Sunday, October 12, 2014

Rat Tickling and the Neuroscience of Emotions

Image: Patterns of emotionally-induced arousal and inhibition. Inhibition (purple) and arousal (red/yellow) within the lateral (outer region-top image pair) and medial (inner region-bottom image pair) regions of both brain hemispheres while human subjects experience emotions produced by personal memories. As indicated by changes in blood flow, inhibition is primarily derived from the outer (neocortical "self-control") regions - downward arrows, while excitation is primarily occurring in deep inner (subcortical "emotion-generating") regions. It is within these regions that Dr. Panksepp has traced seven neural pathways that, when stimulated, generate consistent emotional behaviors in all mammals. Source: Dr. Antonio Damasio/PLOS One. 
Within the dim, red-lit laboratory, a gentle, avuncular man in a white coat reaches into a glass tank and begins studiously tickling its inhabitant. His free hand holds a microphone, which amplifies and records the response - a high-pitched chortling which is, says the good doctor, the joyful giggling of a laboratory rat.

Meet Dr. Jaak Panksepp, colloquially referred to as the Rat Tickler. Here at Bowling Green State University, he has been pioneering the relatively new field of affective neuroscience.

For over five decades, Dr. Panksepp has meticulously mapped out neural circuits responsible for emotions, deep within the brains of humans and other animals. His findings may revolutionize psychiatry - providing powerful new tools to fundamentally alter the deepest instinctual drives and mental states shared by mammals and other animals, including birds, and perhaps to a lesser extent, reptiles, amphibians, fish and even crustaceans and insects.

He has discovered that these primary process systems arise from deep, ancient limbic brain structures, rather than from higher-order cognitive pathways of the neocortex - the brain's outer surface, where conscious thought, planning and judgements are processed.

These emotion-generating primary process systems are found within the same inner brain regions which regulate hormonal control of the body, via the brain's "thermostat" - the hypothalamus and pituitary gland.

The human brain, explains Dr. Panksepp, can be thought of as a nested hierarchy. Visualizing it in this way allows us to understand its layered organization and evolutionary development. His research shows that we have evolved a uniquely human cognitive (computational) mind atop a widely-shared affective (emotional-physical arousal states) mind. In general, the cognitive system uses neurotransmitters to process incoming sensory data, while the affective system uses neuromodulators to control overall brain states.

Unlike a neurotransmitter, a neuromodulator doesn't directly signal a single target neuron; instead, it spreads across a wide region, altering the activity of several neurons at once. Functionally, neuromodulators are thus able to act like chemical spigots - valves controlling the flow of neural signalling, altering the sensitivity of post-synaptic (signal-receiving) neurons or muscles to neurotransmitters, and thus altering signal strength, rhythm and timing.

The most abundant and powerful known neuromodulators include serotonin, dopamine, norepinephrine and acetylcholine. Because they circulate in the cerebrospinal fluid - the liquid bathing the brain and spinal cord, they can remain active for up to several minutes after release, altering widespread brain regions, including the cerebral cortex and deep neural hubs called the basal ganglia, central to learning and behavior. In this way, neuromodulators appear to underlie long-term effects upon mental and physical states - such as moods.

Higher up the heirarchy,  the basal ganglia produce secondary processes - learning, or creating memories, which can link sensory perceptions with emotional evaluations - feelings. This is the basis of conditioned learning - the formation of useful, survival-guiding memories.

At the third, topmost level, the neocortex uses life experiences to execute tertiary processes - higher-level computations which including thinking, ruminating, and planning. Here too, the forebrain and medial (middle) frontal cortex ideally provide control over emotional reactivity.

Certain neurochemicals and hormones produce highly predictable emotional-behavioral responses, by acting globally upon the brain, bringing several regions and various network functions under the "orchestration of one emotional conductor".  Among them are corticotropin releasing hormone (CRH) , which the hypothalamus secretes to start the chemical cascade of the stress response - more commonly known as the fight or flight response.

Three major neuromodulator systems are central to primary process circuitry, affecting the entire human brain and nervous system:

1. The ventral tegmental area (VTA), which supplies dopamine in the brain's "motivation circuit" - the medial forebrain bundle. This deep brain circuit provides pleasant sensations in the form of an excited expectancy - thus acting as a motivation center. Here, dopamine stimulation increases arousal in animals, which become more eager and inquisitive, engaging in exploratory behavior.

The MFB is part of the much larger mesolimbic system, running from the hypothalamus through the basal ganglia and medial frontal cortex. This is the brain's most important circuit for motivation, learning, and, pathologically, addictions. It's this pathway which is hijacked in addictions to drugs such as cocaine and amphetamines, which artificially increase dopamine levels in the synaptic clefts, the gaps between neurons, across which the chemical messengers known as neurotransmitters are delivered.

2. The dorsal raphe nucleus (DRN), a neural cluster in the midbrain and brainstem, which primarily supplies serotonin to the forebrain and limbic system. The serotonergic system is one of the brain's oldest neuromodulatory systems, primarily engaged in inhibition, opposing other neuromodulators, and thus inhibiting both sensory input and behavioral output. Serotonin is key to controlling impulsivity - behavior without forethought.

Laboratory animals low in serotonin are unable to restrain themselves from responding inappropriately. In humans, serotonin system dysfunction has been linked to an inability to suppress aggression. Serotonin is also critical for modulating and coping with stress, and emotional behavior in general. Impairment of the serotonergic system interferes with one's ability to deal with stressful situations.

3. The locus coeruleus (LC), a neural cluster located in the pons of the brainstem, is a region of the reticular activating system, with neurons that project into several regions of the limbic system - including the VTA - and cortex. The LC synthesizes the neuromodulator norepinephrine, used to regulate wakefulness, attentiveness and physiological responses to stress. It sends projections to the VTA (motivation), amygdala (fear, anger and other emotional processing, as well as salience discrimination - determining what specifically is important enough to our future survival for storing in memory), hippocampus (memory generation), thalamus (sensory processing and relaying) cerebral cortex (conscious thought, planning, sensory interpretation, self control) spinal cord and cerebellum (movement and balance coordination, possibly involved in language and learning), and thus also plays a significant role in learning.

Because of its wide effects, the LC system is central to attention, behavioral and cognitive control, memory, emotions, sleep cycles, and posture and balance. In conjunction with the hypothalamus, it also helps control responses to stress, specifically the fight or flight response. Increased sensitivity among neurons running from the LC to the amygdala is thought to be at the heart of learned fear disorders, such as post-traumatic stress disorder (PTSD).

While the dopamine system may induce general exploratory behavior, the LC-NA (noradrenaline is the older name for norepinephrine) system seems to promote goal-directed behavior, by influencing attentiveness.

Cognition - thought - is fed by accumulated life experiences, encoded as memories and factual knowledge. However, the primary processes - ancient affective states - are necessary to help generate these memories. New memories are encoded with the help of affective states, which enable animals to subjectively evaluate their life experiences.

In The Archaeology of Mind: Neuroevolutionary Origins of Human Emotions, Dr. Panksepp explains that these primary-process affects are "...ancient brain processes for encoding value - heuristics* of the brain for making snap judgements as to what will enhance or detract from survival, with rewarding or punishing effects."

"These brain functions provide selective advantages in that they effectively anticipate universal, future survival needs. Animals that had these capacities survived and bred with greater success.... Just imagine how useful pain is."

Dr. Panksepp's life work has been the discovery of seven such primary-process pathways - circuits which trigger distinct mental, physiological and behavioral patterns, including SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF, and PLAY. Because these pathways and their effects are both ubiquitous and fundamental (what evolutionary psychologists call evolutionarily homologous experiences), equivalent across different species of mammals, Dr. Panksepp spells them in capital letters.

To the pet owner, veterinarian or farmer, the notion that non-human animals cannot experience these emotions is patently absurd. Virtually all domesticated animals - dogs, cats, horses, pigs, cows, goats and even birds - display distinct personalities, temperaments and moods, including affection, loyalty, jealousy, fear, shame, pride, peevishness, anticipation, and many more. And mammals emit essentially the same emotionally expressive vocalizations as humans, including howls of rage, wails of grief, hoots or squeals of joy, and growls of anger. The generation of these sounds originates from the same brain region in every mammalian species. Despite all this, however, many modern scientists and corporate interests see animals as nothing more than simple stimulus-response boxes.

Dr. Panksepp's work is destined to permanently dispel such utilitarian illusions. He has been using a three-pronged approach to tracing these networks, homologous throughout the mammalian world: through direct electrical and chemical stimulation; through the rigorous study of instinctual behavior patterns; and through comparing human reports to (non-human) animal responses when these regions are stimulated, via electrodes or chemical injections.

He first became inspired to study neural correlates of emotions at the University of Massachusetts during the 1960s, while studying under Dr. Jay Trowill, who was experimenting with a new technique first introduced by Peter Milner and James Olds of McGill University - the insertion of electrodes into rat brains to create pleasant or unpleasant effects. In these experiments, after an electrode has been surgically implanted, a test rat is able to switch the electrical stimulation on or off with the press of a lever.

In one variation of such experiments, when a rat presses the control lever, the electrode stimulates regions of the medial forebrain bundle. After experiencing just a single stimulation, the experimental rats would immediately begin to repeatedly press the lever, stimulating their reward centers till they literally dropped from physical exhaustion.

However, activating the neural circuitry of the MFB through dopamine administration produces excited exploratory behavior similar to a search for food. Thus, this pathway seems to function as an instinctive motivation system, generating enthusiasm or expectancy, prompting animals to explore their environment for rewards. Amazingly, emotions can be switched on and off with a tiny electrical current.

In these experiments, since animals can activate or deactivate stimulation of each affect-generating regions, they indicate very clearly and consistently that they all dislike rage, fear, panic and grief, but they enjoy seeking, lust, care and play. And even invertebrates show some primitive affective responses: crayfish, for example, show an extreme liking for addictive substances like morphine and amphetamines, and bees display irritation when given inferior ingredients for their honey-making activities.

The primary process circuits are far more ancient than the earliest humans, who first emerged about two and a half million years ago, during the Pleistocene age.

They are at least as old as the divergence of the first mammals from their reptile ancestors.

These deep subcortical circuits encode the brain's basic emotional operating systems - a form of evolutionary memories.

Evolution tends to be parsimonious (stingy). Biological organisms don't constantly develop in radically new directions, or pass along traits which confer no survival value - natural selection ensures such wasteful development quickly fades out of existence. But features which do promote survival are passed on, as new species emerge from existing ones.

From an engineering standpoint, nearly all multicellular animals are basically tubes, optimized for food-harvesting, with a mouth at one end, and an anus at the other. Add wings, flippers, arms or legs, and you've simply created an eating machine that can harvest calories more quickly. Aside from one major apparently failed global experiment, the basic body plan hasn't changed.

Before the advent of modern genetic comparative analyses, scientists primarily used homologous traits - structures shared by diverse species - such as the jointed wings of a bat, the pectoral fins of a whale and the fingers of a human - to build phylogenic trees (ancestral charts). Such homologous traits are said to have been conserved - genetically preserved and passed down through the course of evolution. Among such conserved traits are a number of brain regions shared among vertebrates, particularly mammals.

Across the entire mammalian class, specific neural clusters and neurochemicals are shared, performing identical or nearly identical functions, depending upon each species' environmentally-determined survival needs. (There is greater detail available here for the particularly curious.)

These neural homologies began to emerge among the first chordates - half-a-billion-year-old creatures from which we descended, and among whose family we count ourselves. The first chordates (like the recently-rediscovered Pikaia) evolved in ancient Earth's oceans, and were so successful that some survive nearly unchanged to the present day. Among these living fossils are 32 known species of lancelets, which live half-buried in the sand of temperate and tropical shallows the world over. These segmented marine animals have "lance-shaped" bodies with sturdy, flexible notochords extending from head to tail, and a recognizable mouth for harvesting plankton.

The notochords would eventually evolve into into central nervous systems, which would branch out in ever-growing complexity from spinal cords. These would come to be encased in spinal columns, as animals incorporated the ancient oceans' abundant calcium salts into skeletal backbones.

Over time, the survival advantage of sense organs for sight, (and later taste, hearing and smell) required a concentration of neurons called ganglia in the creatures' foremost body region. As these early marine animals swam, this neural cluster could interpret incoming sensory data as efficiently as possible, enabling rapid navigation and food-harvesting.

As the stresses of environmental change reshaped their genes, ever more sophisticated chordates emerged - fish, amphibians, reptiles, birds and mammals. And as their sensory organs and locomotor systems grew in sophistication, so did their computational organs - their brains.

However, the parsimonious nature of evolution meant that certain features would get reused, rather than being re-engineered out of whole cloth. Because of this, humans share neural and neurochemical homologies with all mammals, including modern rodents, which superficially resemble our earliest mammalian ancestors.

But we share more than mere anatomical features with all Earth's mammals. In The Archaeology of Mind, Dr. Jaak Pansepp outlines what his five decades of experimentation have revealed: that we share our core emotions and drives with all mammals, and to a lesser extent, birds, reptiles and many other creatures.

We've inherited these traits for a good reason: emotions evolved to ensure survival. They serve as behavioral guides. Coupled with (and guiding the formation of) learned behaviors gleaned through experience, emotions prompt behaviors that bring comfort and reduce discomfort, increasing the odds of survival and reproduction. At heart, "affects" - the raw neural-hormonal responses and states which require cognition to be interpreted as emotions - produce the most basic behavior patterns - approach or avoidance.

The ancient circuitry which creates these affective states lies in the deepest, most evolutionarily ancient and conserved regions of the human brain, sprouting from atop the brainstem, which controls our most vital life functions, such as breathing, heartbeat swallowing and sleep-wake states. We know that these affects are limbically generated, because the behaviors continue even after decortication - the surgical removal of an animal's cortex.

These primal instinctive-emotional circuits are altered by experience, becoming more responsive (sensitization) or less so (habituation), depending upon both our experiences and our mental evaluations of them.

Dr. Panksepp's contribution to our understanding of affective neuroscience has been in charting how these seven emotional-behavioral circuits, when stimulated, produce virtually identical affects (though often differing effects) across every mammal species studied to date.

These seven neural systems lie deep below the level of the human cortex - the most recently-evolved, wrinkly outer layer - the seat of conscious thought, planning, evaluation, calculation and consideration. The primal drives and emotions to which they give rise are distinct from the homeostatic (biochemical balance-maintaining) affects such as hunger and thirst, and the purely sensory affects, which include disgust and various types of pain.

Says Dr. Panksepp, the infinite variety of subtle emotional shades we experienced are produced from a combination of these seven core affects, coupled with the unique melange of memories, cognition and bodily sensations each of us uses to interpret and shape them.

The seven core affective systems he has discovered to date are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF, and PLAY. Each of these seven primary-process emotional systems interacts with the others, with inhibitory or synergistic effects, as well as with the arousal systems, moderated by acetylcholine, norepinephrine, dopamine and serotonin, in special neural centers common to all vertebrates.

These neural attention/arousal subsystems are shared - primarily the circuitry concentrated in the brainstem - and are modulated by the neurohormones serotonin, norepinephrine, dopamine and acetylcholine - but overall, each affective circuit follows a distinct, specific path and neurochemistry, and each is shared by all mammalian brains.

As Dr. Panksepp explains: "Dopamine lies at the heart of... [the SEEKING system], controlling practically everything that organisms do. Its interactions with other brain regions are so extensive that it helps to facilitate most other emotional urges.

"likewise, norepinephrine, an even older system (since the cells are further down in the brain) facilitates attention during every kind of emotional arousal but more heavily so for euphoric feelings. Acetylcholine does the same, but often for more negative emotions."

Dr. Panksepp's work revises and expands upon the somewhat dated theory of Dr. Paul D. MacLean, an American neuroscientist who hypothesized in the 1960s that the modern brain evolved in three stages: a reptilian complex, a paleomammalian (ancient mammary-bearing animal) complex called the limbic system, and a neomammalian (new mammal) complex called the neocortex.

However, according to Dr. Panksepp, the circuitry reasonsible for these seven affective states - the "primary processes" - arise from the deepest, most ancient regions of the mammalian brain. They are hardwired - built into all mammalian brains, and not learned, constituting what he calls "ancestral memories".

The seven primary processes - raw emotional states - in turn control higher-order secondary processes - learning mechanisms such as associations. Both combine with tertiary processes - cognition - to create our conscious mind states. Affective states mix with and in turn moderate memories, complex ideas, reflections and subjective experiences.

Our uniquely individual gene patterns control the makeup of these seven primary-process circuits, leading to variability among us - emotional temperaments - which give rise with the force of habit to distinct personalities (which can, in turn, be altered by experience).

Dr. Panksepp describes these systems as "... SEEKING (expectancy), FEAR (anxiety), RAGE (anger), LUST  (sexual excitement), CARE (nurturance), PANIC/GRIEF (sadness), and PLAY (social joy). He addresses "...the primary-process nature of these systems,  and to a lesser extent, "...the secondary process (inbuilt emotional learning mechanisms) and the tertiary process (emotional thoughts and deliberations that are so evident in human experience)." He gives a brief summary of each of the seven affective systems as follows:
1. The SEEKING, or expectancy, system (discussed in Chapter 3) is characterized by a persistent exploratory inquisitiveness. This system engenders energetic forward locomotion—approach and engagement with the world—as an animal probes into the nooks and crannies of interesting places, objects, and events in ways that are characteristic of its species. This system holds a special place among emotional systems, because to some extent it plays a dynamic supporting role for all of the other emotions. When in the service of positive emotions, the SEEKING system engenders a sense of purpose, accompanied by feelings of interest ranging to euphoria. For example, when a mother feels the urge to nurture her offspring, the SEEKING system will motivate her to find food and shelter in order to provide this care. The SEEKING system also plays a role in negative emotions, for example, providing part of the impetus that prompts a frightened animal to find safety. It is not clear yet whether this system is merely involved in helping generate some of the behaviors of negative emotions, or whether it also contributes to negative feelings. For the time being, we assume it is largely the former, but that the positive psychological energy it engenders also tends to counteract negative feelings, such as those that occur during FEARful flight and the initial agitation of PANIC/GRIEF. For this reason, animals may actually find fleeing to be in part a positive activity, since it is on the most direct, albeit limited, path to survival.
2. The RAGE system (see Chapter 4), working in contrast to the SEEKING system, causes animals to propel their bodies toward offending objects, and they bite, scratch, and pound with their extremities. Rage is fundamentally a negative affect, but it can become a positive affect when it interacts with cognitive patterns, such as the experience of victory over one’s opponents or the imposition of one’s own will on others who one is able to control or subjugate. Pure RAGE itself does not entail such cognitive components, but in the mature multi-layered mammalian brain (Fig 1.4), it surely does.
3. The FEAR system (see Chapter 5) generates a negative affective state from which all people and animals wish to escape. It engenders tension in the body and a shivery immobility at milder levels of arousal, which can intensify and burst forth into a dynamic flight pattern with chaotic projectile movement to get out of harm’s way. If, as we surmised above, the flight is triggered when the FEAR system arouses the SEEKING system, then the aversive qualities of primary-process FEAR may be best studied through immobility “freezing” responses and other forms of behavioral inhibition, and reduced positive-affect, rather than flight.
4. When animals are in the throes of the LUST system (see Chapter 7), they exhibit abundant “courting” activities and eventually move toward an urgent joining of their bodies with a receptive mate (Figure 7.1), typically culminating in orgasmic delight—one of the most dramatic and positive affective experiences that life has to offer. In the absence of a mate, organisms in sexual arousal experience a craving tension that can become positive (perhaps because of the concurrent arousal of the SEEKING system) when satisfaction is in the offing. The tension of this craving may serve as an affectively negative stressor when satisfaction is elusive. LUST is one of the sources of love.
5. When people and animals are aroused by the CARE system (see Chapter 8), they have the impulse to envelop loved ones with gentle caresses and tender ministrations. Without this system, taking care of the young would be a burden. Instead, nurturing can be a profound reward—a positive, relaxed affective state that is treasured. CARE is another source of love.
6. When overwhelmed by the PANIC/GRIEF (also often termed “separation distress”) system (see Chapter 9), one experiences a deep psychic wound—an internal psychological experience of pain that has no obvious physical cause. Behaviorally, this system, especially in young mammals, is characterized by insistent crying and urgent attempts to reunite with caretakers, usually mothers. 
If reunion is not achieved, the baby or young child gradually begins to display sorrowful and despairing bodily postures that reflect the brain cascade from panic into a persistent depression. The PANIC/GRIEF system helps to facilitate positive social bonding (a
secondary manifestation of this system), because social bonds alleviate this psychic pain and replace it with a sense of comfort and belonging (CARE-filled feelings). For this reason, children value and love the adults who look after them. When people and animals enjoy secure affectionate bonds, they display a relaxed sense of contentment. Fluctuations in these feelings are yet another source of love.
7. The PLAY system (see Chapter 10) is expressed in bouncy and bounding lightness of movement, where participants often poke— or rib—each other in rapidly alternating patterns. At times, PLAY resembles aggression, especially when PLAY takes the form of wrestling. But closer inspection of the behavior reveals that the movements of rough-and-tumble PLAY are different than any form of adult aggression. Furthermore, participants enjoy the activity. When children or animals play, they usually take turns at assuming dominant and submissive roles. In controlled experiments, we found that one animal gradually begins to win over the other (becoming the top dog, so to speak), but the play continues as long as the loser still has a chance to end up on top a certain percentage of the time. When both the top dog and the underdog accept this kind of handicapping, the participants continue to have fun and enjoy this social activity. If the top dog wants to win all the time, the behavior approaches bullying. As we will see in Chapter 10, even rats clearly indicate where they stand in playful activity with their emotional vocalizations: When they are denied the chance to win, their happy laughter-type sounds cease and emotional complaints begin. The PLAY system is one of the main sources of friendship.
As Dr. Panksepp points out in his newest publication, "The goal of psychotherapy is affect regulation". Thus, his research is likely to be of enormous benefit in improving such therapeutic goals.

In a similar vein, researchers such as Emory University neurologist Dr. Helen Mayberg, have recently begun using electrical stimulation of targeted brain regions in hopes of helping patients whose depression is resistant to pharmacological treatments.

Dr. Mayberg's Deep Brain Stimulation technique may have alleviated severe depression in several patients, but Dr. Panksepp contends that this treatment is both figuratively and literally off the mark. He and his team are currently studying ways of addressing mood disorders through direct manipulation of the seven affective systems.

For example, Dr. Panksepp defines depression as an underactivated seeking urge, hobbled by excessive psychological pain. By directly altering the primary process neural circuits (such as the MFB), Dr. Panksepp hopes to counteract the psychological pain by strengthening the primitive seeking urge, in effect "amplifying eagerness to live". At this point, however, such technology is still very much in the experimental stages.

* heuristics are on-the-fly judgements based upon experience - commonly referred to as "best guesses", "common sense" or "rules of thumb".

Sources: Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals, Dr. Jaak Panksepp, September 07, 2011, Public Library of Science One; 
Discover Interview: Jaak Panksepp Pinned Down Humanity's 7 Primal Emotions, Pamela Weintraub, May 31, 2012, Discover Magazine; The Archaeology of Mind: Neuroevolutionary Origins of Human Emotions, Jaak Panksepp, Lucy Biven, Norton Series on Interpersonal Neurobiology, WW Norton and Company, 2012;
A Depression Switch? David Dobbs, April 2, 2006, New York Times

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