Differential effects of motor cortical excitability and plasticity in young and old individuals: a Transcranial Magnetic Stimulation (TMS) study

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

Examining the relationship between fitness, cortical excitability, and neurochemistry of the brain (GABA, glutamate, and NAA)

L'exercice aérobique (AE) est associé à de nombreuses modifications fonctionnelles et anatomiques dans le cerveau humain. Par exemple, il a été démontré que l'EA modulait l'excitabilité corticale et la neurochimie immédiatement après l'exercice. Les effets d'une activité physique répétée et soutenue sur les fonctions cérébrales restent toutefois mal compris. En effet, peu de données sont disponibles permettant de déterminer si les personnes ayant une bonne condition physique présentent des modifications persistantes de l'excitabilité corticale et du métabolisme cérébral malgré les changements rapportés dans la matière grise et la matière blanche. Dans la présente étude, 20 personnes sédentaires en bonne santé ( 6 heures/semaine d'activité physique) sur la base de mesures de l'excitabilité corticale (rMT, courbe I/O, SICI, ICF) et de la concentration de métabolites (GABA, Glx, NAA) dans la représentation corticale de la main droite. L'épaisseur corticale de la représentation du cortex moteur primaire de la main droite et la densité apparente des fibres de la voie corticospinale (CST) ont également été évaluées. L'aptitude cardiorespiratoire (VO2max) était significativement plus élevée chez les athlètes que chez les sédentaires, ce qui n'était pas le cas de l'indice de masse corporelle. Aucune différence entre les groupes n'a été constatée en ce qui concerne les mesures du rMT, du SICI et de l'ICF. Les valeurs de la courbe I/O étaient significativement plus élevées et la courbe I/O était plus prononcée chez les individus actifs. Aucune différence significative n'a été observée pour l'épaisseur corticale, la concentration de métabolites et les valeurs de diffusion de la CST. La pente de la courbe I/O était positivement corrélée à la VO2max. Les présentes données suggèrent que des niveaux élevés de capacité aérobique sont associés à une excitabilité corticale accrue dans la représentation de la main du cortex moteur primaire.Aerobic exercise is associated with widespread functional and anatomical modifications in the human brain. For example, AE has been shown to modulate cortical excitability and neurochemistry immediately after exercise. The effects of repeated and sustained physical activity on brain function, however, remain poorly understood. Indeed, little is known about whether individuals with high levels of fitness display persistent modifications in cortical excitability and brain metabolism despite reported changes in grey and white matter. In the present study, 20 healthy sedentary individuals ( 6 hours/week AE) on measures of cortical excitability (rMT, I/O curve, SICI, ICF) and metabolite concentration (GABA, Glx, NAA) in the cortical representation of the right hand. Cortical thickness of the primary motor cortex representation of the right hand and corticospinal tract (CST) apparent fiber density (AFD) were also assessed. Cardiorespiratory fitness (VO2max) was significantly higher in athletes compared to sedentary individuals whereas body mass index was not. No group differences were found on measures of rMT, SICI and ICF. I/O curve values were significantly higher, and the I/O curve was steeper in active individuals. No significant differences were observed between the groups for cortical thickness, metabolite concentration and CST diffusion values. I/O curve slope was positively correlated with VO2max. The present data suggest that high levels of aerobic fitness are associated with increased cortical excitability in the hand representation of the primary motor cortex

Using Brain Stimulation to Enhance Working Memory: A Charged Topic

Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task. Pairing repeated performance of a WM task with brain stimulation may encourage plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task. In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In each experiment, participants received either active (2.0 mA) or sham (0.1 mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer (fluid intelligence) task. In Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task

The relationship between cognitive reserve and neuroplasticity in older adults

This item is only available electronically.Background: Cognitive Reserve (CR) is suggested to explain the difference between the expected impact of levels of age-related neuropathology and the real deficits which people experience. Neuroplasticity is speculated to be the neurophysiological mechanism underlying the cognition-protective effects of CR; however, this has not previously been experimentally demonstrated. Aim: To identify whether neuroplasticity mediates the relationship between CR and cognitive ability. Method: 23 healthy older adults participated in this study, which comprised 3 brain stimulation sessions: (1) continuous theta-burst stimulation (cTBS) applied to left dorsolateral prefrontal cortex, (2) cTBS applied to left motor cortex, and (3) a sham session. Resting electroencephalography (EEG) was used to calculate change in the aperiodic slope of neural power spectra (a novel measure of neuroplasticity) following cTBS. Participants were also assessed with measures of CR (lifetime of experiences; crystallised intelligence) and cognitive ability (fluid intelligence; paired associates learning). Results: We induced a neuroplasticity-like effect in both of the active cTBS conditions. This was not observed in the sham condition. We did not observe a significant relationship between neuroplasticity and CR or cognitive ability. This meant mediational analysis was not justified. Conclusions: We successfully demonstrated that analysis of the aperiodic slope is an effective means of identifying neuroplasticity with EEG. While we did not identify a significant relationship between our neuroplasticity measure and CR, we recommend further studies investigate other forms of neuroplasticity. Continued investigation of the neurophysiology underlying CR may facilitate the development of early interventions which could reduce the prevalence of age-related cognitive impairment.Thesis (B.PsychSc(Hons)) -- University of Adelaide, School of Psychology, 202

Inter and intra-hemispheric structural imaging markers predict depression relapse after electroconvulsive therapy: a multisite study.

Relapse of depression following treatment is high. Biomarkers predictive of an individual's relapse risk could provide earlier opportunities for prevention. Since electroconvulsive therapy (ECT) elicits robust and rapidly acting antidepressant effects, but has a >50% relapse rate, ECT presents a valuable model for determining predictors of relapse-risk. Although previous studies have associated ECT-induced changes in brain morphometry with clinical response, longer-term outcomes have not been addressed. Using structural imaging data from 42 ECT-responsive patients obtained prior to and directly following an ECT treatment index series at two independent sites (UCLA: n = 17, age = 45.41±12.34 years; UNM: n = 25; age = 65.00±8.44), here we test relapse prediction within 6-months post-ECT. Random forests were used to predict subsequent relapse using singular and ratios of intra and inter-hemispheric structural imaging measures and clinical variables from pre-, post-, and pre-to-post ECT. Relapse risk was determined as a function of feature variation. Relapse was well-predicted both within site and when cohorts were pooled where top-performing models yielded balanced accuracies of 71-78%. Top predictors included cingulate isthmus asymmetry, pallidal asymmetry, the ratio of the paracentral to precentral cortical thickness and the ratio of lateral occipital to pericalcarine cortical thickness. Pooling cohorts and predicting relapse from post-treatment measures provided the best classification performances. However, classifiers trained on each age-disparate cohort were less informative for prediction in the held-out cohort. Post-treatment structural neuroimaging measures and the ratios of connected regions commonly implicated in depression pathophysiology are informative of relapse risk. Structural imaging measures may have utility for devising more personalized preventative medicine approaches

Brain networks reorganization during maturation and healthy aging-emphases for resilience

Maturation and aging are important life periods that are linked to drastic brain reorganization processes which are essential for mental health. However, the development of generalized theories for delimiting physiological and pathological brain remodeling through life periods linked to healthy states and resilience on one side or mental dysfunction on the other remains a challenge. Furthermore, important processes of preservation and compensation of brain function occur continuously in the cerebral brain networks and drive physiological responses to life events. Here, we review research on brain reorganization processes across the lifespan, demonstrating brain circuits remodeling at the structural and functional level that support mental health and are parallelized by physiological trajectories during maturation and healthy aging. We show evidence that aberrations leading to mental disorders result from the specific alterations of cerebral networks and their pathological dynamics leading to distinct excitability patterns. We discuss how these series of large-scale responses of brain circuits can be viewed as protective or malfunctioning mechanisms for the maintenance of mental health and resilience

Interventional programmes to improve cognition during healthy and pathological ageing: Cortical modulations and evidence for brain plasticity

Available online 06 March 2018A growing body of evidence suggests that healthy elderly individuals and patients with Alzheimer’s disease retain an important potential for neuroplasticity. This review summarizes studies investigating the modulation of neural activity and structural brain integrity in response to interventions involving cognitive training, physical exercise and non-invasive brain stimulation in healthy elderly and cognitively impaired subjects (including patients with mild cognitive impairment (MCI) and Alzheimer’s disease). Moreover, given the clinical relevance of neuroplasticity, we discuss how evidence for neuroplasticity can be inferred from the functional and structural brain changes observed after implementing these interventions. We emphasize that multimodal programmes, which combine several types of interventions, improve cognitive function to a greater extent than programmes that use a single interventional approach. We suggest specific methods for weighting the relative importance of cognitive training, physical exercise and non-invasive brain stimulation according to the functional and structural state of the brain of the targeted subject to maximize the cognitive improvements induced by multimodal programmes.This study was funded by the European Commission Marie-Skłodowska Curie Actions, Individual Fellowships; 655423-NIBSAD, Italian Ministry of HealthGR-2011-02349998, and Galician government (Postdoctoral Grants Plan I2C 2011-2015)

Investigating the Cortical, Metabolic and Behavioral Effects of Transcranial Direct Current Stimulation in Preparation for Combined Rehabilitation

The goal of this thesis was to determine the cortical reorganization that occurs in patients with cervical spondylotic myelopathy (CSM) after surgical decompression and to implement this knowledge into a new rehabilitation strategy. Transcranial direct current stimulation (tDCS) is a non-invasive technique to modulate human behavior. Due to the novel electrode montage used, it was first pertinent that we determine how tDCS would modulate cortical, metabolic and motor behavior in healthy individuals. We observed the longitudinal functional adaptations that occur in patients with CSM using functional MRI. Enhanced excitation of supplementary motor area (SMA) was observed following surgical decompression and associated with increased function following surgery. This novel finding of enhanced excitation of motivated us to use a bihemispheric tDCS protocol, exciting bilateral motor areas to provide optimal motor enhancement. This novel tDCS electrode montage, targeting the SMA and primary motor cortex (M1) was implemented in healthy older adults to determine its effects on enhancing manual dexterity. Furthermore, to determine the frequency with which to apply tDCS, a single and tri session protocol was used. We observed a differential pattern of action with anti-phase and in-phase motor tasks during multisession tDCS. We used ultra-high field (7T) MRI to examined the metabolic changes that occur following tDCS. After the stimulation period we observed no significant metabolite modulation. A trend towards an increase in the NAA/tCr ratio, with a concomitant decrease in the absolute concentration of tCr was observed. Finally, we examined the functional connectivity before, during and after tDCS with the use of resting-state fMRI at 7T. We observed enhanced connectivity within right sensorimotor area after stimulation compared to during stimulation. This result confirmed that cortical modulations differ during versus after tDCS, signifying that optimal modulation of behaviour may be after the stimulation period. Furthermore, we observed an enhanced correlation between motor regions and the caudate, both during and after stimulation. In conclusion, we observed novel cortical adaptations in CSM patients after surgical decompression, which led us to believe that bihemispheric tDCS of M1-SMA network would result in optimal motor enhancement and warrants further investigation in CSM and other neurological disorders