Gian Domenico Iannetti

Sudden and isolated sensory stimuli (SISS) engage the extralemniscal system and elicit widespread electrocortical responses in the brain. These responses, consisting of both time-domain transients and spectral changes, reflect a switch of the global brain state that likely prepares the organism for subsequent urgent behaviours. Crucially, SISS also elicit a short-latency phasic response in a key component of the extralemniscal system in the brainstem, the noradrenergic Locus Coeruleus (LC) nucleus. Such stimulus-evoked LC firing is associated with the electrocortical markers of extralemniscal activation. LC neurons also display burst-like firing spontaneously, i.e., without imposed sensory stimuli, for example, during quiet wakefulness, sleep, or anaesthesia. However, this phenomenon remains underexplored. We therefore measured, in freely behaving rats, the prefrontal electrocorticogram (ECoG) responses following spontaneous LC bursts. In addition, we compared these ECoG responses to those triggered by electrical LC stimulation or auditory SISS. We found that ECoG responses were proportional to the magnitude of the spontaneous LC bursts or microstimulation, and remarkably similar to those elicited by SISS. Finally, suppression of noradrenergic transmission with systemic clonidine administration attenuated the auditory-evoked ECoG response. These results suggest that LC plays a role in generating transient brain state changes elicited by SISS.

Empathy and prosocial behavior are fundamental to social life, and understanding their neural mechanisms is a central goal of social neuroscience. Animal models offer unique opportunities to investigate these mechanisms at the cellular level, but realizing this potential requires rigorous methods. In this commentary, we raise a set of methodological concerns about an article published in Nature by Zhang et al. (2024), who claim to have identified a cortical mechanism in mice for helping conspecifics in pain. We identify several issues that undermine the authors’ conclusions: inconsistent criteria for interpreting neural overlap as evidence for distinct versus shared representations; decoder results that are at odds with the claimed representational structure; potential biases arising from fixed experimental order; and a mismatch between region-wide experimental manipulations and population-specific mechanistic claims. We situate these concerns within a broader methodological challenge in neuroscience: the difficulty of inferring functional specificity from limited experimental contrasts. Wherever feasible, we offer concrete suggestions for future research. By calling attention to these methodological challenges, this commentary aims to strengthen standards for mechanistic inference in social and systems neuroscience.

The modulation of the hand‐blink reflex (HBR), a prototypical nocifensive response, is increasingly used to investigate defensive behaviour, related to the notion of peripersonal space. However, HBR responsiveness is highly variable across participants. This variability has led researchers to use several seemingly arbitrary criteria to determine whether a subject should be included as a participant in a study. But are these criteria justified? Can better and more rigorous criteria be formulated? Does the traditional division into responders and non‐responders reflect a practical decision to exclude participants with very low signal‐to‐noise ratio, or does it reflect two distinct biological categories? Here, we addressed these issues by systematically varying a set of parameters, which together form an objective and quantifiable criterion of HBR responsiveness. We describe classification criteria for HBR responsiveness that were both reliable and consistent with previous studies. We also found no evidence for a clear‐cut biological distinction between HBR responders and non‐responders. We recommend to (1) no longer preliminarily screen subjects, simply collecting data on all subjects, and (2), after collecting the data, only include subjects identified as blinkers using the following criteria: The mean of the rectified HBR must exceed 2.5 SD of the baseline EMG in 40% or more of trials in the hand‐near condition. We formulate rigorous inclusion criteria for HBR studies, which can be adapted for use on other neurophysiological responses in health and disease.

The spinal cord is the key bridge between the brain and the body. However, scientific understanding of spinal cord function has historically been limited because noninvasive measures of its neural activity have proven exceptionally challenging. In this work, we describe an enhanced recording and analysis approach, Electrical Spinal Imaging (ESI), to obtain noninvasive, high-resolution images of the electrical activity of the human spinal cord. ESI is analytically simple, easy to implement, and data-driven: it does not involve template-based strategies prone to produce spurious signals. Using this approach, we provide a detailed description and physiological characterization of the spatiotemporal dynamics of the peripheral, spinal, and cortical activity elicited by somatosensory stimulation. We also demonstrate that attention modulates postsynaptic activity at spinal cord level. Our method has enabled five important insights regarding spinal cord activity. (1) We identified three distinct responses in the time domain: sP9, sN13, and sP22. (2) The sP9 is a traveling wave reflecting the afferent volley entering the spinal cord through the dorsal root. (3) In contrast, the sN13 and sP22 reflect segmental postsynaptic activity. (4) While the sP9 response is first seen on the dorsal electrodes ipsilateral to the stimulated side, the sN13 and sP22 were not lateralized with respect to the side of stimulation. (5) Unimodal attention strongly modulates the amplitude of the sP22, but not that of the sP9 and sN13 components. The proposed method offers critical insights into the spatiotemporal dynamics of somatosensory processing within the spinal cord, paving the way for precise noninvasive functional monitoring of the spinal cord in basic and clinical neurophysiology.

Sudden and isolated sensory stimuli (SISS) likely signal environmental events demanding immediate behavioural responses. These stimuli—which are widely and persistently used in both basic and clinical neuroscience to explore sensory processing and perception—also trigger some of the largest and most widespread electrocortical responses in the awake mammalian brain. These responses are often interpreted as reflecting either modality-specific sensory processing mediated by high-fidelity ‘lemniscal’ thalamocortical pathways to primary sensory cortices, cortico-cortical connections or motor activity. Here we contend that these interpretations are unjustified. We first describe evidence that the electrocortical responses elicited by the SISS used in systems and cognitive neuroscience are strongly contributed to by non–modality-specific processes mediated by diffuse ‘extralemniscal’ thalamocortical projections. In human EEG, this contribution is reflected in the scalp vertex potential. We then discuss the implications of this ‘two-system’ theory for basic and clinical neuroscience studies, including the neural correlates of consciousness, where widespread responses to sudden, isolated or rare stimuli—often interpreted as signatures of awareness—may instead reflect extralemniscal activity. We conclude by suggesting a mechanism through which transient extralemniscal responses affect ongoing brain activity and promote swift reactions to sudden environmental changes.

Sudden and surprising sensory changes signal environmental events that may require immediate behavioral reactions. In mammals, these changes engage nonspecific “extralemniscal” thalamocortical pathways and evoke large and widespread cortical vertex potentials (VPs). Extralemniscal activity modulates cortical motor output in a variety of tasks and facilitates purposeful and immediate behavioral responses. In contrast, whether the extralemniscal system also affects cortical processing of sensory input transmitted through canonical “lemniscal” thalamocortical pathways remains unknown. Here we tested this hypothesis. In 23 healthy human participants (11 females) we continuously probed lemniscal processing in the primary somatosensory cortex (S1) by measuring the early-latency evoked potentials elicited by a stream of high-frequency (9.5 Hz) somatosensory electrical stimuli. We concurrently recorded extralemniscal activity by measuring the large VPs elicited by fast-rising and infrequent (∼0.1 Hz) auditory pure tones. We observed that the amplitude of S1 responses changes as a function of the phase of the VP, an effect consequent to a modulation of lemniscal input at the cortical rather than subcortical level. These findings demonstrate that a transient activation of the extralemniscal system interferes with ongoing cortical functions across different brain systems—i.e., not only at the level of the motor output but already at the sensory input—and thereby influences global brain dynamics.

Body-part-centered response fields are pervasive in single neurons, functional magnetic resonance imaging, electroencephalography and behavior, but there is no unifying formal explanation of their origins and role. In the present study, we used reinforcement learning and artificial neural networks to demonstrate that body-part-centered fields do not simply reflect stimulus configuration, but rather action value: they naturally arise from the basic assumption that agents often experience positive or negative reward after contacting environmental objects. This perspective successfully reproduces experimental findings that are foundational in the peripersonal space literature. It also suggests that peripersonal fields provide building blocks that create a modular model of the world near the agent: an egocentric value map. This concept is strongly supported by the emergent modularity that we observed in our artificial networks. The short-term, close-range, egocentric map is analogous to the long-term, long-range, allocentric hippocampal map. This perspective fits empirical data from multiple experiments, provides testable predictions and accommodates existing explanations of peripersonal fields.

The spinal cord is the key bridge between the brain and the body. However, scientific understanding of healthy spinal cord function has historically been limited because noninvasive measures of its neural activity have proven exceptionally challenging. In this work, we describe a novel recording and analysis approach to obtain non-invasive, high-resolution images of the electrical activity of the spinal cord in humans (Electrical Spinal Imaging, ESI). ESI is analytically simple, easy to implement, and data-driven: it does not involve template-based strategies prone to produce spurious signals. Using this approach we provide a detailed description and physiological characterization of the spatiotemporal dynamics of the peripheral, spinal and cortical activity elicited by somatosensory stimulation. We also demonstrate that attention modulates post-synaptic activity at spinal cord level. Our method has enabled four new insights regarding spinal cord activity. (1) We identified three distinct responses in the time domain: sP9, sN13 and sP22. (2) The sP9 is a traveling wave reflecting the afferent volley entering the spinal cord through the dorsal root. (3) In contrast, the sN13 and sP22 reflect segmental post-synaptic activity. (4) While the sP9 response is first seen on the dorsal electrodes ipsilateral to the stimulated side, the sN13 and sP22 were not lateralised with respect to the side of stimulation. (5) Unimodal attention strongly modulates the amplitude of the sP22, but not that of the sP9 and sN13 components. The proposed method offers critical insights into the spatiotemporal dynamics of somatosensory processing within the spinal cord, paving the way for precise non-invasive functional monitoring of the spinal cord in basic and clinical neurophysiology.