Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson’s disease

BackgroundVerbal fluency relies on the coordinated activity between left frontal and temporal areas. Patients with Parkinson’s disease (PD) present phonemic and semantic fluency deficits. Recent studies suggest that transcranial direct current stimulation (tDCS) enhances adaptative patterns of brain activity between functionally connected areas.ObjectiveThe aim of this study was to assess the differences in the effects induced by tDCS applied to frontal and temporo-parietal areas on phonemic and semantic fluency functional networks in patients with PD.MethodSixteen patients were randomized to receive tDCS to left dorsolateral prefrontal cortex (DLPFC) and left temporo-parietal cortex (TPC) in a counterbalanced order. Immediately following stimulation, patients underwent a verbal fluency paradigm inside a fMRI scanner. Changes induced by tDCS in activation and deactivation task-related pattern networks were studied using free-model independent component analyses (ICA).ResultsFunctional connectivity in verbal fluency and deactivation task-related networks was significantly more enhanced by tDCS to DLPFC than to TPC. In addition, DLPFC tDCS increased performance on the phonemic fluency task, after adjusting for baseline phonemic performance.ConclusionsThese findings provide evidence that tDCS to specific brain regions induces changes in large scale functional networks that underlay behavioural effects, and suggest that tDCS might be useful to enhance phonemic fluency in PD.     

The effects of transcranial direct current stimulation on sleep in patients with multiple sclerosis–A pilot study

BackgroundSleep complaints are commonly reported by patients with multiple sclerosis (PwMS). Several pharmacological and alternative interventions have been tried, but are usually faced by limited efficacy. Hence, exploring other methods such as transcranial direct current stimulation (tDCS), might be of interest. The aim of this study was to assess the effects of bifrontal tDCS on subjective (i.e., Epworth Sleepiness Scale (ESS)) and objective sleep measures (i.e., actigraphy).MethodsSeven patients completed the study. Patients randomly received two blocks of five daily sessions each in a crossover design (active and sham, with a washout interval of three weeks). The anode and cathode were placed over the left and right dorsolateral prefrontal cortices, respectively. Sleep assessment included ESS, sleep onset latency, total sleep duration, time in bed, sleep efficiency, waking after sleep onset, and number of awakenings.ResultsCompared to baseline scores (11.14 ± 4.06), significant decrease in ESS was obtained after active intervention (7.86 ± 4.18; p = 0.011), but not after sham intervention (9.57 ± 5.62; p = 0.142). No significant changes were observed with regards to actigraphy measures. Sessions were well tolerated, and no serious side-effects were reported at any time.ConclusionBifrontal tDCS resulted in significant improvement in daytime sleepiness, but did not yield any effect on objective sleep measures in PwMS. This discrepency might be explained by the modest association that could exist between objective and subjective sleep measures. In addition, it could be assumed that modulating objective sleep measures would require a larger sample size, more stimulation sessions, or modulation of other cortical areas.     

Neuroimaging for Lewy body disease: Is the in vivo molecular imaging of α-synuclein neuropathology required and feasible?

Alpha-synuclein aggregation is a neuropathological hallmark of many neurodegenerative diseases including Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB), collectively termed the α-synucleinopathies. Substantial advances in clinical criteria and neuroimaging technology over the last 20 years have allowed great strides in the detection and differential diagnosis of these disorders. Nevertheless, it is clear that whilst the array of different imaging modalities in clinical use allow for a robust diagnosis of α-synucleinopathy in comparison to healthy subjects, there is no clear diagnostic imaging marker that affords a reliable differential diagnosis between the different forms of Lewy body disease (LBD) or that could facilitate tracking of disease progression. This has led to a call for a biomarker based on the pathological hallmarks of these diseases, namely α-synuclein-positive Lewy bodies (LBs). This potentially may be advantageous in terms of early disease detection, but may also be leveraged into a potential marker of disease progression. We here aim to firstly review the current status of neuroimaging biomarkers in PD and related synucleinopathies. Secondly, we outline the rationale behind α-synuclein imaging as a potential novel biomarker as well as the potential benefits and limitations of this approach. Thirdly, we attempt to illustrate the likely technical hurdles to be overcome to permit successful in vivo imaging of α-synuclein pathology in the diseased brain. Our overriding aim is to provide a framework for discussion of how to address this major unmet clinical need.     

The effect of transcranial direct current stimulation on upper limb motor performance in Parkinson’s disease: a systematic review

Journal of Neurology - Parkinson’s disease (PD) reduces independence and quality of life through deterioration of upper limb motor function. Transcranial direct current stimulation (tDCS) may...     

Bifrontal and bioccipital transcranial direct current stimulation (tDCS) does not induce mood changes in healthy volunteers: A placebo controlled study

Transcranial direct current stimulation (tDCS) is the application of a weak electrical direct current (1.5?mA), which has the ability to modulate spontaneous firing rates of the cortical neurons by depolarizing or hyperpolarizing the neural resting membrane potential. tDCS in patients with depressive disorders has been proven to be an interesting therapeutic method potentially influencing pathologic mood states. Except one study, no alterations in mood could be confirmed applying tDCS in healthy participants. In this study, bifrontal or bioccipital stimulation was applied in 17 healthy subjects during 20 minutes with 1.5 mA in a placebo-controlled manner. Bifrontal stimulation consisted of both anodal and cathodal placement on right and left dorsolateral prefrontal cortex (DLPFC) in two separate sessions. Using a set of self-reported moodscales (SUDS, POMS-32, PANAS, BISBAS) no significant mood changes could be observed, neither with bifrontal nor bioccipital tDCS. As already demonstrated by previous studies, we confirmed the minimal side effects and the safety of this neuromodulation technique.     

How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.     

Induction of long-term potentiation-like plasticity in the primary motor cortex with repeated anodal transcranial direct current stimulation – Better effects with intensified protocols?

BackgroundA single session of anodal tDCS induces LTP-like plasticity which lasts for about 1 h, while repetition of stimulation within a time interval of 30 min results in late-phase effects lasting for at least 24 h with standard stimulation protocols.ObjectiveIn this pilot study, we explored if the after-effects of a recently developed intensified single session stimulation protocol are relevantly prolonged in the motor cortex by repetition of this intervention.Methods16 healthy right-handed subjects participated in this study. The effects of an intensified (3 mA-20min) and a standard anodal tDCS protocol (1 mA-15min) with short (20 min) and long (3 h) repetition intervals were compared with the effects of respective single session tDCS protocols (3 mA-20min, 1 mA-15min, and Sham). Cortical excitability alterations were monitored by single-pulse TMS-elicited MEPs.ResultsCompared to sham, both single session tDCS protocols (1 mA-15min, and 3 mA-20min) resulted in cortical excitability enhancements lasting for about 30 min after stimulation. The short repetition interval (20 min) resulted in a prolongation of after-effects for the standard protocol, which lasted for more than 24 h after stimulation. For the intensified protocol, the prolongation of after-effects was limited to 120 min after stimulation. The long repetition interval (3 h) resulted in no excitability-enhancing after-effects for the intensified, and only minor excitability enhancement within the first 30 min after the intervention for the standard protocol.ConclusionThese results suggest a non-linearity of late-phase LTP-like plasticity induction, which was dependent not only on the interval of intervention repetition, but also on other protocol characteristics, including intensity, and duration of tDCS. Further studies in larger samples are needed to confirm these results.     

Comparison of detection results of hypoxic-ischemic encephalopathy at different degrees in infant patients between brain electrical activity mapping, transcranial Doppler sonography and computer tomography examinations

BACKGROUND: It has been proved that brain electrical activity mapping (BEAM) and transcranial Doppler (TCD) detection can reflect the function of brain cell and its diseased degree of infant patients with moderate to severe hypoxic-ischemic encephalopathy (HIE). OBJECTIVE: To observe the abnormal results of HIE at different degrees detected with BEAM and TCD in infant patients, and compare the detection results at the same time point between BEAM, TCD and computer tomography (CT) examinations. DESIGN: Contrast observation. SETTING: Departments of Neuro-electrophysiology and Pediatrics, Second Affiliated Hospital of Qiqihar Medical College. PARTICIPANTS: Totally 416 infant patients with HIE who received treatment in the Department of Newborn Infants, Second Affiliated Hospital of Qiqihar Medical College during January 2001 and December 2005. The infant patients, 278 male and 138 female, were at embryonic 37 to 42 weeks and weighing 2.0 to 4.1 kg, and they were diagnosed with CT and met the diagnostic criteria of HIE of newborn infants compiled by Department of Neonatology, Pediatric Academy, Chinese Medical Association. According to diagnostic criteria, 130 patients were mild abnormal, 196 moderate abnormal and 90 severe abnormal. The relatives of all the infant patients were informed of the experiment. METHODS: BEAM and TCD examinations were performed in the involved 416 infant patients with HIE at different degrees with DYD2000 16-channel BEAM instrument and EME-2000 ultrasonograph before preliminary diagnosis treatment (within 1 month after birth) and 1,3,6,12 and 24 months after birth, and detected results were compared between BEAM, TCD and CT examinations. MAIN OUTCOME MEASURES: Comparison of detection results of HIE at different time points in infant patients between BEAM, TCD and CT examinations. RESULTS: All the 416 infant patients with HIE participated in the result analysis. ① Comparison of the detected results in infant patients with mild HIE at different time points after birth between BEAM, TCD and CT examinations: BEAM examination showed that the recovery was delayed, and the abnormal rate of BEAM examination was significantly higher than that of CT examination 1 and 3 months after birth [55.4%（72/130）vs. 17.0%（22/130），χ2=41.66；29.2%（38/130） vs. 6.2%（8/130），χ2=23.77，P < 0.01], exceptional patients had mild abnormality and reached the normal level in about 6 months. TCD examination showed that the disease condition significantly improved and infant patients with HIE basically recovered 1 or 2 months after birth, while CT examination showed that infant patients recovered 3 or 4 months after birth. ② Comparison of detection results of infant patients with moderate HIE at different time points between BEAM, TCD and CT examinations: The abnormal rate of BEAM examination was significantly higher than that of CT examination 1,3,6 and 12 months after birth [90.8%（178/196），78.6%（154/196），χ2=4.32，P < 0.05；64.3%（126/196），43.9%（86/196），χ2=16.44；44.9%（88/196），22.4%（44/196），χ2=22.11；21.4%（42/196），10.2%（20/196），χ2=9.27，P < 0.01]. BEAM examination showed that there was still one patient who did not completely recovered in the 24th month due to the relatives of infant patients did not combine the treatment,. TCD examination showed that the abnormal rate was 23.1%（30/196）in the 1st month after birth, and all the patients recovered to the normal in the 3rd month after birth, while CT examination showed that mild abnormality still existed in the 24th month after birth（1.0%，2/196）. ③ Comparison of detection results of infant patients with severe HIE at different time points between BEAM, TCD and CT examinations: The abnormal rate of BEAM examination was significantly higher than that of CT examination in the 1st, 3rd, 6th and 12th months after birth[86.7%（78/90），44.4%（40/90），χ2=35.53；62.2%（56/90），31.1%（28/90），χ2=17.51；37.8%（34/90），6.7%（6/90），χ2=27.14，P < 0.01]. BEAM examination showed that mild abnormality still existed in 4 infant patients in the 24th month after birth. TCD examination showed that the abnormal rate was 11.1% （10/90） in the 3rd month after birth, and all the infant patients recovered in the 6th month after birth. CT examination showed that the abnormal rate was 6.7%（6/90） in the 12th month after birth, and all of infant patients recovered to the normal in the 24th month after birth. CONCLUSION: BEAM is the direct index to detect brain function of infant patients with HIE, and positive reaction is still very sensitive in the tracking detection of convalescent period. The positive rate of morphological reaction in CT examination is superior to that in TCD examination, and the positive rate is very high in the acute period of HIE in examination.     

Histological characterization and development of mesial surface sulci in the human brain at 13–15 gestational weeks through high-resolution histology

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres. Of note at this stage, when most of the cerebrum is occupied by lateral ventricles and the corpus callosum is incompletely developed, we postulate that these mesial infolds represent the primordial stage of cingulate, callosal, and calcarine sulci, features of mesial cortical development. Our observations are based on the multimodal approach and further include histological three-dimensional reconstruction that highlights the importance of the plane of sectioning. We describe the laminar organization of the developing cortical mantle, including these infolds from the marginal to ventricular zone, with Nissl, hematoxylin and eosin, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Despite the absence of major sulci on the dorsal surface, the boundaries among the orbital, frontal, parietal, and occipital cortex were very well demarcated, primarily by the cytoarchitecture differences in the organization of the subplate (SP) and intermediate zone (IZ) in these locations. The parietal region has the thickest cortical plate (CP), SP, and IZ, whereas the orbital region shows the thinnest CP and reveals an extra cell-sparse layer above the bilaminar SP. The subcortical structures show intensely GFAP-immunolabeled soma, absent in the cerebral mantle. Our findings establish a normative neurodevelopment baseline at the early stage.     

Expression of insulin-like growth factor-1 mRNA and protein level of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkeys

IN T R O D U C T IO NC erebralischem ia/reperfusion leads to neuralcellinjury,and itcan al- so initiate the self-protective m echanism oforganism . G row th factor fam ily plays an im portant role in ischem ic cerebralinjury and partici- pants in the regu…