Discrete Brain Lesions Research Articles

Circuit based anti-correlation, attention orienting, and major depression.

Major depression is a multidimensional disorder producing emotional dysregulation, cognitive impairment, and neuro-vegetative symptoms. A pathophysiological model of depression needs to explain how these dimensions interact to produce specific clinical phenotypes and how these interactions may predict remission to specific treatments. It is unlikely that major depression results from discrete brain lesions. Here we propose to define major depression as a disorder of neural networks. We review evidence suggesting that the dynamics of neural networks involved in allocation of attention resources to the internal and external world contribute to cognitive impairment, increased self-focus, and dysfunctional saliency detection in depression. We describe cognitive and emotional tasks that reveal abnormal cooperation between the Central Executive Network and the Default Mode Network. Finally we suggest that depression is associated with increased social rejection sensitivity. Studies on social rejection will shed light on how attachment relates to impairment in allocation of attention resources to produce depressive symptoms such as rumination and cognitive problems.

Application of radiosurgical techniques to produce a primate model of brain lesions.

Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130–150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans.

Stroke recovery and sensory plasticity: Common mechanisms?

Presentations in this symposium are considered in the context of mechanisms of sensory plasticity, particularly in the auditory system. The auditory nervous system has two discrete end organs that are separately vulnerable to clinical and experimental injury, and brainstem processing mechanisms that are highly specialized for temporal, spectral, and spatial coding. These include giant axo-somatic synapses and neurons with spatially segregated bipolar dendrites, each innervated exclusively from one ear. This architecture allows exquisite control of afferent-target interactions, including known excitatory and inhibitory couplings, and consequently enhanced interpretation of data from other brain systems. For example, deafening can silence the auditory nerve, but has surprisingly little impact on normal brain function, as evidenced by the success of cochlear implants. The observed amplification from one brain region to another of degeneration following stroke or discrete brain lesions may thus be due to secondary rather than primary afferent consequences of the lesion.

Asymmetrical Contribution of Brain Structures to Treatment-Resistant Depression As Illustrated by Effects of Right Subgenual Cingulum Stimulation

Major depressive disorder is one of the most common psychiatric disorders, with a worldwide lifetime prevalence rate of 10%-20% in women and a slightly lower rate in men. While many patients are successfully treated using established therapeutic strategies, a significant percentage of patients fail to respond. This report describes the successful recovery of a previously treatment-resistant patient following right unilateral deep brain stimulation of Brodmann's area 25. Current therapeutic approaches to treatment-resistant patients are reviewed in the context of this case with an emphasis on the role of the right and left hemispheres in mediating disease pathogenesis and clinical recovery.

Multifocal epithelioid glioblastoma mimicking cerebral metastasis: case report

Epithelioid glioblastoma is a rare morphologic subtype of glioblastoma that closely mimics metastatic carcinoma or metastatic melanoma histologically. All previous case reports of this unusual glioblastoma variant have been solitary lesions. We report here the first case to our knowledge of multifocal epithelioid glioblastoma mimicking cerebral metastasis. A 67-year-old man with a prior history of mycosis fungoides, a common form of cutaneous T-cell lymphoma, presented with memory loss and impaired peripheral vision. Two discrete brain lesions highly suspicious for metastases were identified by magnetic resonance imaging (MRI). The patient underwent two separate craniotomies; both lesions were successfully resected in toto with an excellent post-surgical outcome. Epithelioid glioblastoma is one of the rarest morphologic subtypes of glioblastoma. Here we describe the first case to our knowledge of multifocal epithelioid glioblastoma that convincingly mimicked a secondary metastatic process. Multifocal epithelioid glioblastoma should be included in the differential diagnosis of patients who present with multiple discrete brain lesions. An attempt at gross total resection is recommended when anatomically feasible for definitive histopathological diagnosis and to improve progression free survival of patients who present with similarly ambiguous and potentially misleading multiple lesions.

Recognition of emotions from visual and prosodic cues in Parkinson’s disease

To assess whether Parkinson Disease (PD) patients are impaired at perceiving emotions from facial and prosodic cues and whether any putative defective performance concerns recognition of a particular emotion. Braak et al. [1] demonstrated that in different stages PD pathology involves the nigrostriatal system, the amygdala, and the insular cortex. Discrete brain lesions to these structures can cause selective deficits in recognising facial and prosodic stimuli expressing particular emotions. However, the investigation of facial and prosodic emotional processing in PD patients has lead to conflicting results. We compared 27 cognitively unimpaired PD patients with control subjects by means of the Facial Emotion Recognition Battery and the Emotional Prosody Recognition Battery. PD patients were impaired in recognising, selecting, and matching facial affects. In particular, the Facial Emotion Recognition Battery demonstrated a severe impairment in recognising sad and fearful faces. In the Emotional Prosody Recognition Battery PD patients demonstrated a diffuse impairment, including the recognition of emotional and propositional prosody. Face emotion processing is impaired in PD patients, with a disproportionate deficit involving fear and sadness. The pattern of face expression processing impairment in PD patients might depend on the regional distribution of the pathology. The widespread involvement of both emotional and propositional prosodic processing parallels the aprosodic characteristics of Parkinsonian speech production.

Disturbed perception of colours associated with localized cerebral lesions. By J. C. Meadows (From the National Hospital for Nervous Diseases, Queen Square, London WCIN 3BG) Brain 1974: 97; 615-632.

Acquired cerebral achromatopsia is, at best, rare and its existence denied altogether by many authorities: thus Sir Gordon Holmes writing in 1918 and basing his views on ‘a very large number of cases’ considered that ‘isolated loss or dissociation of colour vision is not produced by cerebral lesions’. John Meadows aims to draw attention to evidence that bilateral but relatively discrete brain lesions may in fact lead to impaired colour vision. In discussing patients with acquired cerebral achromatopsia, his focus is on loss or impairment of the ability to distinguish hues or perceive the brightness of colours. For affected individuals, the world is grey and some may struggle with everyday activities through their inability to distinguish colours. But confusion has crept into the literature as a result of failure to distinguish the symptom of colour loss from abnormalities found only on formal testing; inability to name rather than perceive colour; situations in which the relevance of colour for interpreting the nature of an object or scene is lost; and failure to recognize that lesions of the anterior visual pathway may result in selective loss of acuity for colour compared with a white target. Starting with the case of McKay and Dunlop (The cerebral lesions in a case of complete acquired colour-blindness. Scot Med Surg J 1899; 5: 503–12), and accepting 14 other examples, Dr Meadows extracts the subtleties of the patients’ descriptions, often verbatim, that allow the distinction between cerebral achromatopsia and defective colour vision better explained by one or other of the ambiguities already listed. Thus, Bodamer's patient—‘speaking’ in 1947—describes everything as black and white as if sitting in the cinema: and Pallis's case feels that ‘my shirts all look dirty … I have no idea what tie to wear … I can tell peas and bananas only by …

Data From the VITA Study Do Not Support the Concept of Vascular Depression

Cerebrovascular lesions that are apparent in magnetic resonance scans and regioselective atrophy of the brain have been proposed as a causative or exacerbating factor in depression with late-life onset. The objective of this study was to investigate whether deep white matter or periventricular hyperintensities, small ischemic lesions, and brain atrophy contribute to late-onset depression in the nondemented elderly. Based on a group of 606 individuals of identical age (75.8 years, standard deviation: 0.45 years) residing in two districts of Vienna, the authors built a case-control cohort (ratio: 1:4) consisting of 51 individuals with late-onset major or minor depression matched with 204 subjects of identical gender and education status without depression, resulting in two groups that were homogenous with respect to age, place of residence, gender, and education. Scores for focal brain lesions, mediotemporal lobe atrophy, and ventricular enlargement as well as risk factors for vascular disease were compared with cognition and depression status. Depressed individuals had significantly lower scores than nondepressed subjects in all measures of cognitive and executive function. No significant relation was found between a diagnosis of depression and any type of discrete brain lesions, but measures of brain atrophy (Cella Media indices, mediotemporal atrophy) showed a clear statistical relation to depression. No relationship was found between depression and lipid parameters. The authors found no indication that white matter hyperintensities or minor ischemic lesions played a role in our depressed cohort, casting doubt on the vascular hypothesis of late-onset depression.

Severe Carbon Monoxide Poisoning Treated by Hyperbaric Oxygen Therapy—A Case Report

Carbon monoxide (CO) poisoning is an important cause of mortality and late neurological sequelae such as memory loss, personality changes, psychosis, dementia, and so on. The benefits of hyperbaric oxygen (HBO) therapy are still discussed, but the majority of trials recommend it in severe cases with coma and/or hemodynamic instability, irrespective of carboxyhemoglobin (COHb) level, to prevent permanent neurological deficits. We present a 35-yr-old woman who underwent accidental CO poisoning. Although breathing 100% oxygen by mask during transfer to the hospital, she was in deep coma, hypotensive, cyanotic, and hypoxic (arterial pO2 7,41 kPa, HbO2 87.8%), with serum COHb 26.7% on hospital admission. Orotracheal intubation, mechanical ventilation, iv fluids, dobutamin, and norepinephrine were administered. COHb level decreased to 17.2% within 1 h. To prevent severe neurological sequelae, the patient was transferred as soon as possible to an HBO center 60 km distant to perform HBO therapy twice at 3.0 and once at 2.2 atm within 24 h. After the second HBO session, the patient regained consciousness, and respiratory failure and shock resolved. She was transferred to our hospital and discharged few weeks later with discrete paresis of peripheral nerves, discrete ischemic brain lesions on computed tomography (CT) scan, and moderately abnormal electroencephalogram (EEG) without cognitive disturbances. She was able to resume her daily activities. We conclude that in severe CO poisoning, normobaric oxygen therapy and resuscitation by fluids, inotropic agents, and catecholamines is essential for survival, but additional HBO therapy seems to prevent major neurological sequelae.

Psychiatry as a clinical neuroscience discipline.

One of the fundamental insights emerging from contemporary neuroscience is that mental illnesses are brain disorders. In contrast to classic neurological illnesses that involve discrete brain lesions, mental disorders need to be addressed as disorders of distributed brain systems with symptoms forged by developmental and social experiences. While genomics will be important for revealing risk, and cellular neuroscience should provide targets for novel treatments for these disorders, it is most likely that the tools of systems neuroscience will yield the biomarkers needed to revolutionize psychiatric diagnosis and treatment. This essay considers the discoveries that will be necessary over the next two decades to translate the promise of modern neuroscience into strategies for prevention and cures of mental disorders. To deliver on this spectacular new potential, clinical neuroscience must be integrated into the discipline of psychiatry, thereby transforming current psychiatric training, tools, and practices.

Cerebral localization, then and now

We review some of the progress made in understanding the nature of functional specialization in the human brain, beginning with the anatomical claim that all mental faculties have their own distinct material substrate in different regions of the brain and the psychological claim that each mental faculty is characterized by the content domain with which it deals. This conceptual framework led behavioral neurologists to show how discrete brain lesions provoked different types of language, praxic, gnostic, spatial, and memory disorders. The simplest way of interpreting these anatomoclinical associations was to conjecture that the normal function (now impaired by brain damage) was localized within that lesioned region. It was also realized that cognitive impairments could arise from lesions that spared the functional centers themselves but disconnected them from other centers. Nonetheless, many neuroscientists remained skeptical of the entire paradigm. Accordingly, in the late 19th century functional localization began to be studied in the intact human brain by such techniques as measuring the temperature of different brain regions when different cognitive tasks were performed. During the 20th century these crude techniques gave way to positron emission tomography, functional magnetic resonance imaging, and magnetoencephalography. The relatively precise spatial and temporal resolution of modern methods now raises a crucial question: Do the functional localizations obtained by the anatomoclinical method converge with those implied by the functional neuroimaging of cognition in healthy volunteers? We then conclude with some recent suggestions that functional specialization is not such a fixed property of brain regions as previously supposed.

Jargonagraphia in a Case of Frontotemporal Dementia

Jargonagraphia is known to occur after discrete brain lesions but not in primary degenerative dementia. We report a patient with frontotemporal dementia who developed jargonagraphia and nonfluent aphasia. Written output was graphically preserved but consisted of short words intermingled with abstruse neologisms. MRI showed predominant right frontotemporal cortical atrophy accompanied by white matter hyperintensities in the right anterior subcallosal periventricular region. Diagnosis and MRI were corroborated by extensive neuropathological findings obtained 8 months later. The agraphia in this case is discussed with reference to both specific macroscopic and microscopic pathoanatomical lesions. We suggest that jargonagraphia can appear in frontotemporal dementia depending on the localization of lesions.

Neural Activity Relating to Generation and Representation of Galvanic Skin Conductance Responses: A Functional Magnetic Resonance Imaging Study

Central feedback of peripheral states of arousal influences motivational behavior and decision making. The sympathetic skin conductance response (SCR) is one index of autonomic arousal. The precise functional neuroanatomy underlying generation and representation of SCR during motivational behavior is undetermined, although it is impaired by discrete brain lesions to ventromedial prefrontal cortex, anterior cingulate, and parietal lobe. We used functional magnetic resonance imaging to study brain activity associated with spontaneous fluctuations in amplitude of SCR, and activity corresponding to generation and afferent representation of discrete SCR events. Regions that covaried with increased SCR included right orbitofrontal cortex, right anterior insula, left lingual gyrus, right fusiform gyrus, and left cerebellum. At a less stringent level of significance, predicted areas in bilateral medial prefrontal cortex and right inferior parietal lobule covaried with SCR. Generation of discrete SCR events was associated with significant activity in left medial prefrontal cortex, bilateral extrastriate visual cortices, and cerebellum. Activity in right medial prefrontal cortex related to afferent representation of SCR events. Activity in bilateral medial prefrontal lobe, right orbitofrontal cortex, and bilateral extrastriate visual cortices was common to both generation and afferent representation of discrete SCR events identified in a conjunction analysis. Our results suggest that areas implicated in emotion and attention are differentially involved in generation and representation of peripheral SCR responses. We propose that this functional arrangement enables integration of adaptive bodily responses with ongoing emotional and attentional states of the organism.

Case report: Delusional jealousy following right-sided cerebral infarct

In this paper we describe a case of delusional jealousy following a right cerebral infarction involving the head of the caudate nucleus, globus pallidus, putamen and internal capsule. There have been a relatively small number of case reports of psychotic symptoms following discrete right cerebral lesions, but none has found Othello syndrome following infarction of these brain areas. We describe the clinical symptoms, signs, course of illness and report the results of CT scans and neuropsychological testing. The patient exhibited symptoms of delusional jealousy that followed an infarction of the perforators of the right middle cerebral artery. The patient also had a left hemiparesis and some cognitive impairment following the stroke. His delusions resolved after treatment with nortriptyline, recurred after a second stroke involving the same area, and again responded to the same medication. Psychotic symptoms including delusions can be caused by a variety of generalized and discrete brain lesions. The striatum, which was infarcted in this patient, may also be important in the genesis of psychotic symptoms.

PK ('peripheral benzodiazepine')--binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to activated microglia.

The isoquinoline PK11195 has been suggested as a marker of glial pathology in the lesioned brain. The aim of the present study is to clarify the precise cellular location of its binding site in the central nervous system. Here, we report that in the facial nucleus after facial nerve axotomy-a lesion causing a retrograde neuronal reaction without nerve cell death while keeping the blood-brain barrier intact--activated microglia are the predominant source of lesion-induced increases of PK11195 binding. Likewise, increased PK11195 binding is seen in the gracile nucleus after anterograde neuronal injury following sciatic nerve transection. The peak of PK11195 binding, using the single isomer R-PK11195, was observed 4 days after the peripheral nerve lesion, consistent with the well-known time course of microglial activation. Photoemulsion microautoradiography confirmed the restriction of PK11195 binding to activated microglia. The increase of PK11195 binding in the facial nucleus seen after selective cell death of facial motoneurons by retrograde suicide transport of toxic ricin, a lesion that is accompanied by the rapid transformation of microglia into phagocytes, was no higher than that seen following axotomy. This suggests that the full transformation of microglia into parenchymal phagocytes is not necessary to reach maximal levels of PK11195 binding. PK11195, therefore, is a well-suited marker to detect microglial activation in areas of subtle brain pathology, where neither a disturbance of the blood-brain barrier function nor the presence of macrophages and inflammatory cells indicate an on-going disease process.

Geniculocalcarine hyperintensities on brain magnetic resonance imaging associated with visual hallucinations in the elderly

Magnetic resonance scans of five geriatic patients presenting with formed visual hallucinations in the absence of other psychopathology were compared with those of 12 healthy elderly subjects for the presence and extent of subcortical and periventricular signal hyperintensity. While the number of discrete brain lesions did not differ between groups, scans from the patient group contained a higher incidence (100% vs. 50%) and greater mean size (11.1 vs. 2.9 mm) of periventricular signal hyperintensity in the posterior region. Peripheral visual acuity was impaired in all of the patients, but cerebrovascular risk factors were not elevated in this group. The authors suggest that structural abnormalities in the area of the primary visual pathway may predispose some older individuals, particularly those with poor peripheral visual acuity, to develop the symptom of visual hallucination.

Long-term abolition of Parkinsonian tremor following attempted ventriculography

Three patients are described who were selected for stereotactic thalamotomy to alleviate the tremor and rigidity of Parkinson's disease but in whom these symptoms were abolished whilst attempting ventriculography. Discrete deep brain lesions were seen on post-operative CT scan and the basis for their relieving the patients' symptoms is discussed. Although the tremor and rigidity was abolished in these cases and a favourable result ensued, ventriculography is an invasive and potentially dangerous procedure and it is therefore recommended that CT-derived thalamic targets should be employed for functional stereotaxy.

Cortical Microcirculation in a New Model of Focal Laser-Induced Secondary Brain Damage

To study the causes of spatial and temporal evolution of progressive neuro-injury in focal brain ischemia, models with consistent lesion topography are required. In such models, continuous monitoring of the microcirculation in a penumbral area undergoing progressive damage could be possible. We used a fixed-pulse (1.0 s, 40 W) Nd-YAG laser (NYL) to produced discrete brain lesions in rats and monitored the cerebral blood flow (CBF) with laser-Doppler flowmetry (LDF) in nonirradiated areas directly adjacent to the maturing lesion. We also examined the time evolution of the lesion topography over a 4 day period. The lesion volume determined by histopathological methods increased from 3.1 +/- 0.5 to 4.5 +/- 0.5 mm3 (p less than 0.05) during the first 2 h. Simultaneously, LDF indicated severe hypoperfusion (-60 +/- 21%, p less than 0.01) at a zone (1 mm distance from the laser lesion) where progressive neuronal degeneration and increased tissue water content (80.0 +/- 3.3% versus 76.8 +/- 2.1% in normal tissue, n = 7, p less than 0.05) were also observed. At a 4 mm distance from the lesion, hyperemic CBF responses were observed, but no histopathological signs or edema. Secondary brain damage progressed up to 4 days (lesion volume of 6.0 +/- 0.7 mm3). The NYL-induced brain lesion produced a highly reproducible focal injury and progressive neuronal death in a spatial relationship with microcirculatory failure and edema formation. The model allows prospective study of tissue state at a discrete zone, which is separate from the initial injury, but susceptible to secondary brain damage.

Effect of discrete brain lesions on hypothalamic and pituitary immunoreactive dynorphin

Radiofrequency lesions of the anterior hypothalamic area reduced immunoreactive dynorphin (ir-DYN) in the hypothalamus and in the neurointermediate lobe of the pituitary. Ablation of the medial preoptic area was not associated with any significant modification of ir-DYN in the tissue examined. Destruction of the medial basal hypothalamus in parallel lowered ir-DYN in the hypothalamus and in both pituitary lobes. Neonatal administration of monosodium glutamate had no significant effect on ir-DYN. These findings indicate that changes of ir-DYN in the hypothalamus and pituitary are associated with the destruction of anatomically and functionally distinct neural systems.

Anterior-posterior locus of lesion and personality: support for the caudality hypothesis.

Investigated the effects of discrete brain lesions on MMPI performance in well-matched samples of patients with anterior and posterior injuries. Because of the nature of the samples and careful matching for potentially confounding variables, particular emphasis could be given to the study of brain-behavior relationships. Patients with posterior lesions produced a significantly more abnormal composite MMPI profile, had a consistent tendency to produce elevated (70+) individual MMPI scales, and had individual profiles that were universally rated as abnormal using standard criteria. The differential MMPI patterns exhibited by these two samples were compatible with traditionally held clinical hypothesis with regard to distinct personality differences secondary to focal lesions in the caudal plane. It is our conclusion that lesion caudality does have a differential effect upon MMPI performance when factors such as cognitive, motor, and sensory defects are controlled adequately. The implications are that this effect is locus specific and is not necessarily related to the degree of other neurobehavioral impairment, as has been hypothesized previously.