COVID-19 after two years: trajectories of different components of mental health in the Spanish population.

AIMS: Our study aimed to (1) identify trajectories on different mental health components during a two-year follow-up of the COVID-19 pandemic and contextualise them according to pandemic periods; (2) investigate the associations between mental health trajectories and several exposures, and determine whether there were differences among the different mental health outcomes regarding these associations. METHODS: We included 5535 healthy individuals, aged 40-65 years old, from the Barcelona Brain Health Initiative (BBHI). Growth mixture models (GMM) were fitted to classify individuals into different trajectories for three mental health-related outcomes (psychological distress, personal growth and loneliness). Moreover, we fitted a multinomial regression model for each outcome considering class membership as the independent variable to assess the association with the predictors. RESULTS: For the outcomes studied we identified three latent trajectories, differentiating two major trends, a large proportion of participants was classified into 'resilient' trajectories, and a smaller proportion into 'chronic-worsening' trajectories. For the former, we observed a lower susceptibility to the changes, whereas, for the latter, we noticed greater heterogeneity and susceptibility to different periods of the pandemic. From the multinomial regression models, we found global and cognitive health, and coping strategies as common protective factors among the studied mental health components. Nevertheless, some differences were found regarding the risk factors. Living alone was only significant for those classified into 'chronic' trajectories of loneliness, but not for the other outcomes. Similarly, secondary or higher education was only a risk factor for the 'worsening' trajectory of personal growth. Finally, smoking and sleeping problems were risk factors which were associated with the 'chronic' trajectory of psychological distress. CONCLUSIONS: Our results support heterogeneity in reactions to the pandemic and the need to study different mental health-related components over a longer follow-up period, as each one evolves differently depending on the pandemic period. In addition, the understanding of modifiable protective and risk factors associated with these trajectories would allow the characterisation of these segments of the population to create targeted interventions.

A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

Sham-derived effects and the minimal reliability of theta burst stimulation.

Theta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation (plasticity) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. In this study we tested the reliability of the effects of two well defined TBS protocols, continuous TBS (cTBS) and intermittent TBS (iTBS), especially in relation to sham TBS, within and across the same 24 participants. All TBS protocols were repeated after approximately 1 month to assess the magnitude and reliability of the modulatory effects of each TBS protocol. Baseline and post-TBS changes in motor evoked potentials (MEP-measure of corticospinal excitability) amplitudes were compared across the cTBS, iTBS and sham TBS protocols and between the initial and retest visits. Overall, across participants, at the initial visit, iTBS facilitated MEPs as compared to baseline excitability, with sham eliciting the same effect. cTBS did not show a significant suppression of excitability compared to baseline MEPs at either visit, and even facilitated MEPs above baseline excitability at a single time point during the repeat visit. Otherwise, effects of TBS were generally diminished in the repeat visit, with iTBS and sham TBS replicating facilitation of MEPs above baseline excitability at similar time points. However, no protocol demonstrated consistent intra-individual modulation of corticospinal excitability upon retest. As the first study to test both iTBS and cTBS against sham TBS across repeat visits, our findings challenge the efficacy and reliability of TBS protocols and emphasize the importance of accounting for sham effects of TBS. Furthermore, given that therapeutic effects of TBS are hypothetically derived from consistent and repeated modulation of brain activity, the non-replicability of plasticity and sham effects call into question these basic mechanisms.

Enhancement of semantic integration reasoning by tRNS.

The right hemisphere is involved with the integrative processes necessary to achieve global coherence during reasoning and discourse processing. Specifically, the right temporal lobe has been proven to facilitate the processing of distant associate relationships, such as generating novel ideas. Previous studies showed a specific swing of alpha and gamma oscillatory activity over the right parieto-occipital lobe and the right anterior temporal lobe respectively, when people solve semantic problems with a specific strategy, i.e., insight problem-solving. In this study, we investigated the specificity of the right parietal and temporal lobes for semantic integration using transcranial Random Noise Stimulation (tRNS). We administered a set of pure semantics (i.e., Compound Remote Associates [CRA]) and visuo-semantic problems (i.e., Rebus Puzzles) to a sample of 31 healthy volunteers. Behavioral results showed that tRNS stimulation over the right temporal lobe enhances CRA accuracy (+12%), while stimulation on the right parietal lobe causes a decrease of response time on the same task (-2,100 ms). No effects were detected for Rebus Puzzles. Our findings corroborate the involvement of the right temporal and parietal lobes when solving purely semantic problems but not when they involve visuo-semantic material, also providing causal evidence for their postulated different roles in the semantic integration process and promoting tRNS as a candidate tool to boost verbal reasoning in humans.

Early diagnosis of Alzheimer's disease: the role of biomarkers including advanced EEG signal analysis. Report from the IFCN-sponsored panel of experts.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to prodromal stages of AD. Thus, the identification of markers of conversion from prodromal form to clinically AD may be crucial for developing strategies of early interventions. The current available markers, including volumetric magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebral spinal fluid (CSF) analysis are expensive, poorly available in community health facilities, and relatively invasive. Taking into account its low cost, widespread availability and non-invasiveness, electroencephalography (EEG) would represent a candidate for tracking the prodromal phases of cognitive decline in routine clinical settings eventually in combination with other markers. In this scenario, the present paper provides an overview of epidemiology, genetic risk factors, neuropsychological, fluid and neuroimaging biomarkers in AD and describes the potential role of EEG in AD investigation, trying in particular to point out whether advanced analysis of EEG rhythms exploring brain function has sufficient specificity/sensitivity/accuracy for the early diagnosis of AD.

Transcranial Direct Current Stimulation over the Left Dorsolateral Prefrontal Cortex Improves Inhibitory Control and Endurance Performance in Healthy Individuals.

The dorsolateral prefrontal cortex (DLPFC) is a crucial brain region for inhibitory control, an executive function essential for behavioral self-regulation. Recently, inhibitory control has been shown to be important for endurance performance. Improvement in inhibitory control was found following transcranial direct current stimulation (tDCS) applied over the left DLPFC (L-DLPFC). This study examined the effect tDCS on both an inhibitory control and endurance performance in a group of healthy individuals. Twelve participants received either real tDCS (Real-tDCS) or placebo tDCS (Sham-tDCS) in randomized order. The anodal electrode was placed over the L-DLPFC while the cathodal electrode was placed above Fp2. Stimulation lasted 30min with current intensity set at 2mA. A Stroop test was administered to assess inhibitory control. Heart rate (HR), ratings of perceived exertion (RPE), and leg muscle pain (PAIN) were monitored during the cycling time to exhaustion (TTE) test, while blood lactate accumulation (∆B[La-]) was measured at exhaustion. Stroop task performance was improved after Real-tDCS as demonstrated by a lower number of errors for incongruent stimuli (p=0.012). TTE was significantly longer following Real-tDCS compared to Sham-tDCS (p=0.029, 17±8 vs 15±8min), with significantly lower HR (p=0.002) and RPE (p<0.001), while no significant difference was found for PAIN (p>0.224). ∆B[La-] was significantly higher at exhaustion in Real-tDCS (p=0.040). Our findings provide preliminary evidence that tDCS with the anodal electrode over the L-DLPFC can improve both inhibitory control and endurance cycling performance in healthy individuals.

Reduction of intratumoral brain perfusion by noninvasive transcranial electrical stimulation.

Malignant brain neoplasms have a poor prognosis despite aggressive treatments. Animal models and evidence from human bodily tumors reveal that sustained reduction in tumor perfusion via electrical stimulation promotes tumor necrosis, therefore possibly representing a therapeutic option for patients with brain tumors. Here, we demonstrate that transcranial electrical stimulation (tES) allows to safely and noninvasively reduce intratumoral perfusion in humans. Selected patients with glioblastoma or metastasis underwent tES, while perfusion was assessed using magnetic resonance imaging. Multichannel tES was applied according to personalized biophysical modeling, to maximize the induced electrical field over the solid tumor mass. All patients completed the study and tolerated the procedure without adverse effects, with tES selectively reducing the perfusion of the solid tumor. Results potentially open the door to noninvasive therapeutic interventions in brain tumors based on stand-alone tES or its combination with other available therapies.

Building emotional resilience over 14 sessions of emotion focused therapy: Micro-longitudinal analyses of productive emotional patterns.

OBJECTIVE: Pascual-Leone and Greenberg's sequential model of emotional processing has been used to explore process in over 24 studies. This line of research shows emotional processing in good psychotherapy often follows a sequential order, supporting a saw-toothed pattern of change within individual sessions (progressing "2-steps-forward, 1-step-back"). However, one cannot assume that local in-session patterns are scalable across an entire course of therapy. Thus, the primary objective of this exploratory study was to consider how the sequential patterns identified by Pascual-Leone, may apply across entire courses of treatment. METHOD: Intensive emotion coding in two separate single-case designs were submitted for quantitative analyses of longitudinal patterns. Comprehensive coding in these cases involved recording observations for every emotional event in an entire course of treatment (using the Classification of Affective-Meaning States), which were then treated as a 9-point ordinal scale. RESULTS: Applying multilevel modeling to each of the two cases showed significant patterns of change over a large number of sessions, and those patterns were either nested at the within-session level or observed at the broader session-by-session level of change. DISCUSSION: Examining successful treatment cases showed several theoretically coherent kinds of temporal patterns, although not always in the same case. Clinical or methodological significance of this article: This is the first paper to demonstrate systematic temporal patterns of emotion over the course of an entire treatment. (1) The study offers a proof of concept that longitudinal patterns in the micro-processes of emotion can be objectively derived and quantified. (2) It also shows that patterns in emotion may be identified on the within-session level, as well as the session-by-session level of analysis. (3) Finally, observed processes over time support the ordered pattern of emotional states hypothesized in Pascual-Leone and Greenberg's (2007) model of emotional processing.

Bilateral extracephalic transcranial direct current stimulation improves endurance performance in healthy individuals.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used to enhance endurance performance but its precise mechanisms and effects remain unknown. OBJECTIVE: To investigate the effect of bilateral tDCS on neuromuscular function and performance during a cycling time to task failure (TTF) test. METHODS: Twelve participants in randomized order received a placebo tDCS (SHAM) or real tDCS with two cathodes (CATHODAL) or two anodes (ANODAL) over bilateral motor cortices and the opposite electrode pair over the ipsilateral shoulders. Each session lasted 10 min and current was set at 2 mA. Neuromuscular assessment was performed before and after tDCS and was followed by a cycling time to task failure (TTF) test. Heart rate (HR), ratings of perceived exertion (RPE), leg muscle pain (PAIN) and blood lactate accumulation (ΔB[La-]) in response to the cycling TTF test were measured. RESULTS: Corticospinal excitability increased in the ANODAL condition (P < 0.001) while none of the other neuromuscular parameters showed any change. Neuromuscular parameters did not change in the SHAM and CATHODAL conditions. TTF was significantly longer in the ANODAL (P = 0.003) compared to CATHODAL and SHAM conditions (12.61 ± 4.65 min; 10.61 ± 4.34 min; 10.21 ± 3.47 min respectively), with significantly lower RPE and higher ΔB[La-] (P < 0.001). No differences between conditions were found for HR (P = 0.803) and PAIN during the cycling TTF test (P = 0.305). CONCLUSION: Our findings demonstrate that tDCS with the anode over both motor cortices using a bilateral extracephalic reference improves endurance performance.

Estimates of peak electric fields induced by Transcranial magnetic stimulation in pregnant women as patients using an FEM full-body model.

Transcranial magnetic stimulation (TMS) for treatment of depression during pregnancy is an appealing alternative to fetus-threatening drugs. However, no studies to date have been performed that evaluate the safety of TMS for a pregnant mother patient and her fetus. A full-body FEM model of a pregnant woman with about 100 tissue parts has been developed specifically for the present study. This model allows accurate computations of induced electric field in every tissue given different locations of a shape-eight coil, a biphasic pulse, common TMS pulse durations, and using different values of the TMS intensity measured in SMT (Standard Motor Threshold) units. Our simulation results estimate the maximum peak values of the electric field in the fetal area for every fetal tissue separately and for the TMS intensity of one SMT unit.

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.

Multifocal tDCS targeting the resting state motor network increases cortical excitability beyond traditional tDCS targeting unilateral motor cortex.

Scientists and clinicians have traditionally targeted single brain regions with stimulation to modulate brain function and disease. However, brain regions do not operate in isolation, but interact with other regions through networks. As such, stimulation of one region may impact and be impacted by other regions in its network. Here we test whether the effects of brain stimulation can be enhanced by simultaneously targeting a region and its network, identified with resting state functional connectivity MRI. Fifteen healthy participants received two types of transcranial direct current stimulation (tDCS): a traditional two-electrode montage targeting a single brain region (left primary motor cortex [M1]) and a novel eight-electrode montage targeting this region and its associated resting state network. As a control, 8 participants also received multifocal tDCS mismatched to this network. Network-targeted tDCS more than doubled the increase in left M1 excitability over time compared to traditional tDCS and the multifocal control. Modeling studies suggest these results are unlikely to be due to tDCS effects on left M1 itself, however it is impossible to completely exclude this possibility. It also remains unclear whether multifocal tDCS targeting a network selectively modulates this network and which regions within the network are most responsible for observed effects. Despite these limitations, network-targeted tDCS appears to be a promising approach for enhancing tDCS effects beyond traditional stimulation targeting a single brain region. Future work is needed to test whether these results extend to other resting state networks and enhance behavioral or therapeutic effects.

The corticomotor projection to liminally-contractable forearm muscles in chronic spinal cord injury: a transcranial magnetic stimulation study.

STUDY DESIGN: A cross-sectional study in chronic spinal cord injury with cervical lesions (cSCI). OBJECTIVE: To determine the corticomotor projection and motor cortex organization of paralyzed forearm muscles that presented only liminal voluntary activation. SETTING: Burke Medical Research Institute, White Plains, NY, USA. METHODS: We identified ten people with chronic SCI who had a wrist flexor or extensor muscle with a motor power (MP) of 1 over 5. We recorded motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) over the primary motor cortex of the hemisphere contralateral to the target muscle. We measured resting motor threshold (RMT), corticomotor latency (LTY), MEP amplitude (AMP) and performed cortical motor mapping to determine the optimal site (OPT) and map area (AREA). Results were compared with the data from 18 controls. RESULTS: A MEP in the target muscle was observed for all cSCI cases. LTY was normal, while corticomotor excitability (as determined by RMT and AMP) was reduced in about half of the group. The OPT site of the motor maps was within control range for all cSCI cases, while AREA was reduced in three cases. CONCLUSIONS: Corticomotor conduction and cortical topography were appreciably normal despite only liminal activation of the target muscle with voluntary effort. Muscles with these characteristics may benefit from a targeted rehabilitation program even in the chronic phase after SCI.

H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report.

Low frequency repetitive TMS (rTMS) of a cortical seizure focus is emerging as an antiepileptic treatment. While conventional rTMS stimulators activate only superficial cortical areas, reaching deep epileptic foci, for example in temporal lobe epilepsy (TLE), is possible using specially designed H-coils. We report the results of rTMS in a young adult with pharmacoresistant bilateral TLE who underwent three courses (of 10, 15, and 30 daily sessions) of unilateral rTMS over the hemisphere from which seizures originated most often. Seizure frequency was assessed before and after each block of rTMS sessions, as was the tolerability of the procedure. Seizure frequency declined significantly, by 50 to 70% following each rTMS course. All sessions were well-tolerated.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

Transcranial direct current stimulation (tDCS) and robotic practice in chronic stroke: the dimension of timing.

BACKGROUND: Combining tDCS with robotic therapy is a new and promising form of neurorehabilitation after stroke, however the effectiveness of this approach is likely to be influenced by the relative timing of the brain stimulation and the therapy. OBJECTIVE: To measure the kinematic and neurophysiological effects of delivering tDCS before, during and after a single session of robotic motor practice (wrist extension). METHODS: We used a within-subjects repeated-measurement design in 12 chronic (>6 months) stroke survivors. Twenty minutes of anodal tDCS was delivered to the affected hemisphere before, during, or after a 20-minute session of robotic practice. Sham tDCS was also applied during motor practice. Robotic motor performance and corticomotor excitability, assessed through transcranial magnetic stimulation (TMS), were evaluated pre- and post-intervention. RESULTS: Movement speed was increased after motor training (sham tDCS) by ∼20%. Movement smoothness was improved when tDCS was delivered before motor practice (∼15%). TDCS delivered during practice did not offer any benefit, whereas it reduced speed when delivered after practice (∼10%). MEPs were present in ∼50% of patients at baseline; in these subjects motor practice increased corticomotor excitability to the trained muscle. CONCLUSIONS: In a cohort of stroke survivors, motor performance kinematics improved when tDCS was delivered prior to robotic training, but not when delivered during or after training. The temporal relationship between non-invasive brain stimulation and neurorehabilitation is important in determining the efficacy and outcome of this combined therapy.

Preserved corticospinal conduction without voluntary movement after spinal cord injury.

STUDY DESIGN: Case report. OBJECTIVES: To identify preserved corticomotor connection in chronic spinal cord injury (SCI) in the absence of clinically observable movement. SETTING: Rehabilitation Hospital and Medical Research Institute, NY, USA. METHODS: The motor-evoked potential (MEP) response to transcranial magnetic stimulation (TMS) was recorded using surface electromyography from the right biceps brachii, extersor carpi radialis (ECR), flexor carpi radialis (FCR) and abductor pollicis brevis (APB) muscles in a 31-year-old male traumatic SCI chronic patient-ASIA B, injury level C5. Motor power scores were additionally obtained from a clinician blinded to the results of TMS. RESULTS: TMS could consistently elicit MEPs of normal latency, phase and amplitude, in the severely affected ECR muscle but not the similarly affected FCR muscle. The response in proximal and unaffected biceps muscle was larger than the healthy subject, whereas no response was obtained in the distal APB muscle as expected. CONCLUSION: TMS can identify residual pathways not apparent from clinical assessment alone, which may have prescriptive value for rehabilitation.

The effects of transcranial direct current stimulation with visual illusion in neuropathic pain due to spinal cord injury: an evoked potentials and quantitative thermal testing study.

BACKGROUND: Neuropathic pain (NP) is common in spinal cord injury (SCI) patients. One of its manifestations is a lowering of pain perception threshold in quantitative thermal testing (QTT) in dermatomes rostral to the injury level. Transcranial direct current stimulation (tDCS) combined with visual illusion (VI) improves pain in SCI patients. We studied whether pain relief with tDCS + VI intervention is accompanied by a change in contact heat- evoked potentials (CHEPs) or in QTT. METHODS: We examined 18 patients with SCI and NP before and after 2 weeks of daily tDCS + VI intervention. Twenty SCI patients without NP and 14 healthy subjects served as controls. We assessed NP intensity using a numerical rating scale (NRS) and determined heat and pain thresholds with thermal probes. CHEPs were recorded to stimuli applied at C4 level, and subjects rated their perception of evoked pain using NRS during CHEPs. RESULTS: Thirteen patients reported a mean decrease of 50% in the NRS for NP after tDCS + VI. Evoked pain perception was significantly higher than in the other two groups, and reduced significantly together with CHEPs amplitude after tDCS + VI with respect to baseline. Pain perception threshold was significantly lower than in the other two groups before tDCS + VI intervention, and increased significantly afterwards. CONCLUSION: Two weeks of tDCS + VI induced significant changes in CHEPs, evoked pain and heat pain threshold in SCI patients with NP. These neurophysiological tests might be objective biomarkers of treatment effects for NP in patients with SCI.

Typical neural representations of action verbs develop without vision.

Many empiricist theories hold that concepts are composed of sensory-motor primitives. For example, the meaning of the word "run" is in part a visual image of running. If action concepts are partly visual, then the concepts of congenitally blind individuals should be altered in that they lack these visual features. We compared semantic judgments and neural activity during action verb comprehension in congenitally blind and sighted individuals. Participants made similarity judgments about pairs of nouns and verbs that varied in the visual motion they conveyed. Blind adults showed the same pattern of similarity judgments as sighted adults. We identified the left middle temporal gyrus (lMTG) brain region that putatively stores visual-motion features relevant to action verbs. The functional profile and location of this region was identical in sighted and congenitally blind individuals. Furthermore, the lMTG was more active for all verbs than nouns, irrespective of visual-motion features. We conclude that the lMTG contains abstract representations of verb meanings rather than visual-motion images. Our data suggest that conceptual brain regions are not altered by the sensory modality of learning.