The overall decline in stroke mortality observed over the past decades is due to a reduction in stroke incidence as well as substantial progress in the acute treatment of stroke and patient care. These improvements are mirrored by an increasing number of stroke survivors, who are left with persistent neurological and neuropsychological deficits despite intensive rehabilitation. Consequently, stroke is the leading cause of acquired long-term disability and globally produces immense health, social and economic burdens. While physiotherapy, language therapy, and occupational therapy are widely accepted elements of rehabilitation, novel approaches to rehabilitation are urgently needed. Such therapies may comprise behavioural, pharmacological or technical approaches, the latter including non-invasive neuromodulatory techniques (i.e., transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) (e.g., Hummel et al., 2005 for hand motor function in hemiparesis; Sparing et al., 2009 for spatial neglect, and Bolognini et al., 2015 for ideomotor apraxia). More than 100 years ago, Constantin von Monakow (1914) introduced the concept of diaschisis, postulating that a lesion to one part of the brain consecutively leads to reduced activity in primarily unaffected but connected brain regions. Critically, the reduced excitatory input into remote but connected areas is assumed to contribute to the patient’s behavioural deficit. Recent advances in the analysis of functional neuroimaging data have enabled us to assess the direct and indirect effects of focal brain damage (Grefkes and Fink, 2014): connectivity analysis can be used to investigate how cerebral networks reorganize their structural and functional anatomy to compensate for both the lesion itself and remote effects. Such analyses also enable a better understanding of the physiology underlying recovery of function by showing, for example, why some patients make a better recovery than others. They also allow investigation of the effect of focal stimulation (e.g., stimulation of ipsilesional M1) on the functional network architecture of the damaged brain. Furthermore, this systems- physiology based approach can provide insights into the individual network pathology underlying a particular neurological deficit, thereby laying the groundwork for tailored neuromodulatory approaches using non-invasive stimulation. In the future, this may lead to patientspecific treatment regimens supporting rehabilitation.
In view of the questions remaining re. the exact mechanisms of tDCS and rTMS and the dynamics of network pathology in the course of stroke, negative metaanalyses (e.g., Elsner et al., 2015) may not come as a surprise. Rather they emphasise the need for systematic investigations of spontaneous, therapy-induced and neuromodulation enhanced recovery of function. It seems likely that such recovery will require pathophysiology-informed interventions, thereby allowing more precise treatment regimens that target specifially both the patient’s deficit and the network pathology. Furthermore, novel computational approaches like multivariate pattern analyses may help to identify neuroimaging markers that predict an individual patient’s response to neuromodulatory interventions (Grefkes and Fink, 2014). Whether this can be reconciled with the equally pressing need for multicentre studies with larger numbers of patients remains an open question.
Bolognini N, Convento S, Banco E, Mattioli F, Tesio L, Vallar G. Improving ideomotor limb apraxia by electrical stimulation of the left posterior parietal cortex. Brain 2015; 138:428-39.
Elsner B, Kugler J, Pohl M, Mehrholz J. Transcranial direct current stimulation (tDCS) for improving aphasia in patients with aphasia after stroke (Review). Cochrane Database Syst Rev 2015; 5:CD009760.
Grefkes C, Fink GR. Connectivity-based approaches in stroke and recovery of function. Lancet Neurol 2014; 13:206-216.
Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, Cohen LG. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain 2005; 128:490-9.
Sparing R, Thimm M, Hesse MD, Küst J, Karbe H, Fink GR. Bidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation. Brain. 2009; 132:3011-20.
von Monakow C. Die Lokalisation im Grosshirn und der Abbau der Funktion durch kortikale Herde. Wiesbaden: Bergmann JF, 1914.
Lunedì 11 giugno 2018, ore 14.30
Sala Lauree del Dipartimento di Psicologia, U6 (3° piano)
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Prof. Eraldo Paulesu