ReviewEnhancement of human cognitive performance using transcranial magnetic stimulation (TMS)
Introduction
Cognitive enhancement can be defined as any augmentation of core information processing systems in the brain, including the mechanisms underlying perception, attention, conceptualization, memory, reasoning and motor performance (Sandburg and Bostrom, 2006). As Sandburg and Bostrom point out, physiological approaches towards cognitive enhancement have tended towards pharmaceutical research. However, this review will suggest that non-invasive brain stimulation, specifically transcranial magnetic stimulation (TMS), may be a promising alternative. TMS uses very brief high intensity magnetic fields to induce currents and thus depolarize neurons in small regions of cortex. The neural effects of TMS depend on the frequency of stimulation. When the frequency of TMS stimulation is 1 Hz or greater, the stimulation is called repetitive TMS (rTMS). If rTMS is pulsed at a low frequency (about 1 Hz), cortical excitability generally decreases, while higher frequency rTMS (usually between 5 and 20 Hz) can increase cortical excitability (Chen et al., 1997, Pascual-Leone et al., 1994). This ability to up- or down-regulate cortical excitability, along with its high temporal resolution, suggests that TMS might be a useful tool to manipulate cortical networks in ways that could alter cognitive performance.
Reports of TMS acting to cause cognitive enhancement occurred soon after its introduction as a research tool, with studies observing speeded response in simple reaction time (RT) tasks (Pascual-Leone et al., 1992) and better memory recall (Pascual-Leone et al., 1993, Wassermann et al., 1996), although in the former case the speeded RTs were explained by a general psychological attention effect rather than a specific effect on the stimulated cortex (Terao et al., 1997), and in the latter cases the effects did not reach statistical significance. Nonetheless, beginning in the late 1990s reports of statistically significant findings of TMS-induced performance enhancements have accumulated.
In the context of cognitive processing, initial reports of facilitated performance were somewhat surprising, as TMS was thought to be a disruptive agent, producing random firing of a population of neurons, generating neural noise that interfered with ongoing processing, thus producing a temporary virtual lesion. Some early studies reporting performance enhancement with TMS suggested a mechanism of “paradoxical” facilitation, in which TMS selectively disrupted the processing of distracting stimulus elements, allowing task-relevant processing occurring at separate locations to proceed more smoothly (e.g., Walsh et al., 1998). In other studies a paradoxical explanation seemed unlikely, as the areas stimulated were thought to be central to the relevant task processing (e.g., Boroojerdi et al., 2001, Grosbras and Paus, 2002). In these cases, TMS may have acted directly on targeted cortex to cause changes that facilitated, rather than disrupted, processing.
While the particular target of stimulation is of course central, whether TMS is disruptive or facilitatory may also depend on other stimulation parameters, such as the frequency, duration, and timing relative to a given task. For example, one form of working memory (WM) task is the delayed-match-to-sample, in which a set of stimulus items is encoded, followed by a delay period, and then a test item which is to be responded to as being a member of the encoded set or not. In an initial finding, a train of 5 Hz rTMS applied to dorsolateral prefrontal cortex during the delay period was shown to increase errors in the task (Pascual-Leone and Hallett, 1994). A number of other studies have also demonstrated disruptive effects of TMS in delayed-match-to-sample tasks (Cattaneo et al., 2009a, Desmond et al., 2005, Feredoes et al., 2007, Hamidi et al., 2009a, Herwig et al., 2003, Koch et al., 2005, Mottaghy et al., 2002). When letter stimuli were used as the encoded items, 15 Hz trains applied during the delay period to left premotor cortex (Herwig et al., 2003) and 10 Hz trains to left temporo-parietal cortex (Feredoes et al., 2007) also decreased accuracy. On the other hand, 5 Hz trains applied during the delay period to midline parietal cortex speeded RT without decreasing accuracy (Luber et al., 2007a). In addition, in Luber et al.'s study, it was only 5 Hz stimulation, and not 1 Hz or 20 Hz that resulted in performance enhancement. These studies suggest that processing essential to the WM task may occur (and be disrupted by rTMS) during the delay period in left premotor and temporo-parietal cortex, while task-related processing occurs in midline parietal cortex in the test phase of the task, with frequency-specific stimulation prior to that phase aiding processing. Task-phase sensitivity to disruption or enhancement by TMS was also demonstrated in Cattaneo et al. (2009a), where single pulses applied to occipital cortex in the test phase slowed RT, while those applied in the delay phase enhanced RT: TMS in the former condition presumably disrupted processing of the test stimulus, while in the latter condition prior TMS aided processing.
After a search of the literature, we found sixty-one instances of performance enhancement associated with TMS. These included reports of better perceptual discrimination and motor learning, faster eye movements, and speeded visual search and object identification, as well as superior performance on tasks involved in attention, memory, and language. Enhancement has been reported using various TMS paradigms, including single pulse, theta burst, paired pulse, and trains of rTMS at both low and high frequencies. These various forms of TMS are thought to affect cerebral cortex differently, some acutely disrupting processing with the addition of neural noise or briefly inhibiting or facilitating activity, and others modulating cortical excitability up or down for periods beyond the stimulation. As such this suggests that multiple mechanisms are involved with TMS enhancement effects, and our survey suggested that these potential mechanisms could be grouped into three classes: nonspecific effects of TMS, direct modulation of a cortical region or network that leads to more efficient processing, and disruption of competing or distracting processing (i.e., addition-by-subtraction). The next three sections discuss these classes. It should be pointed out that the expectation from its beginnings has been that TMS will cause a disruption in processing and performance, and in general the finding of an enhancement has usually been a surprise. The classifications and mechanisms offered in the next sections are an attempt to sort out possibilities behind TMS cognitive enhancement, acknowledging that explanations are still post hoc and in the suggestion, rather than prediction, phase.
Section snippets
Enhancement via nonspecific effects of TMS
Better performance in tasks need not be the result of direct influence on cortical processing. TMS also produces a number of superficial effects, including a clicking sound and mechanical vibrations passed from the coil to the scalp. These peripheral auditory and somatosensory sensations can cause a phenomenon called intersensory facilitation (IF: Terao et al., 1997). Specifically, if the TMS pulse occurs closely in time with the onset of a stimulus to be responded to, speeded RT can result a
Enhancement mechanisms involved with direct TMS to task-related cortex
This class of mechanism relies on direct interaction of TMS with neural activity in an area needed for task performance. Single TMS pulses occurring immediately before the onset of a stimulus to be responded to have produced performance enhancements (Grosbras and Paus, 2002, Grosbras and Paus, 2003, Topper et al., 1998), suggesting the pulse potentiates local neural activity for a brief period. Grosbras and Paus, 2002, Grosbras and Paus, 2003 found that stimulation delivered 40 ms before the
Enhancement via “addition-by-subtraction”
Another class of mechanism by which TMS might produce cognitive enhancement is through disruption of processing which competes or distracts from task performance. This type of mechanism can be thought of as addition-by-subtraction, and can be illustrated by a study of visual search (Walsh et al., 1998). Single pulse TMS applied during stimulus presentation to a superior occipital site resulted in an improvement in performance in a visual search task in certain conditions. The task involved
Potential uses of TMS-induced performance enhancement
Potential applications of TMS cognitive enhancement include research into cortical function, treatment of neurological and psychiatric illness, and skill acquisition in healthy individuals.
Manipulation of enhancement effects adds to the experimental palette of brain stimulation techniques examining cortical processing. For example, 1 Hz rTMS inhibition of V5 led to the understanding of a spatial suppression effect in visual motion perception (Tadin et al., 2011). Right parietal stimulation
Refinement of TMS enhancement induction techniques
The potential applications of TMS cognitive enhancement are exciting, but they presently remain at the stage of promise. This is because the reported enhancement effects are in general weak in size and short-lived, lasting from a few seconds in the case of short stimulation trains to 10 min to an hour with offline stimulation. However, TMS is still a relatively new technology, and there is much that can be done to optimize its use. TMS targeting can still be improved and more fully integrated
Conclusion
Over sixty reports of TMS performance enhancement have accumulated over the last decade and a half, and many more are likely as the technology of TMS is refined, and as knowledge of cortical network dynamics builds. Increasing our understanding of enhancement mechanisms such as addition-by-subtraction, potentiating oscillatory behavior, and promotion of Hebbian-type learning may result in acute facilitation of skills needed to interact with ever more complex information technology as well as
Acknowledgments
This review was funded in part by NIH grant K01 AG031912.
Conflict of interest statement
Dr. Luber has no conflicts of interest. Dr. Lisanby has received research support from Magstim, MagVenture, Neuronetics, Cyberonics, and ANS/St. Jude. Columbia University has applied for a patent for novel TMS technology developed in Dr. Lisanby’s Lab.
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