The nervous system in horses is a complex network responsible for transmitting signals between different parts of the body. It consists of the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which comprises nerves that extend throughout the body. The nervous system regulates various physiological processes, including movement, sensation, and the coordination of bodily functions. It plays a critical role in processing sensory information and initiating appropriate responses. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and clinical implications of the equine nervous system, including its role in behavior, response to stimuli, and neurological disorders.
Nollet H, Vanschandevijl K, Van Ham L, Vanderstraeten G, Deprez P.Transcranial magnetic stimulation and measurement of the magnetic motor-evoked potentials (MMEPs) in the thoracic and pelvic limbs of four recumbent horses and one recumbent donkey were used to assess the integrity of the descending motor pathways, in order to confirm or exclude a descending motor tract lesion as the cause of the recumbency. In two of the animals abnormal MMEPs were recorded; in one of the horses a lesion along the cervical spinal cord due to a fracture of the fifth cervical vertebra was diagnosed and confirmed by radiography and postmortem examination; in another horse, damag...
MacKay RJ.Neurologic examination of the neonatal foal is quite different from the process used to examine older foals and adult horses. Abnormal neurologic signs are best appreciated in the context of a detailed knowledge of general neonatal medicine and awareness of nor-mal foal behavior and milestones of development. A systematic approach to neurologic examination is provided. The results of such examination are used to localize a lesion or lesions in the nervous system. Descriptions and treatment strategies are given for most common and important neonatal neurologic diseases.
Curtis RA, Hahn CN, Evans DL, Williams T, Begg L.Electrolaryngeography was used to study the latencies of the thoracolaryngeal adductor reflex in Thoroughbred horses with and without recurrent laryngeal neuropathy (RLN). Latencies were compared in horses with grades 1 and 2 RLN, diagnosed by endoscopy in resting horses. The reliability of the measurements, effect of sedation and correlations of latencies with age of the horse were also studied. There was no effect of sedation on reflex latency periods. The latency of the reflex period measured to a convolved peak of the electromyographic response was significantly different in horses with gr...
Pumarola M, Vidal E, Trens JM, Serafín A, Marquez M, Ferrer I.Neuronal intranuclear inclusion disease (NIID) is reported in a 16-year-old Pure Spanish breed female horse suffering from progressive ataxia and motor deficiencies. The neuropathological study revealed NIIs throughout the central nervous system, although mainly in the brain stem and spinal cord. This distribution did not correlate with neuron loss, which was marked in the hippocampus and moderate in the neocortex, particularly in the occipital cortex. As in humans, NIIs in the horse were hyaline autofluorescent inclusions composed of non-membrane-bound aggregates of filaments and fine granule...
Milne EM, Fintl C, Hudson NP, Pearson GT, Mayhew IG, Hahn CN.This paper describes the histopathological and immunohistochemical changes in the central, autonomic and enteric nervous systems in a well-documented case of equine dysautonomia (ED), after the animal had recovered without significant residual clinical signs. Evidence of neuronal degeneration, such as neuronal chromatolysis, glial scars or a decrease in density of neurons, was not observed in the midbrain, pons, medulla oblongata or spinal cord, including the nuclei of cranial nerves III, V, VII, X and XII. In addition, no evidence of muscle denervation or re-innervation, such as group atrophy...
Boellaard JW, Schlote W, Hofer W.Lipofuscin represents an integral part of neurons and glial cells in mammals and in submammalian species. It is a special lysosomal organelle, takes part of cellular metabolism, and is a structural expression of catabolic pathways. Species-specific differences of lipofuscin indicate metabolic differences of the relevant neurons. The authors have studied the ultrastructure of neuronal lipofuscin in the hippocampus and cerebral neocortex of dogs, horses, cows, elephants, rats, mice, apes, and humans to answer the question of species-specific differences of this organelle. Paraffin sections of fo...
Wijnberg ID, Back W, de Jong M, Zuidhof MC, van den Belt AJ, van der Kolk JH.Systematically performed EMG needle examination of muscles provides essential information about the functional aspects of the motor unit. However, clinical studies in which information is given on the diagnostic and discriminative values of electromyography (EMG) in the horse are scarce. Objective: To determine to what extent inclusion of EMG analysis in clinical examination contributes to determination of type and localisation of abnormality. Methods: EMG analysis, complete clinical examination and diagnosis of 108 horses (mean +/- s.d. age 75 +/- 3.8 years; bodyweight 548 +/- 86 kg; height 1...
Hilbe M, Guscetti F, Wunderlin S, Ehrensperger F.Equine and feline dysautonomias are characterized histopathologically by degenerating neurons with chromatolysis, pyknotic and sometimes eccentric nuclei, and loss of Nissl substance in the peripheral autonomic ganglia. Because it may be difficult to distinguish pathological from post-mortem changes in affected ganglia by histopathological examination, synaptophysin was evaluated as an immunohistochemical marker. Degenerating neurons showed strong intracytoplasmic labelling indicating abnormal accumulation of synaptophysin. It was concluded that synaptophysin immunohistochemistry is a helpful ...
Spadavecchia C, Andersen OK, Arendt-Nielsen L, Spadavecchia L, Doherr M, Schatzmann U.To investigate whether facilitation of the nociceptive withdrawal reflex (NWR) can be evoked and quantified as a measure of temporal summation from the distal aspect of the left forelimb and hind limb in standing nonsedated horses via repeated stimulations of various subthreshold intensities and frequencies. Methods: 10 adult horses. Methods: Surface electromyographic activity evoked by stimulation of the digital palmar and plantar nerves was recorded from the common digital extensor and cranial tibial muscles. For each horse, the NWR threshold intensity to a single stimulus was determined for...
Ribeiro AA, Davis C, Gabella G.The superior (cranial) cervical ganglion was investigated by light microscopy in adult rats, capybaras (Hydrochaeris hydrochaeris) and horses. The ganglia were vascularly perfused, embedded in resin and cut into semi-thin sections. An unbiased stereological procedure (disector method) was used to estimate ganglion neuron size, total number of ganglion neurons, neuronal density. The volume of the ganglion was 0.5 mm3 in rats, 226 mm3 in capybaras and 412 mm3 in horses. The total number of neurons per ganglion was 18,800, 1,520,000 and 3,390,000 and the number of neurons per cubic millimetre was...
Domeneghini C, Radaelli G, Arrighi S, Bosi G, Dolera M.The small and large intestine of adult horses were histochemically and immunohistochemically investigated in order to evidence components of the intramural nervous system. The general structural organization of the intramural nervous system was examined by using Nissl-thionin staining as well as the anti-neurofilament 200 (NF200) immunoreaction, which demonstrated the presence of neurons in the submucous as well as myenteric plexuses. The additional presence of subserosal ganglia was shown in the large intestine. Acetylcholinesterase (AChEase) activity was observed in both the submucous and my...
Nasu T, Sueishi A, Morimoto M.We used immunohistochemical techniques to analyze the localization and distribution of the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) and the neuropeptides methionine-endephalin (M-Enk), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calretinin (Cal), calcitonin gene-related peptide (CGRP), substance P (SP), and galanin (Gal) in the stellate ganglia of two species of domestic animal (cattle and horses). NPY, VIP and Gal immunoreactive neurons (both cell body and nerve fiber) were observed in the stellate ganglia of both animals. M-Enk and CGRP immunoreactive ne...
Nollet H, Deprez P, van Ham L, Dewulf J, Decleir A, Vanderstraeten G.Cervical spinal cord dysfunction is a common problem in equine medicine and the currently available tests give no objective information about the functionality of the nervous tracts. Therefore, transcranial magnetic stimulation (TMS) was performed in 84 healthy horses of different height in order to have an objective measure for the integrity of the descending motor tracts in normal horses. Objective: To obtain reference values for onset latency and peak-to-peak amplitude of magnetic motor evoked potentials (MMEPs) and to evaluate the possible effect of height, age and gender on the neurophysi...
Nollet H, Van Ham L, Verschooten F, Vanderstraeten G, Deprez P.To determine the usefulness of magnetic motor-evoked potentials (MMEPs) for assessing the integrity of the cervical, thoracic, and thoracolumbar spinal cord in horses with bilateral hind limb ataxia. Methods: 9 horses and 1 donkey with bilateral hind limb ataxia of various degrees. Methods: The motor cortex was stimulated magnetically, and MMEPs were recorded bilaterally from the extensor carpi radialis and cranial tibial muscles. Results: In 5 horses and 1 donkey, MMEPs with normal onset latencies and peak-to-peak amplitude were recorded from the extensor carpi radialis muscles, whereas abnor...
Sisó S, Ferrer I, Pumarola M.Numerous swollen neurons and multiple dystrophic axons were observed in the gracillis and cuneatus nuclei of two male Arabian horses, aged six and 12 months of age, with equine degenerative myeloencephalopathy. Swollen neurons and dystrophic axons showed synaptophysin, synaptosomal-associated protein of 25 kDa, syntaxin-1 and alpha-synuclein immunoreactivity. Moreover, dystrophic axons were strongly immunopositive against the ubiquitin protein and against the anti-phosphorylated 200 kDa neurofilament protein. Abnormal expression of integral synaptic vesicle, synaptic vesicle-associated presyna...
Wilkins PA, Palmer JE.Botulism has been recognized as a clinical entity in foals since the 1960s. Also known as "Shaker foal" disease, the toxicoinfectious form of botulism affects foals, with the highest incidence in the United States seen in Kentucky and the mid-Atlantic region. The disease is characterized by progressive muscular weakness caused by the action of botulism neurotoxin at cholinergic neuromuscular junctions. Increased number of episodes and duration of recumbency, muscular trembling, and dysphagia are seen in affected foals. Left untreated, the disease can be rapidly fatal, with death occuring secon...
Nollet H, Van Ham L, Deprez P, Vanderstraeten G.Transcranial magnetic stimulation is rapidly developing as a powerful, non-invasive tool for studying the descending motor tracts in humans. The applications of the test in animals are for the moment restricted to small animals. However, this non-invasive, sensitive and painless technique appears promising as a test of motor tract function in horses where the neurological examination is mainly restricted to clinical evaluation and some ancillary tests, such as radiography, cerebrospinal fluid analysis and electromyography. In this review, we want to discuss the history, basic principles, techn...
Solbrig MV, Koob GF.Borna Disease Virus (BDV) is a neurotropic RNA virus that is worldwide in distribution, causing movement and behavior disorders in a wide range of animal species. BDV has also been reported to be associated with neuropsychiatric diseases of humans by serologic study and by recovery of nucleic acid or virus from blood or brain. Natural infections of horses and sheep produce encephalitis with erratic excited behaviors, hyperkinetic movement or gait abnormalities; naturally infected cats have ataxic "staggering disease." Experimentally infected primates develop hyperactivity, aggression, disinhib...
Peters M, Graf G, Pohlenz J.A 14-year-old standardbred mare with clinically suspected acute bronchitis was killed because of rapidly progressing central nervous disturbances. Necropsy revealed systemic granulomatous inflammation and vasculitis involving the lungs, thoracic lymph nodes, ribs, and liver. In the cerebrum there was a severe subacute bilateral encephalitis and malacia predominately affecting the white matter, and vasculitis with perivascular infiltration of lymphocytes, macrophages, and giant cells. A causative infectious agent could not be detected by Ziehl-Neelsen, Grocott, or Giemsa stains, by periodic aci...
Berardinelli P, Barazzoni AM, Russo V, Brunetti O, Della Torre G, Scapolo PA, Muttini A, Bortolami R.Based on previous observations that capsaicin can selectively damage group III and IV afferents and induce muscle fibre transformation, we hypothesized that eliminating, by means of capsaicin, the group III and IV afferents of a peripheral territory it could lead to a fibre transformation in a muscle involved in the flexor reflexes of the same peripheral territory. Therefore, capsaicin was injected into the palmar nerves of the forelimb of the horse to investigate if eliminating group III and IV afferents from the hand of the horse a muscle fibre transition would occur in the flexor carpi radi...
Toribio RE, Kohn CW, Leone GW, Capen CC, Rosol TJ.In this study, we describe the cloning and tissue expression of equine calcitonin (CT), calcitonin-gene related peptide (CGRP)-I, and CGRP-II cDNA. We also describe a novel divergent form of CGRP (CGRP-I). Equine CT has greatest homology (>85%) to human, rat and mouse subgroups of calcitonins. Equine CGRP-I has low homology (80% homology to chicken, human, rat, ovine, swine, and bovine CGRPs. The homology between equine CGRP-I and CGRP-II is low (56%). The high homology of equine CGRP-II and the low homology of equine CGRP-I to CGRP in other species were unexpected findings. Northern blot a...
Prince D, Corcoran BM, Mayhew IG.Equine grass sickness is a dysautonomia characterised by widespread destruction of autonomic ganglia, resulting in the clinical signs of dysphagia, constipation, profuse sweating, tachycardia, rhinitis sicca and high mortality rate. Rhinitis sicca is a common finding in horses with the chronic form and we have postulated that alterations in autonomic innervation of the nasal mucosa might underlie this clinical presentation. Objective: In this study, the expression and distribution of nerve fibres immunoreactive for calcitonin gene-related peptide (CGRP), substance P (SP), the general neuronal ...
Ferrell EA, Gavin PR, Tucker RL, Sellon DC, Hines MT.Magnetic resonance (MR) imaging was used as a neurodiagnostic modality in the assessment of 12 horses with neurologic disease localized cranial to the foramen magnum. This retrospective study included a mixed population of horse breeds and consisted of three foals and nine adult horses. MR sequences of the head and central nervous system of each horse were acquired. Routine MR sequences included transverse T1 weighted (T1wt), T2 weighted (T2wt), and proton density images. Additional imaging sequences were obtained on a patient-dependent basis. Eight neurologic related diseases were diagnosed. ...
Matera MG, Amorena M, Lucisano A.Equine obstructive pulmonary disease (COPD), or heaves or recurrent airway obstruction, is a common equine pulmonary disease similar to human asthma and/or CODP. Since bronchospasm and inflammation are the key features in heaves, the purpose of this paper is to review the contribution of neural mechanism that may be relevant to this disease. Equine airway receive cholinergic and adrenergic innervation, as well as observed in many species. It was suggested that the autonomic neural control in asthma might be defective with an imbalance between excitatory and inhibitory pathways, resulting in ex...
Walker AM, Sellon DC, Cornelisse CJ, Hines MT, Ragle CA, Cohen N, Schott HC.A retrospective study of the medical records of 33 horses was performed to determine the clinical and diagnostic abnormalities associated with temporohyoid osteoarthropathy. Data collected from medical records included signalment, presenting complaints, history, physical examination findings, laboratory data, results of diagnostic imaging studies, and treatments. Follow-up information was obtained from a review of case records; by telephone conversation with the owner, veterinarian, or trainer; or by both methods. Of 33 horses with temporohyoid osteoarthropathy, 29 presented with facial nerve ...
Davis JL, Gilger BC, Spaulding K, Robertson ID, Jones SL.A 9-year-old Trakehner gelding was examined because of right exophthalmus. Clinical findings included a lack of menace response in the right eye, reduced direct and consensual right pupillary light reflexes, ventrolateral strabismus of the right eye, mild right-sided facial asymmetry, a head tilt to the left, and increased extensor tone in the right limbs. Findings were suggestive of a multifocal lesion affecting the right forebrain; right optic, oculomotor, and facial nerves; and left vestibulocochlear nerve. Ultrasonographic examination of the right eye revealed a vascular retrobulbar mass. ...
Lian WC, Liau MY, Mao CL.Nervous disorders were found in two horses and verified as aseptic encephalitis by necropsy in the summer of 2000. To investigate agents that affected the horses, diagnostic procedures involving virus isolation, neutralization test and reverse transcription-polymerase chain reaction (RT-PCR) were performed. We intracranially inoculated litters of suckling mice with tissues suspected of containing aseptic encephalitis, including cerebrum, cerebellum, brain stem, thalamus, and cerebrospinal fluids; the mice were then observed for 14 days. Neutralizing antibodies against Japanese encephalitis (JE...
Zabek T, Bugno M, Klukowska-Rötzler J, Uhlmann B, Gerber V, Słota E.The research article focuses on identifying the locations of five horse genes related to the development of the skeletal and nervous systems. Sequence Analysis and Bacterial Artificial Chromosome (BAC) Library […]
Plumlee KH.Toxicosis from pesticides rarely occurs in horses and is usually the result of inappropriate pesticide use or handling by humans. Organophosphorus and carbamate insecticides inhibit acetylcholinesterase and are the insecticide class most frequently associated with toxicosis in domestic animals. Metaldehyde is a molluscicide, and zinc phosphide is a rodenticide, both of which have caused toxicosis in horses. All three of these pesticides affect the nervous system of horses and can be fatal if not treated promptly.
Garcia MC, Freedman LJ, Ginther OJ.A working hypothesis for the regulation of LH secretion in the mare is postulated which involves the following two components: (1) a primary central nervous system (CNS)-pituitary component which is responsible for a basal circannual LH rhythm, entrained to an environmental 'Zeitgeber' (most probably photoperiod) and independent of ovarian influences, and (2) a secondary ovarian (steroidal) component which modifies the primary rhythm during the ovulatory season. This hypothesis does not seem to apply in its entirety to FSH secretion; the CNS-pituitary component is demonstrable within the first...
Bowker RM, Linder K, Sonea IM, Holland RE.The sensory innervation of the navicular bone (os sesamoideum distale) and its suspensory ligaments [ligamenta sesamoidea collateralia (CSL) and ligamentum sesamoideum distale impar or distal sesamoidean impar (DS-impar) ligament] and the navicular bursa (podotrochlearis) was examined in the neonatal foal using immunocytochemistry. With antisera raised to substance P (SP) and human calcitonin gene-related peptide (CGRP), immunoreactive nerves were demonstrated to innervate the CSL and navicular bursa. Within CSL, and SP- and CGRP-like nerves were present in the synovial lining of the navicular...
Basran PS, McDonough S, Palmer S, Reesink HL.Proximal sesamoid bone (PSB) fractures are the most common musculoskeletal injury in race-horses. X-ray CT imaging can detect expressed radiological features in horses that experienced catastrophic fractures. Our objective was to assess whether expressed radiomic features in the PSBs of 50 horses can be used to develop machine learning models for predicting PSB fractures. The μCTs of intact contralateral PSBs from 50 horses, 30 of which suffered catastrophic fractures, and 20 controls were studied. From the 129 intact μCT images of PSBs, 102 radiomic features were computed using a variety of...
Kirker-Head CA, Loeffler D, Held JP.Malignant melanoma in a 21-year-old, gray, Arabian gelding was manifested by rapidly deteriorating lameness of the right pelvic limb. A melanotic, cutaneous mass of small dimensions was identified in the left jugular furrow. Exploratory laparoscopy revealed widespread infiltration of melanotic masses into the structures of the abdominal cavity. Necropsy indicated the lameness to have resulted from infiltration of neoplastic cells into the sacral nerves, dorsal root ganglia, proximal ischiatic nerve, and gluteal muscle fibers. The primary tumor could not be identified.
Force L, Jortner BS, Scarrat K.Suchwann cells from a variety of nerves in two adult horses and one adult pony contained perinuclear intracytoplasmic inclusion complexes consisting of lipid droplets, variably electron-dense rounded to elongated bodies and rod-shaped multilamellar structures. The latter were characteristic of pi granules of Reich. There were no significant axonal or myelin alterations associated with these inclusions. It was concluded that the inclusions are a component of normal equine Schwann cells.
Nout-Lomas YS.Mechanisms of traumatic nervous system injury to a degree are similar, but differences exist in etiology, pathophysiology, and treatment of brain, spinal cord, and peripheral nerve injury. The most common clinical abnormalities seen in the horse are abnormal level of consciousness, abnormal behavior, seizures, cranial nerve deficits, vestibular disease, tetra- and paraparesis or paraplegia, cauda equina syndrome, specific gait deficits, and muscle atrophy. Treatments are directed toward reducing inflammation and swelling, halting secondary injury, and promoting mechanisms of neuroregeneration ...
Forster HV, Pan LG, Bisgard GE, Flynn C, Hoffer RE.We assessed the consequences of respiratory unloading associated with tracheostomy breathing (TBr). Three normal and three carotid body-denervated (CBD) ponies were prepared with chronic tracheostomies that at rest reduced physiological dead space (VD) from 483 +/- 60 to 255 +/- 30 ml and lung resistance from 1.5 +/- 0.14 to 0.5 +/- 0.07 cmH2O . l-1 . s. At rest and during steady-state mild-to-heavy exercise arterial PCO2 (PaCO2) was approximately 1 Torr higher during nares breathing (NBr) than during TBr. Pulmonary ventilation and tidal volume (VT) were greater and alveolar ventilation was le...
Dawson DR.This article provides an overview of the more common toxins and adverse drug reactions, along with more rare toxins and reactions (Table 1), that result in neurologic dysfunction in horses. A wide variety of symptoms, treatments, and outcomes are seen with toxic neurologic disease in horses. An in-depth history and thorough physical examination are needed to determine if a toxin or adverse drug reaction is responsible for the clinical signs. Once a toxin or adverse drug reaction is identified, the specific antidote, if available, and supportive care should be administered promptly.
Sasaki N, Yamada M, Morita Y, Furuoka H, Itoh M, Satoh M, Yamada H.We report a case of EMND in a heavy horse that was bred and trained in Hokkaido, Japan. Clinical symptoms included severe ataxia of all four limbs, tilted head, lethargy, and flaccid lips. Numerous axonal degenerations and swellings were observed in nuclei, mostly in the cerebellar dentate nucleus and the nucleus of the hypoglossal nerve, and in the ventral horn of the spinal cord. In the ventral horn of the spinal cord, neuronal degeneration, swelling, and/or necrosis were observed sporadically. The case was diagnosed as EMND from the clinical symptoms and pathological findings.
Vinardell T, Elestwani S, Jamieson C, Karim E, Robin M, Glynn S, Benini R, Aleman M.A standardized protocol for electroencephalography (EEG) under standing sedation for the investigation of epilepsy in foals is needed. Objective: To evaluate a modified standardized EEG protocol under standing sedation using sublingual detomidine hydrochloride in Egyptian Arabian foals. Methods: Nineteen foals (controls, 9; juvenile idiopathic epilepsy [JIE], 10). Methods: Descriptive clinical study. Foals were classified as controls or epileptic based on history or witnessed seizures and neurological examination. Foals were sedated using sublingual detomidine hydrochloride at a dosage of 0.08...
Rousseaux CG, Futcher KG, Clark EG, Naylor JM.Two cases of cauda equina neuritis are compared and contrasted. Neurological deficits of the tail and perineum were noted and functional deficits were seen in gait, urination, defecation and cranial nerve function. Lesions consisted of nonsuppurative inflammation of the nerve trunks and proliferation of the perineurium of the cauda equina. Cranial nerve involvement in one case supported a diagnosis of polyneuritis equi rather than cauda equina neuritis. The possible etiologies and pathogenesis of this disease are discussed.
Rumbaugh GE.Physical, neurologic, and clinicopathologic findings in a 3-year-old female Morgan horse with anorexia and nasal discharge suggested suppurative meningitis. Necropsy findings substantiated the tentative diagnosis. Actinomyces sp was cultured from a meningeal abscess surrounding the pituitary gland and from resolving lung abscesses.
Schils S, Ober T.When diagnosing neuromuscular injury and pain, the use of biomechanical evaluations to assess the mechanics of movement patterns has been useful in the human population. Functional electrical stimulation (FES) is a technology that can create action potentials to produce musculoskeletal movement that is almost indistinguishable from the voluntary kinematics produced by the nervous system. To create controlled and precise musculoskeletal movements in humans and in horses, FES has been shown to be effective. In humans, the kinematic information obtained from FES data has been utilized to direct f...
Andrews FM, Fenner WR.Electrodiagnostic aids, electromyography, auditory brainstem response testing, and electroencephalography are extensions of the neurologic examination and provide valuable information about the nervous system. This article discusses the use and interpretation of electrodiagnostic aids in equine neurology as well as the equipment that is employed. It is hoped that with a better understanding of the available electrodiagnostic aids, they will come into greater use.
Elliott CR, McCowan CI.Nigropallidal encephalomalacia was diagnosed in two horses in northern Victoria that had a history of long-term pasture access to a dense growth of Rhaponticum repens. The region in which the affected horses lived had received well above average rainfall for several months preceding the poisoning. Affected horses had sudden onset of subcutaneous oedema of the head, impaired prehension and mastication, dullness, lethargy and repeated chewing-like jaw movements. Diagnosis was confirmed at necropsy, with characteristic malacic lesions in the substantia nigra and globus pallidus of the brain. This...