Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness.

Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals.

fMRI and corpus callosum relationships in monozygotic twins discordant for handedness.

To further investigate brain structure and function in 26 handedness discordant monozygotic twin pairs (MzHd), MRI and behavioural assessments were carried out. These showed significant correlation between language-specific functional laterality in inferior and middle frontal gyri, and anterior corpus callosum. Previous studies of handedness discordant monozygotic twins failed to resolve the issue concerning handedness and hemispheric laterality for language due to methodological disparities. The results would be relevant to genetic theories as well as to brain structure:function explanations. MzHd twins underwent MRI and fMRI scanning as well as behavioural assessment of motor performance and cognition. There were significant differences on MRI and fMRI laterality measures, as well as a significant correlation between anterior callosal widths and functional laterality. LH twins showed higher frequencies of atypical functional laterality. There was no significant within-twin pair correlation on fMRI verbal laterality, nor did results show within-twin pair differences on verbal fluency or IQ. Implications for the field of laterality research pertain to frontal hemispheric equipotentiality for verbal processes in healthy individuals. In particular, there can be an apparent lack of cognitive 'cost' to atypical laterality. An fMRI verbal laterality index correlated significantly with corpus callosum widths near Broca's area.

Semantic clustering in verbal fluency: schizophrenic patients versus control participants.

BACKGROUND: Schizophrenic patients generate fewer words than healthy controls during verbal fluency tasks. The structure of output may explain why patients generate fewer exemplars. METHODS: Twenty-four healthy controls and 24 patients with schizophrenia participated in six, 3 min semantic fluency tasks. In a subsequent session, participants were given cards, each printed with one of their own words generated from previous fluency tasks. Participants were to sort the cards into categories (e.g. subcategories of 'animals'), thus defining their own semantic subcategories of words, and thereby eliminating experimenter assumptions about word relatedness. These clusters were matched with fluency output of each participant. The time spent searching through semantic networks within clusters and switching to other clusters when locating and producing associated words were measured. RESULTS: Patients produced fewer words and spent more time switching to words within clusters and to different clusters than controls, but otherwise response profiles were similar. Although controls returned more frequently to clusters and consequently made more switches between these clusters than patients, this group difference disappeared when the total number of words produced was covaried. CONCLUSIONS: Consistent with previous literature, patients produced fewer words and made more errors than controls. The absence of a group difference in number of different clusters or mean number of items per cluster suggests that patients are similar to controls with respect to number of ideas in their semantic network. Patients' longer between-cluster switching times indicate a general slowness that may be attributed to difficulties finding new words within a semantic field.

Dementia with Lewy bodies: a pure case.

A pure case of autopsy-confirmed dementia with Lewy bodies (DLB) is described. The patient presented with distinctive verbal fluency deficits in the context of mild language impairment, intact recognition memory, and impaired paragraph recall. Neuroimaging (CT and SPECT) showed progressive medial temporal lobe atrophy. Neuropathology revealed Lewy bodies, degeneration in the substantia nigra, nucleus basalis of Meynert (Nakano & Hirano, 1984), and locus ceruleus, but no pathology characteristic of Alzheimer's disease. It is in this sense that the case is "pure" DLB. Early neuropsychological diagnosis of DLB is essential (Salmon et al., 1996) given the potentially fatal hazard of neuroleptics (McKeith et al., 1992) and the difficulties associated with clinical neurological diagnoses (Litvan et al., 1998).

Hypometria in Parkinson's disease: automatic versus controlled processing.

OBJECTIVES: The aim was to investigate whether patients with Parkinson's disease (PD) make movements that are of smaller amplitude when required to attend to a secondary task at the same time as performing a motor task. METHODS: Thirteen patients with idiopathic Parkinson's disease (mean age, 67.1 yrs) and 14 healthy control subjects (mean age, 66.2 yrs) were tested. The motor task was repeated opposition of the thumb and forefinger and the secondary task was a lexical decision task. RESULTS: The PD patients made hypometric movements, and the amplitude was further decreased when they performed the secondary task at the same time. There was no significant change for the control subjects. CONCLUSION: The unpaced motor task was less automatic for the PD patients than for the control subjects, and hence more subject to interference from a secondary task. We relate this to the underactivation of the supplementary motor cortex (SMA).

Micrographia in Parkinson's disease: the effect of providing external cues.

OBJECTIVE: To investigate whether micrographia in patients with Parkinson's disease is lessened either by giving visual targets or by continually reminding them that they should write with a normal amplitude. METHODS: Eleven patients with Parkinson's disease (mean age 65.4 years) were compared with 14 control subjects (mean age 67.1 years). The subjects wrote with a stylus on a graphics tablet. There were three conditions: free writing, writing with dots to indicate the required size, and writing with continuous verbal reminders ("big"). Each condition was performed twice. RESULTS: The patients wrote with a more normal amplitude when given either the visual cues or the auditory reminders. This improvement persisted when, shortly afterwards, the patients wrote freely without external cues. The increase in amplitude was achieved mainly by an increase in movement time rather than in peak velocity. CONCLUSION: Whereas the visual cues directly specified the required amplitude the auditory reminders did not. One effect of external cues is that they draw attention to the goal, and thus encourage the patients to write less automatically.

Word-retrieval in two cases of progressive supranuclear palsy.

In this paper, we describe the detailed neuropsychological investigation of two cases of progressive supranuclear palsy (PSP) and demonstrate word-finding difficulties associated with pervasive problems in word-retrieval. The pattern of deficits resembles that seen in Parkinson's Disease (PD) but is more severe, even in very mild PSP, and appears less amenable to cue facilitation. Performance on a variety of word-production tasks is compared, and experimental controls for motor effects on performance are included. The role of stimulus cues in speeded word-finding is addressed experimentally, as are central executive influences on task performance. This combines with functional brain-scan data from single photon emission computed tomography (SPECT) which shows reduced frontal perfusion in one of the two cases.

Semantic category word search impairment in schizophrenia.

Mechanisms of lexical retrieval within natural semantic categories are investigated in patients with schizophrenia. We predicted and found that schizophrenics show lexical retrieval impairments on word search tasks. Experiments are described in which subjects either scan through word lists for single target items (simple search), or search for members of a semantic category (semantic search). Two groups of subjects are employed: medicated schizophrenics, and a comparison group with similar age and premorbid intelligence. A significant between-group difference is reported (for both speed and accuracy) in semantic category search but not in simple search. It is known that many schizophrenic patients have word finding difficulties (Frith, 1992; Frith et al., 1991). Our results support the claim that in some schizophrenics at least, selective lexical-semantic parallel processing deficits may underlie word finding aberrations. It is possible that such dysfunctions reflect weakened connection strengths between units making up a lexical-semantic field (as characterised by proximity to a prototype).

Competitive inhibition models of lexical-semantic processing: experimental evidence.

A modified Neisser word-search (search II) was administered to patients with Parkinson's disease (PD), and significant deficits were found. Given the assumption that the processes are lexical, we interpret the results as support for the claim that there is competition between semantically related words in speech production (Wheeldon, 1989). A related verbal task-switching experiment (continuous series II) is also presented. Although PDs are impaired on task switching, there are double dissociations between verbal task switching (continuous series II) and lexical retrieval (search II). The relationship between performance on these tasks and on verbal fluency is also addressed.

Remote memory and lexical retrieval in a case of frontal Pick's disease.

OBJECTIVE: To examine the status of remote memory and lexical retrieval processes in a patient with frontal lobe-type dementia studied serially during an 18-month period. DESIGN: Longitudinal single-case study. SETTING: University hospital. PATIENT: A 67-year-old man presented to the hospital with progressive frontal lobe dysfunction confirmed by neuropsychological testing and single photon emission-computed tomographic scan. Postmortem brain examination demonstrated focal atrophy of the orbitofrontal region of the frontal lobe and medial temporal structures with abundant Pick's bodies and Pick's cells. MAIN OUTCOME MEASURES: Anterograde memory was assessed on a range of free recall and recognition tests using verbal and nonverbal material. Remote memory was assessed by Famous Faces and Famous Events tests and the Crovitz test of remote personal memory. Lexical retrieval was examined using initial-letter and semantic category-based fluency tasks. RESULTS: Initially there was a dissociation between anterograde memory, which was severely impaired, and relatively spared remote memory. Within retrograde memory there was evidence of selective difficulty in retrieving contextually rich and time-specific personal memories and in dating personal and public memories. In contrast, retrieval of names of famous persons and recognition of famous events was relatively normal. As the disease progressed, performance on all remote memory tests worsened, but without a temporally graded pattern. Lexical retrieval was markedly impaired and affected to an equivalent degree performance on initial-letter and category fluency tasks. CONCLUSION: These findings are interpreted in the context of a general retrieval deficit resulting from the interruption of frontostriatal circuits.

Retrieval from semantic and letter-initial categories in patients with Parkinson's disease.

We report the impaired performance by a group of 27 patients with Parkinson's disease (vs matched controls) on semantic and letter-initial verbal fluency tasks, carried out in both single and alternating category conditions. Individual differences in fluency were significantly correlated with confrontation picture naming scores in the patient group, but not in control subjects. However, the PD patients showed no significant correlation between verbal fluency scores, and rate of reciting days of the week as rapidly as possible. Both controls and patients produced more items when retrieving words from a single category than when alternately retrieving words from two categories. The magnitude of the decrement was nonetheless no greater in the patient than in the control population. This finding shows that "task switching" per se is not impaired in PD. We suggest that the verbal fluency deficit, while it may in part be attributed to motor-speech factors, primarily reflects an underlying cognitive disorder.

A case of foreign accent syndrome, with follow-up clinical, neuropsychological and phonetic descriptions.

We report a comparatively 'pure' case of 'foreign accent syndrome' (FAS) in a right-handed patient who sustained a small, isolated, left basal ganglia infarct. At 3 weeks post-onset FAS persisted in the absence of aphasic disorder. Phonetic analysis of the patient's speech was undertaken at that time and a further, more detailed acoustic and phonetic investigation, was undertaken at 8 months. The validity and significance of the term 'FAS' is discussed.