Mechanisms Of Cortical Plasticity Research Articles

The neural basis of implicit learning and memory: A review of neuropsychological and neuroimaging research

Memory systems research has typically described the different types of long-term memory in the brain as either declarative versus non-declarative or implicit versus explicit. These descriptions reflect the difference between declarative, conscious, and explicit memory that is dependent on the medial temporal lobe (MTL) memory system, and all other expressions of learning and memory. The other type of memory is generally defined by an absence: either the lack of dependence on the MTL memory system (nondeclarative) or the lack of conscious awareness of the information acquired (implicit). However, definition by absence is inherently underspecified and leaves open questions of how this type of memory operates, its neural basis, and how it differs from explicit, declarative memory. Drawing on a variety of studies of implicit learning that have attempted to identify the neural correlates of implicit learning using functional neuroimaging and neuropsychology, a theory of implicit memory is presented that describes it as a form of general plasticity within processing networks that adaptively improve function via experience. Under this model, implicit memory will not appear as a single, coherent, alternative memory system but will instead be manifested as a principle of improvement from experience based on widespread mechanisms of cortical plasticity. The implications of this characterization for understanding the role of implicit learning in complex cognitive processes and the effects of interactions between types of memory will be discussed for examples within and outside the psychology laboratory.

Presynaptic Gating of Postsynaptic Synaptic Plasticity

Sensory cortices can not only detect and analyze incoming sensory information but can also undergo plastic changes while learning behaviorally important sensory cues. This experience-dependent cortical plasticity is essential for shaping and modifying neuronal circuits to perform computations of multiple, previously unknown sensations, the adaptive process that is believed to underlie perceptual learning. Intensive efforts to identify the mechanisms of cortical plasticity have provided several important clues; however, the exact cellular sites and mechanisms within the intricate neuronal networks that underlie cortical plasticity have yet to be elucidated. In this review, we present several parallels between cortical plasticity in the auditory cortex and recently discovered mechanisms of synaptic plasticity gating at thalamocortical projections that provide the main input to sensory cortices. Striking similarities between the features and mechanisms of thalamocortical synaptic plasticity and those of experience-dependent cortical plasticity in the auditory cortex, especially in terms of regulation of an early critical period, point to thalamocortical projections as an important locus of plasticity in sensory cortices.

Evidence for multiple mechanisms of cortical plasticity: A study of humans with late-onset profound unilateral deafness

ObjectiveTo investigate 1: plasticity due to partial unilateral deafness of slow onset and 2: the time course of plasticity following abrupt, profound unilateral deafness in adult humans using cortical auditory evoked potentials. MethodsBaseline data were measured from six participants with partial unilateral deafness due to an acoustic neuroma and compared with data from six controls. Further measurements were made in the unilaterally deaf group at 1-, 3- and 6-months post surgery for acoustic neuroma removal and consequent profound unilateral deafness. Data were recorded from 30 channels in response to pure tones presented to the intact ear. ResultsBaseline data revealed statistically higher amplitudes in unilaterally deaf participants but with normal hemispheric asymmetry. Longitudinal data revealed further increases in P1 amplitudes by 1-month post-surgery, and in N1 and P2 amplitudes by 6-months post-surgery, with statistically different scalp field topographies indicating reduced hemispheric asymmetries. ConclusionDifferent patterns of plasticity occur following partial and profound unilateral deafness. Plasticity occurs both relatively rapidly and more gradually over at least 6-months post-surgery. SignificanceThe different patterns of change over time are consistent with multiple physiological mechanisms of plasticity. Unravelling these mechanisms and their time course in humans may be relevant in understanding and, ultimately, influencing plasticity for therapeutic gain.

Do Studies on Cortical Plasticity Provide a Rationale for Using Non-Invasive Brain Stimulation as a Treatment for Parkinson’s Disease Patients?

Animal models of Parkinson’s disease (PD) have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD-like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of l-DOPA. However, it is still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms by applying repetitive sessions of repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS). The current article will provide an up-to-date overview of these issues together with some reflections on future studies in the field.

Cortical Sensory Plasticity in a Model of Migraine with Aura

The migraine attack is characterized by alterations in sensory perception, such as photophobia or allodynia, which have in common an uncomfortable amplification of the percept. It is not known how these changes arise. We evaluated the ability of cortical spreading depression (CSD), the proposed mechanism of the migraine aura, to shape the cortical activity that underlies sensory perception. We measured forepaw- and hindpaw-evoked sensory responses in rat, before and after CSD, using multielectrode array recordings and two-dimensional optical spectroscopy. CSD significantly altered cortical sensory processing on a timescale compatible with the duration of the migraine attack. Both electrophysiological and hemodynamic maps had a reduced surface area (were sharpened) after CSD. Electrophysiological responses were potentiated at the receptive field center but suppressed in surround regions. Finally, the normal adaptation of sensory-evoked responses was attenuated at the receptive field center. In summary, we show that CSD induces changes in the evoked cortical response that are consistent with known mechanisms of cortical plasticity. These mechanisms provide a novel neurobiological substrate to explain the sensory alterations of the migraine attack.

Frequency dependent effects of rTMS on motor and cognitive functions in Huntington’s disease

Repetitive transcranial magnetic stimulation (rTMS) is an effective non-invasive tool to modulate cortical excitability. In healthy subjects high frequency rTMS applied to primary motor cortex (M1) tends to have excitatory and low frequency rTMS tends to have inhibitory effects. In patients with Huntington’s disease (HD), modulation of M1 excitability with rTMS might be therapeutically beneficial. We therefore studied the effects of M1-rTMS at different frequencies on motor functions in eight patients with genetically confirmed HD. In addition rTMS related effects on cognition and depression were explored. We hypothesized that dependent on the frequency, rTMS of the dominant M1 influences motor functions of ipsi- and contralateral hand differently. In a blinded, sham controlled, cross-over design the effects of 1 and 10Hz rTMS of left M1 on simple (sRT) and choice reaction times (cRT) and time to perform the nine hole peg test (NHPT) were tested for the left and right hand. Additionally digit span test (DST), disability measured by the HD-activity of daily living-score (HD-ADL) and depression according to the Beck Depression Inventory were evaluated. 10Hz rTMS shortened cRT when performed with the left hand and prolonged sRT when performed with the right hand. Unexpectedly, 1Hz rTMS led to a sustained improvement in mood. There was no rTMS related effect on NHPT, DST and the HD-ADL score. Our results are consistent with previous reports of an altered response to rTMS protocols in HD patients and would support the notion of altered cortical plasticity and interhemispheric inhibitory mechanisms in these patients.

CSF Tau Levels Influence Cortical Plasticity in Alzheimer's Disease Patients

Alzheimer's disease (AD) is a neurodegenerative process characterized by progressive neuronal degeneration, reduced levels of neurotransmitters, and altered forms of synaptic plasticity. In animal models of AD, amyloid-β (Aβ) and tau proteins are supposed to interfere with synaptic transmission. In the current study, we investigated the correlation between motor cortical plasticity, measured with 1 Hz repetitive transcranial magnetic stimulation (rTMS), and the levels of Aβ₁₋₄₂, total tau (t-Tau), and phosphorylated tau (p-Tau) detected in cerebrospinal fluid (CSF) of AD patients. We found that the overall rTMS after effects were milder in AD patients in comparison with controls. In AD patients the amount of rTMS-induced inhibition correlated with CSF t-Tau, but not with Aβ₁₋₄₂ CSF levels. Surprisingly, higher CSF t-Tau levels were associated to a stronger inhibition of the motor evoked potentials, implying that the expected effects of the 1 Hz rTMS protocol were more evident in patients with more pathological t-Tau CSF levels. These data could be interpreted as the consequence of CSF t-Tau mediated abnormal excitatory activity and could suggest that CSF t-Tau may impact mechanisms of cortical plasticity.

Naming facilitation induced by transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is able to generate a long-term increase or decrease in the neuronal excitability that can modulate cognitive tasks, similar to repetitive transcranial magnetic stimulation. The aim of this study was to explore the effects of tDCS on a language task in young healthy subjects. Anodal, cathodal and sham tDCS were applied to the left dorsolateral prefrontal cortex (DLPFC) before two picture naming experiments, a preliminary study (i.e., experiment 1) and a main study (i.e., experiment 2). The results show that anodal tDCS of the left DLPFC improves naming performance, speeding up verbal reaction times after the end of the stimulation, whereas cathodal stimulation had no effect. We hypothesize that the cerebral network dedicated to lexical retrieval processing is facilitated by anodal tDCS to the left DLPFC. Although the mechanisms responsible for facilitation are not yet clear, the results presented herein implicate a facilitation lasting beyond the end of the stimulation that imply cortical plasticity mechanisms. The opportunity to non-invasively interact with the functioning of these plasticity mechanisms will surely open new and promising scenarios in language studies in basic and clinical neuroscience fields.

Intracortical Excitability After Repetitive Hand Movements is Differentially Affected in Cortical Versus Subcortical Strokes

Repetitive training of isolated movements induces reorganization of motor cortical representations. To elucidate the mechanisms of practice-dependent cortical plasticity within the lesioned central motor system at the time of the application of a therapeutic intervention, we examined the effect of repetitive movements on intracortical facilitation (ICF) and inhibition of agonist (extensor carpi radialis [ECR]) and antagonist (flexor carpi ulnaris) muscles of the hand shortly after the movements, by the paired-pulse technique in patients with cortical (n = 9) and subcortical strokes (n = 11). Short intracortical inhibition and ICF were studied by using interstimulus intervals of 2 and 8 milliseconds, respectively, and their interaction with active or passive movement. The active movement produced significantly larger motor-evoked potentials in the ECR muscle in both patient groups. Short intracortical inhibition was particularly decreased after cortical stroke, whereas it was still significant after subcortical stroke. ICF increased significantly after movements compared with rest in the ECR for subcortical stroke patients only. We conclude that repetitive active movements increase the excitability of the motor cortex representing the agonist muscle and interact with intracortical facilitatory circuits in the subcortical stroke group but not in the cortical stroke group. This interaction of circuitry has been reported previously in control subjects and seems to still operate after subcortical stroke during active movement. Alternative networks may be recruited for active movement after cortical stroke. This finding proposes lesion-specific mechanisms of reorganization during the same rehabilitative intervention. Distinct rehabilitative strategies may be required to optimize the activation of the physiologic motor network for different lesions.

Dissecting natural sensory plasticity: Hormones and experience in a maternal context

There is a growing consensus that the auditory system is dynamic in its representation of behaviorally relevant sounds. The auditory cortex in particular seems to be an important locus for plasticity that may reflect the memory of such sounds, or functionally improve their processing. The mechanisms that underlie these changes may be either intrinsic because they depend on the receiver’s physiological state, or extrinsic because they arise from the context in which behavioral relevance is gained. Research in a mouse model of acoustic communication between offspring and adult females offers the opportunity to explore both of these contributions to auditory cortical plasticity in a natural context. Recent works have found that after the vocalizations of infant mice become behaviorally relevant to mothers, auditory cortical activity is significantly changed in a way that may improve their processing. Here we consider the hypothesis that maternal hormones (intrinsic factor) and sensory experience (extrinsic factor) contribute together to drive these changes, focusing specifically on the evidence that well-known experience-dependent mechanisms of cortical plasticity can be modulated by hormones.

Regulation of mGluR potentiation by Pin1 peptidyl-prolyl isomerase

Group 1 metabotropic glutamate receptor (mGluR1/5) signaling has been implicated in mechanisms of cortical development, neurodegenerative diseases, associative learning, addiction and neural plasticity. These receptors are localized to the post-synaptic density and upon activation evoke a slow inward current. Strong stimuli, such as seizures, activation of dopamine receptors by amphetamines or exposure to new environment, act via the TrkB kinase cascade to phosphorylate the C-terminal domain of mGluR5 and result in subsequent prolonged potentiation of the mGluR-mediated slow inward current.This phosphorylation dependent signaling pathway has been shown to rely on the rapid upregulation of an immediate early gene coding for Homer 1a protein and its interaction with a specific proline-directed phosphorylation site in the mGluR. Homer 1a was believed to act via simple competition with other Homer family proteins that contain a coiled-coil multimerization domain, absent in Homer1a, thus disrupting physical receptor-receptor couplings maintained by these proteins. More recently, electro-physiological experiments performed at Dr. Worley's lab have indicated that catalytic action of Pin1 peptidyl-prolyl isomerase is essential in the regulation of this pathway. However, the actual mechanism of this three-component switch remains unknown.We are using NMR techniques to investigate the molecular basis for Pin1 and Homer 1a facilitated regulation of the mGluR5. Our results so far suggest a kinetic-trap based switching mechanism for mGluR5-mediated current potentiation.

Alterations of the Visual Perception in Advanced Age-Related Macular Degeneration

Age-related macular degeneration is a retinal disease causing the progressive loss of macular vision, typically in people over 60 years of age. It will become a major public health problem in the next years as the population of aged people is expected to increase. In the advanced stage of the disease, development of the central retinal lesion provokes a central scotoma in the visual fi eld. Consequently, at this stage, patients only rely on the use of peripheral vision to achieve visual tasks. The exclusive use of the peripheral retina itself modifi es visual perception by reducing visual acuity and con- trast sensitivity, and by increasing crowding effects, i.e. contour interaction. Visual perception is further modifi ed by mechanisms of cortical plasticity taking place following the development of the retinal lesion. These mechanisms induce a variety of perceptual changes including fi lling-in, altered perception of space and Charles Bonnet syndrome. While some modifi cations of visual perception, such as reduction of visual acuity and contrast sensitivity are well known, occurrence of other phenomena like crowding effect and Charles Bonnet syndrome is generally underestimated. The aim of this review is to discuss the major factors modifying visual perception in patients with advanced age-related macular degeneration and to relate these phenomena to patients' visual diffi culties in everyday life.

Conditioned lick behavior and evoked responses using whisker twitches in head restrained rats

To examine whisker barrel evoked response potentials in chronically implanted rats during behavioral learning with very fast response times, rats must be calm while immobilized with their head restrained. We quantified their behaviors during training with an ethogram and measured each individual animals’ progress over the training period. Once calm under restraint, rats were conditioned to differentiate between a reward and control whisker twitch, then provide a lick response when presented with the correct stimulus, rewarded by a drop of water. Rats produced the correct licking response (after reward whisker twitch), and learned not to lick after a control whisker was twitched. By implementing a high-density 64-channel electrocorticogram (ECoG) electrode array, we mapped the barrel field of the somatosensory cortex with high spatial and temporal resolution during conditioned lick behaviors. In agreement with previous reports, we observe a larger evoked response after training, probably related to mechanisms of cortical plasticity.

1‐Hz repetitive TMS over ipsilateral motor cortex influences the performance of sequential finger movements of different complexity

To elucidate the role of ipsilateral motor cortex (M1) in the control of unilateral finger movements (UFMs) in humans we used a conditioning protocol of 1-Hz repetitive transcranial magnetic stimulation (1-Hz rTMS) over M1 in 11 right-handed healthy subjects. We analysed the effects of conditioning rTMS on UFMs of different complexity (simple vs sequential finger movements), and performed with a different modality (internally vs externally paced movements). UFMs were monitored with a sensor-engineered glove, and a quantitative evaluation of the following parameters was performed: touch duration (TD); inter-tapping interval (ITI); timing error (TE); and number of errors (NE). 1-Hz rTMS over ipsilateral M1 was able to affect the performance of a sequence of finger opposition movements in a metronome-paced condition, significantly increasing TD and reducing ITI without TE changes. The effects on motor behaviour had a different magnitude as a function of the sequence complexity. Further, we found a different effect of the ipsilateral 1-Hz rTMS on externally paced movements with respect to an internally paced condition. All these findings indicate that ipsilateral M1 plays an important role in the execution of sequential UFMs. Interestingly, NE did not change in any experimental condition, suggesting that ipsilateral M1 influences only the temporal and not the spatial accuracy of UFMs. Finally, the duration (up to 30 min) of 1-Hz rTMS effects on ipsilateral M1 can indicate its direct action on the mechanisms of cortical plasticity, suggesting that rTMS can be used to modulate the communication between the two hemispheres in rehabilitative protocols.

Psychophysiology and imaging of visual cortical functions in the blind: a review.

Imaging, transcranial magnetic stimulation, and psychophysiological recordings of the congenitally blind have confirmed functional activation of the visual cortex but have not extensively explained the functional significance of these activation patterns in detail. This review systematically examines research on the role of the visual cortex in processing spatial and non-visual information, highlighting research on individuals with early and late onset blindness. Here, we concentrate on the methods utilized in studying visual cortical activation in early blind participants, including positron emissions tomography (PET), functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and electrophysiological data, specifically event-related potentials (ERPs). This paper summarizes and discusses findings of these studies. We hypothesize how mechanisms of cortical plasticity are expressed in congenitally in comparison to adventitiously blind and short-term visually deprived sighted participants and discuss potential approaches for further investigation of these mechanisms in future research.

Psychophysiology and Imaging of Visual Cortical Functions in the Blind: A Review

Imaging, transcranial magnetic stimulation, and psychophysiological recordings of the congenitally blind have confirmed functional activation of the visual cortex but have not extensively explained the functional significance of these activation patterns in detail. This review systematically examines research on the role of the visual cortex in processing spatial and non-visual information, highlighting research on individuals with early and late onset blindness. Here, we concentrate on the methods utilized in studying visual cortical activation in early blind participants, including positron emissions tomography (PET), functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and electrophysiological data, specifically event-related potentials (ERPs). This paper summarizes and discusses findings of these studies. We hypothesize how mechanisms of cortical plasticity are expressed in congenitally in comparison to adventitiously blind and short-term visually deprived sighted participants and discuss potential approaches for further investigation of these mechanisms in future research.

Locomotor Training Remodels fMRI Sensorimotor Cortical Activations in Children After Cerebral Hemispherectomy

Purpose. This study examined whether locomotor training, which included body weight—supported treadmill therapy, improved walking and induced cortical representational adaptations using functional magnetic resonance imaging in the remaining sensorimotor network after cerebral hemispherectomy. Methods. Hemispherectomy patients (n = 12) underwent 2 weeks of gait training for at least 30 hours each. They were tested pre- and posttraining with the Fugl-Meyer Motor Assessment, unassisted single-limb stance time, and usual and fastest walking speeds. Three patients performed voluntary ankle movements as the functional magnetic resonance imaging activation task pre- and posttraining. Control subjects included 5 healthy children tested 2 weeks apart, 2 of whom trained on the treadmill, and 2 hemispherectomy patients who received upper extremity rehabilitation and no gait therapy. Results. Although patients reported improvements with gait training, behavioral outcomes did not significantly change. Training was associated with increased volume and intensity of cortical activation in the primary sensorimotor (S1M1), supplementary motor, motor cingulate, and secondary somatosensory cortex for the paretic foot, along with greater overlap in the representation for each moving foot in S1M1 and the supplementary motor area of the remaining hemisphere. Control subjects showed a decrease in activation in these cortical regions after training. Conclusions. Locomotor training of hemispherectomy patients improved mobility subjectively in association with functional magnetic resonance imaging evidence of cortical remodeling with ankle dorsiflexion. These findings support the notion that hemispherectomy patients may respond to rehabilitation interventions through mechanisms of activity-dependent cortical plasticity. The authors hypothesize that developmentally persistent descending ipsilateral and contralateral corticospinal tracts may allow the remaining hemisphere to maintain bilateral lower extremity motor control after surgery.

Multimodal fMRI tractography in normal subjects and in clinically recovered traumatic brain injury patients

In this study, we defined an operator-independent protocol for reconstructing the anatomical connections originating from fMRI activations in order to demonstrate that results obtained with this protocol are affected by alterations of functional activations. Seven healthy volunteers and two patients who sustained traumatic brain injury underwent an fMRI with a finger tapping task and a DTI scan. Cortical fMRI activations were used directly as seed mask for tractography for the reconstruction of individual motor pathways. On patients we observed a different motor network if compared to healthy subjects. However, when the activations of healthy subjects were used as seed masks for the tractography in patients, we observed for the patients a pattern of connectivity more similar to what was observed for healthy subjects. At the same time, when the activations of patients were used for the tractography on healthy subjects, we obtained patterns of connectivity similar to those obtained for patients. These results show the potential of the integration of fMRI and tractography for clarifying the mechanisms of cortical plasticity in the recovery of motor functions.

Cognitive and Behavioral Rehabilitation: from Neurobiology to Clinical Practice

JENNIE PONSFORD (ED): Cognitive and Behavioral Rehabilitation: from Neurobiology to Clinical Practice New York:Guilford Publicatios. 2004, 356 pp., $29.95, ISBN 1-57230-990-3 Cognitive and Behavioral Rehabilitation from Neurobiology to Clinical Practice (the fourth volume in the Guilford Series, The Science and Practice of Neuropsychology) is edited by Jennie Ponsford, Ph.D., M.A., associate professor of psychology at Monash Unviersity and director of the Monash-Epsworth Rehabilitation Research Centre in Melbourne, Australia. Dr. Ponsford has 23 years of experience treating brain injured individuals and with the input of other experts in the field, she presents a volume that seeks to evaluate the scientific evidence available for guiding the timing and duration of treatment and the specific value of interventions for different brain injuries. The foundation for current rehabilitation models is based upon exploration of brain-behavioral relationships and the synthesis of discoveries in neuroscience. The acute brain injury, as defined herein, includes traumatic brain injury (TBI) and strokes, the two most common forms of acute injury. Traumatic brain injury as defined by the National Head Injury Foundation (1989), is an insult to brain caused by external force that may produce diminished or altered states of consciousness, which results in impaired cognitive abilities and/or physical functioning. The primary mechanism of neuronal injury caused by stroke is ischemia, with resulting changes in cell membranes, release of glutamate, and an influx of toxic amounts of calcium into the cells. Diaschisis (distant effects) may also result. Major stroke syndromes are well described in this book. Although there is clear evidence that rehabilitative interventions are effective, we know relatively little about which specific interventions to use for which conditions. There are few good studies that evaluate the scientific evidence and provide guidance as to the timing, duration of treatment, and specific values of interventions for different injuries. And while new tools, such as brain imaging (and eventually tissue transplant and gene manipulations) are helpful, the field of rehabilitation for brain injury is still in its infancy. Chapters 1 and 2 of the book provide valuable information, introducing the neuroscience of acute brain injury, including basic concepts and compensatory processes following injury, mechanisms of cortical plasticity, post-neural injury, and factors affecting recovery. Chapters 3 through 7 cover core cognitive domains: Nonspatial attention, memory, language, visual spatial attention, executive function, and self-awareness. In chapter 8, behavior is addressed, and the final chapter addresses the application of rehabilitation techniques and includes pharmacology, cognitive, and behavioral approaches. It becomes clear that a great deal of work is needed in the development of measures that reflect meaningful behavioral change and in ways of determining injury-related symptoms and/or emotional disorders secondary to handicap, such as depression (there is a 25% incidence of depression in brain injured individuals). …

Recovery in the Blink of an Eye

Sensory deprivation sheds light on cortical plasticity mechanisms, but recovery of lost brain function may bear the greatest clinical relevance. Ramoa and colleagues now find that binocular recovery from monocular occlusion can be extraordinarily rapid, independent of protein synthesis, and precise. Reactivation of latent connections may then reverse amblyopia.