Frontotemporal correlates of impulsivity and machine learning in retired professional athletes with a history of multiple concussions

The frontotemporal cortical network is associated with behaviours such as impulsivity and aggression. The health of the uncinate fasciculus (UF) that connects the orbitofrontal cortex (OFC) with the anterior temporal lobe (ATL) may be a crucial determinant of behavioural regulation. Behavioural changes can emerge after repeated concussion and thus we used MRI to examine the UF and connected gray matter as it relates to impulsivity and aggression in retired professional football players who had sustained multiple concussions. Behaviourally, athletes had faster reaction times and an increased error rate on a go/no-go task, and increased aggression and mania compared to controls. MRI revealed that the athletes had (1) cortical thinning of the ATL, (2) negative correlations of OFC thickness with aggression and task errors, indicative of impulsivity, (3) negative correlations of UF axial diffusivity with error rates and aggression, and (4) elevated resting-state functional connectivity between the ATL and OFC. Using machine learning, we found that UF diffusion imaging differentiates athletes from healthy controls with significant classifiers based on UF mean and radial diffusivity showing 79–84 % sensitivity and specificity, and 0.8 areas under the ROC curves. The spatial pattern of classifier weights revealed hot spots at the orbitofrontal and temporal ends of the UF. These data implicate the UF system in the pathological outcomes of repeated concussion as they relate to impulsive behaviour. Furthermore, a support vector machine has potential utility in the general assessment and diagnosis of brain abnormalities following concussion.     

Misfolded α-Synuclein in Cerebrospinal Fluid of Contact Sport Athletes

Background

Misfolded α-synuclein in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) can be detected using the real-time quaking-induced conversion (RT-QuIC) technique in cerebrospinal fluid (CSF).

Objectives

The objectives are (1) to examine misfolded CSF α-synuclein incidence, and (2) to compare clinical presentation, sports history, brain volumes, and RT-QuIC α-synuclein positivity in former athletes.

Methods

Thirty former athletes with magnetic resonance imaging, neuropsychological testing, and CSF analyzed for phosphorylated tau 181 (p-tau), total tau (t-tau), amyloid-β 42 (Aβ42), and neurofilament light chain (NfL). CSF α-synuclein was detected using RT-QuIC.

Results

Six (20%) former athletes were α-synuclein positive. α-Synuclein positive athletes were similar to α-synuclein negative athletes on demographics, sports history, clinical features, CSF p-tau, t-tau, Aβ42, and NfL; however, had lower grey matter volumes in the right inferior orbitofrontal, right anterior insula and right olfactory cortices.

Conclusions

α-Synuclein RT-QuIC analysis of CSF may be useful as a prodromal biofluid marker of PD and DLB. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

BOLD‐based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease

Cerebrovascular reactivity (CVR) is a dynamic measure of the cerebral blood vessel response to vasoactive stimulus. Conventional CVR measures amplitude changes in the blood‐oxygenation‐level‐dependent (BOLD) signal per unit change in end‐tidal CO₂ (P_ETCO₂), effectively discarding potential timing information. This study proposes a deconvolution procedure to characterize CVR responses based on a vascular transfer function (VTF) that separates amplitude and timing CVR effects. We implemented the CVR‐VTF to primarily evaluate normal‐appearing white matter (WM) responses in those with a range of small vessel disease. Comparisons between simulations of P_ETCO₂ input models revealed that boxcar and ramp hypercapnia paradigms had the lowest relative deconvolution error. We used a T₂* BOLD‐MRI sequence on a 3 T MRI scanner, with a boxcar delivery model of CO₂, to test the CVR‐VTF approach in 18 healthy adults and three white matter hyperintensity (WMH) groups: 20 adults with moderate WMH, 12 adults with severe WMH, and 10 adults with genetic WMH (CADASIL). A subset of participants performed a second CVR session at a one‐year follow‐up. Conventional CVR, area under the curve of VTF (VTF‐AUC), and VTF time‐to‐peak (VTF‐TTP) were assessed in WM and grey matter (GM) at baseline and one‐year follow‐up. WMH groups had lower WM VTF‐AUC compared with the healthy group (p < 0.0001), whereas GM CVR did not differ between groups (p > 0.1). WM VTF‐TTP of the healthy group was less than that in the moderate WMH group (p = 0.016). Baseline VTF‐AUC was lower than follow‐up VTF‐AUC in WM (p = 0.013) and GM (p = 0.026). The intraclass correlation for VTF‐AUC in WM was 0.39 and coefficient of repeatability was 0.08 [%BOLD/mm Hg]. This study assessed CVR timing and amplitude information without applying model assumptions to the CVR response; this approach may be useful in the development of robust clinical biomarkers of CSVD.     

The developing stroke: management decisions.

Radiologists have become important members of a multidisciplinary team aimed at treating stroke. New studies such as the NINDS (National Institute of Neurological Disorders and Stroke) intravenous and PROACT II (prolyse in acute cerebral thromboembolism II) intra-arterial thrombolytic trials for acute stroke have focused attention on the need for rapid management. Radiologists play a key role in the diagnosis and selection of patients who may benefit from these therapies. We review current issues in the computed tomographic and magnetic resonance imaging diagnosis of acute stroke and the data supporting the various treatment options.     

High-grade intracranial chondrosarcoma presenting with haemorrhage

Chondrosarcomas are rare sarcomas that produce malignant cartilage, infrequently arising as a primary intracranial tumour. We present a patient with intracranial chondrosarcoma with intratumoural haemorrhage arising in an unusual location and with unusual imaging findings. A 46-year-old man presented with headache, nausea, and vomiting over the previous 24 hours. Physical and neurological examinations were normal. Cranial CT scans and MRI revealed a large right pre-frontal (subdural) and interhemispheric heterogeneous density associated with a frontal, partially calcified mass and midline shift. An awake craniotomy was performed. With the intra-operative quick section favouring subdural hematoma, the lesion was subtotally resected. Follow-up imaging confirmed residual mass. Pathology examination revealed a high-grade malignant neoplasm with chondroid differentiation, diagnosed as conventional Grade III chondrosarcoma. The patient was referred to oncology for follow-up and radiation therapy. Intracranial chondrosarcoma was first reported in 1899, and since then continues to be an extremely rare malignancy of the brain. These tumours commonly present as extra-axial masses, originating from the skull base, and produce symptoms due to progressive enlargement and compression of local structures. Unusual presentations of these tumours, such as vascularity, intratumoural haemorrhage, and intra-axial location, may complicate pre-surgical decision making by altering the provisional diagnosis prior to intervention. This patient emphasises the importance of careful analysis and incorporation of imaging findings into surgical decision making. Specific imaging characteristics that, in such unusual situations, are suggestive of chondrosarcoma should motivate an aggressive surgical approach to optimise adjuvant interventions.     

The radiology of headache

The patient who presents with a severe and acute headache should be evaluated radiographically with CT. The key diagnosis to make in this situation is hemorrhage, either subarachnoid or intraparenchymal. Computed tomography is more sensitive to acute hemorrhage than is MRI. When the patient is stable, MRI frequently contributes information to narrow the diagnostic possibilities, because vascular malformations and certain parenchymal lesions have a characteristic appearance on MRI. Hydrocephalus may also present acutely and is easily seen on CT or MRI. In a patient may show WMF and atrophy. The patient with trigeminal neuropathy may demonstrate central or peripheral lesions. In temporomandibular joint dysfunction, conventional tomography and MRI are frequently used. Magnetic resonance imaging shows excellent detail of the disk and surrounding soft tissues, whereas tomography better demonstrates bony changes. When a history of trauma is present, MRI may show a subacute subdural hematoma. These collections are easily seen on MRI, even when isodense on CT. Evidence of old shear injury is also well seen on MRI. Finally, neoplastic, inflammatory, congenital, and idiopathic sources of headache may be demonstrated by either MRI or CT, depending on presentation. MRI will generally show superior characterization.     

Plasticity of the human motor system following muscle reconstruction: a magnetic stimulation and functional magnetic resonance imaging study

OBJECTIVE: Although motor system plasticity in response to neuromuscular injury has been documented, few studies have examined recovered and functioning muscles in the human. We examined brain changes in a group of patients who had a muscle transfer. METHODS: Transcranial magnetic stimulation (TMS) was used to study a unique group of 9 patients who had upper extremity motor function restored using microneurovascular transfer of the gracilis muscle. The findings from the reconstructed muscle were compared to the homologous muscle of the intact arm. One patient was also studied with functional magnetic resonance imaging (fMRI). RESULTS: TMS showed that the motor threshold and short interval intracortical inhibition was reduced on the transplanted side while at rest but not during muscle activation. The difference in motor threshold decreased with the time since surgery. TMS mapping showed no significant difference in the location and size of the representation of the reconstructed muscle in the motor cortex compared to the intact side. In one patient with reconstructed biceps muscle innervated by the intercostal nerves, both TMS mapping and fMRI showed that the upper limb area rather than the trunk area of the motor cortex controlled the reconstructed muscle. CONCLUSIONS: Plasticity occurs in cortical areas projecting to functionally relevant muscles. Changes in the neuronal level are not necessarily accompanied by changes in motor representation. Brain reorganization may involve multiple processes mediated by different mechanisms and continues to evolve long after the initial injury. SIGNIFICANCE: Central nervous system plasticity following neuromuscular injury may have functional relevance.