Lindsay M. Oberman

The Simulating Social Mind: The Role of the Mirror Neuron System and Simulation in the Social and Communicative Deficits of Autism Spectrum Disorders.

The mechanism by which humans perceive others differs greatly from how humans perceive inanimate objects. Unlike inanimate objects, humans have the distinct property of being “like me” in the eyes of the observer. This allows us to use the same systems that process knowledge about self-performed actions, self-conceived thoughts, and self-experienced emotions to understand actions, thoughts, and emotions in others. The authors propose that internal simulation mechanisms, such as the mirror neuron system, are necessary for normal development of recognition, imitation, theory of mind, empathy, and language. Additionally, the authors suggest that dysfunctional simulation mechanisms may underlie the social and communicative deficits seen in individuals with autism spectrum disorders.

Face to face: Blocking facial mimicry can selectively impair recognition of emotional expressions

Abstract People spontaneously mimic a variety of behaviors, including emotional facial expressions. Embodied cognition theories suggest that mimicry reflects internal simulation of perceived emotion in order to facilitate its understanding. If so, blocking facial mimicry should impair recognition of expressions, especially of emotions that are simulated using facial musculature. The current research tested this hypothesis using four expressions (happy, disgust, fear, and sad) and two mimicry-interfering manipulations (1) biting on a pen and (2) chewing gum, as well as two control conditions. Experiment 1 used electromyography over cheek, mouth, and nose regions. The bite manipulation consistently activated assessed muscles, whereas the chew manipulation activated muscles only intermittently. Further, expressing happiness generated most facial action. Experiment 2 found that the bite manipulation interfered most with recognition of happiness. These findings suggest that facial mimicry differentially contributes to recognition of specific facial expressions, thus allowing for more refined predictions from embodied cognition theories.

Modulation of mu suppression in children with autism spectrum disorders in response to familiar or unfamiliar stimuli: the mirror neuron hypothesis.

In an early description of the mu rhythm, Gastaut and Bert [Gastaut, H. J., & Bert, J. (1954). EEG changes during cinematographic presentation. Clinical Neurophysiology, 6, 433-444] noted that it was blocked when an individual identified himself with an active person on the screen, suggesting that it may be modulated by the degree to which the individual can relate to the observed action. Additionally, multiple recent studies suggest that the mirror neurons system (MNS) is impaired in individuals with autism spectrum disorders (ASD), which may affect their ability to relate to others. The current study aimed to investigate MNS sensitivity by examining mu suppression to familiarity, i.e., the degree to which the observer is able to identify with the actor on the screen by using familiar versus unfamiliar actors. The participants viewed four 80s videos that included: (1) stranger: an unfamiliar hand performing a grasping action; (2) familiar: the childs guardian or siblings hand performing the same action; (3) own: the participants own hand performing the same action; (4) bouncing balls: two balls moving vertically toward and away from each other. The study revealed that mu suppression was sensitive to degree of familiarity. Both typically developing participants and those with ASD showed greater suppression to familiar hands compared to those of strangers. These findings suggest that the MNS responds to observed actions in individuals with ASD, but only when individuals can identify in some personal way with the stimuli.

The human mirror neuron system: A link between action observation and social skills

The discovery of the mirror neuron system (MNS) has led researchers to speculate that this system evolved from an embodied visual recognition apparatus in monkey to a system critical for social skills in humans. It is accepted that the MNS is specialized for processing animate stimuli, although the degree to which social interaction modulates the firing of mirror neurons has not been investigated. In the current study, EEG mu wave suppression was used as an index of MNS activity. Data were collected while subjects viewed four videos: (1) Visual White Noise: baseline, (2) Non-interacting: three individuals tossed a ball up in the air to themselves, (3) Social Action, Spectator: three individuals tossed a ball to each other and (4) Social Action, Interactive: similar to video 3 except occasionally the ball would be thrown off the screen toward the viewer. The mu wave was modulated by the degree of social interaction, with the Non-interacting condition showing the least suppression, followed by the Social Action, Spectator condition and the Social Action, Interactive condition showing the most suppression. These data suggest that the human MNS is specialized not only for processing animate stimuli, but specifically stimuli with social relevance.

Characterizing Brain Cortical Plasticity and Network Dynamics Across the Age-Span in Health and Disease with TMS-EEG and TMS-fMRI

Brain plasticity can be conceptualized as nature’s invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the lifespan. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable ‘starting-points’ and different ‘slopes of change’ defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer’s disease.

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature.

Theta burst stimulation (TBS) protocols have recently emerged as a method to transiently alter cortical excitability in the human brain through repetitive transcranial magnetic stimulation. TBS involves applying short trains of stimuli at high frequency repeated at intervals of 200 milliseconds. Because repetitive transcranial magnetic stimulation is known to carry a risk of seizures, safety guidelines have been established. TBS has the theoretical potential of conferring an even higher risk of seizure than other repetitive transcranial magnetic stimulation protocols because it delivers high-frequency bursts. In light of the recent report of a seizure induced by TBS, the safety of this new protocol deserves consideration. We performed an English language literature search and reviewed all studies published from May 2004 to December 2009 in which TBS was applied. The adverse events were documented, and crude risk was calculated. The majority of adverse events attributed to TBS were mild and occurred in 5% of subjects. Based on this review, TBS seems to be a safe and efficacious technique. However, given its novelty, it should be applied with caution. Additionally, this review highlights the need for rigorous documentation of adverse events associated with TBS and intensity dosing studies to assess the seizure risk associated with various stimulation parameters (e.g., frequency, intensity, and location).

Changes in Cortical Plasticity Across the Lifespan

Deterioration of motor and cognitive performance with advancing age is well documented, but its cause remains unknown. Animal studies dating back to the late 1970s reveal that age-associated neurocognitive changes are linked to age-dependent changes in synaptic plasticity, including alterations of long-term potentiation and depression (LTP and LTD). Non-invasive brain stimulation techniques enable measurement of LTP- and LTD-like mechanisms of plasticity, in vivo, in humans, and may thus provide valuable insights. We examined the effects of a 40-s train of continuous theta-burst stimulation (cTBS) to the motor cortex (600 stimuli, three pulses at 50 Hz applied at a frequency of 5 Hz) on cortico-spinal excitability as measured by the motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation before and after cTBS in the contralateral first dorsal interosseus muscle. Thirty-six healthy individuals aged 19–81 years old were studied in two sites (Boston, USA and Barcelona, Spain). The findings did not differ across study sites. We found that advancing age is negatively correlated with the duration of the effect of cTBS (r = −0.367; p = 0.028) and the overall amount of corticomotor suppression induced by cTBS (r = −0.478; p = 0.003), and positively correlated with the maximal suppression of amplitude on motor evoked responses in the target muscle (r = 0.420; p = 0.011). We performed magnetic resonance imaging (MRI)-based individual morphometric analysis in a subset of subjects to demonstrate that these findings are not explained by age-related brain atrophy or differences in scalp-to-brain distance that could have affected the TBS effects. Our findings provide empirical evidence that the mechanisms of cortical plasticity area are altered with aging and their efficiency decreases across the human lifespan. This may critically contribute to motor and possibly cognitive decline.

Preliminary evidence for deficits in multisensory integration in autism spectrum disorders: The mirror neuron hypothesis

Abstract Autism is a complex disorder, characterized by social, cognitive, communicative, and motor symptoms. One suggestion, proposed in the current study, to explain the spectrum of symptoms is an underlying impairment in multisensory integration (MSI) systems such as a mirror neuron-like system. The mirror neuron system, thought to play a critical role in skills such as imitation, empathy, and language can be thought of as a multisensory system, converting sensory stimuli into motor representations. Consistent with this, we report preliminary evidence for deficits in a task thought to tap into MSI—“the bouba-kiki task” in children with ASD. The bouba-kiki effect is produced when subjects are asked to pair nonsense shapes with nonsense “words”. We found that neurotypical children chose the nonsense “word” whose phonemic structure corresponded with the visual shape of the stimuli 88% of the time. This is presumably because of mirror neuron-like multisensory systems that integrate the visual shape with the corresponding motor gestures used to pronounce the nonsense word. Surprisingly, individuals with ASD only chose the corresponding name 56% of the time. The poor performance by the ASD group on this task suggests a deficit in MSI, perhaps related to impaired MSI brain systems. Though this is a behavioral study, it provides a testable hypothesis for the communication impairments in children with ASD that implicates a specific neural system and fits well with the current findings suggesting an impairment in the mirror systems in individuals with ASD.

Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile X syndrome and autism spectrum disorder

Fragile X Syndrome (FXS) is the most common heritable cause of intellectual disability. In vitro electrophysiologic data from mouse models of FXS suggest that loss of fragile X mental retardation protein affects intracortical excitability and synaptic plasticity. Specifically, the cortex appears hyperexcitable, and use-dependent long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength are abnormal. Though animal models provide important information, FXS and other neurodevelopmental disorders are human diseases and as such translational research to evaluate cortical excitability and plasticity must be applied in the human. Transcranial magnetic stimulation paradigms have recently been developed to non-invasively investigate cortical excitability using paired pulse stimulation, as well as LTP- and LTD-like synaptic plasticity in response to theta burst stimulation (TBS) in vivo in the human. TBS applied on consecutive days can be used to measure metaplasticity (the ability of the synapse to undergo a second plastic change following a recent induction of plasticity). The current study investigated intracortical inhibition, plasticity and metaplasticity in full mutation females with FXS, participants with autism spectrum disorders (ASD), and neurotypical controls. Results suggest that intracortical inhibition is normal in participants with FXS, while plasticity and metaplasticity appear abnormal. ASD participants showed abnormalities in plasticity and metaplasticity, as well as heterogeneity in intracortical inhibition. Our findings highlight the utility of non-invasive neurophysiological measures to translate insights from animal models to humans with neurodevelopmental disorders, and thus provide direct confirmation of cortical dysfunction in patients with FXS and ASD.

Transcranial Magnetic Stimulation: A Neuroscientific Probe of Cortical Function in Schizophrenia

Transcranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Available evidence suggests benefits of TMS alone or in combination with neurophysiologic and neuroimaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging, functional magnetic resonance imaging, functional near infrared spectroscopy, magnetoencephalography, and electroencephalography, to explore neocortical function. With the multiple TMS techniques including single-pulse, paired-pulse, paired associative stimulation, and repetitive TMS and theta burst stimulation, combined with neurophysiologic and neuroimaging methods, there exists a plethora of TMS experimental paradigms to modulate neocortical physiologic processes. Specifically, TMS can measure cortical excitability, intracortical inhibitory and excitatory mechanisms, and local and network cortical plasticity. Coupled with functional and electrophysiologic modalities, TMS can provide insight into the mechanisms underlying healthy neurodevelopment and aging, as well as neuropsychiatric pathology. Thus, TMS could be a useful tool in the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia armamentarium of biomarker methods. Future investigations are warranted to optimize TMS methodologies for this purpose.