Table 1.
Summary of the methods and results from the studies included in the review
| Reference | Imaging methods | Subjects | Main findings |
| Diagnosis of PD and motor symptoms correlates | |||
| Sang et al., 2015 [24] | Graph-analysis | 26 early PD patients vs 30 HC | Decreased global efficiency in PD compared to HC. Increased nodal centrality in bilateral pallidum, inferior parietal lobule, and medial superior frontal gyrus, and decreased nodal centrality in caudate nucleus, supplementary motor areas, precentral gyrus, and middle frontal gyrus in PD compared to HC |
| Berman et al., 2016 [25] | Graph-analysis | 19 PD patients vs 16 HC | Increased local efficiency in CEN and SN. Levodopa significantly decreased local efficiency in PD in all networks except within the putamen and caudate |
| Fang et al., 2017 [27] | Graph-analysis | 26 early PD vs 19 HC | Decreased nodal degree, global efficiency, local efficiency and characteristic path length within the SMN and VN in PD compared to HC. Higher nodal degree, global efficiency and local efficiency, and lower characteristic path length within DMN and cerebellum in PD compared to HC. Lower cluster coefficient in thalamus and caudate nucleus in PD compared to HC |
| Suo et al., 2017 [28] | Graph-analysis | 153 PD vs 81 HC | Decreased clustering coefficient, global efficiency, and local efficiency, and increased characteristic path length as well as decreased nodal centralities in the SMN, DMN, and temporal-occipital regions in PD compared to HC |
| de Schipper et al., 2018 [30] | Graph-analysis | 107 PD vs 58 HC | Increased eigenvector centrality within frontoparietal regions in PD compared to HC. Increased connectivity in the SMN and VN in PD compared to HC. |
| Hou et al., 2018 31] | Graph-analysis | 20 early akynetic PD vs 20 HC | Lower nodal centralities in the occipital lobe and areas of the limbic system and higher nodal centralities in frontal and temporal regions in PD compared to HC |
| Tuovinen et al., 2018 [51] | Graph-analysis | 16 early PD vs 16 HC | At baseline, increased connectivity between cerebellum and SMN as well as decreased connectivity between motor regions and cingulate cortex in PD compared to HC. At 1.5 years follow-up, increased cerebellum connectivity within itself and to the caudate nucleus, thalamus and amygdala in PD compared to HC |
| Wu et al., 2009 [42] | Seed-based analysis (M1, bilateral cerebellum, SMA, cingulate motor area, globus pallidus, putamen, thalamus, parietal cortex, and DLPFC) | 22 PD vs 22 HC | Decreased functional connectivity in the SMA, left DLPFC and left putamen as well as increased functional connectivity in the left cerebellum, left M1, and left parietal cortex in PD compared to HC. Levodopa relatively normalized functional connectivity in PD |
| Wu et al., 2011 [43] | Seed-based analysis (pre-SMA and M1) | 18 PD vs 18 HC | Increased connectivity between pre-SMA and M1 as well as decreased connectivity between pre-SMA and putamen, right insula, right premotor cortex, and left inferior parietal lobule in PD patients compared to HC |
| Baudrexel et al., 2011 [46] | Seed-based analysis (STN) | 31 early PD vs 44 HC | Increased connectivity between STN and cortical motor areas in PD compared to HC |
| Hacker et al., 2012 [50] | Seed-based analysis (anterior and posterior putamen, caudate) | 13 advanced PD vs 19 HC | Decreased striatal connectivity with thalamus, midbrain, pons and cerebellum in PD compared to HC. Decreased functional connectivity in sensori-motor and visual areas as well the supramarginal gyrus in PD compared to HC |
| Agosta et al., 2014 [45] | Seed-based analysis (caudate and putamen nuclei, globus pallidus, and thalamus) | 69 PD (25 early PD) vs 27 HC | Decreased connectivity within striatal and thalamic regions as well as increased connectivity between striatum and temporal cortex, and between thalamus and several sensorimotor, parietal, temporal, and occipital regions in PD patients compared to early PD and HC |
| Manza et al., 2016 [49] | Seed-based analysis (putamen, caudate and their subregions) | 62 PD (23 drug-naïve) | Higher motor impairment at baseline and over 1 year was correlated with decreased coupling between anterior putamen and midbrain. Higher decline in cognitive function was associated with increased coupling between the dorsal caudate and the rostral anterior cingulate cortex |
| Jech et al., 2013 [53] Mueller et al., 2018 [54] | Eigenvector centrality | 24 PD patients | Increased functional connectivity between cerebellum and thalamus, putamen, globus pallidus, and brainstem in PD after levodopa intake compared to OFF state |
| Esposito et al., 2013 [44] | ICA-based and fALFF analyses (SMN) | 20 early PD vs18 HC | Decreased connectivity within the SMA in PD compared to HC. Levodopa increases SMN connectivity |
| Rolinski et al., 2015 [38] | ICA-based analysis (BGN) | 32 early PD vs 19 HC vs 31 AD | Decreased connectivity within the BGN in PD compared to AD and HC with the greatest change seen in the posterior putamen |
| Tessitore et al., 2012 [61] | ICA-based analysis (DMN, FPN, SN) | 29 PD (16 with vs 13 without FOG) vs 15 HC | Decreased functional connectivity in the right occipito-temporal gyrus within FPN and VS in PD with FOG compared to those without |
| Fling et al., 2014 [62] | Seed-based analysis (SMA, STN, mesencephalic and cerebellar locomotor regions) | 15 PD (8 with vs 7 without FOG) vs 14 HC | Increased functional connectivity between the SMA and mesencephalic as well as cerebellar motor regions in PD with FOG compared to those without and HC |
| Canu et al., 2015 [63] | ICA-based analysis (SMN, DM, VN, SN, and right FPN) | 53 PD (28 with vs 25 without FOG) vs 35 HC | Decreased functional connectivity in the M1 and SMA within the SMN as well as in frontoparietal regions within the DMN, and occipital cortex within the VS in PD with FOG compared to HC |
| Chen et al., 2015 [57] | ALFF analysis | 31 PD (12 TD vs 19 PIGD) vs 22 HC | Increased connectivity in the right cerebellar posterior lobe in TD compared to HC as well as decreased connectivity in the putamen and cerebellar posterior in PIGD compared to HC. Increased connectivity in the bilateral putamen and the cerebellar posterior lobe, as well as decreased connectivity in the bilateral temporal gyrus and the left superior parietal lobule in TD compared to PIGD |
| Karunanayaka et al., 2016 [58] | ICA-based analysis (DMN); ALFF analysis | 17 akynetic PD vs 15 TD vs 24 HC | Decreased connectivity in the left inferior parietal cortex and the left posterior cingulate cortex within the DMN in akynetic PD compared to HC and TD |
| Ma et al., 2017 [29] | Graph-analysis | 31 PD (12 TD vs 19 PIGD) vs 22 HC | Decreased connectivity in the basal ganglia, cerebellum, superior temporal gyrus, pre- and postcentral gyri, inferior frontal gyrus, middle temporal gyrus, lingual gyrus, insula, and parahippocampal gyrus in PD compared to HC. PIGD had more disrupted hubs in the cerebellum than the TD. |
| Premotor phase and non-motor symptoms correlates | |||
| Rolinski et al., 2016 [40] | ICA-based analysis (BGN) | 26 iRBD vs 48 PD vs 23 HC | BGN connectivity of differentiated iRBD and PD from HC. No difference between iRBD and PD |
| Olde Dubbelink et al., 2014 [98] | Seed-based analysis (92 ROI covering the entire brain) | 55 PD vs 15 HC | Progressive connectivity deterioration in precentral gyrus, postcentral gyrus, superior, middle, and inferior occipital gyrus, calcarine cortex, cuneus, and superior temporal gyrus over 3 years in PD patients |
| Tessitore et al., 2012 [97] | ICA-based analysis (DMN) | 16 PD vs 16 HC | Decreased connectivity in the right medial temporal lobe and bilateral inferior parietal cortex within the DMN in PD compared to HC |
| Amboni et al., 2015 [99] | ICA-based analysis (DMN, FPN, VN) | 42 PD (21 with and 21 without MCI) vs 20 HC | Decreased connectivity in bilateral prefrontal cortex within the FPN in PD with MCI compared to HC |
| Baggio et al., 2015 [104] | ICA-based connectivity (DMN, DAN, FPN) | 65 PD (34 with and 31 without MCI) vs 38 HC | Decreased connectivity between DAN and right frontoinsular regions in PD with MCI compared to HC. Increased connectivity between DMN and medial and lateral occipito-parietal regions in PD with MCI compared to HC. Decreased DAN-DAN, DMN-DMN and DAN-FPN connectivity, as well as loss of normal DAN-DMN anticorrelation in PD with MCI compared to HC |
| Chen et al., 2015 [103] | Seed-based analysis (bilateral PCC) | 30 PD (11 with and 19 without dementia) vs 21 HC | Decreased posterior cingulate cortex connectivity with the right medial temporal lobe in PD compared to HC. Decreased posterior cingulate cortex connectivity with right parahippocampal region in PD with dementia compared to those without |
| Putcha et al., 2015 [21] | ICA-based analysis (DMN, CEN, SN) | 24 PD patients vs 20 HC | Decreased SN–CEN coupling and increased DMN–CEN coupling in PD compared to HC |
| Díez-Cirarda et al., 2018 [100] | ICA-based analysis (subcortical, AN, SMN, VN, cognitive-control, DMN and cerebellar network); graph-analysis | 35 PD (23 with and 12 without MCI) vs 26 HC | Decreased dynamic connectivity in PD with MCI compared to HC. Decreased inter-network connectivity between the SMN-central control, SMN-VN, SMN-AN, central-control-VN and subcortical-DMN in PD with MCI compared to HC |
| Zhan et al., 2018 [101] | Seed-based analysis (bilateral posterior cingulate cortex) | 27 PD (9 with and 9 without MCI vs 9 with dementia) vs 9 HC | Increased posterior cingulate cortex connectivity in PD with MCI patients and decreased posterior cingulate cortex connectivity in PD with dementia compared to HC. Increased connectivity between prefrontal cortices and posterior cerebellum in PD with dementia compared to HC |
| Lopes et al., 2017 [26] | Graph-analysis | 119 PD patients (31 cognitively unimpaired vs 31 with slight mental slowing vs 43 with mild to moderate deficits mainly in executive functions vs 14 patients with severe deficits in all cognitive domains | Functional organization decreased as cognitive impairment worsened. Between-group differences in functional connectivity mainly within the ventral prefrontal, parietal, temporal and occipital cortices as well as the basal ganglia |
| Skidmore et al., 2013 [90] | ALFF analysis | 15 PD | Apathy severity is correlated with connectivity in the left supplementary motor cortex, the right orbitofrontal cortex, and the right middle frontal cortex. Depression severity is correlated with connectivity in the right subgenual cingulate |
| Baggio et al., 2015 [89] | Seed-based analysis (limbic, executive, rostral motor, and caudal motor regions) | 62 PD (25 with vs 37 without apathy) vs 31 HC | Decreased connectivity in limbic striatal and frontal regions in PD patients with apathy compared to those without and HC |
| Tessitore et al., 2016 [92] | ICA-based analysis (DMN, FPN, SN, SMN, VS, AN) | 40 PD (20 with vs 20 without distressing fatigue) vs 20 HC | Decreased connectivity in the SMA within the SMN as well as increased connectivity in the prefrontal and posterior cingulate cortices within the DMN in PD patients with fatigue compared to those without |
| Su et al., 2015 [80] | ReHo analysis (left rectal gyrus, orbitofrontal cortex, superior temporal pole, posterior cingulate cortex, right insula, amygdala) | 54 PD (38 with vs 16 without hyposmia) vs 22 HC | Decreased connectivity in olfactory regions (i.e., amygdala, olfactory gyrus, orbital frontal cortex, parahippocampal gyrus and insula) as well as increased connectivity in the left anterior/posterior cingulate cortex in PD with hyposmia compared to those without |
| Yoneyama et al., 2018 [81] | ICA-based (CEN, DMN, SN, VN) and seed-based analysis (amygdala) | 30 PD (15 with and 15 without hyposmia) vs 15 HC | Decreased connectivity between amygdala and olfactory cortices in PD with hyposmia compared to HC; increased connectivity within the CEN, SN and VN in PD patients with hyposmia compared to HC |
| Wen et al., 2013 [84] | ALFF analysis | 33 PD (17 with vs 16 without depression) vs 21 HC | Decreased connectivity in the DLPFC, ventromedial prefrontal and the rostral anterior cingulated cortices in PD with depression compared to those without |
| Sheng et al., 2014 [87] | ReHo analysis (left middle frontal gyrus, right inferior frontal gyrus, left amygdala and bilateral lingual gyrus) | 41 PD (20 with vs 21 without depression) vs 25 HC | Increased connectivity in the left middle frontal gyrus and right inferior frontal gyrus as well as decreased connectivity in the left amygdala and bilateral lingual gyrus in PD with depression compared to those without |
| Lou et al., 2015 [83] | Eigenvector centrality | 34 PD (17 with vs 17 without depression) vs 17 HC | Decreased connectivity in the left DLPFC and right superior temporal gyrus as well as increased connectivity in the right posterior cingulate cortex, in PD with depression compared to those without |
| Hu et al., 2015 [88] | Seed-based analysis (amygdala) | 60 PD (20 with vs 40 without depression) vs 43 HC | Increased connectivity between left amygdala and bilateral mediodorsal thalamus as well as increased connectivity between right amygdala and left superior temporal gyrus and left calcarine gyrus in PD with depression compared to those without |
| Levodopa-induced dyskinesias | |||
| Cerasa et al., 2015 106] | Seed-based analysis (right inferior frontal cortex) | 24 PD (12 with vs 12 without LID) | Decreased connectivity of the right inferior frontal cortex with the left motor cortex as well as increased connectivity with the right putamen in PD with LID compared to those without |
| Herz et al., 2016 [107] | Seed-based analysis (bilateral putamen, M1, SMA and preSMA, right inferior frontal cortex) | 24 PD (12 with vs 12 without LID) | Dopaminergic modulation of connectivity between the putamen and primary sensorimotor cortex predicted LID development with a specificity of 100% and a sensitivity of 91% |
PD, Parkinson’s disease; AD, Alzheimer’s disease; HC, healthy controls; DMN, default-mode network; FPN, frontoparietal network; SN, salience network; CEN, central executive network; DAN, dorsal attention network; SMN, sensorimotor network; VN, visual network; AN: auditory network; BGN, basal ganglia network; ICA, independent component analysis; ALFF, amplitude of the low frequency fluctuations; ReHo, regional homogeneity; ROI, region of interest; STN, subthalamic nucleus; SMA, supplementary motor area; M1, primary motor cortex; DLPFC, dorsolateral prefrontal cortex; TD, tremor-dominant; PIGD, postural instability and gait difficulty; FOG, freezing of gait; MCI, mild cognitive impairment; LID, levodopa-induced dyskinesias; iRBD, idiopathic REM behavioral disorders.