Biology subjects

Raaf, N.

Publications and source records attributed to Raaf, N..

2 recordsLinked to original sources

bioRxiv2026

Striatal Dopaminergic Dysfunction Constrains Motor Invigoration in Parkinson's Disease

Bradykinesia is a cardinal motor feature of Parkinson's disease and is characterised by a reduced ability to generate movements with normal speed and force. Although nigrostriatal dopamine loss is regarded as the primary cause, direct human evidence linking dopaminergic degeneration to striatal dysfunction and impaired motor output and vigour remains limited. To investigate this relationship, we developed a grip-force paradigm that quantified movement vigour as the ability to rapidly generate force. Fifty-three individuals with Parkinson's disease, 30 with levodopa-induced dyskinesia and 23 without, and 25 age-matched healthy controls performed the task during 3T functional MRI. Thirty-five patients additionally underwent dopamine transporter PET imaging to assess associations among nigrostriatal dopaminergic integrity, striatal activity and motor performance. Patients with Parkinson's disease showed marked reductions in initial movement vigour accompanied by reduced bilateral putaminal activation during force generation. Lower putaminal dopamine transporter binding was associated with both poorer movement vigour and weaker grip-related putaminal activation during functional MRI, establishing a direct link between nigrostriatal degeneration, impaired striatal recruitment and motor slowing. Functional MRI further revealed reduced reward-related responses in the nucleus accumbens. Across participants, stronger reward-related ventral striatal activity was associated with greater movement vigour, suggesting that motivational processes contribute independently to motor performance. Patients with levodopa-induced dyskinesia exhibited more severe putaminal dopaminergic denervation than patients without dyskinesia but showed no additional impairment of movement vigour or striatal task responses. These findings provide direct in vivo evidence that dorsal nigrostriatal dopaminergic degeneration constrains movement vigour in Parkinson's disease through reduced striatal recruitment during action generation. Impaired reward-related signalling in ventral striatum emerges as an additional, partly independent mechanism influencing motor performance, highlighting distinct motor and motivational contributions to bradykinesia.

neuroscience↗

bioRxiv2022

Hand preference and the corpus callosum: Is there really no association?

Originating from a series of morphometric studies conducted in the 1980s, it appears a widely held belief in cognitive neuroscience that the corpus callosum is larger in non-right handers than in right handers (RH). However, a recent meta-analysis challenges this belief by not finding significant differences in corpus callosum size between handedness groups. Yet, relying on the available published data, the meta-analysis was not able to account for a series of factors potential influencing its outcome, such as confounding effects of brain size differences and a restricted spatial resolution of previous callosal segmentation strategies. To address these remaining questions, we here analysed the midsagittal corpus callosum of N = 1057 participants from the Human Connectome Project (HCP 1200 Young Adults) to compare handedness groups based on consistency (e.g., consistent RH vs. mixed handers, MH) and direction of hand preference (e.g., RH vs. left handers). A possible relevance of brain-size differences was addressed by analysing callosal variability by both using forebrain volume (FBV) as covariate and utilising relative area (callosal area/thickness divided by FBV) as dependent variable. Callosal thickness was analysed at 100 measuring points along the structure to achieve high spatial resolution to detect subregional effects. However, neither of the conducted analyses was able to find significant handedness-related differences in callosal and the respective effect-sizes estimates were small. For example, comparing MH and consistent RH, the effect sizes for difference in callosal area were below a Cohens d = 0.1 (irrespective of how FBV was included), and narrow confidence intervals allowed to exclude effects above |d| = 0.2. Analysing thickness, effect sizes were below d = 0.2 with confidence intervals not extending above |d| = 0.3. In this, the possible range of population effect sizes of hand preference on callosal morphology appears well below the effects commonly reported for factors like age, sex, or brain size. Effects on cognition or behaviour accordingly can be considered small, questioning the common practise to attribute performance differences between handedness groups to differences in callosal architecture.

neuroscience↗