Top

Published in:

01-06-2018 | Psychiatry and Preclinical Psychiatric Studies - Original Article

Antidepressant treatment effects on dopamine transporter availability in patients with major depression: a prospective ¹²³I-FP-CIT SPECT imaging genetic study

Authors: Sabine Hellwig, Lars Frings, Annette Masuch, Werner Vach, Katharina Domschke, Claus Normann, Philipp T. Meyer

Published in: Journal of Neural Transmission | Issue 6/2018

Abstract

We investigated if sleep deprivation (SD) and electroconvulsive therapy (ECT) affect striatal dopamine transporter (DAT) availability assessed by single-photon emission computed tomography (SPECT) and ¹²³I-FP-CIT, if dopamine transporter gene (SLC6A3; DAT) variation modifies aforementioned parameters, and if SD response or SD-induced DAT changes correlate with ECT response. Sixteen patients with major depression (MDD) referred for ECT and 12 matched controls were prospectively recruited for imaging and SLC6A3 VNTR genotyping. After withdrawal from any psychiatric medication, ¹²³I-FP-CIT-SPECT was acquired at baseline, after SD and after ECT series. Striatal DAT availability was assessed by volume-of-interest analysis of SPECT data. Eleven patients underwent combined treatment with SD and ECT (five ECT responders and six non-responders). Per-protocol analyses yielded no significant effect of SD or ECT on striatal DAT availability using repeated-measures ANOVA. However, intention-to-treat analysis indicated a significant decrease of striatal DAT availability due to SD (paired t test, p < 0.01). Stratification by SLC6A3 VNTR genotype suggested the 9R allele to drive this effect. In an exploratory analysis, SD-induced change in DAT availability of the left caudate nucleus predicted ECT response. This study revealed a treatment effect of SD on striatal DAT availability—possibly depending on SLC6A3 VNTR genotype. This and the observed association between SD-induced change of striatal DAT availability and response to ECT may help to identify treatment mechanisms and response predictors useful for precision medicine approaches in the treatment of MDD.

Amsterdam JD, Newberg AB, Soeller I, Shults J (2012) Greater striatal dopamine transporter density may be associated with major depressive episode. J Affect Disord 141(2–3):425–431. https://doi.org/10.1016/j.jad.2012.03.007 CrossRefPubMed

Argyelan M, Szabo Z, Kanyo B, Tanacs A, Kovacs Z, Janka Z, Pavics L (2005) Dopamine transporter availability in medication free and in bupropion treated depression: a 99mTc-TRODAT-1 SPECT study. J Affect Disord 89(1–3):115–123. https://doi.org/10.1016/j.jad.2005.08.016 CrossRefPubMed

Baldinger P, Lotan A, Frey R, Kasper S, Lerer B, Lanzenberger R (2014) Neurotransmitters and electroconvulsive therapy. J ECT 30(2):116–121. https://doi.org/10.1097/YCT.0000000000000138 CrossRefPubMed

Bartova L, Berger A, Pezawas L (2010) Is there a personalized medicine for mood disorders? Eur Arch Psychiatry Clin Neurosci 260(Suppl 2):S121–S126. https://doi.org/10.1007/s00406-010-0152-8 CrossRefPubMed

Benedetti F, Serretti A, Colombo C, Lilli R, Lorenzi C, Smeraldi E (2003) Dopamine receptor D2 and D3 gene variants are not associated with the antidepressant effect of total sleep deprivation in bipolar depression. Psychiatry Res 118(3):241–247CrossRefPubMed

Brunswick DJ, Amsterdam JD, Mozley PD, Newberg A (2003) Greater availability of brain dopamine transporters in major depression shown by [99m Tc]TRODAT-1 SPECT imaging. Am J Psychiatry 160(10):1836–1841. https://doi.org/10.1176/appi.ajp.160.10.1836 CrossRefPubMed

Bubl E, Kern E, Ebert D, Riedel A, Tebartz van Elst L, Bach M (2015) Retinal dysfunction of contrast processing in major depression also apparent in cortical activity. Eur Arch Psychiatry Clin Neurosci 265(4):343–350. https://doi.org/10.1007/s00406-014-0573-x CrossRefPubMed

Bui E, Delrieu J, Wagner T, Rieu J, Very E, Letamendia C, Payoux P, Schmitt L (2011) Iodine-123 fluoropropyl-carbomethoxy-3-beta-(4-iodophenyltropane) single-photon emission computed tomography findings before and after electroconvulsive therapy in major depressive disorder with Parkinsonism. J ECT 27(4):331–333. https://doi.org/10.1097/YCT.0b013e31821646b6 CrossRefPubMed

Camardese G, Di Giuda D, Di Nicola M, Cocciolillo F, Giordano A, Janiri L, Guglielmo R (2014) Imaging studies on dopamine transporter and depression: a review of literature and suggestions for future research. J Psychiatr Res 51:7–18. https://doi.org/10.1016/j.jpsychires.2013.12.006 CrossRefPubMed

Cheon KA, Ryu YH, Kim JW, Cho DY (2005) The homozygosity for 10-repeat allele at dopamine transporter gene and dopamine transporter density in Korean children with attention deficit hyperactivity disorder: relating to treatment response to methylphenidate. Eur Neuropsychopharmacol 15(1):95–101. https://doi.org/10.1016/j.euroneuro.2004.06.004 CrossRefPubMed

Clark CP, Frank LR, Brown GG (2001) Sleep deprivation, EEG, and functional MRI in depression: preliminary results. Neuropsychopharmacology 25(5 Suppl):S79–S84. https://doi.org/10.1016/S0893-133X(01)00324-4 CrossRefPubMed

Costa A, Riedel M, Muller U, Moller HJ, Ettinger U (2011) Relationship between SLC6A3 genotype and striatal dopamine transporter availability: a meta-analysis of human single photon emission computed tomography studies. Synapse 65(10):998–1005. https://doi.org/10.1002/syn.20927 CrossRefPubMed

Cuijpers P, Vogelzangs N, Twisk J, Kleiboer A, Li J, Penninx BW (2014) Comprehensive meta-analysis of excess mortality in depression in the general community versus patients with specific illnesses. Am J Psychiatry 171(4):453–462. https://doi.org/10.1176/appi.ajp.2013.13030325 CrossRefPubMed

Der-Avakian A, Markou A (2012) The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci 35(1):68–77. https://doi.org/10.1016/j.tins.2011.11.005 CrossRefPubMed

Di Giuda D, Camardese G, Bentivoglio AR, Cocciolillo F, Guidubaldi A, Pucci L, Bruno I, Janiri L, Giordano A, Fasano A (2012) Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a ¹²³I-FP-CIT SPECT study. Eur J Nucl Med Mol Imaging 39(12):1937–1948. https://doi.org/10.1007/s00259-012-2232-7 CrossRefPubMed

Dopierala E, Rybakowski J (2015) Sleep deprivation as a method of chronotherapy in the treatment of depression. Psychiatr Pol 49(3):423–433. https://doi.org/10.12740/PP/30455 CrossRefPubMed

Ebert D, Berger M (1998) Neurobiological similarities in antidepressant sleep deprivation and psychostimulant use: a psychostimulant theory of antidepressant sleep deprivation. Psychopharmacology 140(1):1–10CrossRefPubMed

Ebert D, Feistel H, Kaschka W, Barocka A, Pirner A (1994) Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation—preliminary results. Biol Psychiatry 35(11):880–885CrossRefPubMed

Ebert D, Albert R, Hammon G, Strasser B, May A, Merz A (1996) Eye-blink rates and depression. Is the antidepressant effect of sleep deprivation mediated by the dopamine system? Neuropsychopharmacology 15(4):332–339. https://doi.org/10.1016/0893-133X(95)00237-8 CrossRefPubMed

Fall PA, Ekberg S, Granerus AK, Granerus G (2000) ECT in Parkinson’s disease-dopamine transporter visualised by [¹²³I]-beta-CIT SPECT. J Neural Transm 107(8–9):997–1008. https://doi.org/10.1007/s007020070048 CrossRefPubMed

Felten A, Montag C, Markett S, Walter NT, Reuter M (2011) Genetically determined dopamine availability predicts disposition for depression. Brain Behav 1(2):109–118. https://doi.org/10.1002/brb3.20 CrossRefPubMedPubMedCentral

Fernandez-Corcuera P, Aguilar S, Vicens V, Mora J, Benitez A, Garcia-Burillo A, Pomarol-Clotet E, McKenna P (2011) ECT in a patient with Parkinson’s disease and schizophrenia, with dopamine transporter visualisation using ¹²³I-ioflupane SPET. J Neural Transm 118(4):647–650. https://doi.org/10.1007/s00702-011-0615-8 CrossRefPubMed

Fosse R, Read J (2013) Electroconvulsive treatment: hypotheses about mechanisms of action. Front Psychiatry 4:94. https://doi.org/10.3389/fpsyt.2013.00094 CrossRefPubMedPubMedCentral

Fuke S, Suo S, Takahashi N, Koike H, Sasagawa N, Ishiura S (2001) The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. Pharmacogenomics 1(2):152–156CrossRef

Grace AA (2016) Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nat Rev Neurosci 17(8):524–532. https://doi.org/10.1038/nrn.2016.57 CrossRefPubMedPubMedCentral

Guiraud V, Gallarda T, Calvet D, Turc G, Oppenheim C, Rouillon F, Mas JL (2016) Depression predictors within six months of ischemic stroke: the DEPRESS Study. Int J Stroke. https://doi.org/10.1177/1747493016632257 PubMedCrossRef

Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62CrossRefPubMedPubMedCentral

Hautzinger M, Keller F, Kühner C (2006) BDI-II. Beck Depressions Inventar Revision—Manual. Harcourt Test Services, Frankfurt

Heijnen WT, Birkenhager TK, Wierdsma AI, van den Broek WW (2010) Antidepressant pharmacotherapy failure and response to subsequent electroconvulsive therapy: a meta-analysis. J Clin Psychopharmacol 30(5):616–619. https://doi.org/10.1097/JCP.0b013e3181ee0f5f CrossRefPubMed

Heinz A, Goldman D, Jones DW, Palmour R, Hommer D, Gorey JG, Lee KS, Linnoila M, Weinberger DR (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22(2):133–139. https://doi.org/10.1016/S0893-133X(99)00099-8 CrossRefPubMed

Helmreich I, Wagner S, Konig J, Kohnen R, Szegedi A, Hiemke C, Tadic A (2015) Hamilton depression rating subscales to predict antidepressant treatment outcome in the early course of treatment. J Affect Disord 175:199–208. https://doi.org/10.1016/j.jad.2014.12.043 CrossRefPubMed

Hemmeter UM, Hemmeter-Spernal J, Krieg JC (2010) Sleep deprivation in depression. Expert Rev Neurother 10(7):1101–1115. https://doi.org/10.1586/ern.10.83 CrossRefPubMed

Holst SC, Bersagliere A, Bachmann V, Berger W, Achermann P, Landolt HP (2014) Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans. J Neurosci 34(2):566–573. https://doi.org/10.1523/JNEUROSCI.4128-13.2014 CrossRefPubMed

Hsieh PC, Lee IH, Yeh TL, Chen KC, Huang HC, Chen PS, Yang YK, Yao WJ, Lu RB, Chiu NT (2010) Distribution volume ratio of serotonin and dopamine transporters in euthymic patients with a history of major depression—a dual-isotope SPECT study. Psychiatry Res 184(3):157–161. https://doi.org/10.1016/j.pscychresns.2010.09.004 CrossRefPubMed

Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27(9):1533–1539. https://doi.org/10.1038/sj.jcbfm.9600493 CrossRefPubMed

Jacobsen LK, Staley JK, Zoghbi SS, Seibyl JP, Kosten TR, Innis RB, Gelernter J (2000) Prediction of dopamine transporter binding availability by genotype: a preliminary report. Am J Psychiatry 157(10):1700–1703. https://doi.org/10.1176/appi.ajp.157.10.1700 CrossRefPubMed

Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62(6):617–627. https://doi.org/10.1001/archpsyc.62.6.617 CrossRefPubMedPubMedCentral

Khalid N, Atkins M, Tredget J, Giles M, Champney-Smith K, Kirov G (2008) The effectiveness of electroconvulsive therapy in treatment-resistant depression: a naturalistic study. J ECT 24(2):141–145. https://doi.org/10.1097/YCT.0b013e318157ac58 CrossRefPubMed

Kirchheiner J, Nickchen K, Sasse J, Bauer M, Roots I, Brockmoller J (2007) A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment. Pharmacogenomics 7(1):48–55. https://doi.org/10.1038/sj.tpj.6500398 CrossRef

Laasonen-Balk T, Kuikka J, Viinamaki H, Husso-Saastamoinen M, Lehtonen J, Tiihonen J (1999) Striatal dopamine transporter density in major depression. Psychopharmacology 144(3):282–285CrossRefPubMed

Laasonen-Balk T, Viinamaki H, Kuikka JT, Husso-Saastamoinen M, Lehtonen J, Tiihonen J (2004) ¹²³I-beta-CIT binding and recovery from depression. A six-month follow-up study. Eur Arch Psychiatry Clin Neurosci 254(3):152–155. https://doi.org/10.1007/s00406-004-0458-5 CrossRefPubMed

Landau AM, Chakravarty MM, Clark CM, Zis AP, Doudet DJ (2011) Electroconvulsive therapy alters dopamine signaling in the striatum of non-human primates. Neuropsychopharmacology 36(2):511–518. https://doi.org/10.1038/npp.2010.182 CrossRefPubMed

Lehto SM, Tolmunen T, Kuikka J, Valkonen-Korhonen M, Joensuu M, Saarinen PI, Vanninen R, Ahola P, Tiihonen J, Lehtonen J (2008) Midbrain serotonin and striatum dopamine transporter binding in double depression: a one-year follow-up study. Neurosci Lett 441(3):291–295. https://doi.org/10.1016/j.neulet.2008.06.042 CrossRefPubMed

Lener MS, Iosifescu DV (2015) In pursuit of neuroimaging biomarkers to guide treatment selection in major depressive disorder: a review of the literature. Ann N Y Acad Sci 1344:50–65. https://doi.org/10.1111/nyas.12759 CrossRefPubMed

Martins RC, Andersen ML, Garbuio SA, Bittencourt LR, Guindalini C, Shih MC, Hoexter MQ, Bressan RA, Castiglioni ML, Tufik S (2010) Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery—an in vivo molecular imaging study in humans. Sleep 33(2):243–251CrossRefPubMedPubMedCentral

McIntyre R, Kennedy S, Bagby RM, Bakish D (2002) Assessing full remission. J Psychiatry Neurosci 27(4):235–239PubMedPubMedCentral

Mill J, Asherson P, Browes C, D’Souza U, Craig I (2002) Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: evidence from brain and lymphocytes using quantitative RT-PCR. Am J Med Genet 114(8):975–979. https://doi.org/10.1002/ajmg.b.10948 CrossRefPubMed

Moreira R (2011) The efficacy and tolerability of bupropion in the treatment of major depressive disorder. Clin Drug Investig 31(Suppl 1):5–17. https://doi.org/10.2165/1159616-S0-000000000-00000 CrossRefPubMed

Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B (2007) Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370(9590):851–858. https://doi.org/10.1016/S0140-6736(07)61415-9 CrossRefPubMed

Neumeister A, Willeit M, Praschak-Rieder N, Asenbaum S, Stastny J, Hilger E, Pirker W, Konstantinidis A, Kasper S (2001) Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls. Psychol Med 31(8):1467–1473CrossRefPubMed

Opmeer EM, Kortekaas R, Aleman A (2010) Depression and the role of genes involved in dopamine metabolism and signalling. Prog Neurobiol 92(2):112–133. https://doi.org/10.1016/j.pneurobio.2010.06.003 CrossRefPubMed

Pearson-Fuhrhop KM, Dunn EC, Mortero S, Devan WJ, Falcone GJ, Lee P, Holmes AJ, Hollinshead MO, Roffman JL, Smoller JW, Rosand J, Cramer SC (2014) Dopamine genetic risk score predicts depressive symptoms in healthy adults and adults with depression. PLoS One 9(5):e93772. https://doi.org/10.1371/journal.pone.0093772 CrossRefPubMedPubMedCentral

Price JL, Drevets WC (2012) Neural circuits underlying the pathophysiology of mood disorders. Trends Cogn Sci 16(1):61–71. https://doi.org/10.1016/j.tics.2011.12.011 CrossRefPubMed

Rominger A, Cumming P, Brendel M, Xiong G, Zach C, Karch S, Tatsch K, Bartenstein P, la Fougere C, Koch W, Pogarell O (2015) Altered serotonin and dopamine transporter availabilities in brain of depressed patients upon treatment with escitalopram: a [¹²³I]beta-CIT SPECT study. Eur Neuropsychopharmacol 25(6):873–881. https://doi.org/10.1016/j.euroneuro.2014.12.010 CrossRefPubMed

Roselli F, Pisciotta NM, Perneczky R, Pennelli M, Aniello MS, De Caro MF, Ferrannini E, Tartaglione B, Defazio G, Rubini G, Livrea P (2009) Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: a ¹²³I-FP-CIT SPECT study. Mov Disord 24(14):2097–2103. https://doi.org/10.1002/mds.22702 CrossRefPubMed

Saijo T, Takano A, Suhara T, Arakawa R, Okumura M, Ichimiya T, Ito H, Okubo Y (2010) Electroconvulsive therapy decreases dopamine D(2)receptor binding in the anterior cingulate in patients with depression: a controlled study using positron emission tomography with radioligand [(1)(1)C]FLB 457. J Clin Psychiatry 71(6):793–799. https://doi.org/10.4088/JCP.08m04746blu CrossRefPubMed

Sarchiapone M, Carli V, Camardese G, Cuomo C, Di Giuda D, Calcagni ML, Focacci C, De Risio S (2006) Dopamine transporter binding in depressed patients with anhedonia. Psychiatry Res 147(2–3):243–248. https://doi.org/10.1016/j.pscychresns.2006.03.001 CrossRefPubMed

Trivedi MH, Hollander E, Nutt D, Blier P (2008) Clinical evidence and potential neurobiological underpinnings of unresolved symptoms of depression. J Clin Psychiatry 69(2):246–258CrossRefPubMed

van de Giessen E, de Win MM, Tanck MW, van den Brink W, Baas F, Booij J (2009) Striatal dopamine transporter availability associated with polymorphisms in the dopamine transporter gene SLC6A3. J Nucl Med 50(1):45–52. https://doi.org/10.2967/jnumed.108.053652 CrossRefPubMed

van Dyck CH, Malison RT, Jacobsen LK, Seibyl JP, Staley JK, Laruelle M, Baldwin RM, Innis RB, Gelernter J (2005) Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene. J Nucl Med 46(5):745–751PubMed

Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Wong C, Ma J, Pradhan K, Tomasi D, Thanos PK, Ferre S, Jayne M (2008) Sleep deprivation decreases binding of [¹¹C]raclopride to dopamine D2/D3 receptors in the human brain. J Neurosci 28(34):8454–8461. https://doi.org/10.1523/JNEUROSCI.1443-08.2008 CrossRefPubMedPubMedCentral

Volkow ND, Tomasi D, Wang GJ, Telang F, Fowler JS, Logan J, Benveniste H, Kim R, Thanos PK, Ferre S (2012) Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain. J Neurosci 32(19):6711–6717. https://doi.org/10.1523/JNEUROSCI.0045-12.2012 CrossRefPubMedPubMedCentral

Vriend C, Raijmakers P, Veltman DJ, van Dijk KD, van der Werf YD, Foncke EM, Smit JH, Berendse HW, van den Heuvel OA (2014) Depressive symptoms in Parkinson’s disease are related to reduced [¹²³I]FP-CIT binding in the caudate nucleus. J Neurol Neurosurg Psychiatry 85(2):159–164. https://doi.org/10.1136/jnnp-2012-304811 CrossRefPubMed

Winz OH, Hellwig S, Mix M, Weber WA, Mottaghy FM, Schafer WM, Meyer PT (2012) Image quality and data quantification in dopamine transporter SPECT: advantage of 3-dimensional OSEM reconstruction? Clin Nucl Med 37(9):866–871. https://doi.org/10.1097/RLU.0b013e318251e1b3 CrossRefPubMed

Wu JC, Buchsbaum M, Bunney WE Jr (2001) Clinical neurochemical implications of sleep deprivation’s effects on the anterior cingulate of depressed responders. Neuropsychopharmacology 25(5 Suppl):S74–S78. https://doi.org/10.1016/S0893-133X(01)00336-0 CrossRefPubMed

Wu H, Lou C, Huang Z, Shi G (2011) SPECT imaging of dopamine transporters with (99m)Tc-TRODAT-1 in major depression and Parkinson’s disease. J Neuropsychiatry Clin Neurosci 23(1):63–67. https://doi.org/10.1176/appi.neuropsych.23.1.6310.1176/jnp.23.1.jnp63 CrossRefPubMed

Yang YK, Yeh TL, Yao WJ, Lee IH, Chen PS, Chiu NT, Lu RB (2008) Greater availability of dopamine transporters in patients with major depression—a dual-isotope SPECT study. Psychiatry Res 162(3):230–235. https://doi.org/10.1016/j.pscychresns.2007.08.008 CrossRefPubMed

Zahniser NR, Doolen S (2001) Chronic and acute regulation of Na⁺/Cl⁻-dependent neurotransmitter transporters: drugs, substrates, presynaptic receptors, and signaling systems. Pharmacol Ther 92(1):21–55CrossRefPubMed

Title: Antidepressant treatment effects on dopamine transporter availability in patients with major depression: a prospective 123I-FP-CIT SPECT imaging genetic study
Authors: Sabine Hellwig
Lars Frings
Annette Masuch
Werner Vach
Katharina Domschke
Claus Normann
Philipp T. Meyer
Publication date: 01-06-2018
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 6/2018
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-018-1863-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Antidepressant treatment effects on dopamine transporter availability in patients with major depression: a prospective ¹²³I-FP-CIT SPECT imaging genetic study

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2018

Who will remain tremor dominant? The possible role of cognitive reserve in the time course of two common Parkinson’s disease motor subtypes

Kynurenic acid and its derivatives are able to modulate the adhesion and locomotion of brain endothelial cells

COQ2 variants in Parkinson’s disease and multiple system atrophy

An observational study of rotigotine transdermal patch and other currently prescribed therapies in patients with Parkinson’s disease

The brain as a “hyper-network”: the key role of neural networks as main producers of the integrated brain actions especially via the “broadcasted” neuroconnectomics

The relationship between gait variability and cognitive functions differs between fallers and non-fallers in MS