Phonologically similar items (mell, rell, gell) are more difficult to remember than dissimilar items (shen, floy, stap), likely because of mutual interference of the items in the phonological store. Low-frequency transcranial magnetic stimulation (TMS), guided by functional magnetic resonance imaging (fMRI) was used to disrupt this phonological confusion by stimulation of the left inferior parietal (LIP) lobule. Subjects received TMS or placebo stimulation while remembering sets of phonologically similar or dissimilar pseudo-words. Consistent with behavioral performance of patients with neurological damage, memory for phonologically similar, but not dissimilar, items was enhanced following TMS relative to placebo stimulation. Stimulation of a control region of the brain did not produce any changes in memory performance. These results provide new insights into how the brain processes verbal information by establishing the necessity of the inferior parietal region for optimal phonological storage. A mechanism is proposed for how TMS reduces phonological confusion and leads to facilitation of phonological memory.

Matthew P. Kirschen

Mathew S. Davis-Ratner

Thomas E. Jerde

Pam Schraedley-Desmond

John E. Desmond

Enhancement of Phonological Memory Following Transcranial Magnetic Stimulation (TMS)

Vincent Walsh

Alvaro Pascual-Leone

Manipulating Brains

This paper reviews the effects of single and repetitive transcranial magnetic stimuli (rTMS) delivered to one cortical area and measured across distributed brain regions using electrophysiological measures (e.g. motor thresholds, motor evoked potentials, paired-pulse stimulation), functional neuroimaging (including EEG, PET and fMRI) and behavioural measures. Discussion is restricted to changes in excitability in the primary motor cortex and behaviour during motor tasks following transcranial magnetic stimulation delivered to primary motor and premotor areas. Trains of rTMS have lasting effects on the excitability of intrinsic and corticofugal neurones, altering the responsiveness of local and remote sites. These effects lead to distributed changes in synaptic activity at rest, and during a range of motor tasks. It is possible to impair or improve performance following rTMS, but for most simple motor tasks performance is unaltered. Changes in distributed activity observed with functional imaging during motor behaviour may represent compensatory activity, enabling maintenance of performance; stimulation of additional cortical areas appears to impair performance. A detailed understanding of the distributed changes in excitability following rTMS may facilitate future attempts to modulate motor behaviour in the healthy brain and for therapeutic purposes.

Lucy Lee

Hartwig Siebner

Sven Bestmann

Rapid Modulation of Distributed Brain Activity by Transcranial Magnetic Stimulation of Human Motor Cortex

This paper concerns the ethics of human neuromodulation using transcranial magnetic stimulation (TMS). We examine the challenges of modulating the brain with TMS through the research ethics lens and in clinical medicine for treating frank pathology, primarily in psychiatric diseases. We also consider contemporary issues raised in the neuroethics literature about managing unexpected findings, and relate these to TMS and to other frontier neurotechnology that is becoming openly available in the public domain. We argue that safety and informed consent are of paramount importance for TMS, but that personal values and sociocultural factors must also be considered when examining the promise of this technology and applications that ought to be highlighted for extra precautions.

Judy Illes

Marisa Gallo

An Ethics Perspective on Transcranial Magnetic Stimulation (TMS) and Human Neuromodulation

Hemispatial neglect refers to the defective ability of patients to explore or act upon the side of space contralateral to the lesion and to attend to stimuli presented in that portion of space. Evidence from animal models suggests that many of the behavioural sequelae associated with visual neglect may result not solely from the size of the lesion, but also from a pathological state of increased inhibition exerted on the damaged hemisphere by the contralesional hemisphere. On the basis of these potential mechanisms underlying neglect, in this review we discuss therapeutic approaches, focusing particularly on recent research using transcranial magnetic stimulation (TMS). This technique, besides representing an ideal tool to investigate visuo-spatial attentive mechanisms in humans, has shown promising beneficial effects that might have an impact on clinical practice.

Brigida Fierro

Filippo Brighina

Edoardo Bisiach

Improving Neglect by TMS

We review a series of studies exemplifying some applications of single-pulse and paired-transcranial magnetic stimulation (TMS) in the study of spatial attention and of its deficits. We will focus primarily on sensory extinction, the failure to consciously perceive a contralesional sensory stimulus only during bilateral stimulation of homologous surfaces. TMS studies in healthy controls show that it is possible either to interfere or modulate the excitability of the parietal cortex during sensory (i.e. tactile and visual) attentional tasks, thus reproducing a condition of virtual extinction. TMS studies in patients with unilateral (mainly right) brain damage show that the modulation of the unbalance in cortical excitability between the two cerebral hemispheres transiently improves contralesional sensory extinction. These studies show the possible application of TMS not only as a research method in healthy subjects, but also as a tool for inducing brain excitability changes in patients with sensory extinction, which could be useful for supporting the rehabilitation of this deficit.

Massimiliano Oliveri

Carlo Caltagirone

Suppression of Extinction with TMS in Humans: From Healthy Controls to Patients

Neuroimaging studies and experimental data suggest that symptoms of posttraumatic stress disorder (PTSD) are associated with dysfunctions of neural circuits linking prefrontal cortex and the limbic system that have a role in autobiographic episodic memory. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been suggested to be beneficial to patients with PTSD, transiently alleviating re-experiencing as well as avoidance reactions and associated anxiety symptoms. In healthy humans, converging evidence suggests that rTMS of the right DLPFC interferes with episodic memory retrieval. Hence, we hypothesize that daily applications of rTMS in PTSD patients may reduce access to the set of autobiographical stored events, that, if re-experienced, may cause the overt PTSD symptoms.

Simone Rossi

Stefano F. Cappa

Monica Ulivelli

Alberto De Capua

Sabina Bartalini

Paolo M. Rossini

rTMS For PTSD: Induced Merciful Oblivion or Elimination of Abnormal Hypermnesia?

The enhancement of cognitive function in healthy subjects by medication, training or intervention yields increasing political, social and ethical attention. In this paper facilitatory effects of single-pulse TMS and repetitive TMS on a simple picture naming task are presented. A significant shortening of picture naming latencies was observed after single-pulse TMS over Wernicke's area. The accuracy of the response was not affected by this speed effect. After TMS over the dominant motor cortex or over the non-dominant temporal lobe, however, no facilitation of picture naming was observed. In the rTMS experiments only rTMS of Wernicke&#x2019;s area had an impact on picture naming latencies resulting in a shortening of naming latencies without affecting the accuracy of the response. rTMS over the visual cortex, Broca's area or over the corresponding sites in the non-dominant hemisphere had no effect. Single-pulse TMS is able to facilitate lexical processes due to a general preactivation of language-related neuronal networks when delivered over Wernicke's area. Repetitive transcranial magnetic stimulation over Wernicke&#x2019;s area also leads to a brief facilitation of picture naming possibly by shortening linguistic processing time. Whether TMS or rTMS can be used to aid linguistic therapy in the rehabilitation phase of aphasic patients should be subject of further investigations.

Felix M. Mottaghy

Roland Sparing

Rudolf T&#xf6;pper

Enhancing Picture Naming with Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS)-induced virtual lesions in healthy subjects can be used to test neurofunctional models of disease. The interhemispheric rivalry model of heminglect is well suited for such investigations, as simple predictions derived from clinical data can be tested without the caveats normally associated with lesion studies. One of these predictions is that release from contralateral inhibition should lead to increased parietal responsiveness, which, in turn, would enhance spatial attention. Here, we detail studies showing TMS-induced paradoxical functional facilitation of attention in healthy individuals and highlight their contribution to the understanding and treatment of neglect syndromes.

Shirley Fecteau

Hugo Th&#xe9;oret

Paradoxical Facilitation of Attention in Healthy Humans

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