If serotonin deficiency isn’t the cause of depression, then why do SSRIs work?

Acetaminophen (a.k.a paracetamol) relieves some types of headache. But this does not mean that these headaches are caused by acetaminophen deficiency. The brain doesn’t even produce acetaminophen.

The point of this analogy is to make clear that a medicine can work even if it is not acting on the cause of the symptom. In many cases a medicine can work even when the cause of the symptom is completely unknown.

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Why is the brain so sensitive to early life experiences?

I was asked this question on Quora:

From an evolutionary standpoint, why would the early years of brain development be paramount in determining life-long neurological patterns, when those patterns can often be detrimental to long-term success in life?

Good question. We can restate it as follows:

Why would natural selection allow animals to be so sensitive to negative early experience?

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The neural circuitry of emotion – an interview with me!

I was interviewed by the excellent Allen Saakyan for his Simulation YouTube channel. Check it out if you want to know about my research… and also my take on the question of Life, the Universe, and Everything. 😛

There’s also a shorter excerpt where we speculate about schizophrenia and “hyperrealities”:

Our computational model of visual attention disruptions in schizophrenia

My latest modeling paper has been published in Computational Psychiatry.

Visual Attention Deficits in Schizophrenia Can Arise From Inhibitory Dysfunction in Thalamus or Cortex (Open Access!)

Here’s the abstract:

“Schizophrenia is associated with diverse cognitive deficits, including disorders of attention-related oculomotor behavior. At the structural level, schizophrenia is associated with abnormal inhibitory control in the circuit linking cortex and thalamus. We developed a spiking neural network model that demonstrates how dysfunctional inhibition can degrade attentive gaze control. Our model revealed that perturbations of two functionally distinct classes of cortical inhibitory neurons, or of the inhibitory thalamic reticular nucleus, disrupted processing vital for sustained attention to a stimulus, leading to distractibility. Because perturbation at each circuit node led to comparable but qualitatively distinct disruptions in attentive tracking or fixation, our findings support the search for new eye movement metrics that may index distinct underlying neural defects. Moreover, because the cortico-thalamic circuit is a common motif across sensory, association, and motor systems, the model and extensions can be broadly applied to study normal function and the neural bases of other cognitive deficits in schizophrenia.”

Here’s Figure 1, which shows the circuit we modeled.

Perhaps neurogenesis doesn’t happen in adult humans?

A new study suggests that new neurons are not born very often in human adults.

Birth of New Neurons in the Human Hippocampus Ends in Childhood

“The lab’s new research, based on careful analysis of 59 samples of human hippocampus from UCSF and collaborators around the world, suggests new neurons may not be born in the adult human brain at all. The findings present a challenge to a large body of research which has proposed that boosting the birth of new neurons could help to treat brain diseases such as Alzheimer’s disease and depression. But the authors said it also opens the door to exciting new questions about how the human brain learns and adapts without a supply of new neurons, as in seen in mice and other animals.”

My labmates are all monkey neuroanatomists, and for years they have been skeptical about the neurogenesis narrative, particularly in primates. Another famous dissenter is Pasko Rakic. Read about his complaints in this Guardian article from 2012:

Does your brain produce new cells?

 

Are mental disorders the same as brain disorders? Maybe not!

I am currently reading an excellent paper that will be published in Behavioral and Brain Sciences soon. It raises some very important issues with popular conceptions of mental illness.

Brain disorders? Not really… Why network structures block reductionism in psychopathology research

These two figures capture some of the key points:

Here is the abstract:

“In the past decades, reductionism has dominated both research directions and funding policies in clinical psychology and psychiatry. However, the intense search for the biological basis of mental disorders has not resulted in conclusive reductionist explanations of psychopathology. Recently, network models have been proposed as an alternative framework for the analysis of mental disorders, in which mental disorders arise from the causal interplay between symptoms. In this paper, we show that this conceptualization can help understand why reductionist approaches in psychiatry and clinical psychology are on the wrong track. First, symptom networks preclude the identification of a common cause of symptomatology with a neurobiological condition, because in symptom networks there is no such common cause. Second, symptom network relations depend on the content of mental states and as such feature intentionality. Third, the strength of network relations is highly likely to partially depend on cultural and historical contexts as well as external mechanisms in the environment. Taken together, these properties suggest that, if mental disorders are indeed networks of causally related symptoms, reductionist accounts cannot achieve the level of success associated with reductionist disease models in modern medicine. As an alternative strategy, we propose to interpret network structures in terms of D. C. Dennett’s (1987) notion of real patterns, and suggest that, instead of being reducible to a biological basis, mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority, and that a holistic research strategy is necessary for progress in the study of mental disorders.”

Behavioral and Brain Sciences is one of the premier journals for “big thinking” in cognitive science and neuroscience, so it’s great to see these ideas there.