Limbic System Lesions Research Articles

Association between limbic system lesions and anxiety in persons with multiple sclerosis

BackgroundPersons with Multiple Sclerosis (PwMS) have a higher rate of anxiety and depression than the general population. Depression has been associated with clinical relapses; temporal lesions were shown to predict depression severity. Anxiety is considerably understudied. The role of MS lesions in the limbic system is also understudied, partly due to difficulties identifying limbic lesions on standard 1.5 and 3 Tesla MRI. MethodsThis is a retrospective study of 23 PwMS who underwent 7T MRI on the same day as completing the Hospital Anxiety and Depression Scale (HADS). MRI was performed on a Siemens 7T MRI Plus and an 8-channel transmit coil with 32 receiver channels operating in pTx mode. MP2RAGE and DIR-SPACE sequences were analyzed to determine the number of lesions within the limbic system. ResultsThe median number of lesions in the limbic system was 2.0 (range 0–7). When comparing the presence or absence of lesions in the limbic system, there was a significant relationship with anxiety (X2 (1, N = 23)=4.44, p = 0.035), but not for depression. ConclusionAlthough only a small sample size, this study provides preliminary evidence that lesions in the limbic system are associated with the presence of anxiety in PwMS. This relationship warrants further investigation.

Clinical characteristics and prognosis of anti-GABABR encephalitis: A single-center experience.

The purpose of this study was to assess the demographic data, clinical manifestations, cerebrospinal fluid (CSF), hematology, brain magnetic resonance imaging, electroencephalograms, and therapy and prognosis related to anti-gamma-aminobutyric acid B (anti-GABABR) encephalitis. We retrospectively examined the demographic data, clinical manifestations, laboratory results, brain magnetic resonance imaging, electroencephalograms, and therapy and prognosis of 6 patients with anti-GABABR encephalitis. We used the clinical data of patients with anti-GABABR encephalitis admitted to the Department of Neurology of Mianyang Central Hospital obtained from January 2017 to September 2020. Six patients with anti-GABABR encephalitis were included. Generalized tonic-clonic seizure was the first clinical symptom in 5 patients, while 1 patient first showed behavior disorder. After the first clinical symptom attack, 2 patients developed a memory deficit, 4 cases showed cognitive decline, 3 cases showed behavior disorder, 1 patient developed status epilepticus and only 1 patient returned to normal. CSF testing indicated normal intracranial pressure in 5 patients and elevated pressure in only 1 patient. Additionally, the cerebrospinal fluid tests revealed slight leukocytosis in all patients and elevated protein levels in 5 patients. The anti-GABABR antibody was positive in both serum and CSF in all patients. Brain magnetic resonance imaging showed limbic system lesions in 4 patients. Long-term electroencephalograms revealed abnormal waves in half of the patients. All patients were treated with high dosages of methylprednisolone, which was combined with intravenous immunoglobulin in 2 patients; symptoms were improved in 4 patients, 1 patient showed no significant change and 1 patient with status epilepticus died of severe pneumonia during hospitalization. Epilepsy is the most common initial symptom in patients of anti-GABABR encephalitis. Many patients are also affected by tumors. Early immunotherapy can achieve excellent effects, the long-term prognosis is good for most patients.

Clinical Characteristics and Follow-Up of Seizures in Children With Anti-NMDAR Encephalitis.

Objective: To analyze the seizure characteristics of children with anti-NMDAR encephalitis.Methods: This was a retrospective analysis of 50 children with anti-NMDAR encephalitis between July 1, 2013, and July 1, 2019.Results: Fifty children with anti-NMDAR encephalitis were included in this study, of which 34 (68.0%) had seizures. During the follow-up, three patients with anti-NMDAR encephalitis secondary to herpes simplex virus encephalitis had persistent seizures. The average duration of seizures in the remaining patients was 14.6 days (range 1–47 days). Compared to patients without seizures, those with seizures were more likely to experience consciousness disturbances (p = 0.008) and epileptic form discharge on electroencephalograms (p = 0.002). The Glasgow coma scale scores (p = 0.014), and Rankin scale scores (p = 0.019) were also different. The cranial MRI findings of children were reviewed, and clinical characteristics were compared between children without cranial lesions and those with lesions in the limbic system and neocortex. Compared to children in the non-lesion group, children with lesions in the limbic system and neocortex had a higher incidence of status epilepticus. Further, children in the limbic system and neocortical lesions groups were more likely to be taking anti-seizure medications (ASMs) and receive second-line drugs.Conclusion: Long-term oral ASMs are not recommended for most children with anti-NMDAR encephalitis. Children with involvement of the limbic system and neocortex are prone to status epilepticus, and sequelae of epilepsy may remain when the neocortex is involved.

Patients with anti-GABA (B) receptor encephalitis: 8 cases report

Objective: To discuss the clinical features, diagnosis, therapy and prognosis of anti-GABA (B) receptor encephalitis. Methods: Clinical data of patients with anti-gaba B receptor encephalitis admitted to the department of neurology of the second hospital of hebei medical university from April 2016 to February 2018 were collected and retrospectively analyzed. Results: Eight patients with anti-GABA (B) receptor encephalitis were included. All the eight cases presented with epileptic seizures. The initial symptoms were clinical seizures in six cases, memory deficit in one case, mental and behavior disorder in one case. Cerebrospinal fluid (CSF) test indicated high intracranial pressure in four patients, increased protein in two patients and lymphocytosis in four patients. Long-term electroencephalogram (EEG) showed abnormal in all patients. Brain MRI showed limbic system lesions in four patients. The anti-GABA (B) receptor antibody was positive in both serum and CSF in all patients. Four patients had small cell lung cancer. All the eight patients received immunotherapy and symptoms were improved. After 6-24 months' follow-up, 1 patient recovered completely, and in the remaining 7 patients, mild symptoms were left behind. Conclusions: The anti-GABA (B) receptor encephalitis is characterized by refractory epilepsy. Epilepsy is the most common initial symptom. About 50% patients are accompanied by tumors. Anti-GABA (B) receptor antibodies testing and tumor screening should be actively carried out.

Anti-GABAB receptor encephalitis: clinical analysis of 5 cases

Objective To investigate the clinical manifestation, auxiliary examination characteristics, therapeutic intervention and prognosis of anti-GABAB receptor encephalitis. Methods Clinical data of 5 patients diagnosed as anti-GABAB receptor encephalitis in Neurology Department of Zhengzhou University People′s Hospital were retrospectively analyzed. Results The initial symptom was seizures in all of the 5 patients with anti-GABAB receptor encephalitis. During the course of disease, mental and behavior disorders were found in 4 patients, cognitive disorder in 3 patients, autonomic dysfunction in 1 patient, central hypoventilation and parasomnia in 1 patient. Brain MRI showed limbic system lesions in 3 patients. Cerebrospinal fluid (CSF) test indicated lymphocytosis in three patients. The anti-GABABR antibody was positive in both serum and CSF in all patients. Chest CT showed lung occupying lesions in 4 patients, of which 2 lesions were diagnosed as small cell lung cancer by pathological examination. All patients received immunotherapy after being diagnosed as anti-GABAB receptor encephalitis and responded well to immunotherapy. 1 patient without tumor fully recovered during the follow-up, while residual lesions were left in the other 4 patients with tumors. Conclusions Anti-GABAB receptor encephalitis responds well to immunotherapy, and the early identification, diagnosis and treatment are very important to improve the prognosis of patients. Key words: Gamma-aminobutyric acid; Encephalitis; Epilepsy

Limbic system surgery for treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 64 patients

Obsessive-compulsive disorder (OCD) is a common and disabling psychiatric illness, and in a significant proportion of patients with OCD the disease is refractory to conventional pharmacotherapy and psychotherapy. For more than half a century, patients with severe, treatment-resistant OCD have been treated with stereotactic limbic system lesions, including dorsal anterior cingulotomy. The authors present their results describing the efficacy and durability of limbic system surgery for OCD, characterizing a large cohort of patients treated at a single institution with a mean follow-up of more than 5 years. The authors identified 64 consecutive patients undergoing cingulotomy for refractory OCD at the Massachusetts General Hospital between 1989 and 2009. Changes in OCD and major depressive disorder symptom severity were assessed at both the initial and most recent postoperative follow-up by using the Yale-Brown Obsessive Compulsive Scale and the Beck Depression Inventory, respectively. Full and partial OCD symptom responses were defined as Yale-Brown Obsessive Compulsive Scale score reductions of ≥ 35% and 25%-34%, respectively. Regarding OCD symptom improvement, at the first postoperative follow-up (mean 10.7 months), 35% of patients demonstrated a full response and 7% were partial responders. Thirty patients had a subsequent procedure (repeat cingulotomy or subcaudate tractotomy). By the most recent follow-up (mean 63.8 months), rates climbed to 47% and 22% for full and partial responses, respectively. Of the 24 patients with at least a partial response at initial follow-up, 20 (83%) retained at least a partial response at final follow-up. Comorbid major depressive disorder severity decreased by 17% at the most recent follow-up. Limbic system surgery based on initial cingulotomy offers a durable and effective treatment option for appropriately selected patients with severe OCD who have not responded to conventional pharmacotherapy or psychotherapy.

Principles of Neuropsychiatry: Towards a Neuropsychiatric Epistemology

Abstract Depression, mania, obsessive-compulsive behavior, psychosis and personality changes are common manifestations of brain disorders. These neuropsychiatric syndromes exhibit rule-bound relationships to brain dysfunction and occur most commonly with lesions of the limbic system or frontal-subcortical circuits. They reflect disruption of mechanisms mediating fundamental functions such as mood, emotion, motivation, self-protection and social affiliation. Lesional factors (i.e. size and location of lesion, disruption of transmitter systems) as well as host-related non-lesional factors (i.e. family history of psychiatric illness, age of onset of neurological condition, gender) contribute to determining which patients with specific neurological conditions develop associated neuropsychiatric disturbances. Investigations of the psychiatric aspects of neurological disease and the neurobiology of psychiatric disorders indicate that similar anatomical regions are involved when these conditions have the same sy...

Anatomical Substrates of Behavioral Impairment Induced by Developmental Lead Exposure in Monkeys: Inferences from Brain Lesions

There is a substantial literature exploring the behavioral consequences of developmental lead exposure in the monkey; deficits have been observed on a number of tasks assessing learning and memory including spatial delayed alternation, discrimination reversal, matching to sample, and concurrent discrimination. Differences in performance between control and lead-exposed monkeys have also been observed on intermittent schedules of reinforcement. Comparison of the effects of lead with the extensive literature on the consequences of lesions in discrete areas of brain on the same tasks may provide insight into the possible sites of brain damage responsible for lead-induced behavioral impairment. Available data strongly suggest that prefrontal cortical areas are damaged by lead, based on the pattern of performance deficits across specific tasks. In addition, a constellation of global deficits including perseveration, increased distractibility, inability to change response strategy, and inability to inhibit inappropriate responding are hallmarks of both prefrontal damage and developmental lead exposure. Evidence also implicates basal forebrain structures in behavior impairment produced by lead based on the pattern of deficits across numerous tasks, although the evidence is much weaker than for prefrontal cortex. In contrast, the pattern of behavioral impairment produced by limbic system lesions is different in many respects from that produced by lead; in addition, the scant neuropathological data available suggest that limbic structures are not a target of lead even at high blood lead levels in the monkey. Comparison of the pattern of damage following lead exposure with the effects of lesions, presented here, provides direction for further morphological or neurochemical exploration of lead-induced brain damage in the monkey.

Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys

Object memory processes, evaluated in rhesus monkeys by delayed nonmatching-to-sample with trial-unique stimuli and object reversal learning, were more severely impaired by orbital frontal than by anterior cingulate lesions. Spatial memory processes, assessed by spatial delayed response and spatial reversal learning, showed a weak trend in the opposite direction, though on these tasks neither lesion produced a serious loss. Comparison of the present results with those of earlier studies on the effects of various limbic system lesions suggests that object memory processes, including object recognition and object-reward association, are served by a circuit consisting mainly of the rhinal cortex, orbitofrontal cortex, and the magnocellular division of the medial dorsal thalamic nucleus. Although both the rhinal and orbitofrontal components of this circuit appear to participate in both functions, evidence from the present and earlier studies suggests that the orbitofrontal component is the more important one for associative memory, i.e. the formation across trials of associations between particular objects or classes of objects and reward, whereas the rhinal component is the more critical one for recognition memory, i.e. the storage and retrieval within trials of the representations of particular objects.

Activation, travel distance, and environmental change influence food carrying in rats with hippocampal, medial thalamic and septal lesions: implications for studies on hoarding and theories of hippocampal function.

Rats transport food from exposed areas to covered areas where they eat it or leave it. Although there is evidence that limbic structures play a role in food transport, their role is controversial. Here it was found that although many rats with large hippocampal, septal/diagonal band of Broca or dorsomedial thalamic lesions did not carry food but ate it where they found it, a few presentations of an auditory stimulus could restore food carrying. Once restored, most features of food carrying in hippocampal rats were normal in relation to food presentation schedules, deprivation levels, ambient illumination, circadian cycles, food size, and eating times. Nevertheless, food carrying impairments re-emerged when the testing environment was changed. Hippocampal rats were also excessively responsive to increases in travel distance and stopped carrying food at distances over which control rats would still carry large food pellets. Auditory stimulation did not restore food carrying over long travel distances. The findings that sensory stimulation, environmental change, and travel distance influence food carrying probabilities in rats with limbic system lesions is discussed in relation to research on limbic control of food hoarding and theories of limbic system function.

Microscopic Neuroanatomic Abnormalities in Autism

Since its initial description in 1943,1 autism has been primarily conceptualized as a behavioral disorder, and for many years it was believed to be the result of parental and environmental influences. With heightened clinical interest in the disorder, coincident with advances in medical technology, however, evidence for an underlying neurologic basis for autism has become increasingly apparent. HISTORICAL NEUROPATHOLOGIC PERSPECTIVE Based largely on the constellation of symptoms that characterize the disorder, various anatomical sites within the brain have been suggested as a possible primary source of pathology in autism. Suspected regions have included the medial temporal lobe,2-5 the thalamic nuclei,6 the basal ganglia,7 and the vestibular system.8 Computed tomographic imaging studies have shown inconsistent findings.9-14 More recently, however, magnetic resonance imaging studies have described abnormalities in portions of the cerebellum and posterior fossa.15-17 Direct microscopic examination of the autistic brain has, until recently, yielded little information. Aarkrog18 reported "slight thickening of the arterioles, slight connective tissue increase in the leptomeninges, and some cell increase" in a frontal lobe biopsy performed on an autistic patient. Later, in 1976, 33 cases of childhood psychosis were reviewed by Darby.19 Although he suggested a possible correlation between limbic system lesions and the affective symptomatology of autism, no consistent neuropathologic findings were found. In 1980, Williams et al20 studied sections of brain from four patients with autistic-like behavior; looking primarily for cell loss and gliosis, they failed to find any consistent abnormalities. MICROSCOPIC NEUROANATOMIC OBSERVATIONS In 1984, anatomic abnormalities were reported in the brain of a 29-year-old man with well-documented autism; the technique of whole brain serial section was used, and the patient was studied in comparison with an identically processed age- and sex-matched control subject.21,22

Learning and memory disorders and their assessment

Brain lesions cause memory to break down in several distinct ways in people. First, cortical lesions cause disturbances in short-term memory. Second, other cortical lesions disturb the retrieval of previously well-established semantic and episodic memories. Third, frontal cortex dysfunction seems to be related to a memory syndrome caused by a breakdown in the ability to plan and carry out elaborative processing. Fourth, and most explored, is the amnestic syndrome(s), caused by limbic system or diencephalic lesions. Other less-studied forms of memory breakdown almost certainly exist and some memory syndromes are compounded from these more basic deficits. Appropriate assessment of memory disorders must take this heterogeneity and complexity into account, and is important not only for clinical purposes but also to gain further insight into the precise nature of the different kinds of breakdown. The major theoretical and clinical requirementst that such assessment procedures must meet are outlined.

L'image morphologique des structures du système limbique chez les rats après administration prolongée des antiépileptiques

Morphological changes in the anatomical structures of the limbic system induced by phenytoin and ethosuximide administered in effective doses for 1, 3 and 6 months in rats were analyzed. The clinical symptoms consisted of some vegetative and behavioral disorders, mostly transitory. Differences in gain of body weight depending on the sex of the animal and the drug administered were observed. The morphological changes in the parenchymal and mesenchymal nervous tissue elements were not specific with regard to their topography or to the type of pathological process. Some morphological differences depending on the drug and its period of administration were observed only in rats treated for 1 and 3 months. The neuropathological picture in rats treated with both drugs for 6 months showed a great similarity. The pathological process in the ganglionic cells had the character of degeneration. Morphological changes in the myelin sheaths were due to edema which appeared to be vasculogenic and situated in the white matter. Focal and diffuse proliferation of cellular glia appeared after administration of both drugs for 1 and 3 months while in those treated for 6 months the degenerative changes were seen. The anatomo-comparative study of the neuropathological picture in the rats treated with both drugs and the morphological picture of the limbic system structures in patients with chronic epilepsy indicates that the drugs examined could play some role in the pathogenesis of the limbic system lesions encountered in epileptics.

Corticomedial amygdala lesions, behavior, corticosterone, and prolactin: Unexpected separation of effects

The present experiment examines hormone: behavior relationships following lesions of the amygdala. Affective behavior and levels of corticosterone and prolactin were compared in rats with lesions of the corticomedial amygdala and in nonlesioned and sham-operated controls. Animals with lesions of the corticomedial amygdala were found to be hyperreactive, but to have normal corticosterone and prolactin resting levels and responses to stimulation. The unexpected separation of behavior and hormone responses is compared with behavior and endocrine changes seen following other limbic system lesions, and the implications for the psychoneuroendocrinology of stress are discussed.

Differential effects of double and triple lesions of the cat's limbic system on subsequent learning behavior.

Differential effects of double and triple lesions of the cat's limbic system on subsequent learning behavior.

Differential effects of double and triple lesions of the cat's limbic system on subsequent learning behavior.

On the basis of recent anatomical experiments in which it was found that the anterior thalamus, the subicular cortex, and the mamillary bodies are directly and strongly interconnected, lesions were made in different combinations of two or all three of these regions in four groups of cats. These found groups and a control group were then subjected to two learning tasks: a visual reversal and an active two-way avoidance task. Compared with cats of the control group, cats with lesions of the anterior thalamus and the mamillary bodies (Group AT/MM), of the anterior thalamus and the subiculum (Group AT/SUB), or of the mamillary bodies and the subiculum (Group MM/SUB) were strongly impaired in acquiring the reversal task, whereas cats with lesions of all three structures together (Group AT/MM/SUB) were unimpaired. Similarly, in the active avoidance task, two of the three groups with double lesions (MM/SUB; AT/SUB) were imparied, but cats of Groups AT/MM and AT/MM/SUB were not, compared with the control group. Consideration is made that lesion-induced shifts possibly act upon intact cortical and/or thalamic structures that, prior to massive limbic lesions, remained inhibited or otherwise suppressed. It is assumed the influence of one of the three core regions of the modified Papez-circuit to be sufficient for inhibiting the action of such structures which following a complete lesion of the system may control essential parts of the behaviors tested.

Differential effects of basolateral amygdala lesions on behavior, corticosterone, and prolactin responses

The present experiment examines hormone-behavior relationships following manipulation of the amygdala. Affective behavior and levels of corticosterone and prolactin were compared in rats with lesions of the basolateral amygdala and in nonlesioned and sham-operated controls. Animals with lesions of the basolateral amygdala were found to be hyperreactive and to have normal resting levels of corticosterone and prolactin but potentiated corticosterone responses to stress. Normal prolactin stress responses were unaltered by the lesion. The results are discussed in relation to behavioral and endocrine changes seen following other limbic system lesions.

Differential olfactory bulb contributions to baitshyness and place avoidance learning

Garcia and Ervin [14] hypothesized that neuroanatomically discrete associative mechanisms subserve illness-induced taste aversions and shock-motivated avoidance of telereceptive cues. Such neuroanatomical diversity implies that appropriately placed brain lesions might selectively influence one of these types of learning. While several limbic-system lesions can disrupt shock-motivated compartment avoidance (SMCA) without modifying illness-induced taste aversion (IITA) conditioning, the opposite pattern of selective interference has not been reported. The anterior tips of the olfactory bulbs of male albino rats were removed because neuroanatomical and behavioral data indicated that these lesions might disrupt IITA without influencing SMCA. Larger olfactory-bulb ablations approximating total bulbectomies were also studied for comparison purposes. Both total bulbectomies and anterior bulbectomies partially blocked IITA acquisition. Total bulbectomies also interfered with SMCA conditioning, but this learning was unimpaired by anterior bulbectomies. These anterior-bulbectomy results are consistent with the neuroanatomical-diversity hypothesis. Present findings are also discussed relative to the applied problem of selecting biologically appropriate noxious stimuli for aversion therapy approaches to alcoholism treatment.

Temporal effects of discrete lesions in the olfactory and limbic systems on open-field behavior and dyadic encounters in male hooded rats

The spontaneous and dyadic behavior patterns of five matched groups of male hooded rats were compared to SHAMs following selective lesions of the olfactory and limbic system. One group received bilateral lateral olfactory tract lesions (LOT); a second bilateral anterior olfactory nucleus lesions (AON); a third sham operations (SHAM); a fourth bilateral AON and LOT lesions combined (ANLT); and a fifth cortico-medial amygdalar lesions (AMYG). When tested alone in the open field, LOT, ANLT, and, to some extent, AON lesioned animals were hyperactive. Activity scores for the AMYGs were not significantly different from that of the SHAMs. High rearing time scores were seen in the LOT, ANLT, and AMYG groups while high sniffing frequency and rearing frequency scores were associated with LOT and ANLT lesions. AONs had significantly higher and LOTs significantly lower sniffing time scores than any other groups. The AMYGs had the highest and LOTs the lowest sniffing bout lengths. Sniffing time for the ANLTs did not differ significantly from that of the SHAMs. Freezing was reduced in all lesioned groups as compared to SHAMs. These differences did not become clearly apparent until 7 to 10 days following surgery and were evident 40 days postsurgically. All lesioned animals were hyperirritable and difficult to handle following surgery with the LOTs, ANLTs, and AMYGs particularly so. This irritability was evident on the first day following surgery and persisted through postoperative day 40. When tested in pairs in a circular open field, all animals spent a large proportion of their time in direct contact. All lesioned animals, however, spent more time in aggressive interactions than did the SHAMs. The results were discussed against a background of other olfactory and limbic system lesions with particular reference to possible functional and anatomical substrates mediating behavioral changes typically reported following olfactory system lesions.

Effect of limbic system lesions on acetylcholine release from the cerebral cortex of the rat.

The effect of electrocoagulative lesions placed in the septum, fornix and fimbria, fimbria and hippocampus on ACh release from the cerebral cortex was investigated in rats under urethane anaesthesia. At least 2 weeks elapsed between the stereotactic placement of the lesions and the determination of ACh output. ACh was determined by bioassay on the dorsal muscle of the leech. No lesion affected the spontaneous release of ACh. The increase in ACh output induced by i.p. administration of amphetamine was abolished by the septal lesion only. On the other hand, the increase in ACh output induced by i.p. administration of scopolamine was strongly reduced by lesions of the septum, of the fornix and fimbria and to a lesser extent of the fimbria. The administration of amphetamine and scopolamine discloses therefore a specific functional impairment of the cerebral cholinergic mechanisms in rats with limbic lesions.