New Delhi: Researchers at Columbia University in New York have reported new evidence that cognitive abnormalities observed in neuropsychiatric disorders such as schizophrenia may be due to altered activity in the thalamus during adolescence. This is a time window of increased risk for schizophrenia.
The study, titled "Adolescent thalamic inhibition leads to long-lasting impairments in schizophrenia", was recently published in the journal Nature Neuroscience. It holds promise for a more targeted therapeutic for schizophrenia and other brain disorders where cognitive dysfunction is associated with altered prefrontal cortex function.
In a statement released by Columbia University Irving Medical Center, Christoph Kellendonk, senior author on the paper, said cognitive deficits are central to schizophrenia, but the underlying mechanisms still remain unclear. He added that the study puts emphasis on the thalamus and its importance during adolescence in regulating prefrontal cortex circuit maturation.
Kellendonk said the researchers hope that their findings will inspire future studies to disentangle the influences of thalamic nuclei on the prefrontal cortex and cognitive control, paving the way for new treatment options.
What Brain Abnormalities Are Seen Early?
Schizophrenia is a disabling brain disorder characterised by delusional thinking and hallucinations, and is typically diagnosed in young adults. The average age duration for the onset of schizophrenia in men is the late teens to the early 20s. Meanwhile, for women, the average age duration for the onset of the disease is the late 20s to early 30s.
According to the study, the abnormal developmental trajectory of the brain appears to be established during development of the brain, which happens long before clinical symptoms of the disease appear in early adult life.
The prefrontal cortex is an area of the brain that performs exclusive functions such as planning, working memory, and impulsive control. The region has long been implicated in the pathophysiology of schizophrenia. The thalamus is a structure in the middle of the brain that regulates prefrontal cortex function in the adult, but whose role during adolescent development has been difficult to describe so far.
In order to test how cortical development may go wrong in the disease, Laura Benoit, the first author on the paper, manipulated the activity of thalamic neurons in the brains of mice during adolescence, and examined how it affects prefrontal cortex function later in life.
How Can One Cognitive Impairment Be Prevented?
The study found that thalamic inhibition during adolescence led to adult deficits in attentional set shifting, which is a form of cognitive flexibility impaired in individuals with schizophrenia. The researchers discovered that excitation of the thalamus during adulthood reversed the cognitive deficit in mice with developmentally altered cortical function.
Sarah Canetta, who co-led the study with Dr Kellendonk and Alexander Harris, said the fact that excitation of the thalamus during adulthood reversed the cognitive deficit in mice with developmentally altered cortical function shows that even in a developmentally altered brain, boosting thalamic function can still rescue cognitive impairments.
Canetta further said that the findings in the mouse suggest a neurodevelopmental framework in which the thalamus plays an important role in shaping the maturation of the prefrontal cortex. She explained that the thalamus has translational relevance, particularly for schizophrenia, and proposes a treatment strategy for enhancing cognition in humans.