A parcellation-based connectomic model of hemispatial neglect.

BACKGROUND AND PURPOSE: Hemispatial neglect is characterized by a reduced awareness to stimuli on the contralateral side. Current literature suggesting that damage to the right parietal lobe and attention networks may cause hemispatial neglect is conflicting and can be improved by investigating a connectomic model of the "neglect system" and the anatomical specificity of regions involved in it. METHODS: A meta-analysis of voxel-based morphometry magnetic resonance imaging (MRI) studies of hemispatial neglect was used to identify regions associated with neglect. We applied parcellation schemes to these regions and performed diffusion spectrum imaging (DSI) tractography to determine their connectivity. By overlaying neglect areas and maps of the attention networks, we studied the relationship between them. RESULTS: The meta-analysis generated a list of 13 right hemisphere parcellations. These 13 neglect-related parcellations were predominantly linked by the superior longitudinal fasciculus (SLF) throughout a fronto-parietal-temporal network. We found that the dorsal and ventral attention networks showed partial overlap with the neglect system and included various other higher-order networks. CONCLUSIONS: We provide an anatomically specific connectomic model of the neurobehavioral substrates underlying hemispatial neglect. Our model suggests a fronto-parietal-temporal network linked via the SLF supports the functions impaired in neglect and implicates various higher-order networks which are not limited to the attention networks.

Interventional neurorehabilitation for promoting functional recovery post-craniotomy: a proof-of-concept.

The human brain is a highly plastic 'complex' network-it is highly resilient to damage and capable of self-reorganisation after a large perturbation. Clinically, neurological deficits secondary to iatrogenic injury have very few active treatments. New imaging and stimulation technologies, though, offer promising therapeutic avenues to accelerate post-operative recovery trajectories. In this study, we sought to establish the safety profile for 'interventional neurorehabilitation': connectome-based therapeutic brain stimulation to drive cortical reorganisation and promote functional recovery post-craniotomy. In n = 34 glioma patients who experienced post-operative motor or language deficits, we used connectomics to construct single-subject cortical networks. Based on their clinical and connectivity deficit, patients underwent network-specific transcranial magnetic stimulation (TMS) sessions daily over five consecutive days. Patients were then assessed for TMS-related side effects and improvements. 31/34 (91%) patients were successfully recruited and enrolled for TMS treatment within two weeks of glioma surgery. No seizures or serious complications occurred during TMS rehabilitation and 1-week post-stimulation. Transient headaches were reported in 4/31 patients but improved after a single session. No neurological worsening was observed while a clinically and statistically significant benefit was noted in 28/31 patients post-TMS. We present two clinical vignettes and a video demonstration of interventional neurorehabilitation. For the first time, we demonstrate the safety profile and ability to recruit, enroll, and complete TMS acutely post-craniotomy in a high seizure risk population. Given the lack of randomisation and controls in this study, prospective randomised sham-controlled stimulation trials are now warranted to establish the efficacy of interventional neurorehabilitation following craniotomy.

A connectivity model of the anatomic substrates underlying ideomotor apraxia: A meta-analysis of functional neuroimaging studies.

BACKGROUND: Patients with ideomotor apraxia (IMA) present with selective impairments in higher-order motor cognition and execution without damage to any motor or sensory pathways. Although extensive research has been conducted to determine the regions of interest (ROIs) underlying these unique impairments, previous models are heterogeneous and may be further clarified based on their structural connectivity, which has been far less described. OBJECTIVE: The goal of this research is to propose an anatomically concise network model for the neurophysiologic basis of IMA, specific to the voluntary pantomime, imitation and tool execution, based on intrinsic white matter connectivity. METHODS: We utilized meta-analytic software to identify relevant ROIs in ideomotor apraxia as reported in the literature based on functional neuroimaging data with healthy participants. After generating an activation likelihood estimation (ALE) of relevant ROIs, cortical parcellations overlapping the ALE were used to construct an anatomically precise model of anatomic substrates using the parcellation scheme outlined by the Human Connectome Project (HCP). Deterministic tractography was then performed on 25 randomly selected, healthy HCP subjects to determine the structural connectivity underlying the identified ROIs. RESULTS: 10 task-based fMRI studies met our inclusion criteria and the ALE analysis demonstrated 6 ROIs to constitute the IMA network: SCEF, FOP4, MIP, AIP, 7AL, and 7PC. These parcellations represent a fronto-parietal network consisting mainly of intra-parietal, U-shaped association fibers (40%) and long-range inferior fronto-occipital fascicle (IFOF) fibers (50%). These findings support previous functional models based on dual-stream motor processing. CONCLUSION: We constructed a preliminary model demonstrating the underlying structural interconnectedness of anatomic substrates involved in higher-order motor functioning which is seen impaired in IMA. Our model provides support for previous dual-stream processing frameworks discussed in the literature, but further clarification is necessary with voxel-based lesion studies of IMA to further refine these findings.

The Frontal Aslant Tract and Supplementary Motor Area Syndrome: Moving towards a Connectomic Initiation Axis.

Connectomics is the use of big data to map the brain's neural infrastructure; employing such technology to improve surgical planning may improve neuro-oncological outcomes. Supplementary motor area (SMA) syndrome is a well-known complication of medial frontal lobe surgery. The 'localizationist' view posits that damage to the posteromedial bank of the superior frontal gyrus (SFG) is the basis of SMA syndrome. However, surgical experience within the frontal lobe suggests that this is not entirely true. In a study on n = 45 patients undergoing frontal lobe glioma surgery, we sought to determine if a 'connectomic' or network-based approach can decrease the likelihood of SMA syndrome. The control group (n = 23) underwent surgery avoiding the posterior bank of the SFG while the treatment group (n = 22) underwent mapping of the SMA network and Frontal Aslant Tract (FAT) using network analysis and DTI tractography. Patient outcomes were assessed post operatively and in subsequent follow-ups. Fewer patients (8.3%) in the treatment group experienced transient SMA syndrome compared to the control group (47%) (p = 0.003). There was no statistically significant difference found between the occurrence of permanent SMA syndrome between control and treatment groups. We demonstrate how utilizing tractography and a network-based approach decreases the likelihood of transient SMA syndrome during medial frontal glioma surgery. We found that not transecting the FAT and the SMA system improved outcomes which may be important for functional outcomes and patient quality of life.

Anaplastic Oligodendroglioma - Is Adjuvant Radiotherapy Mandatory following Maximal Surgical Resection?: Grade 3 Oligo Radiotherapy.

BACKGROUND: Current anaplastic oligodendroglioma (AO) management strategies involve surgical resection followed by adjuvant radiotherapy and/or chemotherapy. We investigated a subset of patients at our institution with AO, who, based on their treatment preferences, received surgery without any form of adjuvant therapy. This subset of patients was compared to a cohort with AO who received adjuvant therapy in order to investigate any differences in clinical and survival outcomes. METHODS: A retrospective review of all AO patients treated by the senior author was undertaken between 1994 and 2018. A total of thirty-three cases were identified. Eleven had surgery alone, and twenty-two had surgery with adjuvant therapy. Progression free (PFS) and overall survival (OS) were compared between cohorts and potential confounders were addressed. RESULTS: Gross total resection was achieved in 29 patients, and near total resection in 4 patients. PFS was not statistically different between patients treated with surgery alone versus patients receiving surgery plus adjuvant therapy (surgery alone: 84 ±â€¯16 months; surgery with radiotherapy: 60 ±â€¯9 months; p = 0.08). In addition, OS was also not statistically different between these groups (surgery alone: 215 ±â€¯17 months; surgery with therapy: 241 ±â€¯22 months; p = 0.44). CONCLUSIONS: It is reasonable to consider a "watch and monitor" surveillance strategy in patients who decline adjuvant radiotherapy following surgical resection of their AO. Patients should be made aware that this treatment plan is not standard within current models of care for AO.

Neurochemical supplementation in patients with depressed levels of participation after brain tumor surgery: Rationale and preliminary results.

A unique challenge in some brain tumor patients is the fact that tumors arising in certain areas of the brain involve the neural structures of consciousness or alertness, limiting the patient's ability to participate in rehabilitation following surgery. A critical question is whether neurostimulant therapy can help patients participate in rehabilitation efforts. We performed a retrospective review of all patients undergoing brain tumor surgery by the senior author from 2012 to 2018. We limited this study to patients with tumors occupying critical structures related to consciousness, alertness, and motor initiation. A combination of methylphenidate and levodopa/carbidopa was used to monitor the progress of patients through neurorehabilitation efforts. We identified 101 patients who experienced an inability to participate in rehabilitation (ITPR) in the post-operative period. Of these, 86 patients (85%) were treated with methylphenidate and levodopa/carbidopa. Cases of ITPR were related to dysfunction of the brainstem (12/86 cases, 14%), thalamus (17/86 cases, 20%), hypothalamus (14/86 cases, 16%), basal ganglia (13/86 cases, 15%), and medial frontal lobe (30/86 cases, 35%). Of the 86 individuals treated, 47/86 patients (55%) showed early improvement in their ability to participate with rehabilitation. At three month follow-up, 58/86 patients (67%) had returned to living independently or were at least interactive and cooperative during follow-up examination. This feasibility report suggests that combined therapy with methylphenidate and levodopa/carbidopa may help patients participate in neurorehabilitation efforts in the immediate post-operative period following brain tumor surgery. Randomized, controlled clinical trials are needed to explore this concept more thoroughly.

Measuring graphical strength within the connectome: A neuroanatomic, parcellation-based study.

INTRODUCTION: Graph theory is a promising mathematical tool to study the connectome. However, little research has been undertaken to correlate graph metrics to functional properties of the brain. In this study, we report a unique association between the strength of cortical regions and their function. METHODS: Eight structural graphs were constructed within DSI Studio using publicly available imaging data derived from the Human Connectome Project. Whole-brain fiber tractography was performed to quantify the strength of each cortical region comprising our atlas. RESULTS: Rank-order analysis revealed 27 distinct areas with high average strength, several of which are associated with eloquent cortical functions. Area 4 localizes to the primary motor cortex and is important for fine motor control. Areas 2, 3a and 3b localize to the primary sensory cortex and are involved in primary sensory processing. Areas V1-V4 in the occipital pole are involved in primary visual processing. Several language areas, including area 44, were also found to have high average strength. CONCLUSIONS: Regions of average high strength tend to localize to eloquent areas of the brain, such as the primary sensorimotor cortex, primary visual cortex, and Broca's area. Future studies will examine the dynamic effects of neurologic disease on this metric.

Kidney Tubular Damage and Functional Biomarkers in Acute Kidney Injury Following Cardiac Surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality. We examined the utility of combining biomarkers of kidney function loss (serum cystatin C) and kidney tubular damage (urine neutrophil gelatinase-associated lipocalin [NGAL] and Kidney Injury Molecule-1 [KIM-1]) for the prediction of post-cardiac surgery AKI. METHODS: Single-center prospective cohort study of 106 adults undergoing coronary artery bypass grafting and/or valve surgery with cardiopulmonary bypass (CPB). Primary outcome was postoperative in-hospital AKI defined by serum creatinine (SCr)-Kidney Disease: Improving Global Outcomes criteria. Biomarkers were measured preoperatively, 6 hours after CPB and on postoperative days (PODs) 1 to 4. RESULTS: A total of 23 subjects (21.7%) developed AKI. After adjusting for preoperative left ventricular ejection fraction, body mass index >30 kg/m2, and estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2, the combination of peak serum cystatin C and peak urine KIM-1/creatinine (Cr) (6 hours post-CPB to POD 1) above optimal cutoff significantly associated with postoperative AKI (odds ratio [OR]: 5.32; 95% confidence interval [CI]: 1.31-21.67; P = 0.020). This biomarker combination significantly improved the performance of the clinical model for the prediction of postoperative AKI (area under the curve [AUC]: 0.77, 95% CI: 0.65-0.90 for the clinical model alone versus 0.83, 95% CI: 0.73-0.93 for the clinical model with the addition of biomarker data, P = 0.049). CONCLUSIONS: Combining biomarkers of postoperative kidney function loss and postoperative kidney tubular damage significantly improved prediction of in-hospital AKI following cardiac surgery. Future large, multicenter studies are warranted to assess whether panels of biomarkers reflecting distinct pathobiology can be used to guide interventions and improve short- and long-term outcomes in patients undergoing cardiac surgery.