Table 1.
Magnetic resonance imaging in neurological diseases.
| Reference | Design, methods, participants | Key findings |
|---|---|---|
| A. Parkinson’s disease | ||
| Maidan, 2016 [123] | Cross-sectional, imagery, fMRI, PD vs. controls | Controls, but not PD participants, had increased activation during virtual navigation relative to virtual walking |
| Maidan, 2017 [124] | RCT, imagery, fMRI, PD. Treadmill training + Virtual imagery (TT+VI) vs. Treadmill training (TT) alone | TT+VI relative to TT had: a) Improved attention and gait speed b) Decreased activation in anterior and inferior frontal gyrus c) Decreased activation in left anterior lobe of cerebellum and mid temporal gyrus |
| Peterson, 2014 [160] | Cross-sectional, imagery, fMRI, PD-FOG+ vs. PD-FOG− | During imagined gait, PD-FOG+ had less activation in right globus pallidus and cerebellar regions than PD-FOG− |
| Peterson, 2014 [161] | Cross-sectional, imagery, fMRI, PD vs. controls | During imagery, PD participants had less activation in globus pallidus and more activity in SMA than controls. Activation of SMA, putamen, globus pallidus and brain stem correlated with gait speed in PD, but not in controls |
| Snijders, 2011 [194] | Cross-sectional, imagery, fMRI, PD-FOG+ vs. PD-FOG− | PD FOG+ participants had increased activation during imagery, and more brain volume atrophy in brainstem than PD-FOG− participants |
| Li, 2018 [111] | Cross-sectional, resting-state fMRI, PD-FOG+ vs. PD-FOG− | Reduced interhemispheric functional connectivity was observed in the inferior parietal lobule of PD FOG+ participants compared to PD FOG− and healthy controls |
| Zhou, 2018 [248] | Cross-sectional, resting-state fMRI, PD-FOG+ vs. PD-FOG− | PD FOG+ participants had reduced regional functional connectivity in SMA and left superior PFC relative to PD FOG− and controls |
| Gilat, 2018 [56] | Cross-sectional, resting-state fMRI, PD-FOG+ vs. PD-FOG− | PD-FOG+ participants had increased functional connectivity between right amygdala and putamen compared to PD-FOG− |
| Mi, 2017 [135] | Cross-sectional, resting-state fMRI, PD-FOG+ vs. PD-FOG− | PD FOG+ participants had increased spontaneous neural activity in anterior cingulate, intraparietal lobule, and decreased activity in superior frontal gyrus, bilateral cerebellum, and thalamus |
| Ma, 2017 [118] | Cross-sectional, resting-state fMRI, PD-TD vs. PD-PIGD, controls | PD-PIGD participants had disrupted functional connectivity in cerebellum relative to PD-TD |
| Shen, 2017 [181] | Cross-sectional, resting-state fMRI, PD vs. controls | Increased functional connectivity between substantia nigra and sensory-motor cortex was observed in PD patients on medication |
| Gallea, 2017 [55] | Cross-sectional, resting-state fMRI, PD vs. controls, with or without impaired postural control and/or sleep disorder | PD patients with sleep disorders displayed decreased functional connectivity between peduncolopontine nucleus and anterior cingulate |
| Wang, 2016 [236] | Cross-sectional, resting-state fMRI and DWI, PD-FOG+ vs. PD-FOG−, controls | PD-PIGD participants had reduced functional connectivity between left putamen and substantia nigra and increased connectivity between substantia nigra and occipital lobe |
| Wang, 2016 [234] | Cross-sectional, resting-state fMRI, PD-TD vs. PD-PIGD, controls | PD FOG + participants had abnormal functional connectivity in pedunculopontine nucleus and visual temporal areas |
| Vervoort, 2016 [230] | Cross-sectional, resting-state fMRI, PD-TD vs. PD-PIGD, PD undetermined, controls | PD-PIGD participants had reduced functional connectivity between caudate and putamen compared to PD TD |
| Lenka, 2016 [109] | Cross-sectional, resting-state fMRI, PD-FOG+ vs. PD-FOG− | PD FOG+ participants had reduced interhemispheric functional connectivity between left parietal opercular cortex and primary somatosensory and auditory regions |
| Vervoort, 2016 [231] | Cross-sectional, resting-state fMRI, PD-FOG+ vs. PD-FOG−, controls | PD-PIGD participants had reduced functional connectivity between the caudate and superior temporal lobe and increased connectivity between the dorsal putamen and precuneus, which correlated with worse dual-task gait performance |
| Jiang, 2016 [82] | Cross-sectional, resting-state fMRI, PD-TD vs. PD-PIGD, controls | PD-PIGD participants had reduced synchronicity of activation in frontal, parietal, occipital, temporal, limbic lobes, basal ganglia and thalamus regions |
| Chen, 2015 [32] | Cross-sectional, resting-state fMRI, PD-TD vs. PD-PIGD, controls | PD-PIGD participants had lower spontaneous neural activity in the putamen and cerebellar posterior lobe, and higher spontaneous neural activation in inferior and superior temporal gyrus, superior frontal gyrus, and parietal gyrus |
| Canu, 2015 [25] | Cross-sectional, resting-state fMRI and DWI, PD-FOG+ vs. PD-FOG− | PD-FOG+ participants had decreased functional connectivity in primary motor and supplementary motor regions of the sensorimotor network, frontoparietal regions of the default mode network, and occipital cortex regions of the visual network - as well as reduced white matter integrity in the pendunculopontine tracts, corpus callosum, corticospinal tract, cingulum, superior longitudinal fasciculus |
| Hou, 2015 [72] | Cross-sectional, resting-state fMRI, PD vs. controls | PD-PIGD participants had increased spontaneous neural activity in right postcentral gyrus, and decreased spontaneous neural activity in putamen, pre and supplementary motor area, frontal lobes, temporal lobes, and insula |
| Fling, 2014[51] | Cross-sectional, resting-state fMRI and DWI, PD vs. controls | PD-FOG+ participants had greater functional connectivity between the supplementary motor and cerebellar regions compared to both PD-FOG− and controls - and was correlated with increased (worse) clinical, self-reported and objective ratings of FOG |
| Tessitore, 2012 [212] | Cross-sectional, resting-state fMRI, PD-FOG+ vs. PD-FOG−, controls | PD-FOG+ participants had reduced connectivity in middle frontal gyrus, angular gyrus and right occipito-temporal gyrus |
| Wen, 2018 [239] | Cross-sectional, DWI, PD-TD+ vs. PD-PIGD, controls | White matter integrity in genu of corpus callosum was more strongly associated with motor severity in PD-FOG+ than PD-TD |
| Hall, 2018 [63] | Cross-sectional, DWI, PD-FOG+ vs. PD-FOG− | PD-FOG+ participants had reduced structural modularity and integration in caudate, thalamus, hippocampus, and superior frontal and parietal cortex regions |
| Pietracupa, 2018 [162] | Cross-sectional, DWI, PD-FOG+ vs. PD-FOG− | PD-FOG+ participants had reduced cortical thickness in cerebellar, superior frontal, paracentral, posterior cingulate, precuneus, pericalcarine and dorsolateral prefrontal cortex regions — as well as reduced white matter integrity in superior longitudinal fasciculus, uncinate fasciculus, cingulate, and inferior longitudinal fasciculus |
| Lenfeld, 2016 [108] | Longitudinal, DWI, PD-FOG+ vs. PD-FOG−, PD-undetermined | PD-PIGD participants had reduced white matter integrity in the prefrontal cortex, external capsule, the and lateral horn of the anterior ventricle relative to PD-TD – the integrity of these regions was also lower at baseline among those that developed PIGD symptoms during follow-up |
| Nagae, 2016 [147] | Cross-sectional, DWI, PD-TD vs. PD-PIGD, controls | PD patients had reduced had reduced white matter integrity in the substantia nigra |
| Youn, 2015 [246] | Cross-sectional, DWI, PD-TD vs. PD-PIGD, controls | PD-FOG+ participants had reduced structural connectivity in regions connected to pedunculopontine regions — including basal ganglia, thalamus and cerebellum |
| Chan, 2014 [29] | Case-control, DWI, PD vs. PIGD, controls | Structural connectivity in the body of the corpus callosum body differentiated PD-PIGD from PD |
| Marumoto, 2012 [128] | Cross-sectional, DWI, INPH vs. PD, controls | INPH participants had reduced white matter integrity in anterior thalamic radiation and forceps minor compared to PD participant. The addition of DWI assisted in the differential diagnosis of INPH from PD beyond what could be deduced from ventricular size alone |
| Kanno, 2011 [85] | Cross-sectional, DWI, INPH vs. AD, PD | Reduced white matter integrity is related to motor and cognitive dysfunction in INPH |
| Skorpil, 2012 [191] | Cross-sectional, DWI, PD vs. controls | PD participants had reduced white matter integrity in substantia nigra relative to controls |
| Karagulle Kendi, 2008 [86] | Cross-sectional, DWI, PD vs. controls | PD participant had reduced structural connectivity in the supplementary motor area, pre-supplementary motor area, and cingulum |
| Surova, 2016 [198] | Cross-sectional, DWI, PD vs. controls | PD participants had white matter integrity changes in the putamen, the thalamus, and the superior longitudinal fasciculus — yet, these changes do not aid in the diagnostic work-up of PD |
| Vervoort, 2016 [232] | Cross-sectional, DWI, PD-TD vs. PD-PIGD, controls | PD-PIGD participants had reduced white matter integrity in superior longitudinal fasciculus and corpus callosum compared to controls — as well as increased grey matter atrophy in the rostro dorsal head of the caudate |
| Vercruysse, 2015 [224] | Cross-sectional, DWI, PD vs. controls | PD participants had reduced white matter integrity in striato-frontal tracts including putamen, caudate, pallidum, subthalamic nucleus, cerebellar peduncle, subthalamic nucleus and pedunculopontine nucleus |
| Gu, 2014 [60] | Cross-sectional, DWI, PD-PIGD+ vs. PD-PIGD−, controls | PD-PIGD is associated with reduced white matter integrity was greater in superior longitudinal fasciculus relative to PD-PIGD |
| Lenfeldt, 2013[107] | Longitudinal, DWI, PD-PIGD, PD-TD | White matter integrity in thalamus was reduced in PD-TD than PD-PIGD |
| Al-Bachari, 2017 [3] | Cross-Sectional, WMH, PD-TD vs., PD-PIGD, controls | PD-PIGD participant had more white matter lesions than PD-TD participants |
| Acharya, 2007 [1] | Cross-Sectional, WMH, old-PD young-PD vs. old-controls, young-control | White matter changes was not different between the groups |
| Sartor, 2017 [176] | Cross-Sectional, WMH, PD | Gait performance was poorer, and reduction in bradykinesia following a single dose of levodopa was reduced, in PD participants with WMH than in those without WMH |
| Arena, 2016 [8] | Cross-Sectional, WMH, PD with acute L-DOPA challenge | PD participant with greater deep WMH burden was less responsive to levodopa on axial motor symptoms |
| Herman, 2013 [68] | Cross-Sectional, WMH, PD | The mean WMHs scores and the percent of subjects with lesions in specific brain regions were similar in the two subtypes |
| Moccia, 2016 [141] | Longitudinal, WMH, PD | Developing PIGD symptoms during follow-up was associated with higher WMH burden |
| Kim, 2015 [95] | Longitudinal, SVD, IPD vs. VP | Cerebral microbleeds were more common in vascular parkinsonism than in idiopathic PD. In IPD, cerebral microbleeds were also associated with white matter hyperintensities and concurrent lacunar infarctions |
| Schneider, 2016 [180] | Longitudinal, SVD, PD vs. PIGD | PD-PIGD had less SWI hypointensity in the putamen and globus pallidus PD patients |
| Rosenberg-Katz, 2016 [171] | Cross-Sectional, brain volume, PD-TD vs. PD-PIGD | PD-PIGD had more atrophy in amygdala and globus pallidus relative to PD-TD. In both PD-PIGD and PD-TD, hippocampal volume was positively associated with dual task gait performance, and putamen volume was negatively associated with FOG score |
| Rubino, 2014 [172] | Cross-Sectional, brain volume, PD-FOG+ vs. PD-FOG− | PD-FOG+ participants had more gray matter atrophy in left posterior parietal gyrus compared with PD-FOG− |
| Tessitore, 2012 [211] | Cross-Sectional, brain volume, PD-FOG+ vs. PD-FOG−, controls | PD-FOG+ had less gray matter volume in cuneus, precuneus, lingual gyrus, and posterior cingulate cortex compared to PD-FOG− and controls |
| B. Stroke | ||
| Carter, 2012 [27] | Cross-Sectional, resting-state fMRI, subacute stroke vs. controls | The extent of corticospinal damage was associated with functional connectivity between the left and right central sulcus |
| Peters, 2018[159] | Cross-Sectional, DWI, post-stroke | Structural connectivity between primary and supplementary motor regions and the cerebral peduncle, thalamus, and red nucleus in the same hemisphere as stroke lesion was associated with upper and lower extremity motor functions post-stroke |
| Jang, 2014 [79] | Cross-Sectional, DWI, chronic stroke | White matter integrity was associated with motor functions in chronic stroke |
| Dubey, 2016 [44] | Cross-Sectional, DWI, chronic stroke, controls | Reduced white matter integrity of corpus callosum was observed in chronic stroke relative to controls and was associated with gait speed |
| Jang, 2013 [78] | Cross-Sectional, DWI, stroke with complete injury of CST | White matter integrity (fiber volume) in unaffected (but not in affected) hemisphere was positively associated with the ability to walk |
| Jayaram, 2012 [81] | Cross-Sectional, DWI and TMS, chronic stroke | Greater relative connectivity between motor cortex and lower limbs in affected and unaffected hemisphere was associated with poorer gait speed |
| Yeo, 2011 [243] | Cross-Sectional, DWI, chronic stroke | White matter integrity in pedunculopontine nucleus was greater in stroke patients with the ability to walk |
| Ahn, 2006 [2] | Cross-Sectional, DWI, ambulatory chronic stroke | Some stroke patients retained the ability to walk despite complete lateral corticospinal tract injury in the affected hemisphere |
| Loos, 2017 [115] | Cross-Sectional, SVD, lacunar vs. non-lacunar stroke | Total cerebral small vessel disease burden was associated with gait impairment in non-lacunar (but not lacunar) stroke patients |
| Callisaya, 2014 [24] | Cross-Sectional, WMH, subcortical infarcts vs. controls | The risk of multiple falls was increased in older adults with three or more subcortical infarcts and highest quartile of white matter hyperintensity volume |
| Choi, 2012 [33] | Cross-Sectional, WMH and microbleeds, subcortical infarcts vs. microbleeds | Subcortical infarcts and microbleeds amplified the negative association of WML volume with gait. Subcortical infarcts, but not microbleeds amplified the negative association of WML volume with postural stability |
| C. Alzheimer’s disease and related dementias | ||
| Olazaran, 2013 [152] | Cross-Sectional, brain volume, DWI, probable AD vs. possible AD, AD-CVD+ | Gait dysfunction was related to brain atrophy in motor cortex, cingulate, insula, caudate (total sample), and cerebellar (total sample and probable AD) regions |
| Verwer, 2017 [233] | Cross-Sectional, SVD, AD vs. MCI, vascular brain injury | High small vessel disease burden, particularly white matter hyperintensities, co-occurred with impairments in physical performance (gait speed, short physical performance battery) |
| Nadkarni, 2009 [146] | Cross-Sectional, subcortical hyperintensities, mild AD vs. controls | Subcortical hyperintensity burden — particularly in frontal and basal ganglia – was associated with stride length and velocity in both mild AD and controls |
| D. Multiple sclerosis | ||
| Sbardella, 2015 [177] | Cross-Sectional, DWI, RRMS vs. controls | Gray matter atrophy and white matter integrity in RRMS was associated with upper-limb motion and cognition, but not 25-foot timed walk |
| Li, 2013 [113] | Cross-Sectional, DWI, RRMS vs. controls | RRMS participants had reduced communicability in frontal and hippocampal/parahippocampal regions. Communicability in superior frontal and superior temporal regions was associated with 25-foot timed walk. Increased communicability was observed in thalamus, putamen, corpus callosum and cingulum |
| Anderson, 2011 [7] | Cross-Sectional, DWI and gray and white matter, RRMS vs. PPMS, controls | White matter integrity in cerebellar peduncle was reduced in PPMS relative to RRMS and controls. In PPMS white matter integrity in cerebellar peduncle was also associated with upper limb function and gait speed |
| Kern, 2011 [90] | Longitudinal, DWI, RRMS vs. controls | White matter integrity associated with fine hand motor control but not 25-foot time walk |
| Freund, 2010 [53] | Longitudinal, DWI, MS vs. controls | White matter integrity of the cortico-spinal tract at baseline was associated with better clinical outcomes |
| Wetter, 2016 [240] | Cross-Sectional, White matter lesions, MS (RRMS,SPMS and PPMS) | White matter lesion volume explained additional variance in six-minute-walk performance after adjusting for age, white matter volume and gray matter volume |
| Sanfilipo, 2005 [175] | Cross-Sectional, DWI, MS vs. controls | MS participants had significantly lower gray matter and parenchymal volume, and a trend towards lower white matter volume, relative to controls. Gray matter atrophy was associated with clinical status, lesion load and central brain atrophy. White matter volume was associated with central brain volume |
| Goncalves, 2018 [57] | Cross-Sectional, corpus callosum index and volume, MS vs. controls | Corpus callosum index was associated with white matter and lesion volume, whole brain volume, some (not all) cognitive measures and functional status, but not with clinical status or 25-foot timed walk |
| Cocozza, 2017 [34] | Cross-Sectional, brain volume, PPMS vs. controls | MS participants had reduced cerebellar volume relative to control. Cerebellar lobules VI, Crus I and VIIIa was associated with cognitive measures. Anterior cerebellum and Lobule I-IV atrophy was associated with the 25-foot timed walk |
| Dupuy, 2016 [45] | Longitudinal, brain volume, RRMS with dimethyl fumurate therapy | RRMS patients on dimethyl fumurate therapy had a reduced rate of whole brain and putamen atrophy |
| Khalid, 2017 [91] | Longitudinal, brain volume, RRMS and PPMS with natalizumab therapy | Natalizumab therapy was not associated with any changes in annual gray matter volume, parenchymal volume, lesion load, clinical status or 25-foot time walk |
| Motl, 2016 [143] | Cross-Sectional, brain volume, MS vs. controls | MS participants had reduced subcortical gray matter lesion load and slower 25-foot timed walk. 25-foot timed walk was associated with subcortical gray matter in both MS and controls. Thalamic volume partially accounted for the difference in 25-foot timed walk between MS and controls |
| Ruggieri, 2015 [173] | Cross-Sectional, brain volume, PPMS vs. controls | PPMS was associated with reduced brain, gray and white matter volume relative to controls. Thalamic atrophy was associated with cortical lesions, particularly in frontal lobes |
| Onu, 2015 [154] | Cross-Sectional, brain volume, RRMS vs. controls | RRMS participants had reduced gray matter volume, particularly in thalamic, putamen, caudate, globus pallidus and nucleus accumbens - and volume in these regions (as well as sensory motor and primary motor regions) was associated with 25-foot timed walk |
| Feys, 2017 [142] | Cross-Sectional, brain volume, MS | The 6-minute walk and 25-foot timed walk is associated with gray matter volume of the pallidum and caudate in MS |
| Maghzi, 2014 [119] | Longitudinal, brain and lesion volume, MS | Baseline volume of the whole, the gray matter and normal appearing white matter was associated with changes in a functional and the 25-foot timed walk in MS |
| Wen, 2015 [238] | Cross-section, gray matter volume, MS vs. controls | Age-adjusted differences between MS and control participants were observed in cortical gray matter, normal appearing white matter — and was associated with cognitive measures, but not clinical status or 25-foot timed walk |
| Tovar-Moll, 2015 [216] | Cross-Sectional, DWI, MS (both RRMS & PPMS) | White matter integrity in corticospinal tract was associated with disability status and 25-foot timed walking speed — but correlation with 25-foot timed walking speed disappeared when correcting for lesion volume |
| Tavazzi, 2018 [209] | RCT, fMRI, MS, neurorehabilitation | Increased functional connectivity in precentral and postcentral gyrus, more restricted functional activation, improved gait and improved balance was observed following 4 weeks of neurorehabilitation |
| Sandroff, 2018 [174] | RCT(secondary analysis), resting-state fMRI, MS | Increased functional connectivity in thalamus, superior frontal gyrus and medial frontal gyrus and improved processing speed was observed following 12-week treadmill walking intervention |
| Sbardella, 2015 [178] | Cross-Sectional, resting-state fMRI and DWI, RRMS vs. controls | Decreased functional connectivity in a number of resting-state functional networks (sensorimotor, visual, cerebellar, basal ganglia, and executive control) was observed in RRMS relative to controls. In RRMS white matter integrity of the corpus callosum was also associated with functional connectivity in cerebellar and auditory networks |
| Klineova, 2016 [100] | Cross-Sectional, DWI, MS with gait impairment | White matter integrity in corticospinal tracts and overall gray and white matter volume was associated with 25-foot timed walk |
| Fritz, 2017 [54] | Cross-Sectional, DWI, RRMS | White matter integrity in corticospinal tract was associated with quantitative gait measures in RRMS |
| Hubbard, 2016 [75] | Cross-Sectional, DWI, MS | Some (median diffusivity, radial diffusivity, axial diffusivity), but not all (fractional anisotropy) measure of structural connectivity was associated with quantitative gait measures |
| Deppe, 2016 [40] | Cross-Sectional, DWI, RRMS vs. controls | RRMS participants in general had reduced white matter integrity and white matter volume relative to controls. Early and mild RRMS had reduced white matter integrity, but not white matter volume relative to controls |
| Feys, 2017 [49] | RCT, DWI and gray and white matter, MS, (‘‘start-to-run’’) running program vs. wait list | Pallidum volume increased following start-to-run program |
fMRI: functional magnetic resonance imaging; PD: Parkinson’s disease; RCT: randomized controlled trial; PD-FOG+: PD with freezing of gait; PD-FOG−: PD without freezing of gait; PD-PGID: PD with postural instability and gait difficulty; PD-TD: PD with tremor dominant phenotype; DWI: diffusion-weighted imaging; CST: corticospinal tract; INPH: idiopathic normal pressure hydrocephalus; TMS: transcranial magnetic stimulation; AD: Alzheimer’s disease; MCI: mild cognitive impairment; WMH: white matter hyperintensities; SVD: small vessel disease; CVD: cardiovascular disease; MS: multiple sclerosis; RRMS: relapsing-remitting MS; PPMS: primary progressive MS; SPMS: secondary progressive MS.