Thalamic Damage Research Articles

Impairment in material‐specific long‐term memory following unilateral mediodorsal thalamic damage and presumed partial disconnection of the mammillo‐thalamic tract

Neuropsychological findings suggest material-specific lateralization of the medial temporal lobe's role in long-term memory, with greater left-sided involvement in verbal memory, and greater right-sided involvement in visual memory. Whether material-specific lateralization of long-term memory also extends to the anteromedial thalamus remains uncertain. We report two patients with unilateral right (OG) and left (SM) mediodorsal thalamic pathology plus probable correspondingly lateralized damage of the mammillo-thalamic tract. The lesions were mapped using high-resolution structural magnetic resonance imaging and schematically reconstructed. Mean absolute volume estimates for the mammillary bodies, hippocampus, perirhinal cortex, and ventricles are also presented. Estimates of visual and verbal recall and item recognition memory were obtained using the Doors and People, the Rey Complex Figure Test, and the Logical Memory subtests of the Wechsler Memory Scales. Each patient's performance was compared to a group of healthy volunteers matched for demographic characteristics, premorbid IQ, and current levels of functioning. A striking double dissociation was evident in material-specific long-term memory, with OG showing significant impairments in visual memory but not verbal memory, and SM showing the opposite profile of preserved visual memory and significantly impaired verbal memory. These impairments affected both recall and item recognition. The reported double dissociation provides the strongest evidence yet that material-specific lateralization of long-term memory also extends to the anteromedial thalamus. The findings are also discussed in relation to proposals that distinct anatomical regions within the medial temporal lobe, anteromedial thalamus, and associated tracts make qualitatively different contributions to recall and item recognition.

Autophagosomes accumulation is associated with β‐amyloid deposits and secondary damage in the thalamus after focal cortical infarction in hypertensive rats

Focal cerebral cortical infarction after distal middle cerebral artery occlusion causes β-amyloid deposition and secondary neuronal degeneration in the ipsilateral ventroposterior nucleus of the thalamus. Several studies suggest that autophagy is an active pathway for β-amyloid peptide generation. This study aimed to investigate the role of autophagy in thalamic β-amyloid deposition and neuronal degeneration after cerebral cortical infarction in hypertensive rats. At 7 and 14days after middle cerebral artery occlusion, neuronal death and β-amyloid deposits were evident in the ipsilateral ventroposterior nucleus, and the activity of β-site amyloid precursor protein (APP)-cleaving enzyme 1, required for β-amyloid peptide generation, was elevated in the thalamus. In correlation, both the number of cells showing punctate microtubule-associated protein 1A light chain 3 fluorescence and levels of light chain 3-II protein, an autophagosome marker, were markedly increased. Notably, most of the cells that over-expressed β-site APP-cleaving enzyme 1 displayed punctate light chain 3 staining. Furthermore, the inhibition of autophagy with 3-methyladenine significantly reduced the thalamic neuronal damage, β-amyloid deposits, and β-site APP-cleaving enzyme 1 activity. These results suggest that autophagosomes accumulate within thalamic cells after cerebral cortical infarction, which is associated with thalamic β-amyloid deposition and secondary neuronal degeneration via elevation of β-site APP-cleaving enzyme 1 level.

Altered Error Processing following Vascular Thalamic Damage: Evidence from an Antisaccade Task

Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response – the error-related negativity (ERN) - as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients.

Early detection of secondary damage in ipsilateral thalamus after acute infarction at unilateral corona radiata by diffusion tensor imaging and magnetic resonance spectroscopy

BackgroundTraditional magnetic resonance (MR) imaging can identify abnormal changes in ipsilateral thalamus in patients with unilateral middle cerebral artery (MCA) infarcts. However, it is difficult to demonstrate these early changes quantitatively. Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (MRS) are potentially sensitive and quantitative methods of detection in examining changes of tissue microstructure and metabolism. In this study, We used both DTI and MRS to examine possible secondary damage of thalamus in patients with corona radiata infarction.MethodsTwelve patients with unilateral corona radiata infarction underwent MR imaging including DTI and MRS at one week (W1), four weeks (W4), and twelve weeks (W12) after onset of stroke. Twelve age-matched controls were imaged. Mean diffusivity (MD), fractional anisotropy (FA), N-acetylaspartate (NAA), choline(Cho), and creatine(Cr) were measured in thalami.ResultsT1-weighted fluid attenuation inversion recovery (FLAIR), T2-weighted, and T2-FLAIR imaging showed an infarct at unilateral corona radiate but no other lesion in each patient brain. In patients, MD was significantly increased at W12, compared to W1 and W4 (all P< 0.05). NAA was significantly decreased at W4 compared to W1, and at W12 compared to W4 (all P< 0.05) in the ipsilateral thalamus. There was no significant change in FA, Cho, or Cr in the ipsilateral thalamus from W1 to W12. Spearman's rank correlation analysis revealed a significant negative correlation between MD and the peak area of NAA, Cho, and Cr at W1, W4, and W12 and a significant positive correlation of FA with NAA at W1.ConclusionsThese findings indicate that DTI and MRS can detect the early changes indicating secondary damage in the ipsilateral thalamus after unilateral corona radiata infarction. MRS may reveal the progressive course of damage in the ipsilateral thalamus over time.

Neuropathological Findings in Disabled Survivors of a Head Injury

We investigated how the occurrence and severity of the main neuropathological types of traumatic brain injury (TBI) influenced the severity of disability after a head injury. Eighty-five victims, each of whom had lived at least a month after a head injury but then died, were studied. Judged by the Glasgow Outcome Scale (GOS), before death 35 were vegetative, 30 were severely and 20 were moderately disabled. Neuropathological assessment showed that 71 (84%) victims had sustained cerebral contusions, 49 (58%) had diffuse axonal injury (DAI), 57 (67%), had ischemic brain damage (IBD), 58 (68%) had symmetrical ventricular enlargement, and in 47 (55%) intracranial pressure (ICP) had been increased. Thirty-five (41%) had undergone evacuation of an intracranial hematoma. Brainstem damage was seen in only 11 (13%). Analysis (χ(2) test for trends) of the relationship between these features and outcome showed that findings of DAI, raised ICP, thalamic damage, or ventricular enlargement (all p<0.005), and IBD (p=0.04) were associated with an increasingly worse outcome. Conversely, moderate or severe contusions (p=0.001) were increasingly associated with better outcomes, and evacuation of a hematoma was associated (p=0.001) with outcomes likely to be better than vegetative. We conclude that diffuse or multifocal neuropathological patterns of TBI from primary axonal injury or secondary ischemic damage are most likely to be associated with the most severely impaired outcomes after a head injury.

Thalamic Damage Predicts the Evolution of Primary-Progressive Multiple Sclerosis at 5 Years

Reliable markers to monitor PPMS are still needed. We investigated whether conventional and DTI measures of thalamic damage are predictive of long-term disability accumulation in PPMS. Brain conventional and DTI scans were obtained at baseline and after a mean follow-up of 15 months in 54 patients with PPMS and 8 healthy controls. Patients were reassessed clinically after 5 years. At baseline and follow-up, measures of lesion load, brain atrophy, and NTV were obtained. MD and FA histograms of the NAWM, the whole GM without the thalami, and the thalami were obtained. A multivariate analysis evaluated the predictors of long-term neurologic deterioration. At follow-up, 35 patients showed disability worsening. At baseline, compared with healthy controls, patients with PPMS had lower NTV (P < .001) and thalamic FA (P = .002) and higher thalamic (P = .002) and whole GM without the thalami (P = .005) MD. During follow-up, the change of thalamic FA was higher in PPMS versus healthy controls (P = .01). Baseline NTV and thalamic DTI quantities differed significantly between patients with PPMS with and without thalamic lesions. Baseline thalamic quantities were significantly correlated with the extent of brain T2 lesions and the severity of NAWM damage. The multivariate model included average NAWM MD (OR = 1.46, P = .005) and FA thalamic change (OR = 0.84, P = .02) as independent predictors of EDSS score deterioration (Nagelkerke R(2) = 0.55). Short-term accrual of thalamic damage and the severity of NAWM involvement predict the long-term accumulation of disability in PPMS.

Pseudohypoxic Brain Swelling (Postoperative Intracranial Hypotension-Associated Venous Congestion) After Spinal Surgery: Report of 2 Cases

Pseudohypoxic brain swelling is a rare event that may occur after uneventful brain surgery when subgaleal vacuum drainage is used. To date, such cases of unexpected postoperative disturbances of consciousness associated with radiological signs of basal ganglia, thalamic, brainstem, and cerebellum damage without any signs of vessel occlusion have not been known to occur after spinal surgery. We report for the first time on 2 patients presenting with a clinical and radiological picture of pseudohypoxic brain swelling after spinal surgery. In the first patient, bilateral basal ganglia damage occurred after thoracic spondylodiscitis surgery, manifested by epileptic seizures and coma lasting 1 week postoperatively with subsequent recovery. The second patient suffered basal ganglia and cerebellar and brainstem infarction after lumbar spondylodiscitis surgery, resulting in death. Because intraoperative cerebrospinal fluid leakage and use of postoperative epidural suction drainage with cerebrospinal fluid loss occurred in both cases, they are highly suspected to have potentially caused the complications. Pseudohypoxic brain swelling should be considered in patients with unexpected neurological deterioration after spinal surgery. It might be a form of postoperative intracranial hypotension-associated venous congestion, which should be distinguished from common postoperative cerebral ischemic events caused by arterial or venous occlusions.

Current controversies in states of chronic unconsciousness

Coma resulting from brain injury or illness usually is a transient state. Within a few weeks, patients in coma either recover awareness, die, or evolve to an eyes-open state of impaired responsiveness such as the vegetative or minimally conscious state. These disorders of consciousness can be transient stages during spontaneous recovery from coma or can become chronic, static conditions. Recent fMRI studies raise questions about the accuracy of accepted clinical diagnostic criteria and prognostic models of these disorders that have far-reaching medical practice and ethical implications. A 21-year-old woman lost control of her car and struck a bridge abutment. She sustained a severe traumatic brain injury (TBI) with subdural, subarachnoid, and intracerebral hemorrhages that was complicated by intracranial hypertension and generalized seizures. When examined in the neurorehabilitation center 6 months later, she was in a vegetative state with eyes-open wakefulness but without awareness of herself or her environment, no psychological responsiveness, and marked spasticity with little movement of her limbs. Her eyes were open and moving when she was awake and were closed when she was asleep. Brain CT scan showed bilateral thalamic and multifocal cortical areas of encephalomalacia with ex vacuo hydrocephalus. Her EEG had an irregular 4-Hz background with intermittent sharp waves over the right hemisphere. Six months later, her parents reported that she had become responsive. The examiner could, at times, get her to follow a $20 bill with her eyes and to reach toward it but she followed no commands. Her pupillary light reflexes were normal and she had roving, full eye movements. Most of the time, examiners and staff members could elicit no responsiveness. She breathed spontaneously through a tracheostomy tube and was fed and hydrated by a gastrostomy tube. She required daily physical therapy to prevent contractures that had developed in all her limbs. Repeat brain imaging and EEG were unchanged. Her parents asked if she could undergo fMRI assessment which they discovered on an Internet search might prove that she was aware and could improve. DIAGNOSTIC ISSUES The vegetative state (VS) and minimally conscious state (MCS) are the principal clinical syndromes of patients with chronically disordered consciousness. As syndromes, they encompass a spectrum of severity and can be the consequence of a variety of brain injuries and illnesses. 1 Categorizing patients with disorders of consciousness into the correct diagnostic syndrome is essential, but the prognosis of each patient depends mostly on the cause and extent of the brain damage producing the syndrome. The VS has been epitomized as “wakefulness without awareness” because the brainstem reticular system responsible for alertness and wakefulness remains intact but the thalamocortical systems responsible for awareness have been damaged. The VS is best conceptualized as a disconnection syndrome between the thalami and the cortex resulting from 1) bilateral thalamic damage; 2) diffuse cortical damage, especially involving the precuneus; or 3) damage to the white matter tracts connecting the thalami and cortex. The principal causes of VS are 1) TBI, which can cause damage by all 3 mechanisms, but especially by white matter tract damage from severe diffuse axonal injury because of rotational brain trauma; 2) hypoxic-ischemic neuronal damage to the

Thalamic Damage and Long-term Progression of Disability in Multiple Sclerosis

To estimate the relative contributions of baseline thalamic atrophy and abnormalities shown at magnetization transfer (MT) magnetic resonance (MR) imaging, as well as their 12-month changes, in predicting accumulation of disability in a relatively large sample of patients with relapse-onset multiple sclerosis (MS) during an 8-year period. The study was conducted with approval of the institutional review board. Written informed consent was obtained from each participant. Conventional and MT MR imaging of the brain was performed at baseline and at 12-month follow-up in 13 healthy control subjects and 73 patients with relapse-onset MS; participants were monitored with clinical visits for 8 years. The following parameters were evaluated at baseline and at 12-month follow-up: volume of lesions with high signal intensity at T2-weighted imaging, volume of lesions with low signal intensity at T1-weighted imaging, mean lesion MT ratio, thalamic fraction, and thalamic MT ratio. A multivariate analysis was used to evaluate the predictors of long-term neurologic deterioration. At 8-year follow-up, 44 patients showed worsening disability. During follow-up, reduction in thalamic fraction was more pronounced in patients with relapsing-remitting MS than in those with secondary progressive MS (P = .001); thalamic MT ratio decreased only in patients with secondary progressive MS (P = .007). In the multivariable model, baseline thalamic fraction (odds ratio = 0.62, P = .01) and mean percentage change in lesion MT ratio after 12 months (odds ratio = 0.90, P = .04) were independent predictors of worsening disability at 8 years. At baseline, thalamic fraction was correlated with lesion volumes at T2-weighted imaging (r = -0.75, P < .001) and T1-weighted imaging (r = -0.60, P < .001). Thalamic atrophy is correlated with long-term accumulation of disability in patients with MS. White matter lesions are likely to contribute to the loss of tissue seen in the thalamus of patients with MS.

Reduction of β-Amyloid Deposits by γ-Secretase Inhibitor is Associated with the Attenuation of Secondary Damage in the Ipsilateral Thalamus and Sensory Functional Improvement after Focal Cortical Infarction in Hypertensive Rats

Abnormal β-amyloid (Aβ) deposits in the thalamus have been reported after cerebral cortical infarction. In this study, we investigated the association of Aβ deposits, with the secondary thalamic damage after focal cortical infarction in rats. Thirty-six stroke-prone renovascular hypertensive rats were subjected to distal middle cerebral artery occlusion (MCAO) and then randomly divided into MCAO, vehicle, and N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) groups and 12 sham-operated rats as control. The DAPT was administered orally at 72 hours after MCAO. Seven days after MCAO, sensory function, neuron loss, and glial activation and proliferation were evaluated using adhesive removal test, Nissl staining, and immunostaining, respectively. Thalamic Aβ accumulation was evaluated using immunostaining and enzyme-linked immunosorbent assay (ELISA). Compared with vehicle group, the ipsilateral thalamic Aβ, neuronal loss, glial activation and proliferation, and the mean time to remove the stimulus from right forepaw significantly decreased in DAPT group. The mean time to remove the stimulus from the right forepaw and thalamic Aβ burden were both negatively correlated with the number of thalamic neurons. These findings suggest that Aβ deposits are associated with the secondary thalamic damage. Reduction of thalamic Aβ by γ-secretase inhibitor may attenuate the secondary damage and improve sensory function after cerebral cortical infarction.

Reductions of Thalamic Volume and Regional Shape Changes in the Vegetative and the Minimally Conscious States

The thalamus is known to play a key role in arousal regulation and support of human consciousness. Neuropathological studies have identified thalamic damage as one of the most common abnormalities present in the brains of patients who were in a vegetative state (VS) or a minimally-conscious state (MCS) state at the time of their deaths. Nonetheless, no in vivo studies of thalamic abnormalities in these patients have been conducted. Using high-resolution T1-weighted magnetic resonance images and a novel approach to shape analysis, we investigated thalamic global and regional changes in a sample of patients in a VS or an MCS. Group comparisons and correlations with clinical variables were performed for the total thalamic volume and for each surface vertex. Total thalamic volume was significantly lower in patients than in healthy volunteers. Shape analysis revealed significant bilateral regional atrophy in the dorso-medial body in patients compared to controls; this atrophy was more widespread in VS than in MCS patients. Lower thalamic volume was significantly correlated with worse Disability Rating Scale scores. Shape analysis suggested that the dorso-medial nucleus and the internal medullar lamina were the main regions responsible for this correlation. Our findings suggest that MCS and VS patients present different patterns of regional thalamic abnormalities, and that these differences partially explain their clinical profile.

Bilateral thalamic necrosis following ingestion of ridge gourd infested with coelomycete fungi ( Diplodia)

Bilateral thalamic lesions detected on magnetic resonance imaging have a wide differential diagnosis. This report describes a previously healthy young man who developed bilateral thalamic necrosis with seizures, vomiting, hepatitis, neutrophilic leukocytosis and metabolic acidosis following consumption of raw dried fruits of the ridge gourd plant ( Luffa acutangula) prescribed by a traditional medicine practitioner . These fruits were subsequently shown to be infested with spores and conidiomata of Diplodia, a coelomycete fungus known to cause neurotoxicity in farm animals. The patient made a partial recovery with supportive care, and has persistent deficits consistent with bilateral medial thalamic damage. This is the first report of neurological toxicity attributable to Diplodia in humans, and this entity should be considered in the differential diagnosis of bilateral thalamic lesions in the appropriate clinical setting.

Stuttering after right cerebellar infarction: A case study

We report a male patient with neurogenic stuttering after cerebellar infarction. He had suffered from frontal and thalamus damage and he had exhibited aphasia, but his speech had been fluent until onset of the cerebellar infarction. Results of analysis of speech samples included the following: (1) the patient showed very frequent syllable repetition and part-word repetition. (2) The stuttering occurrence rate at the second test was much higher than at the first test. (3) Almost all stuttering occurred on initial word sounds; stuttering on the medial and final word was less frequent. (4) Adaptation effect was absent. (5) Secondary behaviors such as closing of the eyes and grimacing were observed. The internal model related to cerebellar functions can be modified using feedback-error information. Results suggest that internal model dysfunction caused this patient's stuttering. Educational objectives: After reading this text, the reader will be able to: (1) provide characteristics of neurogenic stuttering after the cerebellum infarction; (2) discuss the relationship between neurogenic stuttering and functions of the cerebellum.

Cortical Visual Impairment

1. Luis H. Ospina, MD* 1. *Assistant Professor, Pediatric Ophthalmology and Neuro-ophthalmology, Ste-Justine Hospital, University de Montreal, Montreal, Quebec, Canada After completing this article, readers should be able to: 1. Recognize cortical visual impairment (CVI) as an important cause of pediatric visual loss. 2. Identify the most frequent causes of pediatric CVI and, more specifically, understand the role of hypoxia as a cause of central visual damage. 3. Describe the different patterns and implications for future vision of hypoxic central visual damage occurring in preterm compared with term babies. 4. Know the clinical signs suggestive of CVI in children. 5. Discuss the involvement of visual functions other than visual acuity (ie, cognitive visual aspects) in CVI and correlate them with the likely affected neuroanatomic substrates. 6. Explain the value of using a multidisciplinary approach in rehabilitating children who have CVI early in their development. Vision loss caused by central nervous system damage often is referred to as CVI but also may be referred to as cerebral visual impairment or neurologic visual impairment. These terms refer to the fact that the primary defect may not necessarily be limited to the striate (primary visual) cortex and may affect other areas subserving vision, such as the visual associative cortex, optic radiations, and visual attention pathways. Although it is not yet certain which of these three terms best describes the visual deficit, it is clear that use of the label cortical blindness must be abandoned. That term not only evokes negative connotations for the child and the family but is inaccurate because in almost every instance, some degree of residual vision remains, and visual improvement can occur. CVI has become the greatest cause of pediatric visual impairment in developed countries (1)(2)(3)(4)(5) and is becoming increasingly prevalent in developing nations. CVI is a problem of increasing frequency for two primary reasons. First, the progress in neonatal care has resulted in improved survival of …

Thalamic Damage in Periventricular Leukomalacia: Novel Pathologic Observations Relevant to Cognitive Deficits in Survivors of Prematurity

Despite major advances in the long-term survival of premature infants, cognitive deficits occur in 30-50% of very preterm (<32 gestational weeks) survivors. Impaired working memory and attention despite average global intelligence are central to the academic difficulties of the survivors. Periventricular leukomalacia (PVL), characterized by periventricular necrosis and diffuse gliosis in the cerebral white matter, is the major brain pathology in preterm infants. We tested the novel hypothesis that pathology in thalamic nuclei critical for working memory and attention, i.e. mediodorsal nucleus and reticular nucleus, respectively, occurs in PVL. In 22 PVL cases (gestational age 32.5 +/- 4.8 wk) and 16 non-PVL controls (36.7 +/- 5.2 wk) who died within infancy, the incidence of thalamic pathology was significantly higher in PVL cases (59%; 13/22) compared with controls (19%; 3/16) (p = 0.01), with substantial involvement of the mediodorsal, and reticular nuclei in PVL. The prevention of thalamic damage may be required for the eradication of defects in survivors with PVL.

Diffuse Axonal Injury in Periventricular Leukomalacia as Determined by Apoptotic Marker Fractin

Periventricular leukomalacia (PVL), the major substrate of neurologic deficits in premature infants, is associated with reduced white matter volume. Using immunomarkers of axonal pathology [beta-amyloid precursor protein (beta-APP) and apoptotic marker fractin], we tested the hypothesis that widespread (diffuse) axonal injury occurs in the gliotic white matter beyond the foci of necrosis in PVL, thus contributing to the white matter volume reduction. In a cohort of 17 control cases and 13 PVL cases with lesions of different chronological ages, diffuse axonal damage in PVL was detected by fractin in white matter sites surrounding and distant from acute and organizing foci of necrosis. Using beta-APP, axonal spheroids were detected within necrotic foci in the acute and organizing (subacute) stages, a finding consistent with others. Interestingly, GAP-43 expression was also detected in spheroids in the necrotic foci, suggesting attempts at axonal regeneration. Thirty-one percent of the PVL cases had thalamic damage and 15% neuronal injury in the cerebral cortex overlying PVL. We conclude that diffuse axonal injury, as determined by apoptotic marker fractin, occurs in PVL and that its cause likely includes primary ischemia and trophic degeneration secondary to corticothalamic neuronal damage.

Anterior but not intralaminar thalamic nuclei support allocentric spatial memory

Medial thalamic damage is a common cause of severe memory disruption in humans. Both the anterior thalamic nuclei (ATN) and the intralaminar thalamic nuclei (ILN) have been suggested as primary sites of diencephalic injury underlying learning and memory deficits, but their respective roles have yet to be resolved. The present study explicitly compared two spatial memory tasks in male PVGc hooded rats with selective neurotoxic lesions to either (1) the ATN or (2) the rostral ILN (and adjacent lateral mediodorsal thalamic nuclei; ILN/LT lesions). As predicted, the ATN group, but not the ILN/LT group, exhibited clear deficits in the Morris water maze task for the initial acquisition of a fixed hidden platform and its reversal to a new position. The second task examined acquisition of egocentric spatial reference memory for a left or right body turn, using any three arms in an 8-arm water maze on any given trial; contrary to predictions, both lesion groups performed as well as the Sham group. The lack of deficits in ILN/LT rats on this second task contrasted with previous findings reporting a detrimental effect of ILN/LT lesions on egocentric working memory. The clear dissociation between the influence of ATN and ILN/LT lesions with respect to allocentric spatial reference memory in the Morris maze emphasizes that caution is required when interpreting the effects of non-ATN thalamic lesions on spatial memory when the lesions encroach substantial areas of the adjacent ATN region.

Thalamic Damage in Periventricular Leukomalacia (PVL)

The thalamus is an integral structure in the processing and relaying of cognitive, emotional, and sensory information, and thalamic damage in the premature period could contribute to long‐term neurological disabilities in survivors. A recent study by us identified that premature infants with PVL had thalamic injury at autopsy, characterized by neuronal loss (38%) and/or gliosis (56%) (Pierson et al. Acta Neuropathol 2007). Here we sought to establish the spectrum and regional pattern of thalamic injury, as well as the role of axonal injury. We studied 21 thalami in PVL cases ranging from 24 to 41 gestational weeks (mean, 33.3 ± 1.0 weeks) and 25 to 56 postconceptional weeks (mean, 37.8 ± 1.5 weeks) from the pathology archives of our hospital. There was a spectrum of injury in 71% of the thalami, from mild (10%) to severe (24%), with profound neuronal loss, gliosis, and mineralization. Parenchymal axonal spheroids were present in 19% of thalami with acute/subacute injury; one case had microinfarction. The mediodorsal nucleus (limbic relay) was involved in 66% of the cases. These data suggest that the incidence of thalamic injury is even more prevalent in PVL then originally reported by us, as determined by more extensive analysis of individual cases, and that the underlying substrate of emotional as well as cognitive disorders in survivors may reflect, at least in part, damage to relevant thalamic subnuclei.

Anterior thalamic lesions produce chronic and profuse transcriptional de-regulation in retrosplenial cortex: A model of retrosplenial hypoactivity and covert pathology.

Anterior thalamic lesions are thought to produce 'covert pathology' in retrosplenial cortex, but the causes are unknown. Microarray analyses tested the hypothesis that thalamic damage causes a chronic, hypo-function of metabolic and plasticity-related pathways (Experiment 1). Rats with unilateral, anterior thalamic lesions were exposed to a novel environment for 20 minutes, and granular retrosplenial tissue sampled from both hemispheres 30 minutes, 2h, or 8h later. Complementary statistical approaches (analyses of variance, predictive patterning and gene set enrichment analysis) revealed pervasive gene expression differences between retrosplenial cortex ipsilateral to the thalamic lesion and contralateral to the lesion. Selected gene differences were validated by QPCR, immunohistochemistry (Experiment 1), and in situ hybridisation (Experiment 2). Following thalamic lesions, the retrosplenial cortex undergoes profuse cellular transcriptome changes including lower relative levels of specific mRNAs involved in energy metabolism and neuronal plasticity. These changes in functional gene expression may be largely driven by decreases in the expression of multiple transcription factors, including brd8, c-fos, fra-2, klf5, nfix, nr4a1, smad3, smarcc2, and zfp9, with a much smaller number (nfat5, neuroD1, RXRγ) showing increases. These findings have implications for conditions such as diencephalic amnesia and Alzheimer's disease, where both anterior thalamic pathology and retrosplenial cortex hypometabolism are prominent.

A serial study of regional cerebral blood flow deficits in patients with left anterior thalamic infarction: Anatomical and neuropsychological correlates

Thalamic damage is associated with a variety of neuropsychological dysfunctions, as well as strategic infarct dementia. However, only a limited number of reports in the medical literature have discussed the correlation between the clinical findings and the specific functional changes observed on images. We investigated the neuropsychological correlation of the regional cerebral blood flow (rCBF) deficits in four patients with left anterior thalamic infarction within two days after their stroke. All of the patients showed anterograde amnesia on the verbal memory test. Some dysexecutive features were present such as decreased word fluency and an impaired performance on the Stroop test. A decreased rCBF was observed in the left supramarginal gyrus, the superior temporal gyrus, the middle and inferior frontal gyri, and the medial dorsal and anterior nuclei of the left thalamus. The changes of rCBF may have been due to remote suppression by the interruption of the thalamo-cortical circuit that connects the anterior thalamic nucleus and various cortical areas. These initial findings remained unchanged even on the follow-up studies.