Single Hemisphere Research Articles

Decoding multi-limb movements from two-photon calcium imaging of neuronal activity using deep learning

Abstract Objective. Brain-machine interfaces (BMIs) aim to restore sensorimotor function to
individuals suffering from neural injury and disease. A critical step in implementing
a BMI is to decode movement intention from recorded neural activity patterns in
sensorimotor areas. Optical imaging, including two-photon (2p) calcium imaging,
is an attractive approach for recording large-scale neural activity with high spatial
resolution using a minimally-invasive technique. However, relating slow twophoton
calcium imaging data to fast behaviors is challenging due to the relatively low
optical imaging sampling rates. Nevertheless, neural activity recorded with 2p calcium
imaging has been used to decode information about stereotyped single-limb
movements and to control BMIs. Here, we expand upon prior work by applying deep
learning to decode multi-limb movements of running mice from 2p calcium imaging
data.
Approach. We developed a recurrent encoder-decoder network (LSTM-encdec) in
which the output is longer than the input.
Main results. LSTM-encdec could accurately decode information about all four limbs
(contralateral and ipsilateral front and hind limbs) from calcium imaging data recorded
in a single cortical hemisphere.
Significance. Our approach provides interpretability measures to validate
decoding accuracy and expands the utility of BMIs by establishing the groundwork for
control of multiple limbs. Our work contributes to the advancement of neural decoding
techniques and the development of next-generation optical BMIs.

Wartime penetrating traumatic brain injury of the anterior skull base involving the paranasal sinuses: a single-center, first-year experience from Dnipro, Ukraine.

Since February 2022, the number of casualties in the Russian-Ukrainian war have dramatically increased, with a high incidence of penetrating traumatic brain injuries (pTBIs). To date, there has been limited evaluation of pTBI of the anterior skull base involving the paranasal sinuses. The objective of this study was to highlight the authors' experience with this injury pattern and identify specific factors associated with favorable short-term (1-month) outcome and survival. The authors conducted a single-institution retrospective review of patient data collected from the 1st year of the Russian-Ukrainian war at a frontline civilian Ukrainian hospital. To prevent complications from conservative treatment of pTBI with paranasal sinus injury, a protocol of early primary neurosurgical treatment including debridement/hematoma evacuation, repair of dural defects with vascularized pericranial flaps, and titanium plating of external/skull base defects was implemented. Using 1-month postoperative Glasgow Outcome Scale scores, the authors defined a favorable outcome as good recovery/moderate disability and a poor outcome as severe disability/vegetative state/death. Patient demographics, injury characteristics, imaging findings, and postoperative complications were assessed. Logistic regression models were used to estimate the effect of patient characteristics on unfavorable outcome or survival. From February 2022 to February 2023, there were 141 pTBIs (20%) involving the paranasal sinuses, 134 (95%) due to blast fragmentation. One hundred eighteen patients (84%) had a favorable outcome. Most patients with pTBIs (69%) had other nonbrain-related injuries. While 48 patients (34%) presented with preoperative CSF leak, only 1 patient (0.7%) had persistent postoperative CSF leak, which was managed with lumbar drainage. High admission Glasgow Coma Scale (GCS) score, favorable injury lateralization (single hemisphere involved), and low Injury Severity Score (ISS) were associated with significantly increased odds of favorable short-term outcome, whereas high admission GCS scores and no midline shift were associated with significantly increased odds of survival. This was the largest single-year study on neurosurgical treatment of wartime pTBI involving the paranasal sinuses. Implementation of primary neurosurgical intervention at the time of presentation demonstrated promising early results and a shift away from expectant management of this injury pattern. The association of high admission GCS score, low ISS, favorable injury lateralization, and no midline shift on favorable short-term outcomes or survival has not been previously documented with this injury pattern.

Gesture encoding in human left precentral gyrus neuronal ensembles.

Understanding the cortical activity patterns driving dexterous upper limb motion has the potential to benefit a broad clinical population living with limited mobility through the development of novel brain-computer interface (BCI) technology. The present study examines the activity of ensembles of motor cortical neurons recorded using microelectrode arrays in the dominant hemisphere of two BrainGate clinical trial participants with cervical spinal cord injury as they attempted to perform a set of 48 different hand gestures. Although each participant displayed a unique organization of their respective neural latent spaces, it was possible to achieve classification accuracies of ~70% for all 48 gestures (and ~90% for sets of 10). Our results show that single unit ensemble activity recorded in a single hemisphere of human precentral gyrus has the potential to generate a wide range of gesture-related signals across both hands, providing an intuitive and diverse set of potential command signals for intracortical BCI use.

Bihemispheric Seizure Without Generalization.

A 70-year-old male without prior psychiatric history presented with recurrent episodes (<60seconds each, every 5-10minutes) of left hemibody and right lower extremity jerking movements concerning for seizure with preserved awareness (Video). Examination showed left hemiparesis (leg > arm) in addition to right lower extremity weakness. Computed tomography showed a right parafalcine acute subdural hematoma (SDH). Clinical events did not recur after intravenous lorazepam (4mg) and levetiracetam load (3500mg), and his weakness improved. He was continued on levetiracetam and has since remained seizure free for 16months. A 60-minute awake/sleep electroencephalogram (EEG) obtained 12hours after administration of antiseizure medications showed low amplitude theta slowing (posterior predominant) in the range of 5-7Hz. There was no apparent epileptiform activity or other abnormalities during the awake and sleep recording or photic stimulation. Focal seizures originate from pathologic disruption of neuronal activity within an isolated brain region, almost exclusively from a single hemisphere. Focal seizures may generalize bilaterally with associated impaired awareness. This is the first visual report demonstrating focal, bihemispheric clinical seizures, without generalization or impaired awareness. Rarely patients with generalized motor involvement from seizures have had retained consciousness and memory. The parafalcine SDH likely promoted epileptogenicity of the bilateral hemispheres. Acute and chronic SDH commonly present with seizures. Although there were no supportive electrographic findings, parasagittal epileptogenic lesions may be difficult for both clinical and electrographic localization. Post-event paresis with clinical improvement in the hours after event cessation supports clinical seizure.

Our experience of pediatric epilepsy surgery

Objective: to evaluate the effectiveness and safety of different operations in children with drug-resistant epilepsy. Materials and Method. 91 children with drug-resistant epilepsy were enrolled in a retrospective study. Mean age was 10.3±5.1 years. Anterior temporal lobectomy was performed in 16 (57.1%) patients, lesionectomy – in 9 (10.0%), microsurgical callosotomy in 18 (19.8%), stereotactic callosotomy in 7 (7.7%), multifocal resections in 4 (4.4%), functional hemispherotomy in 14 (15.6%). Stereotactic radiofrequency callosotomy was performed on a CRW Stereotactic frame (Radionics Inc., USA). Ultrasound navigation and neuronavigation were used in 6 (7%) and 14 (15%) cases correspondingly. Intraoperative corticography was applied in 8 (9%) cases. Postoperative long-term follow-up lasted from 1 to 17 years (mean - 8.2±2.1 years). Results. An epileptogenic zone within single hemisphere was indentified in 66 (72.2%) cases, while bilateral epileptiform activity was observed in 25 (27.5%) children. The most common etiologies of epilepsy included hypoxic-ischemic encephalopathy, intracerebral hemorrhage, meningoencephalitis, Rasmussen syndrome, cortical dysplasia, tumors.After surgery 51 (56%) patients became seizures free (Engel 1), 14 (15.4%) patients had rare auras or focal seizures (Engel 2). In 25 (27.5%) cases, seizure frequency reduction was less than 75% or did not change significantly. The most favorable outcomes were associated with resection procedures, resulting in complete seizure control in 46 (69.7%) out of 66 children, with significant improvement observed in 9 (13.6%) cases. After callosotomy drop-attacks stopped in 14 (78%) out of 18 who had them before surgery. Operative complications were encountered in 6 (6.6%) cases, postoperative mortality occurred in 1 (1.1%) case. Conclusions. The key to the effectiveness of surgical treatment of childhood epilepsy is early surgical intervention, which leads to the control of epileptic seizures, correction of psychological and cognitive emotional disorders and improvement of quality of life. The combination of resection procedures and disconnections contributes to the reduction of epileptogenic neurons and suppression of epileptic discharges.

Hemispherectomy Outcome Prediction Scale: a validity study.

Hemispherectomy is highly effective for patients with medically refractory epilepsy (MRE) arising from a single hemisphere. Recently, the Hemispherectomy Outcome Prediction Scale (HOPS) was developed as a prediction tool for seizure freedom after hemispherectomy. The authors' goal was to perform a validation study to determine the generalizability of the HOPS score. The authors present an observational, retrospective, 20-year, single-institution, two-surgeon experience using the lateral peri-insular hemispherectomy approach to validate the HOPS score. Variables used to derive the HOPS score included seizure onset age, semiology, PET hypometabolism, seizure substrate, and history of prior epilepsy resection. Multivariable logistic regression, multiple imputation, and Bayesian analyses were used to determine validity. The authors' cohort comprised 60 patients; 55% of patients were male and 78% were Caucasian. The median age at first hemispherectomy surgery was 72 months. At 1 year postoperatively, 80% of patients had Engel class I outcomes, analogous to most contemporary series. All patients who experienced seizure recurrence after hemispherectomy did so within the first 2 years postoperatively. Sixteen (27%) and 10 (17%) patients had contralateral MRI findings and hypometabolism on PET, respectively. Both a multivariable logistic regression model using HOPS score variables (model p = 0.2588) and a revised model that included contralateral MRI findings (model p = 0.4715) were not statistically significant in this cohort. Bayesian analysis also did not validate the HOPS score. While seizure outcome prediction tools may be helpful for counseling patients about postoperative outcomes, rigorous validity and reliability testing are required. Prospective, standardized, and longitudinal evaluation of patients undergoing hemispherectomy are needed.

Computational Modeling of the Feasibility of Substituted [1.1.1]Propellane Formation from Anionic Bridgehead Bromide Precursors

[1.1.1]Propellane, a compound whose structure includes two saturated carbons in which all four bonds are directed into a single hemisphere, is of theoretical interest, but has also seen recent practical applications. Mono-, di-, and trisubstituted derivatives of this propellane (by substitution of its CH2 bridges with O, S, NH, CF2, CO, SO, and SO2) remain unknown despite several computational studies that have suggested some may be stable. In this study, we show that, in several cases, substituted propellanes are spontaneously formed upon the attempted computational optimization of the geometries of anionic bridgehead bromide precursors using the ωB97X-D/aug-cc-pVDZ DFT method. Spontaneous formation suggests that these propellanes are at lower energy relative to the precursors and, therefore, are promising synthetic targets. The success or failure to spontaneously form the propellane is considered in relation to the length and strain energy of the central bridgehead-bridgehead bond, as well as the total strain energy of each propellane.

Azimuthal invariance to looming stimuli in the Drosophila giant fiber escape circuit.

Spatially invariant feature detection is a property of many visual systems that rely on visual information provided by two eyes. However, how information across both eyes is integrated for invariant feature detection is not fully understood. Here, we investigated spatial invariance of looming responses in descending neurons (DNs) of Drosophila melanogaster. We found that multiple looming responsive DNs integrate looming information across both eyes, even though their dendrites are restricted to a single visual hemisphere. One DN, the giant fiber (GF), responds invariantly to looming stimuli across tested azimuthal locations. We confirmed visual information propagates to the GF from the contralateral eye, through an unidentified pathway, and demonstrated that the absence of this pathway alters GF responses to looming stimuli presented to the ipsilateral eye. Our data highlight a role for bilateral visual integration in generating consistent, looming-evoked escape responses that are robust across different stimulus locations and parameters.

MP73-12 ARTIFICIAL INTELLIGENCE-BASED CANCER MAPPING TO AID IN PROSTATE CANCER THERAPY

You have accessJournal of UrologyCME1 Apr 2023MP73-12 ARTIFICIAL INTELLIGENCE-BASED CANCER MAPPING TO AID IN PROSTATE CANCER THERAPY Wayne Brisbane, Alan Priester, Sakina Mohammed Mota, Joshua Shubert, Jeremy Bong, James Sayre, Brittany Berry-Pusey, and Shyam Natarajan Wayne BrisbaneWayne Brisbane More articles by this author , Alan PriesterAlan Priester More articles by this author , Sakina Mohammed MotaSakina Mohammed Mota More articles by this author , Joshua ShubertJoshua Shubert More articles by this author , Jeremy BongJeremy Bong More articles by this author , James SayreJames Sayre More articles by this author , Brittany Berry-PuseyBrittany Berry-Pusey More articles by this author , and Shyam NatarajanShyam Natarajan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003341.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal therapy (FT) for prostate cancer is gaining prominence as an alternative to whole-gland treatment. FT efficacy relies on predicting disease margins, but their underestimation and patient-specific optimization remain largely unaddressed problems. An artificial intelligence (AI)-based cancer mapping and decision support tool was built using pre-biopsy MRI, targeted biopsy data, and PSA to aid urologists in identifying cancer margins. A reader study was conducted to compare this AI-based software against the standard of care (SOC) in determining the extent of clinically significant prostate cancer (csPCa). METHODS: Seven urologists and three radiologists from five institutions with 2 – 23 years of expertise each evaluated 50 prostatectomy cases (total of 1000 reads) Cases were prospectively eligible for FT, with GG 2-3 csPCa, ≥1 region of interest (ROI), and disease that appeared localized to a single hemisphere or the anterior gland. Each case included T2-weighted MRI, ROI segmentation, and pathology reports with conventional locations. Readers were asked to produce contours on each image that prioritized the inclusion of all csPCa, excluding non-csPCa tissue as a secondary objective. First, readers manually defined margins using all given data (SOC). Then, after≥4 weeks had passed, readers produced AI-assisted margins using custom software (iQuest, Avenda Health, CA) [Figure B]. Margins from each method [Figure C] were evaluated against WM pathology data [Figure D] as ground truth. Statistical tests were performed using generalized estimating equations. RESULTS: AI margins had superior sensitivity (97.4% vs. 38.2%, p<0.0001) to SOC margins in classifying csPCa [Figure A]. AI-assisted margins also had superior balanced accuracy, i.e. (specificity+sensitivity)/2, to SOC margins (84.7% vs. 67.2%, p<0.0001). On average, AI-assisted margins completely encapsulated csPCa in 72.8% of cases, compared to only 1.6% of cases with SOC methods (p<0.0001). Furthermore, the average time spent fell from 3.5 minutes (SOC) to 2.0 minutes (AI-assisted, p<0.0001). CONCLUSIONS: AI-assisted cancer mapping helps address the systematic underestimation of csPCa by SOC methods. This study establishes that AI-assisted margins greatly improve csPCa encapsulation, which could improve oncological efficacy for focal treatments. Source of Funding: Avenda Health © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1039 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wayne Brisbane More articles by this author Alan Priester More articles by this author Sakina Mohammed Mota More articles by this author Joshua Shubert More articles by this author Jeremy Bong More articles by this author James Sayre More articles by this author Brittany Berry-Pusey More articles by this author Shyam Natarajan More articles by this author Expand All Advertisement PDF downloadLoading ...

Electroencephalography Findings in Wrong Way Eyes: Unilateral Hemispheric Dysfunction Supporting Smooth Pursuit Asymmetry Hypothesis.

Conjugate horizontal eye deviation away from the side of the lesion, termed Wrong Way Eyes (WWE), is a rare manifestation of supratentorial lesions. The proposed etiologic hypotheses include seizure activity, compression of contralateral horizontal gaze pathways from mass effect or midline shift, and asymmetry of hemispheric smooth pursuit mechanisms. We present neurophysiological evidence that favors the asymmetry of hemispheric smooth pursuit hypothesis. Electroencephalography (EEG) was performed in 2 patients with large left hemispheric supratentorial lesions, capturing fluctuating periods of (a) unresponsiveness with WWE and (b) relative alertness without WWE. One patient had 5 days of continuous EEG, and the other routine EEG. Neither patient had seizures. EEG showed normal right hemispheric activity during both unresponsiveness with WWE and alertness without WWE states. By contrast, more severe left hemispheric dysfunction was evident in the WWE state compared with the non-WWE state in both patients. In one patient, during the relatively alert state, right-beating nystagmus was observed, and drift of the eyes away from the side of the lesion was reliably seen to occur on eyelid closure and after ipsiversive volitional saccades. Seizure activity does not account for WWE. Compression of contralateral horizontal gaze pathways is also unlikely to account for WWE as that hypothetical mechanism should produce EEG abnormalities over the nonlesioned hemisphere, which were not seen. The findings suggest instead that a single dysfunctional hemisphere is sufficient to produce WWE. The repeated rightward drift of the eyes and nystagmus seen in one patient during relative alertness, and the observation of unilateral hemispheric dysfunction on EEG during unresponsiveness with WWE in both patients supports the idea that an imbalance of smooth pursuit mechanisms is most likely to account for this rare phenomenon.

Intersectionality of Race and Question-Asking in Women After Right Hemisphere Brain Damage.

Atypical pragmatic language can impede quality health care access. Right hemisphere brain damage (RHD) results in changes in pragmatic language use; however, little is known about whether there are racial/ethnic influences. Recent research indicated differences in question-asking when RHD survivors were compared with healthy controls, prompting the current examination of question production in women by race/ethnicity and the presence of RHD. Participants were eight Black and eight White women who sustained a single right hemisphere stroke at least 6 months prior to data collection (2016-2020), and eight Black and eight White control participants from the Right Hemisphere Damage Bank (https://rhd.talkbank.org). Videos of informal, first-encounter conversational discourse tasks were transcribed and coded. Analyses were conducted for frequency of questions and question type. Race/ethnicity had a statistically significant effect on the total number of questions and number of content and polar questions. The mean total of questions, number of content questions, and mean number of polar questions for Black participants was significantly less than White participants. There was less variability in question type for Black participants than White participants, and a tendency for Black participants to ask fewer questions regardless of RHD or control status. Acquisition of health information and ensuing health care might be less fruitful for Black women communicating with someone who may not know to conduct comprehension checks and be proactive in provision of information. To be culturally responsive to Black patients with communication disorders, providers might apply this awareness of reduced question-asking to their strategies to improve patient-provider communication. https://doi.org/10.23641/asha.21809475.

Chronic electrophysiology reveals age related loss of coherence between hippocampus and entorhinal cortex in ThyTau22 mice

AbstractBackgroundRecent studies suggest spatial learning and memory impairment, which is an early clinical sign of Alzheimer’s disease (AD), is caused by dysfunction of neurons that communicate between the hippocampus and entorhinal cortex. Technological limitations have prevented chronic cellular‐level tracking of these interconnected brain regions during the many months or years before onset of age‐related cognitive deficits. This study aims to take advantage of recent progress in chronic electrophysiology probes to explore how cellular and circuit‐level changes progress with aging across these two brain regions in a mouse model of AD.MethodTwo flexible electrophysiology probes were implanted with into a single hemisphere of ThyTau22 or WT mice. One probe was targeted to the hippocampus, and the other to the medial entorhinal cortex. Recordings were made from 32 electrodes from each probe once per week over 6 months while mice were walking along a linear track in virtual reality.ResultLongitudinal electrophysiology in ThyTau22 mice show an aging and tau‐pathology correlated decrease in local field potential (LFP) coherence at multiple frequencies. Decoherence is observed both within and between the hippocampus and entorhinal cortex.ConclusionThese results suggest that tau pathology plays a significant role in the loss of neuronal network integrity with age.

With childhood hemispherectomy, one hemisphere can support—but is suboptimal for—word and face recognition

The right and left cerebral hemispheres are important for face and word recognition, respectively-a specialization that emerges over human development. The question is whether this bilateral distribution is necessary or whether a single hemisphere, be it left or right, can support both face and word recognition. Here, face and word recognition accuracy in patients (median age 16.7 y) with a single hemisphere following childhood hemispherectomy was compared against matched typical controls. In experiment 1, participants viewed stimuli in central vision. Across both face and word tasks, accuracy of both left and right hemispherectomy patients, while significantly lower than controls' accuracy, averaged above 80% and did not differ from each other. To compare patients' single hemisphere more directly to one hemisphere of controls, in experiment 2, participants viewed stimuli in one visual field to constrain initial processing chiefly to a single (contralateral) hemisphere. Whereas controls had higher word accuracy when words were presented to the right than to the left visual field, there was no field/hemispheric difference for faces. In contrast, left and right hemispherectomy patients, again, showed comparable performance to one another on both face and word recognition, albeit significantly lower than controls. Altogether, the findings indicate that a single developing hemisphere, either left or right, may be sufficiently plastic for comparable representation of faces and words. However, perhaps due to increased competition or "neural crowding," constraining cortical representations to one hemisphere may collectively hamper face and word recognition, relative to that observed in typical development with two hemispheres.

Induction of seizures due to cortical hyperexcitability during a podiatric physical examination in an epileptic patient: A case report

Epilepsy is a neurological disorder affecting the central nervous system and is characterized by recurrent and unprovoked seizures. Seizures often occur due to cortical hyperexcitability because of inappropriate sensory, cognitive, and reflex stimuli. Epilepsy has numerous etiologies, each related to an underlying central nervous system dysfunction. Focal seizures are limited to a single cerebral hemisphere, whereas general seizures involve both hemispheres. Literature review has shown the use of transcranial magnetic stimulation for inciting epileptic seizures, as well as the use of a tuning fork to elicit non-epileptic seizures (NES). However, minimal research exists demonstrating the use of a 128-Hz tuning fork to induce epileptic seizures. Clinical symptoms of psychogenic non-epileptic seizures (PNES) and epileptic seizures are very similar to the untrained eye and without the assistance of an EEG, one cannot distinguish the two. We report a case in which a 71-year-old female experienced symptoms consistent with an “aura” or onset of a seizure when subjected to an examination of vibratory sensation to the left medial malleolus during a general podiatric examination. The patient’s past medical history includes partial symptomatic epilepsy with complex partial seizures in addition to NES. The authors agree that it is imperative to practice with caution when conducting a general podiatric examination on a patient who is predisposed to epileptic activity, as the threshold for an induction of a seizure may be lowered.

The PV2 cluster of parvalbumin neurons in the murine periaqueductal gray: connections and gene expression

The PV2 (Celio 1990), a cluster of parvalbumin-positive neurons located in the ventromedial region of the distal periaqueductal gray (PAG) has not been previously described as its own entity, leading us to study its extent, connections, and gene expression. It is an oval, bilateral, elongated cluster composed of approximately 475 parvalbumin-expressing neurons in a single mouse hemisphere. In its anterior portion it impinges upon the paratrochlear nucleus (Par4) and in its distal portion it is harbored in the posterodorsal raphe nucleus (PDR). It is known to receive inputs from the orbitofrontal cortex and from the parvafox nucleus in the ventrolateral hypothalamus. Using anterograde tracing methods in parvalbumin-Cre mice, the main projections of the PV2 cluster innervate the supraoculomotor periaqueductal gray (Su3) of the PAG, the parvafox nucleus of the lateral hypothalamus, the gemini nuclei of the posterior hypothalamus, the septal regions, and the diagonal band in the forebrain, as well as various nuclei within the reticular formation in the midbrain and brainstem. Within the brainstem, projections were discrete, but involved areas implicated in autonomic control. The PV2 cluster expressed various peptides and receptors, including the receptor for Adcyap1, a peptide secreted by one of its main afferences, namely, the parvafox nucleus. The expression of GAD1 and GAD2 in the region of the PV2, the presence of Vgat-1 in a subpopulation of PV2-neurons as well as the coexistence of GAD67 immunoreactivity with parvalbumin in terminal endings indicates the inhibitory nature of a subpopulation of PV2-neurons. The PV2 cluster may be part of a feedback controlling the activity of the hypothalamic parvafox and the Su3 nuclei in the periaqueductal gray.

Annals of Neurology: Volume 91, Number 2, February 2022

An illustration of lesion network mapping of blindsight‐negative versus blindsight. This begins with representative lesion locations from a blindsight and blindsight‐negative patient. Lesions were consolidated into a single hemisphere for analysis. Connectivity between each lesion location and the rest of the brain was computed using a normative database of resting state functional connectivity from 1000 healthy subjects. Pictured are the connectivity patterns derived from the two representative lesion locations. Connectivity differences between lesion locations from blindsight‐negative (n=35) versus blindsight patients (n=34) were identified using a two‐sample, voxelwise t‐test within a mask of regions previously implicated in blindsight (dark grey). Lesions in blindsight‐negative patients showed greater functional connectivity to the medial pulvinar (pulvinar in blue outline) compared to lesions in blindsight patients. See paper in this issue by Kletenik et al. (pp. 217–224).

Cortical Stimulation Paired With Volitional Unimanual Movement Affects Interhemispheric Communication.

Cortical stimulation (CS) of the motor cortex can cause excitability changes in both hemispheres, showing potential to be a technique for clinical rehabilitation of motor function. However, previous studies that have investigated the effects of delivering CS during movement typically focus on a single hemisphere. On the other hand, studies exploring interhemispheric interactions typically deliver CS at rest. We sought to bridge these two approaches by documenting the consequences of delivering CS to a single motor cortex during different phases of contralateral and ipsilateral limb movement, and simultaneously assessing changes in interactions within and between the hemispheres via local field potential (LFP) recordings. Three macaques were trained in a unimanual reaction time (RT) task and implanted with epidural or intracortical electrodes over bilateral motor cortices. During a given session CS was delivered to one hemisphere with respect to movements of either the contralateral or ipsilateral limb. Stimulation delivered before contralateral limb movement onset shortened the contralateral limb RT. In contrast, stimulation delivered after the end of contralateral movement increased contralateral RT but decreased ipsilateral RT. Stimulation delivered before ipsilateral limb movement decreased ipsilateral RT. All other stimulus conditions as well as random stimulation and periodic stimulation did not have consistently significant effects on either limb. Simultaneous LFP recordings from one animal revealed correlations between changes in interhemispheric alpha band coherence and changes in RT, suggesting that alpha activity may be indicative of interhemispheric communication. These results show that changes caused by CS to the functional coupling within and between precentral cortices is contingent on the timing of CS relative to movement.

Plasticity in the developing brain: neurophysiological basis for lesion-induced motor reorganization.

The plasticity of the developing brain can be observed following injury to the motor cortex and/or corticospinal tracts, the most commonly injured brain area in the pre- or peri-natal period. Factors such as the timing of injury, lesion size and lesion location may affect a single hemisphere’s ability to acquire bilateral motor representation. Bilateral motor representation of single hemisphere origin is most likely to occur if brain injury occurs before the age of 2 years; however, the link between injury aetiology, reorganization type and functional outcome is largely understudied. We performed a retrospective review to examine reorganized cortical motor maps identified through transcranial magnetic stimulation in a cohort of 52 patients. Subsequent clinical, anthropometric and demographic information was recorded for each patient. Each patient’s primary hand motor cortex centre of gravity, along with the Euclidian distance between reorganized and normally located motor cortices, was also calculated. The patients were classified into broad groups including reorganization type (inter- and intrahemispheric motor reorganization), age at the time of injury (before 2 years and after 2 years) and injury aetiology (developmental disorders and acquired injuries). All measures were analysed to find commonalities between motor reorganization type and injury aetiology, function and centre of gravity distance. There was a significant effect of injury aetiology on type of motor reorganization (P < 0.01), with 60.7% of patients with acquired injuries and 15.8% of patients with developmental disorders demonstrating interhemispheric motor reorganization. Within the interhemispheric motor reorganization group, ipsilaterally and contralaterally projecting hand motor cortex centres of gravity overlapped, indicating shared cortical motor representation. Furthermore, the data suggest significantly higher prevalence of bilateral motor representation from a single hemisphere in cases of acquired injuries compared to those of developmental origin. Functional outcome was found to be negatively affected by acquired injuries and interhemispheric motor reorganization relative to their respective counterparts with developmental lesions and intrahemispheric motor reorganization. These results provide novel information regarding motor reorganization in the developing brain via an unprecedented cohort sample size and transcranial magnetic stimulation. Transcranial magnetic stimulation is uniquely suited for use in understanding the principles of motor reorganization, thereby aiding in the development of more efficacious therapeutic techniques to improve functional recovery following motor cortex injury.

Neuropathologic correlates of shape of subcortical brain structures

Age-related neuropathologies have devastating effects on subcortical brain structures. MRI can be used to explore patterns of atrophy associated with various diseases, however, definitive diagnosis of age-related neuropathologies is only possible at autopsy. The purpose of this work was to combine ex-vivo MRI and detailed neuropathology in a large community cohort of older adults to conduct the most comprehensive investigation to-date on the association of age-related neuropathologies with the shape of subcortical brain structures. Cerebral hemispheres were obtained from 814 participants of the Rush Memory and Aging Project and Religious Orders Study, two longitudinal cohort studies of aging (Fig. 1). A single brain hemisphere from each participant was imaged ex-vivo on a clinical 3T MRI scanner, while immersed in 4% formaldehyde solution. Following ex-vivo MRI, all hemispheres underwent detailed neuropathologic examination by a board-certified neuropathologist blinded to clinical and imaging findings (Fig. 2). T2-weighted images from all hemispheres were used to segment nucleus accumbens, amygdala, caudate, hippocampus, putamen, and thalamus. Subcortical shape measures were computed using the ENIGMA-Shape protocol. Vertex-wise linear regression was performed for each subcortical structure, modeling the logarithm of the Jacobian determinant at each vertex as a function of a comprehensive list of age-related neuropathologies controlling for demographics and scanners. The analysis first considered data from all hemispheres (left hemispheres were mirrored to appear like right hemispheres and the opposite), and then was repeated considering left and right hemispheres separately. When considering all hemispheres (Fig. 3), Alzheimer's pathology, atherosclerosis, and TDP-43 pathology were all associated with unique patterns of inward deformation of the hippocampus and amygdala. When considering left and right hemispheres separately (Fig. 4), the results were relatively similar to the combined analysis. Also, when considering the right hemispheres alone, arteriolosclerosis was associated with inward deformation of the putamen and thalamus. Lewy bodies, infarcts and cerebral amyloid angiopathy did not show any links to the shape of subcortical brain structures. Among the different age-related neuropathologies, Alzheimer's pathology, TDP-43 pathology, atherosclerosis and arteriolosclerosis are the ones that have independent contributions on shape abnormalities of subcortical brain structures that could potentially contribute towards in-vivo prediction of these neuropathologies.

Revisiting the attentional bias in the split brain

Previous research has revealed a strong right bias in allocation of attention in split brain subjects, suggesting that a pathological attention bias occurs not only after unilateral (usually right-hemispheric) damage but also after functional disconnection of intact right-hemispheric areas involved in allocation of attention from those in the left hemisphere. Here, we investigated the laterality bias in spatial attention, as measured with the greyscales task, in two split-brain subjects (D.D.C. and D.D.V.) who had undergone complete callosotomy. The greyscales task requires participants to judge the darker (or brighter) of two left-right mirror-reversed luminance gradients under conditions of free viewing, and offers an efficient means of quantifying pathological attentional biases in patients with unilateral lesions. As predicted, the results of the two split-brain subjects revealed a pathological rightward bias in allocation of attention, suggesting strong dependence on a single hemisphere (the left) in spatial attention, which is opposite to what one expects from people with intact commissures, and is remarkable in that it occurs in free viewing. In that sense both split-brain patients are behaving as though the brain is indeed split, especially in D.D.C. who had undergone partial resection of the anterior commissure in addition to complete callosotomy, whereas the anterior commissure is still intact in D.D.V. The findings support the view that the commissural pathways play a significant role in integration of attentional processes across cerebral hemispheres.