Thalamic Connectivity System Across Psychiatric Disorders: Current Status and Clinical Implications

Abstract

The thalamic connectivity system, with the thalamus as the central node, enables transmission of the brain's neural computations via extensive connections to cortical, subcortical, and cerebellar regions. Emerging reports suggest deficits in this system across multiple psychiatric disorders, making it a unique network of high translational and transdiagnostic utility in mapping neural alterations that potentially contribute to symptoms and disturbances in psychiatric patients. However, despite considerable research effort, it is still debated how this system contributes to psychiatric disorders. This review characterizes current knowledge regarding thalamic connectivity system deficits in psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder, across multiple levels of the system. We identify the presence of common and distinct patterns of deficits in the thalamic connectivity system in major psychiatric disorders and assess their nature and characteristics. Specifically, this review assembles evidence for the hypotheses of 1) thalamic microstructure, particularly in the mediodorsal nucleus, as a state marker of psychosis; 2) thalamo-prefrontal connectivity as a trait marker of psychosis; and 3) thalamo-somatosensory/parietal connectivity as a possible marker of general psychiatric illness. Furthermore, possible mechanisms contributing to thalamocortical dysconnectivity are explored. We discuss current views on the contributions of cerebellar-thalamic connectivity to the thalamic connectivity system and propose future studies to examine its effects at multiple levels, from the molecular (e.g., glutamatergic) to the behavioral (e.g., cognition), to gain a deeper understanding of the mechanisms that underlie the disturbances observed in psychiatric disorders.

Keywords: Cerebellum; Psychiatry; Psychosis; Thalamic connectivity system; Thalamocortical; Thalamus.

Figure 1

Schematic diagram of the thalamic connectivity system at the neural and systemic levels. (Left) Schematic diagram showing the neural transmission of first-order (FO) and higher-order (HO) thalamic nuclei. (Right) Schematic diagram of pathways between the frontal and parietal cortices to the thalamus. AMY, amygdala; BG, basal ganglia; BS, brainstem; DCN, deep cerebellar nuclei; LD, lateral dorsal nucleus; LGN, lateral geniculate nucleus; LP, lateral posterior nucleus; LS, limbic system; MB, midbrain; MD, mediodorsal nucleus; MGN, medial geniculate nucleus; ML, medial lemniscus; PFC, prefrontal cortex; Retina IC, retina and intercollicular pathways; SMC, somatosensory cortex; VA, ventral anterior nucleus; VI, ventral intermediate nucleus; VL, ventral lateral nucleus; VP, ventral posterior nucleus; VPL, ventral posterolateral nucleus; VPM, ventral posteromedial nucleus.

Figure 2

A diagram of multiple levels of the system leading to thalamic connectivity system disruptions. The proteins and genes highly implicated in psychiatric disorders are often essential in glutamatergic transmission in the brain, particularly within the thalamic connectivity system, which comprises the thalamus and thalamic connectivity patterns. These effects are taken up to show disease-specific or general psychopathology characteristics within the system. Schizophrenia and bipolar disorder share reduced thalamo-prefrontal connectivity and increased thalamo-somatomotor/parietal connectivity. Major depressive disorder (MDD) is characterized by reduced thalamo-prefrontal connectivity and increased thalamo-temporal and thalamo-somatomotor/parietal connectivity patterns, and autism is characterized by increased thalamo-temporal and thalamo-somatomotor/parietal connectivity patterns. Shaded blue, red, pink, green, and gray areas indicate the prefrontal cortex, somatomotor/parietal cortex, temporal cortex, thalamus, and cerebellum, respectively. GABA, gamma-aminobutyric acid; NAA, N-acetylaspartate.