[Show abstract][Hide abstract] ABSTRACT: Aging is associated with changes in the motor system that, over time, can lead to functional impairments and contribute negatively to the ability to recover after brain damage. Unfortunately, there are still many questions surrounding the physiological mechanisms underlying these impairments. We examined cortico-spinal excitability and plasticity in a young cohort (age range: 19-31) and an elderly cohort (age range: 47-73) of healthy right-handed individuals using navigated transcranial magnetic stimulation (nTMS). Subjects were evaluated with a combination of physiological [motor evoked potentials (MEPs), motor threshold (MT), intracortical inhibition (ICI), intracortical facilitation (ICF), and silent period (SP)] and behavioral [reaction time (RT), pinch force, 9 hole peg task (HPT)] measures at baseline and following one session of low-frequency (1 Hz) navigated repetitive TMS (rTMS) to the right (non-dominant) hemisphere. In the young cohort, the inhibitory effect of 1 Hz rTMS was significantly in the right hemisphere and a significant facilitatory effect was noted in the unstimulated hemisphere. Conversely, in the elderly cohort, we report only a trend toward a facilitatory effect in the unstimulated hemisphere, suggesting reduced cortical plasticity and interhemispheric communication. To this effect, we show that significant differences in hemispheric cortico-spinal excitability were present in the elderly cohort at baseline, with significantly reduced cortico-spinal excitability in the right hemisphere as compared to the left hemisphere. A correlation analysis revealed no significant relationship between cortical thickness of the selected region of interest (ROI) and MEPs in either young or old subjects prior to and following rTMS. When combined with our preliminary results, further research into this topic could lead to the development of neurophysiological markers pertinent to the diagnosis, prognosis, and treatment of neurological diseases characterized by monohemispheric damage and lateralized motor deficits.
Frontiers in Aging Neuroscience 06/2014; 6:111. · 2.84 Impact Factor
Textbook of Neural Repair and Rehabilitation, Volume 1, Neural Repair and Plasticity, 2 edited by Selzer M; Clarke S; Cohen L; Kwakkel G; Miller R, 01/2014; Cambridge University Press., ISBN: 9781107011670
[Show abstract][Hide abstract] ABSTRACT: The precision of navigated transcranial magnetic stimulation (TMS) to map the human primary motor cortex may be effected by the direction of TMS-induced current in the brain as determined by the orientation of the stimulation coil. In this study, the authors investigated the effect of current directionality on motor output mapping using navigated brain stimulation. The goal of this study was to determine the optimal coil orientation (and, thus, induced brain current) to activate hand musculature representations relative to each subject's unique neuroanatomical landmarks. The authors studied motor output maps for the first dorsal interosseous, abductor pollicis brevis, and abductor digiti minimi muscles in 10 normal volunteers. Monopolar current pulses were delivered through a figure-of-eight-shaped TMS coil, and motor evoked potentials were recorded using electromyography. At each targeted brain region, the authors systematically rotated the TMS coil to determine the direction of induced current in the brain for induction of the largest motor evoked potentials. These optimal current directions were expressed as an angle relative to each subject's central sulcus. Consistency of the optimal current direction was assessed by repeating the entire mapping procedure on two different occasions across subjects. The authors demonstrate that systematic optimization of current direction as guided by MRI-based neuronavigation improves the resolution of cortical output motor mapping with TMS.
Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 08/2013; 30(4):390-395. · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the past several years, the number of studies investigating enhancement of cognitive functions through noninvasive brain stimulation (NBS) has increased considerably. NBS techniques, such as transcranial magnetic stimulation and transcranial current stimulation, seem capable of enhancing cognitive functions in patients and in healthy humans, particularly when combined with other interventions, including pharmacologic, behavioral and cognitive therapies. The "net zero-sum model", based on the assumption that brain resources are subjected to the physical principle of conservation of energy, is one of the theoretical frameworks proposed to account for such enhancement of function and its potential cost. We argue that to guide future neuroenhancement studies, the net-zero sum concept is helpful, but only if its limits are tightly defined.
[Show abstract][Hide abstract] ABSTRACT: Brain plasticity can be conceptualized as nature's invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the lifespan. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable 'starting-points' and different 'slopes of change' defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer's disease.
[Show abstract][Hide abstract] ABSTRACT: Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including marketing, off-label use and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand.
Journal of medical ethics 03/2011; 37(3):137-43. · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome. Individuals suffering from FXS display abnormalities in the expression of FMR1--a protein required for typical, healthy neural development. Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity. In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2-5% of autistic children suffer from FXS. Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity. Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum--up to 90 minutes. This extended effect-duration suggests an underlying abnormality in the brain's natural plasticity state in autistic individuals, similar to the hyperexcitability induced by Fragile X Syndrome. In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.
[Show abstract][Hide abstract] ABSTRACT: Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses. Within the field of TMS, the term state dependency refers to the initial, baseline condition of the particular neural region targeted for stimulation. As can be inferred, the effects of TMS can (and do) vary according to this primary susceptibility and responsiveness of the targeted cortical area. In this experiment, we will examine this concept of state dependency through the elicitation and subjective experience of motive phosphenes. Phosphenes are visually perceived flashes of small lights triggered by electromagnetic pulses to the visual cortex. These small lights can assume varied characteristics depending upon which type of visual cortex is being stimulated. In this particular study, we will be targeting motive phosphenes as elicited through the stimulation of V1/V2 and the V5/MT+ complex visual regions.
[Show abstract][Hide abstract] ABSTRACT: The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest." It is thought the default mode network corresponds to self-referential or "internal mentation". It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia and autism spectrum disorders whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases. As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses. In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.
[Show abstract][Hide abstract] ABSTRACT: The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic fields. These rapidly alternating fields induce electrical currents within localized, targeted regions of the cortex which are associated with various physiological and functional brain changes. In 2007, O'Reardon et al., utilizing the NeuroStar device, published the results of an industry-sponsored, multisite, randomized, sham-stimulation controlled clinical trial in which 301 patients with major depression, who had previously failed to respond to at least one adequate antidepressant treatment trial, underwent either active or sham TMS over the left dorsolateral prefrontal cortex (DLPFC). The patients, who were medication-free at the time of the study, received TMS five times per week over 4-6 weeks. The results demonstrated that a sub-population of patients (those who were relatively less resistant to medication, having failed not more than two good pharmacologic trials) showed a statistically significant improvement on the Montgomery-Asberg Depression Scale (MADRS), the Hamilton Depression Rating Scale (HAMD), and various other outcome measures. In October 2008, supported by these and other similar results, Neuronetics obtained the first and only Food and Drug Administration (FDA) approval for the clinical treatment of a specific form of medication-refractory depression using a TMS Therapy device (FDA approval K061053). In this paper, we will explore the specified FDA approved NeuroStar depression treatment protocol (to be administered only under prescription and by a licensed medical profession in either an in- or outpatient setting).