Table 3.
Outcomes of studies with functional and metabolic brain analysis.
| Author, year | Brain area analyzed | Parameter analyzed | Results |
|---|---|---|---|
| fMRI | |||
| Borges et al., 2015 | V1 and V2 areas in both hemisphere | BOLD response within the LPZ and a matched area corresponding to healthy retina (control ROI) Stimulus: central filed (16°) dynamic checkerboard with high and low contrast monocularly presented | Reduction of activation in the LPZ compared to control ROI for stimulus in glaucomatous eye (only for medium and high contrast stimuli) in both V1 and V2. No differences in the fellow eye responses. |
| Duncan et al., 2007a | Visual areas (V1, V2, V3) | BOLD responses after stimuli are presented in the periphery. Different stimuli, all with contrast-reversing checkboard pattern: expanding rings, rotating wedges, meridian-mapping stimulus, 16° isopter, full-field contrast-reversing checkboard. Correlation with ON assessment | Reduced activity in V1. Pattern of deterioration of BOLD activity reflected pattern of deterioration of optic disc (evaluated with three techniques: OCT, HRT, GDx). |
| El-Rafei et al., 2013 | Visual areas (V1, V2, V3) | BOLD responses after stimuli are presented in the periphery. Different stimuli, all with contrast-reversing checkboard pattern: expanding rings, rotating wedges, meridian-mapping stimulus, 16° isopter, full-field contrast-reversing checkboard. Correlation with visual filed defect | The spatial pattern of activity observed in V1 agreed with the pattern of visual field loss. |
| Gerente et al., 2015 | Occipital pole and calcarine ROIs | BOLD responses to binocular stimuli (polar angle stimulus consisting of a rotating wedge). Association with structural and functional ocular findings. | Significant associations between binocular VF sensitivities and RNFL thickness with fMRI responses in the occipital pole and the calcarine ROIs. |
| Jiang et al., 2017 | Whole brain | BOLD responses to 8 Hz black and white checkboard contrast stimuli | Higher brain activation in POAG was primarily located in the R supramarginal gyrus, frontal gyrus, superior frontal gyrus, L inferior parietal lobule, L cuneus, L midcingulate area and frontal lobe. Only the L cuneus negatively correlated with RNFL. R inferior parietal lobule, middle frontal gyrus, middle occipital gyrus, and inferior temporal gyrus showed positive correlations with RNFL. |
| Lestak et al., 2014 | Visual cortex | BOLD responses to stimuli: black/white (BW) and yellow/blue (YB) checkerboard pattern | The extent of activation did not differ statistically between glaucomatous (both POAG and NTG) and controls. The difference in the magnitude of activation during the BW and YB stimulation is markedly higher in the POAG. No differences between BW and YB in NTG and controls. |
| Murphy et al., 2016 | Visual cortex and higher-order visual brain | BOLD responses to 8 Hz Flickering stimuli | Reduced visual cortex activity. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas. The primary VC was reduced before visual field loss. |
| Qing et al., 2010 | Visual cortex | BOLD responses to 8 Hz hemifield checkboard contrast stimuli | The BOLD fMRI signal change in the primary visual cortex corresponding to central visual input from the more severely affected eye was less than that of the fellow eye. |
| Song et al., 2012 | Primary and Secondary visual cortex | BOLD responses to 8 Hz full-screen black and white flip checkboard stimuli. | The extent and intensity of visual cortex activation was decreased. In PACG patients. |
| Zhang et al., 2016 | Different layers of the LGN, superior colliculus (SC), early visual cortices (V1, V2 and MT) | Responses to M stimulus (low spatial frequency at 30% luminance contrast, at 10 Hz) and P stimulus (high spatial frequency, isoluminant red/green square wave pattern, reversing contrast at 0.5 Hz) | Early glaucoma patients showed more reduction of response to transient achromatic stimuli than to sustained chromatic stimuli in the magnocellular layers of the LGN, as well as in the superficial layer of the SC. Magnocellular responses in the LGN were also significantly correlated with the degree of behavioral deficits to the glaucomatous eye. Early glaucoma patients showed no reduction of fMRI response in the early visual cortex. |
| Zhou et al., 2017b | Retinotopic areas (V1, V2, V3) | Cortical magnification factors and BOLD% changes as a function of eccentricity. 2 visual stimuli: a series of rotating wedges and a series of expanding or contracting rings. Correlation analysis between BOLD% changes and visual field scores, and between BOLD% changes and RNFL thicknesses | BOLD changes of POAG were reduced compared to normal. fMRI retinotopic mapping revealed enlarged representation of the parafovea in the visual cortex of POAG. |
| rs-fMRI | |||
| Cai et al., 2015 | Spontaneous brain functional connectivity within the whole brain | Voxel-wise degree centrality (DC) = direct connections for a given voxel in the voxel-wise connectome before and 3 months after surgery. Correlation of DC with clinical values | PACG pre-surgery: decreased DC in bilateral VC, increased DC in left ACC and caudate. PACG post-surgery: increased DC in bilateral VC and L precentral gyrus compared to pre-surgery. Negative correlation between DC in VC and IOP pre-surgery. |
| Chen et al., 2017 | Spontaneous regional brain activity in the visual cortex | Intrinsic functional spontaneous neuronal activity thought regional homogeneity (ReHo). Correlation with clinical measurements | Compared with controls, PACG showed higher ReHo value in the L fusiform gyrus (BA37), L cerebellum anterior lobe, R frontal-temporal space (BA48), and R insula (BA48), and lower ReHo value in the bilateral middle occipital gyrus (BA18), L claustrum, and R paracentral lobule lobe (BA4). Significant correlation with duration disease, RNFL, CDR. |
| Dai et al., 2013 | ROIs defined within Brodmann areas related to vision (BA17, BA18, BA 19, BA7) | Functional connectivity (FC) between the ROIs and other brain areas | Decreased FC in the POAG group between BA17 and R inferior temporal, L fusiform, L middle occipital, R superior occipital, L postcentral, R precentral gyri, and anterior lobe of the left cerebellum. Increased FC was found between BA17 and the L cerebellum, R middle cerebellar peduncle, R middle frontal gyrus, and extra-nuclear gyrus. Positive FC was disappeared between higher visual cortices (BA18/19) with the cerebellar vermis, R middle temporal, and R superior temporal gyri. Negative FC disappeared between BA18/19 and the R insular gyrus |
| Frezzotti et al., 2014 | Spontaneous brain functional connectivity within the whole brain | Functional connectivity (FC) across 8 defined resting state networks (RSNs): visual, auditory, sensorimotor, default mode, working memory (right and left), dorsal attention and executive networks. | Decreased FC in visual, working memory and dorsal attention networks and increased FC in visual and executive networks. |
| Frezzotti et al., 2016 | Spontaneous brain functional connectivity within the whole brain | Functional connectivity (FC) across 13 defined resting state networks (RSNs): visual (VN), auditory, sensorimotor, default mode (DMN, anterior and posterior), working memory (WMN, right and left), fronto-medial and orbitofrontal, executive control, salience, subcortical (ScN), temporal pole networks | POAG patients had lower FC in the VN and in the WMN, higher FC in the DMN and in the ScN. These abnormalities were already present in the subgroup of patients with stage 1. |
| Giorgio et al., 2018 | Spontaneous brain functional connectivity within the whole brain | Functional connectivity (FC) across 12 defined resting state networks (RSNs): default mode, frontal executive control (ECN, medial, and medio-lateral), right and left frontoparietal working memory, dorsal attention, auditory/language ventral attention (VAN), visual (VN, primary, and secondary), medial temporal (limbic) and cerebellar networks | FC was altered in NTG at short-range level [visual network (VN), ventral attention network] and in POAG at long-range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network. |
| Huang et al., 2015 | Spontaneous brain functional connectivity within the whole brain | Amplitude of low-frequency fluctuation (ALFF), an index to detect spontaneous neuronal activity | Compared with healthy, PACG patients had significantly lower ALFF areas in the left precentral gyrus, bilateral middle frontal gyrus, bilateral superior frontal gyrus, right precuneus, and right angular gyrus, and higher ALFF area in the right precentral gyrus. There were significant negative correlations between the mean ALFF signal value of the middle frontal gyrus and the contralateral mean RNFL thickness. |
| Li et al., 2014 | Spontaneous brain functional connectivity within the whole brain | ALFF. Correlation between ALFF and the disease stage | Compared with controls, POAG patients showed significantly decreased ALFF in the visual cortices, posterior regions of the default-mode network (DMN), and motor and sensory cortices. ALFFvalues were increased in the prefrontal cortex, L superior temporal gyrus (STG), R middle cingulate cortex (MCC), and Linferior parietal lobule (IPL). Severity disease stage correlated with ALFF of some areas (L cuneus, bilateral MTG and R prefrontal cortex). |
| Li et al., 2017 | Intrinsic functional connectivity (iFC) in the centers of the V1 | Seed-based iFC analysis before and 3 months after the surgery. Correlation between iFC and clinical variables (disease duration, IOP, RNFLT, CDR, VA) | Pre-PACG: compared to healthy, decreased iFC between L V1 and R V2 (covering the cuneus, calcarine and lingual gyrus) and increased iFC between L V1 and L temporal-parietal, L and R frontal opercula-insula-basal ganglia region, and R inferior parietal lobule. Post-PACG: increased iFC between the L V1 and bilateral V2, and between the L V1 and L or R postcentral gyrus; decreased iFC between the L V1 and the dorsal-attention and frontoparietal control networks. Correlation between iFC and VA |
| Song et al., 2014 | Spontaneous regional brain activity in the visual cortex | Intrinsic functional spontaneous neuronal activity thought regional homogeneity (ReHo). Correlation with clinical parameters | Compared to controls, POAG showed increased ReHo in the R dorsal anterior cingulated cortex, the bilateral medial frontal gyrus and the R cerebellar anterior lobe, and decreased ReHo in the bilateral calcarine, precuneus gryus, pre/postcentral gyrus, L inferior parietal lobule and L cerebellum posterior lobe. Changes in spontaneous activity are associated with clinical parameters. |
| Wang et al., 2016a | Functional communication of anatomically separated structures. | Network analysis at both global and local levels | No significant differences of the global network measures were found between the two groups. However, the local measures were radically reorganized in glaucoma patients. |
| Wang et al., 2016b | Functional connectivity | Alterations of functional connectivity (FC) and connections within and between the subnetworks of the visual network and the default mode network (DMN) in glaucoma | FC analysis showed that the FC in the occipital pole of the visual network was decreased in POAG patients while no alterations were found in the FC of the DMN in patients. |
| MRS | |||
| Boucard et al., 2007 | Occipital pole in both hemisphere | Concentrations of the0 metabolites N-acetylaspartate (NAA), Creatine (Cr) and Choline (Cho) | No significant differences for any metabolites concentration between glaucoma, age-related macular degeneration and healthy groups. |
| Zhang et al., 2013 | Geniculo-calcarine and the striate area of occipital lobe | Ratio of N-acetylaspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, glutamine and glutamate (Glx)/Cr | Significant decreases in NAA/Cr and Cho/Cr but no difference in Glx/Cr was found in glaucoma compared to healthy subjects in both the GCT and the striate area. |
BOLD, blood oxygenation level-dependent; LPZ, lesion projection zone; ROI, region of interest; VC, visual cortex; ACC, anterior cingulate cortex; L, left; R, right; ON, optic nerve.