Stress Hardware Review: Anterior Cingulate

Dolomites_EN-US3033597177The anterior cingulate cortex is a region of the brain that is activated by sensation, cognition, and emotion. It appears to play an important role in autonomic, affective, and cognitive behavior. Because of its position, the anterior cingulate is anatomically and functionally well positioned to integrate information across the physical, intellectual and emotional domains. Important in the stress reaction, the anterior cingulate region is activated during self-regulation of arousal through its connections with the cholinergic basal forebrain. The whole structure, but especially area 32, produces inhibitory inputs that decrease amygdala responsiveness and are helpful in mitigating the effects of fear and in preventing or at least delaying “amygdala hijacks.”

The normal functioning of the anterior cingulate area leads to a normal response to stressful events, which is a psychophysiological arousal or increased emotionality. The normality of the brain response to traumatic stimuli also serves to inhibit feelings of fear when there is no true threat.  Any chemical or structural failure of activation in this area and/or decreased blood flow in the adjacent subcallosal gyrus can lead to an exaggerated response to stress, resulting in significantly higher emotionality and the inability to properly regulate fear. The latter condition provides the inducing cues in anxiety disorders, i.e. increased and persistent fearfulness that is not appropriate for the context.

What the Anterior Cingulate Does

BrodmanBrainAreasPhysically, stimulation of the anterior cingulate (especially in area 24) induces changes in blood pressure, heart rate, respiratory rate, pupillary dilation, skin conductance, thermoregulation, gastrointestinal motility, and changes in adrenal cortical hormone secretion (ACTH). Cognitively, the anterior cingulate cortex plays a leading role in learning new behaviors, whether as a conditioned response to predictors of painful stimuli, as an instrumental response to avoid such stimuli, or in response to reduced reward. Emotionally, the anterior cingulate (along with other structures in the limbic system) mediates emotional responses including fear, agitation, and euphoria, and verbal expression with affective content, such as sighs, cries, and screams.

Neuroimaging studies with powerful fMRI instruments show electrical activation in the rostral–ventral anterior cingulate cortex when individuals under study are asked to recall sad memories or view faces with sad expressions, when they are told to anticipate an upcoming painful electric shock, and when exposed to scenes or words with emotional content. It should come as no surprise that stress-induced activations in the amygdala and orbitofrontal cortex occur simultaneously with those in the anterior cingulate cortex.

Genes, Stress and the Anterior Cingulate

Genetic studies have conclusively demonstrated that the anterior cingulate cortex is highly sensitive to environmental stressors, either physical, psychological, or behavioral. Anoxia (lack of oxygen), maternal separation, amyloid protein expression, and drug abuse all induce hypometabolism, gliosis, and programmed cell death in the anterior cingulate cortex. After prolonged and continued exposure to stress, nerve cells in the anterior cingulate cortex are damaged and killed by excessive stimulation, a process called excitotoxicity.

When the Anterior Cingulate Malfunctions

Several psychiatric disorders are linked with abnormalities in the function of the anterior cingulate cortex. Significantly elevated neurochemical activity in this region of the brain has been observed in obsessive–compulsive disorder, tic disorder, and depression. A normal range of activity is restored with behavioral and pharmacological treatment of these disorders. Other psychiatric disorders that have been associated with abnormal functioning of the anterior cingulate cortex include attention deficit hyperactivity disorder (ADHD) and schizophrenia.

Stress Hardware Update: Limbic System 2.0

LimbicSystemGeographyThe term limbic system designates the entire neuronal circuitry and forebrain structures that control emotional behavior, motivational drives and the processing of present and past sensory experiences. The brain structures of the limbic system are located around the middle edge of the brain. Several limbic structures are involved in determining the affective nature of sensory inputs, i.e., whether the sensations are pleasant or unpleasant. The emotional qualities we attach to the input provided by our five senses are also called reward (when they are pleasing to us and therefore we crave more of them) or punishment (when they are unpleasant and therefore we seek to avoid them), or satisfaction or aversion. Neurobiological research on the functions of the limbic system dating back to its XIX century pioneer Pierre-Paul Broca (1861), later expanded by James Papez (1937), Giuseppe Moruzzi and Horace Magoun (1949), and Ross MacLean (1949, 1952) identified the “reticular” and “limbic” systems as regulating the energizing and expressive roles in the central nervous system.

The limbic system is comprised of numerous structures, the most important of which are the hypothalamus, the amygdala, the hippocampus, the cortex, the cingulate gyrus, the striatum, the pallidum, the thalamus, and Meynert’s nucleus basalis. Each of these structures performs a specific function, and often also serves to receive, transmit and amplify communication within the limbic system, with other areas of the brain, and with other parts of the central nervous system.

The Hypothalamus: The Central Autonomic Controller

A major component of the limbic system is the hypothalamus and its related substructures. The hypothalamus complex controls the internal state of the body, such as temperature, osmolality of the body fluids, appetite and thirst and the regulation of body weight. Despite its very small size of only a few cubic centimeters (which represents less than 1% of the brain mass), the hypothalamic complex has two-way communicating pathways with all levels of the limbic system and is the key structure for higher level coordination of autonomic and endocrine functions. There would not be a stress reaction, with its almost instantaneous activation of physical and psychological defense mechanisms, without the hypothalamus providing the critical signal activation.

The Amygdala: The CPU of Emotional Response

AmygdCingGyrusThe amygdala is a group of nuclei embedded in the anteromedial temporal lobe, which receives input from all five senses. It performs the analysis of form and color and facilitates the recognition of complex stimuli such as human faces. The amygdala can influence heart rate and blood pressure, gut and bowel function, respiratory function, bladder function, and many more instinctive physical reactions. It is in the amygdala and its connection to other limbic structures that the determination of the affective value of sensory stimuli (rewarding or aversive) is made and our mood (or feelings about something) is determined. Stimulation of the amygdala produces the defense reaction that prepares us for fight, flight or freeze, along with complex sensory and experiential phenomena, which may include fear, sensory hallucinations, feelings of deja vu, and memory-related flashbacks and nightmares. The amygdala receives neuronal signals from all portions of the limbic cortex and is the “central processing unit” in which the limbic system produces an emotional response to events, people and situations. The amygdala also interacts with higher brain regions that govern such processes as directed attention, declarative memory, and response inhibition (Davidson, Putnam, & Larson, 2000; LeDoux, 1995).

The Hippocampus: Memory Chips and Orientation

The hippocampus is a highly specialized region of the cerebral cortex, which along with surrounding areas of the parahippocampal gyrus is directly involved in memory processing and spatial orientation. The hippocampus provides the neural mechanism for association of different parameters that is necessary for the moment-to-moment incorporation of experience into our short- and long-term memory banks. Almost any type of input from the five senses causes activation of at least part of the hippocampus, which in turn distributes many outgoing signals to the anterior thalamus, to the hypothalamus, and to other parts of the limbic system, especially through the fornix, a major communicating pathway.

The Orbital and Medial Prefrontal Cortex: Food and Personality

PhineasGageThe cortical areas of the limbic system are divided into two interconnected networks with related but distinct functions. Many of these functions are related to food or eating (e.g., olfaction, taste, visceral afferents, somatic sensation from the hand and mouth, and vision), and neurons in the orbital cortex respond to multisensory stimuli involving the appearance, texture, or flavor of food. Therefore, the orbital and medial prefrontal cortex have the function of evaluating feeding-related sensory information and to stimulate appropriate visceral reactions. More importantly, damage to the ventromedial frontal lobe can produce dramatic behavioral changes, which suggests that the visceral reactions evoked through this cortical area are critical in evaluating alternatives and making choices. As the well-publicized 19th-century case of Mr. Phineas Gage’s accidental head impaling by a steel rod demonstrates, individuals with damage to the ventromedial prefrontal cortex have no problem with their motor or sensory function, their intelligence or cognitive function, but show devastating changes in personality and choice behavior.

The Cingulate Gyrus: The Cement of Society

Intriguing data and ideas have been proposed by several researchers seeking to identify specific functions of the cingulate gyrus. In what has been termed the affiliation/attachment drive theory, Everly (1988) has shown experimentally that the removal of the cingulate gyrus eliminates both affiliative and grooming behaviors. MacLean (1985) has argued that the affiliative drive may be hard-coded in the limbic system and may be the anatomical underpinning of the “concept of family” in humans and primates. The drive toward other-oriented behaviors, such as attachment, nurturing, affection, reliability, and collaborative play, which has been referred to as the “cement of society” (Henry and Stephens, 1977), appears to originate in this relatively small limbic system structure.

The Ventromedial Striatum, Ventral Pallidum, and Medial Thalamus

The nuclei of the ventromedial striatum are also related to reward and reward-related behavior, whereby they inhibit or suppress unwanted behaviors while allowing other behaviors to be freely expressed. The dorsolateral striatum and related areas of the globus pallidus appear to be involved in switching between different patterns of motor behavior, whereas the ventromedial striatum and pallidum may allow changing of stimulus–reward associations when the reward value of a stimulus has changed. These areas are examples of the complexity and redundancies built into limbic system structures that permit multiple iterations of signal transmission and reception, and a much more complex and refined analysis of sensory inputs from the five senses.

Nucleus Basalis (of Meynert)

The nucleus basalis of Meynert is a prominent group of large cells located in the basal forebrain, most of which are involved in the activation of acetylcholine or GABA neurotransmitters, indispensable in activation of the stress reaction and our defense mechanism when a physical or psychological threat is perceived. The magnocellular basal forebrain nuclei are well situated to modulate brain activity in relation to limbic activity.

Disorders of the Limbic System

Although lesions to limbic structures do not necessarily result in sensory or motor deficits, any loss of function in these structures is usually associated with a variety of psychological problems, including depression, bipolar disorder, obsessive–compulsive disorder, and schizophrenia.

Structural changes have been noted in the hippocampal formation, medial thalamus, and prefrontal cortex in schizophrenic subjects. Images obtained through positron emission tomography scans show that the amygdala, prefrontal cortex and medial thalamus are abnormally active in patients suffering from severe unipolar and bipolar depression.

The complete removal of the amygdala and other nearby structures in laboratory settings causes specific changes in animal behavior called the Klüver-Bucy syndrome, whose characteristic symptoms are a complete lack of fear of anything, extreme curiosity about everything, rapid loss of short-term memory, tendency to place everything in the mouth and sometimes even trying to eat solid objects, and a sex drive so strong that it leads to attempts to copulate with immature animals, animals of the wrong sex, or even animals of a different species. Although similar lesions in human beings are rare, afflicted people respond in a manner not too different from that of the affected animal.

Stress Hardware Reviews: The Hippocampus

clip_image001What brain structures rouse us from inactivity and set in motion our defense mechanisms when a stressor is perceived? Predictably, the brain’s older and more primordial area, the so-called animal brain, where the hypothalamus, the amygdala, the hippocampus, the septum area, the basal ganglia and the thalamus are located. These structures, collectively called the limbic system, are interconnected and work together to initiate motor and other functional activities of the brain that mobilize the body. In this post about stress hardware, we discuss the hippocampus.

Virtually any experience perceived by the five senses appears to cause the activation of at least some part of the hippocampus. The hippocampus in turn redistributes these sensory signals to the thalamus, the hypothalamus, and other parts of the limbic system. Thus, the hippocampus acts as an important switching center through which incoming sensory signals are retransmitted and initiate behavioral reactions for different purposes. Its importance has been demonstrated empirically: experimental artificial stimulation of the hippocampus can induce a wide variety of behavioral patterns such as pleasure, rage, passivity, or excessive sexual drive.

The cells of the hippocampus appear to be especially sensitive to the effects of various stressors. Although not directly involved in the stress response, its ventral regions appear to exercise a regulatory influence on the hypothalamic-pituitary-adrenal (HPA) axis activity and are also a primary target for elevated glucocorticoid levels. The glucocorticoid hormones owe their name to their important effects on blood glucose concentration, which is the principal source of energy of the human cell. They also regulate protein and fat consumption, and the utilization of carbohydrates to produce additional quantities of energy. Cortisol is the principal glucocorticoid. Read more

Stress Hardware Review: The Amygdala


There are things I cannot do. I cannot watch my people suffer. I cannot sit when something must be done. I cannot judge those who are different. There are things I cannot do. Run. Hide. Ignore. There are things I cannot do. But there are certainly things I will do!

Padmé Amidala in Star Wars: Clone Wars

One of the most important structures of the brain’s limbic system is the amygdala, which in Queen Amidala’s imaginary brain produced behavior that was characteristically cool and aloof at times, forceful and passionate at others, but always kept in balance by poise and careful deliberation. An exemplar of good stress management.

amygdala The human amygdala is an almond-shaped double  complex (one on each side of the brain) of multiple small nuclei located immediately beneath the cerebral cortex of the medial anterior pole of each temporal lobe. It has abundant bidirectional connections with the hypothalamus as well as with other areas of the limbic system. The amygdala is understood to be a behavioral awareness area that operates at a semiconscious level. It also appears to project into the limbic system one’s current status in relation to both surroundings and thoughts. The most important function of the amygdala is to make the person’s behavioral response appropriate for each occasion… or not, as the case may be.

What specific stress behaviors are directly regulated by the amygdala? We can only infer, as the Maker did not provide a user manual, through observing what happens when the amygdala is accidentally or intentionally removed. Take the jump to find out.

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Stress Hardware Review: The Limbic System

Limbic-System The limbic system is the complex neuronal circuitry that controls emotional behavior and motivational drives. The good news: It comes preinstalled in your brain. The bad news: It controls not only behavior but also body temperature, the drive to eat and drink, and the ability to control body weight. The bottom line: Stressful emotions can set the limbic system on fire, causing overeating (or the opposite), sweating (or chills) and play funny tricks on the motivation to decide whether to fight the stressor, take flight from it or simply freeze in place. Let’s review this all-important structure in the management of stress.


The limbic circuitry is located toward the front of the brain. The limbic system is comprised of numerous structures, the most important of which are the hypothalamus, the amygdala, the hippocampus, the cortex, the cingulate gyrus, the striatum, the pallidum, the thalamus, and Meynert’s nucleus basalis.


The limbic system closely regulates behavior, and more specifically it determines the body’s initial and instinctive reaction to emotional challenges that influences the individual’s ultimate response. For the difference between reaction and response, see this post.

In addition to its primary role in behavior control, the limbic system controls many internal conditions of the body, such as body temperature, concentration of the body fluids, and the impulse to eat and drink, and thus the ability to control body weight.

Since the regulation of these functions is located within the same structure that also processes the first impact of emotions, it is easy to see how a stressor can immediately be felt as a loss of appetite in some of us, or a craving for “comfort” food in others. This design of the system makes it more difficult to keep one’s cool (temperature is affected, too) and to make clear-headed decisions in the face of a serious emotional challenge—exactly when such ability would be needed the most!  Be that as it may, our natural endowment consists of a circuitry that handles the rational and the irrational at the same time and within the same structure, so one must make the best of it in the face of challenges and stressors that can wreak havoc even on the best fine-tuned system.

Technical Specifications (if you really want know all about it)

| References | The outer arc of the limbic system (also called the limbic gyrus) includes the subcallosal area, the cingulate gyrus, the isthmus of the cingulate gyrus, and the parahippocampal gyrus, including the uncus and subiculum. The subcallosal area includes a cluster of small septal nuclei that lie immediately anterior to the paraterminal gyrus and anterior commissure. The septal nuclei receive input from multiple midbrain nuclei, the substantia nigra, the CA1 region of the cornu ammonis, the subiculum, amygdala, lateral hypothalamus, cingulate gyrus, and mamillary bodies. Efferent fibers project to the entire hippocampal formation, the habenula, hypothalamus, thalamus, amygdala, mamillary bodies and the cerebral cortex.

For even more detailed information on the septal region of the limbic system see this article: Cavazos JE, Wang CJ, Sitoh YY, et al: Anatomy and pathology of the septal region. Neuroimag Clin NorthAm 1997; 7:67-78.

br-800epi The middle arc (also referred to as Broca’s intralimbic gyrus) consists of the paraterminal gyrus, the indusium griseum, and the hippocampus. The paraterminal gyrus is wedged between the septal nuclei and the anterior commissure. Posterior to the anterior commissure is the hypothalamus. The indusium griseum, extending from the paraterminal gyrus, consists of gray matter and white matter tracts named the medial and lateral longitudinal stria. The indusium griseum is closely applied to the superior surface of the corpus callosum. Posteriorly, it courses around the splenium and inferiorly merges with the tail of the hippocampus.

The mamillary bodies, fornix, alveus and fimbria form the inner arc. The alveus and fimbria are the major efferent fibers tracts of the hippocampus. Posteriorly, the fimbria form the crura of the fornix that continue upward deep to the splenium of the corpus callosum. As the two crura converge, a thin triangular sheet of fibers passes to the opposite side to form the commissure of the fornix. The crura merge as the body of the fornix, which continues forward along the inferior edge of the septum pellucidum and roof of the third ventricle. At the foramen of Monroe, the fornix divides into two columns which course inferiorly. Just superior to the anterior commissure, the columns divide into pre- and postcommissural tracts. The precommissural fibers connect to the septal nuclei and anterior hypothalamic nuclei. The postcommissural fibers continue inferiorly to end in the mamillary bodies.

Need still more details? See this comprehensive article: Sitoh YY, Tien RD: The limbic system: An overview of the anatomy and its development. Neuroimag Clin North Am 1997; 7:1-10.