Face-Selective Units in Human Ventral Temporal Cortex Reactivate during Free Recall.

Research in functional neuroimaging has suggested that category-selective regions of visual cortex, including the ventral temporal cortex (VTC), can be reactivated endogenously through imagery and recall. Face representation in the monkey face-patch system has been well studied and is an attractive domain in which to explore these processes in humans. The VTCs of 8 human subjects (4 female) undergoing invasive monitoring for epilepsy surgery were implanted with microelectrodes. Most (26 of 33) category-selective units showed specificity for face stimuli. Different face exemplars evoked consistent and discriminable responses in the population of units sampled. During free recall, face-selective units preferentially reactivated in the absence of visual stimulation during a 2 s window preceding face recall events. Furthermore, we show that in at least 1 subject, the identity of the recalled face could be predicted by comparing activity preceding recall events to activity evoked by visual stimulation. We show that face-selective units in the human VTC are reactivated endogenously, and present initial evidence that consistent representations of individual face exemplars are specifically reactivated in this manner.SIGNIFICANCE STATEMENT The role of "top-down" endogenous reactivation of native representations in higher sensory areas is poorly understood in humans. We conducted the first detailed single-unit survey of ventral temporal cortex (VTC) in human subjects, showing that, similarly to nonhuman primates, humans encode different faces using different rate codes. Then, we demonstrated that, when subjects recalled and imagined a given face, VTC neurons reactivated with the same rate codes as when subjects initially viewed that face. This suggests that the VTC units not only carry durable representations of faces, but that those representations can be endogenously reactivated via "top-down" mechanisms.

Medical Student Patient Outreach to Ensure Continuity of Care During the COVID-19 Pandemic.

Background: In response to the COVID-19 pandemic, the Yale New Haven Health System began rescheduling nonurgent outpatient appointments as virtual visits in March 2020. While Yale New Haven Health expanded its telemedicine infrastructure to accommodate this shift, many appointments were delayed and patients faced considerable uncertainty. Objective: Medical students created the Medical Student Task Force (MSTF) to help ensure continuity of care by calling patients whose appointments were delayed during this transition to telemedicine. Methods: Eighty-five student volunteers called 3765 internal medicine patients with canceled appointments, completing screening for 2197 patients. Volunteers screened for health care needs, assessed preferences for future appointments, and offered emotional support and information about COVID-19. Urgent or emergent patient concerns were triaged and escalated to providers. In this analysis, we used a mixed-methods approach: call information and provider responses were analyzed quantitatively, and patient feedback was analyzed qualitatively via thematic analysis. Results: Ninety-one percent of patients screened found the MSTF calls helpful. Twenty-one percent of patients reported health concerns, with 1% reporting urgent concerns escalated to and addressed by providers. Themes of patient comments included gratitude for outreach and social contact, utility of calls, and well-wishes for health care workers. Conclusions: By calling patients whose appointments had been canceled during a rapid transition to telemedicine, the MSTF helped bridge a potential gap in care by offering patients communication with their care teams, information, and support. We propose that this model could be used in other care systems urgently transitioning to outpatient telemedicine, whether during ongoing outbreaks of COVID-19 or other public health emergencies.

Does neurofibromatosis 1 status impact outcomes for pediatric/young adults undergoing spinal fusion?

BACKGROUND: Although spinal deformities are common in patients with neurofibromatosis type 1 (NF1), there is a paucity of data as to how this impacts outcomes of spinal fusion surgery in pediatric/young adult patients. METHODS: Using the Nationwide Inpatient Sample (2005-2014) for all patients undergoing spinal fusion ≤26 years of age, we compared the following factors: demographics, comorbidities, and perioperative variables (e.g., between NF1 vs. non-NF1, and between NF1 and propensity score (PS)-matched non- NF1 spinal fusion patients) using univariate hypothesis tests and multivariate regression analyses. Our main interest focused on length of stay, complication rates, adverse postoperative events, and incidence of nonroutine discharges. RESULTS: In this study, 238 (0.92%) NF1 spine patients were compared to 25,558 (99.08%) non-NF1 spine patients. NF1 fusion patients were younger, included fewer females, and were more likely to be on Medicaid. Perioperatively, NF1 patients underwent more anterior approaches, had more vertebrae fused, required more transfusions, had a longer length of stay (LOS), and were less likely to be discharged home. However, after PS- matching, all differences between NF1 and non-NF1 groups disappeared were similar (P > 0.05). In PS-matched multivariate analyses, NF1-status was not a significant independent predictor of length of stay or nonroutine discharge disposition. CONCLUSION: NF1-status was, therefore, not an independent predictor of complications, adverse postoperative events, longer LOS, or nonroutine hospital discharge in this cohort analysis. Further prospective studies are necessary to understand how outcomes in patients with NF1 compare to non-NF1 pediatric and young adult patients.

The Noisy Brain: Power of Resting-State Fluctuations Predicts Individual Recognition Performance.

The unique profile of strong and weak cognitive traits characterizing each individual is of a fundamental significance, yet their neurophysiological underpinnings remain elusive. Here, we present intracranial electroencephalogram (iEEG) measurements in humans pointing to resting-state cortical "noise" as a possible neurophysiological trait that limits visual recognition capacity. We show that amplitudes of slow (<1 Hz) spontaneous fluctuations in high-frequency power measured during rest were predictive of the patients' performance in a visual recognition 1-back task (26 patients, total of 1,389 bipolar contacts pairs). Importantly, the effect was selective only to task-related cortical sites. The prediction was significant even across long (mean distance 4.6 ± 2.8 days) lags. These findings highlight the level of the individuals' internal "noise" as a trait that limits performance in externally oriented demanding tasks.

Convergent evolution of face spaces across human face-selective neuronal groups and deep convolutional networks.

The discovery that deep convolutional neural networks (DCNNs) achieve human performance in realistic tasks offers fresh opportunities for linking neuronal tuning properties to such tasks. Here we show that the face-space geometry, revealed through pair-wise activation similarities of face-selective neuronal groups recorded intracranially in 33 patients, significantly matches that of a DCNN having human-level face recognition capabilities. This convergent evolution of pattern similarities across biological and artificial networks highlights the significance of face-space geometry in face perception. Furthermore, the nature of the neuronal to DCNN match suggests a role of human face areas in pictorial aspects of face perception. First, the match was confined to intermediate DCNN layers. Second, presenting identity-preserving image manipulations to the DCNN abolished its correlation to neuronal responses. Finally, DCNN units matching human neuronal group tuning displayed view-point selective receptive fields. Our results demonstrate the importance of face-space geometry in the pictorial aspects of human face perception.

Hippocampal sharp-wave ripples linked to visual episodic recollection in humans.

Hippocampal sharp-wave ripples (SWRs) constitute one of the most synchronized activation events in the brain and play a critical role in offline memory consolidation. Yet their cognitive content and function during awake, conscious behavior remains unclear. We directly examined this question using intracranial recordings in human patients engaged in episodic free recall of previously viewed photographs. Our results reveal a content-selective increase in hippocampal ripple rate emerging 1 to 2 seconds prior to recall events. During recollection, high-order visual areas showed pronounced SWR-coupled reemergence of activation patterns associated with recalled content. Finally, the SWR rate during encoding predicted subsequent free-recall performance. These results point to a role for hippocampal SWRs in triggering spontaneous recollections and orchestrating the reinstatement of cortical representations during free episodic memory retrieval.

Validation of corpus callosotomy after laser interstitial thermal therapy: a multimodal approach.

ObjectiveDisconnection of the cerebral hemispheres by corpus callosotomy (CC) is an established means to palliate refractory generalized epilepsy. Laser interstitial thermal therapy (LITT) is gaining acceptance as a minimally invasive approach to treating epilepsy, but this method has not been evaluated in clinical series using established methodologies to assess connectivity. The goal in this study was to demonstrate the safety and feasibility of MRI-guided LITT for CC and to assess disconnection by using electrophysiology- and imaging-based methods.MethodsRetrospective chart and imaging review was performed in 5 patients undergoing LITT callosotomy at a single center. Diffusion tensor imaging and resting functional MRI were performed in all patients to assess anatomical and functional connectivity. In 3 patients undergoing simultaneous intracranial electroencephalography monitoring, corticocortical evoked potentials and resting electrocorticography were used to assess electrophysiological correlates.ResultsAll patients had generalized or multifocal seizure onsets. Three patients with preoperative evidence for possible lateralization underwent stereoelectroencephalography depth electrode implantation during the perioperative period. LITT ablation of the anterior corpus callosum was completed in a single procedure in 4 patients. One complication involving misplaced devices required a second procedure. Adequacy of the anterior callosotomy was confirmed using contrast-enhanced MRI and diffusion tensor imaging. Resting functional MRI, corticocortical evoked potentials, and resting electrocorticography demonstrated functional disconnection of the hemispheres. Postcallosotomy monitoring revealed lateralization of the seizures in all 3 patients with preoperatively suspected occult lateralization. Four of 5 patients experienced > 80% reduction in generalized seizure frequency. Two patients undergoing subsequent focal resection are free of clinical seizures at 2 years. One patient developed a 9-mm intraparenchymal hematoma at the site of entry and continued to have seizures after the procedure.ConclusionsMRI-guided LITT provides an effective minimally invasive alternative method for CC in the treatment of seizures associated with drop attacks, bilaterally synchronous onset, and rapid secondary generalization. The disconnection is confirmed using anatomical and functional neuroimaging and electrophysiological measures.

On the importance of precise electrode placement for targeted transcranial electric stimulation.

Transcranial electric stimulation (TES) is an increasingly popular method for non-invasive modulation of brain activity and a potential treatment for neuropsychiatric disorders. However, there are concerns about the reliability of its application because of variability in TES-induced intracranial electric fields across individuals. While realistic computational models offer can help to alleviate these concerns, their direct empirical validation is sparse, and their practical implications are not always clear. In this study, we combine direct intracranial measurements of electric fields generated by TES in surgical epilepsy patients with computational modeling. First, we directly validate the computational models and identify key parameters needed for accurate model predictions. Second, we derive practical guidelines for a reliable application of TES in terms of the precision of electrode placement needed to achieve a desired electric field distribution. Based on our results, we recommend electrode placement accuracy to be < 1 cm for a reliable application of TES across sessions.

Breathing above the brain stem: volitional control and attentional modulation in humans.

Whereas the neurophysiology of respiration has traditionally focused on automatic brain stem processes, higher brain mechanisms underlying the cognitive aspects of breathing are gaining increasing interest. Therapeutic techniques have used conscious control and awareness of breathing for millennia with little understanding of the mechanisms underlying their efficacy. Using direct intracranial recordings in humans, we correlated cortical and limbic neuronal activity as measured by the intracranial electroencephalogram (iEEG) with the breathing cycle. We show this to be the direct result of neuronal activity, as demonstrated by both the specificity of the finding to the cortical gray matter and the tracking of breath by the gamma-band (40-150 Hz) envelope in these structures. We extend prior observations by showing the iEEG signal to track the breathing cycle across a widespread network of cortical and limbic structures. We further demonstrate a sensitivity of this tracking to cognitive factors by using tasks adapted from cognitive behavioral therapy and meditative practice. Specifically, volitional control and awareness of breathing engage distinct but overlapping brain circuits. During volitionally paced breathing, iEEG-breath coherence increases in a frontotemporal-insular network, and during attention to breathing, we demonstrate increased coherence in the anterior cingulate, premotor, insular, and hippocampal cortices. Our findings suggest that breathing can act as an organizing hierarchical principle for neuronal oscillations throughout the brain and detail mechanisms of how cognitive factors impact otherwise automatic neuronal processes during interoceptive attention. NEW & NOTEWORTHY Whereas the link between breathing and brain activity has a long history of application to therapy, its neurophysiology remains unexplored. Using intracranial recordings in humans, we show neuronal activity to track the breathing cycle throughout widespread cortical/limbic sites. Volitional pacing of the breath engages frontotemporal-insular cortices, whereas attention to automatic breathing modulates the cingulate cortex. Our findings imply a fundamental role of breathing-related oscillations in driving neuronal activity and provide insight into the neuronal mechanisms of interoceptive attention.

Neuronal baseline shifts underlying boundary setting during free recall.

Asked to freely recall items from a predefined set (e.g., animals), we rarely recall a wrong exemplar (e.g., a vegetable). This capability is so powerful and effortless that it is essentially taken for granted, yet, surprisingly, the underlying neuronal mechanisms are unknown. Here we investigate this boundary setting mechanism using intracranial recordings (ECoG), in 12 patients undergoing epilepsy monitoring engaged in episodic free recall. After viewing vivid photographs from two categories (famous faces and places), patients were asked to freely recall these items, targeting each category in separate blocks. Our results reveal a rapid and sustained rise in neuronal activity ("baseline shift") in high-order visual areas that persists throughout the free recall period and reflects the targeted category. We further show a more transient reactivation linked to individual recall events. The results point to baseline shift as a flexible top-down mechanism that biases spontaneous recall to remain within the required categorical boundaries.

Increasing suppression of saccade-related transients along the human visual hierarchy.

A key hallmark of visual perceptual awareness is robustness to instabilities arising from unnoticeable eye and eyelid movements. In previous human intracranial (iEEG) work (Golan et al., 2016) we found that excitatory broadband high-frequency activity transients, driven by eye blinks, are suppressed in higher-level but not early visual cortex. Here, we utilized the broad anatomical coverage of iEEG recordings in 12 eye-tracked neurosurgical patients to test whether a similar stabilizing mechanism operates following small saccades. We compared saccades (1.3°-3.7°) initiated during inspection of large individual visual objects with similarly-sized external stimulus displacements. Early visual cortex sites responded with positive transients to both conditions. In contrast, in both dorsal and ventral higher-level sites the response to saccades (but not to external displacements) was suppressed. These findings indicate that early visual cortex is highly unstable compared to higher-level visual regions which apparently constitute the main target of stabilizing extra-retinal oculomotor influences.

Invariant Temporal Dynamics Underlie Perceptual Stability in Human Visual Cortex.

An inherent limitation of human visual system research stems from its reliance on highly controlled laboratory conditions. Visual processing in the real world differs substantially from such controlled conditions. In particular, during natural vision, we continuously sample the dynamic environment by variable eye movements that lead to inherent instability of the optical image. The neuronal mechanism by which human perception remains stable under these natural conditions remains unknown. Here, we examined a neural mechanism that may contribute to such stability, i.e., the extent to which neuronal responses remain invariant to oculomotor parameters and viewing conditions. To this end, we introduce an experimental paradigm in which intracranial brain activity, a video of the real-life visual scene, and free oculomotor behavior were simultaneously recorded in human patients. Our results reveal, in high-order visual areas, a remarkable level of neural invariance to the length of eye fixations and lack of evidence for a saccade-related neuronal signature. Thus, neuronal responses, while showing high selectivity to the category of visual images, manifested stable "iconic" dynamics. This property of invariance to fixation onset and duration emerged only in high-order visual representations. In early visual cortex, the fixation onset was accompanied with suppressive neural signal, and duration of neuronal responses was largely determined by the fixation times. These results uncover unique neuronal dynamics in high-order ventral stream visual areas that could play an important role in achieving perceptual stability, despite the drastic changes introduced by oculomotor behavior in real life.

Human intracranial recordings link suppressed transients rather than 'filling-in' to perceptual continuity across blinks.

We hardly notice our eye blinks, yet an externally generated retinal interruption of a similar duration is perceptually salient. We examined the neural correlates of this perceptual distinction using intracranially measured ECoG signals from the human visual cortex in 14 patients. In early visual areas (V1 and V2), the disappearance of the stimulus due to either invisible blinks or salient blank video frames ('gaps') led to a similar drop in activity level, followed by a positive overshoot beyond baseline, triggered by stimulus reappearance. Ascending the visual hierarchy, the reappearance-related overshoot gradually subsided for blinks but not for gaps. By contrast, the disappearance-related drop did not follow the perceptual distinction - it was actually slightly more pronounced for blinks than for gaps. These findings suggest that blinks' limited visibility compared with gaps is correlated with suppression of blink-related visual activity transients, rather than with "filling-in" of the occluded content during blinks.

Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates.

Transcranial electric stimulation (TES) is an emerging technique, developed to non-invasively modulate brain function. However, the spatiotemporal distribution of the intracranial electric fields induced by TES remains poorly understood. In particular, it is unclear how much current actually reaches the brain, and how it distributes across the brain. Lack of this basic information precludes a firm mechanistic understanding of TES effects. In this study we directly measure the spatial and temporal characteristics of the electric field generated by TES using stereotactic EEG (s-EEG) electrode arrays implanted in cebus monkeys and surgical epilepsy patients. We found a small frequency dependent decrease (10%) in magnitudes of TES induced potentials and negligible phase shifts over space. Electric field strengths were strongest in superficial brain regions with maximum values of about 0.5 mV/mm. Our results provide crucial information of the underlying biophysics in TES applications in humans and the optimization and design of TES stimulation protocols. In addition, our findings have broad implications concerning electric field propagation in non-invasive recording techniques such as EEG/MEG.

Binocular stereoscopy in visual areas V-2, V-3, and V-3A of the macaque monkey.

Over 40 years ago, Hubel and Wiesel gave a preliminary report of the first account of cells in monkey cerebral cortex selective for binocular disparity. The cells were located outside of V-1 within a region referred to then as "area 18." A full-length manuscript never followed, because the demarcation of the visual areas within this region had not been fully worked out. Here, we provide a full description of the physiological experiments and identify the locations of the recorded neurons using a contemporary atlas generated by functional magnetic resonance imaging; we also perform an independent analysis of the location of the neurons relative to an anatomical landmark (the base of the lunate sulcus) that is often coincident with the border between V-2 and V-3. Disparity-tuned cells resided not only in V-2, the area now synonymous with area 18, but also in V-3 and probably within V-3A. The recordings showed that the disparity-tuned cells were biased for near disparities, tended to prefer vertical orientations, clustered by disparity preference, and often required stimulation of both eyes to elicit responses, features strongly suggesting a role in stereoscopic depth perception.