ObjectiveAmplitude decrease of cortical responses after repeated stimuli (‘habituation’) is a wel... more ObjectiveAmplitude decrease of cortical responses after repeated stimuli (‘habituation’) is a well-known phenomenon, the functional meaning of which is to prevent sensory overflow and to save resources for meaningful and novel stimuli. It is known that the primary low-frequency N20 somatosensory evoked potential (SEP) undergoes habituation in healthy subjects. By contrast, the presence of this phenomenon has never been tested
It has been demonstrated that the early part of 600 Hz High Frequency Oscillations (HFOs), probab... more It has been demonstrated that the early part of 600 Hz High Frequency Oscillations (HFOs), probably generated in the terminal part of thalamo-cortical somatosensory radiations, are abnormally reduced between attacks in migraineurs. We aimed at verifying whether spontaneous clinical fluctuations in migraine are correlated to HFO changes. We recorded somatosensory evoked potentials in 28 migraine patients. Clinical fluctuations (number of attacks in the 6 months preceding and following the test) were correlated to the HFOs' amplitudes. Moreover, eight out of 28 patients underwent a longer follow-up, including HFO control and clinical observation during the 12 months following the baseline recording. The amplitude of early presynaptic HFOs was significantly correlated to the clinical evolution, since spontaneous worsening was associated with reduced presynaptic HFOs, whereas spontaneous improvement was associated with enhanced presynaptic HFOs (correlation test, p<0.05). No correlation was found between the amplitude of postsynaptic HFOs and clinical fluctuations. Patients undergoing longer follow-up showed substantially unchanged HFOs, accordingly with their stable clinical condition. HFOs' enhancement in spontaneously improved patients can reflect the increased activity of brainstem arousal related structures, which in turn increases the thalamo-cortical drive and the cortical lateral inhibition mediated by GABAergic interneurons. HFOs' recording could represent a useful tool in the functional assessment of migraine.
Amplitude decrease of cortical responses after repeated stimuli (&amp... more Amplitude decrease of cortical responses after repeated stimuli ('habituation') is a well-known phenomenon, the functional meaning of which is to prevent sensory overflow and to save resources for meaningful and novel stimuli. It is known that the primary low-frequency N20 somatosensory evoked potential (SEP) undergoes habituation in healthy subjects. By contrast, the presence of this phenomenon has never been tested in High Frequency Oscillations (HFOs), which probably reflect the activity of a somatosensory arousal system. We recorded SEPs after right median nerve stimulation in 19 healthy volunteers. Six consecutive series of 500 sweeps were collected and averaged at a repetition rate of 5 Hz. SEPs were recorded by means of Erb'point-to-Fz, Cv6-to-AC and P3-to-F3 arrays. P3-to-F3 recording further underwent narrow-bandpass (400-800 Hz) digital filtering to selectively analyse high-frequency components. Statistical analysis revealed a significant amplitude decrease of the primary N20 LF-SEP between the first and sixth block of stimuli. By contrast, HFO amplitudes remained substantially unchanged throughout the whole procedure. Differently from the N20 LF-SEP, scalp-recorded HFOs do not undergo habituation. Our findings reinforce the view that HFOs reflect the activity of an arousal somatosensory system, which is able to signal novel stimuli, the relevance of which points out high synaptic efficacy.
Neuropsychological investigations have consistently shown that frontal cortices are relevant in p... more Neuropsychological investigations have consistently shown that frontal cortices are relevant in processing temporal and sequential features of actions. However, one of the main theoretical issues that has been discussed in the last 25 years is whether these brain areas store some abstract representations of actions or, conversely, act upon action representations stored within other posterior associative cortices. We administered to
Neuropsychological consequences of stimulation of the subthalamic nucleus for treatment of drug-r... more Neuropsychological consequences of stimulation of the subthalamic nucleus for treatment of drug-resistant Parkinson's disease (PD) have been studied previously. However, no detailed investigations of linguistic function modifications have been carried out. We studied four consecutive patients with PD who underwent chronic bilateral stimulation of the subthalamic nuclei. Neuropsychological and linguistic evaluations were performed before and 2 weeks after surgery. Linguistic abilities were studied also 1 year after surgery with stimulators both off and on. Intraphrasal hesitation pauses, phonemic paraphasias and morpho-syntactic errors were significantly reduced and lexical retrieval improved with stimulation of the subthalamic nuclei. Implicit linguistic phenomena, mainly occurring within basal ganglia circuitry, benefited by recovery of functional equilibrium within basal nuclei and between overall basal ganglia circuitry and cerebral cortex.
Conclusion Verbal communication impairments frequently follow damage to the right cerebral hemis... more Conclusion Verbal communication impairments frequently follow damage to the right cerebral hemisphere. These deficits are usually underestimated because RHD patients are not routinely referred to speech therapists. The nature of pragmatic disorders in verbal communication in RHD patients still remains to be clarified. In particular, it is still unclear whether these impairments are language-specific or attention-specific (e.g. an attentional deficit with
Background : The field of pragmatic impairments of verbal communication in cerebrally damaged sub... more Background : The field of pragmatic impairments of verbal communication in cerebrally damaged subjects dates back almost three decades. However, a systematic investigation of pragmatic competences has never been completed in a large sample of normal adults controlling for age and education factors. Aims : We aimed to examine the effects of age and education on the main features of
Mutations in the progranulin gene (GRN) were recently identified as an important cause of familia... more Mutations in the progranulin gene (GRN) were recently identified as an important cause of familial frontotemporal dementia (FTD). More than 60 pathogenic mutations have been reported up to now and prominent phenotypic variability within and among affected kindreds has been described. We have studied an Italian family with clinical evidence of dementia, and here we report detailed clinical records, imaging, sequential neurological examinations, cognitive assessments, and genetic analysis of three affected members of the same generation. Genetic analysis revealed the presence of the null mutation IVS6 + 5_8delGTGA in GRN, leading to haploinsufficiency, as documented by mRNA analysis. The mutation is associated with wide variation of the clinical phenotype, ranging from FTD to Alzheimer's disease and to a rapidly-progressive dementia. In summary, the patients of this kindred showed highly variable clinical features that do not have a close correspondence with the pattern of the cer...
BackgroundA combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DW... more BackgroundA combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism.
Terminal and interstitial deletions of 2p25.3 (size < Mb), detected by array-CGH analysis, hav... more Terminal and interstitial deletions of 2p25.3 (size < Mb), detected by array-CGH analysis, have been reported in about 18 patients sharing common clinical features represented by early-onset obesity/ overweightness associated with intellectual disabilities (ID) and behavioural troubles. This observations led to hypothesize that 2p subtelomeric deletion should be associated with syndromic obesity and MYT1L became the main candidate gene for ID and obesity since it is deleted or disrupted in all hitherto published cases. Here we described a 2p25.3 de novo terminal deletion of 1.9 Mb, of paternal origin, detected by array-CGH analysis in a girl of 4.4 years with a distinctive phenotype consisting of early-onset of obesity associated with moderate ID, and hyperkinetic disorder. The deletion disrupted MYT1L and encompassed five other OMIM genes, ACP1, TMEM18, SNTG2, TPO, and PXDN. Here, we discuss the combined functional effects of additional haploinsufficient genes, that may concur w...
Clinical neurolinguistics still lacks consolidated and standardised tools for the assessment of i... more Clinical neurolinguistics still lacks consolidated and standardised tools for the assessment of impairments of pragmatics of verbal communication. In the present paper we present norms of the Italian version of the Right Hemisphere Language Battery (Batteria del Linguaggio dell’Emisfero Destro, BaLED) [1] originally devised by Bryan [2]. The normative study has been conducted with the recruitment of 440 healthy subjects. The battery of tests was not intended to be cognitively oriented, by providing evidence of the cognitive impairments underpinning verbal pragmatic deficits; on the contrary, it permits the detection of the presence/absence of impairments in processing the main pragmatic features of verbal communication traditionally associated with right hemisphere lesions. Thus, apart from being a clinical tool for diagnosing pragmatic impairments of verbal communication, the BaLED represents a useful initial battery of tests for clinical assessment and for selecting specific popul...
24 Italian medical students performed a task of verbal fluency. 12 students (the control group) r... more 24 Italian medical students performed a task of verbal fluency. 12 students (the control group) receiving Normal Auditory Feedback and 12 students receiving Delayed Auditory Feedback (delay of 200 msec.) performed six trials in six different experimental settings: normal or increased speaking rate, and, for each condition, once with bilateral input of the auditory feedback, once to the right ear, and once to the left ear. At the normal speaking rate, the disruptive effect of delayed feedback was confirmed. As the speaking rate increased, the total number of errors increased within the control group but decreased within the group given delayed feedback, although the total number of errors was always greater for the latter. In addition, speech was more disrupted when the auditory input was returned to the right ear (left hemisphere) for all the different conditions: Normal and Delayed Auditory Feedback, normal and increased speaking rate. In particular, the left hemisphere was less resistant to the disruptive effect of the delayed feedback than the right hemisphere. From these results, we suggest that, when speaking more quickly, one uses more central mechanisms of movement programming (cortical-cerebellum-thalamus-cortical, cortical-corpus striatum-thalamus-cortical, and cortical-thalamus-cortical circuits), or attentional control (cortico-reticular-cortical circuits) than peripheral mechanisms (tactile, proprioceptive, and acoustic circuits). This may explain the decreased disruptive influence of delayed auditory feedback on speed, fluency, and quality at increased speaking rates. Hemispheric specialization processes, however, may explain the more pronounced susceptibility of the left hemisphere or the less pronounced susceptibility of the right hemisphere during the delayed feedback condition. In fact, the former processes phonemic, grammatical, and lexical features of words whilst the latter is competent in using metaphors and prosody in controlling the emotional aspects of language. Moreover, the right hemisphere is more active on attentional tasks.
Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has be... more Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has been recently proposed as surgical treatment of advanced Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. STN stimulation alone has been shown to provide selective improvement of the grammatical aspect of language. We studied five advanced Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease patients who underwent combined deep brain stimulation (STN + PPN). Overall cognitive profile did not change. On the contrary, an interesting trend towards reduction of ungrammatical errors (particularly substitution of free and inflectional morphemes) was found when stimulating the STN, and also the PPN, when the STN was switched off. These findings replicate previous observations on the STN, and provide the rationale for further investigation of the role of the PPN in processing linguistic grammar.
ObjectiveAmplitude decrease of cortical responses after repeated stimuli (‘habituation’) is a wel... more ObjectiveAmplitude decrease of cortical responses after repeated stimuli (‘habituation’) is a well-known phenomenon, the functional meaning of which is to prevent sensory overflow and to save resources for meaningful and novel stimuli. It is known that the primary low-frequency N20 somatosensory evoked potential (SEP) undergoes habituation in healthy subjects. By contrast, the presence of this phenomenon has never been tested
It has been demonstrated that the early part of 600 Hz High Frequency Oscillations (HFOs), probab... more It has been demonstrated that the early part of 600 Hz High Frequency Oscillations (HFOs), probably generated in the terminal part of thalamo-cortical somatosensory radiations, are abnormally reduced between attacks in migraineurs. We aimed at verifying whether spontaneous clinical fluctuations in migraine are correlated to HFO changes. We recorded somatosensory evoked potentials in 28 migraine patients. Clinical fluctuations (number of attacks in the 6 months preceding and following the test) were correlated to the HFOs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; amplitudes. Moreover, eight out of 28 patients underwent a longer follow-up, including HFO control and clinical observation during the 12 months following the baseline recording. The amplitude of early presynaptic HFOs was significantly correlated to the clinical evolution, since spontaneous worsening was associated with reduced presynaptic HFOs, whereas spontaneous improvement was associated with enhanced presynaptic HFOs (correlation test, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). No correlation was found between the amplitude of postsynaptic HFOs and clinical fluctuations. Patients undergoing longer follow-up showed substantially unchanged HFOs, accordingly with their stable clinical condition. HFOs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; enhancement in spontaneously improved patients can reflect the increased activity of brainstem arousal related structures, which in turn increases the thalamo-cortical drive and the cortical lateral inhibition mediated by GABAergic interneurons. HFOs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; recording could represent a useful tool in the functional assessment of migraine.
Amplitude decrease of cortical responses after repeated stimuli (&amp;amp;amp;amp;amp;amp;amp... more Amplitude decrease of cortical responses after repeated stimuli (&amp;amp;amp;amp;amp;amp;amp;amp;#39;habituation&amp;amp;amp;amp;amp;amp;amp;amp;#39;) is a well-known phenomenon, the functional meaning of which is to prevent sensory overflow and to save resources for meaningful and novel stimuli. It is known that the primary low-frequency N20 somatosensory evoked potential (SEP) undergoes habituation in healthy subjects. By contrast, the presence of this phenomenon has never been tested in High Frequency Oscillations (HFOs), which probably reflect the activity of a somatosensory arousal system. We recorded SEPs after right median nerve stimulation in 19 healthy volunteers. Six consecutive series of 500 sweeps were collected and averaged at a repetition rate of 5 Hz. SEPs were recorded by means of Erb&amp;amp;amp;amp;amp;amp;amp;amp;#39;point-to-Fz, Cv6-to-AC and P3-to-F3 arrays. P3-to-F3 recording further underwent narrow-bandpass (400-800 Hz) digital filtering to selectively analyse high-frequency components. Statistical analysis revealed a significant amplitude decrease of the primary N20 LF-SEP between the first and sixth block of stimuli. By contrast, HFO amplitudes remained substantially unchanged throughout the whole procedure. Differently from the N20 LF-SEP, scalp-recorded HFOs do not undergo habituation. Our findings reinforce the view that HFOs reflect the activity of an arousal somatosensory system, which is able to signal novel stimuli, the relevance of which points out high synaptic efficacy.
Neuropsychological investigations have consistently shown that frontal cortices are relevant in p... more Neuropsychological investigations have consistently shown that frontal cortices are relevant in processing temporal and sequential features of actions. However, one of the main theoretical issues that has been discussed in the last 25 years is whether these brain areas store some abstract representations of actions or, conversely, act upon action representations stored within other posterior associative cortices. We administered to
Neuropsychological consequences of stimulation of the subthalamic nucleus for treatment of drug-r... more Neuropsychological consequences of stimulation of the subthalamic nucleus for treatment of drug-resistant Parkinson's disease (PD) have been studied previously. However, no detailed investigations of linguistic function modifications have been carried out. We studied four consecutive patients with PD who underwent chronic bilateral stimulation of the subthalamic nuclei. Neuropsychological and linguistic evaluations were performed before and 2 weeks after surgery. Linguistic abilities were studied also 1 year after surgery with stimulators both off and on. Intraphrasal hesitation pauses, phonemic paraphasias and morpho-syntactic errors were significantly reduced and lexical retrieval improved with stimulation of the subthalamic nuclei. Implicit linguistic phenomena, mainly occurring within basal ganglia circuitry, benefited by recovery of functional equilibrium within basal nuclei and between overall basal ganglia circuitry and cerebral cortex.
Conclusion Verbal communication impairments frequently follow damage to the right cerebral hemis... more Conclusion Verbal communication impairments frequently follow damage to the right cerebral hemisphere. These deficits are usually underestimated because RHD patients are not routinely referred to speech therapists. The nature of pragmatic disorders in verbal communication in RHD patients still remains to be clarified. In particular, it is still unclear whether these impairments are language-specific or attention-specific (e.g. an attentional deficit with
Background : The field of pragmatic impairments of verbal communication in cerebrally damaged sub... more Background : The field of pragmatic impairments of verbal communication in cerebrally damaged subjects dates back almost three decades. However, a systematic investigation of pragmatic competences has never been completed in a large sample of normal adults controlling for age and education factors. Aims : We aimed to examine the effects of age and education on the main features of
Mutations in the progranulin gene (GRN) were recently identified as an important cause of familia... more Mutations in the progranulin gene (GRN) were recently identified as an important cause of familial frontotemporal dementia (FTD). More than 60 pathogenic mutations have been reported up to now and prominent phenotypic variability within and among affected kindreds has been described. We have studied an Italian family with clinical evidence of dementia, and here we report detailed clinical records, imaging, sequential neurological examinations, cognitive assessments, and genetic analysis of three affected members of the same generation. Genetic analysis revealed the presence of the null mutation IVS6 + 5_8delGTGA in GRN, leading to haploinsufficiency, as documented by mRNA analysis. The mutation is associated with wide variation of the clinical phenotype, ranging from FTD to Alzheimer's disease and to a rapidly-progressive dementia. In summary, the patients of this kindred showed highly variable clinical features that do not have a close correspondence with the pattern of the cer...
BackgroundA combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DW... more BackgroundA combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism.
Terminal and interstitial deletions of 2p25.3 (size < Mb), detected by array-CGH analysis, hav... more Terminal and interstitial deletions of 2p25.3 (size < Mb), detected by array-CGH analysis, have been reported in about 18 patients sharing common clinical features represented by early-onset obesity/ overweightness associated with intellectual disabilities (ID) and behavioural troubles. This observations led to hypothesize that 2p subtelomeric deletion should be associated with syndromic obesity and MYT1L became the main candidate gene for ID and obesity since it is deleted or disrupted in all hitherto published cases. Here we described a 2p25.3 de novo terminal deletion of 1.9 Mb, of paternal origin, detected by array-CGH analysis in a girl of 4.4 years with a distinctive phenotype consisting of early-onset of obesity associated with moderate ID, and hyperkinetic disorder. The deletion disrupted MYT1L and encompassed five other OMIM genes, ACP1, TMEM18, SNTG2, TPO, and PXDN. Here, we discuss the combined functional effects of additional haploinsufficient genes, that may concur w...
Clinical neurolinguistics still lacks consolidated and standardised tools for the assessment of i... more Clinical neurolinguistics still lacks consolidated and standardised tools for the assessment of impairments of pragmatics of verbal communication. In the present paper we present norms of the Italian version of the Right Hemisphere Language Battery (Batteria del Linguaggio dell’Emisfero Destro, BaLED) [1] originally devised by Bryan [2]. The normative study has been conducted with the recruitment of 440 healthy subjects. The battery of tests was not intended to be cognitively oriented, by providing evidence of the cognitive impairments underpinning verbal pragmatic deficits; on the contrary, it permits the detection of the presence/absence of impairments in processing the main pragmatic features of verbal communication traditionally associated with right hemisphere lesions. Thus, apart from being a clinical tool for diagnosing pragmatic impairments of verbal communication, the BaLED represents a useful initial battery of tests for clinical assessment and for selecting specific popul...
24 Italian medical students performed a task of verbal fluency. 12 students (the control group) r... more 24 Italian medical students performed a task of verbal fluency. 12 students (the control group) receiving Normal Auditory Feedback and 12 students receiving Delayed Auditory Feedback (delay of 200 msec.) performed six trials in six different experimental settings: normal or increased speaking rate, and, for each condition, once with bilateral input of the auditory feedback, once to the right ear, and once to the left ear. At the normal speaking rate, the disruptive effect of delayed feedback was confirmed. As the speaking rate increased, the total number of errors increased within the control group but decreased within the group given delayed feedback, although the total number of errors was always greater for the latter. In addition, speech was more disrupted when the auditory input was returned to the right ear (left hemisphere) for all the different conditions: Normal and Delayed Auditory Feedback, normal and increased speaking rate. In particular, the left hemisphere was less resistant to the disruptive effect of the delayed feedback than the right hemisphere. From these results, we suggest that, when speaking more quickly, one uses more central mechanisms of movement programming (cortical-cerebellum-thalamus-cortical, cortical-corpus striatum-thalamus-cortical, and cortical-thalamus-cortical circuits), or attentional control (cortico-reticular-cortical circuits) than peripheral mechanisms (tactile, proprioceptive, and acoustic circuits). This may explain the decreased disruptive influence of delayed auditory feedback on speed, fluency, and quality at increased speaking rates. Hemispheric specialization processes, however, may explain the more pronounced susceptibility of the left hemisphere or the less pronounced susceptibility of the right hemisphere during the delayed feedback condition. In fact, the former processes phonemic, grammatical, and lexical features of words whilst the latter is competent in using metaphors and prosody in controlling the emotional aspects of language. Moreover, the right hemisphere is more active on attentional tasks.
Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has be... more Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has been recently proposed as surgical treatment of advanced Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. STN stimulation alone has been shown to provide selective improvement of the grammatical aspect of language. We studied five advanced Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease patients who underwent combined deep brain stimulation (STN + PPN). Overall cognitive profile did not change. On the contrary, an interesting trend towards reduction of ungrammatical errors (particularly substitution of free and inflectional morphemes) was found when stimulating the STN, and also the PPN, when the STN was switched off. These findings replicate previous observations on the STN, and provide the rationale for further investigation of the role of the PPN in processing linguistic grammar.
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