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Tuesday, February 2, 2016

Laughing Rats

I attended a talk a couple weeks ago at The New York Psychoanalytic Society and Institute (NYPSI), given by Jaak Panksepp, and entitled, Cross Species Affective Neuroscience. It was a really good talk that I'll try to summarize here. Panksepp spoke using a power point that didn't quite work right, through no fault of his own, and gave a talk similar to his TEDx talk about affect in non-human animals, and the way humans can be understood by studying these animals, particularly with respect to depression. His part was followed by the discussant, Jean Roiphe, who presented a corresponding analytic perspective, and highlighted points of overlap and divergence.

First, the speakers. This is from Wikipedia:



And Jean Roiphe's description from the NYPSI site is:

Clinical Associate Professor of Psychiatry, Weill-Cornell Medical College
Associate Attending Psychiatrist, New York-Presbyterian Hospital
Training and Supervising Analyst, New York Psychoanalytic Institute


One of Panksepp's main points is that affect is the foundation for all consciousness, and that most learning takes place through affective shifts. This reminded me of a guy from my medical school class who decided he should memorize everything by singing, because while the Complement pathways eluded him, he could still remember every TV commercial jingle he learned as a kid.

Panksepp briefly addressed the question of why one would choose to study emotional feelings in animals, which is to say, whether animals have minds at all, and pointed out that animal lovers' beliefs that this is the case is an argument from empathy, and that LeDoux is skeptical about whether animals have feelings.

Panksepp, himself, believes that animals have feelings and that all their experiences are labeled "good" or "bad"; that animals can tell us if something is rewarding or punishing. And here, the definition of "good" = leads to survival, while the definition of "bad" = leads to destruction.

He noted, quite emphatically, that in his opinion, all feelings are based in the subcortical system, and pointed out that while Damasio initially believed feelings are generated in the neocortex, he later switched to Panksepp's position, and acknowledged so, which earned him Panksepp's label of, "mensch". Panksepp does not feel similarly about LeDoux.

Panksepp described the seven emotional systems in the brain. This is one of the places where his slides malfunctioned, so I'm taking this from the slide in his TEDx talk:


SEEKING----Enthusiastic
RAGE---------Pissed Off
FEAR---------Anxious
LUST---------Horny
CARE--------Tender and Loving
PANIC-------Lonely and Sad
PLAY--------Joyous

He mentioned that dopamine and the nucleus accumbens are the foundation for all positive emotions, and that this probably represents a general purpose learning system. He also mentioned the association between the Hypothalamus/PAG/Amygdala and the ANGER system.

He returned to his discussion about the subcortical system as the foundation of feelings and consciousness, and pointed out that rats with no neocortex behave "normally", and that raters were not able to differentiate these from rats with neocortices.  In fact, the neocortex-less rats showed more interest in their environment than the normal rats. No inhibition, I suppose.

He focused particularly on the SEEKING, PLAY, and PANIC systems, because these were areas of exploration that have shown promise for the treatment of depression.

SEEKING is associated with the Medial Forebrain Bundle. Bilateral lesions in this region yield profound depression, while bilateral deep brain stimulation in this region yields an antidepressant effect.

One medication that usefully impacts the SEEKING system and acts as an antidepressant is very low dose buprenorphine, which makes juvenile animals play more. He claimed that drug withdrawal shows similarities to the experience of separation distress, which is a model for depression via the PANIC system.

Opioids mediate every good feeling ever studied, and in fact, contact comfort, known to be effective at soothing panic, doesn't work as well if opioid receptors are blocked.

Oxytocin is just as powerful as opioids with respect to depression, in its re-creation of mothering attachment. This has implications for placebo effect, since handing someone a placebo is an act of caring.

Panksepp cited a very small study he did with Yovell using buprenorphine to treat depression and suicidality. The suicidality results are what he included in his slides:


He also spoke about a study using bilateral Deep Brain Stimulation (DBS) to act on the SEEKING system in 7 subjects with treatment resistant depression. 6/7 responded well, with a marked improvement in planning for their futures. It turned out that in the one non-responder, the DBS had missed on one side.

Finally, and to me this was the most important part, he talked about an antidepressant he has been researching, a tetrapeptide called, GLYX-13, that acts on the PLAY system. The results have been promising, with decreases in depression thought to be mediated by promoting positive social feelings, including laughter. Panksepp is big on laughter, and is known for tickling rats to get them to laugh. Unfortunately, he seemed to indicate that GLYX-13 was bought up by a company with a competing antidepressant, so it may not make it to market.

His slides really gave out at this point, so he handed the stage over to Jean Roiphe for her discussion. Spoiler alert: It's quite brilliant, and if you don't think so after reading my summary, it's only because I didn't do it justice.


Roiphe described being on safari a decade ago, watching animals spending their days grazing on the veldt, except when they sensed a predator, at which point they would take evasive action. This was pretty much all they did, and it correlates well with the SEEKING and FEAR systems. It made her wonder, now that our survival is so much more assured, at least in some parts of the world, what has happened to our emotional meanings? We now fill our free time with things like art and science and architecture and literature and blogging, but we also fill it with neuroses, anxiety, eating disorders, perversions, and all the many clinical presentations we see in our work.

She noted that while the seven emotional systems are preserved in our brains, it's important to remember that, paraphrasing Kandel, humans now change more by cultural than by biological evolution. At the same time, it's also important to establish a line of communication between those who study the subjective aspects of the mental apparatus, such as psychoanalysts, and those who study its objective aspects, such as neuroscientists. And that the mind is simultaneously and always both a psychological and a biological entity.

She spoke about the value of linking the two approaches, in both directions. For psychoanalysis, the value is having neurological correlates to analytically abstract concepts of the mind, because the former are technologically easier to study, with the proviso that this may not simplify matters all that much, since different neuroscientists can interpret "brain data" differently, as in the above example of Panksepp vs. LeDoux.

And for neuroscience, the value is in learning about the complexity of subjective experience, and recognizing that the human condition is impossible to understand or even study without taking the subjective into account.

In some respects, the emotional systems described by Panksepp correlate with Freud's affect theory, in which affect is a way for a person to tell if his or her drives are being satisfied. Or not. I feel good or I feel bad. This experience is pleasant, that one is unpleasant. However, the seven emotional systems are instinctual, do not need to be learned, and involve behavioral responses, whereas Freud's affect theory involves only a pressured sense that something needs to be fulfilled, and this may or may not lead to a behavioral response, but always leads to mental activity, to thought as trial action. This is a good example of why it's important to avoid the trap of trying to create one to one correspondences between approaches.

Freud's ideas about affect evolved over time, along with his changing theory of anxiety, and his shift from the topographic model (unconscious vs. conscious) to the structural model (id, ego, superego), but ultimately, affect became tied to ego function, as a way for the ego (which acts as a combination of party coordinator and chaperone) to mark the need for some kind of response to something, whether that something is internal or external.

This is similar to the concept of the seven emotional systems as survival mechanisms-X happened, I feel Y in response, and now I need to do Z. The difference lies in the connections between affect, ego function, and object relationships. Human emotions such as guilt, shame, and envy, are generated by the development of the ego in a complicated social context. Uniquely human affects and moods and their corresponding pathologies arise from the interactions of cortical regulatory effects on subcortical systems, and these are mediated by the ego, which becomes itself under the influence of the people around it.

Ego functioning often involves "taming" certain affects, especially through thought and language, but it also involves intensifying some affects, so that people can feel truly alive. A full human life can't be reduced to an all or nothing switch of feeling in response to external events.

We can illustrate the role of the ego in human experience by examining Panksepp's model for depression, which involves the malfunction of the PANIC, SEEKING, and/or PLAY systems. This model corresponds well with anaclitic depression, in which babies separated from their mothers for extended periods became despondent, emotionally withdrawn, and frequently died. Strikingly, Spitz, who studied the syndrome, noted that a way to prevent this deterioration was to find a suitable substitute caregiver, and to allow the babies to move around outside their cribs (see this post). This meshes well with the involvement of both the PANIC/separation distress and SEEKING systems.

Spitz attributed the need for the babies to move around not to an innate SEEKING system, but to a need for discharge of aggression. The absence of aggression is where Panksepp's model for depression diverges from psychoanalytic models, in which aggression is central. Freud's, Mourning and Melancholia, reflects the idea that sadness is not the same as depression, which results when a loss, usually of an ambivalently loved object, precipitates rage, which is then directed towards the self.

There are other types of depression, as well. In an ego depression, the actual self falls short of the wished-for self, as in the loss of a job, or the limitations that come with aging. Depression results when there is an aggressive attack on the self for these losses, "I have failed." In a superego depression, the actual self falls short of the wished for self in moral or ethical values, which results in an aggressive attack on the self: "I'm bad, I should be punished."

Panksepp also considered the evolutionary advantage of depression as a shut down mechanism in PANIC situations. But a psychoanalytic perspective includes not only the concept of depressive pathology, which is a source of immense suffering and need for treatment, but also depressive capacity.

Depressive capacity includes the ability to tame or appropriately redirect aggression, and to tolerate the inevitable disappointments and losses of life. It involves the willingness to accept responsibility for our moral failings by not hiding behind depression-inducing guilt, or other defenses such as blame or projection. And it requires the ability to relinquish ones unattainable dreams, to accept the lack of fulfillment of ones impossible wishes, and to bear the limitations in ones self.

That was pretty heavy. Now this. I mentioned the problem with Panksepp's power point for a reason. He didn't get to show the video of himself tickling rats. So here it is:



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