Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.

/pdf/the-cerebellar-cognitive-affective-syndrome-2qlts0j1w1.pdf

The cerebellar cognitive affective syndrome.

Abnormalities of prefrontal cortical function are prominent features of schizophrenia and have been associated with genetic risk, suggesting that susceptibility genes for schizophrenia may impact on the molecular mechanisms of prefrontal function. A potential susceptibility mechanism involves regulation of prefrontal dopamine, which modulates the response of prefrontal neurons during working memory. We examined the relationship of a common functional polymorphism (Val(108/158) Met) in the catechol-O-methyltransferase (COMT) gene, which accounts for a 4-fold variation in enzyme activity and dopamine catabolism, with both prefrontally mediated cognition and prefrontal cortical physiology. In 175 patients with schizophrenia, 219 unaffected siblings, and 55 controls, COMT genotype was related in allele dosage fashion to performance on the Wisconsin Card Sorting Test of executive cognition and explained 4% of variance (P = 0.001) in frequency of perseverative errors. Consistent with other evidence that dopamine enhances prefrontal neuronal function, the load of the low-activity Met allele predicted enhanced cognitive performance. We then examined the effect of COMT genotype on prefrontal physiology during a working memory task in three separate subgroups (n = 11-16) assayed with functional MRI. Met allele load consistently predicted a more efficient physiological response in prefrontal cortex. Finally, in a family-based association analysis of 104 trios, we found a significant increase in transmission of the Val allele to the schizophrenic offspring. These data suggest that the COMT Val allele, because it increases prefrontal dopamine catabolism, impairs prefrontal cognition and physiology, and by this mechanism slightly increases risk for schizophrenia.

http://enigma.ini.usc.edu/wp-content/uploads/2010/04/Effect-of-COMT-Val108-158-Met-genotype-on-frontal-lobe-function-and-risk-for-schizophrenia.pdf

Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.

The neurocognitive literature on test performance in schizophrenia is reviewed quantitatively. The authors report 22 mean effect sizes from 204 studies to index schizophrenia versus control differences in global and selective verbal memory, nonverbal memory, bilateral and unilateral motor performance, visual and auditory attention, general intelligence, spatial ability, executive function, language, and interhemispheric tactile-transfer test performance. Moderate to large raw effect sizes (d > .60) were obtained for all 22 neurocognitive test variables, and none of the associated confidence intervals included zero. The results indicate that schizophrenia is characterized by a broadly based cognitive impairment, with varying degrees of deficit in all ability domains measured by standard clinical tests.

Neurocognitive Deficit in Schizophrenia: A Quantitative Review of the Evidence

Currently, there is debate among scholars regarding how to operationalize and measure executive functions. These functions generally are referred to as “supervisory” cognitive processes because they involve higher level organization and execution of complex thoughts and behavior. Although conceptualizations vary regarding what mental processes actually constitute the “executive function” construct, there has been a historical linkage of these “higher-level” processes with the frontal lobes. In fact, many investigators have used the term “frontal functions” synonymously with “executive functions” despite evidence that contradicts this synonymous usage. The current review provides a critical analysis of lesion and neuroimaging studies using three popular executive function measures (Wisconsin Card Sorting Test, Phonemic Verbal Fluency, and Stroop Color Word Interference Test) in order to examine the validity of the executive function construct in terms of its relation to activation and damage to the frontal lobes. Empirical lesion data are examined via meta-analysis procedures along with formula derivatives. Results reveal mixed evidence that does not support a one-to-one relationship between executive functions and frontal lobe activity. The paper concludes with a discussion of the implications of construing the validity of these neuropsychological tests in anatomical, rather than cognitive and behavioral, terms.

http://sites.oxy.edu/clint/physio/article/ExecutiveFunctionandtheFrontalLobes.pdf

Executive Function and the Frontal Lobes: A Meta-Analytic Review

https://pure.uva.nl/ws/files/7917900/56487_2006.Huizinga.Dolan.VanderMolen.pdf

Age-related change in executive function: developmental trends and a latent variable analysis.

Correlation between intelligence test score and executive function measures. Archives Wisconsin Card Sorting Test manual: Revised and expanded. Odessa. The Wisconsin Card Sorting Test (WCST) was the most commonly used task Although the examiner did not provide instructions prior to or during the performance of the task, Wisconsin Card Sorting Test manual: revised and expanded. Wisconsin card sorting tests manual revised and expanded. Amsterdam short-term memory test: a new procedure for the detection of feigned memory deficits.

GG Kay

Papers

Wisconsin Card Sorting Test Manual – Revised and Expanded