While previous studies have suggested mirror system alterations in BPD, still little is
known about the integrity of a basic neurophysiological mechanism such as brain
plasticity within these systems. Considering that the development of mentalization and
empathic abilities appears to rely on early associative learning and metaplasticity, it
has been suggested that the pathophysiology of BPD may be associated with alterations in
neuronal plasticity, mediated by N-methyl-D-aspartate (NMDA) neurotransmission; however,
evidence is still lacking. Importantly, the integrity of plasticity mechanisms may
represent a critical factor for the effectiveness of therapeutic interventions.
Paired associative stimulation (PAS) protocols represent a well-established tool to
non-invasively induce brain plasticity effects in humans. To induce changes in synaptic
efficacy, PAS protocols exploit the Hebbian learning rule and the concept of spike-timing
dependent plasticity observed at the cellular level, namely that neural connections are
strengthened (or weakened) in the case of repeated activations of the presynaptic neuron
before the postsynaptic neuron (or vice-versa) in a critical time interval of a few tens
of ms. In classical PAS protocols targeting the somatosensory system (S1-PAS), a
peripheral electrical stimulus over the wrist (acting as presynaptic activation) is
repeatedly paired with a transcranial magnetic stimulation (TMS) pulse over S1 in the
contralateral hemisphere (acting as postsynaptic activation). Depending on the time
interval between the two stimuli, the S1-PAS may induce long-term potentiation or
depression (LTP- or LTD-like, respectively) effects, lasting up to 30 minutes after
protocol delivery. In addition to neurophysiological effects (i.e., somatosensory evoked
potential modulation), these plastic mechanisms have also been detected by exploiting
behavioral measures of S1 functioning, such as tactile acuity.
PAS protocols have also been used to target multisensory integration networks: here, the
peripheral and cortical stimuli belong to different systems. Recently, a cross-modal PAS
(cm-PAS) has been developed in the visuo-tactile domain, with the aim of targeting the
Tactile Mirror System. Compared to classical S1-PAS, in cm-PAS the peripheral electrical
stimulus on the wrist is replaced by a visual stimulus of a hand being touched. The
efficacy of the cm-PAS in inducing LTP-like mechanisms has been shown in a series of
experiments, consisting of an increase in tactile acuity that was specific for the time
interval between the visual stimulus and the TMS, for the site of cortical stimulation,
and for the content of the visual stimulus. Moreover, cm-PAS modulated a
neurophysiological correlate of S1 activity, namely, the amplitude of the P40 component
of somatosensory-evoked potentials increased after cm-PAS. Overall, these findings are
consistent with the hypothesis that when seeing a human touch on someone else's body, S1
is recruited by mirror-like mechanisms and can be involved in plasticity mechanisms.
Taking together the existing evidence, the present study aims to shed light on the neural
basis of interpersonal dysfunction in BPD by bridging the gap between the literature on
empathic alterations in BPD patients on the one hand and on the neurophysiological
underpinnings of TaMS and its plastic properties in the healthy population on the other
hand. Specifically, the integrity of plastic modulations within the Tactile Mirror System
will be investigated in BPD patients, by employing the previously described cm-PAS.
The present study will involve BPD 24 patients and 24 healthy controls (HCs) undergoing
two sessions of cm-PAS, i.e., an experimental session and a control session. BPD patients
will be matched one-to-one with HCs for gender and age. The two groups will be compared
in the cognitive dimensions of empathic abilities, measured by means of a self-report
questionnaire (Questionnaire for Cognitive and Affective Empathy). To assess the effects
of the cm-PAS, both groups will undergo a behavioral task involving visuo-tactile
stimuli, before and after the cm-PAS protocol, and performance will be evaluated in terms
of accuracy and reaction times.