Changes in the hyperpolarization-activated cation currents may represent a protective reaction and act by damping the NMDA receptor-mediated hyperexcitability, rather than converting inhibition into excitation. These findings provide a new hypothesis of cellular changes following hyperthermic seizures in predisposed individuals, and may help in the design of therapeutic strategies to prevent epileptogenesis following prolonged febrile seizures. “
“Most candidate genes and genetic
abnormalities linked to autism spectrum disorders (ASD) are thought to play a role in developmental and experience-dependent plasticity. As a possible index of plasticity, we assessed the modulation selleck screening library of motor corticospinal excitability in individuals with Asperger’s syndrome (AS) using transcranial magnetic stimulation (TMS). We measured the modulatory effects of theta-burst stimulation (TBS) on motor evoked potentials (MEPs) induced GSK 3 inhibitor by single-pulse TMS in individuals with AS as compared with age-, gender- and IQ-matched neurotypical controls. The effect of TBS lasted significantly longer in the AS group. The duration of the TBS-induced modulation alone
enabled the reliable classification of a second study cohort of subjects as AS or neurotypical. The alteration in the modulation of corticospinal excitability in AS is thought to reflect aberrant mechanisms of plasticity, and might provide a valuable future diagnostic biomarker for the disease and ultimately offer a target for novel therapeutic interventions. Autism spectrum disorders (ASD) have become the most prevalent of the developmental disorders, affecting an estimated 1 in every 110 births (Baird et al., 2006; Baron-Cohen et al., 2009) yet their etiology remains unknown. Several investigators
have proposed that aberrant cortical plasticity may play a role in the pathogenesis of ASD (Tsai, 2005; Markram et al., 2007; Dolen & Bear, 2009). Consistent with this hypothesis, many of the genes associated with ASD are involved in various aspects of synaptic development and plasticity (Morrow et al., 2008). Additionally, several animal models of ASD exhibit altered cortical plasticity as characterised by various different measures (for a review see Tordjman et al., 2007). In humans, some neuroanatomical, brain imaging and neurophysiological Quisqualic acid studies in ASD subjects have demonstrated anomalies in cortical excitability and connectivity (Rubenstein & Merzenich, 2003; Belmonte et al., 2004; Geschwind & Levitt, 2007), and these might be consistent with alterations of mechanisms of plasticity (Oberman & Pascual-Leone, 2008). In the present study, we used transcranial magnetic stimulation (TMS) to explore this issue further. Repetitive TMS (rTMS) enables the safe and noninvasive characterization of cortical reactivity mechanisms in humans (Kobayashi & Pascual-Leone, 2003).