Neuropsychological consequences of right thalamic haemorrhage: case study and review

The neuropsychological performance of a right-handed man is examined following haemorrhage from the anterior sections of the right thalamus. A pattern of temporally graded retrograde amnesia, global anterograde amnesia, impaired short-term memory, behavioural changes, and severe executive deficits were identified. The deficits evident in this case are discussed in reference to existing neuropsychological literature regarding the consequences of thalamic infarction. It is proposed that damage to the anterior thalamic nuclei results in a frontal dysexecutive syndrome and that such a dysexecutive syndrome can explain the neuropsychological deficits observed in this case.     

Impairment of syntax and lexical semantics in a patient with bilateral paramedian thalamic infarction

Bilateral vascular thalamic lesions are rare. Although a variety of neurobehavioral manifestations have been described, the literature is less documented with regard to accompanying linguistic disturbances. This article presents an in-depth neurolinguistic analysis of the language symptoms of a patient who incurred bilateral paramedian ischemic damage of the thalamus. In the post-acute phase of the stroke, a unique combination of transcortical sensory aphasia with syntactic impairment was found. Because of this atypical semiological association, additional analyses of spontaneous speech were performed. In spite of the typological affinity with the grammatic characteristic of marked simplification of syntax observed in Broca's aphasia, only a wordclass specific, lexical-semantic deficit for verbs was objectified. The hypothesis that lexical-semantic disturbances in our patient might result from a functional deafferentiation of both thalami with the frontal lobe is supported by: (1) associated neuropsychological deficits of frontal origin and (2) frontal-like behavioral disturbances.     

Cortical neuroanatomical correlates of behavioral deficits produced by lesion of the basal forebrain in rats

Morphological changes in the frontoparietal cortex were assessed in rats that exhibited deficits in a go/no go alternation task due to electrolytic lesion of the basal forebrain. Cortical area, laminar thickness, neuronal density, and soma area were examined in frontal, hindlimb, forelimb, and parietal areas of the cortex. Quantitative morphological analysis of the frontoparietal cortex in lesioned rats revealed a decrease in laminar thickness due to reduced soma size in particular cortical laminae. Neuronal density was not affected. These effects were present in all cortical areas examined and most pronounced in laminae II-III. Similar morphological changes were observed in the same cortical areas following lesions of the basal forebrain made with ibotenic acid, allowing a discrimination of lesion effects from those induced by damage to fibers of passage or differential behavioral testing. Lesions of the basal forebrain have previously been shown to produce both behavioral deficits and changes in cortical cholinergic activity. The cortical morphological changes observed in the present study following basal forebrain lesion provide further evidence for the importance of ascending cholinergic inputs to the cortex and their role in learning and memory.     

DISCRIMINATION LEARNING IN ADULTS WITH NEUROCOGNITIVE DISORDERS

Alzheimer's disease is the most commonly known neurocognitive disorder characterized by deterioration in areas such as memory, attention, and activities of daily living. From a behavioral perspective, memory and attentional deficits may be described as deterioration of stimulus control. This paper provides a case study of discrimination behavior in a patient with neurocognitive disorder. The purpose of the current study was twofold: (i) to study the effect of using presumed familiar pictures in arbitrary matching‐to‐sample tasks and (ii) to study variables that affect stimulus control in a patient diagnosed with vascular dementia. There were 12 conditional discrimination experimental conditions with various types of stimuli, from familiar pictures to identity matching. The results showed that the participant's responses were not in accord with experimenter‐defined stimulus classes when using familiar pictures. However, intact stimulus control by sample stimulus was established following systematic procedural changes in the conditional discrimination tasks. Copyright © 2014 John Wiley & Sons, Ltd.     

Subcortical Aphasia

We critically review the literature on subcortical aphasia, suggest that a number of traditional concepts regarding mechanisms of aphasia are inconsistent with now abundant data, and propose several new hypotheses. The absence of aphasia in 17 reported cases of dominant hemisphere striatocapsular infarction and the finding of nearly every conceivable pattern of language impairment in 33 different reported cases of striatocapsular infarction provide strong evidence against a major direct role of the basal ganglia in language and against disconnection or diaschisis as mechanisms of nonthalamic subcortical aphasia. However, detailed consideration of the vascular events leading to striatocapsular infarction strongly suggests that associated linguistic deficits are predominantly related to sustained cortical hypoperfusion and infarction not visible on structural imaging studies. Thalamic disconnection, as may occur with striatocapsular infarcts with extension to the temporal stem and putamenal hemorrhages, may also contribute to the language deficits in some patients. Review of the literature on thalamic infarction, in conjunction with previously unreported anatomic details of four cases, suggests that what infarcts in the tuberothalamic artery territory and the occasional infarcts in the paramedian artery territory associated with aphasia have in common is damage to the frontal lobe–inferior thalamic peduncle–nucleus reticularis–center median system that may be involved in regulating the thalamic gate in attentional processes. Disruption of attentional gating in the pulvinar and lateral posterior nuclei resulting from such lesions may impair selection of specific neuronal networks in the projection field of these nuclei that serve as the substrate for lexical–semantic function, which is in effect a disruption of a type of working memory, as defined by Goldman–Rakic. We define this as a defect of selective engagement.     

ADHD outside the laboratory: boys' executive function performance on tasks in videogame play and on a visit to the zoo

One current theory of attention-deficit/hyperactivity disorder (ADHD) proposes that a primary deficit in behavioral inhibition gives rise to secondary deficits in 4 executive functions and motor control. To date, empirical support for this model is based primarily on laboratory-based cognitive methods. This study assessed behavioral inhibition and executive functioning in children with ADHD in 2 real-life contexts: videogames (motor-skill target game, cognitively demanding adventure game) and an outing at the zoo (route tasks). Participants were a community sample of 57 boys diagnosed with ADHD (20 inattentive, 37 combined type) and 57 normally developing control boys, matched individually for age and nonverbal IQ. Operationally defined measures of behavioral inhibition and specific executive functions were derived from these activities and assessed under contrasting conditions of low or high working memory and distractor loads. There were no group differences in basic motor skills on the target game, nor in terms of the ability to inhibit a prepotent or ongoing response in the adventure videogame. However, boys with ADHD exhibited more self-talk, more effortful response preparation, and completed fewer challenges in the latter videogame. Also, they manifested inhibition deficits in terms of interference control during the route task at the zoo and took longer to complete the tasks. Typically, these differences were greatest under conditions of high working memory and distractor loads. Findings from this study suggest that cognitive difficulties in ADHD may be context dependent and that ADHD is associated with deficits in some but not all aspects of behavioral inhibition.     

Neuropsychological profiles of six children with anoxic brain injury

Anoxic brain injury (ABI) often results in severe memory impairment and other cognitive and behavioral deficits, although limited information is available regarding pediatric cases. This study reported the neuropsychological outcomes in six children and adolescents who sustained ABI. Profiles were compared by mechanism of injury (ischemic vs. hypoxemic) and three cases were evaluated more than once. Severe intellectual, attention, memory, and behavioral impairments were observed in all six cases although academic achievement, internalizing behavioral problems, and visuospatial deficits were in general less severe than other cognitive and behavioral deficits. The longitudinal case studies varied but showed steady increases in memory and intellectual performance in the younger children with strongest improvement in nonverbal abilities and little change in parent-reported behavior. This study raises several possible hypotheses about specific cognitive and behavioral outcomes observed in pediatric ABI.     

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.     

Lateral and anterior thalamic lesions impair independent memory systems

Damage to the medial region of the thalamus, both in clinical cases (e.g., patients with infarcts or the Korsakoff's syndrome) and animal lesion models, is associated with variable amnesic deficits. Some studies suggest that many of these memory deficits rely on the presence of lateral thalamic lesions (LT) that include the intralaminar nuclei, presumably by altering normal function between the striatum and frontal cortex. Other studies suggest that the anterior thalamic nuclei (AT) may be more critical, as a result of disruption to an extended hippocampal system. Here, highly selective LT and AT lesions were made to test the prediction that these two regions contribute to two different memory systems. Only LT lesions produced deficits on a preoperatively acquired response-related (egocentric) working memory task, tested in a cross-maze. Conversely, only AT lesions impaired postoperative acquisition of spatial working memory, tested in a radial maze. These findings provide the first direct evidence of a double dissociation between the LT and AT neural aggregates. As the lateral and the anterior medial thalamus influence parallel independent memory processing systems, they may each contribute to memory deficits, depending on lesion extent in clinical and experimental cases of thalamic amnesia.     

The role of the human thalamus in language and memory: evidence from electrophysiological studies

The data reviewed here indicate that electrical stimulation of the dominant ventrolateral thalamus can produce deficits in language processing that are not seen after similar stimulation of the nondominant ventrolateral thalamus. The nature of the language deficit produced varies, depending upon the rostrocaudal location of the stimulation site. Stimulation of the anterior left ventrolateral thalamus in right-handed patients resulted in production of a repeated erroneous word, stimulation of the medial ventrolateral thalamus evoked perseveration, and stimulation of the posterior ventrolateral thalamus and anterior pulvinar resulted in misnaming and omissions. Additional studies have examined the effect of electrical thalamic stimulation on verbal and nonverbal short-term memory. Left (but not right) ventrolateral thalamic stimulation during verbal memory input greatly decreased subsequent recall errors, while stimulation during verbal memory retrieval increased recall errors. This finding contrasted with those obtained from studies on nonverbal memory, in which right ventrolateral stimulation during memory input decreased recall errors, while left thalamic stimulation at the same stage increased recall errors. Left pulvinar stimulation disrupted verbal memory processing, while right pulvinar stimulation disrupted nonverbal memory processing. Limited evidence suggests that the effects of thalamic electrical stimulation on verbal memory may persist for several days after the stimulation has ended. The lateralization of thalamic functions also affects the motoric aspects of speech production. Left (but not right) ventrolateral thalamic stimulation disrupted speech articulation and increased the expiratory phase of respiration. The fact that these motor effects were evoked from the same general area of the thalamus that produced the language deficits discussed above raises the possibility that the thalamus is involved in coordinating the cognitive and motoric aspects of language production. A model of thalamic function is discussed in which defined regions of the thalamus operate as a "specific alerting response," increasing the input to memory of category-specific material while simultaneously inhibiting retrieval from memory.     

Episodic memory, amnesia, and the hippocampal-anterior thalamic axis

By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an "extended hippocampal system" comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon. These are necessary for the encoding and, hence, the effective subsequent recall of episodic memory. An additional feature of this hippocampal-anterior thalamic axis is the presence of projections back from the diencephalon to the temporal cortex and hippocampus that also support episodic memory. In contrast, this hippocampal system is not required for tests of item recognition that primarily tax familiarity judgements. Familiarity judgements reflect an independent process that depends on a distinct system involving the perirhinal cortex of the temporal lobe and the medial dorsal nucleus of the thalamus. In the large majority of amnesic cases both the hippocampal-anterior thalamic and the perirhinal-medial dorsal thalamic systems are compromised, leading to severe deficits in both recall and recognition.     

Competing Core Processes in Attention-Deficit/Hyperactivity Disorder (ADHD): Do Working Memory Deficiencies Underlie Behavioral Inhibition Deficits?

The current study examined competing predictions of the working memory and behavioral inhibition models of ADHD. Behavioral inhibition was measured using a conventional stop-signal task, and central executive, phonological, and visuospatial working memory components (Baddeley 2007) were assessed in 14 children with ADHD and 13 typically developing (TD) children. Bootstrapped mediation analyses revealed that the visuospatial working memory system and central executive both mediated the relationship between group membership (ADHD, TD) and stop-signal task performance. Conversely, stop-signal task performance mediated the relationship between group membership and central executive processes, but was unable to account for the phonological and visuospatial storage/rehearsal deficits consistently found in children with ADHD. Comparison of effect size estimates for both models suggested that working memory deficits may underlie impaired stop-signal task performance in children with ADHD. The current findings therefore challenge existing models of ADHD that describe behavioral inhibition as a core deficit of the disorder.     

The Study of Language in the Amyotrophic Lateral Sclerosis - Frontotemporal Spectrum Disorder: a Systematic Review of Findings and New Perspectives

Amyotrophic Lateral Sclerosis is a neurodegenerative disorder characterized primarily by motor network disruption. Extra-motor manifestations including executive functions, social cognition, and behavioral changes are now well recognized as important features of ALS, and are associated with frontotemporal and frontostriatal network disruption. However, the presence and characterization of language changes has received less attention. This systematic review characterizes the profile of reported language dysfunction in ALS. PRISMA guidelines were implemented to carry out and report the review. Current evidence suggests that areas of neuroanatomical disruption in ALS spread to language centers such as posterior, inferior frontal and superior temporal areas leading to deficits in word retrieval, syntactic and grammatical processing, and spelling. However, the majority of studies of language in ALS have been limited by the recruitment of small clinic-based prevalent samples and important questions remain regarding the incidence and progression of language impairment in ALS. Further studies from population-based incident cohorts will help to determine the range of language deficits in ALS, and how these relate to previously defined executive and behavioral sub-phenotypes.     

Inhibition and working memory in young preschool children with symptoms of ADHD and/or oppositional-defiant disorder

Background: Early symptoms of attention deficit/hyperactivity disorder (ADHD) and oppositional-defiant disorder (ODD) are associated with deficits in cognitive self-regulatory processes or executive functions (EF)s. However, the hypothesis that neurocognitive deficits underlying the two disorders are already evident during early preschool years still has limited empirical support. The present study investigated associations between symptoms of ADHD and/or ODD and two core EFs, inhibition and working memory, in a large nonclinical sample of 3-year old children. Method: Participants were 1045 children (554 boys, age 37–47 months), recruited from the population based Norwegian Mother and Child Cohort Study (MoBa). Relations between behavioral symptoms and measures of inhibition and working memory were studied both categorically and dimensionally. Results: Children with co-occurring symptoms of ADHD and ODD performed at a significantly lower level than typically developing children in 4 out of 5 EF measures. Symptoms of ADHD, both alone and in combination with ODD, were associated with reduced performance on tests of inhibition in the group comparisons. Dimensional analyses showed that performance within both EF domains contributed to variance primarily in ADHD symptom load. The associations between test results and behavioral symptoms remained significant after gender and verbal skills had been controlled. Conclusion: Young preschoolers show the same pattern of relations between EF and behavioral symptoms of ADHD and/or ODD as previously described in older children diagnosed with ADHD and/or ODD. Effect sizes were generally small, indicating that measures of EF have limited clinical utility at this stage in development.     

Working Memory Deficits and Social Problems in Children with ADHD

Social problems are a prevalent feature of ADHD and reflect a major source of functional impairment for these children. The current study examined the impact of working memory deficits on parent- and teacher-reported social problems in a sample of children with ADHD and typically developing boys (N = 39). Bootstrapped, bias-corrected mediation analyses revealed that the impact of working memory deficits on social problems is primarily indirect. That is, impaired social interactions in children with ADHD reflect, to a significant extent, the behavioral outcome of being unable to maintain a focus of attention on information within working memory while simultaneously dividing attention among multiple, on-going events and social cues occurring within the environment. Central executive deficits impacted social problems through both inattentive and impulsive-hyperactive symptoms, whereas the subsidiary phonological and visuospatial storage/rehearsal systems demonstrated a more limited yet distinct relationship with children’s social problems.     

Strategy-dependent changes in memory: Effects on behavior and brain activity

In the present study, an implicit strategy manipulation was used to explore the contribution of memory strategy to brain activation and behavioral performance. Participants were biased to use either a short-term (maintenance-focused) or long-term (retrieval-focused) memory strategy within a single memory task through manipulation of task context. In comparing directly matched trials across the different task contexts, we observed clear changes in both behavioral performance and brain activity across a network of regions located primarily within lateral and medial frontal cortex. These effects of the memory strategy manipulation suggest that when a retrieval-focused strategy is induced, mnemonic processes are preferentially engaged during the encoding period. In contrast, when a maintenance-focused strategy is induced, mnemonic processes are preferentially engaged during the delay and response periods. Taken together, the results imply that covert cognitive strategies play an important role in modulating brain activation and behavior during memory tasks.     

Changes of Cingulothalamic Topographic Excitation Patterns and Avoidance Response Incubation over Time Following Initial Discriminative Conditioning in Rabbits

Neurons in particular layers of cingulate cortex and in limbic thalamic nuclei exhibit peak firing rates in response to a positive conditional stimulus (CS+) in particular stages of discriminative learning. A given area is maximally activated by the CS+ in the initial, an intermediate, or a late stage of behavioral acquisition, and activation in all of the areas diminishes as training continues after the peak of activation occurs. Thus, the topographic distribution of activation in these areas depends on the stage of behavioral acquisition. The present study determined whether the acquisition-related changes of the topographic distributions of peak firing rates in CS-elicited activity are driven exclusively by the repetition of conditioning trials (i.e., practice) or may occur as well with the passage of time, similar to putative processes of memory consolidation. Multiunit activity was recorded in cingulate cortex and in the anterior dorsal (AD), anterior ventral (AV), and medial dorsal (MD) thalamic nuclei as rabbits learned to step in response to a warning tone (CS+) to prevent a scheduled foot-shock, and to ignore a different tone (CS-) not predictive of foot-shock. The rabbits received two training sessions, S1 and S2. S2 followed S1 immediately in one group of rabbits and after 48 h in a different group. Significant neuronal discharge increments occurred from S1 to S2 in the 48-h group but not in the 0-h group, for the areas (posterior cingulate cortex, AV thalamic nucleus) that previously showed only late-stage activation. Significant discharge increments occurred from S1 to S2 in the 0-h group but not in the 48-h group in areas (anterior cingulate cortex, the AD, and MD thalamic nuclei) that previously exhibited early stage activation. These results indicate that the trial-driven topographic distribution changes also occur with the passage of time after limited initial training. It is suggested that the trial-driven and time-related changes may have a common functional relevance concerning memory consolidation.     

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.     

Thalamic Amnesia Following Venous Infarction: Evidence from a Single Case Study

The present paper describes the case of a right-handed Italian–English bilingual male patient suffering from amnesia following a bilateral thalamic lesion due to venous infarction. Within a few months from the onset, the lesion gradually shrank and was finally confined to the left thalamus only, in particular to the antero-medial portion and the pulvinar. The mammillary bodies and the cortical areas of both hemispheres were spared. After the regression of a series of generalized cognitive deficits implying slow psychic activity, confusion, and spatial and temporal disorientation, the patient presented a persistent amnesic syndrome with mild language disorders, both in Italian and in English. Major disorders of memory included a dissociation between verbal memory, which was severely impaired, and spatial memory, which was largely preserved.     

Working memory and behavioral inhibition in boys with ADHD: An experimental examination of competing models

Working memory (WM) and behavioral inhibition impairments have garnered significant attention as candidate core features, endophenotypes, and/or associated neurocognitive deficits of attention-deficit/hyperactivity disorder (ADHD). The relationship between ADHD-related WM and inhibition deficits remains relatively unclear, however, with inferences about the constructs’ directional relationship stemming predominantly from correlational research. The current study utilized a dual-task paradigm to experimentally examine the relationship between ADHD-related WM and behavioral inhibition deficits. A total of 31 boys (15 ADHD and 16 typically developing [TD]) aged 8–12 years completed WM (1-back and 2-back), behavioral inhibition (stop-signal task [SST]), and dual-condition (1-back/SST and 2-back/SST) experimental tasks. Children with ADHD exhibited significant, large-magnitude WM deficits for the 1-back condition but were not significantly different from children in the TD group for the 2-back, 1-back/SST, and 2-back/SST conditions. Children with ADHD also exhibited significant inhibition deficits for the SST, 1-back/SST, and 2-back/SST conditions, but the within-group effect was not significant. The findings suggest that ADHD-related stop-signal demands are upstream, or compete for, resources involved in controlled-focused attention and/or other central executive (CE), WM processes.