Jose M. Tormos

Study and modulation of human cortical excitability with transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) can be applied in different paradigms to obtain a measure of various aspects of cortical excitability. These different TMS paradigms provide information about different neurotransmitter systems, enhance our understanding about the pathophysiology of neuropsychiatric conditions, and in the future may be helpful as a guide for pharmacological interventions. In addition, repetitive TMS (rTMS) modulates cortical excitability beyond the duration of the rTMS trains themselves. Depending on rTMS parameters, a lasting inhibition or facilitation of cortical excitability can be induced. These effects can be demonstrated neurophysiologically or by combining rTMS with neuroimaging techniques. The effects do not remain limited to the cortical area directly targeted by rTMS, but affect a wider neural network transynaptically. Modulation of cortical excitability by rTMS may in the future be useful not only as a research tool but also as a therapeutic intervention in neurology, psychiatry, and neurorehabilitation.

Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation

OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) is able to modulate the corticospinal excitability and the effects appear to last beyond the duration of the rTMS itself. Different studies, employing different rTMS parameters, report different modulation of corticospinal excitability ranging from inhibition to facilitation. Intraindividual variability of these effects and their reproducibility are unclear. METHODS We examined the modulatory effects of rTMS to the motor cortex at various frequencies (1, 10, 20 Hz) and at different time-points in twenty healthy volunteers. RESULTS We observed significant inhibition of MEPs following 1 Hz rTMS and significant facilitation of MEPs following 20 Hz rTMS for both day1 and day 2. Interestingly, at 1 Hz and 20 Hz rTMS, the modulatory effect produced by rTMS was greater on day 2. However, there was no significant change in corticospinal excitability following 10 Hz rTMS neither on day 1 nor day 2. CONCLUSION Our findings raise questions as to how stimulation parameters should be determined when conducting studies applying rTMS on multiple days, and in particular, studies exploring rTMS as a treatment modality in neuropsychiatric disorders.

Transcranial magnetic stimulation and neuroplasticity.

We review past results and present novel data to illustrate different ways in which TMS can be used to study neural plasticity. Procedural learning during the serial reaction time task (SRTT) is used as a model of neural plasticity to illustrate the applications of TMS. These different applications of TMS represent principles of use that we believe are applicable to studies of cognitive neuroscience in general and exemplify the great potential of TMS in the study of brain and behavior. We review the use of TMS for (1) cortical output mapping using focal, single-pulse TMS; (2) identification of the mechanisms underlying neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the information of other neuroimaging techniques by transient disruption of cortical function using repetitive TMS; and finally (4) modulation of cortical function with repetitive TMS to influence behavior and guide plasticity.

Modulation of input-output curves by low and high frequency repetitive transcranial magnetic stimulation of the motor cortex.

OBJECTIVES Exploring the modulatory effects of different frequencies of repetitive transcranial magnetic stimulation (rTMS) on the excitability of the motor cortex as measured by the input-output curve technique (I-O curve). METHODS Sixteen healthy subjects participated in this experiment. On two different sessions, conducted 1 week apart, rTMS was applied either at a frequency of 20 or 1 Hz at 90% of individual motor threshold (MT) for a total of 1600 pulses each. Before and after rTMS, the cortical excitability was assessed by measuring MT and the size of motor evoked potentials (MEPs) collected at different intensities of stimulation. RESULTS The analysis on the whole population showed a significant decrease of cortical excitability after 1 Hz rTMS and an increase after 20 Hz rTMS. A subsequent cluster analysis pointed out the presence of two distinct groups of subjects with opposite responses at the same frequency of stimulation. Significant variations on MT were found for both groups only for the facilitatory effect irrespective of the frequency of stimulation. CONCLUSIONS The results provide further insight into interindividual differences in the effects of rTMS and suggest the existence of subpopulations with specific patterns of response to rTMS.

Improved naming after TMS treatments in a chronic, global aphasia patient – case report

We report improved ability to name pictures at 2 and 8 months after repetitive transcranial magnetic stimulation (rTMS) treatments to the pars triangularis portion of right Broca’s homologue in a 57 year-old woman with severe nonfluent/global aphasia (6.5 years post left basal ganglia bleed, subcortical lesion). TMS was applied at 1 Hz, 20 minutes a day, 10 days, over a two-week period. She received no speech therapy during the study. One year after her TMS treatments, she entered speech therapy with continued improvement. TMS may have modulated activity in the remaining left and right hemisphere neural network for naming.

Changes in Cortical Plasticity Across the Lifespan

Deterioration of motor and cognitive performance with advancing age is well documented, but its cause remains unknown. Animal studies dating back to the late 1970s reveal that age-associated neurocognitive changes are linked to age-dependent changes in synaptic plasticity, including alterations of long-term potentiation and depression (LTP and LTD). Non-invasive brain stimulation techniques enable measurement of LTP- and LTD-like mechanisms of plasticity, in vivo, in humans, and may thus provide valuable insights. We examined the effects of a 40-s train of continuous theta-burst stimulation (cTBS) to the motor cortex (600 stimuli, three pulses at 50 Hz applied at a frequency of 5 Hz) on cortico-spinal excitability as measured by the motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation before and after cTBS in the contralateral first dorsal interosseus muscle. Thirty-six healthy individuals aged 19–81 years old were studied in two sites (Boston, USA and Barcelona, Spain). The findings did not differ across study sites. We found that advancing age is negatively correlated with the duration of the effect of cTBS (r = −0.367; p = 0.028) and the overall amount of corticomotor suppression induced by cTBS (r = −0.478; p = 0.003), and positively correlated with the maximal suppression of amplitude on motor evoked responses in the target muscle (r = 0.420; p = 0.011). We performed magnetic resonance imaging (MRI)-based individual morphometric analysis in a subset of subjects to demonstrate that these findings are not explained by age-related brain atrophy or differences in scalp-to-brain distance that could have affected the TBS effects. Our findings provide empirical evidence that the mechanisms of cortical plasticity area are altered with aging and their efficiency decreases across the human lifespan. This may critically contribute to motor and possibly cognitive decline.

Long-term declarative memory deficits in diffuse TBI: Correlations with cortical thickness, white matter integrity and hippocampal volume

We investigated structural brain damage in subjects who had suffered severe and diffuse traumatic brain injury (TBI), and examined its relationship with declarative memory impairment. Cortical thickness, diffusion tensor imaging (DTI), and volumetric and shape data of the hippocampus were assessed in a group of 26 adults with severe TBI in the chronic stage and 22 healthy matched controls. Declarative memory was evaluated by Reys Auditory Verbal Learning Test (RAVLT). TBI patients performed significantly worse than controls on all RAVLT measures. The group comparison for cortical thickness and DTI revealed a pattern of widespread atrophy in TBI patients. In the TBI group DTI measures correlated with cortical thickness in the prefrontal and parietal regions, including the precuneus. Declarative memory correlated with both cortical thickness and DTI measures. However, although hippocampal volume was significantly decreased in TBI patients, no correlations were found. Multiple regression analysis of all the structural measures revealed that decreases in Fractional anisotropy (FA) and thinning of the left parietal region were the best predictors of memory impairment. In conclusion, cortical thickness reductions in the left hemisphere and a lack of white matter integrity are the main contributors to long-term impairment in declarative memory among patients suffering from severe and diffuse TBI. In this study the hippocampus did not make a significant contribution to memory dysfunctions, suggesting that damage to this structure is compensated for by other regions, with the definitive sequelae being mainly explained by alterations in cortico-subcortical connectivity.

Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua

OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) is a technique for noninvasive focal brain stimulation by which small intracranial electrical currents are generated by a fluctuating extracranial magnetic field. In clinical epilepsy, rTMS has been applied most often interictally to reduce seizure frequency. Less often, rTMS has been used to terminate ongoing seizures, as in instances of epilepsia partialis continua (EPC). Whether ictal rTMS is effective and safe in the treatment of EPC has not been extensively studied. Here, we describe our recent experience with rTMS in the treatment of EPC, as an early step toward evaluating the safety and efficacy of rTMS in the treatment of intractable ongoing focal seizures. METHODS Seven patients with EPC of mixed etiologies were treated with rTMS applied over the seizure. rTMS was delivered in high-frequency (20-100 Hz) bursts or as prolonged low-frequency (1 Hz) trains. The EEG was recorded for three of the seven patients. RESULTS rTMS resulted in a brief (20-30 min) pause in seizures in three of seven patients and a lasting (>or=1 day) pause in two of seven. A literature search identified six additional reports of EPC treated with rTMS where seizures were suppressed in three of six. Seizures were not exacerbated by rTMS in any patient. Generally mild side effects included transient head and limb pain, and limb stiffening during high-frequency rTMS trains. CONCLUSIONS Our clinical observations in a small number of patients suggest that rTMS may be safe and effective in suppressing ongoing seizures associated with EPC. However, a controlled trial is needed to assess the safety and anticonvulsive efficacy of rTMS in the treatment of EPC.

Resting-State Functional Magnetic Resonance Imaging Activity and Connectivity and Cognitive Outcome in Traumatic Brain Injury

IMPORTANCE The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of the brain substrates of cognitive outcome after traumatic axonal injury. This knowledge may contribute to improve clinical management and rehabilitation programs. OBJECTIVE To study functional magnetic resonance imaging abnormalities in signal amplitude and brain connectivity at rest and their relationship to cognitive outcome in patients with chronic and severe traumatic axonal injury. DESIGN Observational study. SETTING University of Barcelona and Hospital Clinic de Barcelona, Barcelona, and Institut Guttmann-Neurorehabilitation Hospital, Badalona, Spain. PARTICIPANTS Twenty patients with traumatic brain injury (TBI) were studied, along with 17 matched healthy volunteers. INTERVENTIONS Resting-state functional magnetic resonance imaging and diffusion tensor imaging data were acquired. After exploring group differences in amplitude of low-frequency fluctuations (ALFF), we studied functional connectivity within the default mode network (DMN) by means of independent component analysis, followed by a dual regression approach and seed-based connectivity analyses. Finally, we performed probabilistic tractography between the frontal and posterior nodes of the DMN. MAIN OUTCOMES AND MEASURES Signal amplitude and functional connectivity during the resting state, tractography related to DMN, and the association between signal amplitudes and cognitive outcome. RESULTS Patients had greater ALFF in frontal regions, which was correlated with cognitive performance. Within the DMN, patients showed increased connectivity in the frontal lobes. Seed-based connectivity analyses revealed augmented connectivity within surrounding areas of the frontal and left parietal nodes of the DMN. Fractional anisotropy of the cingulate tract was correlated with increased connectivity of the frontal node of the DMN in patients with TBI. CONCLUSIONS AND RELEVANCE Increased ALFF is related to better cognitive performance in chronic TBI. The loss of structural connectivity produced by damage to the cingulum tract explained the compensatory increases in functional connectivity within the frontal node of the DMN.

TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia

This study sought to discover if an optimum 1 cm(2) area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions.