Impairments in trace EB conditioning by knife-cut lesions to the fornix in rabbits: reversal by galantamine

Previous work in our laboratory demonstrated that galantamine, a cholinesterase inhibitor and weak cholinergic agonist, facilitated classical trace eyeblink conditioning in healthy, young rabbits [Simon, B. B., Knuckley, B., & Powell, D. A. (2004). Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits. Learning & Memory, 11(1), 116-122.]. The current study investigated the effects of galantamine (0.0 or 3.0mg/kg) in rabbits sustaining knife-cut lesions to the fimbria-fornix, a major projection pathway connecting the hippocampus to cortical and subcortical brain structures involved in the formation of long-term memories. Two experiments were conducted. Experiment one assessed the effects of knife-cut lesions to the fornix or sham surgeries on trace eyeblink (EB) conditioning. Results indicate that fornix lesions significantly retarded EB conditioning when trace parameters were employed. Experiment 2 assessed whether treatment with galantamine would reverse the deficits caused by fornix damage. Results indicate that 3.0mg/kg GAL reversed trace EB conditioning deficits in animals with fornix knife-cut lesions. These findings suggest that galantamine may provide benefit in the reversal of cognitive dysfunction following certain types of brain damage, especially damage involving hippocampal structures.     

SUPPORT FOR A NEUROPSYCHOLOGICAL MODEL OF SPIRITUALITY IN PERSONS WITH TRAUMATIC BRAIN INJURY

Recent research suggests that spiritual experiences are related to increased physiological activity of the frontal and temporal lobes and decreased activity of the right parietal lobe. The current study determined if similar relationships exist between self‐reported spirituality and neuropsychological abilities associated with those cerebral structures for persons with traumatic brain injury (TBI). Participants included 26 adults with TBI referred for neuropsychological assessment. Measures included the Core Index of Spirituality (INSPIRIT); neuropsychological indices of cerebral structures: temporal lobes (Wechsler Memory Scale‐III), right parietal lobe (Judgment of Line Orientation), and frontal lobes (Trail Making Test, Controlled Oral Word Association Test). As hypothesized, spirituality was significantly negatively correlated with a measure of right parietal lobe functioning and positively correlated (nonsignificantly) with measures of left temporal lobe functioning. Contrary to hypotheses, correlations between spirituality and measures of frontal lobe functioning were zero or negative (and nonsignificant). The data support a neuropsychological model that proposes that spiritual experiences are related to decreased activity of the right parietal lobe, which may be associated with decreased awareness of the self (transcendence) and increased activity of the left temporal lobe, which may be associated with the experience of specific religious archetypes (religious figures and symbols).     

Memory in traumatic brain injury: The effects of injury severity and effort on the Wechsler Memory Scale‐III

This study examined the effects of traumatic brain injury (TBI) on Wechsler Memory Scale‐III (WMS‐III) performance. Since poor effort potentially contaminates results, effort was explicitly assessed and controlled using two well‐validated cognitive validity indicators, the Portland Digit Recognition Test (PDRT) and Reliable Digit Span (RDS). Participants were 44 mild TBI patients with good effort, 48 mild TBI patients with poor effort, and 40 moderate–severe TBI patients with good effort. A dose–response relationship between injury severity and WMS‐III performance was demonstrated. Effect size calculations showed that the good effort mild TBI patients did not differ from normal (average Cohen's d= 0.07) while moderate–severe TBI had a moderate effect on WMS‐III scores (average Cohen's d=?0.52). Consistent with previous literature, the moderate–severe TBI group scored the lowest on WMS‐III Visual indices. Effort had a larger effect than injury severity on WMS‐III scores (average Cohen's d=?1.27). Clinical implications of these findings are discussed.     

Neuropsychological correlates of impaired emotion recognition following traumatic brain injury

Previous research has shown that individuals with traumatic brain injury (TBI) are significantly impaired on emotion recognition tasks. In this study, the relationship between neuropsychological functioning and emotion recognition was examined in 11 individuals with moderate to severe TBI and a control group of 13 individuals matched for age,sex, and education. Emotion recognition stimuli were from Ekman and Friesen's pictures of facial affect. The group with TBI showed neuropsychological deficits consistent with those commonly found following moderate to severe TBI. The group with TBI also identified significantly fewer emotion recognition stimuli than the control group.The number of correctly identified emotion recognition stimuli was significantly correlated with measures of verbal cognitive processing in the group with TBI. These findings suggest that the role of left hemisphere brain mechanisms in the recognition of facial (nonverbal)emotion may be more important than previously recognized.     

The clinical utility of the Rey Auditory-Verbal Learning Test in medical rehabilitation

Recent research has reported the Rey Auditory-Verbal Learning Test Trial V (RAVLT-V) score to be a sensitive indicator of global cognitive functioning, not merely verbal learning skills. The concurrent validity of the RAVLT-V relative to other neuropsychological measures frequently utilized in medical rehabilitation was investigated in a sample of 64 outpatients diagnosed with traumatic brain injury (TBI). The sample was predominantly male (77%), white (97%), youthful (31.4±11.5 years), high school educated, and an average of 53 months postinjury. Using stepwise multiple regression analysis, a three-variable model consisting of gender, Wechsler Memory Scale-Revised Delayed Memory Index, and Trailmaking Part B (time) accounted for 61% of the variance in RAVLT-V scores. These findings suggest that in TBI patients, the RAVLT taps not only specific verbal learning and memory, but also global cognitive functions. Sensitivity to diffuse neuropsychological changes and ease/speed of administration make the RAVLT a valuable tool in medical rehabilitation settings.     

Transection of direct anterior thalamic afferents from the hippocampus: effects on activity and active avoidance in rats

This investigation demonstrates the importance of the direct hippocampo-anterior thalamic component of the postcommissural fornix in the control of general locomotion and active avoidance. Transection of anterior thalamic afferents from the hippocampal formation (subicular cortex), at the point where they exit from the fornix posterior to the septum, is sufficient to enhance bidirectional active avoidance acquisition and increase general activity. This transection may also interrupt fibers to or from other thalamic nuclei and the anterior septum. However, destruction of connections of the anterior septum with the hippocampus, habenula, and thalamus by transection in the coronal plane anterior to the descending fornix columns, without damage to the subiculothalamic fibers, increases general activity levels without damage to the subiculothalamic fibers, increases general activity levels without affecting active avoidance behavior. The activity increase in this case resembles that seen after septal lesions rather than that seen after hippocampal lesions. Thus, destruction of a single fornix component contributing afferents to the anterior thalamic nuclei reproduces at least part of the hippocampal syndrome. This suggests that these fibers contribute significantly to the control of these behaviors and may mediate active avoidance changes resulting from hippocampal and fornix damage.     

Structural-functional correlations between hippocampal volume and cortico-limbic emotional responses in depressed children

Although hippocampal atrophy and altered functional brain responses to emotional stimuli have been found in major depressive disorder (MDD), the relationship between the two is not yet well understood. The present study focused on children with and without a history of preschool onset MDD (PO-MDD) and directly examined the relations between hippocampal volume and functional brain activation to affect-eliciting stimuli. Children completed annual diagnostic assessments starting at preschool. When children were school-aged, high-resolution structural MRI and task-related functional MRI data were acquired from N = 64 nonmedicated children. During fMRI, subjects were shown emotional faces. Results from the total sample indicated that smaller bilateral hippocampal volumes were associated with greater cortico-limbic (e.g., amygdala, hippocampus, dorsolateral prefrontal cortex) activation to sad or negative faces versus neutral faces. Left hippocampal volume was negatively associated with the cortico-limbic activation in both the PO-MDD and healthy children. Right hippocampal volume was negatively correlated with amygdala responses in the PO-MDD group, but not in the healthy comparison group. These findings suggest that there may be important interrelationships between reduced hippocampal volume and hyperactivation of brain responses in children, both those with and those without a history of PO-MDD.     

Memory and brain volume in adults prenatally exposed to alcohol

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.     

The effect of age-at-testing on verbal memory among children following severe traumatic brain injury

Memory deficits are a common sequelae following childhood traumatic brain injury (TBI), which often have serious implications on age-related academic skills. The current study examined verbal memory performance using the Rey Auditory Verbal Learning Test (RAVLT) in a pediatric TBI sample. Verbal memory abilities as well as the effect of age at-testing on performance were examined. A sample of 67 children following severe TBI (age average = 12.3 ± 2.74) and 67 matched controls were evaluated using the RAVLT. Age effect at assessment was examined using two age groups: above and below 12 years of age during evaluation. Differences between groups were examined via the 9 RAVLT learning trials and the 7 composite scores conducted out of them. Children following TBI recalled significantly less words than controls on all RAVLT trials and had significantly lower scores on all composite scores. However, all of these scores fell within the low average range. Further analysis revealed significantly lower than average performance among the older children (above 12 years), while scores of the younger children following TBI fell within average limits. To conclude, verbal memory deficits among children following severe TBI demonstrate an age-at-testing effect with more prominent problems occurring above 12 years at the time of evaluation. Yet, age-appropriate performance among children below 12 years of age may not accurately describe memory abilities at younger ages following TBI. It is therefore recommended that clinicians address child’s age at testing and avoid using a single test as an indicator of verbal memory functioning post TBI.     

Individual differences in the Behavioral Inhibition System are associated with orbitofrontal cortex and precuneus gray matter volume

The Behavioral Inhibition System (BIS) is described in Gray's Reinforcement Sensitivity Theory as a hypothetical construct that mediates anxiety in animals and humans. The neuroanatomical correlates of this system are not fully clear, although they are known to involve the amygdala, the septohippocampal system, and the prefrontal cortex. Previous neuroimaging research has related individual differences in BIS with regional volume and functional variations in the prefrontal cortex, amygdala, and hippocampal formation. The aim of the present work was to study BIS-related individual differences and their relationship with brain regional volume. BIS sensitivity was assessed through the BIS/BAS questionnaire in a sample of male participants (N = 114), and the scores were correlated with brain regional volume in a voxel-based morphometry analysis. The results show a negative correlation between the BIS and the volume of the right and medial orbitofrontal cortices and the precuneus. Our results and previous findings suggest that individual differences in anxiety-related personality traits and their related psychopathology may be associated with reduced brain volume in certain structures relating to emotional control (i.e., the orbitofrontal cortex) and self-consciousness (i.e., the precuneus), as shown by our results.     

Place and response learning of rats in a Morris water maze: differential effects of fimbria fornix and medial prefrontal cortex lesions

The question examined in this study is concerned with a possible functional dissociation between the hippocampal formation and the prefrontal cortex in spatial navigation. Wistar rats with hippocampal damage (inflicted by a bilateral lesion of the fimbria fornix), rats with damage to the medial prefrontal cortex, and control-operated rats were examined for their performance in either one of two different spatial tasks in a Morris water maze, a place learning task (requiring a locale system), or a response learning task (requiring a taxon system). Performance of the classical place learning (allocentric) task was found to be impaired in rats with lesions of the fimbria fornix, but not in rats with damage of the medial prefrontal cortex, while the opposite effect was found in the response learning (egocentric) task. These findings are indicative of a double functional dissociation of these two brain regions with respect to the two different forms of spatial navigation. When the place learning task was modified by relocating the platform, the impairment in animals with fimbria fornix lesions was even more pronounced than before, while the performance of animals with medial prefrontal cortex lesions was similar to that of their controls. When the task was again modified by changing the hidden platform for a clearly visible one (visual cue task), the animals with fimbria fornix lesions had, at least initially, shorter latencies than their controls. By contrast, in the animals with medial prefrontal cortex damage this change led to a slight increase in escape latency.     

Impaired discourse gist and working memory in children after brain injury

Emerging evidence suggests that a traumatic brain injury (TBI) in childhood may disrupt the ability to abstract the central meaning or gist-based memory from connected language (discourse). The current study adopts a novel approach to elucidate the role of immediate and working memory processes in producing a cohesive and coherent gist-based text in the form of a summary in children with mild and severe TBI as compared to typically developing children, ages 8-14 years at test. Both TBI groups showed decreased performance on a summary production task as well as retrieval of specific content from a long narrative. Working memory on n-back tasks was also impaired in children with severe TBI, whereas immediate memory performance for recall of a simple word list in both TBI groups was comparable to controls. Interestingly, working memory, but not simple immediate memory for a word list, was significantly correlated with summarization ability and ability to recall discourse content.     

Regional cortical volume and cognitive functioning following traumatic brain injury

There has been limited examination of the effect of brain pathology on subsequent function. The current study examined the relationships between regional variation in grey matter volume, age and cognitive impairment using a semi-automated image analysis tool. This study included 69 individuals with mild-to-severe TBI, 41 of whom also completed neuropsychological tests of attention, working memory, processing speed, memory and executive functions. A widespread reduction in grey matter volume was associated with increasing age. Regional volumes that were affected also related to the severity of injury, whereby the most severe TBI participants displayed the most significant pathology. Poorer retention of newly learned material was associated with reduced cortical volume in frontal, parietal, and occipital brain regions. In addition, poorer working memory and executive control performance was found for individuals with lower cortical volume in temporal, parietal, and occipital regions. These findings are largely in line with previous literature, which suggests that frontal, temporal, and parietal regions are integral for the encoding of memories into long-term storage, memory retrieval, and working memory. The present study suggests that automated image analysis methods may be used to explore the relationships between regional variation in grey matter volume and cognitive function following TBI.     

Processing speed in normal aging: Effects of white matter hyperintensities and hippocampal volume loss

Changes in cognitive functioning are said to be part of normal aging. Quantitative MRI has made it possible to measure structural brain changes during aging which may underlie these decrements which include slowed information processing and memory loss. Much has been written on white matter hyperintensities (WMH), which are associated with cognitive deficits on tasks requiring processing speed and executive functioning, and hippocampal volume loss, which is associated with memory decline. Here we examine volumetric MRI measures of WMH and hippocampal volume loss together in relation to neuropsychological tests considered to be measures of executive functioning and processing speed in 81 non-demented elderly individuals, aged 75–90. Correlational analysis showed that when controlling for age, both greater WMH volume and smaller hippocampal volume were correlated with slower performances on most tests with the exception of a battery of continuous performance tests in which only WMH was correlated with slower reaction time (RT). We then performed a series of hierarchical multiple regression analyses to examine the independent contributions of greater WMH volume and reduced hippocampal volume to executive functioning and processing speed. The results showed that for the four measures requiring executive functioning and speed of processing, WMH volume and hippocampal volume combined predicted between 21.4% and 37% of the explained variance. These results suggest that WM integrity and hippocampal volume influence cognitive decline independently on tasks involving processing speed and executive function independent of age.     

Meal patterns following changes in procurement cost for rats with fornix transection

The purpose of the present study was to explore the effects of a varied procurement cost on the foraging behavior of rats with fornix transection. An operant analog of foraging requirements was used to examine the feeding patterns of the animals under free feeding, low procurement cost (FR5), and high procurement cost (FR80) situations, in an environment with minimal sensory distraction. It was found that animals with fornix transection did not differ from control rats in general consumption. Both groups were also able to adapt their feeding behavior to the varied procurement cost. As the procurement cost increased, the number of meals consumed decreased while the meal duration increased. The meal patterns themselves were different for the fornix transected animals and the control group. Animals with fornix transections ate more meals over the course of a day than did control animals; their meals were of a longer duration, and their intermeal intervals were shorter than those of control animals. During the course of a meal, the rats with fornix transections took a larger number of breaks, during which they drank, explored, or engaged in activities other than eating. These differences in the feeding patterns were seen across all procurement cost levels. The data support the possibility of hippocampal involvement in behavioral organization or sequencing.     

Construct and Criterion Validity of the Comprehensive Trail Making Test in Children and Adolescents with Traumatic Brain Injury

The current study examined the construct and criterion validity of the Comprehensive Trail Making Test (CTMT) when used to evaluate children and adolescents with traumatic brain injury (TBI). Participants included 100 children and adolescents, 50 who had sustained TBI and 50 normal comparisons (NC). Analyses indicated that the CTMT factor scores were significantly correlated with tests of perceptual organizational ability, processing speed, and motor function and provided support for its construct validity. Additionally, correlations between the various CTMT scores suggested that a different pattern of associations was present in the TBI group compared to the NC group. Finally, the TBI group performed significantly worse (p < .001) on all of the CTMT scores, including each of the five CTMT trails as well as the factor and composite index scores. Results support the construct and criterion validity of the CTMT when used to assess children and adolescents with TBI.     

Children's spatial behavior is differentially affected after traumatic brain injury.

Spatial behavior in 20 children with severe traumatic brain injury (TBI) and 20 healthy controls was investigated using the Kiel Locomotor Maze. Children had to remember defined locations in an experimental chamber with completely controlled intra- and extra-maze cues until learning criterion was reached. In a second experiment, spatial orientation strategies were assessed. Children with TBI were shown to be impaired in spatial learning and spatial memory. Spatial orientation was found to be deficient even in cases where spatial learning and memory proved to be unimpaired, especially in tasks that demanded the use of relational place strategies. Children who suffered a TBI at an early age proved to be more severely impaired in spatial learning and orientation than older children.     

Children's Spatial Behavior is Differentially Affected After Traumatic Brain Injury

Spatial behavior in 20 children with severe traumatic brain injury (TBI) and 20 healthy controls was investigated using the Kiel Locomotor Maze. Children had to remember defined locations in an experimental chamber with completely controlled intra- and extra-maze cues until learning criterion was reached. In a second experiment, spatial orientation strategies were assessed. Children with TBI were shown to be impaired in spatial learning and spatial memory. Spatial orientation was found to be deficient even in cases where spatial learning and memory proved to be unimpaired, especially in tasks that demanded the use of relational place strategies. Children who suffered a TBI at an early age proved to be more severely impaired in spatial learning and orientation than older children.     

Contributions of volumetrics of the hippocampus and thalamus to verbal memory in temporal lobe epilepsy patients

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However, dissociating the memory impairment that occurs following thalamic injury as distinguished from that following hippocampal injury has proven difficult. This study examined relationships between MRI volumetric measures of the hippocampus and thalamus and their contributions to prose and rote verbal memory functioning in 18 patients with intractable temporal lobe epilepsy (TLE). Results revealed that bilateral hippocampal and thalamic volume independently predicted delayed prose verbal memory functioning. However, bilateral hippocampal, but not thalamic, volume predicted delayed rote verbal memory functioning. Follow-up analyses indicated that bilateral thalamic volume independently predicted immediate prose, but not immediate rote, verbal recall, whereas bilateral hippocampal volume was not associated with any of these immediate memory measures. These findings underscore the cognitive significance of thalamic atrophy in chronic TLE, demonstrating that hippocampal and thalamic volume make quantitatively, and perhaps qualitatively, distinct contributions to episodic memory functioning in TLE patients. They are also consistent with theories proposing that the hippocampus supports long-term memory encoding and storage, whereas the thalamus is implicated in the executive aspects of episodic memory.