Background: Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disorders, fibromyalgia, irritable bowel syndrome and temporomandibular joint disorder. However, the neural underpinnings of these associations still remain unclear. This study explored brain responses to facial visual stimuli with emotional cues using fMRI techniques in general population with different ranges of hypermobility.Methods: Fifty-one non-clinical volunteers (33 women) completed state and trait anxiety questionnaire measures, were assessed with a clinical examination for hypermobility (Beighton system) and performed an emotional face processing paradigm during functional neuroimaging.Results: Trait anxiety scores did significantly correlate with both state anxiety and hypermobility scores. BOLD signals of the hippocampus did positively correlate with hypermobility scores for the crying faces versus neutral faces contrast in ROI analyses. No results were found for any of the other studied ROIs. Additionally, hypermobility scores were also associated with other key affective processing areas (i.e. the middle and anterior cingulate gyrus, fusiform gyrus, parahippocampal region, orbitofrontal cortex and cerebellum) in the whole brain analysis.Conclusions: Hypermobility scores are associated with trait anxiety and higher brain responses to emotional faces in emotion processing brain areas (including hippocampus) described to be linked to anxiety and somatic symptoms. These findings increase our understanding of emotion processing in people bearing this heritable variant of collagen and the mechanisms through which vulnerability to anxiety and somatic symptoms arises in this population.

Functional magnetic resonance imaging (fMRI) in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.31 ± 4.07 years. Before and after the intervention program, the body mass index (BMI) (kg/m²) was 38.15 ± 4.7 vs. 34.18 ± 4.5 (p < 0.02), and body weight (kg) was 98.5 ± 13.1 vs. 88.28 ± 12.2 (p < 0.03). All subjects underwent a pre- and post-intervention fMRI under fasting conditions. Functional connectivity was assessed using seed-based correlations. After the intervention, we found decreased connectivity between the left inferior parietal cortex and the right temporal cortex (p < 0.001), left posterior cingulate (p < 0.001), and right posterior cingulate (p < 0.03); decreased connectivity between the left superior frontal gyrus and the right temporal cortex (p < 0.01); decreased connectivity between the prefrontal cortex and the somatosensory cortex (p < 0.025); and decreased connectivity between the left and right posterior cingulate (p < 0.04). Results were considered significant at a voxel-wise threshold of p ≤ 0.05, and a cluster-level family-wise error correction for multiple comparisons of p ≤ 0.05. In conclusion, functional connectivity between brain structures involved in the pathophysiology of obesity (the inferior parietal lobe, posterior cingulate, temporo-insular cortex, prefrontal cortex) may be modified by a weight loss program including a Mediterranean diet and physical exercise.

Donepezil (DP), a cognitive-enhancing drug targeting the cholinergic system, combined with massed sentence repetition training augmented and speeded up recovery of speech production deficits in patients with chronic conduction aphasia and extensive left hemisphere infarctions (Berthier et al., 2014). Nevertheless, a still unsettled question is whether such improvements correlate with restorative structural changes in grey matter and white matter pathways mediating speech production. In the present study, we used pharmacological magnetic resonance imaging (phMRI) to study treatment-induced brain changes in grey matter and white matter tracts in a right-handed male with chronic conduction aphasia and a right subcortical lesion (crossed aphasia). A single-patient, open-label multiple-baseline design incorporating two different treatments and two posttreatment evaluations was used. The patient received an initial dose of DP (5 mg/day) which was maintained during 4 weeks and then titrated up to 10 mg/day and administered alone (without aphasia therapy) during 8 weeks (Endpoint 1). Thereafter, the drug was combined with an audiovisual repetition-imitation therapy (Look-Listen-Repeat - LLR) during 3 months (Endpoint 2). Language evaluations, diffusion weighted imaging (DWI) and voxel-based morphometry (VBM) were performed at baseline and at both endpoints in JAM and once in 21 healthy control males. Treatment with DP alone and combined with LLR therapy induced marked improvement in aphasia and communication deficits as well as in selected measures of connected speech production, and phrase repetition. The obtained gains in speech production remained well-above baseline scores even four months after ending combined therapy. Longitudinal DWI showed structural plasticity in the right frontal aslant tract and direct segment of the arcuate fasciculus with both interventions. VBM revealed no structural changes in other white matter tracts nor in cortical areas linked by these tracts. In conclusion, cholinergic potentiation alone and combined with a model-based aphasia therapy improved language deficits by promoting structural plastic changes in right white matter tracts.

Foreign accent syndrome (FAS) is a speech disorder that is defined by the emergence of a peculiar manner of articulation and intonation which is perceived as foreign. In most cases of acquired FAS (AFAS) the new accent is secondary to small focal lesions involving components of the bilaterally distributed neural network for speech production. In the past few years FAS has also been described in different psychiatric conditions (conversion disorder, bipolar disorder, schizophrenia) as well as in developmental disorders (specific language impairment, apraxia of speech). In the present study, two adult males, one with atypical phonetic production and the other one with cluttering, reported having developmental FAS (DFAS) since their adolescence. Perceptual analysis by naïve judges could not confirm the presence of foreign accent, possibly due to the mildness of the speech disorder. However, detailed linguistic analysis provided evidence of prosodic and segmental errors previously reported in AFAS cases. Cognitive testing showed reduced communication in activities of daily living and mild deficits related to psychiatric disorders. Psychiatric evaluation revealed long-lasting internalizing disorders (neuroticism, anxiety, obsessive-compulsive disorder, social phobia, depression, alexithymia, hopelessness, and apathy) in both subjects. Diffusion tensor imaging (DTI) data from each subject with DFAS were compared with data from a group of 21 age- and gender-matched healthy control subjects. Diffusion parameters (MD, AD, and RD) in predefined regions of interest showed changes of white matter microstructure in regions previously related with AFAS and psychiatric disorders. In conclusion, the present findings militate against the possibility that these two subjects have FAS of psychogenic origin. Rather, our findings provide evidence that mild DFAS occurring in the context of subtle, yet persistent, developmental speech disorders may be associated with structural brain anomalies. We suggest that the simultaneous involvement of speech and emotion regulation networks might result from disrupted neural organization during development, or compensatory or maladaptive plasticity. Future studies are required to examine whether the interplay between biological trait-like diathesis (shyness, neuroticism) and the stressful experience of living with mild DFAS lead to the development of internalizing psychiatric disorders.

Background: Mitigated echolalia (ME) is a symptom of aphasia which refers to a seemingly deliberate repetition of just-heard words and phrase fragments. ME has historically been viewed as a compensatory strategy aimed to strengthen auditory comprehension. Nevertheless, this hypothesis and other possible functional deficits underlying ME have not been evaluated so far. Aims: This study aimed to (a) reappraise ME in the frame of modern neuroscience; (b) report the effects of Constraint-Induced Aphasia Therapy (CIAT) and a cognition-enhancing drug (memantine) on detrimental ME in a patient (CCR) with fluent aphasia; and (c) analyse the functional and structural brain correlates of ME in CCR with multimodal neuroimaging. Methods & Procedure: Tasks tapping verbal expression and auditory comprehension were administered to CCR to evaluate ME. After baseline testing, evaluations were performed under placebo alone (weeks 0–16), combined placebo with CIAT (weeks 16–18), placebo treatment alone (weeks 18–20), washout (weeks 20–24) and memantine (weeks 24–48). Instructions to reduce ME during CIAT were provided to CCR. Language evaluation and multimodal neuroimaging were also performed 10 years after ending treatment. Outcomes & Results: At baseline, ME occurred in spontaneous speech and in difficult-to-understand single words, indicating impaired meaning access. However, more instances of ME were heard in sentence comprehension, reflecting additional impairment in short-term memory. ME also occurred in words that were correctly defined and understood to the extent that even after accessing word meaning successfully, CCR repeated the same word several times, suggesting impaired inhibitory response control. In comparison with baseline, analysis of auditory sentence comprehension under treatment revealed significant decrements of ME just after ending CIAT and 2 weeks later. These gains were maintained under memantine 6 months later. No changes in ME were found during both placebo and washout phases. Instructions to constrain ME reduced the time to complete a sentence comprehension task 2 weeks after CIAT. ME returned to baseline levels 10 years later. Multimodal imaging suggested that ME in CCR resulted from residual activity of remnants of the left dorsal stream and the intact right white matter tracts after extensive damage to the left ventral stream. Conclusions: ME in CCR interfered with functional communication, and it may be attributed to deficits in sound-meaning mapping, auditory short-term memory, attentional control, and inhibition of repetition mechanisms. Our preliminary evidence suggests that ME, in patients like CCR, may be modulated with specific instructions during aphasia therapy and drugs.