Long-Lasting Enhancement of Visual Perception with Repetitive Noninvasive Transcranial Direct Current Stimulation

Understanding processes performed by an intact visual cortex as the basis for developing methods that enhance or restore visual perception is of great interest to both researchers and medical practitioners. Here, we explore whether contrast sensitivity, a main function of the primary visual cortex (V1), can be improved in healthy subjects by repetitive, noninvasive anodal transcranial direct current stimulation (tDCS). Contrast perception was measured via threshold perimetry directly before and after intervention (tDCS or sham stimulation) on each day over 5 consecutive days (24 subjects, double- blind study). tDCS improved contrast sensitivity from the second day onwards, with significant effects lasting 24 h. After the last stimulation on day 5, the anodal group showed a significantly greater improvement in contrast perception than the sham group (23 vs. 5%). We found significant long-term effects in only the central 2–4° of the visual field 4 weeks after the last stimulation. We suspect a combination of two factors contributes to these lasting effects. First, the V1 area that represents the central retina was located closer to the polarization electrode, resulting in higher current density. Second, the central visual field is represented by a larger cortical area relative to the peripheral visual field (cortical magnification). This is the first study showing that tDCS over V1 enhances contrast perception in healthy subjects for several weeks. This study contributes to the investigation of the causal relationship between the external modulation of neuronal membrane potential and behavior (in our case, visual perception). Because the vast majority of human studies only show temporary effects after single tDCS sessions targeting the visual system, our study underpins the potential for lasting effects of repetitive tDCS-induced modulation of neuronal excitability

Evolution of premotor cortical excitability after cathodal inhibition of the primary motor cortex: a sham-controlled serial navigated TMS study.

BACKGROUND: Premotor cortical regions (PMC) play an important role in the orchestration of motor function, yet their role in compensatory mechanisms in a disturbed motor system is largely unclear. Previous studies are consistent in describing pronounced anatomical and functional connectivity between the PMC and the primary motor cortex (M1). Lesion studies consistently show compensatory adaptive changes in PMC neural activity following an M1 lesion. Non-invasive brain modification of PMC neural activity has shown compensatory neurophysiological aftereffects in M1. These studies have contributed to our understanding of how M1 responds to changes in PMC neural activity. Yet, the way in which the PMC responds to artificial inhibition of M1 neural activity is unclear. Here we investigate the neurophysiological consequences in the PMC and the behavioral consequences for motor performance of stimulation mediated M1 inhibition by cathodal transcranial direct current stimulation (tDCS). PURPOSE: The primary goal was to determine how electrophysiological measures of PMC excitability change in order to compensate for inhibited M1 neural excitability and attenuated motor performance. HYPOTHESIS: Cathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability. METHODS: We enrolled 16 healthy participants in this randomized, double-blind, sham-controlled, crossover design study. All participants underwent navigated transcranial magnetic stimulation (nTMS) to identify PMC and M1 corticospinal projections as well as to evaluate electrophysiological measures of cortical, intracortical and interhemispheric excitability. Cortical M1 excitability was inhibited using cathodal tDCS. Finger-tapping speeds were used to examine motor function. RESULTS: Cathodal tDCS successfully reduced M1 excitability and motor performance speed. PMC excitability was increased for longer and was the only significant predictor of motor performance. CONCLUSION: The PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance

Multiple, Successful Pregnancies in Pompe Disease.

Pompe disease is an autosomal recessive lysosomal storage disease characterized in adult patients by slowly progressive limb-girdle muscle weakness and respiratory insufficiency. Data on pregnancy in women with Pompe disease, intrauterine development of the fetus and parturition are rare. Here we describe a twin pregnancy followed by a second pregnancy in a 38-year-old female patient with Pompe disease. We report the impact of pregnancy on muscle and respiratory functions as well as the neurological and endocrine systems and discuss the medical consequences for anaesthetic management at parturition

Summary of experimental results.

<p>ANOVA results have been categorized with respect to whether data was compared between brain <i>region</i>s (i.e. primary motor cortex (M1) and dorsal premotor cortex (PMC)) or <i>intervention</i>s (i.e. cathodal and sham stimulation) and whether they examine functional performance or electrophysiological properties. The test of MEP latency contains the two-level factor <i>muscle</i> for forearm and hand muscles. The two-level factor <i>time</i> distinguishes between early(<40 min) and late (>40 min) period aftereffects. The four-level factor <i>TMS intensity</i> refers to 10% increments of the individual resting motor threshold (RMT) used as stimulation intensities to assess input-output curves. Paired-pulse stimulation sequences contain the two-level factor ISI reflecting SICI and ICF protocols. Please refer to the methods section for further details. * p<0.05.</p

Diagram illustrating the randomization of parameters to be examined in one exemplary subject.

<p>Parameters of motor cortical excitability and function were assessed at two time intervals (early or late) following transcranial direct current stimulation (indicated by a flash symbol). Changes in measures recorded 0–40 minutes after discontinuation of the stimulation were considered to be due to early aftereffects. Changes recorded in the successive 40 minutes were considered to be due to late aftereffects. Aftereffects which occured in only one recording period were considered to be short-lasting; others were considered to be long-lasting. Immediately before and after tDCS, 20 stimuli were applied at a fixed intensity (see methods section for details) over M1 to examine tDCS-induced changes of corticospinal excitability. Afterwards, the five neurophysiological or functional parameters being evaluated were randomly assigned to one of four time slots in the overall 80-minute post-stimulation period. IO  =  input-output curve, TAP  =  finger-tapping, ICE  =  intracortical excitability (Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), IHI  =  interhemispheric inhibition, MT  =  motor threshold; Pos1 – Pos4: Random position in time for each parameter.</p

Results and comparison of electrophysiological responses to either cathodal or sham stimulation in the primary motor area.

<p>A) Cortical excitability estimates. MEP average amplitude in the early and later period. In contrast to sham tDCS, cathodal tDCS significantly diminished mean MEP amplitudes by about 50%. B) Input-output curves. MEP average amplitudes at 110% through 140% RMT. In contrast to sham tDCS, cathodal tDCS significantly diminished mean MEP amplitudes at stimulation strengths of 130% and 140% RMT. C) Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Average amplitudes of the test MEP at 2 and 5 ms ISI. SICI is enhanced in the early and significantly reduced in the late post-stimulation period after cathodal stimulation. ICF is not significantly affected by the cathodal stimulation. The time periods in all figures correspond to the definition of time intervals in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057425#pone-0057425-g001" target="_blank">Figure 1</a>. Error bars represent the standard error of the mean. * p<0.05</p

Input-output curves over PMC. MEP average amplitudes defined by stimulation at 110% through 140% RMT.

<p>In contrast to sham tDCS, cathodal tDCS significantly enhanced cortical excitability. Significant results were found at 130% (late period) and 140% (both periods) RMT. Error bars represent the standard error of the mean. * p<0.05</p

Maximum finger-tapping frequency reached in 30 seconds before and after 40 minutes (see Figure 1).

<p>Error bars represent the standard error of the mean. Finger-tapping speed is significantly slowed directly after cathodal stimulation as compared to sham stimulation or the late period. * p<0.05</p