Publications

Abstract

The field of neuroanatomy of language is moving forward at a fast pace. This
progression is partially due to the development of diffusion tractography, which
has been used to describe white matter connections in the living human brain.
For the field of neurolinguistics this advancement is timely and important for
two reasons. First, it allows clinical researchers to liberate themselves from
neuroanatomical models of language derived from animal studies. Second, for
the first time, it offers the possibility of testing network correlates of
neurolinguistic models directly in the human brain. This chapter introduces the
reader to general principles of diffusion imaging and tractography. Examples of
its applications, such as tract analysis, will be used to explicate its potentials and
limitations.

Abstract

Our understanding of the functioning of the brain is primarily based on an average model of the brain's functional organisation, and any deviation from the standard is considered as random noise or a pathological appearance. Studying pathologies has, however, greatly contributed to our understanding of brain functions. For instance, the study of naturally-occurring or surgically-induced brain lesions revealed that language is predominantly lateralised to the left hemisphere while perception/action and emotion are commonly lateralised to the right hemisphere. The lateralisation of function was subsequently replicated by task-related functional neuroimaging in the healthy population. Despite its high significance and reproducibility, this pattern of lateralisation of function is true for most, but not all participants. Bilateral and flipped representations of classically lateralised functions have been reported during development and in the healthy adult population for language, perception/action and emotion. Understanding these different functional representations at an individual level is crucial to improve the sophistication of our models and account for the variance in developmental trajectories, cognitive performance differences and clinical recovery. With the availability of in vivo neuroimaging, it has become feasible to study large numbers of participants and reliably characterise individual differences, also referred to as phenotypes. Yet, we are at the beginning of inter-individual variability modelling, and new theories of brain function will have to account for these differences across participants.

Abstract

The possible role of emotion in anosognosia for hemiplegia (i.e., denial of motor deficits contralateral to a brain lesion), has long been debated between psychodynamic and neurocognitive theories. However, there are only a handful of case studies focussing on this topic, and the precise role of emotion in anosognosia for hemiplegia requires empirical investigation. In the present study, we aimed to investigate how negative and positive emotions influence motor awareness in anosognosia. Positive and negative emotions were induced under carefully-controlled experimental conditions in right-hemisphere stroke patients with anosognosia for hemiplegia (n = 11) and controls with clinically normal awareness (n = 10). Only the negative, emotion induction condition resulted in a significant improvement of motor awareness in anosognosic patients compared to controls; the positive emotion induction did not. Using lesion overlay and voxel-based lesion-symptom mapping approaches, we also investigated the brain lesions associated with the diagnosis of anosognosia, as well as with performance on the experimental task. Anatomical areas that are commonly damaged in AHP included the right-hemisphere motor and sensory cortices, the inferior frontal cortex, and the insula. Additionally, the insula, putamen and anterior periventricular white matter were associated with less awareness change following the negative emotion induction. This study suggests that motor unawareness and the observed lack of negative emotions about one's disabilities cannot be adequately explained by either purely motivational or neurocognitive accounts. Instead, we propose an integrative account in which insular and striatal lesions result in weak interoceptive and motivational signals. These deficits lead to faulty inferences about the self, involving a difficulty to personalise new sensorimotor information, and an abnormal adherence to premorbid beliefs about the body.

Abstract

Stroke-induced aphasia is associated with adverse effects on quality of life and the ability to return to work. For patients and clinicians the possibility of relying on valid predictors of recovery is an important asset in the clinical management of stroke-related impairment. Age, level of education, type and severity of initial symptoms are established predictors of recovery. However, anatomical predictors are still poorly understood. In this prospective longitudinal study, we intended to assess anatomical predictors of recovery derived from diffusion tractography of the perisylvian language networks. Our study focused on the arcuate fasciculus, a language pathway composed of three segments connecting Wernicke’s to Broca’s region (i.e. long segment), Wernicke’s to Geschwind’s region (i.e. posterior segment) and Broca’s to Geschwind’s region (i.e. anterior segment). In our study we were particularly interested in understanding how lateralization of the arcuate fasciculus impacts on severity of symptoms and their recovery. Sixteen patients (10 males; mean age 60 ± 17 years, range 28–87 years) underwent post stroke language assessment with the Revised Western Aphasia Battery and neuroimaging scanning within a fortnight from symptoms onset. Language assessment was repeated at 6 months. Backward elimination analysis identified a subset of predictor variables (age, sex, lesion size) to be introduced to further regression analyses. A hierarchical regression was conducted with the longitudinal aphasia severity as the dependent variable. The first model included the subset of variables as previously defined. The second model additionally introduced the left and right arcuate fasciculus (separate analysis for each segment). Lesion size was identified as the only independent predictor of longitudinal aphasia severity in the left hemisphere [beta = −0.630, t(−3.129), P = 0.011]. For the right hemisphere, age [beta = −0.678, t(–3.087), P = 0.010] and volume of the long segment of the arcuate fasciculus [beta = 0.730, t(2.732), P = 0.020] were predictors of longitudinal aphasia severity. Adding the volume of the right long segment to the first-level model increased the overall predictive power of the model from 28% to 57% [F(1,11) = 7.46, P = 0.02]. These findings suggest that different predictors of recovery are at play in the left and right hemisphere. The right hemisphere language network seems to be important in aphasia recovery after left hemispheric stroke.

Abstract

Background Stroke-induced aphasia is associated with adverse effects on quality of life and the ability to return to work. However, the predictors of recovery are still poorly understood. Anatomical variability of the arcuate fasciculus, connecting Broca’s and Wernicke’s areas, has been reported in the healthy population using diffusion tensor imaging tractography. In about 40% of the population the arcuate fasciculus is bilateral and this pattern is advantageous for certain language related functions, such as auditory verbal learning (Catani et al. 2007). Methods In this prospective longitudinal study, anatomical predictors of post-stroke aphasia recovery were investigated using diffusion tractography and arterial spin labelling. Patients An 18-subject strong aphasia cohort with first-ever unilateral left hemispheric middle cerebral artery infarcts underwent post stroke language (mean 5±5 days) and neuroimaging (mean 10±6 days) assessments and neuropsychological follow-up at six months. Ten of these patients were available for reassessment one year after symptom onset. Aphasia was assessed with the Western Aphasia Battery, which provides a global measure of severity (Aphasia Quotient, AQ). Results Better recover from aphasia was observed in patients with a right arcuate fasciculus [beta=.730, t(2.732), p=.020] (tractography) and increased fractional anisotropy in the right hemisphere (p<0.05) (Tract-based spatial statistics). Further, an increase in left hemisphere perfusion was observed after one year (p<0.01) (perfusion). Lesion analysis identified maximal overlay in the periinsular white matter (WM). Lesion-symptom mapping identified damage to periinsular structure as predictive for overall aphasia severity and damage to frontal lobe white matter as predictive of repetition deficits. Conclusion These findings suggest an important role for the right hemisphere language network in recovery from aphasia after left hemispheric stroke.

Abstract

The occipital and frontal lobes are anatomically distant yet functionally highly integrated to generate some of the most complex behaviour. A series of long associative fibres, such as the fronto-occipital networks, mediate this integration via rapid feed-forward propagation of visual input to anterior frontal regions and direct top–down modulation of early visual processing.

Despite the vast number of anatomical investigations a general consensus on the anatomy of fronto-occipital connections is not forthcoming. For example, in the monkey the existence of a human equivalent of the ‘inferior fronto-occipital fasciculus’ (iFOF) has not been demonstrated. Conversely, a ‘superior fronto-occipital fasciculus’ (sFOF), also referred to as ‘subcallosal bundle’ by some authors, is reported in monkey axonal tracing studies but not in human dissections.

In this study our aim is twofold. First, we use diffusion tractography to delineate the in vivo anatomy of the sFOF and the iFOF in 30 healthy subjects and three acallosal brains. Second, we provide a comprehensive review of the post-mortem and neuroimaging studies of the fronto-occipital connections published over the last two centuries, together with the first integral translation of Onufrowicz's original description of a human fronto-occipital fasciculus (1887) and Muratoff's report of the ‘subcallosal bundle’ in animals (1893).

Our tractography dissections suggest that in the human brain (i) the iFOF is a bilateral association pathway connecting ventro-medial occipital cortex to orbital and polar frontal cortex, (ii) the sFOF overlaps with branches of the superior longitudinal fasciculus (SLF) and probably represents an ‘occipital extension’ of the SLF, (iii) the subcallosal bundle of Muratoff is probably a complex tract encompassing ascending thalamo-frontal and descending fronto-caudate connections and is therefore a projection rather than an associative tract.

In conclusion, our experimental findings and review of the literature suggest that a ventral pathway in humans, namely the iFOF, mediates a direct communication between occipital and frontal lobes. Whether the iFOF represents a unique human pathway awaits further ad hoc investigations in animals.

Abstract

Introduction

The atlas by Heinrich Sachs (1892) provided an accurate description of the intralobar fibres of the occipital lobe, with a detailed representation of the short associative tracts connecting different parts of the lobe. Little attention has been paid to the work of Sachs since its publication. In this study, we present the results of the dissection of three hemispheres, performed according to the Klingler technique (1935). Our anatomical findings are then compared to the original description of the occipital fibres anatomy as detailed by Sachs.
Methods

Three hemispheres were dissected according to Klingler's technique (1935). Specimens were fixed in 10% formalin and frozen at −15 °C for two weeks. After defreezing, dissection of the white matter fibres was performed with blunt dissectors. Coronal sections were obtained according to the cuts originally described by Sachs. In addition, medial to lateral and lateral to medial dissection of the white matter of the occipital lobe was also performed.

Results

A network of short association fibres was demonstrated in the occipital lobe, comprising intralobar association fibres and U-shaped fibres, which are connecting neighbouring gyri. Lateral to the ventricles, longitudinal fibres of the stratum sagittale were also identified that are arranged as external and internal layers. Fibres of the forceps major were also found to be in direct contact with the ventricular walls. We were able to replicate all tracts originally described by Sachs. In addition, a previously unrecognised tract, connecting the cuneus to the lingual gyrus, was identified. This tract corresponds to the “sledge runner”, described in tractography studies.

Conclusions

The occipital lobe shows a rich network of intralobar fibres, arranged around the ventricular wall. Good concordance was observed between the Klingler dissection technique and the histological preparations of Sachs.

Abstract

Last year was the 150th anniversary of Paul Broca's landmark case report on speech disorder that paved the way for subsequent studies of cortical localization of higher cognitive functions. However, many complex functions rely on the activity of distributed networks rather than single cortical areas. Hence, it is important to understand how brain regions are linked within large-scale networks and to map lesions onto connecting white matter tracts. To facilitate this network approach we provide a synopsis of classical neurological syndromes associated with frontal, parietal, occipital, temporal and limbic lesions. A review of tractography studies in a variety of neuropsychiatric disorders is also included. The synopsis is accompanied by a new atlas of the human white matter connections based on diffusion tensor tractography freely downloadable on http://www.natbrainlab.com. Clinicians can use the maps to accurately identify the tract affected by lesions visible on conventional CT or MRI. The atlas will also assist researchers to interpret their group analysis results. We hope that the synopsis and the atlas by allowing a precise localization of white matter lesions and associated symptoms will facilitate future work on the functional correlates of human neural networks as derived from the study of clinical populations. Our goal is to stimulate clinicians to develop a critical approach to clinico-anatomical correlative studies and broaden their view of clinical anatomy beyond the cortical surface in order to encompass the dysfunction related to connecting pathways.