of the fore-brain, and that it developed to manage fight or flight circuitry, which is an evolutionary necessity for reptiles as well as humans. MacLean postulated that the human brain has evolved three components, that evolved successively, with more recent components developing at the top/front. These components are, respectively:
1 – The archipallium or primitive (“reptilian”) brain, comprising the structures of the brain stem – medulla, pons, cerebellum, mesencephalon, the oldest basal nuclei – the globus pallidus and the olfactory bulbs.
2 – The paleopallium or intermediate (“old mammalian”) brain, comprising the structures of the limbic system.
3 – The neopallium, also known as the superior or rational (“new mammalian”) brain, comprises almost the whole of the hemispheres (made up of a more recent type of cortex, called neocortex) and some subcortical neuronal groups. It corresponds to the brain of the superior mammals, thus including the primates and, as a consequence, the human species.
According to Maclean, each of the components, although connected with the others, retained “their peculiar types of intelligence, subjectivity, sense of time and space, memory, mobility and other less specific functions”.
However, while the categorizaton into structures is reasonable, the recent studies of the limbic system of tetrapods, both living and extinct, have challenged several aspects of this hypothesis, notably the accuracy of the terms “reptilian” and “old mammalian”. The common ancestors of reptiles and mammals had a well-developed limbic system in which the basic subdivisions and connections of the amygdalar nuclei were established. further, birds, which evolved from the dinosaurs, which in turn evolved separately but around the same time as the mammals, have a well-developed limbic system. While the anatomic structures of the limbic system are different in birds than in mammals, there are functional equivalents.
from “Atlas of the Human Brain Connections”. Catani, Thiebaut de Schotten – Oxford, 2012
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