Disruption of posteromedial large-scale neural communication predicts recovery from coma

Objective: We hypothesize that the major consciousness deficit observed in coma is due to the breakdown of long-range neuronal communication supported by precuneus and posterior cingulate cortex (PCC), and that prognosis depends on a specific connectivity pattern in these networks.

Methods: We compared 27 prospectively recruited comatose patients who had severe brain injury (Glasgow Coma Scale score <8; 14 traumatic and 13 anoxic cases) with 14 age-matched healthy participants. Standardized clinical assessment and fMRI were performed on average 4 ± 2 days after withdrawal of sedation. Analysis of resting-state fMRI connectivity involved a hypothesis-driven, region of interest–based strategy. We assessed patient outcome after 3 months using the Coma Recovery Scale–Revised (CRS-R).

Results: Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with PCC, globally notwithstanding etiology. The functional connectivity strength between PCC and medial prefrontal cortex (mPFC) was significantly different between comatose patients who went on to recover and those who eventually scored an unfavorable outcome 3 months after brain injury (Kruskal-Wallis test, p < 0.001; linear regression between CRS-R and PCC-mPFC activity coupling at rest, Spearman ρ = 0.93, p < 0.003).

Conclusion: In both etiology groups (traumatic and anoxic), changes in the connectivity of PCC-centered, spontaneously synchronized, large-scale networks account for the loss of external and internal self-centered awareness observed during coma. Sparing of functional connectivity between PCC and mPFC may predict patient outcome, and further studies are needed to substantiate this potential prognosis biomarker.

Reference: Neurology 10.1212/WNL.0000000000002196 (Full text)

Thalamic amnesia after infarct: the role of the mammillothalamic tract and mediodorsal nucleus

Objective: To improve current understanding of the mechanisms behind thalamic amnesia, as it is unclear whether it is directly related to damage to specific nuclei, in particular to the anterior or mediodorsal nuclei, or indirectly related to lesions of the mammillothalamic tract (MTT).

Methods: We recruited 12 patients with a left thalamic infarction and 25 healthy matched controls. All underwent a comprehensive neuropsychological assessment of verbal and visual memory, executive functions, language, and affect, and a high-resolution structural volumetric MRI scan. Thalamic lesions were manually segmented and automatically localized with a computerized thalamic atlas. As well as comparing patients with controls, we divided patients into subgroups with intact or damaged MTT.

Results: Only one patient had a small lesion of the anterior nucleus. Most of the lesions included the mediodorsal (n = 11) and intralaminar nuclei (n = 12). Patients performed worse than controls on the verbal memory tasks, but the 5 patients with intact MTT who showed isolated lesions of the mediodorsal nucleus (MD) only displayed moderate memory impairment. The 7 patients with a damaged MTT performed worse on the verbal memory tasks than those whose MTT was intact.

Conclusions: Lesions in the MTT and in the MD result in memory impairment, severely in the case of MTT and to a lesser extent in the case of MD, thus highlighting the roles played by these 2 structures in memory circuits.

Reference: Neurology 10.1212/WNL.0000000000002226  (Full text)

Brainbow Hippocampus

Transparent Brain

Diagram of striatal afferent projections from cortex

Diagram demonstrating the functional organization of A. frontal cortex and B. striatal afferent projections. (A) Schematic illustration of the functional connections linking frontal cortical brain regions. (B) Organization of cortical and subcortical inputs to the striatum. In both (A) and (B), the colors denote functional distinctions. Blue: motor cortex, execution of motor actions; green: premotor cortex, planning of movements; yellow: dorsal and lateral prefrontal cortex, cognitive and executive functions; orange: orbital prefrontal cortex, goal-directed behaviors and motivation; red: medial prefrontal cortex, goal-directed behaviors and emotional processing. (Reproduced with permission from Haber, 2003, fig 3.)

Schematic showing anatomy of the striatum (a). Representative lateral (b) and medial (c) illustrations of cortical areas and their connections to the striatum. The colored segment in the striatum represents the area of the striatum receiving projections from the cortical area of the same color. Abbreviations: AC, anterior cingulate cortex; dlPFC, dorsal lateral prefrontal cortex; FEF, frontal eye field; lOFC, lateral orbitofrontal cortex; MC, motor cortex; PPC, posterior parietal cortex; SMA, supplementary motor area; SSC, somatosensory cortex. Compiled from Alexander et al. (1986). (Reproduced  from Utter and Basso, 2008, Fig.2)

Corpus callosum

The corpus callosum (CC) links the cerebral cortex of the left and right cerebral hemispheres and is the largest fibre pathway in the brain.

Gross anatomy

The corpus callosum is ~10cm in length and is C-shaped, like most of the supratentorial structures, in a gentle upwardly convex arch.

It is divided into four parts (anterior to posterior):

• rostrum (continuous with the lamina terminalis)
• genu
• trunk/body
• splenium

Relations

Immediately above the body of the CC, lies the interhemispheric fissure in which runs the falx cerebri, the anterior cerebral vessels. The superior surface of the CC is covered by a thick layer of grey matter known as the indusium griseum.

On either side, the body is seperated from cingulate gyrus by the callosal sulcus.

Attached to the concave undersurface of the CC is the septum pellucidum anteriorly, and the fornix and its commissure posteriorly.

Fibre tracts

Although the CC can be seen as a single large fibre bundle connecting the two hemispheres, an number of individual fibre tracts can be identified. These include:

• genu: forceps minor : connect medial and lateral surfaces of the frontal lobes
• rostrum: connecting the orbital surfaces of the frontal lobes
• trunk (body): pass through the corona radiata to the surfaces of the hemispheres
• trunk and splenium: tapetum; extends along the lateral surface of the occipital and temporal horns of the lateral ventricle
• splenium: forceps major; connect the occipital lobes

These connections can also be divided into :

• homotopic connections  those that link similar regions on each side e.g. visual fields of motor/sensory areas of the trunk
• heterotopic connections: those that link dysimilar areas

Blood supply

The corpus callosum (CC) has a rich blood supply, relatively constant and is uncommonly involved by infarcts. The majority of the CC is supplied by the pericallosal arteries (the small branches and accompanying veins forming the pericallosal moustache) and the posterior pericallosal arteries, branches from the anterior and posterior cerebral respectively. In 80% of patients additional supply comes from the anterior communicating artery, via either subcallosal artery or median callosal artery.

• subcallosal artery (50% of patients) is essentially a large version of a hypothalmic branch, which in addition to supplying part of the hypothalamus also supplies the medial portions of the rostrum and genu

• median callosal artery (30% of patients) can be thought of as a more extended version of the subcallosal artery, in that it travels along the same course, supplies the same structures but additionally reaches the body of the corpus callosum

• posterior pericallosal artery (also known as splenial artery) supplies a variable portion of the splenieum. Its origin is inconstant, arising from P3 or branches there of

The hippocampus on MRI

Coronal images of the head (A), body (B) and tail (C) and a sagittal cross-section of the hippocampus (D) on low resolution 1mm3 T1 1.5 T images (A–D) and on high resolution 0.7 mm3 T2 7 T images (E–H). Note the white matter bands between the dentate gyrus and cornu ammonis on the high resolution T2 images (indicated by arrows). Although we show high resolution 7 T T2 images here, the white matter bands between the dentate gyrus and the cornu ammonis can also be visualized on high resolution T2 3–4 T images