When the BOLD signal changes, the ALFF value indirectly reflects the spontaneous activation of the brain, which can indicate brain abnormalities at rest [19,23,24]. By increasing the ALFF, neurons in the corresponding brain region are more likely to be activated spontaneously, and activating this functional region may compensate for certain cognitive function impairments. A decreased ALFF value indicates that the intensity of the spontaneous activity of neurons in corresponding brain regions decreased, meaning that a neural activity decrease in these brain regions may be related to the loss of corresponding cognitive function. Thus, the ALFF value can be used to probe the basic brain activity of diseases.
ReHo applies the KCC to assess the resemblance between the temporal patterns of a specific voxel to those of adjacent voxels in spatial proximity, illustrating the state of spontaneous brain activity regions with notable synchronization features, serving as a crucial measure to determine abnormal neuronal activity [20,25]. Changes in ReHo values indicate either heightened or diminished spontaneous neuronal activity in the specific brain region.
ALFF and ReHo values are frequently used for investigating brain functional activities through the lens of functional specialization, offering distinct benefits in identifying brain regions that exhibit sustained activity in the resting state and providing a deeper insight into the alterations in brain activity among patients with DoC from varying forms of trauma. In this study, activated brain regions with elevated ALFF values in the TBI group included the bilateral insula, Postcentral gyrus_L, right torque-like gyrus, Superior parietal gyrus_L, Inferior temporal gyrus_L, and brain stem. In contrast, ALFF decreased in the anterior cuneiform, right superior frontal, middle frontal, right occipital gyri, and right hippocampi. The insula and Postcentral gyrus primarily handle sensation, temperature, language, and place perception [26,27]. However, evidence suggests that the precuneus, one of the most active cortical regions in the default mode network [28], is inactivated in altered consciousness. The precuneus is believed to be a central component in functional networks involved in consciousness owing to its extensive connections to the cortices and subcortices. Many metabolic and structural cascades are associated with precuneus-related diseases as it is one of the brain’s most tightly connected central regions. For patients with DoC who recover consciousness, the precuneus is among the earliest brain areas to regain activity, and the more pronounced the decline in precuneus activity, the deeper the neurological disorder. Laureys et al. [29] reported that the posterior medial cortex and the thalamus had a different functional relationship during the VS, but it returned to a near-normal level once the patient regained consciousness. The anterior cuneus and posterior cingulate cortex also appear to be brain regions that distinguish patients in an MSC from those in a VS [34]. The medial frontal gyrus is an important part of the dorsolateral prefrontal lobe, and a component of this system participates in cognitive formation, emotional regulation, working memory, behavioral decision-making, attention regulation, abstract reasoning, behavioral inhibition, and pain inhibition [30,31]. In the frontal lobe, which is closely linked to cognitive and memory functions, decreased ALFF values may indicate that the brain is no longer functioning correctly [32].
Assessing clinical symptoms and cognitive dysfunction is also possible using ReHo values [33]. In this study, the ReHo values were higher in the TBI group than in the CVD group for the Precental gyrus_L and Postcentral gyrus, Middle temporal gyrus_R, Superior parietal gyrus_L, Superior frontal gyrus_R, right superior temporal gyrus, Superior temporal gyrus_R, and Inferior frontal gyrus, Orbital part_L, but they were lower for the Postcentral gyrus_R, right posterior superior frontal gyrus, Inferior frontal gyrus, Orbital part_L, and orbital and straight gyrus. The medial temporal gyrus performs language-related tasks, such as word understanding and semantic cognition, which receive input from the occipital lobe [34]. The brain’s language network has two key nodes: the middle temporal gyrus and the inferior frontal gyrus [36,36]. The Superior frontal gyrus contributes to motor control, working memory, resting state, cognitive control, and resting state information processing [34]. As an important part of the limbic system, the cingulate gyrus usually receives bottom-up emotional feedback information from the limbic system and then projects it to the higher-order cognitive control system (such as the area of the prefrontal cortex) through extensive connections for top-down cognitive control, mainly involved in the emotional motivation of pain perception and cognitive attention [37]. Finally, the medial frontal gyrus is an important part of the dorsolateral prefrontal lobe, involved in cognitive formation, emotional regulation, working memory, behavioral decision-making, attention regulation, abstract reasoning, behavioral inhibition, and pain inhibition. [30,31].
In this study, ALFF and ReHo values decreased in the TBI group compared to the CVD (control) group in various brain regions. As the brain’s higher attention center, the Superior frontal gyrus plays a key role in cognitive functions. A decrease in ALFF in these areas may indicate reduced brain function. Zhou et al [38] used ALFF at 0.01-0.08 Hz to detect thalamic and cortical damage in patients with traumatic brain injury and found that the thalamus and frontotemporal lobe had lower ALFF values. Depending on the etiology, shear or penetrating mechanical injuries in patients with traumatic brain injury are usually the result of acute, intense external forces that lead to skull fractures, intracranial hemorrhage, and more extensive injuries [39]. Vessel stenosis in patients with CVD is a slow process and is confined to specific vasculature-supplied brain regions, which to a certain extent still provides an opportunity for reorganization of the cerebral network. Three months after implantation of the SCS, one patient in the TBI group and three patients in the CVD group had improved consciousness according to the CRS-R score. Furthermore, the ALFF and ReHo values in the anterior cuneiform and frontal lobes of the TBI group were lower than those in the CVD group. In contrast, the ALFF and ReHo values were elevated in the precuneus and frontal brain regions of the CVD group compared to the TBI group, which could explain the improved levels of consciousness.
This study is subject to certain limitations. Primarily, the inclusion of only two DoC injury types and a relatively small sample size necessitates the conduct of large multicenter studies encompassing multiple injury types to enable a comprehensive evaluation of the impact of network connectivity on patient prognosis. In this study, DoC patients with cardiovascular disease were utilized as a control group. However, the inclusion of additional suitable control groups, such as normal participants, is essential to effectively observe differences in injury types and to determine treatment effects. Furthermore, this study is a retrospective study with information bias. To mitigate this, we have blinded the data collection and used objective criteria to obtain the information, thereby minimizing bias. Nevertheless, this study is the first to evaluate the performance of ALFF and ReHo in resting patients with cardiovascular disease using fMRI techniques.
This study identified ALFF and ReHo enhancement in the precuneus and frontal lobes of patients with DoC, which might be the anatomical basis for possible improvements in consciousness. Routine preoperative rs-fMRI should be considered to improve awakening therapy recovery rates.