Cognitive planning in humans: neuropsychological, neuroanatomical and neuropharmacological perspectives

In recent years, considerable progress has been made in understanding the cognitive and neuroanatomical basis of high-level planning behaviour through a combination of neuropsychological, neuropharmacological and functional neuroimaging approaches. In this article, early evidence suggesting a relationship between planning impairments and damage to the frontal lobe is reviewed and several contemporary studies of planning behaviour in patients with circumscribed frontal lobe excisions are described in detail. These neuropsychological investigations, together with recent functional neuroimaging studies of normal control subjects, have identified a specific area within the mid-dorsolateral frontal cortex of humans which appears to be critically involved in the cognitive processes that mediate efficient planning. The functions of this region, both in cognitive planning and in related functions such as working memory, are then discussed in the context of a general theoretical framework for understanding the functional organization of "executive" processes within the human lateral frontal cortex. In the final sections, the relationship between the planning deficits observed after intrinsic frontal lobe damage and those exhibited by patients with neuropathology of primarily sub-cortical origin, such as Parkinson's disease, is discussed. A central model for much of this work has been the concept of cortico-striatal circuitry which emphasizes the relationship between the neocortex and the striatum. The combined evidence from comparative studies in patients and from functional neuroimaging studies on Parkinson's disease suggests that altered cortico-striatal interactions may disrupt normal planning function at a number of levels, possibly consequent upon intrinsic striatal pathology on the one hand and the partial loss of (frontal) cortical input to the basal ganglia on the other.     

Distinctive forms of partial retrograde amnesia after asymmetric temporal lobe lesions: possible role of the occipitotemporal gyri in memory

We tested the hypothesis that partial forms of retrograde amnesia were associated with highly asymmetric lesions to the inferior and anterior-medial temporal lobe. Postencephalitic subjects EK and DR were both impaired on standardized retrograde memory tests, but showed strikingly different profiles in cognitive tasks of name stem completion, name:face matching, temporal ordering, forced choice recognition, and occupational judgments of famous names and faces from the past 3 decades. EK sustained left inferior and anterior-medial temporal lobe lesion with a small right temporal polar lesion, and showed near-complete loss of retrieval, knowledge, and familiarity associated with famous names but minimal deficiencies with famous faces. DR sustained right inferior and anterior-medial temporal lobe lesion and showed a milder retrograde loss limited to utilizing famous face prompts in name stem completion, name:face matching, occupational judgments, and forced choice recognition. These impairments were also different from the memory retrieval deficit, but intact recognition shown by a case of ruptured anterior communicating artery aneurysm with presumed basal forebrain damage. We hypothesize that EK's extensive loss of famous name knowledge was related to left inferior temporal lobe damage, particularly in the lateral and medial occipitotemporal gyri. This region in the left temporal lobe may serve as a critical processing area for retrograde memory that permits activation of established semantic, temporal, and visual (i.e., facial) associations biographically dependent on the category of proper names. On the basis of connectional anatomy patterns in the nonhuman primate, this region receives extensive hippocampal output and is interconnected with the temporal polar region and cortical association areas, which have been implicated in retrieval and storage aspects of retrograde memory. In the right hemisphere, the occipitotemporal gyri may serve an important role in famous face processing as part of a bilateral neural network.     

Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis

OBJECTIVE: This study correlated the extent of abnormalities detected by different magnetic resonance imaging (MRI) techniques [proton density (PD)-weighted, T1-weighted, and magnetization transfer imaging (MTI)] with the overall cognitive, frontal lobe, and memory impairments in patients with MS. PATIENTS: There were 30 clinically definite MS patients, with different disease courses. Exclusion criteria: psychoactive/steroid treatments, mood disorders, acute relapse phase. MAIN OUTCOME MEASURES: Neuropsychological test results. Total (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22 patients), and MTI (22 patients) MRI scans. Average lesion MT ratios (MTR) and analysis of the MTR histograms from brain tissue axial slabs on MTI scans. RESULTS: Patients with frontal lobe deficits (n=15) or memory impairment (n-17) had a higher TLL on PD scans (p=0.04 and p=0.01, respectively). Patients with frontal lobe deficits had higher FLL on PD scans (p=0.01) and TLL on MTI (p=0.03) scans. No significant relationships between the extent of T1-weighted lesion loads and the presence of any neuropsychological impairment. Mean MTR of both MS lesions and whole brain tissue was lower in patients with frontal lobe impairment (p=0.04). MRI lesion loads correlated significantly with some neuropsychological test scores. CONCLUSIONS: Lesion loads on PD-weighted MRI and MTI-derived measures are associated with cognitive decline in MS patients. Overall macroscopic and microscopic brain damage is more important than the corresponding regional brain disease in determining deficits of selective cognitive domains.     

A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge Neuropsychological Test Automated Battery

Several tests from the CANTAB neuropsychological test battery previously shown to be sensitive to frontal lobe dysfunction were administered to a large group of normal volunteers (N = 341) ranging in age from 21 to 79 years. The main tests included a computerized form of the Tower of London test of planning, a self-ordered spatial working memory task, and a test of attentional set formation and shifting. A computerized form of the Corsi spatial span task was also given. Age-related graded declines in performance were seen, sometimes in a discontinuous manner, especially for the attentional set shifting task (at the extradimensional shift stage). Patterns of deficits reminiscent of frontal lobe or basal ganglia damage were observed in the oldest age group (74-79). However, overall the data were only partially consistent with the hypothesis that frontal lobe functions are the most sensitive to effects of aging. Factor analyses showed that performance in the executive tests was not simply related to a measure of fluid intelligence, and their performance had a factor loading structure distinct from that for the CANTAB tests of visual memory and learning previously administered to the same sample. Finally, only limited support was found for the hypothesis that cognitive aging depends on slowed information processing.     

Frontal lobe functions in psychopaths.

Hypothesized that psychopaths would exhibit deficits on tasks tapping the frontal lobe functions of cognitive flexibility and perseverance. 20 male psychopaths (mean age 26.5 yrs), 23 male psychiatric controls, and 18 normal male controls (18–20 yrs old) completed the Socialization scale of the California Psychological Inventory, a behavioral checklist, and a task battery. Relative to controls, psychopaths exhibited the performance pattern of frontal lesion patients on all measures empirically related to frontal dysfunction: perseverative errors on the Wisconsin Card Sorting Task, errors on a sequential matching memory task, and Necker Cube reversals. Results encourage the pursuit of a conceptualization of psychopathy based on deficits in cognitive functions previously associated with frontal lobe. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tower of London performance in relation to Magnetic Resonance Imaging following closed head injury in children.

To investigate the relationship of severity of pediatric closed head injury (CHI), the contribution of frontal lobe lesions, and age at testing (6–10 yr olds vs 11–15 yr olds) to cognitive deficit, 134 head-injured patients were given the Tower of London (TOL) task and underwent magnetic resonance imaging. 89 normal controls were given the TOL for comparison. Severity of CHI and age at testing were strongly related to cognitive performance on the TOL, including the frequency of breaking the rules. Volume of frontal lobe lesion (but not extrafrontal lesion) contributed to the prediction of perfomance on the TOL even after severity of injury was taken into account. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic carbon disulfide encephalopathy

To understand central nervous damage after long-term exposure to carbon disulfide (CS2), 10 patients who had polyneuropathy with various neuropsychiatric symptoms in a viscose rayon plant were studied. Clinical and laboratory examinations including electroencephalography (EEG), brain computed tomography (CT), brain magnetic resonance images (MRI), and carotid duplex sonography were carried out. Clinically, headache, unpleasant dreams, memory impairment, fatigue, anorexia and emotional lability were common in these patients while 2 patients had stroke episodes. EEGs were all normal. Brain CT scan showed mild cortical atrophy in 3 and low density lesions in the basal ganglia in 3. Brain MRI studies also disclosed mild cortical atrophy in 4 and multiple lesions involving the basal ganglia and corona radiata in 4. Carotid duplex sonography revealed mild atherosclerosis with plaques (< 20% stenosis) of extracranial vessels in 6. However there was no significant difference in flow velocities and flow volumes in the extracranial carotid arteries between patients and the normal controls. Interestingly, 2 patients had multiple brain lesions in the subcortical white matter but without strokes. In conclusion, encephalopathy with possible strokes may occur after chronic exposure to CS2, as well as polyneuropathy. The lesions usually involve the basal ganglia and subcortical white matter. Furthermore, MRI study may detect brain lesions particularly in the subcortical white matter areas before the occurrence of stroke.     

Inhibition of ongoing responses following frontal, nonfrontal, and basal ganglia lesions.

The authors investigated the role of the frontal lobes and the basal ganglia in the inhibition of ongoing responses. Seventeen patients with frontal lesions (FG), 20 patients with lesions outside the frontal cortex (NFG), 8 patients with lesions to the basal ganglia (BG), and 20 orthopedic controls (OG) performed the stop-signal task that allows the estimation of the time it takes to inhibit an ongoing reaction (stop signal reaction time [SSRT]). The FG and the BG showed significantly longer SSRTs than the OG. Within the FG, patients with right and bilateral lesions showed significantly longer SSRTs than patients with left lesions. Results provide evidence for a role of the frontal lobes and the basal ganglia in the inhibition of ongoing responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationships between normal aging, frontal lobe function, and memory for temporal and spatial information.

Young and old participants were evaluated on tests of frontal lobe function, recognition memory, and memory for temporal and spatial information. Older participants showed significant impairments on memory for temporal order, and this impairment was found to correlate with deficits on frontal lobe tests measuring spontaneous flexibility but not reactive flexibility. However, spatial memory showed no evidence of an age effect. An interpretation of this latter finding based on the differential availability of contextual cues is ruled out because similar results were obtained when spatial memory was assessed in a different context to that used during learning. The researchers concluded that memory for temporal order and spatial memory are affected differentially by age. Theoretical interpretations of this difference are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective lesions of the nucleus basalis magnocellularis impair cognitive flexibility.

The authors tested the hypothesis that the cholinergic nucleus basalis magnocellularis (NBM) is involved in solving problems requiring cognitive flexibility. Rats with 192 IgG-saporin lesions of the NBM were assessed for perseveration (i.e., cognitive inflexibility) in the serial reversal of an operant discrimination and during subsequent extinction testing. It was hypothesized that the NBM lesion and control groups would not differ in the acquisition of the initial, simple discrimination, because this task does not demand cognitive flexibility. In contrast, it was hypothesized that the NBM lesion group would show perseveration during serial reversal and extinction testing. Results generally supported these hypotheses, suggesting that the NBM plays an important role in mediating cognitive flexibility. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relationship between remembering and knowing: a cognitive neuroscience perspective

Cognitive neuroscience has provided strong support for the idea that there are multiple memory systems. Recent evidence suggests that remembering and knowing may be two types of recognition with different neural substrates. The remember/know distinction is not equivalent to the explicit/implicit distinction because both remembering and knowing are impaired after damage to medial temporal lobe structures. A number of converging lines of evidence suggest that the relationship between remembering and knowing is one redundancy, with "knowing" processes also active during remembering. Remembering appears to depend additionally on frontal lobe functioning.     

Distribution of hepatic glycosaminoglycans during acute schistosomiasis: modulation by IFN gamma treatment

The neuropsychological characteristics of frontal lobe epilepsy have rarely been reported, with neuropsychological indicators usually being related to subjects with other forms of neurological damage. In this study we assessed the performance of 74 subjects with frontal lobe epilepsy (42 with left, 32 with right frontal epileptic foci) on a series of measures thought to be sensitive to frontal lobe dysfunction and compared to 57 subjects with temporal lobe epilepsy (31 with left, 26 with right epileptic foci). The results indicated a number of measures that could be considered sensitive to frontal lobe epileptic dysfunction. However, the pattern of results did not indicate consistent deficits to be associated with frontal lobe epileptic dysfunction. There are a number of unique factors associated with epilepsy that need to be considered, and these may account for the variable pattern of results obtained. In particular, the rapid propagation of frontal lobe seizures both bilaterally and to other cortical regions has to be considered.     

Expression of multidrug resistance (mdr) gene(s) in primary lymphoid organs of chicken immune system during embryonic development

The present study investigated the processing of painful electrical stimuli in patients with unilateral frontal or parietal lobe damage and matched control subjects. Patients with frontal lesions showed increased pain thresholds when the stimuli were administered contralateral to the lesion. While the peak-to-peak amplitudes of the N150/P250 components of the somatosensory potentials increased linearly with stimulus intensity in the control subjects, the responses in the frontal group did not change significantly between stimulation at pain and tolerance threshold. There was no evidence for altered pain processing in patients with parietal lobe lesions. The findings of the present study support the hypothesis of an involvement of the frontal cortex in pain perception in humans.     

Cognitive impairment following frontal lobe damage and its relevance to human amnesia.

Whether frontal lobe pathology can account for some of the cognitive impairment oberved in amnesic patients with Korsakoff's syndrome was investigated. Various cognitive and memory tests were given to patients with circumscribed frontal lobe lesions, patients with Korsakoff's syndrome, non-Korsakoff amnesic patients, and control Ss. Patients with frontal lobe lesions were not amnesic. Nevertheless, they exhibited 2 deficits that were also exhibited by patients with Korsakoff's syndrome but not by other amnesic patients: (a) impairment on the Wisconsin Card Sorting Test and (b) impairment on the Initiation and Perseveration subscale of the Dementia Rating Scale. Thus, frontal lobe pathology can explain some of the cognitive deficits observed in patients with Korsakoff's syndrome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protein kinase C from rainbow trout brain: identification and characterization of three isozymes

This study examines the hypothesis that patients with frontal lobe lesions are impaired on tests of letter but not category fluency. This hypothesis was proposed by Moscovitch (1994), based on a series of cognitive studies with young, normal participants. A group of patients with lateral prefrontal lesions and age-matched controls were tested on 2 tests of verbal fluency, the FAS task and a category fluency task that used semantic categories as cues (e.g., animals). Patients with frontal lobe lesions generated fewer items than controls on both letter and category fluency. This effect did not interact with the type of fluency test, suggesting that the frontal lobes are more generally involved in verbal fluency. Moreover, this pattern of findings, along with previous results of impaired free recall and remote retrieval in this patient group, suggests that patients with frontal lobe lesions do not efficiently organize and develop retrieval strategies.     

Melatonin as an antiaging drug: between facts and fantasy

Structural neuroimaging has been used to correlate lesional patterns with the cognitive profile of patients with multiple sclerosis (MS), especially for "frontal" dysfunction. However, a clear-cut anatomical explanation has yet to be found for the long-term memory deficit which is a hallmark of MS cognitive impairment. We have used PET to measure regional cerebral glucose metabolism (rCMRglc) in a group of 15 MS patients with involvement of verbal and/or spatial long-term memory. These patients were compared with 10 normal controls and 13 MS patients unimpaired on all neuropsychological tests. Relative to the controls, MS patients with memory deficits showed a significant bilateral reduction of rCMRglc in the hippocampus, cingulate gyrus, thalamus, associative occipital cortex, and cerebellum. Direct comparisons between patients with memory deficits and the group of unimpaired MS patients showed a metabolic reduction in the left thalamus and in both hippocampi. Seven of the memory-impaired patients also had neuropsychological signs of frontal dysfunction. These patients were compared with patients who had isolated memory deficit. Here we observed a further metabolic reduction in a number of brain regions including bilateral prefrontal cortex, inferior parietal cortex, and basal ganglia. Our findings indicate that hypometabolism of thalamic and deep cortical gray structures of the temporal lobe is associated with episodic memory dysfunction in MS. On the other hand, pathological performance on tests designed to assess frontal functions was associated with widespread reduction of glucose metabolism.     

Genetic relationship between dopamine transporter gene and schizophrenia: linkage and association

This experiment was aimed at comparing the sensorimotor correlates of fimbria-fornix lesions made with either a classical aspiration technique that also removes part of the overlying cortical structures, or an electrolytic one that does not encroach upon these cortical structures. About 4 months after lesion surgery, Long-Evans female rats which had sustained an aspiration or an electrolytic fimbria-fornix lesion at the age of 90 days were tested to measure their beam-walking performance as an index for their sensorimotor capabilities. We found that after an aspiration lesion, the rats presented sensorimotor deficits which did not occur after an electrolytic lesion. After having found that electrolytic lesions of the fimbria and the fornix produced neurochemical deficits (in the dorsal hippocampus) and cognitive alterations close to those resulting from aspiration lesions, it is concluded from the present experiment that the electrolytic lesion technique is an interesting alternative to an aspiration technique, essentially because the former does not induce the sensorimotor deficits due to the partial damage that an aspiration technique produces in the medial parietal cortex. As the electrolytic lesion technique may minimize the risk of introducing a sensorimotor bias in the accuracy of cognitive evaluations, the present result might be of interest to neuroscientist using a fimbria-fornix lesion paradigm in order to investigate the efficacy of drugs, grafts or other treatments on the recovery from cognitive deficits.     

CD46 (membrane cofactor protein of complement, measles virus receptor): structural and functional divergence among species (review)

OBJECT: In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. CONCLUSIONS: The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.     

Letter and category fluency in patients with frontal lobe lesions.

This study examines the hypothesis that patients with frontal lobe lesions are impaired on tests of letter but not category fluency. This hypothesis was proposed by Moscovitch (1994), based on a series of cognitive studies with young, normal participants. A group of patients with lateral prefrontal lesions and age-matched controls were tested on 2 tests of verbal fluency, the FAS task and a category fluency task that used semantic categories as cues (e.g., animals). Patients with frontal lobe lesions generated fewer items than controls on both letter and category fluency. This effect did not interact with the type of fluency test, suggesting that the frontal lobes are more generally involved in verbal fluency. Moreover, this pattern of findings, along with previous results of impaired free recall and remote retrieval in this patient group, suggests that patients with frontal lobe lesions do not efficiently organize and develop retrieval strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lateralized response to cortical injury in the rat: Interhemispheric interaction.

Two experiments, with 92 male Sprague-Dawley rats, examined the role of interhemispheric interaction in the production of spontaneous hyperactivity following right but not left frontal cortical suction lesions. Bilateral lesions, either simultaneous or left followed 1 wk later by right, led to spontaneous hyperactivity and bilateral depletions of cortical norepinephrine concentrations. Ss given corpus callosum sectioning as neonates and frontal cortical suction lesions as adults developed spontaneous hyperactivity only when the right hemisphere was injured. Data suggest that lateralized spontaneous hyperactivity as elicited by small suction lesions of the right hemisphere does not depend on interhemispheric release or interaction and that at least the cortical mechanism is in the right hemispere itself. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)