Voltage-gated potassium channel complex antibodies, particularly those directed against leucine-rich glioma inactivated 1, are associated with a common form of limbic encephalitis that presents with cognitive impairment and seizures. Faciobrachial dystonic seizures have recently been reported as immunotherapy-responsive, brief, frequent events that often predate the cognitive impairment associated with this limbic encephalitis. However, these observations were made from a retrospective study without serial cognitive assessments. Here, we undertook the first prospective study of faciobrachial dystonic seizures with serial assessments of seizure frequencies, cognition and antibodies in 10 cases identified over 20 months. We hypothesized that (i) faciobrachial dystonic seizures would show a differential response to anti-epileptic drugs and immunotherapy; and that (ii) effective treatment of faciobrachial dystonic seizures would accelerate recovery and prevent the development of cognitive impairment. The 10 cases expand both the known age at onset (28 to 92 years, median 68) and clinical features, with events of longer duration, simultaneously bilateral events, prominent automatisms, sensory aura, and post-ictal fear and speech arrest. Ictal epileptiform electroencephalographic changes were present in three cases. All 10 cases were positive for voltage-gated potassium channel-complex antibodies (346-4515 pM): nine showed specificity for leucine-rich glioma inactivated 1. Seven cases had normal clinical magnetic resonance imaging, and the cerebrospinal fluid examination was unremarkable in all seven tested. Faciobrachial dystonic seizures were controlled more effectively with immunotherapy than anti-epileptic drugs (P = 0.006). Strikingly, in the nine cases who remained anti-epileptic drug refractory for a median of 30 days (range 11-200), the addition of corticosteroids was associated with cessation of faciobrachial dystonic seizures within 1 week in three and within 2 months in six cases. Voltage-gated potassium channel-complex antibodies persisted in the four cases with relapses of faciobrachial dystonic seizures during corticosteroid withdrawal. Time to recovery of baseline function was positively correlated with time to immunotherapy (r = 0.74; P = 0.03) but not time to anti-epileptic drug administration (r = 0.55; P = 0.10). Of 10 cases, the eight cases who received anti-epileptic drugs (n = 3) or no treatment (n = 5) all developed cognitive impairment. By contrast, the two who did not develop cognitive impairment received immunotherapy to treat their faciobrachial dystonic seizures (P = 0.02). In eight cases without clinical magnetic resonance imaging evidence of hippocampal signal change, cross-sectional volumetric magnetic resonance imaging post-recovery, after accounting for age and head size, revealed cases (n = 8) had smaller brain volumes than healthy controls (n = 13) (P < 0.001). In conclusion, faciobrachial dystonic seizures can be prospectively identified as a form of epilepsy with an expanding phenot...

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

Subjective inner experiences, such as mind-wandering, represent the fundaments of human cognition. Although the precise function of mind-wandering is still debated, it is increasingly acknowledged to have influence across cognition on processes such as future planning, creative thinking, and problem-solving and even on depressive rumination and other mental health disorders. Recently, there has been important progress in characterizing mind-wandering and identifying the associated neural networks. Two prominent features of mind-wandering are mental time travel and visuospatial imagery, which are often linked with the hippocampus. People with selective bilateral hippocampal damage cannot vividly recall events from their past, envision their future, or imagine fictitious scenes. This raises the question of whether the hippocampus plays a causal role in mind-wandering and, if so, in what way. Leveraging a unique opportunity to shadow people (all males) with bilateral hippocampal damage for several days, we examined, for the first time, what they thought about spontaneously, without direct task demands. We found that they engaged in as much mind-wandering as control participants. However, whereas controls thought about the past, present, and future, imagining vivid visual scenes, hippocampal damage resulted in thoughts primarily about the present comprising verbally mediated semantic knowledge. These findings expose the hippocampus as a key pillar in the neural architecture of mind-wandering and also reveal its impact beyond episodic memory, placing it at the heart of our mental life.SIGNIFICANCE STATEMENT Humans tend to mind-wander ∼30–50% of their waking time. Two prominent features of this pervasive form of thought are mental time travel and visuospatial imagery, which are often associated with the hippocampus. To examine whether the hippocampus plays a causal role in mind-wandering, we examined the frequency and phenomenology of mind-wandering in patients with selective bilateral hippocampal damage. We found that they engaged in as much mind-wandering as controls. However, hippocampal damage changed the form and content of mind-wandering from flexible, episodic, and scene based to abstract, semanticized, and verbal. These findings expose the hippocampus as a key pillar in the neural architecture of mind-wandering and reveal its impact beyond episodic memory, placing it at the heart of our mental life.

Autoantibodies linked with voltage-gated potassium channel (VGKC)-complex antibody-mediated limbic encephalitis (LE) bind to hippocampal subfields. Miller et al. report that chronic LGI1 antibody VGKC-complex LE is associated with focal CA3 atrophy on 7.0-Tesla neuroimaging and autobiographical episodic amnesia. The results point to antibody-mediated pathogenicity and CA3-mediated impairment of episodic memory.

Motor sequence learning on the serial reaction time task involves the integration of response-, stimulus-, and effector-based information. Human primary motor cortex (M1) and the inferior parietal lobule (IPL) have been identified with supporting the learning of effectordependent and -independent information, respectively. Current neurocognitive data are, however, exclusively based on learning complex sequence information via perceptual-motor responses. Here, we investigated the effects of continuous theta-burst transcranial magnetic stimulation (cTBS)-induced disruption of M1 and the angular gyrus (AG) of the IPL on learning a probabilistic sequence via sequential perceptual-motor responses (experiment 1) or covert orienting of visuospatial attention (experiment 2). Functional effects on manual sequence learning were evident during 75% of training trials in the cTBS M1 condition, whereas cTBS over the AG resulted in interference confined to a midpoint during the training phase. Posttraining direct (declarative) tests of sequence knowledge revealed that cTBS over M1 modulated the availability of newly acquired sequence knowledge, whereby sequence knowledge was implicit in the cTBS M1 condition but was available to conscious awareness in the cTBS AG and control conditions. In contrast, perceptual sequence learning was abolished in the perceptual cTBS AG condition, whereas learning was intact and available to conscious awareness in the cTBS M1 and control conditions. These results show that the right AG had a critical role in perceptual sequence learning, whereas M1 had a causal role in developing experience-dependent functional attributes relevant to conscious knowledge on manual but not perceptual sequence learning.