Tactile Prepuff Inhibition of Startle in Children with Tourette’s Syndrome In Search of an “fMRI-

Tactile Prepuff Inhibition of Startle in Children with Tourette’s Syndrome:In Search of an“fMRI-Friendly”Startle Paradigm

Neal R.Swerdlow,Blythe Karban,Yvonne Ploum,Richard Sharp,Mark A.Geyer, and Angela Eastvold

Background:Functional magnetic resonance imaging (fMRI)studies in neuropsychiatric populations will be enhanced by“on-line”tasks that assess brain activation linked to neurocognitive and psychophysiological func-tions.In some cases,task modifications may be required for use in an fMRI environment.Prepulse inhibition(PPI) of the startle reflex is an operational measure of sensori-motor gating that is deficient in specific neuropsychiatric disorders,including schizophrenia,Huntington’s disease, and Tourette’s syndrome(TS).This study examined whether a modified“fMRI-friendly”PPI paradigm is suitable for use in children and adequately sensitive to detect PPI deficits in TS.

Methods:Bilateral eyeblink PPI was measured in chil-dren using chin air puffs to elicit startle and prepuffs to the dorsal hand surface as inhibiting stimuli.This paradigm involved no metallic objects or acoustic stimuli,making it suitable for an fMRI environment that is magnetically sensitive and acoustically complex.Children were also assessed in a“standard”acoustic PPI paradigm. Results:Robust startle was elicited via either puffs or noise bursts,and these responses were inhibited by pre-puffs and prepulses,https://www.wendangku.net/doc/e71145934.html,pared to control subjects,children with TS exhibited comparable startle magnitude and habituation but significantly reduced pre-puff inhibition and acoustic PPI.

Conclusions:Sensorimotor gating can be assessed in an “fMRI-friendly”paradigm that detects inhibitory deficits in TS.Biol Psychiatry2001;50:578–585?2001Society of Biological Psychiatry

Key Words:Functional magnetic resonance imaging, prepulse inhibition,sensorimotor gating,startle,Tourette’s syndrome Introduction

T ourette’s syndrome(TS)is a childhood-onset disorder of multiple motor tics and at least one phonic tic. Roughly half of all TS patients experience a significant diminution of symptoms in their early20s,but others experience persistent,lifelong symptoms(Leckman et al 1998).Estimates of TS prevalence vary across clinical and field samples because of differences in diagnostic criteria and thresholds,but recent studies suggest a prevalence on the order of0.1%to1.0%(Kadesjo and Gillberg2000; Mason et al1998).

Although there is converging evidence for basal gan-glia,or distributed cortico-striato-pallido-thalamic(CSPT) dysfunction in TS,the precise pathophysiology of this disorder is not known.Neuropathologic studies are limited and inconclusive(cf.Swerdlow and Young1999).Neu-roimaging findings in TS have been generally consistent with cortico-striatal dysfunction but have failed to impli-cate a more specific neural substrate for this disorder. Studies of regional brain volume and hemispheric symme-try have not always been replicated;even when replicable, the magnitude of such changes is small,typically on the order of5%(Baumgardner et al1996;Castellanos et al. 1996b;Moriarty et al1997;Peterson et al1993;Singer et al1993).Resting metabolic neuroimaging and blood flow studies in TS report distributed reductions in limbic and motor CSPT circuitry(Braun et al1993;Eidelberg et al 1997;Moriarty et al1995;Riddle et al1992;Sieg et al 1993).

Functional neuroimaging studies have also been applied toward the study of TS.During active tic suppression, activation in the right caudate nucleus and bilaterally diminished neuronal activity in the putamen,globus pal-lidus,and thalamus in TS is measured by fMRI(Peterson et al.1998).In a recent study using[O15]H2O positron emission tomography(PET),activation during“nonsup-pressed”tics was observed in a number of brain regions, including the anterior cingulate cortex,inferior parietal cortex,prefrontal cortex,caudate,putamen,and primary

From the Department of Psychiatry,UCSD School of Medicine,La Jolla,California

(NRS,BK,RS,MAG,AE);and the Department of Pharmacy,Utrecht

University,The Netherlands(YP).

Address reprint requests to N.R.Swerdlow,Department of Psychiatry,UCSD

School of Medicine,9500Gilman Drive,La Jolla,CA92093-0804.

Received December29,2000;revised March26,2001;accepted April5,2001.

?2001Society of Biological Psychiatry0006-3223/01/$20.00

PII S0006-3223(01)01164-7

motor cortex (Stern et al 2000).As with glucose metabolic studies,these newer reports suggest distributed cortico-striatal or CSPT dysfunction but do not identify a more localized regional abnormality in TS.

In August 1998,an advisory board of the Tourette Syndrome Association 1(TSA)recommended the develop-ment of behavioral,neuropsychologic,or psychophysio-logic paradigms that can be used within an fMRI environ-ment to activate brain regions of relevance to TS and to detect specific cognitive or behavioral abnormalities in TS children.Importantly,fMRI techniques avoid exposure of TS and control children to radioisotopes used in PET imaging.Studies in TS children (rather than adults)may be particularly important —not only to avoid the potential confounds of chronic medication exposure,but also be-cause it is not clear that studies of an adult,persistent form of this illness are directly relevant to the pathophysiology of the approximately 50%of TS cases that resolves by early adulthood (Leckman et al 1998).

One simple behavioral measure that detects inhibitory deficits in children with TS is prepulse inhibition (PPI),which is the reduction in startle reflex magnitude when the startling stimulus is preceded 30to 500msec by a weak stimulus,or prepulse.Prepulse inhibition is an operational measure of sensorimotor gating.Conceptually,the pre-pulse activates automatic brain mechanisms that protect the information it contains,for a very brief temporal window (?500msec;Blumenthal et al 1996;Braff et al 1992;Cohen et al 1981;Graham 1975;Norris and Blu-menthal 1996;Peak et al 1939;Swerdlow et al 1999).Motor responses to stimuli arriving during that protected period are normally suppressed,or gated;PPI was reported to be significantly diminished in children with TS (Cas-tellanos et al 1996a)in a study using electrocutaneous stimuli to elicit the eye-blink component of the startle reflex.An earlier report noted a similar loss of inhibition in TS adults using a related electrocutaneous paired-pulse paradigm (Smith and Lees 1989).These deficits in inhib-itory gating in TS may be consistent with the diminished ability to normally inhibit or gate intrusive sensory,cognitive,and motor information in this disorder.

A substantial body of work has characterized the regu-lation of PPI by CSPT circuitry in laboratory animals (cf.Koch and Schnitzler 1997;Reijmers et al.1995;Swerdlow and Geyer 1999;Swerdlow et al 1992,2000),and the loss of PPI in patients with Huntington ’s disease (Swerdlow et al 1995),suggests that the basal ganglia may regulate PPI in humans.Several features thus suggest that PPI might be a useful paradigm for functional neuroimaging studies in

TS children:it is an automatic,reflex-based measure of central inhibitory functions that is impaired in TS and that is thought to be regulated by brain circuitry that is directly relevant to this disorder.The magnetic environment of an fMRI scanner might complicate measures of electrocuta-neous PPI,however,and the intense,fluctuating acoustic environment might complicate measures of acoustic PPI.In our study,we attempted to develop an “fMRI-friendly ”PPI paradigm,using air puffs (which require only plastic tubing for stimulus delivery)as both prepulses and pulses and to determine whether this paradigm was adequately sensitive to detect inhibitory deficits in children with TS.

Methods and Materials

This study was approved by the Human Subjects Institutional Review Board at the University of California,San Diego (IRB #991176).Normal control subjects (n ?14),aged 9to 17years,were recruited using advertisements in the San Diego commu-nity.Children with TS (n ?10),aged 9to 17years,were recruited with the assistance of the San Diego TS Support Group of the TSA,Southern California Chapter.The study was ex-plained to each child in the presence of at least one parent,as were the potential risks (e.g.,possible skin irritation from electrode placement)and benefits (e.g.,possible information that will facilitate our understanding of the causes of TS)of study participation.In each case,the child and parent both indicated that they understood these risks and benefits,were able to describe them to the satisfaction of the principal investigator,and signed a consent for study participation.Each subject and one parent per subject underwent a semistructured clinical interview (Swerdlow et al 1996)with an experienced clinician (NRS)to assess the child ’s past medical and psychiatric illness and family history;in addition to these general areas,specific inquiries were made regarding the child ’s birth complications,developmental course and milestones,history of head injury,loss of conscious-ness,learning disabilities,hearing or vision problems,enuresis,encopresis,sleep patterns,rage attacks,premonitory urges,de-pression or eating disorders,past and present medications,and caffeine,nicotine,or recreational drug use.Control subjects were excluded for a history of any known major psychiatric or neurologic disorder;head injury with sustained loss of con-sciousness;seizures;psychotropic medications;or a family history of TS,obsessive compulsive disorder (OCD),attention-deficit/hyperactivity disorder (ADHD),autism,or schizophrenia in a first-degree relative (because of potential genetic associa-tions with TS [cf.Cohen et al 1997]or associated abnormalities in PPI [Adler et al 1999;Braff et al 1978;Swerdlow et al 1993]).Children with TS were excluded for a family history of schizo-phrenia.We assessed TS symptom characteristics,with parental input,using the Yale Brown Obsessive Compulsive Scale,Children ’s Version (CYBOCS;Goodman et al 1989)and the Yale Global Tic Severity Scale (YGTSS;Leckman et al 1989).Demographic and clinical characteristics are seen in Table 1.Control and TS groups did not differ significantly in age,gender distribution,or handedness.Mean TS symptom severity was

1

Tourette Syndrome Association,Neuroimaging Advisory Board:Allen Braun,F.Xavier Castellanos,David Eidelberg,Kirk Frey,Stephan Heckers,Scott Rauch,David Rosenberg,Clifford Saper,Jonathan Stoessl,Neal Swerdlow,John Walkup,Dean Wong.

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moderate (mean YGTSS ?40.8,range 18–63;mean motor ?12.0,mean vocal ?7.8).Four TS subjects had no OCD symptoms (three male subjects and one female subject);6of 10TS subjects scored ?10(four male and two female subjects)on the CYBOCS,and three of these scored ?20(two male subjects and one female subject).Two TS children carried diagnoses of ADHD (both male subjects),two met criteria for enuresis (both male subjects),and four experienced significant rage attacks (three male subjects and one female subject).Notable birth or perinatal complications were identified in four TS children:1)28.5week term,pneumothorax/intubation;2)fetal distress,forceps/C-section,Apgars 5/6;3)fetal distress,postdelivery seizures ?2;4)35–36week term,low birth weight,pyloric stenosis with surgical repair at 6weeks.A family history of TS was identified in seven of nine TS children;no paternal family history was available from one TS subject.Three TS subjects were unmedicated;medications in the remaining seven included dopamine antagonists (n ?3),serotonin reuptake inhibitors (n ?6),methylphenidate (n ?1),alpha-noradrenergic antagonists (n ?3),and bupropion (n ?1).

Hearing was screened with a Saico Audiometer (Assens,Denmark),with exclusion for impairment at 40dB(A)at 500,1000,and 6000Hz (no subjects were excluded on this basis).Two miniature silver/silver chloride electrodes (Sensor Medics,Anaheim,CA)were positioned below and to the outer canthus of each eye over the orbicularis oculi muscle.A ground electrode was placed behind the left ear over the mastoid.Electrode resistances were ?10kOhm.Eye blink was measured using electromyographic recordings (San Diego Instruments,San Di-ego,CA).Recorded electromyogram (EMG)activity was band-pass filtered (1–1000Hz),rectified,and integrated,with a sensitivity of 7.67?V/digital unit.A 60-Hz notch filter was used to eliminate 60-Hz interference.Five hundred 1-msec readings were recorded,starting in advance of prestimulus onset,to assess any EMG response to the prestimulus (none were observed in our study;see below).Response criteria were based on those used in previous reports (e.g.,Braff et al 1992;Graham 1975).

Subjects sat upright during the startle sessions and were told to look straight ahead and stay awake.Acoustic stimuli were delivered by Telephonics (TDH-39-P,Maico,Minnesota,MN)

headphones.Two test sessions were used,separated by approx-imately 5min.Background 70-dB(A)white noise continued throughout both sessions and was followed 5min after onset by the startle trials.First,a tactile startle session consisted of 24trials that included two conditions:1)a 40-psi,40-m/sec air burst delivered via a pressure regulator and delivered below the subjects ’chin via a small plastic tube (PUFF)or 2)the same 40-psi,40-m/sec air burst preceded 120m/sec by a prepuff (6-psi,20-m/sec air burst delivered to the dorsal surface of the right hand via a small plastic tube [PREPUFF]).Next,an acoustic startle session consisted of 24trials that included two conditions:1)a 105-dB(A),40-m/sec noise burst presented alone (P-ALONE)and 2)the same 105-dB(A),40-m/sec noise burst preceded 120msec by a prepulse (20-m/sec noise burst)that was 16dB(A)above background (PP16).For each session,the two trial types were each repeated five times in pseudorandom order to form one trial block;this block was repeated to yield 20trials per session.These two blocks of 10trials were preceded and followed by two P-ALONE (acoustic session)or PUFF trials (tactile session);these “initial ”and “final ”trials were used to calculate reflex habituation but not PPI.Intertrial intervals were variable (range ?15–42sec)and included a “NOSTIM ”measurement,in which baseline EMG activity was measured without stimulus delivery.The NOSTIMs were “invisible ”(i.e.,interspersed between each trial pair in a way that did not alter the intertrial interval (total 23trials per session)).The 16-dB prepulse intensity was selected for this study based on previous experience that it yields robust levels of approximately 70%PPI in control subjects (Swerdlow et al 2001).The 6-psi prepuff was selected based on preliminary studies suggesting that this inten-sity was marginally below startle threshold (even 7-psi puffs to the dorsal surface of the hand tended to elicit startle responses in some individuals).Responses were observed on-line to confirm that prestimuli did not elicit startle responses.Preliminary studies also demonstrated that the maximal level of PPI using any tactile prepuff in normal control subjects was approximately 35%.Hence,we did not attempt to psychometrically equilibrate the stimulus parameters in acoustic and tactile startle paradigms.We defined PPI as the percent reduction in startle magnitude in the presence of the prepulse compared with the magnitude in the absence of the prepulse (100?[100?magnitude on prepulse trial/magnitude on pulse alone trial]).As we have described previously (Swerdlow et al 1995,2001),PPI was not analyzed in two control subjects in whom mean tactile startle magnitude was below 10units (5.31and 7.45respectively vs.control mean ?122.78).In one control subject,acoustic startle data were lost from the left eye because of electrode malfunction,and only right eye data were used for this subject.Thus,auditory PPI was calculated for 24children (control ?14,TS ?10),and tactile PPI was recorded from 22children (control ?12,TS ?10).Data were analyzed with mixed-design ANOVAs,with alpha ?.05.Startle magnitude and PPI were analyzed with repeated measures on trial block.An overall ANOVA was first examined using the 22children who successfully completed both startle sessions;in this ANOVA,diagnosis was a between-subject factor,and stimulus modality (acoustic vs.tactile),eye (left vs.right),and trial block were within-subject factors.Data from each modality were also examined in separate ANOVAs

Table 1.Subject Characteristics

Control group (n ?14)

Tourette ’s Syndrome group (n ?10)

Age:in years;mean (range)11.9(9–17)

12.1(9–17)

Male:Female

9:57:3Handedness;right:left 13:1

8:2YGTSS:mean (SEM)Total —40.80(5.10)Motor —12.00(1.83)Vocal

—7.80(1.94)CYBOCS:mean (SEM)Total —10.40(3.38)Obsession — 3.80(1.65)Compulsion

—

6.60(1.96)

CYBOCS,Yale Brown Obsessive Compulsive Scale,Children ’s Version;YGTSS,Yale Global Tic Severity Scale.

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using diagnosis as a between-subject factor and eye and trial block as within-subject factors.One-factor ANOVAs assessed the potential impact of specific categorical clinical variables on PPI in TS children (e.g.,comorbid diagnoses,family history,and medication).Because there were no significant gender differ-ences in any startle variables,gender was not used as a grouping factor.No significant right-versus left-eye differences or inter-actions were noted in these measures and thus are not reported.Peak latency facilitation was assessed via ANOVA with repeated measures on trial type and stimulus modality;trials in which startle magnitude was zero were not assigned a latency value.Simple regression analyses were used to assess correlations between clinical and experimental variables.

Results

ANOVA of PPI using the 22subjects for whom data from both sessions was successfully recorded revealed a signif-icant effect of diagnosis (F ?7.41df 1,20,p ?.015),a significant effect of stimulus modality (F ?23.08,df 1,20,p ?.0001)and no diagnosis ?modality interaction (F ?2.00,df 1,20,ns )(Figure 1).There were no effects of trial block or relevant interactions (p ?.25,all comparisons).In both acoustic and tactile startle modalities,PPI was reduced in TS versus control children;effect sizes were d ?.75and .93,respectively.One TS subject had tactile PPI values ?3SD below the mean of the combined groups (control and TS),and ?3SD below the mean of the remaining nine TS subjects;this subject also recorded the highest YGTSS score (63)of the entire TS group.The critical group difference (PPI control ?TS)remained statistically significant even after exclusion of this poten-tial “outlier ”from analyses (F ?5.72,df 1,19,p ?.03).With the specific stimulus parameters and test order (tactile followed by acoustic)used in this study,PPI of

acoustic startle was greater than PPI of tactile startle.Independent ANOVAs for each stimulus modality yielded comparable group effects.

The small sample of TS subjects precluded any defini-tive assessment of the potential impact of comorbid diagnoses on these PPI findings.Still,it would be difficult to attribute group differences in PPI to any of the identi-fied comorbid clinical conditions or medications (Fig.1).One previous report described elevated levels of PPI in adults with ADHD (Adler et al,1999),and indeed elimi-nation of the two children with comorbid TS and ADHD increased effect sizes in acoustic and tactile PPI to d ?.99and 1.15,respectively.Enuretic children have been re-ported to exhibit PPI deficits (Ornitz et al 1992);however,group differences could not be accounted for by the two TS children with comorbid Enuresis (Fig.1).The two unmedicated TS children exhibited acoustic and tactile PPI levels well below the control group means;the one TS child treated with methylphenidate exhibited the highest acoustic and tactile PPI levels among the entire TS group.Finally,no significant correlations were observed between YGTSS or CYBOCS scores (including subscales)and either acoustic or tactile PPI.

Reduced prestimulus effects on startle magnitude in TS subjects could not be easily explained by impaired sensory processing or elevated sensory thresholds in these chil-dren.Thus,in addition to reducing startle magnitude,prestimuli are known to reduce the latency to reflex onset and peak,a process known as latency facilitation (Ison et al 1973).As seen in Table 2,TS children exhibited robust facilitation of peak startle latency in both acoustic and tactile modalities,providing clear evidence that these prestimuli caused the expected physiologic impact on startle latency in these children.Analyses of variance with repeated measures on stimulus modality and trial type revealed no significant effect of diagnosis (F ?1)or modality (F ?1),a significant effect of trial type (F ?42.50,df 1,14,p ?.0001)and a significant interaction of diagnosis ?trial type (F ?5.30,df 1,14,p ?.04).As seen in Table 2,this interaction reflected the arithmetically larger impact of prestimuli on reflex latency in TS chil-dren,the result of both nonsignificantly slower reflex latencies in P-ALONE and PUFF conditions (F ?1.73,df 1,20,ns )and nonsignificantly faster latencies under pre-stimulus conditions (F ?1).

There were no group differences in startle magnitude or habituation in either acoustic or tactile startle modalities (Table 2).ANOVA of startle magnitude during the portion of testing in which PPI was assessed revealed no signifi-cant effect of diagnosis (F ?1)or modality (F ?1),a significant effect of trial block (F ?14.94,df 1,20,p ?.001;indicative of habituation)and no significant diagno-sis ?block interaction (F ?1).Similarly,comparison

of

Figure 1.Mean percent prepulse inhibition in acoustic and tactile startle paradigms in control and TS groups.Individual data points are shown for children with comorbid attention-deficit/hyperactivity disorder (ADHD),Enuresis (E),or who were using a prescribed stimulant (S).*Significantly lower than control group,p ?.05,by analysis of variance (see text).

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startle magnitude in the initial versus final pair of P-ALONE or PUFF trials revealed no significant effect of diagnosis (F ?1),a significant effect of trial block (F ?19.52,df 1,20,p ?.0005),and no significant diagnosis ?block interaction (F ?1).Group differences were noted in the level of baseline EMG activity measured during NOSTIM trials (F ?5.75,df 1,20,p ?.03;Table 2),consistent with observations that some TS children exhibited facial tics during startle testing.There was no significant correlation between mean NOSTIM activity and mean PPI among TS children (r ?.10,ns ),or among the combined group of control and TS children (r ??.15,ns ).

Finally,cross-modal correlations were examined for startle magnitude and PPI.We recently reported test –retest correlations in adult control subjects for startle magnitude (r ?.69–.76)and PPI within modality (R ?.50–.58)(Swerdlow et al 2001).In our present study,startle magnitude correlated significantly across modali-ties (r ?.76,df 1,20,p ?.0001),but PPI was only modestly correlated across modalities (r ?.35,df 1,20,p ?.12).

Discussion

The main aim of this study was to determine whether a paradigm could be developed that could detect PPI deficits in TS children using stimuli that are compatible with the magnetic and acoustic constraints of an fMRI environ-ment.Implicit within this aim was an attempt to extend previous reports of electrocutaneous PPI deficits in TS children (Castellanos et al 1996a)to acoustic (noise bursts)and tactile (air puffs)modalities.Our findings demonstrate that these startle inhibitory deficits in TS children can be detected using either noise bursts or air

puffs.Thus,PPI deficits in TS children generalize across these stimulus modalities.This observation parallels re-ports in Huntington ’s disease patients,in which PPI deficits are observed with either acoustic or tactile startle stimuli (Swerdlow et al 1995),and in schizophrenia patients,in which PPI deficits are observed with acoustic,tactile,or electrocutaneous startle stimuli (Bolino et al 1994;Braff et al 1978,1992).Based on the PPI deficits observed in our study using the tactile prepuff paradigm,it should be possible to deliver stimuli that will generate cortico-striato-pallido-thalamic (CSPT)-related inhibitory deficits in TS children within an fMRI environment that is both magnetically and acoustically complex.

Although the critical dependent measure was prepulse inhibition,there are occasions when the prestimulus can increase rather than decrease the magnitude of the startle reflex (Hoffman and Searle 1968;Ison et al 1973),a process known as prepulse potentiation or prepulse facil-itation (PPF).Prepulse facilitation can occur in normal laboratory animals at very short (?15-m/sec)prepulse intervals and in humans at very long (e.g.,2000-m/sec)prepulse intervals.We previously reported PPF of acoustic and tactile startle in patients with Huntington ’s disease at intervals that elicit PPI in normal controls subjects (Swer-dlow et al 1995).In our present study,PPF of tactile startle was observed in some TS subjects.There is some evidence that PPF and PPI reflect two opposing behavioral effects of the prepulse and that the preponderance of PPF and PPI expressed for any specific stimulus condition is under neurochemical regulation (e.g.,by forebrain dopamine systems)(Swerdlow et al,in press).Presumably,the expression of tactile PPF by TS subjects might reflect either an excessive expression of the facilitatory effects of the prepuff,a deficient expression of the inhibitory effects of the prepuff,or a shift in the nature of the stimulus

Table 2.Startle Characteristics:Mean (SEM)

P-ALONE and PUFF startle magnitude and habituation,and NOSTIM values (7.67?V/unit)

P-ALONE magnitude PUFF magnitude P-ALONE habituation

PUFF habituation

NOSTIM Block 1

Block 2

Block 1

Block 2

Initial trials

Final trials

Initial trials

Final trials

Block 1

Block 2

Control Group 125.23(20.61)93.42(14.61)148.91(24.67)96.62(18.59)170.98(25.15)104.88(20.69)158.02(32.51)79.54(15.87)8.02(1.27) 6.83(0.96)TS Group

145.82(21.24)125.15(21.24)139.64(26.02)99.96(18.61)168.33(24.64)116.80(24.92)160.13(30.06)100.63(25.08)17.41(2.91)17.57(3.06)Peak startle latency (msec)

P-ALONE prepulse ?P-ALONE

PUFF PREPUFF ?PUFF

Control Group 63.00(1.05)54.06(2.01)53.75(2.43)53.60(1.71)TS Group

64.56(1.23)

48.76(2.53)

59.62(2.41)

56.40(1.70)

P-ALONE,a 105dB(A)40m/sec noise burst presented alone;PUFF,a 40psi 40m/sec air burst delivered below the subjects ’chin via a small plastic tube;PREPUFF,6psi 20m/sec air burst delivered to the dorsal surface of the right hand via a small plastic tube,120m/sec prior to PUFF;NOSTIM,baseline EMG activity measured without stimulus delivery;TS,Tourette ’s syndrome.

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properties that trigger PPF versus PPI.This last possibility might be demonstrated via more comprehensive paramet-ric manipulations of prepulse characteristics(e.g.,Swerd-low et al,in press).

Psychiatric comorbidity is particularly common in TS children(cf.Cohen et al.1997)and can have a dominant impact on psychophysiologic measures(Ozonoff et al 1998).To the degree that this could be assessed in one previous report(Castellanos et al1996a)and in our study, comorbidity with ADHD,OCD,or both could not easily account for the group differences.Clearly,larger study samples would be needed to address this issue in a convincing manner.

Larger samples,and perhaps alternative experimental designs,would also be needed to fully assess the relation-ship between acoustic and tactile PPI in children;this was clearly not a major goal of our study.Based on the different sensory receptive processes involved in acoustic and tactile PPI(proximal to any common central gating circuitry),one would predict differences in these measures within individuals.Our previous experience suggests that maximal correlations are achieved when acoustic and tactile PPI are assessed within the same test session using stimuli that are psychometrically matched(i.e.,yield similar overall amounts of reflex inhibition).Even within a single stimulus modality,PPI elicited by weak and intense prepulses might be only modestly correlated.For example,in a recent study from our group of14normal men(Swerdlow et al1999),PPI of acoustic startle elicited by4-and16-dB(A)acoustic prepulses exhibited only a trend toward a positive correlation(r?.46,p?.10),not dissimilar to the findings in our present study across different stimulus modalities in a diagnostically heteroge-neous group of boys and girls.Thus,it is likely that the disparate levels of PPI elicited by acoustic versus tactile stimuli might be most relevant to the weak trend toward correlated acoustic and tactile PPI in our present study. Studies in laboratory animals demonstrate that PPI elicited across a number of different stimulus modalities(visual, acoustic,tactile)exhibits similar changes in response to some,but not all,experimental manipulations,suggesting some degree of commonality at the level of central gating circuitry(Padich et al1996;Palmer et al1999;Taylor et al1995;Varty et al1999).

How will the tactile prepuff paradigm help elucidate abnormal patterns of regional brain activity in TS?Con-ceivably,differences in brain activation patterns during PUFF and PREPUFF trials should yield a map of the neural processes responsible for startle inhibition,includ-ing on the afferent side the inhibitory mechanisms trig-gered by the prepuff and on the efferent side the mecha-nisms responsible for generating a diminished startle reflex.By comparing these maps between control and TS children,it should be possible to identify brain regions in which abnormal patterns of activation accompany dimin-ished sensorimotor gating in TS.Existing data from preclinical and clinical studies suggest that substrates responsible for a reduction in PPI might include the mesial temporal cortex or prefrontal cortex,the striatum,the globus pallidus,or the pontine tegmentum(Hazlett et al 1998;Swerdlow et al1995;cf.Swerdlow et al2000). Resting metabolic neuroimaging studies have identified abnormalities in many of these regions in TS.Conceiv-ably,an activation paradigm based on tactile PPI might be better able to identify regional brain dysfunction by increasing the demand on specific circuit elements(those that regulate sensorimotor gating)and thereby enhance the signal-to-noise ratio for those elements.At rest,pathology within interconnected brain circuits can blend into the compensatory neural milieu;in contrast,under the impact of the increased functional load of a tactile PPI paradigm, regional deficits might be detected more easily.Similar strategies have proven successful in disorders such as OCD(Rauch et al1997).

Studies are now in progress that will test the utility of this tactile PPI paradigm in fMRI studies with TS children (S.Rauch,personal communication)and normal adults. This paradigm might also have utility for fMRI studies in other clinical populations that exhibit PPI deficits,includ-ing patients with schizophrenia(Braff et al1978).Al-though this initial study was designed to test a specific hypothesis in TS children,it might be important to optimize the tactile prepuff paradigm via a variety of parametric manipulations(e.g.,testing different prepulse intervals)or structural modifications(e.g.,body surface used for prepuff application).For example,although a 70-dB(A)white noise background was used in our studies, louder or different types of background noise might be necessary in the MRI environment to overcome the poten-tial cross-modal inhibiting effects of phasic noises on puff-elicited startle.Thus,our results might be best viewed as a proof of concept rather than a finished product. Supported by awards from the M.I.N.D.Institute,NIH(Grant Nos. MH42228and MH01436)and NARSAD.The authors gratefully ac-knowledge formative discussions with Drs.David Braff and Scott Rauch and are indebted to the San Diego TS Support Group of the Tourette Syndrome Association,Southern California Chapter,for their participa-tion in this https://www.wendangku.net/doc/e71145934.html,ura Ross provided valuable technical assistance.

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RTHJ_Manual

RTHJ熱阻測試儀 操作手冊 冠魁電機股份有限公司 TEL:02-26642120 FAX:02-26641610

目錄 簡介 (3) 安裝密封箱 (4) 測試流程範例 (8) 烤箱操作 (8) 軟體操作：「順向偏壓-溫度」曲線之量測 (9) 密封箱操作 (10) 軟體操作：熱阻量測 (12) 軟體操作說明 (13) 基本操作 (13) 報表 (14) 通訊埠設定 (15) 光功率設定 (15) 熱阻量測 (18) 附錄 (20) 計算公式一（由K係數推算T J）： (20) 計算公式二（內插法求T J）： (20)

簡介 RTHJ是用來搭配PTJ6000系列測試機及BC-02小烤箱之連線軟體，其主要功能是借由電腦來控制「順向偏壓-溫度」曲線之量測，以簡化熱阻量測之流程，其架構圖如下圖所示。 [電腦 PTJ6000測試機] 1.傳送測試指令。 2.接收測試讀值。 [電腦 BC-02小烤箱] 1.設定小烤箱溫度。 2.讀取小烤箱即時溫度。 [電腦 SE3000記錄器] 1.讀取密封箱即時溫度。

安裝密封箱1將測試線從密封箱左邊孔由下往上穿出。 2將感溫棒從密封箱右邊孔由下往上穿出。 3測試線、感溫棒安裝示意圖。

4感溫棒接SE3000溫度記錄器方法如圖。 a. 安裝感溫棒前 指撥開關預設全在OFF(左側)，請勿更變。 若非使用本公司所提供的0.5mm K Type 感溫棒，請確認您所使用的感溫棒為非接觸式。以免量測時電流回灌傷及SE3000。 c. 依序安裝所有感溫棒(Channel 1~4) b. 安裝一組感溫棒(Channel 2) Ch1 ＋ Ch2 － 未使用 Ch3 Ch4 Ch6 Ch5

(完整)人教版七年级英语上册starterunit1-3模拟测试题

人教版英语七年级上册Starter Unit 1-3模拟测试 (满分100分时间90分钟) 学校____________ 班级____________ 姓名____________ 得分____________ 第一部分听力(20分） Ⅰ.听录音，选出你所听到的字母组合或单词。录音读两遍。(5分) （）1. A. CD B. DG C.CG （）2. A. NBA B. CBA C. MPN （）3. A. thank B. Frank C. Eric （）4. A. Grace B. Alice C. thanks （）5. A. jacket B. key C. quilt Ⅱ.听录音，填入所缺的字母(大小写与字母组合的其余部分一致)。录音读两遍。（5分） 6. F 7. E 8.B 9. h l 10. n c Ⅲ.听句子，选择恰当的答语。每个句子读两遍。（5分） （）11.A. Good morning, Jim. B. Goodbye, class. C. Good afternoon, Tony. （）12.A. Fine, thank you. B. Hello, Alan. C. It’s a pen. （）13. A. This is a pen. B. It’s an orange. C. That is an apple. （）14. A. Green. B. It’s green. C. G-R-E-E-N. （）15. A. Yes, it is. B. No, I’m not. C. Yes, he is. Ⅳ.听对话，补全所缺内容。对话读两遍。（5分） M: Good morning, Helen. W: Good morning, 16 . M: What’s this in English? W: It’s a17 . M: What color is it? W: It’s18 . M: 19 it, please. W: 20 . 第二部分笔试(80分） Ⅰ.找出与其他三个划线部分读音不同的单词。(5分) （)21.A.what B.that C.map D.bag ( ) 22.A.pen B.yes C.me D.red ( ) 23.A.this B.that C.thank D.these ( ) 24.A.color B.on C.dog D.not

cloudera-quickstart安装使用总结

一、cloudera-quickstart的安装 （1）在官网上下载一种版本的cloudera-quickstart（有三种不同版本分别对应的可以在三种不同的虚拟机上运行） （2）根据下载的不同版本下载虚拟机（VMware or VisualBox） （3）以VisualBox虚拟机为例则可以运行cloudera-quickstar的基本配置如下： RAM内存至少为8G 虚拟处理器分配为两个

（4）虚拟机配置好以后，不用先安装Linux操作系统。因为cloudera-qiuckstart对包括操作系统在内的都已经打好包了，所以只需将下载的cloudera-quickstart的虚拟磁盘（比如：cloudera-quickstart-vm-5.1.0-1-virtualbox-disk1.vmdk）添加到虚拟机控制器的位置然后启动虚拟机中的该的系统，cloudera-quickstart所包含的一整套系统就可以使用了，这就是quickstart 版本的方便之处。 具体操作如下： 进入配置好的虚拟机页面，选择“存储”，然后点下图红圈标注的位置

会弹出来如下对话框，选择“使用现有的虚拟盘” 然后再找到你下载的cloudera-quickstart的虚拟磁盘所在的位置，点击“打开” 则虚拟磁盘就被添加进去了，如下图所示

最后启动该系统 对于win7系统上如果安装VMware虚拟机有可能在启动虚拟磁盘时会提示出现内部错误（如下图所示），此时只需要以管理员身份运行虚拟机就可以解决该问题了。

二、cloudera manager控制页面 启动虚拟机进入cloudera-quickstart操作系统桌面后，会自动跳出浏览器上cloudera的控制平台。但有可能会出现接口连接不上服务器的状况，如下图所示： 此时有两种解决方法：（1）点击桌面上的“Launch cloudera manager”(2)打开Linux的控制终端输入：“sudo/home/cloudera/cloudera-manager--force”一般我比较喜欢采取第二种方法。 做完这些后就可以单击浏览器窗口上的“cloudera manager”、“Hue”、“Hoop”、“Spark”等进去其相应的控制平台了，打开这些控制平台还可以直接在浏览器的地址栏输入相应的端口号进入，比如cloudera manager在服务器端的端口号为：7180，则可在浏览器中输入：quickstart.cloudera:7180直接进入。在实际操作中我比较喜欢在浏览器中更改端口号切换控制台。

新目标初中英语七年级上册 Start Unit1--3

新目标初中英语七年级上册 Class name Starter Unit 1 Good morning Activevity 1b 1.A:Good morning, Helen! B: ,Bob! 2.A:Good morning, Alice! B: ,Cindy! 3.A: , Frank! Hello,Eric! B/C: , Dale! Activevity 3a 1.A:Good morning, Helen! B: , Dale! 2.A:Good afternoon, Eric! B: ,Frank! 3.A:Good evening, Bob! B: , Alice! Activevity 3c A:Good afternoon, Dale! B:Hi, Cindy! ? A: .How are you? B:I’m OK.

Start Unit 2 What's this in English Activevity 1b A: ? B:It’s an orange. A:What’s that in English? B:It’s . Activevity 3c A:What’s this ? B:It’s a map. A: . B:M-A-P. Activevity 3d 1.A:What’s this in English? B:It’s . A:Spell it,please. B: . 2.A: ? B:It’s a cup. A:Spell it,please. B:C-U-P. 3.A:What’s that ? B:It’s .

onStartCommand(android service用法)

onStartCommand(Intent intent, int flags, int startId) Service原理这里不介绍，只介绍onStartCommand的返回和Android Reference中的问题。 onStartCommand方法必须具有一个整形的返回值，这个整形的返回值是一个描述性质的数值，用来告诉系统在服务启动完毕后，一旦遇到服务被系统销毁（System kill），系统将如何继续（操作），这些返回值必须是以下一个： START_NOT_STICKY 如果系统在onStartCommand返回后被销毁，系统将不会重新创建服务，除非收到一个未处理（pending悬而未决地）的Intent，当不是必须（necessary）并且Android应用能够自行简单地（simply）重启未完成业务（不通过服务），那么这样的设定是最安全的（safest）。 START_STICKY 如果系统在onStartCommand返回后被销毁，系统将会重新创建服务并依次调用onCreate和onStartCommand（注意：根据测试Android2.3.3以下版本只会调用onCreate根本不会调用onStartCommand，Android4.0可以办到），重新创建的操作将会作为事件日程序列（schedule）加入到系统事件日程列表中，在延迟一个计算时间（如：5000ms）后重新启动。但是不会重新将之前的传入的Intent创新传递给、 onStartCommand，除非重新收到一个未处理（pending悬而未决地）的Intent，在这种情况下（inwhich case），未处理的心得Intent仍然按照流程被传入和处理，但是前一次操作的Intent将会变null（等同于一次带null intent的启动）。对于不需要立刻执行命令的服务，如多媒体播放器（或者其他类似（similar）的服务）那么这样的设定是非常适合的，但是服务会无限期的运行，并等待一个适合的工作（个人理解：就是服务等于又重新启动恢复到之前的状态了）。 START_REDELIVER_INTENT 同START_STICKY，在重新调用onStartCommand的时候，之前的Intent将会被保留，并重新传递给该方

Start与 begin作动词的区别

Start与begin作动词的区别 1. 表示（机器）开始、启动时，用start ，不用begin ，时此的start 相当于set going 。 如：How do you start the washing machine? 洗衣机怎么启动？ The man can't start the car. 这个人无法发动这辆车。 2. 表示创办、开设时，用start ，不用begin 。此时的start 相当于set up 或establish 。 如：He started a new shop last year. 去年他新开了一家商店。 3. 表示动身、出发、启程时，用start ，不用begin ，此时的start 相当于set out 或set off 。 如：He started for America last week. 他上周动身去美国了。 4. 表示开始使用时，用start ，不用begin ，此时的start 相当于begin to use 。 如：You have used up this bottle of ink. Will you start another one? 你已用完了这瓶墨水，打算再用一瓶吗？ 5. 表示惊动、惊起时，用start ，不用begin ，此时的start 相当于be started 。 如：She started at the sound of my voice. 她听到我的声音吓了一跳。 6. 表示提出问题时，用start ，不用begin ，此时的start 相当于raise 或put up 。 如：John started a question at the meeting. 约翰在会上提出了一个问题。 7. 表示怀孕（口语）时，用start ，不用begin ，此时的start 相当于carry 或be in a family way 。如：Linda has started a baby. 琳达怀孕了。 8. 指一段时间的开始常用begin ，而不用start 。 如：The new school year will begin soon. 新学年很快就要开始了。 另外，begin 表示的开始往往指从起点开始，而start 则不一定。 因此当一件事中断后再开始时应用start again ，而begin again 则含有“从头再来”（= begin afresh ）的意思。 如：Conversation started and stopped ，and after a long pause ，started again. 谈话开始后又停止了，过了好长一会儿才又开始。 Don't lose heart; let's begin again （afresh ）. 别灰心，让我们从头再来。

turn的用法总结

turn的用法 一、turn 用作名词时,意为“轮流”“依次轮流的顺序”。例如: Now it’s your turn to read the text. 现在轮到你读课文了。 It's my turn to use the bike. 该轮到我用自行车了。 Y ou must stand in line and wait for your turn. 你必须排队等候。 含turn 的短语有: take turns 意为“替换”“轮流”; by turns 意为“轮流地”。例如: Please take turns to ask questions. 请轮流提问。 We looked after the little boy by turns. 我们轮流照看这个小男孩。 We take turns to make dinner. 我们轮流做晚饭。(=We make dinner by turns.) 注：take one's turn to do sth. = do sth. in turn =do sth. by turns轮流做某事 =take turns to do sth.=take turns at doing sth.=take turns doing sth. The nurses attended the patient in turn / by turns. =The nurses took turns to attend the patient. Th e twins take turns to make dinner. =The twins take turns at making dinner. =The twins take turns making dinner. 二、turn 用作系动词时,意为“变得”。例如: In spring the trees turn green and the flowers start to come out. 春天,树变绿了,花儿开了? In autumn the leaves turn yellow. 秋天树叶变黄。 She turned pale. 她的脸变得苍白。 三turn 用作不及物动词时,意为“转向”“翻转”. turn right / left = turn to the right / left 例如: Turn right. At the end of the road you’ll see the hospital. 向右拐,在路的尽头就是那家医院? Just go straight and turn left. 一直往前走,然后向左拐? Turn to Page 12 in your workbook. 翻到练习册第12页? He turned his face to the wall. 他转过脸面向墙壁。 The road turns south outside town. 此路在城外转弯向南。 turn to sth. / sb. (for help) When I am in difficulty, I always turn to him for help. 我有困难时总是找他帮忙。 四、转动,旋转 The wheel turns when its axis moves. 轮轴动时,轮子也跟着转动。 He turned the key in the lock. 他旋动插进锁里的钥匙。 五、使倒置,使颠倒;倾倒[O] He turned the glass upside down. 他将玻璃杯子倒置。 六、turn 可以和介词或副词一起构成短语动词,表达不同的意思?常见的这些短语动词有: 1. turn over 意为“翻过来”例如: Tom turned over the note and read, “Come and look for me in the study.” 汤姆把便条翻过来读道,“到书房来找我.”

begin与start区别

Start与begin区别 一 . 相同之处 1. 意为“开始；发生；发起”时，两者可互换。如： Then he began/ started a series of experiments. 然后他就开始做一系列的实验。 How did the accident begin/ start? 事故是怎样发生的？ 2. 表示开始某一动作时，后面跟不定式或动名词所表达的意思是相同的。但当表示开始一项较长时间或经常性的活动时，后接动名词的形式则更为常见。如： The child began crying/ to cry. 那小孩开始哭了。 3. 两者在下列情况下常接不定式，不接动名词： （1 ）主语是无生命的事物，而不是人时。如： The ice began/ started to melt. 冰开始融化了。 （2 ）当began 和start 用于进行时态时。如： he plaster was beginning / starting to fall from the walls. 墙上的灰泥开始脱落了。 （3 ）当begin 和start 后接表示心理状态或精神活动的动词时。如： Mary began/ started to guess what is in the bag. 玛丽开始猜包里有什么东西了。 4. 两者都具有及物动词词性和不及物物动词词性。如： What time do you begin/ start school? 你是什么时候开始上学的？ His work starts/ begins at half past eight and finishes at a quarter to five. 他的工作八点半开始，四点四十五分结束。 5. begin/ start with 意为“从……开始”。如： Which lesson shall I begin / start with? 我应从哪一课开始？ 6. begin 和start 均为终止性动词，因此不能与段时间状语连用。如： 电影开始10 分钟了。 误：The film has begun/ started for ten minutes. 正：The film began ten minutes ago. 正：The film has been on for ten minutes. 正：It's ten minutes since the film began. 二 . 不同之处 1. 表示（机器）开始、启动时，用start ，不用begin ，时此的start 相当于set going 。如： How do you start the washing machine? 洗衣机怎么启动？ The man can't start the car. 这个人无法发动这辆车。 2. 表示创办、开设时，用start ，不用begin 。此时的start 相当于set up 或establish 。如： He started a new shop last year. 去年他新开了一家商店。 3. 表示动身、出发、启程时，用start ，不用begin ，此时的start 相当于set out 或set off 。如： He started for America last week. 他上周动身去美国了。 4. 表示开始使用时，用start ，不用begin ，此时的start 相当于begin to use 。如：You have used up this bottle of ink. Will you start another one? 你已用完了这瓶墨水，打算再用一瓶吗？

新人教版七年级英语上册Starter

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2) What‘s this/that? 这/那是什么？ It’s a ruler. （这/那是）直尺。 It’s an apple. （这/那是）苹果。 2.What‘s this/that in English? 这/那用英语怎么说？ It’s a/an + 单数物品 （△不说This/That is）What’s this in English? 这用英语怎么说？ It’s a jacket. 夹克衫 What‘s that in English? 那用英语怎么说？ It’s an orange. 橘 子。 in + 语言：用某种语言 in Chinese/English/Japanese 用汉/英/日语 英语中还可用What‘s the English for….?表达同样的含 义。 What’s the English for直尺？直尺用英语怎么说？ It‘s a ruler.是ruler 3.a 和an是不定冠词，只用在可数名词单数前面，表示― a用在以辅音音素开头的单词前； an用在以元音音素开头的单词前。这里的元音音素和辅音音素是指读音，而不是指字 母。如：a pen /pen/ 一支钢笔 (/p/为辅音音素) an orange 一个桔子(为元音音素) 4.P停车场；停车位 NBA（美国）全国篮球协会kg千克；公斤 5.Spell it, please. = Please spell it. 请拼读它。 K – E - Y. Spell ―pen‖, please. = Please spell pen. 请拼读―pen‖。 P – E - N. 注：please置于句末时，前面要加逗号

begin与start区别

Start与begin区别 一.相同之处 1.意为“开始；发生；发起”时，两者可互换。如： Then he began/ started a series of experiments.然后他就开始做一系列的实验。 How did the accident begin/ start?事故是怎样发生的？ 2.表示开始某一动作时，后面跟不定式或动名词所表达的意思是相同的。但当表示开始一项较长时间或经常性的活动时，后接动名词的形式则更为常见。如： The child began crying/ to cry.那小孩开始哭了。 3.两者在下列情况下常接不定式，不接动名词： （1）主语是无生命的事物，而不是人时。如： The ice began/ started to melt.冰开始融化了。 （2）当began和start用于进行时态时。如： he plaster was beginning / starting to fall from the walls.墙上的灰泥开始脱落了。 （3）当begin和start后接表示心理状态或精神活动的动词时。如： Mary began/ started to guess what is in the bag.玛丽开始猜包里有什么东西了。 4.两者都具有及物动词词性和不及物物动词词性。如： What time do you begin/ start school?你是什么时候开始上学的？ His work starts/ begins at half past eight and finishes at a quarter to five.他的工作八点半开始，四点四十五分结束。

七年级上册英语Starter Unit1教案

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Ⅲ.教学重点 (1)词汇：good，morning，hi，hello (2)字母：Aa，Bb，Cc，Dd，Ee，Ff，Gg，Hh (3)句型：Good morning！Hello/Hi! Ⅳ.教学难点 让学生会读英文名字；将英语字母打乱顺序进行认 读和书写。 Ⅴ.教学步骤：Warm­up 1．教师向学生播放英国人说英语的视频，激发学生学习英语的兴趣。 2．教师可以利用英语歌曲、英文电影渲染气氛，营造学习英语的环境。然后可向学生展示自己的英语水平，让学生“亲其师，信其道”。 建议1：用英语进行自我介绍，可介绍自己的姓名、毕业学校、从教时间，以及自己取得的成就。但要注意 一定要口齿清晰、语音语调正确，说出英语的韵味来。 例如： T：Do you like English？Is English vg？day， let's learn English.And I'm your English teacher.Lduce myself.My n aI'I have tauglars.Duringars，I have g建议2：播放一段中国人说英语非常流利的视频，然后用英语介绍，告诉学生如

start-to-do-sth-与start-doing-sth的区别

s t a r t t o d o s t h与s t a r t d o i n g s t h的区别start doing sth和start to do的区别 begin / start to do sth begin / start doing sth. 1) 谈及一项长期活动或开始一种习惯时，使用doing. How old were you when you first started playing the piano? 你几岁时开始弹钢琴？ 2) begin, start用进行时时，后面动词用不定式to do I was beginning to get angry。 我开始生起气来。 3) 在attempt, intend, begin, start 后接know, understand, realize这类动词时，常用不定式to do。 I begin to understand the truth。 我开始明白真相。 4) 物作主语时 It began to melt 另：英语中的begin 与start 都有“开始”的意思，但在实际运用中，却有很多不同 一 . 相同之处 1. 意为“开始；发生；发起”时，两者可互换。如： Then he began/ started a series of experiments. 然后他就开始做一系列的实验。 How did the accident begin/ start？事故是怎样发生的？ 2. 表示开始某一动作时，后面跟不定式或动名词所表达的意思是相同的。但当表示开始一项较长时间或经常性的活动时，后接动名词的形式则更为常见。如： The child began crying/ to cry. 那小孩开始哭了。 3. 两者在下列情况下常接不定式，不接动名词： （1 ）主语是无生命的事物，而不是人时。如： The ice began/ started to melt. 冰开始融化了。 （2 ）当began 和start 用于进行时态时。如： The plaster was beginning / starting to fall from the walls. 墙上的灰泥开始脱落了。 （3 ）当begin 和start 后接表示心理状态或精神活动的动词时。如： Mary began/ started to guess what is in the bag. 玛丽开始猜包里有什么东西了。 4. 两者都具有及物动词词性和不及物物动词词性。如： What time do you begin/ start school？你是什么时候开始上学的？ His work starts/ begins at half past eight and finishes at a quarter to five. 他的工作八点半开始，四点四十五分结束。 5. begin/ start with 意为“从……开始”。如： Which lesson shall I begin / start with？我应从哪一课开始？ 6. begin 和start 均为终止性动词，因此不能与段时间状语连用。如： 电影开始10 分钟了。 误：The film has begun/ started for ten minutes.

最新人教版七年级上册英语starter unit1教学设计

Starter Unit 1 Good morning ! Starter Unit 1是Go for it!预备篇三个单元的第一单元。预备篇是为了使那些没有英语基础的学生更好地使用本套教材而编写的。它的主要内容为26个字母和最基本的英语日常用语。 本单元的教学内容为： 1．学习Aa --- Hh八个字母。 2．学习八个人名。Alice, Bob, Cindy, Dale, Eric, Frank, Grace, Helen 3．学习打招呼的用语： Hello!/ Good morning!/ Good afternoon!/ Good evening! 4．学会问候熟识的朋友和应答：-- How are you? -- I’m fine, thanks. How are you? -- I’m OK 教学重点： Aa --- Hh的字母教学。 Hello! Good morning. Good afternoon. Good evening. -- How are you? -- I’m fine, thanks. How are you? -- I’m OK. 教学难点：课本中英语人名的学习和大、小写字母的学习及书写。 单元课时:5个课时 第一课时：完成Section A 1a, 1b 第二课时；完成Section A 2a, 2b,2c, 2d, 3, 4a 第三课时：完成Section A 4b, 4c, Section B 1, 2a, 2b 第四课时：完成Section B 3a, 3b, 4, 5 第五课时：完成Self Check and Just for Fun 教学目标 A.语言知识目标 1．词汇: Letters Aa --- Hh 八个人名Alice, Bob, Cindy, Dale, Eric, Frank, Grace, Helen 2．句型：Good morning. Good afternoon. Good evening. -- How are you? -- I’m fine, thanks. How are you? -- I’m OK. B. 语言技能目标 通过游戏等多种形式的学习活动，培养学生对初学知识的听、说、读、写能力和灵活运用初学的日常交际用语的能力。 C. 情感目标 1. 激发学生学习英语的兴趣，发挥学生学习英语的积极性和主动性。 2．通过小组活动，培养学生的合作意识和团队精神。 3．在活动中培养学生的思维能力和创新能力。

新概念青少版入门级测试题

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( ) 1. A. It’s an orange. B. It’s orange. ( ) 2. A. That’s my sister. B. That is my sister. ( ) 3. A. What’s this? B. What’s that? ( ) 4. A. You’re ten. B. You aren’t ten. ( ) 5. A. It’s next to the bedroom. B. It’s next to the bathroom. 笔试50% 一、看图片，写单词10% ________ ________ ________ ________ ________ 二、划掉错误选项10% 例：a an ball 1. a an jelly 2. a an umbrella 3. a an red apple 4. a an anorak 5. a an orange 6. a an dining room 7.8. It is isn’t an insect. She is isn’t a postman. 9. 10. It is isn’t in front of the table. This is his her frog. 三、写出下列短语的缩写或完整形式6% 1.I’m = 2. you’re = 3. isn’t =

start-to-do-sth-与start-doing-sth的区别

start to do sth 与start doing sth的区别 start doing sth和start to do的区别 begin / start to do sth begin / start doing sth. 1) 谈及一项长期活动或开始一种习惯时，使用doing. How old were you when you first started playing the piano? 你几岁时开始弹钢琴？ 2) begin, start用进行时时，后面动词用不定式to do I was beginning to get angry。 我开始生起气来。 3) 在attempt, intend, begin, start 后接know, understand, realize这类动词时，常用不定式to do。 I begin to understand the truth。 我开始明白真相。 4) 物作主语时 It began to melt 另：英语中的begin 与start 都有“开始”的意思，但在实际运用中，却有很多不同 一 . 相同之处 1. 意为“开始；发生；发起”时，两者可互换。如：

Then he began/ started a series of experiments. 然后他就开始做一系列的实验。 How did the accident begin/ start？事故是怎样发生的？ 2. 表示开始某一动作时，后面跟不定式或动名词所表达的意思是相同的。但当表示开始一项较长时间或经常性的活动时，后接动名词的形式则更为常见。如： The child began crying/ to cry. 那小孩开始哭了。 3. 两者在下列情况下常接不定式，不接动名词： （1 ）主语是无生命的事物，而不是人时。如： The ice began/ started to melt. 冰开始融化了。 （2 ）当began 和start 用于进行时态时。如： The plaster was beginning / starting to fall from the walls. 墙上的灰泥开始脱落了。

外研版 七年级英语上册 starter 单词表

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sorry ['s?r?]对不起，抱歉的 can [k?n, k?n]能，能够 you [ju?] 你，你们 spell [spel] 拼写 it [?t]它 yes [jes] 是，是的 thank[θ??k]谢谢 how [ha?] 怎样，如何 are[ɑ?]是（动词be的复数和第二人称单数现在式） fine [fa?n] 很好的，不错的 thanks [θ??ks]谢谢 Mrs ['m?s?z]夫人，太太 too [tu:]也，还 this [e?s]这，这个（指较近的人或事物） she [?i:] 她 teacher ['ti:t??] 老师 friend [frend]朋友 her [h??]她的 his [h?z]他的 nice [na?s] 美好的，令人愉快的 to [tu?](与原形动词一起构成动词不定式)

start的用法和辨析

start的用法和辨析 你们知道start用法吗?我们一起来学习学习吧，下面就和大家分享，来欣赏一下吧。 词汇精选：start的用法和辨析 一、详细释义： n. 开始，起点 例句： After several starts, she read the report properly. 经过几次断续后，她开始顺利地念报告了。 例句： She demanded to know why she had not been told from the start. 她想知道为什么一开始没有告诉她。 例句：

Lets start cooking. 我们开始做饭吧。 动身;开动 例句： Lets see how fast you can pick up from a standing start. 看看你站着起跑后能加速多快。 例句： An early start will get us well ahead before the crowds. 早点动身，我们会远远走在人们的前面。 震惊，震动 例句： He gave a slight start. 他微微地震动了一下。 例句： She gave a shuddering start as she became aware of someone standing behind her. 当她觉察到有人站在背后时，她吓得浑身一打战。

v. 出发，起程[I,T] 例句： Well have to start out early and start back for home in the afternoon. 我们必须早点出发，并在下午就动身回家。 例句： I should be instructed when to start. 应当通知我出发的时间。 开始，着手[T] 例句： We have many problem to surmount before we can start the project. 我们得克服许多困难才能着手做这项工作。 例句： I start to earn my own living this very afternoon. 就在今天下午我要开始自己挣钱了。