Our findings described FC alterations in thalamic subregions between patients with BG stroke and HCs, and the correlations of FCs with motor and cognitive functions. It is suggested that motor and cognitive impairments at post-BG stroke not only directly arise from the brain region with cerebral infarctions, but also indirectly from abnormal FCs between thalamic subregions and distant brain areas. A previous study consistently showed that BG stroke leads to severe cognitive and sensorimotor deficits20. Our results illustrated the neurological mechanisms underlying motor and cognitive impairment in patients with BG stroke.
The thalamus comprises several distinct nuclei, including the medial dorsal (MD), pulvinar, ventral lateral, ventral anterior, and ventral posterior (VP) nuclei. Anatomically, overlapping regions exist within the SC_thalamus versus ventral posterior nuclei, the M1_thalamus versus ventral lateral nuclei, the PFC_thalamus versus MD nucleus, and the TC_thalamus versus pulvinar nucleus versus MD nucleus9,21. The MD and pulvinar nuclei are higher-order thalamic nuclei responsible for cognitive control22-24. The MD nucleus of the thalamus is especially important for higher-order valuation or motivation and cognitive function owing to its extensive connectivity25. The VP nucleus of the thalamus receives somatosensory inputs from the face and body26. Ascending projections within the VP nucleus provide the pathway running to the motor cortex27,28. Additionally, the VL nucleus exhibits activity changes in preceding voluntary movements.
Compared with those of HCs, alterations in the increased FC in patients with BG stroke was observed in the left precuneus gyrus (ROI in the left SC_thalamus) and the left angular gyrus (ROI in the right SC_thalamus). The angular gyrus is a component of the inferior parietal lobule that participates in semantic processing, default mode network, attention, spatial cognition and responses to salient stimuli 29. The precuneus is a region of the medial posterior parietal cortex that is similarly involved in reflective and self-related processing, awareness and conscious information processing30,31. It exhibits a greater activity at rest than the expose of external tasks32. An increased FC is reported within the right supramarginal gyrus, right angular gyrus and right precuneus increases in patients with post-stroke aphasia33. Our data consistently revealed an increased FC within the SC_thalamus, left angular gyrus and left precuneus gyrus in patients with BG stroke, which could be attributed to the enhanced illness perception correlated with an angular gyrus response in a sustained attention task and a stronger response of the precuneus gyrus at rest.
In addition, a decreased FC in patients with BG stroke was found within the right supramarginal gyrus versus the left middle cingulate gyrus, with the left PFC_thalamus as the ROI. The FC within the left PFC_thalamus versus right supramarginal gyrus was in a positive correlation with the MMSE scores. The cingulate gyrus is a component of the limbic system that mediates cognitive function. The supramarginal gyrus is an important branch of the control network that is engaged in processing emotion and cognition34. A previous study reported a decreased FC between the right supramarginal gyrus and the hippocampus in patients with ischemic stroke detected by rsfMRI35. We consistently disclosed a FC within the PFC_thalamus versus the right supramarginal gyrus, which was correlated with cognitive impairment in patients with BG stroke.
The decreased FC was also observed within the left cuneus and right postcentral gyrus with the ROI of the left TC_thalamus between patients with BG stroke and HCs. The cuneus is capable of combining somatosensory pathways with sensory stimuli and cognitive processes (e.g., attention, learning and memory)36. The postcentral gyrus is also involved in processing sensory information and every step to processing emotions (identifying emotional significance within stimuli, generating emotional states, and regulating emotions)37. Su et al.38 consistently detected a decreased FC between the bilateral lingual gyrus versus right cuneus, and the right cuneus versus right postcentral gyrus in patients with subcortical infarction using rsfMRI. The decrease in FC of patients with BG stroke could be explained by a strong association with cognition-related functions involving the cingulate and supramarginal gyrus, providing novel insights to the treatment of cognitive decline.
Furthermore, a decreased FC was detected in the right medial superior frontal gyrus with the ROI of the right M1_thalamus between patients with BG stroke and HCs, which was correlated with the FMA scores. The medial superior frontal gyrus is a part of the prefrontal cortex that controls the switch of the primary motor cortex39,40. A decreased FC in homologous brain regions of the bilateral cerebral hemispheric motor cortex is found to associate with motor function impairments in upper limbs after acute cerebral infarction41. A longitudinal study employing FC-based seeds revealed that an increased FC between the ipsilateral and contralateral primary motor cortex, and posterior central gyrus is ascribed to motor rehabilitation42. Therefore, we hypothesized that the decreased FC observed in patients with BG stroke was linked to the modulation of the primary motor cortex and M1_thalamus functions by the medial superior frontal gyrus.
Four limitations of the study are concerned. First, longer scanning time and stricter requirements of rsfMRI reduce the clinical feasibility. Second, it was a single-center study with a small sample size, and our findings need further validations. Third, we only recruited right-handedness participants, and whether our findings are suitable for left-handedness people remain unclear. Fourth, the correlation of the prognosis with FC alterations in thalamic subregions needs a long-term follow-up in patients with BG stroke.
Overall, alterations in FC exhibit between thalamic subregions and certain brain regions of patients with BG stroke, shedding light on the pathophysiological changes in motor thalamus and cognitive function at the subnuclear realm. This study holds the advent of new treatment of BG stroke.