This scientific commentary refers to ‘Thalamic alterations remote to infarct appear as focal iron accumulation and impact clinical outcome’, by Kuchcinski et al. (doi:10.1093/brain/awx114).

This scientific commentary refers to ‘Tremor stability index: a new tool for differential diagnosis in tremor syndromes’, by di Biase et al. (doi:10.1093/brain/awx104).

This scientific commentary refers to ‘Cerebrovascular resistance and cerebral amyloidosis: effects on cognitive decline, cortical atrophy and progression to dementia’, by Yew and Nation (doi:10.1093/brain/awx112).

This scientific commentary refers to ‘Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer’s disease’, by Parbo et al., (doi:10.1093/brain/awx120).

Sporadic cerebral amyloid angiopathy is a common small vessel disease and a largely untreatable cause of ICH and contributor to age-related cognitive decline and Alzheimer’s disease. Charidimou et al. provide an interdisciplinary review of emerging concepts in the field, illustrating mechanisms associated with amyloid cerebrovascular pathology and neurological dysfunction.

Delmont et al. identify neurofascin-186, the isoform of neurofascin at nodes of Ranvier, as the target of autoantibodies in a subset of patients with chronic inflammatory neuropathies. These patients have a distinct clinical presentation and reversible conduction deficits. The antibodies are IgG4 and target a different epitope to anti-neurofascin-155 IgG4.

Glutamate has been implicated in migraine pathophysiology, but direct evidence for altered glutamate levels is lacking. Using 7 Tesla MR spectroscopy, Zielman et al. report that glutamate levels are indeed increased in the visual cortex of patients with migraine without aura. These results strengthen the link between glutamate and migraine.

Ictal SPECT is used in presurgical evaluations of refractory epilepsy. Tousseyn et al. examine whether ictal perfusion changes correspond to electrically connected networks. Using evoked responses following direct electrical stimulation during stereo-electroencephalography as a connectivity measure, they show that ictal perfusion is not random but is supported by underlying connectivity.

Current antiepileptic drugs cannot prevent the onset of epilepsy or its progression. Pauletti et al. show that antioxidant drugs in medical use administered early post-injury block spontaneous seizure progression and neurodegeneration in an epilepsy model, and rescue cognitive deficits. This intervention may be considered for patients exposed to potential epileptogenic insults.

Zrzavy et al. analyse the phenotype of microglia in evolving lesions from patients with multiple sclerosis. Microglia lose their homeostatic phenotype in active lesions and express activation markers functionally related to tissue injury. Macrophages in the lesions are derived in part from resident microglia and in part from recruited myeloid cells.

Delayed treatment with recombinant tissue plasminogen activator (tPA) for ischaemic stroke may exacerbate blood-brain barrier breakdown and lead to lethal haemorrhagic transformation. Mao, Li et al. report that regulatory T cell adoptive transfer reduces tPA-mediated blood-brain barrier damage and brain haemorrhage after stroke by two inhibitory mechanisms involving CCL2 and MMP9.

See Duering and Schmidt (doi:10.1093/awx135) for a scientific commentary on this article.

Thalamic alterations can occur remote from infarcts through thalamo-cortical or cortico-thalamic degeneration. By quantifying iron with R2* as a marker of neurodegeneration, Kuchcinski et al. show that secondary thalamic alterations are focally located within specific nuclei depending on infarct location, and independently contribute to post-stroke functional, cognitive and emotional outcomes.

The pre-supplementary motor area/dorsal anterior cingulate (SMA/dACC) has a broad role in cognition. Geranmayeh et al. perform longitudinal fMRI in 27 patients after stroke, and show that preSMA/dACC activity during speech production positively correlates with levels of spontaneous recovery. Recruitment of domain-general systems can thus help to restore language function.

Parkinson’s disease varies greatly in terms of clinical manifestation and prognosis. Fereshtehnejad et al. propose clinical criteria for ‘mild motor-predominant’, ‘diffuse malignant’ and ‘intermediate’ subtypes. Patients with ‘diffuse malignant’ subtype demonstrate more profound dopaminergic deficits, increased atrophy in disease-associated networks, a more Alzheimer’s disease-like CSF profile and more rapid progression.

See Vidailhet et al. (doi:10.1093/brain/awx140) for a scientific commentary on this article.

About two out of ten patients with Parkinson’s disease, and three out of ten with essential tremor, are initially misdiagnosed. di Biase, Brittain et al. report a novel neurophysiological measure, the Tremor Stability Index (TSI), which can discriminate Parkinson’s disease tremor and essential tremor with high diagnostic accuracy (92%).

See Markus (doi:10.1093/awx161) for a scientific commentary on this article.

Abnormalities in cerebral blood pressure and flow have been implicated in Alzheimer’s disease. Yew and Nation show that elevated cerebrovascular resistance, defined as the ratio of blood pressure to cerebral blood flow, is associated with greater cognitive decline, brain atrophy, and likelihood of progression to dementia over two years in older adults.

See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.

Using the PET ligands ¹¹C-PK11195 and ¹¹C-PiB, Parbo et al. demonstrate cortical inflammation in more than two-thirds of subjects with mild cognitive impairment due to Alzheimer’s disease. PET-based imaging of cortical inflammation in prodromal Alzheimer’s disease may have application in future anti-inflammatory drug trials.

Aberrant insulin-like growth factor-1 receptor (IGF-1R) signalling is observed in Alzheimer’s disease. George et al. report that blocking neuronal IGF-1R signalling in elderly mice protects against Aβ-induced cognitive impairments and neuroinflammation. Neuronal defences against Alzheimer’s disease rely on an endogenous gene expression programme similar to that activated by IGF-1R suppression.

Calretinin+ neurons help maintain the excitation–inhibition balance. Adorjan et al. show that the caudate nucleus of individuals with autism spectrum disorder (ASD) contains a lower density of calretinin+ interneurons than that of matched controls. This is one of the most striking examples of altered forebrain neuronal densities in ASD.

Patients with PTSD exhibit hypersensitivity to a broad range of threat-neutral stimuli. Clancy et al. demonstrate intrinsic sensory hyperactivity and sensory-driven inhibition deficits, which could overwhelm frontal processing and disrupt executive control. This sensory pathology, implicating dysregulated triangular sensory-prefrontal cortex-amygdala circuitry, suggests potential utility of sensory-based interventions in PTSD.

Fifty years ago, one of the first studies to show the neuropsychological consequences of sectioning the corpus callosum was published in Brain. Volz and Gazzaniga review key findings from studies of ‘split-brain’ patients, before considering topics that remain the subject of ongoing debate, such as the concept of cross-cueing.