We designed a case-control proton magnetic resonance spectroscopic study comparing the cerebellar and prefrontal regions of a group of 17 ADHD (attention deficit/hyperactivity disorder) medicated children and a group of 17 control children matched for laterality, gender and age. As we had found decreased gray matter volume in the right prefrontal region and the left ...

BackgroundFunctional neuroimaging data from adults have, in general, found frontocerebellar dysfunction associated with acute and chronic marijuana (MJ) use (Loeber & Yurgelun-Todd, 1999). One structural neuroimaging study found reduced cerebellar vermis volume in young adult MJ users with a history of heavy polysubstance use (Aasly et al., 1993). The goal of this study ...

Despite common reports in Parkinson's disease (PD), in other parkinsonian syndromes, sleep disturbances have been less frequently described. This study evaluated and compared sleep disturbances in patients with PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and analyzed associations with brain magnetic resonance imaging (MRI) morphometry. This was a ...

Background: MRI studies have shown a decreased cerebellum volume in individuals with ADHD. However, most of these studies were conducted with male children, many of whom were medicated with stimulants. As such, unmedicated, non-White girls are underrepresented in such MRI studies. Objective: The aim of the present study was to compare the density of gray matter (GM) in the ...

ObjectiveX linked spinobulbar muscular atrophy (Kennedy disease (KD)), which is clinically characterised mainly by neuromuscular and endocrine symptoms, has to be considered as a multisystem disorder. Based on clinical evidence of central nervous system involvement, potential KD associated cerebral volume alterations were analysed in vivo.MethodsWhole brain based analysis of optimised voxel based ...

Cerebellar hypoplasia and hydrocephalus were detected in day-old broiler chickens. Brains of chickens evaluated at necropsy appeared to be abnormal; some were disfigured and cerebellae appeared to be smaller than normal. Histopathologic examination of brains revealed cerebellar folia that were sho...

... and spinal cord transmissible spongiform encephalopathies (such as Creutzfeldt-Jakob disease) in which abnormal proteins cause inflammation in the ...

Tumors of the cerebellum and brainstem account for half of all brain tumors in children. The realization that cerebellar lesions produce clinically relevant intellectual disability makes it important to determine whether neuropsychological abnormalities occur in long-term survivors of pediatric cerebellar tumors. Little is known about ...

Voxel-based morphometry of unilateral temporal lobe epilepsy reveals abnormalities in cerebral April 2004; accepted 5 May 2004 Voxel-based morphometric (VBM) investigations of temporal lobe epilepsy identified the expected abnormalities in hippocampus and extrahippocampal temporal lobe, as well as more

In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit hyperactivity disorder and autism spectrum disorders in childhood, and ...

BackgroundAbnormal repeat length has been associated with an earlier age of onset and more severe disease progression in the rare neurodegenerative disorder spinocerebellar ataxia 17 (SCA17).Methodology/Principal FindingsTo determine whether specific structural brain degeneration and rate of disease progression in SCA17 might be associated with the CAG repeat size, ...

Children with autism spectrum disorder (ASD) exhibit characteristic cognitive and behavioral differences, but no systematic pattern of neuroanatomical differences has been consistently found. Recent neurodevelopmental models posit an abnormal early surge in subcortical white matter growth in at least some autistic children, perhaps normalizing by adulthood, but other studies ...

A 10-year-old girl exhibited severe cerebellar ataxia following acute enterocolitis, and was diagnosed as having acute cerebellar ataxia (ACA). MRI of the brain in the acute stage revealed moderate swelling of the cerebellum and abnormal signal intensity enhanced with gadolinium in the cerebellar hemisphere. This ...

Following a high fever, a healthy woman became comatose within a few days. Severe cerebellar symptoms appeared when she regained consciousness. The brain MRIs revealed abnormal signal intensity of the cerebellar cortex and brainstem gray matter, however, no abnormalities were revealed in the cerebral hemispheres. ...

Cerebellar agenesis is a rare disorder. We present the neurological and neuropsychological features of a patient with partial cerebellar agenesis (TZ), together with SPECT perfusion and fMRI activation during a finger tapping task. TZ shows only mild cerebellar signs, while neuropsychological testing discloses severe deficits in many ...

AbstractObjectiveCo-occurrence of substance use and bipolar disorders is both common and associated with poor treatment response and greater functional impairment than either disorder alone. The neurophysiological correlates of this co-morbidity however, remain unclear. In this pilot study, we compared brain morphometry between bipolar adolescents with co-occurring cannabis ...

(Bauman et al. 1995), Asperger syndrome (El-Badri and Lewis 1993, Ciaranello and Ciaranello 1995Cerebellar abnormalities in infants and toddlers with Williams syndrome Wendy Jones* PhD, The Salk-mail: jones@crl.ucsd.edu One commonly observed neuroanatomical abnormality in adults with Williams syndrome

Although accumulating evidence suggests that cerebellar abnormalities may be linked to the symptoms and course of schizophrenia, few studies have related structural and functional indices of cerebellar integrity. The present study examined the relationship between the volume of specific subregions of the cerebellum and ...

Ataxia is a lethal neurological disease characterized by incoordination, postural abnormalities, difficulties with gait, and problems with clarity of speech. The etiology of ataxia is divided equally between hereditary and sporadic forms. Regardless of cause, the cerebellar cortex is often a target in ataxia. Thus, how a disruption in ...

Fragile X-associated tremor/ataxia syndrome is a neurodegenerative disorder that primarily affects older male premutation carriers of the fragile X mental retardation gene. Although its core symptoms are mainly characterized by motor problems such as intention tremor and gait ataxia, cognitive decline and psychiatric problems are also commonly observed. Past radiological and histological ...

Children with spina bifida meningomyelocele (SBM) are impaired relative to controls in terms of discriminating strong-meter and weak-meter rhythms, so congenital cerebellar dysmorphologies that affect rhythmic movements also disrupt rhythm perception. Cerebellar parcellations in children with SBM showed an abnormal configuration of ...

A 51-year-old male with a history of insulin-dependent diabetes and polysubstance abuse presented after overdose on insulin. Soon after resuscitation, he displayed a severe ataxia in all 4 limbs and was unable to walk; all of which persisted for at least 5�days. Laboratory testing was unrevealing, including relatively normal brain magnetic resonance imaging. He had recovered full neurologic ...

Background Autism spectrum disorder (ASD) is defined on a clinical basis by impairments in social interaction, verbal and non-verbal communication, and repetitive or stereotyped behaviours. Voxel based morphometry (VBM), a technique that gives a probabilistic measure of local grey matter (GM) and white matter concentration, has been used to study ASD PATIENTS: modifications in ...

BACKGROUND AND PURPOSE: Imaging studies have revealed brain abnormalities in the regions involved in functions impaired in ASD (social relations, verbal and nonverbal communication, and adaptive behavior). We performed a VBM whole-brain analysis to assess the areas involved in autistic children with DD. MATERIALS AND METHODS: Twenty-one developmentally delayed children with ...

Patients with obstructive sleep apnea (OSA) show neuropsychological impairments ranging from vigilance decrements, attentional lapses and memory gaps to decreased motor coordination, but their cognitive profile, and the origin of the impairments, remain unclear. We sought to establish the neuropsychological profile of 16 newly diagnosed apneics and to highlight both their morphological and ...

Autosomal dominant motor system degeneration (ADMSD) is a hereditary ataxia that has been reported previously only in Portuguese families from the Azores Islands. Cerebellar ataxia, pyramidal and extrapyramidal signs, amyotrophy, dystonia, abnormal eye movements, and prominent eyes are variably present. Four members of a family had ...

Brain abnormality in surviving premature infants is associated with an enormous amount of neurodevelopmental disability, manifested principally by cognitive, behavioral, attentional, and socialization deficits, most commonly with only relatively modest motor deficits. The most recognized contributing neuropathology is cerebral white matter injury. The thesis of this review is ...

We recently encountered a 13-year-old girl who developed persistent cerebellar symptoms one month after mixed measles/rubella vaccination, making it difficult to distinguish this condition from conversion disorders. Severe truncal ataxia was the initial manifestation in this case. The patient had no abnormalities in objective tests but began to show ...

This study was designed to investigate cerebellar lobular contributions to specific cognitive deficits observed after cerebellar tumor resection. Verbal working memory (VWM) tasks were administered to children following surgical resection of cerebellar pilocytic astrocytomas and age-matched controls. Anatomical MRI scans were used to ...

Three cases of cerebellar ectopia first producing symptoms in adult life are reported. This potentially remediable anomaly may not be suspected in adults, in whom associated congenital bony abnormalities of the skull and cervical spine are often absent. In these cases diagnosis depends on radiological contrast studies; in particular it is important to ...

Two male cousins are reported with arachnodactyly, selective aminoaciduria, congenital cataracts, cerebellar ataxia, and delayed developmental milestones, and a distant female relative with similar abnormalities. The syndrome is thought to be previously undescribed, though it has resemblances to Marinesco-Sj�gren and Marfan's syndromes. Images

The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that prevents the normal

The cerebellum is implicated in maintaining the saccadic subsystem efficient for vision by minimizing movement inaccuracy and by learning from endpoint errors. This ability is often disrupted in degenerative cerebellar diseases, as demonstrated by saccade kinetic abnormalities. The study of saccades in these patients may therefore provide insights into the ...

A female patient presented with horizontal gaze nystagmus, mild cerebellar ataxia, recurrent headache and hemiplegia since childhood with cerebellar atrophy on magnetic resonance imaging. Genetic analysis revealed a CACNA1A gene mutation, leading to a diagnosis of familial hemiplegic migraine (FHM1). FHM is very rare, but should be considered as a ...

We report an unusual case of sporadic adult onset cerebellar ataxia with hypogonadism. A 40-year-old unmarried man presented with progressive ataxia and dysarthria along with complaints of non-development of secondary sexual characteristics and erectile dysfunction. There were complaints of intermittent diarrhea. Clinical examination revealed a ...

Thunderclap headache (TCH) refers to a sudden-onset, severe headache that features in subarachnoid hemorrhage, unruptured intracranial aneurysm, cerebral venous thrombosis, pituitary apoplexy, cervical artery dissection, and hypertensive reversible posterior leukoencephalopathy. TCH is a rare manifestation in cerebral or cerebellar infarctions. Herein, we report on a ...

The phenotypic association between fragile X syndrome (FXS) and autism is well established, but no studies have directly compared whole-brain anatomy between the two disorders. We performed voxel-based morphometry analyses of MRI scans on ten individuals with FXS, ten individuals with autism, and ten healthy comparison subjects to identify volumetric changes in each disorder. ...

Patients with cerebellar deficits made elbow flexion movements as rapidly as possible for three different angular distances. Electromyographic activity of biceps and triceps and the kinematics of the movements were analysed. Results were compared with those of normal subjects making both rapid and slow movements. In the patients, the first agonist burst of the biceps was ...

Malformations of cortical development (MCD) are a common etiology for epilepsy. Laminar heterotopia, bilateral subependymal heterotopia, and lissencephaly have a genetic basis. No gene mutations have yet been identified in patients with focal cortical dysplasias. The aim of this study was to use quantitative morphometric tools to determine if there were gray matter ...

Malfunctions of potassium channels are increasingly implicated as causes of neurological disorders. However, the functional roles of the large-conductance voltage- and Ca²⁺-activated K⁺ channel (BK channel), a unique calcium, and voltage-activated potassium channel type have remained elusive. Here we report that mice lacking BK channels ...

Children and young adolescents with chronic surgical cerebellar lesions show persistent balance control problems during standing when lesions affect the deep cerebellar fastigial and adjacent interposed nuclei. The purpose of this study is to confirm that the same lesion sites are also associated with permanent signs of trunkal ataxia during sitting. A ...

Besides supratentorial abnormalities, spina bifida menigomyelocele (SBM) is typically associated with Chiari-II malformation comprising a small cerebellum, which herniates downward due to a shallow posterior fossa. We used diffusion tensor imaging to probe additional microstructural alterations of the major cerebellar white matter tracts, the ...

We define the neurological characteristics of familial cases from multiple branches of a large consanguineous family with cerebellar ataxia, mental retardation (MR), and dysequilibrium syndrome type 3 caused by a mutation in the recently cloned CA8 gene. The linkage analysis revealed a high logarithm of the odds (LOD) score region on 8q that harbors the CA8 in which a novel ...

Heterozygous deletions encompassing the ZIC1;ZIC4 locus have been identified in a subset of individuals with the common cerebellar birth defect Dandy-Walker malformation (DWM). Deletion of Zic1 and Zic4 in mice produces both cerebellar size and foliation defects similar to human DWM, confirming a requirement for these genes in ...

Cerebellar dysfunction has been proposed to lead to "cognitive dysmetria" in schizophrenia via the cortico-cerebellar-thalamic-cortical circuit, contributing to a range of cognitive and clinical symptoms of the disorder. Here we investigated total cerebellar grey and white matter volumes and cerebellar regional ...

Sonic Hedgehog and its GLI transcriptional effectors control foliation complexity during cerebellar morphogenesis by promoting granule cell precursor proliferation. Here, we reveal a novel contribution of Sonic Hedgehog-GLI signaling to cerebellar patterning and cell differentiation by generating mice with targeted deletion of Suppressor of Fused (SuFu), a ...

Although cerebellar injury in the premature infant is an increasingly recognized form of neonatal brain injury, its structural and functional outcomes remain poorly defined in the term infant. The objective of this cross-sectional study was to characterize the clinical and magnetic resonance imaging features and neurodevelopmental outcome in children, born at term, with ...

Structural cerebral deficiencies in smokers have been well characterized by morphometric investigations focussing on cortical and subcortical structures. Although the role of the cerebellum is increasingly noted in mental and addiction disorders, no reports exist regarding cerebellar alterations in smokers employing a methodology specifically designed to assess the ...

Single photon emission computed tomography (SPECT) was performed in 31 patients with cerebral infarction and 13 who had had transient ischemic attacks, using iodine-123-labeled N,N,N'-trimethyl-N'-(2-hydroxyl-3-methyl-5-iodobenzyl)-1,3-propanediamin e (I-123-HIPDM) as the radiopharmaceutical. SPECT scans were compared with computed tomographic (CT) scans. SPECT was as sensitive ...

Magnetic resonance imaging has revolutionized the detection of structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we use an automated, surface-based method for quantifying morphometric features related to epileptogenic cortical malformations to detect ...

Magnetic resonance imaging has revolutionized the detection of structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we use an automated, surface-based method for quantifying morphometric features related to epileptogenic cortical malformations to detect ...

BackgroundThe cerebellum is composed of a diverse array of neuronal subtypes. Here we have used a candidate approach to identify Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, as a new player in the transcriptional network required for the development of a specific subset of cerebellar nuclei and a population of Golgi cells in the ...

The role of the cerebellum in schizophrenia has been highlighted by Andreasen's hypothesis of �cognitive dysmetria,� which suggests a general dyscoordination of sensorimotor and mental processes. Studies in schizophrenic patients have brought observations supporting a cerebellar impairment: high prevalence of neurological soft signs, dyscoordination, ...

Recent studies have suggested that there may be functional and structural changes in the cerebellum of patients with adult onset primary focal dystonia. The aim of this study was to establish whether there is any neurophysiological indicator of abnormal cerebellar function, using the classic eyeblink conditioning paradigm. This paradigm at short intervals ...

The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and cerebellar loops have been assumed to be anatomically ...

The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and cerebellar loops have been assumed to be anatomically ...

The authors studied cerebellar metabolism under varying conditions of sensory stimulation. Cerebellar glucose consumption was measured by positron emission scanning and 18F-fluorodeoxyglucose in 64 subjects. Cerebellar metabolism relative to the whole brain (CM), and the asymmetry of metabolism between the ...

This study examined regional gray matter abnormalities across the whole brain in 19 patients with schizophrenia (12 males and 7 females), comparing with 11 normal volunteers (7 males and 4 females). The customized brain templates were created in order to improve spatial normalization and segmentation. Then automated preprocessing of magnetic resonance imaging (MRI) data was ...

HUMAN retinitis pigmentosa represents a class of diseases, the principal characteristic of which is the slow and progressive degeneration of photoreceptor cells. In several human neurological syndromes, photoreceptor degeneration accompanies cerebellar ataxia, deafness, mental retardation or other abnormalities. Some examples of such syndromes are ...

abnormalities. Multivariate Hotelling's T 2 statistics on the local Riemannian metric tensors, computed in a log statistics to the same dataset. The proposed multivariate TBM proved to have more detection power1, w2 - w1][v3 - v1, v2 - v1]-1 . (1) 3.2. Multivariate Tensor-Based Statistics In our work, we use

abnormalities. Multivariate Hotelling's T2 statistics on the local Riemannian metric tensors, computed in a log statistics to the same dataset. The proposed multivariate TBM proved to have more detection power.2. Multivariate Tensor-Based Statistics In our work, we use multivariate statistics on deformation tensors [13

subject was co-registered to the ICBM53 average brain template (Mazziotta et al., 2001) using 9-parameter-resolution brain MRI scans (n=53) in the ICBM standard space to improve the signal-to-noise ratio, after nonlinear by scaling images from scanner space to the ICBM space (see below), a zoom factor was computed from

Slowly progressive ataxia accompanied by cerebellar degeneration is often genetic in origin. The past fifteen years have witnessed a revolution in our understanding of the causes of dominantly inherited ataxias, now known as the spinocerebellar ataxias (SCAs). Nearly 30 distinct genetic causes of SCA are known, numbered chronologically in order of discovery. All SCAs display ...

Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the ...

Anti?glutamic acid decarboxylase (GAD) antibodies are described in stiff?person syndrome and also in other neurological syndromes, including cerebellar ataxia and epilepsy. This paper reports the case of a patient who had chronic focal epilepsy, upbeat nystagmus and cerebellar ataxia, associated with a polyautoimmune response including anti?GAD antibodies. ...

Clinico-anatomical correlations in multiple sclerosis patients presenting with central positional vertigo are lacking. We report on a patient with acute onset positional vertigo mimicking benign paroxysmal positional vertigo with a single enhancing lesion in the inner part of the superior cerebellar peduncle, disclosed only after thin slice MR-imaging. This location appears to ...

We have generated and made publicly available two very large networks of molecular interactions: 49,493 mouse-specific and 52,518 human-specific interactions. These networks were generated through automated analysis of 368,331 full-text research articles and 8,039,972 article abstracts from the PubMed database, using the GeneWays system. Our networks cover a wide spectrum of molecular ...

BACKGROUND AND PURPOSECrossed cerebellar diaschisis (CCD), the decrease in blood flow and metabolism in the cerebellar hemisphere contralateral to a supratentorial stroke, is frequently reported on positron-emission tomography (PET) and single-photon emission CT (SPECT) but is rarely described with MR perfusion techniques. This study was undertaken to ...

Background: Friedreich's ataxia (FA) is essentially characterized by degeneration of the dorsal root ganglia, the dorsal nuclei of Clarke, and the long spinal fiber tracts, yet there is accumulating evidence that neurodegeneration extends beyond these predilection sites. Transcranial sonography (TCS) has evolved as a valuable complementary neuroimaging tool in the assessment of neurodegenerative ...

Nineteen patients with organic mercury poisoning were examined clinically and electrophysiological studies were carried out on their peripheral nerves. Four severely affected patients were disorientated, restless, and unable to speak. Vision was abnormal in nearly half the patients, usually consisting of gross constriction of visual fields with preservation of central acuity. ...

The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. ...

The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. ...

The conjunctival microcirculation in 14 pediatric and eight adult sickle cell anemia (SCA) patients was studied using computer-assisted intravital microscopy. The bulbar conjunctiva in SCA patients in both age groups exhibited a blanched/avascular appearance characterized by decreased vascularity. SCA patients from both age groups had many of the same abnormal morphometric ...

A 10-year-old male koala started to fall from the tree while sleeping. Subsequently, the koala often fell down while walking and showed a gait abnormality, abnormal nystagmus and hypersalivation. At 12 years of age, the koala became ataxic and seemed blind. At 13 years of age, the koala exhibited signs of dysstasia and was euthanased. Necropsy revealed ...

Cineradiographic and spectrographic analyses were performed to study the speech production of a subject who presented the classical neurologic signs of cerebellar lesion and who had speech characteristics like those that have been reported for ataxic dysarthria. These analyses were conducted with special attention to the deviant perceptual dimensions that have been described ...

Schizophrenia has been the focus of intense neuroimaging research. Although its fundamental pathobiology remains elusive, neuroimaging studies provide evidence of abnormalities of cerebral structure and function in patients with schizophrenia. We used morphometry as a quantitative method for estimation of volume of brain structures. Seventy eight ...

To date, few studies have addressed the relationship between brain structure alterations and responses to atypical antipsychotics in schizophrenia. To this end, in this study, magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) were used to assess the relationship between the brain volumes of gray (GM) and white (WM) matters and the clinical response to ...

... Title : Morphometry of Landforms: Drumlins. ... were measured in the field as a basis for quantitative description of a glacial landform significant to ...

Kinematic abnormalities of fast multijoint movements in cerebellar ataxia include abnormally increased curvature of hand trajectories and an increased hand path and are thought to originate from an impairment in generating appropriate levels of muscle torques to support normal coordination between shoulder and elbow joints. Such a ...

Fibroblast growth factors (FGFs) and regulators of the FGF signalling pathway are expressed in several cell types within the cerebellum throughout its development. Although much is known about the function of this pathway during the establishment of the cerebellar territory during early embryogenesis, the role of this pathway during later developmental stages is still poorly ...

Deficiency of thyroid hormone (TH) during the perinatal period results in severe neurological abnormalities in rodent cerebellar development. However, the molecular mechanisms of TH action in the developing cerebellum are not fully understood. Of note, a mutant mouse, staggerer, in which the orphan nuclear hormone receptor ROR alpha gene is disrupted, ...

Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the ...

Older male premutation carriers of the FMR1 gene are associated with the risk of developing a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome. Although previous postmortem and in vivo magnetic resonance imaging studies have indicated white matter pathology, the regional selectivity of abnormalities, as well as their relationship with ...

Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-related cognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and ...