Degeneration of core neural tracts for emotional regulation in a patient with traumatic brain injury: A case report.

RATIONALE: Several brain structures, including the orbital prefrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, amygdala, and anterior cingulate cortex, are considered key structures in the neural circuitry underlying emotion regulation. We report on a patient showing behavior changes and degeneration of core neural tracts for emotional regulation following traumatic brain injury (TBI). PATIENT CONCERNS: A 51-year-old male patient suffered an in-car accident. The patient lost consciousness for approximately 30 days, and his Glasgow Coma Scale score was 3. He underwent stereotactic drainage for traumatic intraventricular and intracerebral hemorrhages. At approximately 6.5-year after onset, he began to show disinhibition behaviors such as shouting with anger, which worsened over time. At approximately 8-year after onset, he showed severe depression signs and disinhibition, including violence. DIAGNOSES: The patient who showed delayed-onset behavioral changes (disinhibition and depression). INTERVENTIONS: Diffusion tensor imaging data were acquired at 3 months and 8 years after TBI onset. OUTCOMES: The patient showed degeneration of core neural tracts for emotional regulation that was associated with delayed behavioral changes following TBI. On both 3-month and 8-year diffusion tensor tractographies (DTTs), the right dorsolateral prefronto-thalamic tract, ventrolateral prefronto-thalamic tract, orbital prefronto-thalamic tract, uncinate fasciculus, and both cinguli were reconstructed whereas other neural tracts were not reconstructed. Compared with the 3-month DTT, all reconstructed neural tracts on the 8-year DTT were narrow, except for the left cingulum, which showed new transcallosal fibers between both anterior cingula. The fractional anisotropy and tract volume of all reconstructed neural tracts were lower on the 8-year DTT than the 3-month DTT, except for the tract volume of left cingulum. LESSONS: The evaluation of dorsolateral, ventrolateral, and orbital prefronto-thalamic tract, uncinate fasciculus, and cingulum using follow-up DTTs is useful when a patient with TBI shows delayed-onset behavioral problems.

Title: Injury characteristics of the Papez circuit in patients with diffuse axonal injury: a diffusion tensor tractography study.

We investigate the characteristics of injury of four portions of the Papez circuit in patients with diffuse axonal injury (DAI), using diffusion tensor tractography (DTT). Thirty-four consecutive patients with DAI and 30 normal control subjects were recruited. Four portions of the Papez circuit were reconstructed: the fornix, cingulum, thalamocingulate tract, and mammillothalamic tract. Analysis of DTT parameters [fractional anisotropy (FA) and tract volume (TV)] and configuration (narrowing, discontinuation, or non-reconstruction) was performed for each portion of the Papez circuit. The Memory Assessment Scale (MAS) was used for the estimation of cognitive function. In the group analysis, decreased fractional anisotropy and tract volume of the entire Papez circuit were observed in the patient group compared with the control group (p < 0.05). In the individual analysis, all four portions of the Papez circuit were injured in terms of DTT parameters or configuration. Positive correlation was observed between TV of the fornix and short-term memory on MAS r = 0.618, p < 0.05), and between FA of the fornix and total memory on MAS (r = 0.613, p < 0.05). We found that all four portions of the Papez circuit in the patient group were vulnerable to DAI, and among four portions of the Papez circuit, the fornix was the most vulnerable portion in terms of injury incidence and severity.

Impact of mild traumatic brain injury on cingulate functions.

Mild traumatic brain injury (mTBI) is a condition of normal neuroimaging, because conventional MRI is not sensitive to brain lesions. Neurocognitive deficits persist for years after injury in 15% of patients. Persistent TAI can continue after the trauma and contribute to progressive disability. Neuropathologic studies underestimate the total axonal damage, by failure to identify fine-caliber unmyelinated fiber. Swollen axons represent the "tip of the iceberg" of damage. Progression of molecular changes, including mitochondrial dysfunction, leads to secondary injuries. Primary low-intensity "invisible injury" is solely detectable at ultrastructural levels. Over the long term, mTBI is not a static event but a progressive injury, increasing risk of neurodegenerative diseases. Lack of evidence of brain injury has led to the development of more sensitive methods: morphometric MRI (VBM, DTI) and functional techniques (fMRI, PET, SPECT). By deformation of the surface of gray matter cingulate gyrus and disruption of long-coursing WM of CB structures, striking the falx, mTBI causes alteration of cingulate functions. Postconcussion, blast, and whiplash-associated disorders are the main mechanisms providing behavior and cognitive symptoms after mTBI.

Retrosplenial cortex damage produces retrograde and anterograde context amnesia using strong fear conditioning procedures.

Contextual fear conditioning relies upon a network of cortical and subcortical structures, including the hippocampus and the retrosplenial cortex (RSC). However, the contribution of the hippocampus is parameter-dependent. For example, with "weak" training procedures, lesions of the hippocampus produce both retrograde and anterograde context amnesia. However, with "strong" training procedures (e.g., more trials and/or higher levels of footshock), lesions of the hippocampus produce retrograde context amnesia but not anterograde amnesia (Wiltgen et al., 2006). Likewise, prior studies have shown that with weak training, RSC lesions produce both retrograde and anterograde context amnesia (Keene & Bucci, 2008). The purpose of the current study was to examine the effects of RSC damage on contextual fear conditioning following strong training. In Experiment 1, lesions of the RSC resulted in both retrograde and anterograde context amnesia following strong training using the same unsignaled fear conditioning procedures described by Wiltgen et al. (2006). In Experiment 2, using a signaled fear conditioning procedure, we replicated these effects on context memory observing both retrograde and anterograde context amnesia. In contrast, there were no lesion effects on tone-fear memory. Thus, unlike lesions of the hippocampus, lesions of RSC produce both retrograde and anterograde context amnesia even when rats undergo strong fear conditioning. These findings suggest that the RSC has an essential role in contextual fear conditioning and that other systems or pathways are unable to compensate for the loss of RSC function.

MRS and DTI evidence of progressive posterior cingulate cortex and corpus callosum injury in the hyper-acute phase after Traumatic Brain Injury.

The posterior cingulate cortex (PCC) and corpus callosum (CC) are susceptible to trauma, but injury often evades detection. PCC Metabolic disruption may predict CC white matter tract injury and the secondary cascade responsible for progression. While the time frame for the secondary cascade remains unclear in humans, the first 24 h (hyper-acute phase) are crucial for life-saving interventions. Objectives: To test whether Magnetic Resonance Imaging (MRI) markers are detectable in the hyper-acute phase and progress after traumatic brain injury (TBI) and whether alterations in these parameters reflect injury severity. Methods: Spectroscopic and diffusion-weighted MRI data were collected in 18 patients with TBI (within 24 h and repeated 7-15 days following injury) and 18 healthy controls (scanned once). Results: Within 24 h of TBI N-acetylaspartate was reduced (F = 11.43, p = 0.002) and choline increased (F = 10.67, p = 0.003), the latter driven by moderate-severe injury (F = 5.54, p = 0.03). Alterations in fractional anisotropy (FA) and axial diffusivity (AD) progressed between the two time-points in the splenium of the CC (p = 0.029 and p = 0.013). Gradual reductions in FA correlated with progressive increases in choline (p = 0.029). Conclusions: Metabolic disruption and structural injury can be detected within hours of trauma. Metabolic and diffusion parameters allow identification of severity and provide evidence of injury progression.

Recovery of an injured cingulum concurrent with improvement of short-term memory in a patient with mild traumatic brain injury.

OBJECTIVES: We reported on a patient with mild traumatic brain injury (TBI) who showed recovery of an injured cingulum concurrent with improvement of short-term memory, which was demonstrated on follow-up diffusion tensor tractography (DTT). METHODS: A 55-year-old male patient suffered head trauma resulting from falling from approximately 2 m while working at a construction site. The patient showed mild memory impairment (especially short-term memory impairment) at 3 months after onset: Memory Assessment Scale (global memory: 95 (37%ile), short-term memory: 75 (5%ile), verbal memory: 80 (9%ile) and visual memory: 112 (79%ile)). By contrast, at 2 years after onset, his mild memory impairment had improved to a normal state: Memory Assessment Scale (global memory: 104 (61%ile), short-term memory: 95 (37%ile), verbal memory: 101 (53%ile) and visual memory: 106 (66%ile)). RESULTS: On 3-month DTT, discontinuation of the right anterior cingulum was observed over the genu of the corpus callosum, while on 2-year DTT, the discontinued right anterior cingulum was elongated to the right basal forebrain. CONCLUSION: In conclusion, recovery of an injured cingulum concurrent with improvement of short-term memory was demonstrated in a patient with mild TBI.

The rat retrosplenial cortex as a link for frontal functions: A lesion analysis.

Cohorts of rats with excitotoxic retrosplenial cortex lesions were tested on four behavioural tasks sensitive to dysfunctions in prelimbic cortex, anterior cingulate cortex, or both. In this way the study tested whether retrosplenial cortex has nonspatial functions that reflect its anatomical interactions with these frontal cortical areas. In Experiment 1, retrosplenial cortex lesions had no apparent effect on a set-shifting digging task that taxed intradimensional and extradimensional attention, as well as reversal learning. Likewise, retrosplenial cortex lesions did not impair a strategy shift task in an automated chamber, which involved switching from visual-based to response-based discriminations and, again, included a reversal (Experiment 2). Indeed, there was evidence that the retrosplenial lesions aided the initial switch to response-based selection. No lesion deficit was found on an automated cost-benefit task that pitted size of reward against effort to achieve that reward (Experiment 3). Finally, while retrosplenial cortex lesions affected matching-to-place task in a T-maze, the profile of deficits differed from that associated with prelimbic cortex damage (Experiment 4). When the task was switched to a nonmatching design, retrosplenial cortex lesions had no apparent effect on performance. The results from the four experiments show that many frontal tasks do not require the retrosplenial cortex, highlighting the specificity of their functional interactions. The results show how retrosplenial cortex lesions spare those learning tasks in which there is no mismatch between the internal and external representations used to guide behavioural choice. In addition, these experiments further highlight the importance of the retrosplenial cortex in solving tasks with a spatial component.

Left Anterior Temporal Lobe and Bilateral Anterior Cingulate Cortex Are Semantic Hub Regions: Evidence from Behavior-Nodal Degree Mapping in Brain-Damaged Patients.

The organizational principles of semantic memory in the human brain are still controversial. Although studies have shown that the semantic system contains hub regions that bind information from different sensorimotoric modalities to form concepts, it is unknown whether there are hub regions other than the anterior temporal lobe (ATL). Meanwhile, previous studies have rarely used network measurements to explore the hubs or correlated network indexes with semantic performance, although the most direct supportive evidence of hubs should come from the network perspective. To fill this gap, we correlated the brain-network index with semantic performance in 86 brain-damaged patients. We especially selected the nodal degree measure that reflects how well a node is connected in the network. The measure was calculated as the total number of connections of a given node with other nodes in the resting-state functional MRI network. Semantic ability was measured using the performance of both general and modality-specific (object form, color, motion, sound, manipulation, and function) semantic tasks. We found that the left ATL and the bilateral anterior cingulate cortex could be semantic hubs because the reduced nodal degree values of these regions could effectively predict the deficits in both general and modality-specific semantic performance. Moreover, the effects remained when the analyses were performed only in the patients who did not have lesions in these regions. The two hub regions might support semantic representations and executive control processes, respectively. These data provide empirical evidence for the distributed-plus-hub theory of semantic memory from the network perspective. SIGNIFICANCE STATEMENT: Although the distributed-plus-hub organization of semantic memory has been proposed for several years, it remains unclear which hubs other than the anterior temporal lobe are included in the semantic system. Here, we identified such hubs from an innovative network perspective. The voxelwise nodal degree values were correlated with the performance of general and modality-specific semantic tasks in 86 patients with brain damage. We observed that the left anterior temporal lobe and bilateral anterior cingulate cortex could be semantic hubs because their decreased nodal degree values were significantly correlated with the severity of the deficit in semantic performance. The two hub regions might contribute to semantic representational and control processes, respectively. These findings offer new evidence for the distributed-plus-hub theory.

Severe disinhibition due to injuries of neural tracts related to emotion circuit in a patient with traumatic brain injury: A case report.

RATIONALE: Approximately 30% of patients with traumatic brain injury (TBI) develop disinhibition, a condition that involves several brain structures, including the amygdala, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Using diffusion tensor tractography (DTT), we report on a patient with severe disinhibition and injuries of the amygdala, OFC, and ACC following TBI. PATIENT CONCERNS: A 27-year-old male patient suffered an in-car accident. DIAGNOSES: Since the onset of the TBI, the patient showed severe disinhibition including violence, as follows: 1) he sometimes attacked therapists and nurses with no provocation, 2) while he was laying on a bed, he shouted and kicked the bed when asked questions, and 3) during therapy with a difficult task, he behaved violently to a therapist. The subscale of disinhibition in Neuropsychiatric Inventory scored three points for severity and for distress. INTERVENTIONS: N/A. OUTCOMES: On 10-month DTT, the connectivity of amygdala to the prefrontal cortex including the medial prefrontal cortex and OFC had decreased in both hemispheres. In the prefronto-thalamic tracts, the orbitofronto-thalamic tractshad narrowed (the right hemisphere), and were non-reconstructed (the left hemisphere). Discontinuations of both anterior cingulums were observed in both hemispheres. LESSONS: Using DTT, concurrent injuries of the amygdala, OFC, and ACC were demonstrated in a patient with severe disinhibition following TBI. Our result suggests the need to assess these neural structures in patients with disinhibition after brain injury.

Recovery of an injured cingulum via an aberrant neural tract in a patient with traumatic brain injury: A case report.

BACKGROUND: We report on a patient who appeared to show recovery of an injured anterior cingulum via an aberrant neural tract between an injured cingulum and the basalis nucleus of Meynert following traumatic brain injury (TBI), which was demonstrated on diffusion tensor tractography (DTT). METHODS: A 47-year-old male who had suffered a pedestrian traffic accident underwent conservative management for diffuse traumatic axonal injury. When starting rehabilitation at 6 weeks after onset, evaluation using the Mini-Mental State Examination (MMSE) could not be performed due to the severity of his cognitive dysfunction. The patient showed improvement of cognitive dysfunction on MMSE with 10 at 2 months, 13 at 6 months, and 26 at 10 months after onset. RESULTS: On 6-week DTT, discontinuation superior to the genu of the corpus callosum was observed in both cingulums. However, on 6-month DTT, the discontinued anterior part of the right cingulum was elongated anteriorly, not through the cingulum, but through the anterolateral subcortical white matter of the cingulum, while on 10-month DTT, this elongated neural tract of the right cingulum was connected to the right basalis nucleus of Meynert in the basal forebrain. CONCLUSION: Recovery of an injured anterior cingulum via an aberrant neural tract between an injured cingulum and Ch 4 was demonstrated in a patient with TBI. Our result appears to suggest a mechanism for recovery of an injured cingulum following brain injury.

Injury of the Thalamocingulate Tract in the Papez Circuit in Patients with Mild Traumatic Brain Injury.

The thalamocingulate tract between the anterior thalamic nuclei and the cingulate gyrus is a part of the Papez circuit. Using diffusion tensor tractography, injury of the thalamocingulate tract was investigated in patients with mild traumatic brain injury. Two patients (patient 1: a 58-yr-old woman and patient 2: a 49-yr-old man) with head trauma resulting from a car accident were enrolled. They were classified as mild traumatic brain injury and no specific lesion was observed on brain magnetic resonance imaging. These patients complained of memory impairment after head trauma. The entire Papez circuits, including thalamocingulate tract, fornix, mammillothalamic tract, and cingulum, were reconstructed in both hemispheres except for the left thalamocingulate tract: patient 1, it was thinner and discontinued compared with the right thalamocingulate tract; and patient 2, it was not reconstructed. The injury of the left thalamocingulate tract appeared to be related to the memory impairment in these patients.

Recovery of an Injured Cingulum via the Lateral Cholinergic Pathway in a Patient with Traumatic Brain Injury.

We report on a patient with traumatic brain injury who showed recovery of an injured cingulum via the lateral cholinergic pathway, using diffusion tensor tractography (DTT). A 63-year-old man underwent craniotomy for subarachnoid hemorrhage and subdural hemorrhage in both frontotemporal lobes, which occurred by hitting his head against a floor after falling from approximately 2 m. The Wechsler Intelligence Scale and the Seoul neuropsychological screening battery were used for evaluation of cognitive function. At 4 weeks after onset, the patient exhibited mild cognitive impairment (total IQ, 85; verbal immediate recall, 26.76 percentile; visual immediate recall, 29.81 percentile; verbal delayed recall, 24.51 percentile; visual delayed recall, 11.70 percentile). By contrast, at the 9-month evaluation, the cognitive impairment had improved as much as total IQ, 96; verbal immediate recall, 56.75 percentile; visual immediate recall, 89.49 percentile; verbal delayed recall, 78.23 percentile; and visual delayed recall, 89.07 percentile. On 4-week DTT, discontinuations were observed superior to the genu of the corpus callosum in both cingula. However, on 9-month DTT, the discontinued anterior part of the right cingulum was elongated inferoposteriorly through an unusual neural tract, which ran through the external capsule and the white matter of the temporo-occipital lobes. The results of this study seem to suggest a mechanism for recovery of an injured cingulum after brain injury.

Modelo de conectividad de la circunvolución angular en el lenguaje: metaanálisis de neuroimágenes funcionales / Angular gyrus connectivity model for language: a functional neuroimaging meta-analysis

Introducción. Las técnicas modernas de neuroimagen funcional permiten analizar la activación simultánea de diversas áreas cerebrales y sugerir modelos de conectividad para funciones cognitivas específicas. Objetivo. Realizar un metaanálisis de las redes funcionales de la región angular (área de Brodmann 39) con relación al lenguaje. Materiales y métodos. Partiendo de la base de datos BrainMap, se analizaron las coordenadas de activación en estudios de resonancia magnética funcional que mostraban una activación del área de Brodmann 39 durante la realización de tareas lingüísticas. Se seleccionaron ocho artículos con 13 experimentos, que incluían un total de 155 sujetos, y 265 localizaciones. Resultados. Los resultados mostraron 16 conglomerados de activación significativos que conformaban una red de coactivación, la cual incluía las dos regiones angulares, el lóbulo parietal superior y la circunvolución supramarginal derechos, el lóbulo temporal izquierdo (cara lateral medial y cara medial inferior) y el lóbulo frontal (premotor bilateral y prefrontal izquierdo). Conclusiones. Estos resultados coinciden con los hallazgos obtenidos con técnicas de conectividad estructural y apoyan el papel integrador de la región angular en funciones lingüísticas (AU)

Introduction. Modern functional neuroimaging techniques permit the analysis of the simultaneous activation of diverse brain areas to suggest cognitive connectivity models related to specific cognitive functions. Aim. To analyze the functional networks of the angular gyrus (Brodmann area 39) related to language functions. Materials and methods. The database of BrainMap was used to analyze the activation coordinates of the angular gyrus and brain related areas while performing different language tasks. Eight articles were selected that included 13 experiments, 155 participants and 265 loci. Results. Sixteen activation clusters made a network that included the activation of the two angular gyri, the superior right parietal lobe and right supramarginal gyri; the superior left temporal lobe (middle lateral and medial inferior), and the frontal lobe (bilateral premotor and left prefrontal). Conclusions. Our findings are in agreement with previous findings using structural connectivity techniques and support the integrative role of the angular gyrus in language functions (AU)

XVII Curso Internacional de Actualización en Neuropediatría y Neuropsicología Infantil / No disponible

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Cognitive control and the anterior cingulate cortex: how conflicting stimuli affect attentional control in the rat.

Converging evidence supports the hypothesis that the prefrontal cortex is critical for cognitive control. One prefrontal subregion, the anterior cingulate cortex, is hypothesized to be necessary to resolve response conflicts, disregard salient distractors and alter behavior in response to the generation of an error. These situations all involve goal-oriented monitoring of performance in order to effectively adjust cognitive processes. Several neuropsychological disorders, e.g., schizophrenia, attention deficit hyperactivity and obsessive compulsive disorder, are accompanied by morphological changes in the anterior cingulate cortex. These changes are hypothesized to underlie the impairments on tasks that require cognitive control found in these subjects. A novel conflict monitoring task was used to assess the effects on cognitive control of excitotoxic lesions to anterior cingulate cortex in rats. Prior to surgery all subjects showed improved accuracy on the second of two consecutive, incongruent trials. Lesions to the anterior cingulate cortex abolished this. Lesioned animals had difficulty in adjusting cognitive control on a trial-by-trial basis regardless of whether cognitive changes were increased or decreased. These results support a role for the anterior cingulate cortex in adjustments in cognitive control.

Relation between cognition and neural connection from injured cingulum to brainstem cholinergic nuclei in chronic patients with traumatic brain injury.

BACKGROUND: This study investigated the relation between cognition and the neural connection from injured cingulum to brainstem cholinergic nuclei in patients with traumatic brain injury (TBI), using diffusion tensor tractography (DTT). METHODS: Among 353 patients with TBI, 20 chronic patients who showed discontinuation of both anterior cingulums from the basal forebrain on DTT were recruited for this study. The Wechsler Intelligence Scale and the Memory Assessment Scale (MAS; short-term, verbal, visual and total memory) were used for assessment of cognition. Patients were divided into two groups according to the presence of a neural connection between injured cingulum and brainstem cholinergic nuclei. RESULTS: Eight patients who had a neural connection between injured cingulum and brainstem cholinergic nuclei showed better short-term memory on MAS than 12 patients who did not (p < 0.05). However, other results of neuropsychological testing showed no significant difference (p > 0.05). CONCLUSIONS: Better short-term memory in patients who had the neural connection between injured cingulum and brainstem cholinergic nuclei appears to have been attributed to the presence of cholinergic innervation to the cerebral cortex through the neural connection instead of the injured anterior cingulum. The neural connection appears to compensate for the injured anterior cingulum in obtaining cholinergic innervation.

Contribution of anterior cingulate cortex and descending pain inhibitory system to analgesic effect of lemon odor in mice.

BACKGROUND: Affections are thought to regulate pain perception through the descending pain inhibitory system in the central nervous system. In this study, we examined in mice the affective change by inhalation of the lemon oil, which is well used for aromatherapy, and the effect of lemon odor on pain sensation. We also examined the anterior cingulate cortex (ACC) and descending pain inhibitory system to such regulation of pain. RESULTS: In the elevated plus maze, the time spent in the open arms was increased by inhalation of lemon oil. The pain behavior induced by injection of formalin into the hind paw was decreased. By inhalation of lemon oil, the number of c-Fos expression by formalin injection was significantly increased in the ACC, periaqueductal grey (PAG), nucleu raphe magnus (NRM) and locus ceruleus, and decreased in the spinal dorsal horn (SDH). The destruction of the ACC with ibotenic acid led to prevent the decrease of formalin-evoked nocifensive behavior in mice exposed to lemon oil. In these mice, the change of formalin-induced c-Fos expression in the ACC, lateral PAG, NRM and SDH by lemon odor was also prevented. Antagonize of dopamine D1 receptor in the ACC prevented to the analgesic effect of lemon oil. CONCLUSIONS: These results suggest that the analgesic effect of lemon oil is induced by dopamine-related activation of ACC and the descending pain inhibitory system.

Virtual lesion of angular gyrus disrupts the relationship between visuoproprioceptive weighting and realignment.

Posterior parietal cortex is thought to be involved in multisensory processes such as sensory weighting (how much different modalities are represented in sensory integration) and realignment (recalibrating the estimates given by unisensory inputs relative to each other, e.g., when viewing the hand through prisms). Sensory weighting and realignment are biologically independent but can be correlated such that the lowest-weighted modality realigns most. This is important for movement precision because it results in the brain's estimate of hand position favoring the more reliable (higher-weighted) modality. It is unknown if this interaction is an emergent property of separate neural pathways for weighting and realignment or if it is actively mediated by a common substrate. We applied disruptive TMS to the angular gyrus near the intraparietal sulcus (PGa) before participants performed a task with misaligned visual and proprioceptive information about hand position. Visuoproprioceptive weighting and realignment were unaffected. However, the relationship between weighting and realignment, found in control conditions, was absent after TMS in the angular gyrus location. This suggests that a specific region in the angular gyrus actively mediates the interaction between visuoproprioceptive weighting and realignment and may thus play a role in the decreased movement precision associated with posterior parietal lesions.