Affiliations:
1 Department of Neurology, School of Medicine and St Anne’s University Hospital, Brno, Czech Republic
2 Applied Neuroscience Research Group, Central European Institute of Techology, CEITEC, Masaryk University, Brno, Czech Republic
The following updates were focused specifically on clinically relevant neuroimaging studies in patients with Parkinson’s disease and in migraine patients.
Christopher L, Duff-Canning S, Koshimori Y, Segura B, Boileau I, Chen R, Lang AE, Houle S, Rusjan P, Strafella AP.
Network and Parahippocampal Dopamine Dysfunction in Memory-Impaired Parkinson Disease.
ANN NEUROL 2015.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/25448687
The contribution of dopaminergic dysfunction to memory impairment in patients with Parkinson’s disease and mild cognitive impairment (PD-MCI) remains unclear.
Objectives were (1) to assess whether dopaminergic differences in the selected nodes of central executive network, salience network (SAL), striatum and/or the medial temporal lobe (MTL) contribute to memory deficits in amnestic PD-MCI; (2) to determine whether dopaminergic changes could explain variance in memory performance.
The authors used PET imaging to compare dopamine D2 receptor availability in the cortex ([11C]FLB 457, a D2 receptor ligand), and striatal dopamine neuron integrity (VMAT2, a radioligand binding to vesicular monoamine transporter) in: amnestic PD-MCI, nonamnestic MCI, PD without MCI, and healthy controls (HC).
Results: amnestic PD-MCI demonstrated significant D2 receptor reductions in the SAL and in the right MTL when compared to HC and PD patients with no cognitive impairment, and significant D2 reductions in the SAL when compared to nonamnestic PD-MCI patients. D2 receptor levels in the left insula (SAL) and right MTL were positively associated with memory performance even after controlling for executive composite z-score. A strong correlation was found between D2 receptor levels in the SAL and executive performance, when including all PD-MCI patients. Dopaminergic degeneration was demonstrated in both PD-MCI groups in the associative striatum.
Key points:
The current findings provide novel insight into the mechanism of memory impairment in PD.
· Dopaminergic changes within the major nodes of the SAL and the MTL contribute to memory impairment in PD.
· The SAL seems to be particularly vulnerable to PD pathology and has potential role in both memory and executive dysfunction in this patient cohort.
Links to addition information in the recent literature:
Criaud et al. Contribution of Insula in Parkinson’s Disease: A Quantitative Meta-Analysis Study. Hum Brain Mapp 2016.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/26800238
This study provides evidence of an important functional distribution of different
domains within the insular cortex in PD, particularly in relation to non-motor aspects, with an
influence of medication effect.
Herz DM, Haagensen BN, Nielsen SH, Madsen KH, Løkkegaard A, Siebner HR.
Resting-State Connectivity Predicts Levodopa-Induced Dyskinesias in Parkinson’s Disease.
Mov Disord 2016.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/26954295
Levodopa-induced dyskinesias (LIDs) are a common side effect of dopaminergic therapy in Parkinson’s disease (PD), but their neural correlates remain poorly understood.
Objective was to determine (1) whether LIDs are associated with abnormal dopaminergic modulation of resting-state cortico-striatal functional connectivity (rs-CSFC) and (2) whether a pharmaco-fMRI study can be used to predict development of LIDs and their severity in individual patients.
Levodopa-induced changes of rs-CSFC were assessed between the putamen and supplementary motor area (SMA), primary sensorimotor cortex (SM1), and right inferior frontal gyrus (rIFG). Patients with and without LIDs received a single dose of fast-acting soluble levodopa after a 12-hour withdrawal of dopaminergic medication and underwent MR scanning before any LIDs emerged. A linear support vector classifier was used to predict LIDs.
Results: In LIDs patients, levodopa-induced rs-CSFC between the SM1 and putamen decreased, whereas it increased in NO-LIDs patients. Dopaminergic modulation of rs-CSFC between these regions in the most affected hemisphere predicted whether patients would develop LIDs with an accuracy of 95% (specificity 100%, sensitivity of 91%) while structural changes of the regions did not predict LIDs. Modulation of rs-CSFC between the SMA and putamen predicted LIDs severity.
Key points:
This finding highlights the usefulness of pharmacological fMRI in a clinical setting.
· Altered dopaminergic modulation of rs-CSFC plays a key role in the pathophysiology of LIDs.
· Neural response to levodopa encodes important information about a patient’s clinical response.
Links to addition information in the recent literature:
Cerasa et al. A network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias. Brain 2015;138:414-427.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/25414038
The authors used combined resting state functional MRI and transcranial magnetic stimulation and demonstrated that pathophysiological mechanisms underlying LIDs may extend to the neural network centred on the inferior frontal cortex.
Elfmarková N, Gajdoš M, Mračková M, Mekyska J, Mikl M, Rektorová I.
Impact of Parkinson's disease and levodopa on resting state functional connectivity related to speech prosody control.
Parkinsonism Relat Disord 2016
http://www.ncbi.nlm.nih.gov/pubmed?term=Elfmarkova%5Bfirst+author%5D&cmd=detailssearch
Speech prosody is impaired in Parkinson's disease (PD), however, neural mechanisms underlying disturbed speech prosody control in PD are not fully understood and effects of dopaminergic medication remain inconclusive.
Objective was (1) to assess the impact of PD and levodopa on MR resting-state functional connectivity (rs-FC) underlying speech prosody control, (2) to determine association between levodopa-induced rs-FC and speech prosody changes in the PD group.
PD patients and age-matched healthy controls (HC) were studied using functional MRI and seed partial least squares correlation (PLSC) analysis. The right orofacial primary sensorimotor cortex (OF_SM1), the anterior cingulate cortex (ACC) and the right caudate nucleus (CN) were used as seed regions of interest (ROIs). PD patients were scanned and clinically assessed (acoustic analysis) in the OFF dopaminergic conditions (after a 12-hour withdrawal of dopaminergic medication) and in the ON state (after taking a single short-acting dose of L-dopa).
Results: There were no significant differences between the ON and OFF states in any of the studied speech parameters. The PLCS analysis revealed a significant impact of PD but not of medication on the rs-FC strength of spatial correlation maps seeded by specific ROIs. When only the PD group was assessed separately, the association was found between treatment-induced changes in acoustic parameters underlying speech prosody and changes in rs-FC within the cognitive basal ganglia-thalamo-prefrontal loop and the motor speech network.
Key points:
The findings showed an impact of PD but not of levodopa on rs-FC within the brain networks related to speech prosody control.
· Dopaminergic medication did not significantly improve speech prosody or seed-based rs-FC in PD.
· However, levodopa may improve prosody in some PD patients via increased connectivity within the associative striato-prefrontal and motor speech network.
Links to addition information in the recent literature:
Arnold et al. Pathomechanisms and compensatory efforts related to Parkinsonian speech. Neuroimage Clin 2013.
http://www.ncbi.nlm.nih.gov/pubmed/24319656
The authors compared speech-related brain activity and effective connectivity in early PD patients (ON and OFF levodopa) who did not yet develop voice or speech symptoms and matched controls.
Tedeschi G, Russo A, Conte F, Corbo D, Caiazzo G, Giordano A, Conforti R, Esposito F, Tessitore A.
Increased interictal visual network connectivity in patients with migraine with aura.
Cephalalgia 2016
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/25926619
An altered cortical excitability in the visual cortices and its correlation to cortical spreading depression seem to underlie the aura symptoms in migraine patients, however, the visual network (VN) integrity in patients with migraine with aura (MwA) has not been studied.
Objective was (1) to evaluate the resting-state functional connectivity (rs-FC) of the VN in MwA and migraine without aura (MnoA) patients during an interictal period, (2) to assess whether possible rs-FC disturbances were dependent on structural or microstructural brain differences.
The authors used functional MRI (3T) and independent component analysis (ICA) approach to evaluate the resting-state VN integrity in MwA patients, age- and sex-matched MnoA patients and healthy controls (HC). Structural sequences (voxel-based morphometry analysis) and diffusion tensor imaging (tract-based spatial statistics analysis, TBSS) were employed to assess whether between-groups differences in rs-FC could be explained by structural or microstructural changes.
Results: Patients with MwA compared to MnoA and HC showed increased rs-FC in the right lingual gyrus (rLG) within the VN (p<0.05, cluster-level corrected). No between-group differences in grey/white matter volumes or TSBB measures were detected using either the whole-brain or ROI-based analysis. Individual ROI averaged ICA scores in the rLG did not correlate with the disease severity in the whole group of patients with migraine and in patients with MwA and MnoA separately.
Key points:
· The rLG seems to be engaged in pathophysiological mechanisms of MwA.
· Visual aura phenomenon per se could justify VN rs-FC abnormality observed exclusively in patients with MwA.
· Based on a peculiar extrastriate cortex functional pattern MwA may be viewed as a relatively distinct entity from MnoA.