Prefronto-thalamic tract injury and cognitive outcome according to external ventricular drainage location in stroke patients.

OBJECTIVES: We investigated the characteristics of prefronto-thalamic tract (PF-TT) injuries in stroke patients using diffusion tensor tractography (DTT) and assessing cognitive outcome according to location of the external ventricular drainage (EVD). METHODS: Forty-five consecutive stroke patients who underwent EVD and 24 control subjects were recruited. The patients were classified into three groups: group A (EVD on the lesion or one side, 17 patients), group B (EVD on the hemisphere opposite to the lesion, 12 patients), and group C (EVD on both sides, 16 patients). Mini-Mental State Examination (MMSE) results were performed at the beginning (average 2.27 months from onset) and end (average 4.19 months from onset) of rehabilitation. Three parts of the PF-TT (dorsolateral PF-TT[DLPF-TT], ventrolateral PF-TT[VLPF-TT], orbitofronto-thalamic tract[OF-TT]) were reconstructed and the fractional anisotropy (FA) and tract volume (TV) measurements were obtained. RESULTS: With the EVD on the stroke-affected side, the values of FA and TV of all three parts of the PF-TTs in three patient groups were lower than those of the control group (p < 0.05). With the EVD on the unaffected side, the FA values of the DLPF-TT in groups B and C and the OF-TT in group C were lower than those of the control group (p < 0.05). There was no difference in initial MMSE score among three patient groups; however, group A had a higher mean follow-up MMSE score than that of groups B and C (p < 0.05). CONCLUSIONS: Patients who underwent EVD of the affected hemisphere showed better results in terms of the PF-TT injury and cognitive outcome than patients who underwent EVD through the unaffected hemisphere or through both hemispheres.

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.

Relationship between depression and dorsolateral prefronto-thalamic tract injury in patients with mild traumatic brain injury.

The prefrontal lobe has been considered to be closely related to depression. This study examined the relationship between depression and three prefronto-thalamic tract (PF-TT) regions (the dorsolateral prefronto-thalamic tract [DLPF-TT], ventrolateral prefronto-thalamic tract [VLPF-TT], and the orbitofronto-thalamic tract [OF-TT]) in patients with mild traumatic brain injury (TBI), using diffusion tensor tractography (DTT). Thirty-seven patients with depression following mild TBI were recruited based on Beck Depression Inventory-II (BDI-II) scores. Thirty-one normal control subjects were also recruited. The three regions of the PF-TTs were reconstructed using probabilistic tractography and DTT parameters for each of the three PF-TT regions were determined. The tract volume of the DLPF-TT and OF-TT in the patient group showed a significant decrease compared to that of the control group (p < 0.05). The BDI-II score of the patient group showed a moderate negative correlation with the tract volume value of the right (r = - 0.33) and left (r = - 0.41) DLPF-TT (p < 0.05). On the other hand, no significant correlations were detected between the BDI-II score of the patient group and the values of the other DTT parameters values for the three PF-TT regions (p > 0.05). Using DTT, depression was found to be closely related to a DLPF-TT injury in patients with mild TBI. We believe that evaluation of the DLPF-TT using DTT would be helpful when assessing patients with depression following mild TBI. These results can provide useful information regarding the proper application of neuromodulation in the management of depression.

Scene processing following damage to the ventromedial prefrontal cortex.

It has been suggested that the mental construction of scene imagery is a core process underpinning functions such as autobiographical memory, future thinking and spatial navigation. Damage to the ventromedial prefrontal cortex in humans can cause deficits in all of these cognitive domains. Moreover, it has also been reported that patients with ventromedial prefrontal cortex lesions are impaired at imagining fictitious scenes, although they seem able to describe specific scenes from autobiographical events. In general, not much is known about how ventromedial prefrontal cortex patients process scenes. Here, we deployed a recently-developed task to provide insights into this issue, which involved detecting either semantic (e.g. an elephant with butterflies for ears) or constructive (e.g. an endless staircase) violations in scene images. Identifying constructive violations typically provokes the formation of internal scene models in healthy control participants. We tested patients with bilateral ventromedial prefrontal cortex damage, brain-damaged control patients and healthy control participants. We found no evidence for statistically significant differences between the groups in detecting either type of violation. These results suggest that an intact ventromedial prefrontal cortex is not necessary for some aspects of scene processing, with implications for understanding its role in functions such as autobiographical memory and future thinking.

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Injury of the dorsolateral prefronto-thalamic tract in a patient with depression following mild traumatic brain injury: A case report.

BACKGROUND: Depression, a prevalent psychiatric disorder, is associated with abnormality in the prefrontal cortex, particularly the left dorsolateral prefrontal cortex. In this study, we report on a patient with severe depression who showed injury of the dorsolateral prefronto-thalamic tract following mild traumatic brain injury, which was demonstrated by diffusion tensor tractography (DTT). METHODS AND RESULTS: A 63-year-old female patient suffered an in-car accident. The patient lost consciousness for approximately 10 minutes and experienced posttraumatic amnesia approximately 30 minutes from the time of the accident. Her Glasgow Coma Scale score was 15. No specific lesion was observed on the conventional brain magnetic resonance imaging. Since the onset of head trauma, she had shown continuous depression and on 32 month evaluation, she exhibited severe depression (Beck Depression Inventory-II: 42 [full score: 63 score] and Patient Health Questionnaire-9: 24 [full score: 27 score]). RESULTS: On 32-month DTT, partical tearing of the dorsolateral prefronto-thalamic tract was observed in the right hemisphere and thinning in the left hemisphere. CONCLUSION: Injury of the dorsolateral prefronto-thalamic tract was demonstrated in a patient with depression following mild traumatic brain injury, using DTT. We believe that injury of the dorsolateral prefronto-thalamic tract might be a pathogenetic mechanism of depression in patients with brain injury.

Thalamic and Entorhinal Network Activity Differently Modulates the Functional Development of Prefrontal-Hippocampal Interactions.

Precise information flow during mnemonic and executive tasks requires the coactivation of adult prefrontal and hippocampal networks in oscillatory rhythms. This interplay emerges early in life, most likely as an anticipatory template of later cognitive performance. At neonatal age, hippocampal theta bursts drive the generation of prefrontal theta-gamma oscillations. In the absence of direct reciprocal interactions, the question arises of which feedback mechanisms control the early entrainment of prefrontal-hippocampal networks. Here, we demonstrate that prefrontal-hippocampal activity couples with discontinuous theta oscillations and neuronal firing in both lateral entorhinal cortex and ventral midline thalamic nuclei of neonatal rats. However, these two brain areas have different contributions to the neonatal long-range communication. The entorhinal cortex mainly modulates the hippocampal activity via direct axonal projections. In contrast, thalamic theta bursts are controlled by the prefrontal cortex via mutual projections and contribute to hippocampal activity. Thus, the neonatal prefrontal cortex modulates the level of hippocampal activation by directed interactions with the ventral midline thalamus. Similar to the adult task-related communication, theta-band activity ensures the feedback control of long-range coupling in the developing brain. SIGNIFICANCE STATEMENT: Memories are encoded by finely tuned interactions within large-scale neuronal networks. This cognitive performance is not inherited, but progressively matures in relationship with the establishment of long-range coupling in the immature brain. The hippocampus initiates and unidirectionally drives the oscillatory entrainment of neonatal prefrontal cortex, yet feedback interactions that precisely control this early communication are still unresolved. Here, we identified distinct roles of entorhinal cortex and ventral midline thalamus for the functional development of prefrontal-hippocampal interactions. While entorhinal oscillations modulate the hippocampal activity by timing the neuronal firing via monosynaptic afferents, thalamic nuclei act as a relay station routing prefrontal activation back to hippocampus. Understanding the mechanisms of network maturation represents the prerequisite for assessing circuit dysfunction in neurodevelopmental disorders.

Adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs) after left orbital contusion.

We report a patient who presented with adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs), a month after head trauma. The PLEDs predominantly involving the left frontal contacts became more frequent at the onset of adversive seizures during EEG. Brain MRI demonstrated a contusion scar in the left orbital cortex with reduced diffusion, not only around this orbital lesion but also in the ipsilateral anteromedial thalamus. Single photon emission computed tomography revealed focal cerebral hyperperfusion in the left medial orbitofrontal region, basal ganglia, and thalamus. The abnormal metabolism involving the thalamus and striatum could be associated with the ipsilateral orbital contusion and might have been caused by cortical-subcortical, trans-synaptic hyperactivity. Further studies are warranted to determine the role of subcortical structures in the generation of PLEDs and adversive seizures. [Published with video sequences].

Noise benefit in prepulse inhibition of the acoustic startle reflex.

RATIONALE: Under some conditions, external sensory noise enhances cognitive functions, a phenomenon possibly involving stochastic resonance and/or enhanced central dopamine transmission. Prepulse inhibition (PPI) of the startle reflex is a robust measure of sensorimotor gating and can be modulated by activity in the cortex and basal ganglia, including the central dopamine pathways. OBJECTIVES: Previous empirical studies suggest a differential effect of acoustic noise in normal children and children with attention-deficit hyperactivity disorder (ADHD). This study investigated the effect of acoustic noise on PPI and if dopamine transmission interacts with acoustic noise effects in a rat ADHD model. METHODS: The effect of background acoustic noise on acoustic startle response and PPI were measured with a constant prepulse to background noise ratio of 9 dB(A). Spontaneously hypertensive (SH) rats were used as the ADHD model and compared with Wistar and Sprague-Dawley rats. Microdialysis, methylphenidate treatment and 6-OHDA lesions were used to investigate interaction with dopamine transmission. RESULTS: Background noise facilitated PPI differently in SH rats and controls. The prefrontal cortex in SH rats had low basal dopamine concentrations, a high DOPAC/dopamine ratio and blunted dopamine release during PPI testing. Methylphenidate had small, but strain-specific, effects on startle and PPI. Bilateral 6-hydroxydopamine lesions did not alter startle or PPI. CONCLUSIONS: Prefrontal dopamine transmission is altered in SH rats during the sensorimotor gating task of PPI of the acoustic startle, indicating increased dopamine reuptake in this ADHD rat model. We propose that noise benefit could be explored as a non-pharmacological alternative for treating neuropsychiatric disorders.

The medial prefrontal cortex and memory of cue location in the rat.

We developed a single-trial cue-location memory task in which rats experienced an auditory cue while exploring an environment. They then recalled and avoided the sound origination point after the cue was paired with shock in a separate context. Subjects with medial prefrontal cortical (mPFC) lesions made no such avoidance response, but both lesioned and control subjects avoided the cue itself when presented at test. A follow up assessment revealed no spatial learning impairment in either group. These findings suggest that the rodent mPFC is required for incidental learning or recollection of the location at which a discrete cue occurred, but is not required for cue recognition or for allocentric spatial memory.

Neurotoxic lesions of the medial prefrontal cortex or medial striatum impair multiple-location place learning in the water task: evidence for neural structures with complementary roles in behavioural flexibility.

This series of experiments assessed the effects of neurotoxic damage to either the medial prefrontal cortex or the medial striatum on the acquisition of multiple-location place learning in the water task. During training, normal subjects learn to search for a new hidden platform location at the beginning of each training session and to continue to swim to that location until the end of training during that session. By the end of training, normal subjects show one-trail place learning in which they find the new location on the first trial and swim directly to that location on the second swim. Rats with damage to either the medial prefrontal cortex or dorso-medial striatum showed deficits in learning to swim to the new location each day. These deficits were interpreted as impairments in behavioural flexibility. The lesion-induced impairment was not caused by perseverative errors but was manifested in an inability to rapidly acquire a new spatial position in conflict with the previous position. Interestingly, the subjects from both lesion groups were able to show normal place learning and memory after repeated training within a session. The results were interpreted as suggestive of a complementary role of these neural structures in behavioural flexibility.

Basal ganglia play a unique role in task switching within the frontal-subcortical circuits: evidence from patients with focal lesions.

The performance of patients with lesions involving the basal ganglia (BG) was compared to that of patients with prefrontal (PFC) lesions, thalamic (TH) lesions, and age-matched controls in order to examine the specific role of the BG within the frontal-subcortical circuits (FSCC) in task switching. All the BG patients and none of the other participants showed a marked increase in error rate in incongruent trials where correct responses depended upon the choice of the correct task rule. Some BG patients erred in failing to switch tasks and others failed despite their attempt to switch tasks. Additionally, reaction time results indicate abnormal response repetition effects among the BG patients; failure in benefiting from advance task information among all the patients; and increased task mixing costs following PFC lesions. The authors conclude that although the frontal-subcortical circuits jointly determine some behaviors (such as benefiting from preparation), the BG play a unique role within the FSCC in action selection and/or the inhibition of irrelevant information.

Medial prefrontal cortex lesions in the female rat affect sexual and maternal behavior and their sequential organization.

Temporal sequences of sexual and maternal behaviors in female rats and their correlation with each other and with performance on a sensory-motor gating response inhibition task assessed by prepulse inhibition (PPI) were investigated following medial prefrontal cortex (mPFC) lesions. Following excitotoxic mPFC (n = 10) or sham (n = 9) lesions, sexual behaviors across the ovarian cycle were scored. After mating and parturition, maternal interactions were scored until pups reached postnatal Day 10. After resumption of the ovarian cycle, the female rats were tested for PPI. Compared with sham lesions, mPFC lesions impaired proceptive behaviors and some maternal behaviors (e.g., pup retrieval, pup licking) but did not affect others (e.g., nest building, pup mouthing). Lesions disrupted temporal sequences of solicitations (number of male orientations followed, within 4 s, by a level change) and pup retrievals (number of pup retrievals followed, within 5 s, by another retrieval). These sequential behavior patterns were significantly correlated with each other and with PPI. However, when PPI effects were partialled out, group differences were less strong, but persisted. This study demonstrated that mPFC manipulations affect actions rich in sequential structure in response to biologically relevant stimuli.

cerebellar atrophy after moderate-to-severe pediatric traumatic brain injury.

BACKGROUND AND PURPOSE: Although the cerebellum has not attracted the same degree of attention as cortical areas and the hippocampus in traumatic brain injury (TBI) literature, there is limited structural and functional imaging evidence that the cerebellum is also vulnerable to insult. The cerebellum is emerging as part of a frontocerebellar system that, when disrupted, results in significant cognitive and behavioral consequences. We hypothesized that cerebellar volume would be reduced in children following TBI and wished to examine the relation between the cerebellum and known sites of projection, including the prefrontal cortex, thalamus, and pons. MATERIALS AND METHODS: Quantitative MR imaging was used to measure cerebellar white and gray matter and lesion volumes 1-10 years following TBI in 16 children 9-16 years of age and 16 demographically matched typically developing children 9-16 years of age. Cerebellar volumes were also compared with volumetric data from other brain regions to which the cerebellum projects. RESULTS: A significant group difference was found in cerebellar white and gray matter volume, with children in the TBI group consistently exhibiting smaller volumes. Repeating the analysis after excluding children with focal cerebellar lesions revealed that significant group differences still remained for cerebellar white matter (WM). We also found a relation between the cerebellum and projection areas, including the dorsolateral prefrontal cortex, thalamus, and pons in 1 or both groups. CONCLUSION: Our finding of reduced cerebellar WM volume in children with TBI is consistent with evidence from experimental studies suggesting that the cerebellum and its related projection areas are highly vulnerable to fiber degeneration following traumatic insult.

Forebrain D1 function and sensorimotor gating in rats: effects of D1 blockade, frontal lesions and dopamine denervation.

Prefrontal D1 hypoactivity is implicated in the pathophysiology of schizophrenia, and might contribute to sensorimotor gating deficits in schizophrenia patients, based on evidence that D1 blockade in the medial prefrontal cortex (MPFC) reduces prepulse inhibition of startle (PPI) in animal models. PPI is disrupted by systemic and intra-MPFC infusion of the D1 antagonist, SCH23390. We investigated the role of the MPFC in the PPI-disruptive effects of systemic SCH23390 administration, and more generally, in the dopaminergic regulation of PPI. PPI was measured in rats after forebrain manipulations, including systemic administration of SCH23390, ibotenic acid lesions of the MPFC, and 6OHDA-induced dopamine (DA) depletion from MPFC or nucleus accumbens. Systemic SCH23390 disrupted PPI; these effects were not opposed by ibotenic acid lesions of the MPFC. PPI remained intact after MPFC DA depletion, but--as predicted by Bubser and Koch [M. Bubser, M. Koch, Prepulse inhibition of the acoustic startle response of rats is reduced by 6 hydroxydopamine lesions of the medial prefrontal cortex, Psychopharmacology 113 (1994) 487-492]--a reduction in PPI from pre- to post-surgery correlated significantly with MPFC DA loss. The effects of systemic SCH23390 were not opposed by NAC DA depletion. D1 receptors regulate PPI in rats, but this effect does not appear to be mediated either by the MPFC or by increased mesolimbic DA activity.

Emotional impairment after right orbitofrontal lesion in a patient without cognitive deficits.

The present study describes a patient, M.L., with right orbitofrontal lesion, who showed no impairment on main neuropsychological tests, including those measuring frontal functions. Nevertheless, he had deeply affected emotional responses. In line with Damasio's work, the patient had lower skin conductance during the projection of a standardized set of emotional slides. Furthermore, he showed altered facial expressions to unpleasant emotions, displaying low corrugator supercilii electromyographical activity associated with reduced recall of unpleasant stimuli. During a task focusing on imagery of emotional situations, M.L.'s heart rate and skin conductance responses were affected during both pleasant and unpleasant conditions. Facial expressions to unpleasant imagery scripts were also impaired. Thus, the orbitofrontal cortex proved to play a critical role in retrieval of psychophysiological emotional patterns, particularly to unpleasant material. These results provide the first evidence that orbitofrontal lesions are associated with emotional impairment at several psychophysiological levels.