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Background: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is the most widely used screening tool for cognitive impairment in Multiple Sclerosis (MS). However, the administration and scoring procedures of the paper version are time consuming and prone to errors. Aim of our study was to develop a tablet version of BICAMS (iBICAMS), and to assess its reliability compared to the paper version.Methods: We administered both BICAMS and iBICAMS to 139 MS patients in two different sessions. We compared scores on both versions using a paired t-test. We used a repeated measures ANOVA to test the impact of rater, order of administration and test-retest time on test-retest performances. We used the Intraclass Correlation Coefficient (ICC) to assess the reliability between BICAMS and iBICAMS.Results: All three sub-tests of the BICAMS (SDMT, CVLT-II and BVMT-R) were different between the paper and the tablet versions. Order of administration influenced test-retest performances at the SDMT (pConclusions: Results suggest that using the iBICAMS guarantees a better adherence to standardized procedures in both administration and scoring phase of tests. The high reliability between the two versions and the inherent advantages of automated scoring, favor the iBICAMS as the most appropriate method.

Purpose To investigate in multiple sclerosis (MS) patients, the relationship between pain and religiosity and to determine whether distinct dimensions of religiosity were associated with quality of life. Methods MS patients during clinical follow-up filled out the visual analogue scale for pain (VAS), the Mc Gill questionnaire (McGQ), the 36-Item Short Form Health Survey (SF-36), and the religious attitude scale (RAS), and expanded disability status scale (EDSS) was assessed. Results Ninety-two MS patients were enrolled, only two declined. There was a negative correlation between religious practice and faith and some domains of the SF-36 and a positive correlation between sensory, affective, and evaluative aspects of pain (at McGQ) and religious practices, and between evaluative aspects of pain (at McGQ) and faith. EDSS was significantly higher in practitioner believers compared to not practitioners. Conclusions More disabled MS patients, with worse quality of life, also due to physical pain, find a source of comfort in faith and religious practices. Pain is not relieved by prayer; therefore, we may guess that in MS the poor beneficial effect of religiosity and practice on pain perception may be linked to a structural/functional damage of neural circuits involved in reducing pain during prayer.

Background Migraine affects more than a billion people all over the world and requires critical employment of healthcare resources. Telemedicine could be a reasonable tool to manage people suffering from headaches, and it received a big push from the COVID-19 pandemic. Objective This review aims to propose a practical approach for the virtual management of these patients. Methods To do this, we conducted a literature search, including 32 articles relevant to the topic treated in this review. Results The most challenging step in telemedicine applied to practical neurology remains the clinical assessment, but through a careful headache history and a recently proposed entirely virtual neurological assessment, this hitch can be easily overcome. Electronic diary compilations and virtual administration of disability-measuring scales, conversely, are the key features of effective long-term follow-up although we do not have apps that met the criteria of scientific reliability. Furthermore, tele-rehabilitation seems to be effective and has demonstrated to be a solution to alternatively treat chronic patients at home, and can be considered part of the remote management of headache patients. Moreover, virtual management of headaches finds an application in specific communities of patients, as pediatric patients and for rural communities of low- and middle-income countries suffer from health disparities, with inadequate resources and knowledge gaps. Conclusion Telemedicine could be promising for patients with no regular or convenient access to headache specialists and seems to be a priority in managing migraine patients to avoid non-urgent hospitalizations

IntroductionNatalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population.Materials and methodsThis retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the ‘Italian MS Register’. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment.ResultsOut of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups.DiscussionThe use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety.

Supplemental material, sj-docx-1-msj-10.1177_13524585221102918 for Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies by Irene Schiavetti, Cinzia Cordioli, Maria Laura Stromillo, Maria Teresa Ferrò, Alice Laroni, Eleonora Cocco, Gaia Cola, Livia Pasquali, Maria Teresa Rilla, Elisabetta Signoriello, Rosa Iodice, Alessia Di Sapio, Roberta Lanzillo, Francesca Caleri, Pietro Annovazzi, Antonella Conte, Giuseppe Liberatore, Francesca Ruscica, Renato Docimo, Simona Bonavita, Monica Ulivelli, Paola Cavalla, Francesco Patti, Diana Ferraro, Marinella Clerico, Paolo Immovilli, Massimiliano Di Filippo, Marco Salvetti and Maria Pia Sormani in Multiple Sclerosis Journal

Over the last months, due to coronavirus disease (COVID-19) pandemic, containment measures have led to important social restriction. Healthcare systems have faced a complete rearrangement of resources and spaces, with the creation of wards devoted to COVID-19 patients. In this context, patients affected by chronic neurological diseases, such as amyotrophic lateral sclerosis (ALS), are at risk to be lost at follow-up, leading to a higher risk of morbidity and mortality. Telemedicine may allow meet the needs of these patients. In this commentary, we briefly discuss the digital tools to remotely monitor and manage ALS patients. Focusing on detecting disease progression and preventing life-threatening conditions, we propose a toolset able to improve ALS management during this unprecedented situation.

Introduction: With the spread of the SARS-CoV2 pandemic, telemedicine has become the safest way to guarantee care continuity, especially for chronic disabling diseases requiring frequent medical consultations and therapeutic adjustments, such as Parkinson's disease (PD). The age-related prevalence of PD, combined with increased vulnerability due to age-related comorbidities, makes PD patients protection a priority. Methodology: We reviewed potentials and limitations of teleneurology in PD and suggested a specific battery of tests, including patient-reported outcomes, smartphone applications, and neurological examination through telemedicine. Conclusions: These tools can provide full neurological consultations, with the engagement of both patients and caregivers, and can support clinicians in defining whether patients need to access diagnostic and therapeutic procedures. Telemedicine will also carry a value in the future, within conventional health care, to support clinicians in decision making, enabling more efficacious follow-up, reducing burden for caregivers, and delivering neurological expertise to local realities. These advantages are very important when there is physical distance between patients and neurologists, and when patients are not recommended to attend in-person consultations.

Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has demonstrated a good efficacy as treatment in patients with resistant Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but it is highly immunogenic due to its structure. Ocrelizumab (OCR) is a humanized anti-CD20 antibody, with higher tolerability and lower immunogenic profile compared to RTX. We present a case of refractory CIDP effectively treated with OCR switched from RTX after the development of anti-drug antibodies (ADA).

Supplemental material, sj-pdf-1-taj-10.1177_20406223211029616 for Digital work engagement among Italian neurologists by Francesco Brigo, Marta Ponzano, Maria Pia Sormani, Marinella Clerico, Gianmarco Abbadessa, Giovanni Cossu, Francesca Trojsi, Fabiana Colucci, Carla Tortorella, Giuseppina Miele, Emanuele Spina, Carlo Alberto Artusi, Luca Carmisciano, Giovanna Servillo, Marco Bozzali, Maddalena Sparaco, Letizia Leocani, Roberta Lanzillo, Gioacchino Tedeschi, Simona Bonavita and Luigi Lavorgna in Therapeutic Advances in Chronic Disease

Supplemental material, sj-pdf-2-taj-10.1177_20406223211029616 for Digital work engagement among Italian neurologists by Francesco Brigo, Marta Ponzano, Maria Pia Sormani, Marinella Clerico, Gianmarco Abbadessa, Giovanni Cossu, Francesca Trojsi, Fabiana Colucci, Carla Tortorella, Giuseppina Miele, Emanuele Spina, Carlo Alberto Artusi, Luca Carmisciano, Giovanna Servillo, Marco Bozzali, Maddalena Sparaco, Letizia Leocani, Roberta Lanzillo, Gioacchino Tedeschi, Simona Bonavita and Luigi Lavorgna in Therapeutic Advances in Chronic Disease

Supplemental material, sj-pdf-2-taj-10.1177_20406223211029616 for Digital work engagement among Italian neurologists by Francesco Brigo, Marta Ponzano, Maria Pia Sormani, Marinella Clerico, Gianmarco Abbadessa, Giovanni Cossu, Francesca Trojsi, Fabiana Colucci, Carla Tortorella, Giuseppina Miele, Emanuele Spina, Carlo Alberto Artusi, Luca Carmisciano, Giovanna Servillo, Marco Bozzali, Maddalena Sparaco, Letizia Leocani, Roberta Lanzillo, Gioacchino Tedeschi, Simona Bonavita and Luigi Lavorgna in Therapeutic Advances in Chronic Disease

Objective Cladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data. Methods Data from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity. Results All weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis. Conclusion In patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity. Classification of evidence This study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

Patients with multiple sclerosis (MS) are considered at higher risk of COVID-19 infection due to treatment with immune modulators and immune-suppressive agents. The exact risk factors are not clear. So, we aimed to conduct a study to determine the predictors of catching COVID-19 infection during the pandemic stage in patients with multiple sclerosis (MS).We conducted a multicenter screening study and developed an online questionnaire to collect patients' self-reported demographic features along with MS-related and COVID-19-related information. The online questionnaire link was released by the Iran Multiple Sclerosis Society (IMSS) social media channel, accessible for 4160 MS patients totally and also was sent by WhatsApp for nonmember cases.Totally, 1448 MS patients participated in our study. Twenty-five (1.7%) patients were diagnosed with COVID-19, from which 4 were hospitalized, 4 were treated with medical therapy, and 17 patients had home-quarantine. The patients with COVID-19 diagnosis were more frequently treated with rituximab (28% vs 24%,Patients with MS who have cardiovascular disease should be more monitored for COVID-19 infection as they are at higher risk of infection.

Supplemental material, MSJ892552_supplemental_material for Regional changes in thalamic shape and volume are related to cognitive performance in multiple sclerosis by Alvino Bisecco, Rocco Capuano, Giuseppina Caiazzo, Alessandro d’Ambrosio, Renato Docimo, Mario Cirillo, Antonio Russo, Manuela Altieri, Simona Bonavita, Maria A Rocca, Massimo Filippi, Gioacchino Tedeschi and Antonio Gallo in Multiple Sclerosis Journal

Supplemental material, MSJ872889_supplemental_table for Treatment of multiple sclerosis with rituximab: A multicentric Italian–Swiss experience by Chiara Zecca, Francesca Bovis, Giovanni Novi, Marco Capobianco, Roberta Lanzillo, Jessica Frau, Anna Maria Repice, Bahia Hakiki, Sabrina Realmuto, Simona Bonavita, Erica Curti, Laura Brambilla, Giorgia Mataluni, Paola Cavalla, Alessia Di Sapio, Elisabetta Signoriello, Stefania Barone, Giorgia T Maniscalco, Ilaria Maietta, Isabella Maraffi, Giacomo Boffa, Simona Malucchi, Agostino Nozzolillo, Giancarlo Coghe, Claudia Mechi, Giuseppe Salemi, Antonio Gallo, Rosaria Sacco, Maria Cellerino, Maria Malentacchi, Marcello De Angelis, Lorena Lorefice, Eliana Magnani, Elio Prestipino, Francesca Sperli, Vincenzo Brescia Morra, Giuseppe Fenu, Alessandro Barilaro, Gianmarco Abbadessa, Alessio Signori, Franco Granella, Maria Pia Amato, Antonio Uccelli, Claudio Gobbi and Maria Pia Sormani in Multiple Sclerosis Journal

Lesbian, gay, bisexual and transgender (LGBT) patients might experience unique difficulties and barriers to treatment of chronic diseases related to their sexual orientation. Thus, we investigated concerns experienced by LGBT patients with multiple sclerosis (MS). We conducted a web-based survey using a multi-choice questionnaire published in an Italian social-network (www.smsocialnetwork.com) for MS patients. The survey investigated: socio-demographic factors, lifestyle habits, MS-related health status and LGBT specific issues (e.g. friendliness to their sexual orientation and eventual homophobic behaviors in the MS Center). Among MS patients willing to use psychological services, LGBT patients were associated with a smaller number of psychological consultations, compared to heterosexuals (Coeff.=-0.449; p < 0.001; 95% CI=-0.682 to -0. 217). LGBT patients were more likely to change MS Center, compared to heterosexuals (OR=2.064; p=0.046; 95% CI=1.011-4.212). The number of MS Center changes was associated with MS Center friendliness (p=0.037; rho=-0.229) and with the occurrence of homophobic behaviors (p=0.036; rho=0.234). LGBT MS patients more frequently changed MS Center and had a reduced use of psychological services, compared to heterosexuals. The attitude towards LGBT MS patients might affect resource utilizations and LGBTs health status.

Background: Social media are a vital link for people with health concerns who find in Web communities a valid and comforting source for information exchange, debate, and knowledge enrichment. This aspect is important for people affected by chronic diseases like multiple sclerosis (MS), who are very well informed about the disease but are vulnerable to hopes of being cured or saved by therapies whose efficacy is not always scientifically proven. To improve health-related coping and social interaction for people with MS, we created an MS social network (SMsocialnetwork.com) with a medical team constantly online to intervene promptly when false or inappropriate medical information are shared. Objective: The goal of this study was to assess the impact of SMsocialnetwork.com on the health-related coping and social interaction of people with MS by analyzing areas of interest through a Web-based survey. Methods: Referring to previous marketing studies analyzing the online platform’s role in targeted health care, we conducted a 39-item Web-based survey. We then performed a construct validation procedure using a factorial analysis, gathering together like items of the survey related to different areas of interest such as utility, proximity, sharing, interaction, solving uncertainty, suggestion attitude, and exploration. Results: We collected 130 Web-based surveys. The areas of interest analysis demonstrated that the users positively evaluated SMsocialnetwork.com to obtain information, approach and solve problems, and to make decisions (utility: median 4.2); improve feeling of closeness (proximity: median 5); catalyze relationships and text general personal opinions (sharing: median 5.6); get in touch with other users to receive innovative, effective, and practical solutions (interaction, solving uncertainty, and suggestion attitude medians were respectively: 4.1, 3, and 3); and share information about innovative therapeutic approaches and treatment options (suggestion attitude: median: 3.3). Conclusions: SMsocialnetwork.com was perceived by users to be a useful tool to support health-related coping and social interaction, and may suggest a new kind of therapeutic alliance between physicians and people with MS. [Interact J Med Res 2017;6(2):e10]

Supplemental material, MSJ790390_supplementary_material for Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study by Francesco Saccà, Roberta Lanzillo, Alessio Signori, Giorgia T Maniscalco, Elisabetta Signoriello, Salvatore Lo Fermo, Annamaria Repice, Pietro Annovazzi, Damiano Baroncini, Marinella Clerico, Eleonora Binello, Raffaella Cerqua, Giorgia Mataluni, Simona Bonavita, Luigi Lavorgna, Ignazio Roberto Zarbo, Alice Laroni, Silvia Rossi, Lorena Pareja Gutierrez, Sara La Gioia, Barbara Frigeni, Valeria Barcella, Jessica Frau, Eleonora Cocco, Giuseppe Fenu, Valentina Torri Clerici, Arianna Sartori, Sarah Rasia, Cinzia Cordioli, Alessia Di Sapio, Simona Pontecorvo, Roberta Grasso, Caterina Barrilà, Cinzia Valeria Russo, Sabrina Esposito, Domenico Ippolito, Francesca Bovis, Fabio Gallo and Maria Pia Sormani in Multiple Sclerosis Journal

Multiple sclerosis (MS) is the most common neurological disorder in young adults. The prevalence of walking impairment in people with MS (pwMS) is estimated between 41% and 75%. To evaluate the walking capacity in pwMS, the patient reported outcomes (PROs) and performance-based tests (i.e., the 2-minute walk test, the 6-minute walk test, the Timed 25-Foot Walk Test, the Timed Up and Go Test, and the Six Spot Step Test) could be used. However, some studies point out that the results of both performance-based tests and objective measures (i.e., by accelerometer) could not reflect patient reports of walking performance and impact of MS on daily life. This review analyses different motion sensors embedded in smartphones and motion wearable device (MWD) that can be useful to measure free-living walking behavior, to evaluate falls, fatigue, sedentary lifestyle, exercise, and quality of sleep in everyday life of pwMS. Caveats and limitations of MWD such as variable accuracy, user adherence, power consumption and recharging, noise susceptibility, and data management are discussed as well.

White matter changes are one of the several aging brain alterations. Actually, magnetic resonance imaging is the best diagnostic tool in investigation and monitoring these lesions that determine some common clinical manifestations in the elderly population

To investigate the possible occurrence of a conversion event in three patients with adult-onset spinal muscular atrophy (SMA) type IV, which represents the mildest form within the spectrum of the SMA phenotype.We observed three patients with adult onset SMA and apparent isolated deletion of telomeric survival motor neuron (SMN1) exon 7. To distinguish between a deletion and a sequence conversion event of exon 7, these patients were analyzed in greater detail by a simple PCR-based assay.Analysis by DdeI digestion showed products for both telomeric and centromeric copies of exon 8. These findings indicated a gene conversion event as the site for primer R111 was retained at least in one of two alleles.These results provide first evidence that a conversion event may be also associated with adult-onset SMA, and further support the notion that a gene conversion event is usually associated with a milder SMA phenotype and a later onset of disease.

Resting State fMRI (RS-fMRI) represents an emerging and powerful tool to explore brain functional connectivity (FC) changes associated with neurologic disorders. Compared to activation/task-related fMRI, RS-fMRI has the advantages that (i) BOLD fMRI signals are self-generated and independent of subject’s performance during the task and (ii) a single dataset is sufficient to extract a set of RS networks (RSNs) that allows to explore whole brain FC. According to these features RS-fMRI appears particularly suitable for the study of FC changes related to multiple sclerosis (MS). In the present review we will first give a brief description of RS-fMRI methodology and then an overview of most relevant studies conducted so far in MS by using this approach. The most interesting results, in particular, regard the default-mode network (DMN), whose FC changes have been correlated with cognitive status of MS patients, and the visual RSN (V-RSN) whose FC changes have been correlated with visual recovery after optic neuritis. The executive control network (ECN), the lateralized frontoparietal network (FPN), and the sensory motor network (SMN) have also been investigated in MS, showing significant FC rearrangements. All together, RS-fMRI studies conducted so far in MS suggest that prominent RS-FC changes can be detected in many RSNs and correlate with clinical and/or structural MRI measures. Future RS-fMRI studies will further clarify the dynamics and clinical impact of RSNs changes in MS.

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

OBJECTIVES: To determine whether anti-GM1 antibodies are increased in Parkinson's disease (PD). METHODS: Serum immunoglobulin M (IgM) and IgG anti-GM1 antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 147 patients with PD and in 186 age-matched normal control subjects. Sera were assayed at initial dilution of 1:800 for IgM and 1:200 for IgG and were considered positive at absorbance values exceeding the value of 0.05 for IgM and 0.1 for IgG. RESULTS: Forty patients with PD (27.2%) had sera positive for IgM anti-GM1 antibodies, whereas only five normal controls (2.7%) resulted positive (P < 0.0001). Most of patients (75%) with positive sera had a tremor-dominant form of PD. Only two patients with PD (1.4%) and none of normal controls had sera positive for IgG anti-GM1 antibodies. CONCLUSION: A consistent portion of parkinsonians, mainly with a tremor-dominant form of PD, may have increased circulating IgM anti-GM1 antibodies.

BackgroundSteroid-responsiveencephalopathy associated with autoimmune thyroiditis (SREAT) is a rare butpotentially reversible autoimmune encephalopathy. The most frequentneuroimaging correlates are normal brain MRI or non-specific white matterhyperintensities.MethodsWe present the first description of conus medullaris involvement, also providing an extensive review of MRI patterns described so far.ResultsOur results show that in less than 30% of cases, it is possible to find focal SREAT neuroanatomical correlates. Among these, T2w/FLAIR temporal hyperintensities are the most frequent, followed by basal ganglia/thalamic and brainstem involvement, respectively.ConclusionsUnfortunately, spinal cord investigation is an uncommon practice in the diagnostic approach of encephalopathies, thus neglecting potential pathological lesions of the medulla spinalis. In our opinion, the extension of the MRI study to the cervical, thoracic, and lumbosacral regions may allow finding new, and hopefully specific, anatomical correlates.