bluuebunny/crossref_metadata_2025_split huggingface dataset:
16 Noninvasive deep brain stimulation via delivery of temporally interfering electric fields
Authors: Grossman Nir 
Published: July 2020

Nir is a Lecturer (Assistant Professor) at Imperial College London and a founding fellow of the UK Dementia Research Institute (UK-DRI). The long-term goal of his research is to develop neuromodulatory interventions for neurodegenerative diseases by direct modulation of the underlying aberrant network activity. Nir received a BSc in Physics from the Israeli Institute of Technology (Technion), an MSc in Electromagnetic Engineering from the Technical University of Hamburg-Harburg, and a PhD in Neuroscience from Imperial College London. He then completed a postdoc training, as a Wellcome Trust Fellow, at the Massachusetts Institute of Technology (MIT) and Harvard University. Nir was recently awarded the prestige prize for Neuromodulation from the Science magazine for describing how temporal interfering of kHz electric fields can non-invasively stimulate focal neural structures deep in the brain.Electrical brain stimulation is a key technique in research and clinical neuroscience studies, and also is in increasingly widespread use from a therapeutic standpoint. However, to date all methods of electrical stimulation of the brain either require surgery to implant an electrode at a defined site, or involve the application of non-focal electric fields to large fractions of the brain. We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice.
4 Delusional misidentification syndrome in basal forebrain lesion
Authors: Ting Simon Kang Seng , Hameed Shahul 
Published: July 2020

IntroductionDelusional misidentification syndrome (DMS) is where a patient reduplicates or incorrectly identifies persons, places, objects or events due to false beliefs. DMS owning to brain lesions are heterogenous in locations, although it has been shown to be more commonly associated with lesions in the right frontal lobe areas. We describe a patient with basal forebrain lesion resulting in amnesia compounded with features of delusional misidentification and specific impairments in emotional perception.Case ReportA 68-year-old man had undergone pituitary surgery for cyst removal, and had developed basal forebrain bleed postoperatively. Four month after, family members noted significant impairments in cognition, including delusional misidentification of his daughter and his house (feeling that his daughter is not his daughter and the house is not his house). Neurobehavioral examination showed Mini Mental State Exam score of 18/30, impaired visual and verbal memory, and executive function.Comprehensive Affect Testing System (CATS) showed impaired emotional affect perception.DiscussionBasal forebrain lesion typically produced amnestis syndrome. While DMS typically seen in right hemispheric or bifrontal lesion, its description in basal forebrain is uncommon. In this case, we demonstrated DMS from a basal forebrain lesion likely results from mismatch between factual retrieval and emotional processing, as basal forebrain lesion typically affects the neuroanatomy that processes and regulates memory, executive functions, and emotions. This case highlights the importance recognizing DMS in basal forebrain lesion and reaffirms the brain-behavior correlation underpinning DMS phenomenon.
21 Psychedelic treatment of functional neurological disorder – a systematic review
Authors: Butler Matthew , Seynaeve Mathieu , Nicholson Timothy R , Pick Susannah , Kanaan Richard A , Lees Andrew , Young Allan H , Rucker James 
Published: July 2020

AimsFunctional neurological disorder (FND), formerly known as conversion disorder, causes a high burden of disability and distress, and is amongst the most commonly encountered conditions in neurology clinics and neuropsychiatry services, yet the therapeutic evidence base is limited. Research into psychedelics such as psilocybin and lysergic acid diethylamide (LSD) is currently being undertaken with significant renewed interest, and in recent studies psychedelics have shown promise in treating a range of psychiatric conditions. Modification of neural circuits associated with self-representation is thought to underlie some of this effect, and as some contemporary theories of FND focus on aberrant somatic self-representation, psychedelics may therefore represent an unexplored treatment option for FND. METHODS: We systematically reviewed studies involving the use of psychedelics in FND. Nine studies published between 1954 – 1967, with a total of 26 patients, were identified. Due to restriction of licencing of psychedelic drugs since this period, no modern studies were identified.ResultsLSD was the most commonly used psychedelic, with some studies also using psilocybin and/or mescaline. The number of therapeutic sessions of psychotherapy ± psychedelic substance administration ranged from one to 26, with descriptions of therapeutic methods used widely varying, and in some cases not described in any detail. Psychedelics were given either orally or intramuscularly, with doses of LSD ranging from 25 to 2,000 micrograms (mcg), and doses of psilocybin ranging from 3 to 15 milligrams (mg). Of those treated, 69% (n=18) were found to have made at least some recovery, with 23% (n=6) having completely recovered after psychedelic therapy. Adverse events were typically mild and transient.ConclusionsStudies were generally of low quality, often lacking control groups and valid outcome measures. Despite this, the degree of improvement is considerable, even if the presumptive bias in favour of the treatment in the studies is taken into consideration. Furthermore, good therapeutic outcomes and lack of adverse events in modern open-label trials utilising psychedelic therapy for neuropsychiatric disorders is encouraging. Advances in the understanding of the neurobiology of FND, as well as further modern clinical research into the therapeutic utility of psychedelics, may help to determine whether psychedelics offer a feasible, safe and effective treatment for FND.
4 Psychedelics: therapeutic mechanisms
Authors: Carhart-Harris Robin 
Published: July 2020

Robin Carhart-Harris moved to Imperial College London in 2008 after obtaining a PhD in Psychopharmacology from the University of Bristol and an MA in Psychoanalysis from Brunel University. At Imperial, he has designed and/or carried out brain imaging studies involving LSD, psilocybin, MDMA and DMT, plus a clinical trial of psilocybin for treatment-resistant depression, and an ongoing study comparing psilocybin with escitalopram for major depressive disorder. In 2019, he set-up the Centre for Psychedelic Research at Imperial and he also an honorary position with the University of Oxford.The talk takes a multi-level approach to the question of how psychedelics work in the brain. Key themes include: the pharmacology of classic serotonergic psychedelics, what this tells us about the function and evolutionary purpose of the serotonin 2A receptor, the acute brain effects of psychedelics as determined by functional brain imaging, the entropic brain hypothesis, current evidence for psychedelic therapy, the ‘REBUS’ hierarchical predictive processing model of the action of psychedelics, and how this maps on to the phenomenology of the acute psychedelic experience and therapeutic outcomes.
23 Limbic neurochemical changes in patients with functional motor symptoms
Authors: Demartini Benedetta , Gambini Orsola , Uggetti Carla , Cariati Maurizio , Eng MarcelloCadioli , Goeta Diana , Marceglia Sara , Ferrucci Roberta , Priori Alberto 
Published: July 2020

ObjectivesTo assess by magnetic resonance spectroscopy (MRS) the N-Acetyl- aspartate, myo-inositol, choline, sum of glutamate and glutamine (Glx), and creatine (Cr) content in the anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC) and in the occipital cortex (OCC) (control region) in patients with functional motor symptoms (FMS) and healthy controls, and to determine whether neurochemical limbic changes as estimated by MRS correlate with FMS-related motor symptom severity, alexithymia, anxiety, depression and quality of life.MethodsThis case-control study enrolled 10 patients with FMS and 10 healthy controls. Participants underwent MRS and were tested with the Mini Mental State Examination, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, 20- Item Toronto Alexithymia Scale and EuroQol 5D.ResultsIn patients with FMS, MRS showed increased Glx/Cr in the ACC/mPFC but normal content in the control OCC. All the other metabolites tested were normal in both regions. The increased Glx/Cr content in the ACC/mPFC correlated with alexithymia, anxiety and severity of symptoms.ConclusionsThe abnormal limbic Glx increase could have a crucial pathophysiological role in FMS possibly by altering limbic-motor interactions, ultimately leading to abnormal movements.
25 Cerebellar cognitive affective syndrome – a case report of diagnosis and management using selective serotonin and norepinephrine reuptake inhibitors
Authors: Sridharan B , Liao YW 
Published: July 2020

Objectives/aimsThe objective of this case is to describe and report on a case of Cerebellar Cognitive Affective Syndrome (CCAS) which improved after the use of high dose venlafaxine therapy. To our knowledge, there are only a few case reports discussing on the effectiveness of various drug therapies in CCAS patients and none had reported on the use of Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRI).MethodsWe describe a 55-year-old male with a history of partially excised grade 1 left cerebellar haemangioblastoma in 2005 followed by Gamma Knife in 2006.Unfortunately, he suffered a recurrence in 2018 requiring embolisation of the haemangioblastoma followed with surgery to resect the tumour. He presented to our specialist neuropsychiatric unit following episodes of new acute unprovoked behavioural changes after surgery. During these episodes, he would become verbally abusive, refuse to engage in any rehab activity, refuse any oral intake, become sexually disinhibited, and experience distressing hallucinations. On the neuropsychiatric ward, he continued to have episodes of severe emotional regulation difficulties. There were no obvious triggers identified and it was noted that the peaks and troughs in his behaviour lasted for a few days before self-resolving and did not follow any particular pattern. In between these episodes, the patient was pleasant, engaging in physiotherapy, and conversed normally with staff.ResultsHe scored a total of 4 out of 10 on the CCAS-scale. A diagnosis of CCAS was concluded given the extensive history of cerebellar injury, nature of presenting complain, and his CCAS-scale score. He was started on high dose SNRI (Venlafaxine XL 150 mg BD). On repeating the CCAS-scale after being on SNRI for 4 months, his score was worse at 6 out of 10. However, we observed a decrease in the frequency, duration, and severity of behavioural change after commencement of SNRI. He benefited greatly from physiotherapy on the ward however despite our best efforts functional independence was not regained. He had to be transferred with the aid of 2 members of staff and mobilises with the aid of an electronic wheelchair.ConclusionsCCAS is a complex disease and the management is yet to be agreed on by the neuropsychiatry community. Our case report illustrated the therapeutic benefit of venlafaxine in the treatment of severe emotional regulation difficulties associated with resection of a cerebellar haemangioblastoma. Furthermore, patients with cerebellar injuries should be managed in a multi-disciplinary manner with input from neurology, neuropsychiatry, neuropsychology, occupational therapist, and physiotherapist.
26 Can an automated assessment of language help distinguish between Functional Cognitive Disorder and early neurodegeneration?
Authors: O’Malley Ronan , Morris Lee-Anne , Longden Chloe , Turner Alex , Walker Traci , Venneri Annalena , Mirheidari Bahman , Christensen Heidi , Reuber Markus , Blackburn Daniel 
Published: July 2020

Objectives/AimsWe used our automated cognitive assessment tool to explore whether responses to questions probing recent and remote memory could aid in distinguishing between patients with early neurodegenerative disorders and those with Functional Cognitive Disorders (FCD).Hypotheses: pwFCD would have no significant differences in pause to speech ratio and measures of linguistic complexity compared to healthy controls. pwFCD would have significant differences in pause to speech ratio and measures of linguistic complexity compared to pwMCI and pwAD.MethodsWe recruited 15 participants with FCD, MCI and AD each as well as 15 healthy controls. Participants answered 12 questions posed by the ‘Digital Doctor’. Automatic processing of the audio-recorded answers involved automatic speech recognition including detecting length of pauses. Two questions probe recent memory, exploring knowledge of current affairs. Two probe remote memory, asking for autobiographical details.We analysed the data using: Pause to speech time ratio. Moving average type token ratio (MATTR): An automated measure of vocabulary richness. Computerised propositional idea density rater (CPIDR): An automated measure of propositional idea density.ResultsThere was a significant difference in the pause to speech ratio for recent memory questions for HC versus AD (P=0.0012) and MCI (p<0.0001) but also compared to those with FCD (p=0.0128). There was a significant difference in the pause to speech ratio for remote memory questions for HC vs AD (p=0.0008) and MCI (p=0.0049) but not FCD (p=0.0613). There was no significant difference between FCD v AD or FCD v MCI. The MATTR and CPIDR were similar across all groups but highest in HC and FMD.ConclusionsThis study rejects both hypotheses. However, the data supports the application of linguistic measures to recent and remote memory questions in distinguishing those with MCI & AD from HC’s. Further work will investigate the utility of incorporating additional measures of lexical and grammatical complexity (word frequency, sentence structure). Longitudinal study will provide insights into which features may predict stability in FCD and HC’s and progression from MCI to AD, supporting the system’s promise as a monitoring tool.
31 Measuring Initiation Impairments Post Brain Injury: Behavioural Initiation Rating Scale (BIRS)
Authors: Lam Joseph , Minioza Dennis , Tyagi Himanshu 
Published: July 2020

ObjectivesBehavioural Initiation is defined as the innate ability to trigger action. There is rich literature describing the high prevalence of motivational disorders and poor behavioural initiation during rehabilitation following acquired brain injury. This is not only due to their neurological conditions, but also that they might have spent many weeks in the wrong environment, with no stimulation other than receiving essential care. There is no established measure for behaviour initiation specific for a rehabilitation setting. This project aim to develop a tool that is sensitive to patients’ level of behavioural initiation, and support evidence-based decision making in formulating treatments in the Multi-Disciplinary Teams (MDT).MethodsWe proposed the 10-item nurse-rated Behavioural Initiation Rating Scale (BIRS). BIRS items were tailored to measure patient behaviour in day-to-day scenarios in inpatient rehabilitation. Included statements were shortlisted from a large pool of comments and observations from the MDT, and a review of literature on the topic. Following basic training with the nursing staff, we piloted a feasibility trial of BIRS for 4 weeks at an 18-bed Neurorehabilitation Unit. We arranged two focus-groups with MDT therapists and the nursing team, to reflect on the implementation of BIRS, and further refinement of scale items. Opinions from the focus-groups were used to revise the current version of BIRS.ResultsIt takes less than 2 minutes to administer and score BIRS. BIRS appears to be sensitive to improvement in behavioural initiation, and in agreement with clinical impressions from MDT and feedback from carers. BIRS has been well-implemented into routine practice, and has resulted a cultural shift in the unit. We identified some levels of between-rating variation in using BIRS, which was addressed by clarifying the instruction manual and giving specific examples for the ambiguous items.Secondary to our aim, the implementation of BIRS has improved the communication between nursing staff and therapists in delivering cohesive neurorehabilitation.ConclusionsBIRS appears to be a promising tool to evaluate patient behavioural initiation in a rehabilitation setting. A multi-centre trial of BIRS is currently being planned to establish its psychometric properties.
32 An interesting case of a stroke involving the primary auditory cortex in a patient with paranoid schizophrenia
Authors: Tyagi Himanshu , Goodison William 
Published: July 2020

IntroductionAuditory verbal hallucinations (AVH): the ‘subjective experience of hearing voices speaking in the absence of corresponding physical stimulation’ (Kompus et al 2013) are part of Schneider’s first rank symptoms. They are included in the American Psychiatric Association DSM-5 diagnostic criteria for Schizophrenia and can be difficult to treat in a proportion of patients with drug resistance in up to 25% of casesCaseOur case is a 52 year old gentleman with a background of treatment resistant schizophrenia, who presented to hospital with a right sided hemiplegia and aphasia. He was diagnosed with a left middle cerebral artery territory stroke. A post CVA MRI showed ‘an extensive mature infarct in the left middle cerebral artery territory and encompassed the left superior temporal gyrus (STG) where the primary auditory cortex (PAC) is located’. He was known to a mental health team from 1989 and had eight inpatient psychiatric admissions, under section, with thought disorder and paranoid thoughts with aggressive behaviour endangering himself and the public.Prior to the stroke he was treated with monthly Pipothiozine Depot Injections, however, these were missed post stroke; he remained untreated for his paranoid schizophrenia and no signs of distress or paranoia were identified by any of the treating staff. Due to his speech impairments, his mental state remained difficult to assess, however, in conjunction with speech and language colleagues the Neuropsychiatrist ascertained that there was no evidence of psychosis, beliefs or behaviours similar to his pre-morbid mental state.DiscussionThe human PAC is part of the temporal lobe and is the final target for afferent auditory signals. It is found bilaterally, specifically within the STG, occupying the dorsal and lateral surface of the STG and encompassing Heschl’s gyrus. There are several different hypotheses regarding the neural mechanisms behind auditory verbal hallucinations. Multiple studies have implicated the primary auditory cortex as being central to this process and functional imaging has shown the STG to be activated in patients with schizophrenia during hallucinations. The resolution of symptoms in this case supports the involvement of the PAC in AVH and could represent a target for future therapies.
9 Aberrant striatal value representation in Huntington’s disease gene carriers 25 years before onset
Authors: Nair Akshay , Johnson Eileanoir B , Gregory Sarah , Osborne-Crowley Katherine , Zeun Paul , Scahill Rachel I , Lowe Jessica , Papoutsi Marina , Palminteri Stefano , Rutledge Robb B , Rees Geraint , Tabrizi Sarah J 
Published: July 2020

AimsHuntington’s disease (HD) is a devastating genetic neurodegenerative condition typically manifesting clinically in the fourth or fifth decade. With the advent of genetic therapies there is increased need to identify the earliest changes associated with carrying the HD gene. In this study we sought to determine the earliest functional imaging differences between HD gene carriers and matched controls. Based on previous work, we hypothesised that as compared to controls, HD gene carriers decades from onset would show a neural ‘reward bias’ – an exaggerated striatal response to gains as compared to losses.MethodsWe recruited 35 HD gene carriers, estimated to be on average 26 years from motor onset, and 35 controls. Groups were well matched for age, gender and education level.Participants completed a reinforcement learning task in a fMRI scanner using a sequence optimised for orbitofrontal and striatal signal. In this task participants were required to learn to choose between stimuli with the aim of maximise rewards and avoiding losses. Task behaviour was modelled using a computational model and computational variables from the best fitting model was used to probe fMRI data.ResultsAs hypothesised, we found that, in comparison to matched controls, gene carriers over 25 years from motor onset showed exaggerated striatal responses to gain as compared to loss predicting stimuli (p=0.003) in a reinforcement learning task. Using computational analysis, we also found group differences in striatal representation of stimulus value (p=0.0007).ConclusionThese represent the earliest functional imaging differences between HD gene carriers and controls. Behaviourally gene carriers, 9 years from predicted onset, have shown enhanced learning from gains as compared to losses. Importantly, we found no group differences in behaviour, or caudate volumes. Our data suggests a therapeutic window exists whereby HD- related functional neural changes are detectable 25 years before predicted onset.
Telomere shortening velocity of patients administered with hypnotics is accelerated in a gender-differential manner
Authors: Maeda Toyoki , Horiuchi Takahiko , Makino Naoki 
Published: July 2020

The telomere length and its distribution were compared between patients administered with and without hypnotics to see if regular administration of hypnotics is associated with their aging-related somatic telomere shortening. Male patients presented significant shortening of telomere length of circulating leukocytes in association with age (–41.9 bp/year, p = 0.045) in contrast with controls (–18.3 kb/year, p = 0.155). On the other hand, female patients presented no significant shortening of telomere length with aging (–16.4 bp/year, p = 0.372) in contrast with controls (–55.9 bp/year, p = 0.00005). These results suggested that regular administration of hypnotics is associated with aging progression in a gender-related manner. The administration of hypnotics could be an indicator as the somatic aging status and for the screening of background lifestyle-associated diseases promoting biological aging.