The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions
(such as planning, cognitive control, working memory, and decision-making) because of
its significant interconnectivity with the prefrontal cortex (PFC). Yet, whilst the roles of the
PFC have been extensively studied, how the MD contributes to these cognitive functions
remains relatively unclear. Recently, causal evidence in monkeys has demonstrated
that in everyday tasks involving rapid updating (e.g., while learning something new,
making decisions, or planning the next move), the MD and frontal cortex are working
in close partnership. Furthermore, researchers studying the MD in rodents have been
able to probe the underlying mechanisms of this relationship to give greater insights
into how the frontal cortex and MD might interact during the performance of these
essential tasks. This review summarizes the circuitry and known neuromodulators of
the MD, and considers the most recent behavioral, cognitive, and neurophysiological
studies conducted in monkeys and rodents; in total, this evidence demonstrates that
MD makes a critical contribution to cognitive functions. We propose that communication
occurs between the MD and the frontal cortex in an ongoing, fluid manner during rapid
cognitive operations, via the means of efference copies of messages passed through
transthalamic routes; the conductance of these messages may be modulated by other
brain structures interconnected to the MD. This is similar to the way in which other
thalamic structures have been suggested to carry out forward modeling associated with
rapid motor responding and visual processing. Given this, and the marked thalamic
pathophysiology now identified in many neuropsychiatric disorders, we suggest that
changes in the different subdivisions of the MD and their interconnections with the cortex
could plausibly give rise to a number of the otherwise disparate symptoms (including
changes to olfaction and cognitive functioning) that are associated with many different
neuropsychiatric disorders. In particular, we will focus here on the cognitive symptoms
of schizophrenia and suggest testable hypotheses about how changes to MD-frontal
cortex interactions may affect cognitive processes in this disorder