Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the ...understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit ...activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities.
This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment.
The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs.
Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them.
These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders.
•This NIMH workshop report seeks to promote the science, technology and effective clinical applications of tDCS and tACS.•Knowledge of how tES induces behavioral change in humans is limited. Mechanistic studies aimed at this question are needed.•Improved reporting of protocols and use of computational models to relate dose to current flow in brain will be important.•Predictive biomarkers, target engagement measures, and rigorous study designs are critical for advancing clinical trials.•The above elements align with requirements in NIMH funding opportunity announcements and are important for reproducibility.
Minicolumnar changes that generalize throughout a significant portion of the cortex have macroscopic structural correlates that may be visualized with modern structural neuroimaging techniques. In ...magnetic resonance images (MRIs) of fourteen autistic patients and 28 controls, the present study found macroscopic morphological correlates to recent neuropathological findings suggesting a minicolumnopathy in autism. Autistic patients manifested a significant reduction in the aperture for afferent/efferent cortical connections, i.e., gyral window. Furthermore, the size of the gyral window directly correlated to the size of the corpus callosum. A reduced gyral window constrains the possible size of projection fibers and biases connectivity towards shorter corticocortical fibers at the expense of longer association/commisural fibers. The findings may help explain abnormalities in motor skill development, differences in postnatal brain growth, and the regression of acquired functions observed in some autistic patients.
It is widely accepted that dyslexics have deficits in reading and phonological awareness, but there is increasing evidence that they also exhibit visual processing abnormalities that may be confined ...to particular portions of the visual system. In primate visual pathways, inputs from parvocellular or magnocellular layers of the lateral geniculate nucleus remain partly segregated in projections to extrastriate cortical areas specialized for processing colour and form versus motion. In studies of dyslexia, psychophysical and anatomical evidence indicate an anomaly in the magnocellular visual subsystem. To investigate the pathophysiology of dyslexia, we used functional magnetic resonance imaging (fMRI) to study visual motion processing in normal and dyslexic men. In all dyslexics, presentation of moving stimuli failed to produce the same task-related functional activation in area V5/MT (part of the magnocellular visual subsystem) observed in controls. In contrast, presentation of stationary patterns resulted in equivalent activations in V1/V2 and extrastriate cortex in both groups. Although previous studies have emphasized language deficits, our data reveal differences in the regional functional organization of the cortical visual system in dyslexia.
Recent research in neurodevelopment, neuroplasticity and genetics is providing new insights into the etiogenesis of psychopathology, but progress in treatment development has been hampered by ...reliance on diagnostic categories that are characterized by heterogeneity and based primarily on phenomenology. The NIMH Research Domain Criteria (RDoC) initiative seeks to provide a neuroscience-based nosological framework for future research on psychopathology, categorizing individuals for research purposes using a dimensional approach that capitalizes on advances in modern neuroscience. These scientific advances and new approaches to classification can inform the development of novel, circuit-based interventions and the personalization of treatment. In this paper, we review key advances areas in clinical neuroscience, describe the RDoC project and highlight some emerging treatment approaches that are consistent with these developments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Dyslexia is a specific learning disability that affects the way in which a person acquires reading skills. The pathologic substrate of the condition has been debated in the literature. Conclusions ...from postmortem studies remain controversial because series have been based on few and often ill-characterized cases. The present article expands on one of the reported neuropathologic findings in dyslexia, that is, wider minicolumns. Measurements were made of magnetic resonance images in a series of 16 dyslexic and 14 age- and sex-matched controls. Dyslexic patients had significantly smaller total cerebral volume (P = .014) and reduced gyrification index (P = .021). No changes were noted in cortical thickness, the ratio of gray to white matter, or the cross-sectional areas of the corpus callosum and medulla oblongata. The findings, although not conclusive, are in keeping with a minicolumnar defect in dyslexia. The decreased gyrification and preserved cortical thickness can alter the information processing capacity of the brain by providing a greater degree of cortical integration at the expense of a slower response time. The article also emphasizes the contrast between findings in dyslexia and in autism. (J Child Neurol 2004;19:275-281).
Recent studies provide credence to the minicolumnar origin of several developmental conditions, including dyslexia. Characteristics of minicolumnopathies include abnormalities in how the cortex ...expands and folds. This study examines the depth of the gyral white matter measured in an MRI series of 15 dyslexic adult men and eleven age-matched comparison subjects. Measurements were based upon the 3D Euclidean distance map inside the segmented cerebral white matter surface. Mean gyral white matter depth was 3.05 mm (SD ± 0.30 mm) in dyslexic subjects and 1.63 mm (SD ± 0.15 mm) in the controls. The results add credence to the growing literature suggesting that the attained reading circuit in dyslexia is abnormal because it is inefficient. Otherwise the anatomical substratum (i.e., corticocortical connectivity) underlying this inefficient circuit is normal. A deficit in very short-range connectivity (e.g., angular gyrus, striate cortex), consistent with results of a larger gyral window, could help explain reading difficulties in patients with dyslexia. The structural findings hereby reported are diametrically opposed to those reported for autism.
Pronunciation (of irregular/inconsistent words and of pseudowords) and lexical decision-making tasks were used with 15O PET to examine the neural correlates of phonological and orthographic ...processing in 14 healthy right-handed men (aged 18-40 years). Relative to a visual-fixation control task, all four experimental tasks elicited a left-lateralized stream of activation involving the lingual and fusiform gyri, perirolandic cortex, thalamus and anterior cingulate. Both pronunciation tasks activated the left superior temporal gyrus, with significantly greater activation seen there during phonological (pseudoword) than during orthographic (real word) pronunciation. The left inferior frontal cortex was activated by both decision-making tasks; more intense and widespread activation was seen there during phonological, than during orthographic, decision making, with the activation during phonological decision-making extending into the left insula. Correlations of reference voxels in the left superior temporal gyrus and left inferior frontal region with the rest of the brain were highly similar for the phonological and orthographic versions of each task type. These results are consistent with connectionist models of reading, which hypothesize that both real words and pseudowords are processed within a common neural network.
Functional imaging studies of developmental dyslexia have reported reduced task-related
neural activity in the temporal and inferior parietal cortices. To examine the possible
contribution of subtle ...anatomic deviations to these reductions, volumes were measured for
the major lobes of the brain, the subcortical nuclei, cerebellum, and lateral ventricles on
magnetic resonance imaging (MRI) scans from 16 right-handed dyslexic men, ages 18 to 40,
and 14 matched controls, most of whom had previously undergone PET imaging. A specific
decrease in tissue volume was localized to the temporal lobes and was particularly prominent
on the left (p < .01). An analysis of tissue composition revealed that this reduction was
primarily attributable to decreased gray matter within the left temporal lobe (p < .002).
Further segmentation of the temporal lobe showed that this reduction was not confined to
the superior temporal gyrus, the primary location of primary auditory cortex. Reductions of
temporal lobe gray matter may reflect a regional decrease in neuronal number or neuropil,
which in turn may result in reading impairment.
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