Sara Marceglia

Improved naming after transcranial direct current stimulation in aphasia

Transcranial direct current stimulation (tDCS) has been proposed as an adjuvant technique to improve functional recovery after ischaemic stroke. This study evaluated the effect of tDCS over the left frontotemporal areas in eight chronic non-fluent post-stroke aphasic patients. The protocol consisted of the assessment of picture naming (accuracy and response time) before and immediately after anodal or cathodal tDCS (2 mA, 10 minutes) and sham stimulation. Whereas anodal tDCS and sham tDCS failed to induce any changes, cathodal tDCS significantly improved the accuracy of the picture naming task by a mean of 33.6% (SEM 13.8%).

Transcranial direct current stimulation improves recognition memory in Alzheimer disease

Objective: To evaluate the cognitive effect of transcranial direct current stimulation (tDCS) over the temporoparietal areas in patients with Alzheimer disease (AD). Methods: In 10 patients with probable AD, we delivered anodal tDCS (AtDCS), cathodal tDCS (CtDCS), and sham tDCS (StDCS) over the temporoparietal areas in three sessions. In each session recognition memory and visual attention were tested at baseline (prestimulation) and 30 minutes after tDCS ended (poststimulation). Results: After AtDCS, accuracy of the word recognition memory task increased (prestimulation: 15.5 ± 0.9, poststimulation: 17.9 ± 0.8, p = 0.0068) whereas after CtDCS it decreased (15.8 ± 0.6 vs 13.2 ± 0.9, p = 0.011) and after StDCS it remained unchanged (16.3 ± 0.7 vs 16.0 ± 1.0, p = 0.75). tDCS left the visual attention-reaction times unchanged. Conclusion: Transcranial direct current stimulation (tDCS) delivered over the temporoparietal areas can specifically affect a recognition memory performance in patients with Alzheimer disease (AD). Because tDCS is simple, safe and inexpensive, our finding prompts studies using repeated tDCS, in conjunction with other therapeutic interventions for treating patients with AD.

Cerebellar transcranial direct current stimulation impairs the practice-dependent proficiency increase in working memory

How the cerebellum is involved in the practice and proficiency of non-motor functions is still unclear. We tested whether transcranial direct current stimulation (tDCS) over the cerebellum (cerebellar tDCS) induces after-effects on the practice-dependent increase in the proficiency of a working memory (WM) task (Sternberg test) in 13 healthy subjects. We also assessed the effects of cerebellar tDCS on visual evoked potentials (VEPs) in four subjects and compared the effects of cerebellar tDCS on the Sternberg test with those elicited by tDCS delivered over the prefrontal cortex in five subjects. Our experiments showed that anodal or cathodal tDCS over the cerebellum impaired the practice-dependent improvement in the reaction times in a WM task. Because tDCS delivered over the prefrontal cortex induced an immediate change in the WM task but left the practice-dependent proficiency unchanged, the effects of cerebellar tDCS are structure-specific. Cerebellar tDCS left VEPs unaffected, its effect on the Sternberg task therefore seems unlikely to arise from visual system involvement. In conclusion, tDCS over the cerebellum specifically impairs the practice-dependent proficiency increase in verbal WM.

Improved isometric force endurance after transcranial direct current stimulation over the human motor cortical areas

Neuromuscular fatigue is the exercise‐dependent decrease in the ability of muscle fibres to generate force. To investigate whether manipulation of brain excitability by transcranial direct current stimulation (tDCS; 1.5 mA, 10 min, 0.026 C/cm2) modulates neuromuscular fatigue, we evaluated the effect of brain polarization over the right motor areas of the cerebral cortex of healthy subjects on the endurance time for a submaximal isometric contraction of left elbow flexors. In 24 healthy volunteers the study protocol comprised an assessment of the maximum voluntary contraction (MVC) for the left elbow flexors and a fatiguing isometric contraction (35% of MVC), before and immediately after brain polarization. One hour elapsed between baseline (T0) and postconditioning (T1) evaluation. After tDCS, MVC remained unchanged from baseline (mean ± SEM; anodal tDCS: T0, 154.4 ± 18.07; T1, 142.8 ± 16.62 N; cathodal tDCS: T0, 156 ± 18.75; T1, 141.86 ± 17.53 N; controls: T0, 148.8 ± 6.64; T1, 137.6 ± 7.36 N; P > 0.1). Conversely, endurance time decreased significantly less after anodal than after cathodal tDCS or no stimulation (−21.1 ± 5.5%, −35.7 ± 3.3% and −39.3 ± 3.3%, respectively; P < 0.05). None of the evaluated electromyographic variables changed after tDCS. Anodal tDCS could improve endurance time by directly modulating motor cortical excitability, modulating premotor areas, decreasing fatigue‐related muscle pain, increasing motivation and improving synergist muscle coupling. Our findings, showing that anodal tDCS over the motor areas of the cerebral cortex improves muscle endurance, open the way to increasing muscle endurance and decreasing muscle fatigue in normal (i.e. sports medicine) and pathological conditions.

Dopamine‐dependent non‐linear correlation between subthalamic rhythms in Parkinson's disease

The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single neurones in normal animals, suggesting a segregated parallel processing scheme. In 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated monkeys and in parkinsonian patients single neurones become linearly correlated, thus leading to a loss of segregation between neurones. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non‐linearly correlated, thus leading to a loss of segregation between rhythms. Non‐linear correlation was particularly consistent between the low‐beta rhythm (13–20 Hz) and the high‐beta rhythm (20–35 Hz). Levodopa administration significantly decreased these non‐linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurones, but is not sufficient to induce correlated firing between neurone pairs. Conversely, loss of dopamine generates pathological linear correlation between neurone pairs, alters the patterns within LFP rhythms, and induces non‐linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also interactions between rhythms.

The effects of levodopa and ongoing deep brain stimulation on subthalamic beta oscillations in Parkinson's disease

Local field potentials (LFPs) recorded through electrodes implanted in the subthalamic nucleus (STN) for deep brain stimulation (DBS) in patients with Parkinsons disease (PD) show that oscillations in the beta frequency range (8-20 Hz) decrease after levodopa intake. Whether and how DBS influences the beta oscillations and whether levodopa- and DBS-induced changes interact remains unclear. We examined the combined effect of levodopa and DBS on subthalamic beta LFP oscillations, recorded in nine patients with PD under four experimental conditions: without levodopa with DBS turned off; without levodopa with DBS turned on; with levodopa with DBS turned on; and with levodopa with DBS turned off. The analysis of STN-LFP oscillations showed that whereas levodopa abolished beta STN oscillations in all the patients (p=0.026), DBS significantly decreased the beta oscillation only in five of the nine patients studied (p=0.043). Another difference was that whereas levodopa completely suppressed beta oscillations, DBS merely decreased them. When we combined levodopa and DBS, the levodopa-induced beta disruption prevailed and combining levodopa and DBS induced no significant additive effect (p=0.500). Our observations suggest that levodopa and DBS both modulate LFP beta oscillations.

Effect of spinal transcutaneous direct current stimulation on somatosensory evoked potentials in humans

OBJECTIVE Invasive stimulation of the spinal cord is used to treat a number of pathological conditions. Aiming to modulate human spinal cord function non-invasively, we evaluated whether transcutaneous direct current (DC) stimulation induces long-lasting changes in conduction along the sensory spinal pathways. METHODS Somatosensory evoked potentials (SEPs) by posterior tibial nerve and by median nerve stimulation were recorded, before, at current offset and at 20 min after transcutaneous anodal or cathodal DC stimulation over the thoracic spinal cord (2.5 mA, 15 min) in a group of 12 healthy subjects. RESULTS Whereas both polarities left the spinal (N22) and the cortical potentials (P39) unchanged, anodal transcutaneous spinal DC stimulation decreased significantly by about 25% the amplitude of the cervico-medullary component of posterior tibial nerve SEPs (P30) for at least 20 min. Thoracic transcutaneous spinal cord stimulation left median nerve SEPs unchanged. CONCLUSIONS Transcutaneous DC stimulation over the thoracic spinal cord induces changes in conduction along human lemniscal pathway that persist after stimulation ends. SIGNIFICANCE Our results support the use of transcutaneous DC stimulation as a novel tool for non-invasive spinal neuromodulation. Because the method is non-expensive and simple, it can be tested in patients with disorders presently treated with invasive procedures.

Subthalamic local field potential oscillations during ongoing deep brain stimulation in Parkinson's disease

How deep brain stimulation (DBS) acts and how the brain responds to it remains unclear. To investigate the mechanisms involved, we analyzed changes in local field potentials from the subthalamic area (STN-LFPs) recorded through the deep brain macroelectrode during monopolar DBS of the subthalamic nucleus area (STN-DBS) in a group of eight patients (16 nuclei) with idiopathic Parkinsons disease. Monopolar STN-DBS was delivered through contact 1 and differential LFP recordings were acquired between contacts 0 and 2. The stimulating contact was 0.5 mm away from each recording contact. The power spectral analysis of STN-LFPs showed that during ongoing STN-DBS whereas the power of beta oscillations (8-20 Hz) and high beta oscillations (21-40 Hz) remained unchanged, the power of low-frequency oscillations (1-7 Hz) significantly increased (baseline=0.37+/-0.22; during DBS=7.07+/-15.10, p=0.0003). Despite comparable low-frequency baseline power with and without levodopa, the increase in low-frequency oscillations during STN-DBS was over boosted by pretreatment with levodopa. The low-frequency power increase in STN-LFPs during ongoing STN-DBS could reflect changes induced at basal ganglia network level similar to those elicited by levodopa. In addition, the correlation between the heart beat and the low-frequency oscillations suggests that part of the low-frequency power increase during STN-DBS arises from polarization phenomena around the stimulating electrode. Local polarization might in turn also help to normalize STN hyperactivity in Parkinsons disease.

Gender-related differences in moral judgments

The moral sense is among the most complex aspects of the human mind. Despite substantial evidence confirming gender-related neurobiological and behavioral differences, and psychological research suggesting gender specificities in moral development, whether these differences arise from cultural effects or are innate remains unclear. In this study, we investigated the role of gender, education (general education and health education) and religious belief (Catholic and non-Catholic) on moral choices by testing 50 men and 50 women with a moral judgment task. Whereas we found no differences between the two genders in utilitarian responses to non-moral dilemmas and to impersonal moral dilemmas, men gave significantly more utilitarian answers to personal moral (PM) dilemmas (i.e., those courses of action whose endorsement involves highly emotional decisions). Cultural factors such as education and religion had no effect on performance in the moral judgment task. These findings suggest that the cognitive–emotional processes involved in evaluating PM dilemmas differ in men and in women, possibly reflecting differences in the underlying neural mechanisms. Gender-related determinants of moral behavior may partly explain gender differences in real-life involving power management, economic decision-making, leadership and possibly also aggressive and criminal behaviors.

Brain Switches Utilitarian Behavior: Does Gender Make the Difference?

Decision often implies a utilitarian choice based on personal gain, even at the expense of damaging others. Despite the social implications of utilitarian behavior, its neurophysiological bases remain largely unknown. To assess how the human brain controls utilitarian behavior, we delivered transcranial direct current stimulation (tDCS) over the ventral prefrontal cortex (VPC) and over the occipital cortex (OC) in 78 healthy subjects. Utilitarian judgment was assessed with the moral judgment task before and after tDCS. At baseline, females provided fewer utilitarian answers than males for personal moral dilemmas (p = .007). In males, VPC-tDCS failed to induce changes and in both genders OC-tDCS left utilitarian judgments unchanged. In females, cathodal VPC-tDCS tended to decrease whereas anodal VPC-tDCS significantly increased utilitarian responses (p = .005). In males and females, reaction times for utilitarian responses significantly decreased after cathodal (p<.001) but not after anodal (p = .735) VPC-tDCS. We conclude that ventral prefrontal tDCS interferes with utilitarian decisions, influencing the evaluation of the advantages and disadvantages of each option in both sexes, but does so more strongly in females. Whereas cathodal tDCS alters the time for utilitarian reasoning in both sexes, anodal stimulation interferes more incisively in women, modifying utilitarian reasoning and the possible consequent actions. The gender-related tDCS-induced changes suggest that the VPC differentially controls utilitarian reasoning in females and in males. The gender-specific functional organization of the brain areas involved in utilitarian behavior could be a correlate of the moral and social behavioral differences between the two sexes.