Facilitative effects of bi-hemispheric tDCS in cognitive deficits of Parkinson disease patients Jorge Leite a,⇑ , Oscar F. Gonçalves b,a , Sandra Carvalho a a Neuropsychophysiology Laboratory, CIPsi, School of Psychology (EPsi), University of Minho, Braga, Portugal b Department of Counseling and Applied Educational Psychology, Bouvé College of Health Sciences, Northeastern University, Boston, USA article info Article history: Received 20 August 2013 Accepted 23 November 2013 abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder, primarily characterized by motor symptoms such as tremor, rigidity, bradykinesia, stiffness, slowness and impaired equilibrium. Although the motor symptoms have been the focus in PD, slight cognitive deficits are commonly found in non-demented and non-depressed PD patients, even in early stages of the disease, which have been linked to the subsequent development of pathological dementia. Thus, strongly reducing the quality of life (QoL). Both levodopa therapy and deep brain stimulation (DBS) have yield controversial results concerning the cognitive symptoms amelioration in PD patients. That does not seems to be the case with transcranial direct current stimulation (tDCS), although better stimulation parameters are needed. Therefore we hypothesize that simultaneously delivering cathodal tDCS (or ctDCS), over the right prefrontal cortex delivered with anodal tDCS (or atDCS) to left prefrontal cortex could be potentially beneficial for PD patients, either by mechanisms of homeostatic plasticity and by increases in the extracellular dopamine levels over the striatum. Ó 2013 Elsevier Ltd. All rights reserved. Introduction Parkinson’s disease (PD) is a progressive neurodegenerative dis- order, primarily characterized by motor symptoms such as tremor, rigidity, bradykinesia, stiffness, slowness and impaired equilibrium [1]. Etiologically, PD has been associated to dopaminergic (DA) cells degeneration in the midbrain causing DA depletion in the stri- atum [2]. This depletion seems to trigger compensatory DA strate- gies in several areas of the brain that gradually decline with the progression of the disease [3]. Although the motor symptoms have been the focus in PD, slight cognitive deficits, are commonly found in non-demented and non- depressed PD patients, even in early stages of the disease, which have been linked to subsequent pathological dementia [4]. Thus, strongly reducing the quality of life (QoL) [5]. Other studies sug- gested that these cognitive deficits could even be considered as a mild cognitive impairment (MCI) [6]. These cognitive deficits constitute a heterogeneous profile of impairments that have been already shown to be present at the time of diagnosis [7]. Other studies have suggested potential brain alter- ations [8] that even precede the onset of the cognitive impairments. Despite this heterogeneity, most of the cognitive deficits in PD are executive functioning driven [9], involving update or maintenance of information within working memory (WM). In early stages of PD, rule shifting, planning, attentional set shifting, WM, feedback based learning and delayed response inhibition are common cogni- tive impairments (see [1] for review). Without a global cognitive impairment, these deficits can be similar to a fronto-striatal dysex- ecutive syndrome [1], and therefore are thought to be related to spe- cific under activations in regions of the basal ganglia or prefrontal cortex (PFC) [10,11]. At later stages of the disease, patients could exhibit dementia with impairments in semantic fluency, auditory verbal learning, visuospatial skills, verbal and visual memory, as well as suffering from hallucinations [1]. Based on animal and com- putational models, as well as in human cognitive data, Cools [12] proposed an interesting framework where striatal DA would be re- lated to the flexible shift between mental representations, whereas prefrontal DA would be related to the maintenance of such repre- sentations. Therefore in early stages of PD, patients would reveal difficulties in the updating of WM, as well as impaired ability to adapt in tasks that required continuous changes in the S–R mappings (i.e. set shifting and task switching tasks). Only in poster- ior phases of the disease progression, ventral striatum dependent tasks (such as probabilistic reversal learning) would be affected [13]. This could explain why levodopa (or L-DOPA) has yield both positive and negative results in terms of cognitive symptoms 0306-9877/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.mehy.2013.11.021 ⇑ Corresponding author. Address: School of Psychology (EPSI), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Tel.: +351 253604220; fax: +351 253604224. E-mail address: jorgel@psi.uminho.pt (J. Leite). Medical Hypotheses 82 (2014) 138–140 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy