How Many Subjects Constitute a Study?
ABSTRACT In fMRI there are two classes of inference: one aims to make a comment about the "typical" characteristics of a population, and the other about "average" characteristics. The first pertains to studies of normal subjects that try to identify some qualitative aspect of normal functional anatomy. The second class necessarily applies to clinical neuroscience studies that want to make an inference about quantitative differences of a regionally specific nature. The first class of inferences is adequately serviced by conjunction analyses and fixed-effects models with relatively small numbers of subjects. The second requires random-effect analyses and larger cohorts.
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ABSTRACT: One working hypothesis behind transsexuality is that the normal sex differentiation of certain hypothalamic networks is altered. We tested this hypothesis by investigating the pattern of cerebral activation in 12 nonhomosexual male-to-female transsexuals (MFTRs) when smelling 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST). These steroids are reported to activate the hypothalamic networks in a sex-differentiated way. Like in female controls the hypothalamus in MFTRs activated with AND, whereas smelling of EST engaged the amygdala and piriform cortex. Male controls, on the other hand, activated the hypothalamus with EST. However, when restricting the volume of interest to the hypothalamus activation was detected in MFTR also with EST, and explorative conjunctional analysis revealed that MFTR shared a hypothalamic cluster with women when smelling AND, and with men when smelling EST. Because the EST effect was limited, MFTR differed significantly only from male controls, and only for EST-AIR and EST-AND. These data suggest a pattern of activation away from the biological sex, occupying an intermediate position with predominantly female-like features. Because our MFTRs were nonhomosexual, the results are unlikely to be an effect of sexual practice. Instead, the data implicate that transsexuality may be associated with sex-atypical physiological responses in specific hypothalamic circuits, possibly as a consequence of a variant neuronal differentiation.Cerebral Cortex 09/2008; 18(8):1900-8. DOI:10.1093/cercor/bhm216 · 8.31 Impact Factor
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ABSTRACT: We used functional magnetic resonance imaging in 18 normal volunteers to determine whether there is separate representation of syntactic, semantic, and verbal working memory processing in the left inferior frontal gyrus (GFi). We compared a sentence comprehension task with a short-term memory maintenance task to identify syntactic and semantic processing regions. To investigate the effects of syntactic and verbal working memory load while minimizing the differences in semantic processes, we used comprehension tasks with garden-path (GP) sentences, which require re-parsing, and non-garden-path (NGP) sentences. Compared with the short-term memory task, sentence comprehension activated the left GFi, including Brodmann areas (BAs) 44, 45, and 47, and the left superior temporal gyrus. In GP versus NGP sentences, there was greater activity in the left BAs 44, 45, and 46 extending to the left anterior insula, the pre-supplementary motor area, and the right cerebellum. In the left GFi, verbal working memory activity was located more dorsally (BA 44/45), semantic processing was located more ventrally (BA 47), and syntactic processing was located in between (BA 45). These findings indicate a close relationship between semantic and syntactic processes, and suggest that BA 45 might link verbal working memory and semantic processing via syntactic unification processes.Neuroscience Research 08/2008; 61(3):309-18. DOI:10.1016/j.neures.2008.03.013 · 2.15 Impact Factor
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ABSTRACT: In this functional magnetic resonance imaging (fMRI) study, we examined changes--relative to healthy controls--in the cortical activation and connectivity patterns of two patients who had undergone unilateral heterotopic hand replantation. The study involved the patients and a group of control subjects performing visually paced hand movements with their left, right, or both hands. Changes of effective connectivity among a bilateral network of core motor regions comprising M1, lateral premotor cortex (PMC), and the supplementary motor area (SMA) were assessed using dynamic causal modelling. Both patients showed inhibition of ipsilateral PMC and SMA when moving the healthy hand, potentially indicating a suppression of inference with physiological motor execution by the hemisphere controlling the replanted hand. Moving the replanted hand, both patients showed increased activation of contralateral PMC, most likely reflecting the increased effort involved, and a pathological inhibition of the ipsilateral on the active contralateral M1 indicative of an unsuccessful modulation of the inhibitory M1-M1 balance. In one patient, M1 contralateral to the replanted hand experienced increased tonic (intrinsic connectivity) and phasic (replanted hand movement) facilitating input, whereas in the other, pathological suppression was present. These differences in effective connectivity correlated with decreased behavioural performance of the latter as assessed by kinematic analysis, and seemed to be related to earlier and more intense rehabilitative exercise commenced by the former. This study hence demonstrates the potential of functional neuroimaging to monitor plastic changes of cortical connectivity due to peripheral damage and recovery in individual patients, which may prove to be a valuable tool in understanding, evaluating and enhancing motor rehabilitation.Experimental Neurology 08/2008; 212(1):132-44. DOI:10.1016/j.expneurol.2008.03.025 · 4.62 Impact Factor