bioRxiv Science⌕ Search

Biology subjects

Iannetti, G. D.

Publications and source records attributed to Iannetti, G. D..

6 recordsLinked to original sources

Electrical Spinal Imaging (ESI): Analysing spinal cord activity with non-invasive, high-resolution mapping

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.

neuroscience↗

Widespread, perception-related information in the human brain scales with levels of consciousness

How does the human brain generate coherent, subjective perceptions--transforming yellow and oblong visual sensory information into the perception of an edible banana 1? This is a hard problem. The standard viewpoint posits that anatomical and functional networks integrate local, specialized processing across the brain to somehow construct unique percepts. Here, we provide evidence for a novel organizational concept by uncovering task-specific information distributed across the human brain. First, we show that functional magnetic resonance imaging (fMRI) can uncover task-specific information throughout the neocortex, even across voxels traditionally discarded as "noise" (t-statistics {approx} 0), challenging the sensitivity of traditional linear, univariate analytical approaches. Remarkably, task-specific signals could also be uncovered from across-subject variances and were ubiquitous even in the subcortex and cerebellum. Finally, we show that the widespread signal in regions remote from a tasks primary and secondary sensory cortices depends on the level of sedation, suggesting it is related to perception{dagger} rather than sensory stimulus encoding. We hypothesize that these widespread, task-specific, and consciousness level-dependent signals may be the basis for coherent, subjective perceptions.

neuroscience↗

Egocentric value maps of the near-body environment

Body-part centric response fields are pervasive: they are observed in single neurons, fMRI, EEG, and multiple behavioural measures. This prevalence across scales and measures makes them excellent candidates for studying systems-level neuroscience. Nonetheless, they remain poorly understood because we lack a unifying formal explanation of their origins and role in wider brain function. Here, we provide such explanation. We use reinforcement learning to analytically explain the existence of body-part centric receptive fields, also known as peripersonal field. We then simulate multiple experimental findings considered foundational in the peripersonal space literature. Our results demonstrate that peripersonal fields naturally arise from two simple and plausible assumptions about living agents: 1) they experience reward when they contact objects in the environment, and 2) they act to maximise reward. These simple assumptions are enough to explain empirical findings on stimulus kinematics, tool use, valence, and network-architecture. Our explanation provides further insight. First, it offers multiple empirically testable predictions. Second, it offers a formal description of the notion that the world-agent state is encoded in parieto-premotor cortices, using motor primitives: peripersonal fields provide building blocks that together create a short-term model of the world near the agent in terms of its future states; a successor representation. This short-term, close-range egocentric peripersonal map is analogous to the long-term, long-range allocentric spatial map of place and grid cells, which underlie locomotion and navigation to reach distant objects. Together, these allocentric and egocentric maps allow efficient interactions with a changing environment across multiple spatial and temporal scales. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/504456v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@1c9d635org.highwire.dtl.DTLVardef@e4b1corg.highwire.dtl.DTLVardef@65390borg.highwire.dtl.DTLVardef@1840160_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

The mechanism of analgesia in Nav1.7 null mutants

Deletion of SCN9A encoding the voltage-gated sodium channel NaV1.7 in humans leads to profound pain insensitivity and anosmia. Conditional deletion of NaV1.7 in sensory neurons of mice also abolishes pain suggesting the locus of analgesia is the nociceptor. Here we demonstrate that NaV1.7 knockout mice have essentially normal nociceptor activity using in vivo calcium imaging and extracellular recording. However, glutamate and substance P release from nociceptor central terminals in the spinal cord is greatly reduced by an opioid-dependent mechanism. Analgesia is also substantially reversed by central but not peripheral application of opioid antagonists. In contrast, the lack of neurotransmitter release from olfactory sensory neurons is opioid-independent. Male and female humans with NaV1.7 null mutations show naloxone reversible analgesia. Thus opioid-dependent inhibition of neurotransmitter release is the principal mechanism of NaV1.7 null analgesia in mice and humans.

neuroscience↗

Within-finger maps of tactile and nociceptive input in the human parietal cortex

The spatial representation of nociceptive input in the human parietal cortex is not fully understood. For instance, it is known that the primary somatosensory cortex (S1) contains a representation of nociceptive-selective input to different fingers, but it is unclear whether S1 subdivisions contain finer-grained, within-finger maps of nociceptive input. It is also unknown whether within-finger maps of somatosensory input exist in intraparietal regions. Therefore, we used high-field 7T functional MRI to reveal within-finger maps of nociceptive and tactile inputs in the human parietal cortex. Although we replicated the previous findings of between-finger maps of nociceptive input spanning S1 subdivisions, we found weak and inconsistent evidence for within-finger maps of nociceptive input in S1 subdivisions. In the same subjects, we found mirrored, within-finger maps of tactile input in areas 3a, 3b, and 1. Importantly, we discovered a within-finger map of nociceptive input, but not of tactile input, in the human intraparietal area 1 (hIP1). In conclusion, our study indicates that the spatial representation of nociceptive input in the parietal cortex partly differs from that of tactile input and reports the discovery of a within-finger map of nociceptive input in hIP1.\n\nNew & NoteworthyWe report the discovery of a fine-grained map of nociceptive input to finger segments in the human intraparietal area 1.

neuroscience↗

Characterising the short-term habituation of event-related evoked potentials

Fast-rising sensory events evoke a series of functionally heterogeneous event-related potentials (ERPs). Stimulus repetition at 1 Hz is known to induce a strong habituation of the largest ERP responses, the vertex waves, which are elicited by stimuli regardless of their modality7, provided that they are salient and behaviourally-relevant. In contrast, the effect of stimulus repetition on the earlier sensor)7 components of ERls has been less explored, and the few existing results are inconsistent. To characterize how the different ERP waves habituate over time, we recorded the responses elicited by 60 identical somatosensory stimuli (activating either non-nociceptive A {beta} or nociceptive A5 afferents), delivered at 1 Hz to healthy human participants. We show that the well-described spatiotemporal sequence of lateralised and vertex ERP components elicited by the first stimulus of the series is largely preserved in the smaller-amplitude, habituated response elicited by the last stimuli of the series. We also found that the earlier lateralised sensory waves habituate across the 60 trials following the same decay function of the vertex waves: this decay function is characterised by a large drop at the first stimulus repetition followed by smaller decreases at subsequent repetitions. Interestingly, the same decay functions described the habituation of ERPs elicited by repeated non-nociceptive and nociceptive stimuli. This study provides a neurophysiological characterization of the effect of prolonged and repeated stimulation on the main components of somatosensory ERPs. It also demonstrates that both lateralised waves and vertex waves are obligator}7 components of ERPs elicited by non-nociceptive and nociceptive stimuli.\n\nSignificance statementOur results provide a functional characterization of the decay of the different ERP components when identical somatosensory (nociceptive and non-nociceptive) stimuli are repeated at 1Hz. East-rising stimuli elicit ERPs obligator)7 contributed by both early lateralised components and late vertex components, even when stimulus repetition minimizes stimulus relevance. This challenges the view that lateralised waves are not obligatorily elicited by nociceptive stimuli. Furthermore, the lateralised and vertex waves habituate to stimulus repetition following similar decay functions, which are unlikely explained in terms of fatigue or adaptation of skin receptors.

neuroscience↗