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Carmona, J.

Publications and source records attributed to Carmona, J..

10 recordsLinked to original sources

Atypical myxomatosis in European rabbits is caused by the recombinant myxoma virus involved in species jumping into hares

Myxoma virus (MYXV), a member of the Leporipoxvirus genus (species Leporipoxvirus myxoma; family Poxviridae), causes a highly lethal disease known as myxomatosis in European rabbits. In late 2018, a new natural MYXV isolate, MYXV-Tol (a.k.a. hare MYXV; ha-MYXV), emerged and caused myxomatosis-like disease with high mortality in Iberian hares, European brown hares, and European rabbits. This variant contains an approximately 2.8-kb insertion of a recombination cassette within the M009L gene encoding four additional genes, including the C7-like host range gene, M159L. M159 is essential for replication of MYXV-Tol in hare cells and is likely a key determinant of its pathogenicity in both hares and rabbits. Here, we compared the pathogenicity of wild-type MYXV-Tol (vMyx-Tol), an M159 deletion strain (vMyx-Tol-M159KO), and the classical MYXV-Lau strain (vMyx-Lau) in European rabbits. All three viruses caused systemic disease; however, vMyx-Tol and vMyx-Tol-M159KO produced clinical signs distinct from classical myxomatosis. Infection with vMyx-Tol and vMyx-Tol-M159KO was characterized by the absence of the typical primary and secondary nodular lesions, and caused severe edema, marked fluid accumulation, lymphocyte infection, and significantly reduced or no virus-neutralizing antibody responses. The disease caused by both vMyx-Tol and vMyx-Tol-M159KO progressed rapidly within 9-11 days, resulting in animals reaching humane euthanasia endpoints like vMyx-Lau. Deletion of M159 did not significantly alter MYXV-Tol pathogenicity in rabbits. Collectively, these findings demonstrate that MYXV-Tol has evolved to cause an atypical, amyxomatous-like acute to hyperacute disease in European rabbits and likely in hares. SignificanceNatural evolution enables viruses to cross species barriers and adapt to new hosts. Myxoma virus (MYXV), released in the 1950s in Australia and Europe as a biocontrol agent against European rabbits, became a classic model for real-time monitoring of virus evolution, virulence, and host adaptation. Although MYXV is typically host-restricted, a newly emerged natural isolate, MYXV-Tol, causes lethal disease in both hares and rabbits. Here, we show that MYXV-Tol induces an atypical, amyxomatous-like disease characterized by the absence of nodular lesions, severe edema, lymphocyte infection, and markedly reduced virus-neutralizing antibody responses. These findings reveal previously unrecognized virus-host interactions that shape disease outcome and provide new insight into the mechanisms driving viral adaptation and evolution.

microbiology↗

Input-dependent directionality of interactions between cortical areas

Tracking signal flow across areas is essential for understanding brain function. Recent studies using cross-covariances show that activity directionality can shift rapidly with behavioral or task demands; yet, the circuit mechanisms underlying these changes remain unclear. Here, we use recurrent network models to investigate how directional interactions emerge and are flexibly reconfigured in multi-area cortical circuits. We show that, for fixed connectivity, directionality is shaped by how common inputs align with recurrent connectivity and the associated internal timescales of activity. In multi-area circuits with locally balanced excitation and inhibition, this reveals a predominant role for inputs to excitatory over inhibitory populations in controlling directionality. These inputs govern the directionality of the latent signals that account for most of the shared activity across areas, predominantly reflecting widespread and coherent activity fluctuations. Our models capture key features of cross-covariances from primate areas V1 and V2 and suggest parsimonious mechanisms for the shift in directionality reported in these areas. This work establishes a mechanistic framework for understanding dynamic changes in signal flow between brain areas.

neuroscience↗

Investigating the Dynamic Relationship Between Anxiety and Spatial Memory Using Autonomous Ecological Momentary Assessment

Anxiety has been extensively studied in relation to memory, yet its dynamic association with spatial episodic memory in naturalistic clinical settings remains largely unexplored. We developed an anxiety-spatial-memory EMA protocol (asm-EMA) and deployed it in 30 epilepsy patients undergoing inpatient EEG monitoring, delivering combined momentary anxiety ratings and a validated spatial memory task pseudo-randomly every 90-150 minutes across multiple days. Subject-level asm-EMA means and session-to-session variability both correlated significantly with standard neuropsychological assessments, supporting the clinical validity of our design. Elevated within-person STAI-6 was selectively associated with faster retrieval responses, yet spatial memory accuracy was independent of all three anxiety measures, suggesting a shift in response strategy rather than memory impairment. Within-day anxiety showed short-term carryover between consecutive sessions, with little persistence beyond the next session. The asm-EMA protocol provides a feasible, autonomous framework for capturing moment-to-moment anxiety-memory dynamics in naturalistic settings.

neuroscience↗

Stochastic activity in low-rank recurrent neural networks

The geometrical and statistical properties of brain activity depend on the way neurons connect to form recurrent circuits. However, the link between connectivity structure and emergent activity remains incompletely understood. We investigate this relationship in recurrent neural networks with additive stochastic inputs. We assume that the synaptic connectivity can be expressed in a low-rank form, parameterized by a handful of connectivity vectors, and examine how the geometry of emergent activity relates to these vectors. Our findings reveal that this relationship critically depends on the dimensionality of the external stochastic inputs. When inputs are low-dimensional, activity remains low-dimensional, and recurrent dynamics influence it within a subspace spanned by a subset of the connectivity vectors, with dimensionality equal to the rank of the connectivity matrix. In contrast, when inputs are high-dimensional, activity also becomes potentially high-dimensional. The contribution of recurrent dynamics is apparent within a subspace spanned by the totality of the connectivity vectors, with dimensionality equal to twice the rank of the connectivity matrix. Applying our formalism to excitatory-inhibitory networks, we discuss how the input configuration also plays a crucial role in determining the amount of amplification generated by non-normal dynamics. Our work provides a foundation for studying activity in structured brain circuits under realistic noise conditions, and offers a framework for interpreting stochastic models inferred from experimental data.

neuroscience↗

Transverse Sheet Illumination Microscopy (TranSIM): A High-Speed Platform for Large-Scale Volumetric Imaging

Recording the neural activity of biological organisms is paramount in understanding how they process the world around them. Fluorescence microscopy has served as the standard in recording this neural activity due to its ability to capture large populations of neurons simultaneously. Recent efforts in fluorescence microscopy have been concentrated in imaging large scale volumes, however, most of these efforts have been limited by spatiotemporal and bandwidth constraints. We present a novel system called Transverse-Sheet Illumination Microscopy (TranSIM), which captures spatially separated planes onto multiple two-dimensional sCMOS sensors at near diffraction limited resolution with 1.0 {micro}m, 1.4 {micro}m, and 4.3 {micro}m (x, y, and z respectively). The parallel use of sensors reduces the bandwidth bottlenecks typically found in other systems. TranSIM allows for the capturing of data at large-scale volumetric field-of-views up to 748 x 278 x 100 {micro}m3 at 100 Hz. Moreover, we were able to capture smaller field-of-views of 374 x 278 x 100 {micro}m3 at a faster volumetric rate of 200 Hz. Additionally, we found that the systems versatile design allowed us the ability to change the vertical magnification programmatically rather than necessitating a change of objectives. With this system we were able to observe intricate communication between neuron populations separated by vast three-dimensional distances, raising the potential to answer complex questions in Neurobiology.

bioengineering↗

EEG responses to auditory cues predict fluency variability and stuttering intervention outcome

Stuttering is a variable speech disorder whose brain mechanisms remain unknown. Sensorimotor brain circuits, critical for motor-speech control, including auditory processing necessary for speech prediction and monitoring, have been linked to the disorder. Despite considerable advances, it remains unclear whether auditory circuits relate to stuttering variability, and whether the panoply of interventions for persons who stutter can lead to brain changes within these circuits. We employed electroencephalography (EEG), in a group of persons who stutter, in combination with auditory probes to tap onto the importance of auditory cortical regions in stuttering variability. Participantsproduced flexible speech (i.e., describing visual scenes) and non-flexible speech (i.e., reading syllables), following an auditory cue. More pronounced P200 auditory evoked potentials were observed in participants with higher dysfluency rates, mainly in the spontaneous speech task. Interestingly, speech therapy intervention led to a reduction of the P200 potential, which was in turn significantly related to fluency improvements. Furthermore, EEG response patterns discriminative of cue frequency (400 or 800 Hz tones) were also predictive of dysfluency scores. Our study highlights the involvement of auditory cortical processing and that of auditory attention in stuttering variability. We support that a higher state of auditory alertness may be implicated in the sensorimotor mechanisms of stuttering, and that speech therapy interventions promoting more self-confident communication can restraint auditory alertness, and potentially reduce speech dysfluencies. HighlightsO_LIAuditory probes can assess the auditory cortex in speech production and stuttering. C_LIO_LIStuttering severity correlates to EEG auditory responses during speech preparation. C_LIO_LIHigher states of auditory alertness in stuttering may be reduced by speech therapy. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/635719v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@18a639dorg.highwire.dtl.DTLVardef@91efc6org.highwire.dtl.DTLVardef@114dd97org.highwire.dtl.DTLVardef@e01024_HPS_FORMAT_FIGEXP M_FIG C_FIG Speaking requires orchestrating several brain processes at a time. The auditory system assumes a central role, not only in waiting for the right moment to initiate speech, listening to self-produced speech, predicting the consequence of future speech, but also adjusting these processes to the intermittent nature of stuttering.

neuroscience↗

Visual Perception of 3D Space and Shape in Time - Part I: 2D Space Perception by 2D Linear Translation

Visual perception plays a critical role in navigating space and extracting useful semantic information crucial to survival. To identify distant landmarks, we constantly shift gaze vectors through saccades, while still maintaining the visual perception of stable allocentric space. How can we sustain stable allocentric space so effortlessly? To solve this question, we have developed a new concept of NHT (Neural Holography Tomography). This model states that retinotopy is invisible (not available to consciousness) and must be converted to a time code by traveling alpha brainwaves to perceive objects consciously. According to this framework, if identical alpha phases are continually assigned to a landmark, we perceive its exact and consistent allocentric location. To test this hypothesis, we designed reaction time (RT) experiments to observe evidence of the predicted space-to-time conversion. Various visual stimuli were generated at a wide range of eccentricities either on a large TV (up to 40{degrees}) or by LED strips on a hemispherical dome (up to 60{degrees}). Participants were instructed to report the observed patterns promptly under either covert (no eye movement) or overt (with eye movement) conditions. As predicted, stimuli presented at the center of fixation always produced the fastest RTs. The additional RT delay was precisely proportional to the eccentricity of the peripheral stimulus presentation. Furthermore, both covert and overt attention protocols created the same RT delays, and trajectories of saccadic eye motions were in parallel to the overt RT vs. eccentricity. These findings strongly support our NHT model, in which the observed RT-eccentricity dependence is indicative of the spatiotemporal conversion required for maintaining a stable allocentric frame of reference. That is, we perceive space by time.

neuroscience↗

Visual Perception of 3D Space and Shape in Time - Part III: 2D Shape Recognition by Log-Scaling

Human vision has a remarkable ability to recognize complex 3D objects such as faces that appear with any size and 3D orientations at any 3D location. If we initially memorize a face only with a normalized size and viewed from directly head on, the direct comparison between the one-sized memory and a new incoming image would demand tremendous mental frame translations in 7D. How can we perform such a demanding task so promptly and reliably as we experience the objects in the world around us? Intriguingly, our primary visual cortex exhibits a 2D retinotopy with a log-polar coordinate system, where scaling up/down of shape is converted to linear frame translation. As a result, mental scaling can be performed by linearly translating the memory or the perceptual image until they overlap with each other. According to our new model of NHT (Neural Holography Tomography), alpha brainwaves traveling at a constant speed can conduct this linear translation. With this scheme, every scaling up/down by a factor of two should take the same amount of extra mental time to recognize a smaller/larger face. To test this hypothesis, we designed a reaction time (RT) experiment, where participants were first asked to memorize sets of unfamiliar faces with a given specific size (4{degrees} or 8{degrees}). Following the memorization phase, similar stimuli with a wide range of sizes (from 1{degrees} to 32{degrees}) were presented, and RTs were recorded. As predicted, the increase in RT was proportional to the scaling factor in the log scale. Furthermore, we observed that RTs were fastest for 8{degrees} faces even if the memorized face was 4{degrees}. This supports our hypothesis that we always memorize faces at the exact size of ~8 {degrees}. To our surprise, the increases in RT were also consistent with the mentally-estimated depth sensation, which indicates that the apparent size of the recognized face can create a proper depth sensation.

neuroscience↗

Visual Perception of 3D Space and Shape In Time - Part IV: 3D Shape Recognition by 3D Rotation

Human vision has a remarkable ability to recognize complex 3D objects such as faces that appear at any size and 3D orientations at any 3D location. If we initially memorize a face only with a normalized size upfront at the object center, the direct comparison between the one-sized memory and an incoming new image would demand tremendous mental frame translations in 7D. How can we perform such a demanding task so promptly as we experience it in our daily lives? This paper specifically addresses the recognition of human faces with arbitrary 3D orientation in the [Roll, Yaw, Pitch] axes. According to our new model of NHT (Neural Holography Tomography), space is represented by time utilizing the phase of the alpha brainwave. This principle should be applicable to any mental rotation in 3D; thus, it predicts that extra time is required to perceive a rotated face to revolve it back to upright by the constant-speed alpha wave. To assess this hypothesis, we designed a reaction time (RT) experiment, where participants were first asked to memorize sets of upright unfamiliar faces. Following the memorization phase, similar stimuli with a wide range of rotating faces in 3D were presented, and RTs were recorded. As expected, the memorized upfront face was the fastest RT. The excess of the RT was observed proportional to the rotating angle in all [Roll, Yaw, Pitch] axes. Roll had the flattest slope, whereas upper Pitch was the steepest. We suspect that Roll is the swiftest mental operation because it can be conducted by the linear frame translation on the log-polar retinotopy of the visual cortex.

neuroscience↗

Visual Perception of 3D Space and Shape in Time - Part II: 3D Space Perception with Holographic Depth

Visual perception plays a critical role in navigating 3D space and extracting semantic information crucial to survival. Even though visual stimulation on the retina is fundamentally 2D, we seem to perceive the world around us in vivid 3D effortlessly. This reconstructed 3D space is allocentric and faithfully represents the external 3D world. How can we recreate stable 3D visual space so promptly and reliably? To solve this mystery, we have developed new concepts MePMoS (Memory-Prediction-Motion-Sensing) and NHT (Neural Holography Tomography). These models state that visual signal processing must be primarily top-down, starting from memory and prediction. Our brains predict and construct the expected 3D space holographically using traveling alpha brainwaves. Thus, 3D space is represented by the three time signals in three directions. To test this hypothesis, we designed reaction time (RT) experiments to observe predicted space-to-time conversion, especially as a function of distance. We placed LED strips on a horizontal plane to cover distances from close up to 2.5 m or 5 m, either using a 1D or a 2D lattice. Participants were instructed to promptly report observed LED patterns at various distances. As expected, stimulation at the fixation cue location always gave the fastest RT. Additional RT delays were proportional to the distance from the cue. Furthermore, both covert attention (without eye movements) and overt attention (with eye movements) created the same RT delays, and both binocular and monocular views resulted in the same RTs. These findings strongly support our predictions, in which the observed RT-depth dependence is indicative of the spatiotemporal conversion required for constructing allocentric 3D space. After all, we perceive and measure 3D space by time as Einstein postulated a century ago.

neuroscience↗