Remembering Steven F. Maier

Steven F. Maier, Distinguished Professor, died unexpectedly on July 20 at age 83. Steve was one of the most distinguished and influential faculty members in the history of the University of Colorado Boulder’s Department of Psychology and Neuroscience. Steve’s death is a profound loss to our department and university, as well as to the numerous students and postdoctoral fellows he mentored throughout his career.

“He loved his work, and he was, in my view, the most significant scientist working at the border between neuroscience and behavioral psychology in the world,” noted his long-time colleague Martin Seligman, Professor of Psychology at the University of Pennsylvania. 

These words speak to the magnitude of what has been lost: an intellectual giant with boundless curiosity and encyclopedic knowledge, who lived for tackling new fields and applying his analytic and experimental talents to them to create new understanding. What is lost is his willingness to share his knowledge and to contribute tirelessly to the advancement of science through service on national committees, journal editorships, and professional associations. Most importantly, what is lost are the scientific discoveries he would have made and the knowledge he would have shared with future generations of students and scientists.

When someone of Steve’s intellect and accomplishments passes, it is important to reflect on what made such an extraordinary scientific career possible. Like the operatic singers he admired, Steve’s achievements were not the product of talent alone, but of decades of disciplined study, practice, and devotion to his craft. Steve loved identifying an important problem, mastering the relevant literature, and applying his analytic/experimental skills to advance understanding of the problem at hand. We describe below a few of Steve’s major accomplishments to illustrate the impact of his approach.

The Penn Years

Steve was born and raised in New York City.He was the only child of German Jewish immigrants, Leo and Gertrude Maier. He graduated with a biology degree at New York University in 1963 and joined the psychology graduate program at the University of Pennsylvania the following year. At that time, Penn’s Psychology department was viewed as the best in the country. Its illustrious faculty attracted exceptionally bright and ambitious students. As a field, Psychology was beginning to shed the shackles of behaviorism and embrace what came to be called the cognitive revolution. Yet, an amazing cadre of graduate students (including Robert Rescorla, Martin Seligman, Bruce Overmier, and Vincent LoLordo), presided over by Richard L. Solomon, remained deeply engaged with important questions in animal learning. This was a tough, combative bunch. 

During this period, Steve formed a lasting partnership with Marty Seligman that would shape the course of both their careers. Previously, what started out as a routine test of two-process avoidance learning theory, Overmier and Seligman (1967) reported a surprising result–animals exposed to an inescapable aversive event prior to avoidance training subsequently failed to learn the avoidance response–they failed to act even when they could escape.

Although others in the lab regarded the finding as an experimental complication or annoyance, Steve and Marty joined forces to explain it. In their seminal experiment, they introduced what became known as the triadic design: subjects were assigned to one of three conditions in which they experienced an escapable, inescapable, or no aversive event. Only subjects that lacked control over the aversive event subsequently failed to learn the avoidance response. Thus, it was not exposure to the aversive event per se, but whether the animal could control it, that proved to be the determining factor. 

To explain this outcome, Maier and Seligman (1967) offered what became one of the most influential and controversial theories in the history of psychology–Learned Helplessness. Briefly, after experiencing inescapable aversive events, especially those that are unpredictable as well, subjects learned that their actions have no effect on what happened to them. Consequently, when placed in a situation in which escape was possible, they failed to act–they had learned to be helpless. 

Central to the phenomenon was the belief that nothing one does matters. But what were the objective conditions that give rise to this belief? How could it be reversed, and how could it be prevented? Maier and Seligman assumed that subjects are sensitive to what they called objective controllability. Formally, an animal or a person is objectively helpless with respect to an outcome when the probability of that outcome, given a response, is equal to the probability of the outcome in the absence of that response:

P (O | R ) = P (O | NR )

When this relationship holds across all available responses, then objective helplessness exists. What began as laboratory curiosity would ultimately permeate much of psychology, shaping how researchers thought about motivation, stress, psychopathology, and eventually optimism and positive psychology.

The 70s

If the significance of a scientific idea is measured by how vehemently it is attacked, then the theory of learned helplessness was an enormously influential. While Seligman explored the clinical and broader implications of the theory, Steve spent many years in the trenches defending and refining it. He never backed down from the critics, but it was not a fun time. By the late 1970’s, Steve believed that the behavioral analysis of learned helpless had largely run its course. At that point, Steve had something of a conversion experience: “It’s the brain, dummy.” Further progress would require the understanding of its neurobiological underpinnings, which led Steve to retrain in the rapidly developing field of neuroscience. Thus began a remarkable intellectual transition that set the stage for the remainder or his career. 

Uncovering the Neural Basis of Helplessness

There are many dimensions to this story, but a major part of it centered on uncovering the neural basis for the differences in behavioral outcomes between uncontrollable and controllable aversive events. Over the next four decades, Steve and his colleagues developed a neurobiological account of controllability that, as his nomination for the American Psychological Association’s 2009 Award for Distinguished Scientific Contributions described it, ranks among “the most elegant series of causal studies in the history of behavioral neuroscience.” It is important to tell this story because it illustrates Steve’s scientific flexibility–his willingness to revise his ideas in the face of new findings.

Ultimately, it is a story of two neural circuits. 

One system revolves around the dorsal raphe nucleus, a midbrain structure whose activation releases serotonin (5-HT) onto a variety of target regions throughout the brain. In a remarkable series of papers Steve and his colleagues demonstrated that: 

1. Uncontrollable, but not physically identical controllable, stressors intensely activate raphe 5-HT cells
2. This robust activation of 5-HT results in a period of sensitization during which subsequent inputs to the raphe evoke exaggerated 5-HT release in its projection regions, thereby mediating the behavioral sequelae of uncontrollable stress
3. Inhibiting raphe 5-HT prevents helplessness behaviors
4. In the absence of stress, pharmacological activation of raphe 5-HT recapitulates helplessness behaviors

So, the important question became, why doesn’t the identical aversive event produce these outcomes when it is controllable? As mentioned above, learning about control requires the integration of two conditional probabilities–the probability of an outcome given a response and the probability of that outcome in the absence of the response. Although the serotonergic dorsal raphe is a key structure in mediating helplessness behaviors, it seemed unlikely that this relatively small nucleus had the intrinsic capacity to compute/detect whether a response controlled the outcome. Around this time, researchers studying the neurobiology of instrumental conditioning that was motivated by rewarding outcomes, such as food or drug, demonstrated that the medial prefrontal cortex was critical for extracting these types of conditional relationships.

Steve recognized that the medial prefrontal cortex also might be critical to understanding learned helplessness. This thinking resulted in a complete reconceptualization of the entire problem.

Reconceptualization

Learned helplessness theory originally assumed that when events are uncontrollable, the animal learns that outcomes are independent of its behavior. That is, control fails to activate the serotonergic dorsal raphe and produce helplessness because it lacks the active ingredient of uncontrollability. Steve’s work with the prefrontal cortex led to a surprising reversal: animals do indeed process the controllability of the stressor; but what is detected and learned is the presence, not the absence, of control. The behavioral consequences of uncontrollable aversive events are not learned. They are the default response to prolonged aversive stimulation. These default responses can be inhibited by learning control through activation of specific circuits in the prefrontal cortex which provide top-down inhibition over the serotonergic dorsal raphe response, thereby preventing helplessness behaviors. 

This was perhaps Steve’s most important scientific contribution. By shifting to the study of the brain, he transformed learned helplessness from a psychology theory to a neurobiological account of how identifiable neural systems determine how stressful events impact us. It reflects Steve’s intellectual curiosity, willingness to reconceptualize a problem, and learn the methods needed to advance a problem.

A Broad View

Steve’s scientific impact was remarkably broad. His work on the neurobiology of learned helplessness evolved to provide a major link between psychological concepts like stress and perceived control and the brain and immune system. It is also fair to say that initially, with Mark Laudenslager at the University of Denver and later with Linda Watkins, Steve’s contributions were among the first to target biological mechanisms and reveal causal links underlying bidirectional communication between the immune system and the central nervous system. This remains a pillar in the field of Psychoneuroimmunology. 

Through both neural and blood-borne routes, peripheral immune mediators called proinflammatory cytokines signal the nervous system that immune activation has occurred. These signals initiate neural cascades that lead to the induction of proinflammatory cytokines in the brain. This process initiates adaptive changes in a constellation of behaviors, referred to as sickness behavior. Hallmarks of sickness behavior include reduced social interaction and locomotion, and increased rest and sleep. Collectively, these behaviors reduce the spread of infection and redirect energy to immune processes. 

The work of Steve and his colleagues played a major role in convincing the field that behavioral experiences also activate the immune system, and that this, in turn, can have major consequences for the brain and behavior. They showed that stressful events like brief, intermittent, uncontrollable, and inescapable tailshock can trigger many of the hallmarks of sickness behavior, and these outcomes can last for several days. Furthermore, they reported that a variety of stressful stimuli increase proinflammatory cytokines both in the periphery and in the central nervous system (brain and spinal cord). In some circumstances, the inflammatory response is inappropriately triggered by these stimuli, resulting in exaggerated pain and mood disorders. 

Steve’s work touched deeply on so many subfields that it is impossible to do justice to it here. However, the breadth and depth of Steve’s intellectual powers are on full display in his paper based on his Norman Cousins lecture. It is a tour de force that begins by introducing the pro-inflammatory immune system, traces the history of early work linking it to behavior, and provides insight into its evolution. He then surveys the modern literature connecting this system to psychology and behavior and outlines the future. 

Steve’s integration of psychological processes, neural systems, immune function, and behavior places him among the dominant scientific figures of his generation.

Linda Watkins

In the summer of 1981, when Steve returned from his sabbatical with Jack Barkus, a young postdoctoral student, Linda Watkins from the Medical College of Virginia arrived to work with him. This was a hectic summer highlighted by a flurry of experiments investigating the impact of stress on pain– and by Linda wrecking Steve’s car. 

A few years later, Linda returned to work with Steve, supported by an NSF fellowship for Women in Science. One cannot overstate the importance of her return. Steve often acknowledged Linda's critical contribution to his scientific career. Their professional relationship was truly symbiotic. More importantly, however, was the personal relationship that developed between them. Steve and Linda fell in love and married in 2002. As the saying goes, Steve and Linda were joined at the hip. To our amusement, going out to dinner with them was always accompanied by the moment when, without a word or cue, they would swap their dinner plates. Linda brought Steve not only three decades of tremendous scientific success but also a lifetime of personal joy. 

According to the ancient Greeks, the true form of immortality is kleos– what is said about you or the legacy you left behind. We hope that we have done justice to his life and legacy. He will live on in our minds and hearts. 

Rest in peace, Steve.

Jerry W. Rudy, Michael V. Baratta , and Monika Fleshner