Brain plasticity-based therapeutics

Michael M Merzenich, Thomas M Van Vleet, Mor Nahum, Michael M Merzenich, Thomas M Van Vleet, Mor Nahum

Abstract

The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from (a) the more-behavioral, traditional clinical strategies of professional therapy practitioners, and (b) an even more widely applied pharmaceutical treatment model for neurological and psychiatric treatment domains. With that background, we shall argue that neuroplasticity-based treatments will be an important part of future best-treatment practices in neurological and psychiatric medicine.

Keywords: aging; brain plasticity; computerized training; hemispatial neglect; neuroplasticity; schizophrenia.

Figures

Figure 1
Figure 1
Illustrating positive far-transfer chemical, behavioral, and brain response changes attributable to intensive brain training in patients with chronic schizophrenia (SZ). Tasks targeted the auditory-aural language/perceptual-cognitive system. Training was via computers, over a 40–50 hour-long training period. (A) Brain-Derived Neurotrophin Factor (BDNF) in its “pro” and mature (“m”) forms is down-regulated in schizophrenia and in other chronic neurological and psychiatric illnesses (e.g., healthy aging). As a result of this brain plasticity-based training, serum levels of BDNF were elevated to normal levels; no changes were recorded in subjects who worked with equivalent intensity on progressive control video games. The up-regulated of BDNF to near-normal levels was sustained for more than a year following training program completion. Similar effects have been recorded in aging brains. Data are from Vinogradov et al. (2009). (B) Left: Re-normalization of abilities in a behavioral task in which subjects with SZ identify whether they or an outside agent was the source of an immediate-past action. Again, this is a transfer effect of training; no aspect of this task is represented in the completed training regime. Right: Strengthening of BOLD responses in a medial prefrontal cortical area hypothesized to be the primary cortical site for the assignment of agency in the brain. No measurable task-related activity was recorded in this area in subjects with SZ prior to training, or in computer brain-engaged SZ controls before or after training. From Subramaniam et al. (2012). (C) Brain images showing changes in responses recorded in this task. Abbreviations: CG, computer games control; AT, auditory training; SZ-AT, schizophrenia patients in the auditory training group; SZ-CG, schizophrenia patients in the computer games group; HC, healthy controls.
Figure 2
Figure 2
Hemispatial neglect syndrome patients are slow to identify target stimuli arising in the neglected visual hemifield. Training designed to recover the functionality of intrincsic alertness over a period of 6 h was adequate for achieving recovery when examined within 48 h post-training. Data from 20 neglect patients with a wide panoply of brain-injury etiologies. (e.g., tumor, stroke, TBI). Display time significantly shortened following training. Note that this is a “transfer” effect, as training involving the identification of objects, scenes, or tones was presented at central fixation (i.e., not in the neglected field). Redrawn from DeGutis and Van Vleet (2010) and Van Vleet and DeGutis (2013).
Figure 3
Figure 3
Illustrating the magnitudes of gains for a limited computer delivered epoch of training (about 10 h) in a large (n = 670) cohort of healthy aged participants. Training was conducted “at home” or in a clinical center at the University of Iowa. One population in the clinical center completed a 4-h “booster” training session 6 months after initial training program completion. All patients were behaviorally assessed before, immediately after, and 1 year after training program completion. Here, gains are expressed as an estimate of the number of years before assessment scores would be predicted to fall below pre-training scores; these highly significant gains had an average endurance of 3–4 years. Note that the “UFOV composite” reflects the approximately 1 SD gain in brain speed and visual control within an expanded visual field achieved directly from the training. All other measures represent near and far-transfer effects (i.e., benefits shown in untrained cognitive domains). Adapted from Wolinsky et al. (2013).

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